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BACKGROUND OF THE INVENTION
Field of the Invention
The invention relates to an office chair, in particular an office chair having a backrest that can be tilted into a rest position.
As a rule, such an office chair is configured as an office swivel chair and has various forms of adjustment in order to permit a high degree of seating comfort. Modern office swivel chairs are provided with a “synchronous mechanism” via which a seat can be combined with the backrest in such a way that the seat is oriented in an ergonomic manner in each tilted position of the backrest. On account of the tilting capacity of the backrest, the office chair can be shifted into a rest position. In order to permit a position which is as relaxed as possible, it is advantageous if the feet can be put on a footrest. Such a footrest is configured, for example, as a separate piece of furniture or is fastened to a writing table. U.S. Pat. No. 5,727,848 discloses a chair for a computer workplace having a footrest fastened to the seat of the chair via an extendable rod.
SUMMARY OF THE INVENTION
It is accordingly an object of the invention to provide an office chair that overcomes the above-mentioned disadvantages of the prior art devices of this general type, having a high degree of comfort.
With the foregoing and other objects in view there is provided, in accordance with the invention, an office chair. The office chair contains a backrest which can be tilted into a rest position, a support column supporting the backrest, a footrest, and a telescopically extendable connecting element connected on a first end to the support column and on a second end to the footrest. The connecting element is extendable from a basic position into an extended position. The connecting element has a restoring element exerting a restoring force on the connecting element in a direction of the basic position.
The object is achieved according to the invention by the office chair, in particular by the office chair having a backrest that can be tilted into a rest position. The footrest is fastened to the office chair via the telescopically extendable connecting element that is extendable from the basic position into the extended position. In this case, the restoring element configured in particular as a spring element is provided. The restoring element exerts a restoring force on the connecting element in the direction of the basic position of the connecting element.
The fastening of the footrest to the office chair, compared with a footrest configured as a separate piece of furniture, achieves the advantage that, when the feet are supported on the footrest, the office chair is not pushed away from the footrest. The distance between the footrest and the office chair therefore stays the same. Furthermore, associated with the telescopic extendability is the advantage that the footrest can be positioned at different distances from the office chair and, can be pulled up to the office chair in a space-saving manner when it is not required. The configuration of the restoring element is especially useful, since in this way the footrest is automatically retracted into the basic position when it is not required. In addition, favorable ergonomic positioning of the footrest is automatically effected without manual adjustments having to be made. In particular, an ergonomically favorable adjustment to different users is effected, or if a user changes his seating position, for example by leaning back.
For a simple configuration of the connecting element, it is preferably configured as a telescopic tube.
In this case, the connecting element is expediently configured in such a way that it is moved evenly from the extended position into the basic position. The automatic retraction of the connecting element, in particular, is therefore not effected suddenly, and is also effected sufficiently slowly, in order not to form any source of danger due to the footrest springing back too quickly.
In this case, a valve is expediently provided on the telescopic tube, and the valve has a large outflow resistance, compared with the inflow resistance, for the air flowing out of the telescopic tube during the movement into the basic position. The outflowing air is thus choked and provides for uniform retraction into the basic position. The valve is preferably configured as a simple check valve that clears an air opening in the telescopic tube when the telescopic tube is being extended. When the telescopic tube is being retracted, the check valve at least partly covers the air opening.
In an expedient development, the extension length of the connecting element is adjustable. In preferred variants, the adjustability has a displacement limit and/or a fixing device. With the displacement limit, extension of the connecting element beyond a desired extension length is prevented. It thus permits an optimum adaptation to the body size of a person using the office chair. The fixing device, in addition to the displacement limit, additionally achieves the effect that the footrest—if desired—is not automatically retracted and remains in a predefined position.
In an especially advantageous embodiment variant, the connecting element is fastened so as to be pivotable about a perpendicular chair axis. This makes it possible to bring the footrest around the office chair into a rear position when it is not required in order to prevent the footrest from getting in the way in the foot region of the office chair.
The connecting element is also expediently pivotable in a plane spread out by the chair axis and the connecting element in order to be able to compensate for any possible unevenness in the floor.
For as simple a fastening of the connecting element as possible, the connecting element is fastened to, in particular clipped onto, a supporting column of the office chair, the supporting column holding a seat carrier. As an alternative to this, the connecting element may also be fastened directly to the seat carrier. With the fastening to the seat carrier, especially stable mechanical guidance of the connecting element is possible.
For a mechanically simple and robust embodiment, a supporting element for supporting the footrest on the floor is provided on the connecting element at the foot end in the region of the footrest. The force exerted on the footrest is therefore transmitted via the supporting element to the floor and does not need to be absorbed via the fastening to the office chair. In order to ensure the mobility of the footrest, the supporting element has casters.
As an alternative to this, the footrest is fastened to the office chair in a freely floating manner, that is to say without a supporting element on the floor. The seat carrier, on account of the stable mechanical guidance for the connecting element, is suitable for the freely floating fastening.
In order to permit an ergonomic seating position that is as comfortable as possible, the footrest contains a pivotable foot support which, in particular by a spring, is held in an initial position and/or can be latched in a pivoted position. In addition to or as an alternative to the spring element, the pivoting capacity is kept tight on account of friction forces.
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 an office chair, 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 DRAWINGS
FIG. 1 is a diagrammatic, side-elevational view of an office chair with a footrest, which is attached thereto via a connecting element, in an extended position, according to the invention; and
FIG. 2 is a side-elevational view of the office chair according to FIG. 1 with the footrest in a retracted basic position.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the figures of the drawing in detail and first, particularly, to FIG. 1 thereof, there is shown in a greatly simplified manner an office chair 2 , in particular an office swivel chair, that has a backrest 4 and a seat 6 . The seat 6 is held by a seat carrier 8 (shown by broken line). The seat carrier 8 is connected via a vertically adjustable supporting column 10 to a pedestal 14 mounted on casters 12 . The backrest 4 can be tilted into a rest position, as shown in FIG. 1 . In this case, the office chair 2 has in particular a “synchronous mechanism” which connects the backrest 4 and the seat carrier 8 to one another in such a way that, when the backrest 4 is adjusted, the seat carrier 8 is at the same time adjusted in an especially ergonomic manner.
A connecting element configured as a telescopic tube 16 is fastened to the supporting column 10 , in particular by being clipped on, by a fastening element 18 . In this case, the fastening element 18 preferably encloses the supporting column 10 in a loose manner, so that the connecting element can be pivoted about a perpendicular chair axis 20 running through the supporting column 10 . The fastening element 18 is connected to the telescopic tube 16 via a joint 21 . The joint 21 permits pivoting of the telescopic tube 16 in a plane spread out by the chair axis 20 and the telescopic tube 16 . The telescopic tube 16 can therefore be pivoted relative to the horizontal, so that, for example, unevenness in the floor can be compensated for.
At the foot end, a footrest 22 having a foot support 24 is disposed on the telescopic tube 16 . The footrest 22 is supported on a floor (not shown in any more detail) via a supporting element 26 and a caster 28 . The foot support 24 formed in one piece with the footrest 22 is held in a pivotable manner on the supporting element 26 via a swivel joint 30 . The pivoting capacity is kept tight, for example by an adjustable friction force. In addition, the inclination of the foot support 24 can be fixed by corresponding latching in the swivel joint 30 . As an alternative to this, it is possible to provide a spring 33 in the swivel joint, and this spring 33 brings the foot support 24 in each case into a predefined initial position when not in use.
Provided in the telescopic tube 16 is a spring element 32 that automatically retracts the footrest 22 from an extended position according to FIG. 1 into a retracted position according to FIG. 2 . It is additionally shown in FIG. 2 that the footrest 22 is swung to the rear side of the office chair 2 in order not to get in the way in the front foot region.
The spring element 32 is preferably configured in such a way that the footrest 22 is moved evenly and sufficiently slowly from the extended position into the basic position in order not to represent a risk of injury. A valve 34 , shown schematically, is provided in order to assist the even retraction. This causes the air which is to be displaced from the telescopic tube 16 during the retraction into the basic position to escape slowly and evenly, so that the footrest 22 does not spring back suddenly into the basic position. The valve 34 is configured as a simple check valve for example.
Furthermore, provision is preferably made for the extension length of the telescopic tube 16 to be adjustable and in particular fixable. It is thus possible, on the one hand, to limit the distance between the footrest 22 and the seat 6 , so that the footrest is not pushed away from the office chair to an undesirable extent. On the other hand, automatic retraction into the basic position is prevented by the fixing device.
The office chair 2 with the footrest directly attached thereto has the substantial advantage that the office chair 2 mounted on the casters 12 cannot be pushed away when using the footrest 22 on account of the muscle power exerted on the footrest 22 . A distance between the footrest 22 and the seat 6 is therefore kept constant. In addition, the footrest 22 is always directly accessible and can be positioned in an ergonomically favorable manner relative to the seat 6 . Operation is also especially user-friendly, since the footrest 22 can be extended in a simple manner by muscle power when required from the retracted basic position into the desired extended position. In addition, due to the pivoting capacity about the chair axis 20 , the footrest 22 can be put away in a space-saving manner. Given a suitable subdivision of the individual telescopic elements of the telescopic tube 16 , the footrest 22 can also be pulled nearer to the supporting column 10 than as shown in FIG. 2 . It is thus possible to pull the footrest near to the supporting column 10 in such a way that it does not project beyond the pedestal 14 . | A footrest is fastened via a telescopically extendable connecting element to an office chair, in particular to an office chair having a backrest that can be tilted into a rest position. This results in an especially comfortable and ergonomic seating position, and in particular a situation in which the office chair is pushed away from the footrest when the footrest is not needed. | 0 |
TECHNICAL FIELD
[0001] The present invention relates to a liquid transfer device and a liquid transfer method for transferring a liquid to a sheet, and is particularly effective when applied to a sheet-fed offset printing press which prints ink on a sheet.
BACKGROUND ART
[0002] For example, a sheet-fed offset printing press which prints ink on a sheet is configured such that the ink is supplied from an ink form roller of an inking device to a plate of a plate cylinder, then transferred to a blanket of a blanket cylinder in a pattern corresponding to a pattern of the plate, and thereafter transferred (printed) to a sheet held by an impression cylinder.
[0003] In such a sheet-fed offset printing press, the ink is transferred from an ink supply source to the sheet via many rollers and the like. Accordingly, a large amount of work is required to appropriately adjust an ink supply amount for the sheet at the start of a printing operation. To solve this problem, for example, Patent Literature 1 listed below and the like propose a sheet-fed offset printing press configured to detect an ink density on a printed sheet and adjust an ink supply amount from an inking device on the basis of the detected ink density.
CITATION LIST
Patent Literature
[0004] Patent Literature 1: Japanese Patent Application Publication 2006-103050
[0005] Patent Literature 2: Japanese Patent No. 3501844
SUMMARY OF INVENTION
Technical Problem
[0006] However, in the sheet-fed offset printing press described in Patent Literature 1 and the like, the ink density cannot be appropriately adjusted for a sheet printed immediately after start of the printing operation and the ink density on the sheet printed immediately after start of the printing operation is low. Accordingly, the sheet printed immediately after the start of the printing operation needs to be discarded as waste paper and sheets and ink are wasted.
[0007] Such a problem occurs not only in a sheet-fed offset printing press like one described above and may occur in a similar way in a case where a liquid is transferred from liquid transfer means to an outer peripheral surface of a liquid transfer cylinder and the liquid on the outer peripheral surface of the liquid transfer cylinder is transferred to a sheet held on an outer peripheral surface of an impression cylinder, as in a varnish transfer device configured to transfer varnish on a sheet, and the like.
[0008] In view of this, an object of the present invention is to provide a liquid transfer device and a liquid transfer method which can transfer a liquid to a sheet at a sufficient density even immediately after start of a running operation.
Solution to Problem
[0009] A liquid transfer device of the present invention for solving the problem described above is a liquid transfer device including:
[0010] a rotatably-provided impression cylinder configured to hold a sheet on an outer peripheral surface thereof;
[0011] a rotatably-provided liquid transfer cylinder configured to be movable to be brought into contact with and separated from the impression cylinder;
[0012] liquid transfer means for transferring a liquid to an outer peripheral surface of the liquid transfer cylinder; and
[0013] control means for controlling contact and separating movement of the liquid transfer cylinder, rotating operations of the impression cylinder and the liquid transfer cylinder, and transferring operation of the liquid from the liquid transfer means to the liquid transfer cylinder, the liquid transfer device characterized in that
[0014] the control means controls the liquid transfer cylinder, the impression cylinder, and an operation of the liquid transfer means in such a way that: in a period between start of a running operation and transfer of the liquid to a first sheet, the liquid is repeatedly transferred from the liquid transfer means to the outer peripheral surface of the liquid transfer cylinder with the liquid transfer cylinder and the impression cylinder, which are separated from each other, being rotated; and thereafter the liquid on the outer peripheral surface of the liquid transfer cylinder is transferred to the first sheet.
[0015] Moreover, the liquid transfer device of the present invention is the aforementioned liquid transfer device characterized in that
[0016] the liquid is ink,
[0017] the liquid transfer means includes: a rotatably-provided plate cylinder with a plate attached to an outer peripheral surface thereof; and ink transfer means for transferring the ink to the plate of the plate cylinder,
[0018] the liquid transfer cylinder is a blanket cylinder with a blanket attached to an outer peripheral surface thereof, the blanket cylinder configured to be movable to be brought into contact with and separated from the impression cylinder and the plate cylinder, and
[0019] the control means controls the impression cylinder, the plate cylinder, an operation of the blanket cylinder, and the ink transfer means in such a way that: the ink is repeatedly transferred from the ink transfer means to the plate of the plate cylinder with the blanket cylinder separated from the plate cylinder and the impression cylinder and with the impression cylinder, the plate cylinder, and the blanket cylinder being rotated; then the ink on the plate cylinder is repeatedly transferred to the blanket cylinder by bringing the blanket cylinder into contact with the plate cylinder; and thereafter the ink on the blanket cylinder is transferred to the first sheet by bringing the blanket cylinder into contact with the impression cylinder.
[0020] Furthermore, the liquid transfer device of the present invention is the aforementioned liquid transfer device characterized in that
[0021] each of the plate cylinder, the blanket cylinder, and the impression cylinder has a gap portion formed on the outer peripheral surface thereof, and
[0022] the control means controls the operation of the blanket cylinder in such a way that: the blanket cylinder and the plate cylinder are brought into contact with each other when the gap portion of the plate cylinder and the gap portion of the blanket cylinder come to face each other; and the blanket cylinder and the impression cylinder are brought into contact with each other when the gap portion of the impression cylinder and the gap portion of the blanket cylinder come to face each other.
[0023] Meanwhile, a liquid transfer method of the present invention for solving the problems described above is a liquid transfer method of transferring a liquid from liquid transfer means to an outer peripheral surface of a liquid transfer cylinder and transferring the liquid on the outer peripheral surface of the liquid transfer cylinder to a sheet held on an outer peripheral surface of an impression cylinder, characterized in that the liquid transfer method comprises:
[0024] a liquid transfer cylinder transfer step of, in a period between start of a running operation and transfer of the liquid to a first sheet, repeatedly transferring the liquid from the liquid transfer means to the outer peripheral surface of the liquid transfer cylinder with the liquid transfer cylinder and the impression cylinder, which are separated from each other, being rotated; and
[0025] a sheet transfer step of transferring the liquid to the first sheet by bringing the liquid transfer cylinder and the impression cylinder into contact with each other after the liquid transfer cylinder transfer step.
[0026] Moreover, the liquid transfer method of the present invention is the aforementioned liquid transfer method characterized in that
[0027] the liquid is ink,
[0028] the liquid transfer means includes: a rotatably-provided plate cylinder with a plate attached to an outer peripheral surface thereof; and ink transfer means for transferring the ink to the plate of the plate cylinder,
[0029] the liquid transfer cylinder is a blanket cylinder with a blanket attached to an outer peripheral surface thereof, the blanket cylinder configured to be movable to be brought into contact with and separated from the impression cylinder and the plate cylinder, and
[0030] the liquid transfer cylinder transfer step is a step including:
a plate cylinder transfer step of repeatedly transferring the ink from the ink transfer means to the plate of the plate cylinder with the blanket cylinder separated from the plate cylinder and the impression cylinder and with the impression cylinder, the plate cylinder, and the blanket cylinder being rotated; and a blanket cylinder transfer step of repeatedly transferring the ink on the plate cylinder to the blanket cylinder by bringing the blanket cylinder into contact with the plate cylinder, and
[0033] the sheet transfer step is a step of transferring the ink on the blanket cylinder to the first sheet by bringing the blanket cylinder into contact with the impression cylinder.
[0034] Furthermore, the liquid transfer method of the present invention is the aforementioned liquid transfer method characterized in that
[0035] each of the plate cylinder, the blanket cylinder, and the impression cylinder has a gap portion formed on the outer peripheral surface thereof, and
[0036] the blanket cylinder transfer step is a step of bringing the blanket cylinder and the plate cylinder into contact with each other when the gap portion of the plate cylinder and the gap portion of the blanket cylinder come to face each other, and
[0037] the sheet transfer step is a step of bringing the blanket cylinder and the impression cylinder into contact with each other when the gap portion of the impression cylinder and the gap portion of the blanket cylinder come to face each other.
Advantageous Effects of Invention
[0038] In the liquid transfer device and the liquid transfer method of the present invention, the liquid can be transferred at a sufficient density from the first sheet even immediately after the start of the liquid transfer operation. Accordingly, it is possible to eliminate generation of sheets with low liquid density immediately after the start of the liquid transfer operation and effectively use the sheets and the liquid.
BRIEF DESCRIPTION OF DRAWINGS
[0039] FIG. 1 is a schematic configuration diagram of a main portion of a main embodiment in which a liquid transfer device of the present invention is applied to a sheet-fed offset printing press.
[0040] FIG. 2 is a control block diagram of the main portion of the sheet-fed offset printing press of FIG. 1 .
[0041] FIG. 3 is a diagram explaining an operation of the main portion of the sheet-fed offset printing press of FIG. 1 .
[0042] FIG. 4 is a diagram explaining an operation subsequent to FIG. 3 .
[0043] FIG. 5 is a diagram explaining an operation subsequent to FIG. 4 .
[0044] FIG. 6A is a chart showing change in ink transfer amount in phase states of the sheet-fed offset printing press in the embodiment, and FIG. 6B is a chart showing the same in the conventional technique.
[0045] FIG. 7 is a graph showing relationships between the ink thickness on the printed sheet and the number of printed sheets.
[0046] FIG. 8 is a schematic configuration view of a main portion of an embodiment in which the liquid transfer device of the present invention is applied to a varnish transfer device.
DESCRIPTION OF EMBODIMENTS
[0047] Embodiments of a liquid transfer device and a liquid transfer method of the present invention are described based on the drawings. However, the liquid transfer device and the liquid transfer method of the present invention are not limited to the embodiments described below based on the drawings.
Main Embodiment
[0048] A main embodiment in which a liquid transfer device of the present invention is applied to a sheet-fed offset printing press is described based on FIGS. 1 to 7 .
[0049] As shown in FIG. 1 , a rotatably-supported blanket cylinder B which is a liquid transfer cylinder with a rubber blanket detachably attached to an outer peripheral surface is into contact with an outer surface of a rotatably-supported impression cylinder I configured to detachably hold a sheet on the outer peripheral surface. A rotatably-supported plate cylinder P with a plate detachably attached to an outer peripheral surface is into contact with the outer peripheral surface of the blanket cylinder B. An ink form roller R of an inking device configured to supply ink which is a liquid is into contact with the outer peripheral surface of the plate cylinder P. Sheets are fed to the impression cylinder I one by one from a not-illustrated sheet feeding device which is sheet feeding means for feeding the sheets. The impression cylinder I can pass and send out the held sheet to a not-illustrated delivery device which is sheet delivering means for delivering the sheets.
[0050] Gap portions Ia each housing a gripping unit (not illustrated) configured to detachably hold a sheet are formed on an outer peripheral surface of the impression cylinder I in such a way that the longitudinal directions of the gap portions Ia extend along an axial direction. The impression cylinder I has two gap portions Ia arranged at equal intervals in a circumferential direction of the outer peripheral surface (double-size cylinder). A gap portion Ba housing a blanket holding unit (not illustrated) configured to detachably hold the blanket is formed on the outer peripheral surface of the blanket cylinder B in such a way that the longitudinal direction of the gap portion Ba extends along the axial direction. The blanket cylinder B has one notch portion Ba on the outer peripheral surface (single-size cylinder). A gap portion Pa housing a plate holding unit (not illustrated) configured to detachably hold the plate is formed on the outer peripheral surface of the plate cylinder P in such a way that the longitudinal direction of the gap portion Pa extends along the axial direction. The plate cylinder P has one gap portion Pa on the outer peripheral surface (single-size cylinder).
[0051] Rotary shafts of the cylinders I, B, and P are connected to each other by gear trains and the cylinders I, B, and P can rotate synchronously with each other. Moreover, the inking device is movable in such a way that the ink form roller R can be brought into contact with (see FIGS. 1 , 4 , and 5 ) and separated from (see FIG. 3 ) the plate cylinder P.
[0052] The blanket cylinder B is rotatably supported via an eccentric bearing. By turning the eccentric bearing, the blanket cylinder B can be separated from both of the impression cylinder I and the plate cylinder P (impression throw-off) (see FIGS. 3 and 4 ), brought into contact with the plate cylinder P while being separated from the impression cylinder I (see FIG. 5 ), and brought into contact with both of the impression cylinder I and the plate cylinder P (impression on) (see FIG. 1 ). Note that the blanket cylinder B is connected to the impression cylinder I and the plate cylinder P via the gear trains not only in the impression on state but also in the impression throw-off state.
[0053] As shown in FIG. 2 , output portions of a control device C which is control means are electrically connected respectively to: a drive motor M 1 configured to synchronously drive and rotate the cylinders I, B, and P; an ink supply motor M 2 configured to cause the inking device to operate in such a way that the ink is supplied to the ink form roller R; an inking device engagement-disengagement motor M 3 configured to move the inking device in such a way that the ink form roller R is brought into contact with and separated from the plate cylinder P; a blanket cylinder engagement-disengagement motor M 4 configured to turn the eccentric bearing in such a way that the blanket cylinder B is brought into contact with and separated from the impression cylinder I and the plate cylinder P; and a feeding device drive source M 5 configured to cause the feeding device to operate. An input unit D 1 which starts or stops a printing operation, a rotational speed detecting unit D 2 which is rotational speed detecting means for detecting the rotational speeds of the cylinders I, B, and P, and a phase detecting unit D 3 which is phase detecting means for detecting rotational phases of the cylinders I, B, and P are electrically connected respectively to input portions of the control device C. The control device C can control operations respectively of the motors M 1 to M 4 and the drive source M 5 on the basis of information from the input unit D 1 , the rotational speed detecting unit D 2 , and the phase detecting unit D 3 (details are described later).
[0054] Note that, in the embodiment, the inking device having the ink form roller R forms ink transfer means, and the ink transfer means and the plate cylinder P form liquid transfer means.
[0055] Next, description is given of operations (liquid transfer method) of the sheet-fed offset printing press in the embodiment described above.
[0056] Before the start of the printing operation, the eccentric bearing is turned in such a way that the inking device is located at a position where the ink form roller R is separated from the plate cylinder P and that the blanket cylinder B is located at a position separated from the impression cylinder I and the plate cylinder P (see FIG. 3 ). When a command to start the operation is inputted to the control device C from the input unit D 1 in this state, the control device C controls the operation of the drive motor M 1 on the basis of information from the input unit d 1 , in such a way that the cylinders I, B, and P are synchronously rotated. Moreover, the control device C controls the operation of the ink supply motor M 2 in such a way that the ink is supplied to the ink form roller R of the inking device.
[0057] When the ink form roller R of the inking device is rotated a predetermined number of times and the ink of a necessary and sufficient thickness (for example, film thickness: 8 μm) is supplied to the outer peripheral surface of the ink form roller R, the control device C controls the operations of the motors M 2 to M 4 and the drive source M 5 at the following timings on the basis of information from the rotational speed detecting unit D 2 and the phase detecting unit D 3 .
[0058] First, the control device C moves the inking device by controlling (see FIG. 4 ) the operation of the inking device engagement-disengagement motor M 3 on the basis of information from the rotational speed detecting unit D 2 and the phase detecting unit D 3 in such a way that the ink form roller R is brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the ink form roller R come to face each other (section α 1 in FIG. 6A ).
[0059] This causes the ink of the preset thickness (for example, film thickness: 8 μm) formed on the outer peripheral surface of the ink form roller R to be transferred (generally, transfer ratio is 50%) to the plate on the outer peripheral surface of the plate cylinder P, and a film of the ink (film thickness: 4 μm) is formed on the plate of the plate cylinder P. Note that a film of the ink (film thickness: 4 μm) not transferred onto the plate of the plate cylinder P is left on the outer peripheral surface of the ink form roller R.
[0060] When the plate cylinder P is rotated one turn with the ink form roller R brought into contact with the plate cylinder P as described above, the film of ink (film thickness: 4 μm) is formed over the entire periphery of the plate of the plate cylinder P. At this time, the blanket cylinder B and the impression cylinder I are also synchronously rotated (first turn). However, since the blanket cylinder B is separated from the impression cylinder I and the plate cylinder P without coming into contact therewith, no ink is transferred to the blanket cylinder B and the impression cylinder I (film thickness: 0 μm).
[0061] Next, in the second turn of the plate cylinder P after the ink form roller R is brought into contact with the plate cylinder P, a film of the ink of the same thickness (for example, film thickness: 8 μm) as the last time is formed on the outer peripheral surface of the ink form roller R continuously supplied with the ink. Due to this, the ink on the ink form roller R is applied in an overlaid manner (total thickness: 12 μm) and transferred (transfer ratio: 50%) to the film of ink (film thickness: 4 μm) on the plate cylinder P. A film of repeatedly-applied ink (film thickness: 6 μm) is thereby formed on the plate of the plate cylinder P (the above step is referred to as plate cylinder transfer step S 1 ).
[0062] After the film of ink (film thickness: 6 μm) is formed on the plate cylinder P as described above, the film of ink is transferred to the blanket of the blanket cylinder B. Specifically, at the start of the second turn of the blanket cylinder B after the ink form roller R is brought into contact with the plate cylinder P, the control device C turns the eccentric bearing and moves the blanket cylinder B by controlling (see FIG. 5 ) the operation of the blanket cylinder engagement-disengagement motor M 4 on the basis of information from the rotational speed detecting unit D 2 and the phase detecting unit D 3 in such a way that the blanket cylinder B is brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P comes to face the gap portion Ba of the blanket cylinder B (section α 2 in FIG. 6A ).
[0063] This causes the ink to be transferred (transfer ratio: 50%) to the blanket of the blanket cylinder B from the film of ink (film thickness: 6 μm) formed on the plate of the plate cylinder P by being repeatedly applied, and a film of the ink (film thickness: 3 μm) is thereby formed on the blanket.
[0064] When the blanket cylinder B is rotated one turn while being brought into contact with the plate cylinder P, the film of ink (film thickness: 3 μm) is formed over the entire periphery of the blanket of the blanket cylinder B. At this time, the impression cylinder I is also synchronously rotated (second turn). However, since the blanket cylinder B is into contact only with the plate cylinder P and is separated from the impression cylinder I without coming into contact therewith, no ink is transferred to the impression cylinder I (film thickness: 0 μm).
[0065] Next, in the third turn after the ink form roller R is brought into contact with the plate cylinder P, the film of ink (film thickness: 8 μm) on the outer surface of the ink form roller R continuously supplied with the ink is applied again in an overlaid manner (total film thickness: 11 μm) and transferred (transfer ratio: 50%) to the film of ink (film thickness: 3 μm) left on the plate of the plate cylinder P after the transfer of the ink to the blanket cylinder B. A film of the repeatedly-applied ink (film thickness: 5.5 μm) is thereby formed on the plate of the plate cylinder P. The film of ink on the plate of the plate cylinder P is thus replenished (replenishment film thickness: 2.5 μm).
[0066] When a plate portion of the plate cylinder P replenished with the ink comes into contact with the blanket cylinder B, i.e. in the third turn of the blanket cylinder B after the ink form roller R is brought into contact with the plate cylinder P, the ink is applied in an overlaid manner (total film thickness: 8.5 μm) and transferred (transfer ratio: 50%) to the film of ink (film thickness: 3 μm) on the blanket cylinder B from the film of ink (film thickness: 5.5 μm) transferred to the plate of the plate cylinder P. A film of the repeatedly-applied ink (film thickness: 4.25 μm) is thereby formed on the blanket of the blanket cylinder B. The film of ink on the blanket of the blanket cylinder B is thus replenished (replenishment film thickness: 1.25 μm) (the above step is referred to as blanket cylinder transfer step S 2 ).
[0067] After the ink is repeatedly transferred to the blanket cylinder B as described above, the ink is transferred to the first sheet on the impression cylinder I. Specifically, when the impression cylinder I is rotated one and a half turn (in the third turn in terms of a single-size cylinder) after the ink form roller R is brought into contact with the plate cylinder P, the control device C turns the eccentric bearing and moves the blanket cylinder B by controlling (see FIG. 1 ) the operation of the blanket cylinder engagement-disengagement motor M 4 on the basis of information from the rotational speed detecting unit D 2 and the phase detecting unit D 3 in such a way that the blanket cylinder B is brought into contact with the outer peripheral surface of the impression cylinder I when the gap portion Ba of the blanket cylinder B and one of the gap portions Ia of the impression cylinder I come to face each other (section γ 3 in FIG. 6A ).
[0068] At this time, since the first sheet is held on the outer peripheral surface of the impression cylinder I, the ink is transferred (transfer ratio: 50%) onto the first sheet held on the outer peripheral surface of the impression cylinder I from the film of ink (film thickness: 4.25 μm) repeatedly formed on the blanket of the blanket cylinder B, and a film of the ink is thereby formed (film thickness: 2.125 μm) on the first sheet.
[0069] Hereafter, by continuing the operation, the ink can be sequentially transferred (printed) to sheets supplied one after another from the feeding device to the impression cylinder I (the above step is referred to as sheet transfer step S 3 ). Here, as shown in FIG. 6A , the film thickness of the ink to be transferred (printed) becomes smaller sequentially for the second and subsequent sheets and gradually converges to a predetermined target film thickness.
[0070] As described above, the control device C controls the start timings of the steps S 1 to S 3 in a manner synchronized with the timing of supplying the first sheet.
[0071] Specifically, the following operations are performed in the conventional technique. As shown in FIG. 6B , when the ink form roller R of the inking device is rotated a predetermined number of times and the ink of a necessary and sufficient thickness is supplied to the outer peripheral surface of the ink form roller R, the inking device is moved in such a way that the ink form roller R is brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the ink form roller R come to face each other (section β 1 in FIG. 6B ). Next, the blanket cylinder B is moved to be brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the gap portion Ba of the blanket cylinder B come to face each other (section β 1 in FIG. 6B ). Subsequently, the blanket cylinder B is moved to be brought into contact with the outer peripheral surface of the impression cylinder I when the gap portion Ba of the blanket cylinder B and one of the gap portions Ia of the impression cylinder I come to face each other (section γ 1 in FIG. 6B ). In summary, when the ink form roller R is brought into contact with the plate cylinder P, in the first turn after the ink form roller R is brought into contact with the plate cylinder P, the blanket cylinder B is moved in such a way that the cylinders P, B, and I are all brought into contact with one another. However, the following operations are performed in the embodiment. As shown in FIG. 6A , when the ink form roller R of the inking device is rotated a predetermined number of times and the ink of a necessary and sufficient thickness is supplied to the outer peripheral surface of the ink form roller R, the inking device is moved in such a way that the ink form roller R is brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the ink form roller R come to face each other (section α 1 in FIG. 6A ). Thereafter, the ink is transferred from the ink form roller R of the inking device to the plate of the plate cylinder P with the blanket cylinder B separated from the plate cylinder P and the impression cylinder I, and the ink is thereby transferred in an overlaid manner from the ink form roller R of the inking device to the ink transferred to the plate of the plate cylinder P (step S 1 in FIG. 6A ). Then, the blanket cylinder B is moved to be brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the gap portion Ba of the blanket cylinder B come to face each other (section β 2 in FIG. 6A ). Thereafter, the ink is transferred from the plate of the plate cylinder P to the blanket of the blanket cylinder B with the blanket cylinder B separated from the impression cylinder I, and the ink is thereby transferred in an overlaid manner from the plate of the plate cylinder P to the ink transferred to the blanket of the blanket cylinder B (step S 2 in FIG. 6A ). Then, the blanket cylinder B is moved to be brought into contact with the outer peripheral surface of the plate cylinder P when the gap portion Pa of the plate cylinder P and the gap portion Ba of the blanket cylinder B come to face each other (section γ 3 in FIG. 6A ). The blanket cylinder B and the impression cylinder I are thus brought into contact with each other and the ink is transferred from the blanket of the blanket cylinder B to the sheet on the impression cylinder I. The ink repeatedly transferred to the blanket of the blanket cylinder B is thereby printed on the sheet (step S 3 in FIG. 6A ). In summary, when the ink form roller R is brought into contact with the plate cylinder P, in the first turn of the plate cylinder P after the ink form roller R is brought into contact with the plate cylinder P, the cylinders P, B, and I are not brought into contact with and separated from one another to transfer the ink only to the plate cylinder P and the ink is thereby repeatedly transferred to the plate cylinder P. In the second turn of the blanket cylinder B after the ink form roller R is brought into contact with the plate cylinder P, the plate cylinder P and the blanket cylinder B are brought into contact with each other and the ink is thereby repeatedly transferred also to the blanket cylinder B. When the impression cylinder I is rotated one and a half turn (in the third turn in terms of a single-size cylinder) after the ink form roller R is brought into contact with the plate cylinder P, the blanket cylinder B is moved in such way that the blanket cylinder B and the impression cylinder I are brought into contact with each other and the ink repeatedly transferred to the blanket cylinder B is thereby printed on the sheet.
[0072] Hence, as shown in FIG. 7 , in the conventional technique, the ink to be printed (transferred) on the sheet gradually becomes thicker (higher in density) and reaches the target thickness (for example, 2±0.2 μm) in the fourth sheet. Meanwhile, in the embodiment, the ink can reach the target thickness (for example, 2±0.2 μm) in the first sheet.
[0073] Accordingly, in the embodiment, the ink can be transferred at a sufficient density from the first sheet even immediately after the start of the printing operation. Hence, it is possible to eliminate generation of waste paper with low ink density immediately after the start of the printing operation and effectively use the sheets and the ink.
Other Embodiments
[0074] In the aforementioned embodiment, in the first turn after the ink form roller R is brought into contact with the plate cylinder P, the cylinders P, B, and I are not brought into contact with and separated from one another to transfer the ink only to the plate cylinder P and the ink is thereby repeatedly transferred to the plate cylinder P, in the second turn after the ink form roller R is brought into contact with the plate cylinder P, only the plate cylinder P and the blanket cylinder B are brought into contact with each other and the ink is thereby repeatedly transferred also to the blanket cylinder B, and in the third turn after the ink form roller R is brought into contact with the plate cylinder P, the blanket cylinder B is moved in such way that the blanket cylinder B and the impression cylinder I are brought into contact with each other and the ink repeatedly transferred to the blanket cylinder B is thereby printed on the sheet. In other words, the number of turns for repeatedly transferring the ink by sequentially bringing the cylinders into contact with one another is one for each cylinder. However, as another embodiment, for example, the number of turns for repeatedly transferring the ink by sequentially bringing the cylinders into contact with one another may be two or more for each cylinder.
[0075] Moreover, in the aforementioned embodiment, description is given of the case where the invention is applied to the sheet-fed offset printing press including the impression cylinder I, the blanket cylinder B, the plate cylinder P, and the inking device. However, as another embodiment, the invention can be applied to a case where a liquid is transferred from liquid transfer means to an outer surface of a liquid transfer cylinder and the liquid on the outer surface of the liquid transfer cylinder is transferred to a sheet held on an outer peripheral surface of an impression cylinder, as in, for example, a varnish transfer device shown in FIG. 8 which is provided with an varnish supplying device (liquid transfer means) V including the impression cylinder I, the blanket cylinder (liquid transfer cylinder) B, and an anilox roller A and which transfers varnish being the liquid to the sheet. In this case, operations and effects similar to those of the aforementioned embodiment can be obtained.
[0076] In the varnish transfer device described above, there is no member corresponding to the plate cylinder P in the sheet-fed offset printing press described in the aforementioned embodiment. Accordingly, there is performed a liquid transfer cylinder transfer step in which the plate cylinder transfer step S 1 and the blanket cylinder transfer step S 2 are integrated. Specifically, in the liquid transfer cylinder transfer step, the control means controls the blanket cylinder B, the impression cylinder I, and an operation of the varnish supply device V in such a way that the varnish is transferred from the anilox roller A of the varnish supply device V to the outer peripheral surface of the blanket cylinder B with the blanket cylinder B and the impression cylinder I separated from each other and with the blanket cylinder B and the impression cylinder I being rotated, and the varnish from the varnish supply device V is thereby transferred in an overlaid manner to the varnish transferred to the outer peripheral surface of the blanket cylinder B. Then, when the varnish is to be transferred to the sheet by bringing the blanket cylinder B into contact with the impression cylinder I, there is performed a sheet transfer step in which the operation of the blanket cylinder B is controlled to start transfer of the varnish to the sheet from the varnish repeatedly transferred on the outer peripheral surface of the blanket cylinder B.
INDUSTRIAL APPLICABILITY
[0077] The liquid transfer device and the liquid transfer method of the present invention can eliminate generation of a sheet with low liquid density immediately after the start of the liquid transfer operation and effectively use the sheets and the ink. Accordingly, the liquid transfer device and the liquid transfer method can be highly useful in printing industries and the like when applied to, for example, a sheet-fed offset printing press.
REFERENCE SIGNS LIST
[0000]
I Impression cylinder
Ia Gap portion
B Blanket cylinder
Ba Gap portion
P Plate cylinder
Pa Gap portion
R Ink form roller
C Control device
D 1 Input unit
D 2 Rotational speed detecting unit
D 3 Phase detecting unit
M 1 Drive motor
M 2 Ink supply motor
M 3 Inking device engagement-disengagement motor
M 4 Blanket cylinder engagement-disengagement motor
M 5 Feeding device drive source | In the present invention, the following steps are carried out: a plate drum transfer step (S 1 ) in which a rubber drum (B), a plate drum (P), and an impression drum (I) are caused to separate, and in a state where the impression drum (I), the plate drum (P), and the rubber drum (B) are caused to rotate, ink is transferred to the plate drum (P) from an ink application roller (R) and the ink from the ink application roller (R) is transferred so as to be further layered onto the ink transferred onto the plate drum (P); a blanket drum transfer step (S 2 ) in which when the rubber drum (B) and the plate drum (P) are opposingly brought into contact with each other and ink from the plate drum (P) is transferred to the rubber drum (B), the transfer of ink is begun from the transferred ink that was layered onto the plate drum (P), and ink from the plate drum (P) is transferred so as to be further layered onto the ink transferred onto the rubber drum (B); and a sheet transfer step (S 3 ) in which when the rubber drum (B) and the impression drum (I) are opposingly brought into contact with each other and ink from the rubber drum (B) is transferred to a sheet of the impression drum (I), the transfer of ink is begun from the transferred ink that was layered onto the rubber drum (B) to the sheet of the impression drum (I). | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] Not applicable.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not applicable.
REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISC APPENDIX
[0003] Not applicable.
BACKGROUND OF THE INVENTION
[0004] This invention relates to shopping bag holders, specifically to an improved method of carrying plastic shopping bags and closing shopping bags during travel.
[0005] Supermarkets and other merchandisers often utilize plastic bags for packaging consumer products. These bags include integrally formed loop handles that permit a user to carry a bag with its content with ease and reliability by simply gripping the handles and carrying these bags in one's hand. However, while these plastic bags may facilitate a reliable means of transporting goods, the bag loop handles have a tendency to bite into the customer's fingers causing discomfort. This is especially the case when a bag needs to be carried over a long distance and when the content of the bag is heavy. Furthermore, the plastic bag tend to collapse when placed on a surface like a car seat, a bus floor, a car boot or other surface, with the result that its content frequently spills out.
[0006] Many attempts have been made to overcome some or all of the above discussed problems by utilizing bag holders to carry bags and bag holders that can also maintain the bag in a closed position when placed on a surface like the floor of an autobus.
[0007] The applicant has found many different patents of shopping bags holders and 136 patents that he has identified as being the most relevant to his application are shown below. Because of the sheer volume, discussing all of the patents as prior art, would be quite time consuming. The applicant has identified three main categories. He will indicate which those categories are and discuss patents from each category with regard to his present invention.
[0008] The first category he has identified comprises those bag holders that are light weight and of limited life span manufactured from textile, cardboard, vinyl and similar materials. Examples of these but to mention a few are:
Bourgeois et al, U.S. Pat. No. 5,487,582; Jan. 30, 1996 Franko, U.S. Pat. No. 5,658,029; Aug. 19, 1997 Tipp, U.S. Pat. No. 5,775,757; Jul. 7, 1998 Lisbon, U.S. Pat. No. 5,803,522; Sep. 8, 1998
[0013] All four bag holders have limited usefulness in reducing discomfort when carrying a shopping bag with three out of the four keeping the shopping bag closed when placed on a flat surface. However, the choice of material reduces greatly the amount of bags that these bag holders are able to take and the load these bag holders can withstand and even the weather condition that one of them can be used in, as it is made out of carton. All in all, they are very restrictive in their use and their ease of use apart from their cost price and longevity because of the choice of materials like hook and pile type fastener (Bourgeois), a clumsy tab to be inserted in a slot (Franko), a vinyl type material lacking strength and the ability to close the bag (Tipp) and the use of carton (Lisbon). Especially U.S. Pat. No. 5,487,582, Bourgeois et al, Jan. 30, 1996, could well be expensive to make as it appears that manufacturing would require considerable labor input.
[0014] The second category the applicant has identified comprises those bag holders that are still reasonable simple of design and mainly manufactured from plastic type materials. Many have in common that they have a groove where the handles of the shopping bag have to be inserted into and are designed to take the bags ‘lengthwise’, that is to say that the handles of the shopping bag run in a direction across the palm of the hand. Some have little cuts or hooks or even a number of hooks to hang bags on. Most will require initial outlay to make a mold if manufactured. Some will not be very sturdy and all large enough as to extend past both sides of the palm of a hand to allow for room for bag handles beyond that point. Very few can keep the shopping bag closed when placed on a surface and the ones that do can be difficult to operate and expensive to manufacture. Also, when the length of a bag holder increases, it will become more difficult to carry a heavy load. Examples of these but to mention a few are:
Fink, U.S. Pat. No. 4,841,596; Jun. 27, 1989 Schulten, U.S. Pat. No. 4,890,355; Jan. 2, 1990 Nobakht, U.S. Pat. No. 4,902,060; Feb. 20, 1990 Dieterich, Jr., U.S. Pat. No. 5,029,926; Jul. 9, 1991 Blocker et al, Pat. No. Des. 323,968; Feb. 18, 1992 Du Buisson, U.S. Pat. No. 5,433,494; Jul. 18, 1995 Giocanti, U.S. Pat. No. 5,667,266; Sep. 16, 1997 LeRoux, U.S. Pat. No. 5,992,803; Nov. 30, 1999 Palmer, U.S. Pat. No. 7,302,735; Dec. 4, 2007
and many more.
[0024] The third category of bag holders that the applicant has identified comprises larger sized bag holders. They usually consist of a carrying handle and attached to the carrying handle a separate construction where the bags are attached to, rather than to the carrying handle itself. Their main disadvantage is their large size that makes it inconvenient to carry them along when going shopping. Because of their size and often much more complicated construction, especially when designed to keep the bags closed when placed on a surface, most or all will be quite expensive to manufacture. Examples of these but to 101 mention a few are:
Griffin, U.S. Pat. No. 1,572,006; Feb. 9, 1926 Montoya, U.S. Pat. No. 5,181,757; Jan. 26, 1993 Daigle, Pat. No. Des. 340,863; Nov. 2, 1993 Richardson et al, Pat. No. Des. 386,682; Nov. 25, 1997 Gurry et al, Pat. No. Des. 388,326; Dec. 30, 1997 Randall, Pat. No. Des. 400,785; Nov. 10, 1998 Seibel, U.S. Pat. No. 5,904,388; May 18, 1999 DiMeo et al, Pat. No. Des. 417,393; Dec. 7, 1999 LeRoux, Pat. No. D441,653; May 8, 2001 LeRoux, Pat. No, D483,668; Dec. 16, 2003
[0035] A number of patents that the applicant has studied and that he found relevant to his application are:
[0000]
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Kempshall
257,721
May 9, 1882
# 2
Turner
270,917
Jan. 23, 1883
# 3
Bridwell
399,180
Mar. 5, 1889
# 4
Pusey
609,946
Aug. 30, 1898
# 5
Nakamura
1,564,101
Jun. 18, 1925
# 6
Griffin
1,572,006
Jan. 26, 1924
# 7
Worth
1,618,854
Jun. 18, 1925
# 8
Wolf
1,675,439
Oct. 15, 1923
# 9
Poyer
2,023,098
Jun. 14, 1934
# 10
Becklin
2,041,691
May 11, 1934
# 11
Crary
2,122,025
Feb. 1, 1937
# 12
Crary
2,215,116
May 24, 1937
# 13
Santa Maria et al
2,287,329
May 9, 1941
# 14
Goza
2,394,050
Feb. 5, 1946
# 15
Elliott
2,444,558
Jul. 6, 1948
# 16
Laus
2,448,894
Jul. 2, 1947
# 17
Elliott
2,506,781
Jun. 25, 1948
# 18
Herbert et al
2,519,186
Apr. 12, 1949
# 19
Schulte
2,684,797
Jul. 27, 1954
# 20
Taipale
2,717,411
Mar. 19, 1954
# 21
Poryle
2,778,555
Jan. 22, 1957
# 22
Charlick
2,846,714
May 14, 1956
# 23
Dills
3,149,367
Dec. 4, 1962
# 24
Wilson
3,207,397
Dec. 9, 1963
# 25
Stauffer
3,800,361
Apr. 2, 1974
# 26
Franges
3,912,140
Oct. 14, 1975
# 27
Richards et al
3,913,172
Oct. 21, 1975
# 28
Olivier
4,004,722
Jan. 25, 1977
# 29
Taylor et al
4,420,178
Dec. 13, 1983
# 30
Enersen
4,590,640
May 27, 1986
# 31
Kroll
4,621,855
Nov. 11, 1986
# 32
Holem
4,657,295
Apr. 14, 1987
# 33
Parry et al
4,772,059
Sep. 20, 1988
# 34
Rimland
4,796,940
Jan. 10, 1989
# 35
Fink
4,841,596
Jan. 27, 1989
# 36
Leonard
4,846,519
Jul. 11, 1989
# 37
Schulten
4,890,355
Jan. 2, 1990
# 38
Nabakht
4,902,060
Feb. 20, 1990
# 39
Sweeny
4,932,702
Jun. 12, 1990
# 40
Rutens
4,991,894
Feb. 12, 1991
# 41
Lunsford
5,005,891
Apr. 9, 1991
# 42
Dieterich Jr.
5,029,926
Jul. 9, 1991
# 43
Phillips
5,060,998
Oct. 29, 1991
# 44
Montoya
5,181,757
Jan. 26, 1993
# 45
Howell
5,199,758
Apr. 6, 1993
# 46
Torres
5,356,190
Oct. 18, 1994
# 47
Bartocci
5,364,148
Nov. 15, 1994
# 48
Normann
5,368,393
Nov. 29, 1994
# 49
Roberts
5,411,307
May 2, 1995
# 50
Du Buisson
5,433,494
Jul. 18, 1995
# 51
Goddard
5,441,323
Aug. 15, 1995
# 52
Bourgeois et al
5,487,582
Jan. 30, 1996
# 53
Randels
5,527,076
Jun. 18, 1996
# 54
Van Davelaar
5,599,052
Feb. 4, 1997
# 55
Marley et al
5,615,921
Apr. 1, 1997
# 56
Kosteniuk
5,645,306
Jul. 8, 1997
# 57
Bystrom et al
5,651,575
Jul. 29, 1997
# 58
Franko
5,658,029
Aug. 19, 1997
# 59
Giocanti
5,667,266
Sep. 16, 1997
# 60
Robinson Sr. et al
5,697,661
Dec. 16, 1997
# 61
Fan
5,738,401
Apr. 14, 1998
# 62
Tipp
5,775,757
Jul. 7, 1998
# 63
Lisbon
5,803,522
Sep. 8, 1998
# 64
Harper
5,855,403
Jan. 5, 1999
# 65
Good
5,881,432
Mar. 16, 1999
# 66
Brown
5,894,972
Apr. 20, 1999
# 67
Seibel
5,904,388
May 18, 1999
# 68
LeRoux
5,992,803
Nov. 30, 1999
# 69
Moses
6,045,019
Apr. 4, 2000
# 70
Leonardi
6,049,948
Apr. 18, 2000
# 71
Lyon
6,247,739
Jun. 19, 2001
# 72
Miller Jr.
6,347,822
Feb. 19, 2002
# 73
Bozlee
6,354,645
Mar. 12, 2002
# 74
Greenlee
6,378,925
Apr. 30, 2002
# 75
Oien
6,395,319
May 28, 2002
# 76
Wickson
6,623,056
Sep. 23, 2003
# 77
Flynn
6,499,781
Dec. 31, 2002
# 78
Graham
6,824,182
Nov. 30, 2004
# 79
Scholes
7,024,730
Apr. 11, 2006
# 80
Hajianpour
7,125,061
Oct. 24, 2006
# 81
Orefice
7,232,168
Jun. 19, 2007
# 82
Palmer
7,302,735
Dec. 4, 2007
# 83
Sharpe
7,387,324
Jun. 17, 2008
# 84
Miano
Des. 137,712
Apr. 18, 1944
# 85
Marshall
Des. 266,488
Oct. 12, 1982
# 86
Gagnon
Des. 269,253
Jun. 7, 1983
# 87
O'Neill
Des. 305,297
Jan. 2, 1990
# 88
Preciutti
Des. 314,150
Jan. 29, 1991
# 89
Cloonan et al
Des. 318,213
Jul. 16, 1991
# 90
Clark
Des. 319,569
Sep. 3, 1991
# 91
Blocker et al
Des. 323,968
Feb. 18, 1992
# 92
Sweeny
Des. 325,156
Apr. 7, 1992
# 93
Montoya
Des. 325,169
Apr. 7, 1992
# 94
Schuttinga
Des. 329,973
Oct. 6, 1992
# 95
Fleming
Des. 332,918
Feb. 2, 1993
# 96
Oden
Des. 337,053
Jul. 6, 1993
# 97
Daigle
Des. 340,863
Nov. 2, 1993
# 98
Kennedy et al
Des. 359,235
Jun. 13, 1995
# 99
Meyers et al
Des. 362,181
Sep. 12, 1995
# 100
Muchnick
Des. 363,664
Oct. 31, 1995
# 101
Halpin et al
Des. 367,817
Mar. 12, 1996
# 102
Kitazaki
Des. 369,745
May 14, 1996
# 103
Kirkwood
Des. 372,425
Aug. 6, 1996
# 104
Stowell et al
Des. 372,865
Aug. 20, 1996
# 105
Salazar Jr.
Des. 374,621
Oct. 15, 1996
# 106
Hepworth
Des. 384,279
Sep. 30, 1997
# 107
Risser
Des. 385,788
Nov. 4, 1997
# 108
Richardson et al
Des. 386,682
Nov. 25, 1997
# 109
Gurry et al
Des. 388,326
Dec. 30, 1997
# 110
Henderson
Des. 394,351
May 19, 1998
# 111
Randall
Des. 400,785
Nov. 10, 1998
# 112
Ball
Des. 404,645
Jan. 20, 1999
# 113
Selig et al
Des. 411,093
Jun. 15, 1999
# 114
DiMeo
Des. 417,393
Dec. 7, 1999
# 115
Le Roux
Des. 423,348
Apr. 25, 2000
# 116
Lademann, III
Des. 429,454
Aug. 15, 2000
# 117
Folmar
Des. 430,029
Aug. 29, 2000
# 118
Manseau et al
D436,036
Jan. 9, 2001
# 119
Ellers
D440,492
Apr. 17, 2001
# 120
Le Roux
D441,653
May 8, 2001
# 121
Bozlee
D442,085
May 15, 2001
# 122
Pruitt et al
D442,487
May 22, 2001
# 123
Quintana
D446,652
Aug. 21, 2001
# 124
Nakagawa
D447,947
Sep. 18, 2001
# 125
Bargsten et al
D448,992
Oct. 9, 2001
# 126
Lalande
D456,264
Apr. 30, 2002
# 127
Foster
D458,120
Jun. 4, 2002
# 128
Ronne et al
D458,130
Jun. 4, 2002
# 129
Taylor
D467,498
Dec. 24, 2002
# 130
Putnam
D480,645
Oct. 14, 2003
# 131
Le Roux
D483,668
Dec. 16, 2003
# 132
Baum
D528,413
Sep. 19, 2006
# 133
Palmer
D528,414
Sep. 19, 2006
# 134
Williamson
D566,546
Apr. 15, 2008
# 135
Novakovich et al
D567,648
Apr. 29, 2008
# 136
Puerta
D624,411
Sep. 28, 2010
BRIEF SUMMARY OF THE INVENTION
[0036] In accordance with the present invention my mini bag holder and bag closure combination for plastic shopping bags has the following attributes: light, strong, ultra compact, durable, cheap to produce, made from a renewable source, able to take advertising, able to keep the bag closed when put down on a flat surface, able to be produced easily in different colors, able to take several bags at a time, taking the load in a central position so that it extends from the arm and therefore the load becomes easier to carry and small enough that it will fit in a shirt pocket or a small purse.
[0037] Accordingly several objects and advantages of my invention are:
(a) to provide a bag holder that is compact measuring not more than 10 cm in length and not more than 2 cm in diameter; (b) to provide a bag holder that is light, weighing only approximate 16 gram when made out of dry wood; (c) to provide a bag holder that is strong and able to carry loads in excess of 40 pounds (d) to provide a bag holder that is durable and will serve for many years; (e) to provide a bag holder that is user-friendly; (f) to provide a bag holder made from a renewable source like pine timber; (g) to provide a bag holder that can be produced from many other materials like recycled plastic; (h) to provide a bag holder that is cheap to manufacture; (i) to provide a bag holder that holds a bag closed to prevent the content from spilling when placed on a flat surface; (j) to provide a bag holder that can take several bags like up to 4 or 5 at a time; (k) to provide a bag holder that lays pleasant in the hand; (l) to provide a bag holder that is so designed that the centre of the load becomes like an extension of the arm making it easier to carry a load; (m) to provide a bag holder that can take a logo or advertising; (n) to provide a bag holder that can be produced in a natural timber look or in any other desired color; (o) to provide a bag holder that has no moving parts; (p) to provide a bag holder that can be of benefit to countless people, especially those that lack the luxury of a car; (q) to provide a bag holder that is so small that shoppers can easily take along two bag holders when shopping, allowing for shopping bags to be carried and balanced in two hands; (r) to provide a bag holder that is so small that a person can hold two bag holders in one hand if a free hand is needed for example when unlocking a car or when boarding a bus; (s) to provide a bag holder that can be ‘hung’ of an arm when two free hands are needed; (t) to provide a bag holder that, when made from timber, is not likely to cause sweating of the hand when carrying it in warm weather; (u) to provide a bag holder that is cheap to distribute; (v) to provide a bag holder that requires a minimum amount of packaging; (w) to provide a bag holder that can be sold in pairs in a little pouch/key ring avoiding altogether the need for individual packaging material; (x) to provide a bag holder that is innovative and attractive.
[0062] Still further objects and advantages will become apparent from a consideration of the ensuing description and drawing.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0063] In the drawings closely related figures have the same number but different alphabetical suffixes.
Page 1/7
[0064] FIG. 25 shows a front elevation of cylindrical body with a length of approximate 10 cm and a diameter of approximate 2 cm ( FIG. 25A ) that forms the basic structure of all embodiments in this patent application.
Page 2/7
[0065] FIG. 1 shows a bag holder with 1 aperture (perspective)
[0066] FIG. 2 shows a bag holder with 2 apertures (perspective)
[0067] FIG. 3 shows a bag holder with 3 apertures (perspective)
[0068] FIG. 4 shows a bag holder with 2 apertures and 1 groove (perspective)
Page 3/7
[0069] FIG. 2A shows a bag holder with 2 apertures (perspective)
[0070] FIG. 2B shows a bag holder with 2 apertures (perspective)
[0071] FIG. 2C shows part of a shopping bag attached to a bag holder with 2 apertures (perspective)
[0072] FIG. 2D shows part of an integrally formed loop handle of a shopping bag being attached to or being removed from a bag holder with 2 apertures (perspective)
Page 4/7
[0073] FIG. 2E shows part of a shopping bag attached to a bag holder with 2 apertures being carried in a hand and showing the integrally formed loop handles of the shopping bag exiting from between the fingers of the hand being a vital feature that enables the compact design of the bag holder (perspective)
Page 5/7
[0074] FIG. 5A shows a bag holder with 2 vertical cuts (top plan)
[0075] FIG. 5 shows a bag holder with 2 vertical cuts (perspective)
[0076] FIG. 6 shows a bag holder with 2 vertical cuts and 1 aperture (perspective)
[0077] FIG. 7 shows a bag holder with 2 vertical cuts and 1 groove (perspective)
[0078] FIG. 5B shows part of a shopping bag attached to a bag holder with 2 (perspective) vertical cuts being carried in a hand and showing the integrally formed loop handles of the shopping bag firmly held in place as they exit from between the fingers of the hand being a vital feature that enables the compact design of the bag holder (perspective)
Page 6/7
[0079] FIG. 8 shows a bag holder with 1 vertical groove (perspective)
[0080] FIG. 9 shows a bag holder with 2 vertical grooves (perspective)
[0081] FIG. 10 shows a bag holder with 3 vertical grooves (perspective)
Page 7/7
[0082] FIG. 10A and FIG. 10B show how to make a simple knot to attach a shopping bag to a bag holder with one or more grooves when the requirement exists for the bag to remain closed when put down on a flat surface (perspective)
NUMERALS IN DRAWINGS
[0000]
11 Body of a bag holder with one aperture
12 Body of a bag holder with two apertures
13 Body of a bag holder with three apertures
14 Body of a bag holder with two apertures and one groove
15 Body of a bag holder with two cuts
16 Body of a bag holder with two cuts and one aperture
17 Body of a bag holder with two cuts and one groove
18 Body of a bag holder with one groove
19 Body of a bag holder with two grooves
20 Body of a bag holder with three grooves
21 Oval aperture
22 Round aperture
23 Groove
24 Cut
DETAILED DESCRIPTION OF THE INVENTION
[0097] It will be readily understood that the lay-out of my bag holder as generally described and illustrated in the drawings herein, could be arranged and designed in a wide variety of different configurations. Thus the following more detailed description of the bag holder, the different configurations of the bag holder and methods of attaching and carrying bags as represented in the drawings, is not intended to limit the scope of the invention but is merely representative of the bag holder.
[0098] A preferred embodiment of the bag holder is illustrated in FIG. 2 on drawing page 2/7, FIG. 2A , in FIG. 2B , FIG. 2C and FIG. 2D on drawing page 2/7 and in FIG. 2E on drawing page 3/6. The bag holder comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises two oval shaped apertures of approximate 1.5 cm long and 1 cm wide perpendicular to the length of the bag holder in the centre of the cylindrical shaped body leaving 0.5 cm material on either side of the apertures with the edges of the apertures being rounded and with the centers of both apertures being at a distance of 2.5 cm from both outer ends of the bag holder.
[0099] A second additional embodiment of the bag holder of the present invention is illustrated in FIG. 1 on drawing page 2/7. The bag holder comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and having one oval shaped aperture of approximate 1.5 cm long and 1 cm wide perpendicular to the length of the bag holder in the centre of the cylindrical shaped body leaving 0.5 cm material on either side of the aperture with the edges of the aperture being rounded and having a distance from the centre of the aperture to both outer ends of the bag holder of 5 cm.
[0100] A third additional embodiment for this bag holder is illustrated in FIG. 3 on drawing page 2/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises three apertures with a diameter of approximate 1 cm perpendicular to the length of the bag holder in the centre of the cylindrical shaped body leaving 0.5 cm material on either side of the apertures and the edges of the apertures being rounded. The centers of the three apertures are at a distance of 2.5 cm from each other and the centers of the two outer apertures have a distance of 2.5 cm to both outer ends of the bag holder.
[0101] A fourth additional embodiment for this bag holder is illustrated in FIG. 4 on drawing page 2/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises two oval apertures of approximate 1.5 cm long and 1 cm wide perpendicular to the length of the bag holder in the centre of the cylindrical shaped body leaving 0.5 cm material on either side of the aperture and the edges of the apertures being rounded. The centers of both apertures are at a distance of 2.5 cm from both outer ends of the bag holder. In addition the bag holder comprises one groove of approximate 1 cm wide and 0.2 cm deep in the middle of the bag holder with the two edges of the groove being rounded and with the running direction of the groove being around the bag holder like a ring around a finger.
[0102] A fifth additional embodiment for this bag holder is illustrated in FIG. 5 , FIG. 5A and FIG. 5B on drawing page 5/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body.
[0103] A sixth additional embodiment for this bag holder is illustrated in FIG. 6 on drawing page 5/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body and further comprises one aperture with a diameter of approximate 1 cm perpendicular to the length of the bag holder in the centre of the cylindrical shaped body leaving 0.5 cm material on either side of the aperture with the edges of the aperture being rounded and having a distance from the centre of the aperture to both outer ends of the bag holder of 5 cm.
[0104] A seventh additional embodiment for this bag holder is illustrated in FIG. 7 on drawing page 5/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body and in addition the bag holder comprises one groove of approximate 1 cm wide and 0.2 cm deep in the middle of the bag holder with the two edges of the groove being rounded and with the running direction of the groove being around the bag holder like a ring around a finger.
[0105] An eighth additional embodiment for this bag holder is illustrated in FIG. 8 on drawing page 6/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises one groove of approximate 1 cm wide and 0.2 cm deep in the middle of the bag holder with the two edges of the groove being rounded and with the running direction of the groove being around the bag holder like a ring around a finger.
[0106] An ninth additional embodiment for this bag holder is illustrated in FIG. 9 on drawing page 6/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises two grooves of approximate 1 cm wide and 0.2 cm deep with the two edges of each groove being rounded and with the running direction of the grooves being around the bag holder like a ring around a finger, the centre of both grooves being 2.5 cm from both the ends of the cylindrical shaped body.
[0107] A tenth additional embodiment for this bag holder is illustrated in FIG. 10 on drawing page 6/7 and comprises a rigid cylindrical shaped body with a length of approximate 10 cm and a diameter of approximate 2 cm and further comprises three grooves of approximate 1 cm wide and 0.2 cm deep with the two edges of each groove being rounded and with the running direction of the grooves being around the bag holder like a ring around a finger, the centre of two grooves being 2.5 cm from both the ends of the cylindrical shaped body and the third groove being in the middle of the bag holder.
[0108] From the description above, a number of advantages of my shopping bag holder become evident:
(a) It is cheap to construct. (b) It may be manufactured in a variety of materials. (c) It may be manufactured in a variety of colors. (d) It may be manufactured in a variety of shapes, like round, half round or oval. (e) It may be manufactured in a variety of other dimensions, like 11 cm or 12 cm long. (f) It may be manufactured in a variety of diameters, like 2.5 cm or 3 cm diameter. (g) It may be manufactured in a variety of models to cater for individual needs
Process of Using the Invention
[0116] The preferred embodiment of the bag holder as illustrated in FIG. 2 on drawing page 2/7, FIG. 2A , FIG. 2B , FIG. 2C and FIG. 2D on drawing page 3/7 and in FIG. 2E on drawing page 4/7 comprises a rigid cylindrical shaped body with two apertures. The procedure to attach shopping bags to the bag holder is as described bellow.
1 Firstly feed one integrally formed loop handle of a shopping bag through one aperture of the bag holder as shown in FIG. 2D on drawing page 3/7. 2 Secondly pull the integrally formed loop handle of the shopping bag up and in an open spread position around the end of the bag holder so that the end comes to rest below the bag holder as shown in FIG. 2D on drawing page 3/7. 3 Pull the shopping bag firmly down to secure the shopping bag to the bag holder. 4 Repeat this procedure for the second integrally formed loop handle of the shopping bag using the second aperture of the bag holder with the result showing in FIG. 2C on drawing page 3/7 and FIG. 2E on drawing page 4/7.
[0121] Any bag thus attached will be firmly secured to the bag holder and will not detach itself from it even when put down, held upside down or tossed around.
[0122] If keeping the bag closed is not a requirement when just walking a short distance, one can simply hang a few bags over the bag holder, especially over the recessed area where the apertures are, and carry the bags using the bag holder.
[0123] A second additional embodiment of the bag holder of the present invention as illustrated in FIG. 1 on drawing page 2/7 comprises a rigid cylindrical shaped body with one aperture. One can attach one or two bags to the bag holder by feeding all integrally formed loop handles through the one aperture and pulling all handles in open spread position over and around one end of the bag holder and securing the bags by pulling the bags down. If keeping the bag closed is not a requirement when just walking a short distance, one can simply hang one or more bags over the recessed area where the aperture is, and carry the bag(s) using the bag holder.
[0124] A third additional embodiment for this bag holder as illustrated in FIG. 3 on drawing page 2/7 comprises a rigid cylindrical shaped body with three apertures. If one expects to require more than say three shopping bags, one can attach one or two bags first to the bag holder by feeding all integrally formed loop handles through the middle aperture and pulling all handles in open spread position over and around one end of the bag holder and secure the bags by pulling the bags down. After that, one can proceed by attaching more bags to the bag holder as described above in the 4 steps for attaching bags to the preferred embodiment of the bag holder as illustrated in FIG. 2D and FIG. 2C on drawing page 3/7.
[0125] A fourth additional embodiment for this bag holder as illustrated in FIG. 4 on drawing page 2/7 comprises a rigid cylindrical shaped body with two apertures and one groove in the middle of the bag holder.
[0000] Firstly one can simply hang one or more bags in the groove of the bag holder.
[0126] The bag or bags will be held in place as their handles are held between the middle finger and the ring finger of the hand.
[0000] Secondly one can secure shopping bags to the bag holder in the following way: Take a shopping bag in the left hand and the integrally formed loop handles of the shopping bag in the right hand. Push thumb and index finger through the opening of the loop handles of the shopping bag and push thumb and index finger apart as shown in FIG. 10A on drawing page 7/7. Now surrounding the loop handles of the shopping bag close the thumb and index finger until they touch. Hold firmly and pull the straps up a bit and past the point where they have the appearance of the handle of a pair of scissors and create a double loop opening as shown in FIG. 10B on drawing page 7/7 and insert the bag holder into this opening with the double loop opening surrounding the middle of the bag holder. Pull the bag down till firmly settled in the groove of the bag holder. Further bags can be attached to the bag holder as described above in the 4 steps for attaching bags to the preferred embodiment of the bag holder as illustrated in FIG. 2D and FIG. 2C on drawing page 3/7.
[0127] A fifth additional embodiment for this bag holder as illustrated in FIG. 5 , FIG. 5A and FIG. 5B on drawing page 5/7 comprises a rigid cylindrical shaped body with a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body. To attach shopping bags to the bag holder simply lead the handles of one or more bags through both the cuts of the bag holder. The cuts being 2.5 cm deep will cause the handles to settle at that distance of 2.5 cm from both ends of the bag holder and when carried, the handles of the shopping bag(s) will be securely held between the index finger and middle finger and between middle finger and ring finger of the hand carrying the bag holder as shown in FIG. 5B on drawing page 5/7.
[0128] A sixth additional embodiment for this bag holder as illustrated in FIG. 6 on drawing page 5/7 comprises a rigid cylindrical shaped body with a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body as well as one aperture in the middle of the bag holder. Firstly one can attach one or two bags to the bag holder as described in the instructions of the third embodiment. Further bags can be attached to the bag holder as described in the instructions for the fifth embodiment as shown in FIG. 5B on drawing page 5/7.
[0129] A seventh additional embodiment for this bag holder as illustrated in FIG. 7 on drawing page 5/7 comprises a rigid cylindrical shaped body with a vertical cut of approximate 2.5 cm deep and 0.5 cm wide at both ends in the centre of the cylindrical shaped body as well as one groove in the middle of the bag holder. To attach one or more bags utilizing the groove of the bag holder proceed as described in both instructions for embodiment four and to attach one or more bags utilizing the cuts of the bag holder proceed as described in the instructions for the fifth embodiment.
[0130] An eighth additional embodiment for this bag holder as illustrated in FIG. 8 on drawing page 6/7 comprises a rigid cylindrical shaped body with one groove in the middle of the bag holder. To attach one or more bags utilizing the groove of the bag holder proceed as described in both instructions for embodiment four.
[0131] A ninth additional embodiment for this bag holder as illustrated in FIG. 9 on drawing page 6/7 comprises a rigid cylindrical shaped body with two grooves 2.5 cm from both the ends of the cylindrical shaped body. To attach one or more bags utilizing the grooves of the bag holder proceed as described in both instructions for embodiment four.
[0132] A tenth additional embodiment for this bag holder as illustrated in FIG. 10 on drawing page 6/7 comprises a rigid cylindrical shaped body with three grooves having one groove 2.5 cm from both the ends of the cylindrical shaped body and the third groove being in the middle of the bag holder. To attach one or more bags utilizing the grooves of the bag holder proceed as described in both instructions for embodiment four. | An ultra compact, lightweight, sturdy bag holder that comprises an elongated shaped body of rigid material having a predetermined cross-sectional shape and strength that can easily be carried in the palm of ones' hand (FIG. 25 ; FIG. 25 A). The bag holder further comprises a predetermined number of apertures (FIG. 1/21 ; FIG. 2/21 , FIG. 3/22 ) or a predetermined number of grooves (FIG. 8/23 ; FIG. 9/23 ; FIG. 10/23 ) or a vertical cut at either end of the bag holder (FIG. 5/24 ) or a combination of two apertures (FIG. 4/21 ) and one groove (FIG. 4/23 ), or one aperture (FIG. 6/22 ) and two cuts (FIG. 6/24 ) or one groove (FIG. 7/23 ) and two cuts (FIG. 7/24 ). The aperture(s), cuts and groove(s) are designed to allow the integrally formed loop handle of shopping bags to be attached to the bag holder and depending on the configuration of the bag holder to keep the shopping bag closed and to prevent the content from spilling when placed on a flat surface. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
This application is the U.S. National Phase of PCT Appln. No. PCT/EP2013/072096 filed Oct. 22, 2013, which claims priority to German Application No. 10 2012 220 954.9 filed Nov. 16, 2012, the disclosures of which are incorporated in their entirety by reference herein.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a product formulation based on silicone elastomer compositions for the temporary adhesive bonding to a carrier substrate of a workpiece that is to be ground or polished, wherein the silicone elastomer composition is grindable or polishable after curing.
2. Description of the Related Art
The expression “temporary adhesive bonding” refers to the joining of two substrates which are to be detached again at a suitable point in time. Workpieces may have to be fixed mechanically for a grinding operation. In the case of high-priced workpieces for example, gemstones, optical lenses, works of art or semiconductor wafers, this often causes damage to the workpiece, or the fixing does not have the desired stability. There is therefore a need for alternative fastening methods. One possibility consists in fixing the workpiece by means of temporary adhesive bonding. Because it is unavoidable in the operation of grinding or polishing that the grinding device may also come into contact with the adhesive, the adhesive must also be grindable since it would otherwise lead, for example, to material failures or contamination or damage to the grinding apparatus. In addition, good temperature resistance to over 300° C. is necessary to withstand the friction, and thus the temperature increase, caused by the grinding or polishing. Temperature resistance is additionally necessary because subsequent processing steps carried out on the workpiece can take place in a high temperature range. Chemical resistance is also an important property for such an adhesive, such as resistance to cleaning chemicals. Current market requirements for semiconductor components are directed to ever smaller overall heights. One possibility for reducing the overall height of a molded component such as a chip is to thin the wafer that is used. This is effected by a grinding operation and can be carried out before or after dicing.
However, this step leads to a reduction in the structural strength of the wafer. As a result, the large, thin wafers can break during processing by means of the devices and materials that are conventionally used, such as the dicing tapes that are employed today, owing to a lack of mechanical support. In addition, the wafer structures (bumps) which protrude by up to 100 μm or more may in some cases not be enclosed completely or include voids caused by the tapes (adhesive films) that are used today, so that the voids that remain generally lead to damage or impairment of the thin wafer during processing in vacuo. A possible process-related solution to this problem is to bond the wafer to a hard substrate (for example to another wafer or a wafer carrier, for example glass) by means of a temporary adhesive layer, in order to increase its mechanical strength, then carry out the desired processing operations, and subsequently detach the wafer, which is then only 10-100 μm thick, from the substrate again. The substrate attached by means of the temporary adhesive layer serves as a mechanical reinforcement during the grinding operation and subsequent processing operations.
The later post-processing of the thinned wafer also includes the creation of resist structures by plasma etching and operations such as metal plating and the cleaning of residues.
Further important aspects are the minimal release of volatile by-products and the viscosity of the uncrosslinked silicone elastomer composition, in order, for example, to minimize the risk of contamination and health risks, and to permit suitable application to the workpiece. In addition, it must be possible after grinding or polishing to detach the adhesive from the workpiece simply, leaving as little residue as possible.
In the semiconductor industry there is, therefore, a need for an adhesive for a temporary wafer bonding process, the properties of which allow the wafer to be processed without breaking or being damaged. The adhesive must be suitable for application by an industrially viable process (for example spray coating, printing, dipping, spin coating) and must be able to be detached from the wafer at the desired point in time by suitable processes without leaving a residue.
The necessary fastening of the supporting substrate to the wafer prior to thinning could ideally be effected by thermoplastic or elastic polymers, whereby the front structures of the wafer must be enclosed in a supporting manner.
Several possibilities for temporary adhesive bonding to a carrier are described in the prior art, but they have various disadvantages.
One possibility of fixing the semiconductor wafer to a carrier is provided by so-called “adhesive tapes”. EP 0838086 B1 describes a tape made of a thermoplastic elastomer block copolymer for use in the processing of semiconductor wafers. However, the limited elasticity of the material leads to problems with the use of wafers having surface structures (“bumped wafers”). The thermoplastic properties of the material additionally lead to reduced heat stability. This is an important requirement, however, for the back-side operations (plasma processes, CVD, etc.) that follow the thinning of the wafer (“back-side grinding”).
WO 2009/003029 A2 claims thermoplastic organic polymers (imides, amideimides and amideimide-siloxanes) for use as a temporary adhesive between a wafer and a carrier. WO 2009/094558 A2 describes the temporary adhesive bonding of a wafer and a carrier, wherein the adhesive bonding does not take place over the entire surface but only in the edge region. When the grinding process and any back-side operations have been carried out, the adhesive bond is destroyed chemically, photochemically, thermally or thermo-mechanically. EP0603514 A2 describes a method for thinning a semiconductor wafer, wherein the adhesive material used is suitable for a maximum of 200° C. In US application US2004/0121618 A1, a liquid adhesive suitable for spin-coating processes is described which consists of a thermoplastic polyurethane as well as dimethylacetamide and propylene glycol monomethyl ether as the main components. All these proposals have the disadvantage of reduced heat stability of the cured adhesive.
EP1089326 B1 claims a carrier for wafers which consists of a silicone elastomer covered with a dust-tight film, wherein the separating force between the film and the silicone layer is from 5 to 500 g/25 mm (according to JIS K 6854). The disadvantage is that this film must be removed in an additional process step before the carrier is used, so that the adhesive is accessible.
SUMMARY OF THE INVENTION
An object of the present application was, therefore, to provide a suitable adhesive for the reversible fixing of workpieces, which is grindable or polishable after curing and is resistant to heat and chemicals. In addition, the adhesive must be able to be applied with a minimal number of simple process steps, and to be removed from the workpiece again without difficulty, without damaging or contaminating the workpiece or the grinding or polishing device. A further object was to provide an adhesive with good mechanical strength towards compressive stress, which is particularly important when adhesively bonded thin workpieces are subject to compressive stress over a small area.
These and other objects have been achieved, surprisingly, by an addition-crosslinkable silicone elastomer compositions, comprising
(A1) 1-10% by weight of at least one linear organopolysiloxane containing at least 2 SiC-bonded radicals having aliphatic carbon-carbon multiple bonds, wherein the mean molar mass of (A1) is not more than 15,000 g/mol,
(A2) 1-20% by weight of at least one linear organopolysiloxane containing at least 2 SiC-bonded radicals having aliphatic carbon-carbon multiple bonds, wherein the mean molar mass of (A2) is at least 40,000 g/mol,
(B) 1-40% by weight of at least one organopolysiloxane containing at least three Si-bonded hydrogen atoms per molecule, having a content of Si-bonded hydrogen of from 0.04 to 1.7% by weight and a mean molar mass of not more than 20,000 g/mol,
(D) 1-100 ppm (based on the metal) of a hydrosilylation catalyst,
(E) 50-99% by weight of at least one branched silicone resin of the general empirical formula (I)
(R 3 3 SiO 1/2 ) l (R 4 R 3 2 SiO 1/2 ) t (R 4 R 3 SiO) u (R 3 2 SiO) p (R 4 SiO 3/2 ) q (R 3 SiO 3/2 ) r (SiO 4/2 ) s (I),
wherein
R 3 denotes a linear aliphatic radical,
R 4 denotes an aliphatic unsaturated radical having a terminal
C═C double bond,
l, t, u, p, q, r and s denote integers,
wherein the following apply:
l≧0, t≧0, u≧0, p≧0, q≧0, r≧0 and s≧0; and
the content of aliphatic unsaturated groups in (E) is between
0.2 and 10 mmol/g; and
(E) has a mean molar mass of not more than 10 5 g/mol,
with the proviso that the ratio of the Si—H groups provided by component (B) to the aliphatically unsaturated groups provided by components (A1), (A2) and (E) is between 0.5 and 5 and the ratio of the dynamic viscosity of the silicone elastomer composition at shear rates of 1 s −1 and 100 s −1 and a temperature of 20° C. is not more than 1.2 and after crosslinking has a Shore D hardness of at least 25.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The silicone elastomer compositions according to the invention can be applied to the substrates by conventional industrial processes (for example spray coating, printing, dipping, spin coating).
They further exhibit approximately Newtonian flow behavior with low shear thinning (no gel state at zero shear), in order to ensure the application of a uniform layer thickness over the entire wafer or substrate. The silicone elastomer compositions according to the invention have a ratio of dynamic viscosity at shear rates of 1 s −1 and 100 s −1 at 20° C. of not more than 1.2; preferably not more than 1.1; particularly preferably not more than 1.05. The dynamic viscosity of the silicone elastomer compositions at 20° C. and a shear rate of 1 s −1 is between 10 and 20,000 mPa·s, preferably between 50 and 10,000 mPa·s and most preferably between 500 and 5000 mPa·s.
The silicone elastomer compositions according to the invention have very low contents of volatile constituents, in order to prevent contamination and blistering during processing, even in vacuo and with the simultaneous action of heat. The difference in mass of the cured silicone rubber between room temperature and 300° C. in a thermogravimetric analysis (TGA), at a rate of heating of 10 K/min to 300° C. and under an air or nitrogen stream of 30 ml/min, is not more than 2% by weight, preferably not more than 1% by weight and most preferably not more than 0.5% by weight. They further exhibit low rates of subsequent formation of volatile constituents.
The silicone rubber according to the invention is prepared after application by crosslinking of the silicone elastomer compositions according to the invention and forms the reversible adhesive layer between the workpiece and the substrate.
The crosslinked silicone rubber so prepared exhibits a Shore D hardness according to DIN 53505 of between 25 and 80, preferably between 25 and 75 and most preferably between 30 and 65; tear propagation resistance according to ASTM D624-B-91 of at least 2 N/mm, preferably at least 5 N/mm; elongation at break according to DIN 53504-85S1 of not more than 100%, preferably not more than 50%; and tear strength according to DIN 53504-85S1 of not more than 8 N/mm 2 , preferably not more than 5 N/mm 2 . The mechanical strength towards compressive stress is given by the flexural modulus from the 3-point flexural test. The flexural modulus according to EN ISO 178 of the silicone rubbers according to the invention is at least 30 N/mm 2 , preferably at least 50 N/mm 2 and particularly preferably at least 70 N/mm 2 .
Advantages of the silicone rubbers according to the invention are that, owing to the unusually high Shore D hardness for an elastomer and the above-mentioned mechanical values, they are grindable or polishable. The modulus of elasticity, which is increased significantly compared with other silicone elastomers, ensures that even a thin workpiece does not break or is not damaged under punctual compressive stress. The silicone rubbers according to the invention can additionally be detached from the workpiece by suitable processes at the desired point in time without leaving a residue. On separation of the bond between the wafer and the carrier, the silicone rubber layer in most cases remains complete either on the side of the carrier or on the side of the wafer. Removal of the silicone rubber layer can be carried out, for example, with the aid of an adhesive tape, whereby the silicone rubber layer, after contact with the adhesive tape, is detached from the wafer or carrier surface with the adhesive tape. In an alternative process, the silicone rubber layer can be removed with the aid of suitable solvents and depolymerization agents known in the prior art.
The silicone rubbers according to the invention have high temperature stability, >250° C. over several hours and, at peaks, up to >300°. Under a temperature load of 250° C. over a period of one hour, the mechanical properties change only minimally. An increase in the Shore hardness of a maximum of 5 points, preferably a maximum of 3 points and most preferably a maximum of 2 points is observed. The elongation at break is lower by a maximum of 5%, preferably by a maximum of 3%, and the tear strength falls by a maximum of 5 N/mm 2 , preferably by a maximum of 3 N/mm 2 and most preferably by a maximum of 1 N/mm 2 . The tear propagation resistance falls by a maximum of 3 N/mm, preferably by a maximum of 2 N/mm and most preferably by a maximum of 1 N/mm. The flexural modulus changes by a maximum of 10%, preferably by a maximum of 5%.
The crosslinkable silicone elastomer compositions according to the invention have the advantage that they can be prepared in a simple process using readily available starting materials, and can thus be prepared economically. In addition, as a one-component formulation, they have good storage stability at 25° C. and ambient pressure and crosslink rapidly only at elevated temperature. The silicone compositions according to the invention have the advantage that, in a two-component formulation, after mixing of the two components, they yield a crosslinkable silicone composition, the processability of which is retained over a long period of time at 25° C. and ambient pressure. Accordingly, they exhibit extremely long pot lives and crosslink rapidly only at elevated temperature.
Formulating the silicone compositions according to the invention as a two-component formulation has the advantage that higher crosslinking speeds can be achieved compared with one-component compositions, which can lead to shorter processing times during production.
The use of the silicone elastomer compositions of the invention is very varied because, as well as being used for temporary adhesive bonding, such as, for example, in wafer production, they can also be used for the production of moldings, for adhesive bonding in general, but also for optical applications. The silicone elastomer compositions of the invention can be processed by all processes known in the prior art, for example, casting, molding, extrusion, etc. The field of application extends from compositions for moldmaking applications, the production of optical moldings such as, for example, lenses, disks, light guides, through compositions for the production of thin layers or coatings, to extruded products such as hoses, profiles, etc.
The silicone elastomer compositions according to the invention further have the advantage that they have high transparency. The transmission in the wavelength range between 400 and 800 nm is >90%, preferably >95%. For this reason, these materials are suitable for all optical applications such as, for example, LED lenses or the adhesive bonding of transparent materials. They are also suitable for the adhesive bonding of non-transparent materials. In combination with the high Shore D hardness, the products produced from the compositions according to the invention are suitable for producing therefrom transparent articles or moldings which have hitherto been produced from other transparent materials such as, for example, glass, polycarbonate (PC), polystyrene, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene terephthalate glycol-modified (PETG), polymethyl methacrylate (PMMA), polyethylene (PE), polypropylene (PP), etc. The moldings so produced can additionally be after-processed, for example by grinding or polishing.
The silicone elastomer compositions according to the invention can be one-component silicone compositions as well as two-component silicone compositions. In the latter case, the two components of the compositions according to the invention can contain all the constituents in any desired combination, generally with the proviso that one component does not simultaneously comprise siloxanes having aliphatic multiple bond, siloxanes having Si-bonded hydrogen and catalyst, that is to say substantially does not simultaneously comprise constituents (A1), (A2), (B) and (D). However, the compositions according to the invention are preferably one-component compositions. The silicone elastomer compositions according to the invention, in particular the one-component composition, are prepared by mixing all the constituents according to the prior art.
Compounds (A1), (A2) and (B) used in the addition-crosslinking compositions according to the invention are so chosen such that crosslinking is possible. Thus, for example, compounds (A1) and (A2) may contain at least two aliphatically unsaturated radicals and (B) contains at least three Si-bonded hydrogen atoms, or compounds (A1 and (A2)) may contain at least three aliphatically unsaturated radicals and (B) contains at least two Si-bonded hydrogen atoms.
As organosilicon compounds (A1) and (A2) containing SiC-bonded radicals having aliphatic carbon-carbon multiple bonds, linear organopolysiloxanes comprising units of the general formula (II) are preferably used:
R a R 1 b SiO (4-a-b)/2 (II)
wherein
R are identical or different and, independently of one another, denote an organic or inorganic radical that is free of aliphatic carbon-carbon multiple bonds, R 1 are identical or different and, independently of one another, denote a monovalent, substituted or unsubstituted, SiC-bonded hydrocarbon radical having at least one aliphatic carbon-carbon multiple bond, a is 1, 2 or 3, and b is 1 or 2,
with the proviso that the sum a+b is less than or equal to 3 and at least 2 radicals R 1 are present per molecule, and
wherein the mean molar mass of (A1) is not more than 20,000 g/mol, preferably not more than 18,000 g/mol and most preferably not more than 15,000 g/mol, and
the mean molar mass of (A2) is at least 35,000 g/mol, preferably at least 40,000 g/mol and most preferably at least 45,000 g/mol.
The radical R can be mono- or polyvalent radicals, wherein the polyvalent radicals, such as, for example, divalent, trivalent and tetravalent radicals, then join together a plurality of siloxy units of formula (II), such as, for example, two, three or four siloxy units of formula (II).
Further examples of R are the monovalent radicals —F, —Cl, —Br, OR 2 , —CN, —SCN, —NCO and SiC-bonded, substituted or unsubstituted hydrocarbon radicals, which can be interrupted by oxygen atoms or the group —C(O)—, as well as divalent radicals Si-bonded on both sides according to formula (II). If the radical R is SiC-bonded, substituted hydrocarbon radicals, preferred substituents are halogen atoms, phosphorus-containing radicals, cyano radicals, —OR 2 , —NR 2 —, —NR 2 2 , —NR 2 —C(O)—NR 2 2 , —C(O)—NR 2 2 , —C(O)R 2 , —C(O)OR 2 , —SO 2 -Ph and —C 6 F 5 , wherein R 2 , which are identical or different, independently of one another denote a hydrogen atom or a monovalent hydrocarbon radical having from 1 to 20 carbon atoms and Ph is the phenyl radical.
Examples of radicals R are alkyl radicals such as the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl radicals, hexyl radicals such as the n-hexyl radical, heptyl radicals such as the n-heptyl radical, octyl radicals such as the n-octyl radical, and isooctyl radicals such as the 2,2,4-trimethylpentyl radical, nonyl radicals such as the n-nonyl radical, decyl radicals such as the n-decyl radical, dodecyl radicals such as the n-dodecyl radical, and octadecyl radicals such as the n-octadecyl radical; cycloalkyl radicals such as the cyclopentyl, cyclohexyl, cycloheptyl and methylcyclohexyl radicals; aryl radicals such as the phenyl, naphthyl, anthryl and phenanthryl radicals, alkaryl radicals such as the o-, m-, and p-tolyl radicals, xylyl radicals and ethylphenyl radicals; and aralkyl radicals such as the benzyl radical, and the α- and the β-phenylethyl radicals.
Examples of substituted radicals R are haloalkyl radicals such as the 3,3,3-trifluoro-n-propyl radical, the 2,2,2,2′,2′,2′-hexafluoroisopropyl radical, and the heptafluoroisopropyl radical; haloaryl radicals such as the o-, m- and p-chlorophenyl radicals, —(CH 2 )—N(R 2 )C(O)NR 2 2 , —(CH 2 ) n —C(O)NR 2 2 , —(CH 2 ) n —C(O)R 2 , —(CH 2 ) n —C(O)OR 2 , —(CH 2 ) n —C(O)NR 2 2 , —(CH 2 )—C(O)—(CH 2 ) m C(O)CH 3 , —(CH 2 )—O—CO—R 2 , —(CH 2 )—NR 2 —(CH 2 ) m —NR 2 2 , —(CH 2 ) n —O—(CH 2 ) m CH(OH)CH 2 OH, —(CH 2 ) n (OCH 2 CH 2 ) m OR 2 , —(CH 2 ) n —SO 2 —Ph and —(CH 2 ) n —O—C 6 F 5 , wherein R 2 and Ph have the meaning given above therefor and n and m denote identical or different integers between 0 and 10.
Examples of R as divalent radicals Si-bonded on both sides according to formula (II) are those which are derived from the monovalent examples mentioned above for the radical R in that an additional bond is obtained by substitution of a hydrogen atom: —(CH 2 )—, —CH(CH 3 )—, —C(CH 3 ) 2 —, —CH(CH 3 )—CH 2 —, —C 6 H 4 —, —CH(Ph)—CH 2 —, —C(CF 3 ) 2 —, —(CH 2 ) n —C 6 H 4 —(CH 2 ) n —, —(CH 2 ) n —C 6 H 4 —C 6 H 4 —(CH 2 ) n —, —(CH 2 O) m , (CH 2 CH 2 O) m , —(CH 2 ) n —O x —C 6 H 4 —SO 2 —C 6 H 4 —O x —(CH 2 ) n —, wherein x is 0 or 1 and Ph, m and n have the meaning given above.
The radical R is preferably a monovalent, SiC-bonded, optionally substituted hydrocarbon radical having from 1 to 18 carbon atoms that is free of aliphatic carbon-carbon multiple bonds, more preferably a monovalent, SiC-bonded hydrocarbon radical having from 1 to 6 carbon atoms that is free of aliphatic carbon-carbon multiple bonds, and in particular the methyl or phenyl radicals.
The radical R 2 can be any desired groups amenable to an addition reaction (hydrosilylation) with an SiH-functional compound. If the radical R 2 is SiC-bonded, substituted hydrocarbon radicals, preferred substituents are halogen atoms, cyano radicals and —OR 2 , wherein R 2 has the meaning given above.
The radical R 2 is preferably an alkenyl or alkynyl radical having from 2 to 16 carbon atoms, such as the vinyl, allyl, methallyl, 1-propenyl, 5-hexenyl, ethynyl, butadienyl, hexadienyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, vinylcyclohexylethyl, divinylcyclohexylethyl, norbornenyl, vinylphenyl and styryl radicals, with vinyl, allyl and hexenyl radicals most preferably being used.
As organopolysiloxanes (B) containing Si-bonded hydrogen atoms there linear organopolysiloxanes comprising units of the general formula (III) are preferably used:
R c H d SiO (4-c-d)/2 (III)
wherein
R has the meaning given above, c is 0, 1 2 or 3, and d is 0, 1 or 2,
with the proviso that the sum of c+d is less than or equal to 3 and at least two Si-bonded hydrogen atoms are present per molecule, the content of Si-bonded hydrogen is from 0.04 to 1.7% by weight, and the mean molar mass is not more than 20,000 g/mol.
Organopolysiloxane (B) preferably contains Si-bonded hydrogen in the range from 0.04 to 1.7% by weight, based on the total weight of the organopolysiloxane (B). Most preferably, component (B) contains between 0.5 and 1.7% by weight of Si-bonded hydrogen.
The mean molar mass of (B) is not more than 20,000 g/mol, more preferably not more than 10,000 g/mol.
The structure of the molecules forming constituent (B) is also not fixed; in particular, the structure of a higher molecular weight, that is to say oligomeric or polymeric, SiH-containing siloxane can be linear. Linear polysiloxanes (B) are preferably composed of units of the formula R 3 SiO 1/2 , HR 2 SiO 1/2 , HRSiO 2/2 and R 2 SiO 2/2 , wherein R has the meaning given above.
Of course, mixtures of different siloxanes that satisfy the criteria of constituent (B) can also be used. In particular, the molecules forming constituent (B), as well as containing the obligatory SiH groups, can optionally also comprise aliphatically unsaturated groups. Particular preference is given to the use of low molecular weight SiH-functional compounds such as tetrakis(dimethylsiloxy)silane and tetramethylcyclotetrasiloxane, as well as higher molecular weight, SiH-containing siloxanes, such as poly(hydrogen-methyl)siloxane and poly(dimethylhydrogenmethyl)siloxane having a viscosity at 25° C. of from 10 to 10,000 mPa·s, or analogous SiH-containing compounds in which some of the methyl groups have been replaced by 3,3,3-trifluoropropyl or phenyl groups.
Constituent (B) is preferably present in the crosslinkable silicone compositions according to the invention in an amount such that the molar ratio of SiH groups to aliphatically unsaturated groups from (A1), (A2) and (E) is between 0.5 and 5, more preferably between 0.7 and 3.
Components (A1), (A2) and (B) used according to the invention are commercial products or can be prepared by processes conventional in chemistry.
As the hydrosilylation catalyst (D), which are also referred to as catalysts for the crosslinking of addition-crosslinking silicones, there can be used all catalysts known in the art. Component (D) can be a platinum group metal, for example platinum, rhodium, ruthenium, palladium, osmium or iridium, an organometallic compound or a combination thereof. Examples of component (D) are compounds such as hexachloroplatinic(IV) acid, platinum dichloride, platinum acetylacetonate, and complexes of said compounds which are encapsulated in a matrix or a core-shell-type structure. The platinum complexes of low molecular weight of the organopolysiloxanes include 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane complexes with platinum. Further examples are platinum-phosphite complexes, platinum-phosphine complexes or alkyl-platinum complexes. These compounds can be encapsulated in a resin matrix.
The concentration of component (D) is sufficient for catalyzing the hydrosilylation reaction of components (A1), (A2), (E) and (B) on exposure. The amount of component (D) is 1-100 ppm (based on the metal), preferably between 1 and 25 ppm of the platinum group metal, according to the total weight of the components. The curing rate can be low if the constituent of the platinum group metal is less than 1 ppm. The use of more than 100 ppm of the platinum group metal is uneconomical or can reduce the stability of the composition.
Compound class (E) is understood as including branched silicone resins which, by their chemical structure, already form a three-dimensional network. They are described by the general empirical formula (I)
(R 3 3 SiO 1/2 ) l (R 4 R 2 SiO 1/2 ) t (R 4 RSiO) u (R 3 2 SiO) p (R 4 SiO 3/2 ) q (R 3 SiO 3/2 ) r (SiO 4/2 ) s (I)
wherein
R 3 denotes a linear aliphatic radical,
R 4 denotes an aliphatically unsaturated radical having a terminal C═C double bond,
l, t, u, p, q, r and s denote integers,
wherein the following apply:
l≧0, t≧0, u≧0, p≧0, q≧0, r≧0 and s≧0;
the content of aliphatically unsaturated groups in (E) is between 0.2 and 10 mmol/g.
Preferred radicals R 3 are short (C1-C4) linear aliphatic radicals, and the methyl radical is particularly preferred. Preferred radicals R 4 are short (C1-C4) linear aliphatically unsaturated radicals which have a terminal C═C double bond, the terminal vinyl radical being particularly preferred. In a preferred form, the indices are l≧0, t≧0, u=0, p=0, q≧0, r≧0 and s≧0, in a particularly preferred form the indices are l≧0, t≧0, u=0, p=0, q=0, r=0 and s≧0. The content of aliphatically unsaturated groups is preferably between 0.5 and 5 mmol/g and more preferably between 0.8 and 4 mmol/g.
The mean molar mass of this compound class (E) can vary within wide limits between 10 2 and 10 6 g/mol. Preferred mean molar masses are between 10 2 and 10 5 g/mol, and more preferred mean molar masses are between 10 3 and 5·10 4 g/mol.
The silicone elastomer compositions according to the invention can optionally comprise all further additives that have hitherto also been used in the preparation of addition-crosslinkable compositions. Examples of reinforcing fillers (F) which can be used as a component in the silicone compositions according to the invention are fumed or precipitated silicas having BET surface areas of at least 50 m 2 /g as well as carbon blacks and activated carbons, such as furnace black and acetylene black, preference being given to fumed and precipitated silicas having BET surface areas of at least 50 m 2 /g. The mentioned silica fillers can be hydrophilic in nature or can have been hydrophobized by known methods. When incorporating hydrophilic fillers, the addition of a hydrophobizing agent is necessary. The content of actively reinforcing filler in the crosslinkable composition according to the invention is in the range from 0 to 70% by weight, preferably from 0 to 50% by weight.
The silicone elastomer composition according to the invention can optionally comprise as constituents further additives (G) in an amount of up to 70% by weight, preferably from 0.0001 to 40% by weight. These additives can be rheological additives, corrosion inhibitors, oxidation inhibitors, light stabilizers, flame-retarding agents and agents for influencing the electrical properties, dispersing agents, solvents, adhesion promoters, pigments, dyes, plasticizers, organic polymers, heat stabilizers, etc. They include additives such as clays, lithopones, carbon blacks, graphite, metal oxides, metal carbonates, metal sulfates, metal salts of carboxylic acids, metal dusts, fibers such as glass fibers, plastics fibers, plastics powders, metal dusts, dyes, pigments, etc.
These fillers can additionally be heat-conducting or electrically conducting. Examples of heat-conducting fillers are aluminum nitride; barium titanate; beryllium oxide; boron nitride; diamond; graphite; magnesium oxide; particulate metal such as, for example, copper, gold, nickel or silver; silicon carbide; tungsten carbide; zinc oxide and a combination thereof. Heat-conducting fillers are known in the prior art and are available commercially. A combination of fillers with different particle sizes and different particle size distribution can be used.
The silicone elastomer composition according to the invention can additionally optionally comprise solvents (H). It must be ensured, however, that the solvent does not adversely affect the system as a whole. Suitable solvents are known in the prior art and are available commercially. The solvent can be, for example, an organic solvent having from 3 to 20 carbon atoms. Examples of solvents include aliphatic hydrocarbons such asnonane, decalin and dodecane; aromatic hydrocarbons such as mesitylene, xylene and toluene; esters such as ethyl acetate and butyrolactone; ethers such as n-butyl ether and polyethylene glycol monomethyl ether; ketones such as methyl isobutyl ketone and methyl pentyl ketone; silicone fluids such as linear, branched and cyclic polydimethylsiloxanes, and combinations of these solvents. The optimal concentration of a particular solvent in the silicone elastomer composition according to the invention can easily be determined by routine experiments. According to the weight of the compound, the amount of solvent can be, for example, between 0 and 95% or between 1 and 95%.
Inhibitors and stabilizers can be added as further optional components (K). They are used for purposively adjusting the processing time, response temperature and crosslinking speed of the silicone compositions according to the invention. These inhibitors and stabilizers are very well known in the field of addition-crosslinking compositions. Examples of conventional inhibitors are acetylenic alcohols, such as 1-ethynyl-1-cyclohexanol, 2-methyl-3-butyn-2-ol and 3.5-dimethyl-1-hexyn-3-ol, 3-methyl-1-dodecyn-3-ol, polymethylvinylcyclosiloxanes such as 1,3,5,7-tetravinyltetramethyltetracyclosiloxane low molecular weight silicone oils with methylvinyl-SiO 1/2 groups and/or R 2 vinylSiO 1/2 end groups, such as divinyltetramethyldisiloxane, tetravinyldimethyldisiloxane, trialkyl cyanurates, alkyl maleates, such as diallyl maleate, dimethyl maleate and diethyl maleate, alkyl fumarates, such as diallyl fumarate and diethyl fumarate, organic hydroperoxides such as cumene hydroperoxide, tert-butyl hydroperoxide and pinane hydroperoxide, organic peroxides, organic sulfoxides, organic amines, diamines and amides, phosphates and phosphites, nitriles, triazoles, diaziridines and oximes. The action of these inhibitor additives (K) depends on their chemical structure, so that the concentration must be determined individually. Inhibitors and inhibitor mixtures are preferably added in an amount of from 0.00001% to 5%, based on the total weight of the mixture, preferably from 0.00005 to 2% and most preferably from 0.0001 to 1%.
One or more adhesion-promoting or adhesion-preventing substances can be added as further optional components (L). A combination of two or more adhesion-promoting and adhesion-preventing substances is also possible. There can be used as adhesion promoters transition metal chelates, in particular alkoxysilanes or a combination of alkoxysilane and a hydroxy-functional polyorganosiloxane. Unsaturated or epoxy-functional compounds can additionally be used, for example 3-glycidoxypropyl-alkoxy-alkylsilanes or (epoxycyclohexyl)-ethyl-alkoxy-alkylsilanes. Silanes carrying unsaturated organic groups are also suitable for this purpose, such as, for example, 3-methacryloyloxypropyl-alkoxysilanes, 3-acryloxypropyl-alkoxysilanes, vinyl-, allyl-, hexenyl- or undecenyl-alkoxysilanes.
Examples of epoxy-functional silanes are 3-glycidoxypropyl-trimethoxysilane, 3-glycidoxypropyltriethoxysilane, (epoxy-cyclohexyl)ethyldimethoxysilane, (epoxycyclohexyl)ethyl-diethoxysilane and a combination thereof. Examples of suitable unsaturated alkoxysilanes include vinyltrimethoxy-silane, allyltrimethoxysilane, allyltriethoxysilane, hexenyltrimethoxysilane, undecylenyltrimethoxysilane, 3-methacryloyloxypropyl trimethoxysilane, 3-methacryloyloxy-propyl-triethoxysilane, 3-acryloyloxypropyl-trimethoxysilane, 3-acryloyloxypropyl-triethoxysilane and a combination thereof.
Functional siloxanes can likewise be used. The siloxane corresponds to the reaction product of a hydroxy-terminated polyorganosiloxane with one or more above-described alkoxysilanes or a blend of the hydroxy-terminated polyorganosiloxane with one or more of the above-mentioned functional silanes. For example, a mixture of 3-glycidoxypropyltrimethoxysilane and the reaction product of hydroxy-terminated methylvinylsiloxane and 3-glycidoxypropyl-trimethoxysilane can be used.
These components can also be used in the form of a physical blend instead of a reaction product.
Partial hydrolysates of the above-described functional silanes can further be used. These are conventionally prepared either by reaction of the silane with water and subsequent preparation of the mixture, or by preparation of the mixture with subsequent partial hydrolysis.
The suitable transition metal chelates include titanates, zirconates such as, for example, zirconium acetylacetonate, aluminum chelates such as, for example, aluminum acetylacetonate, and a combination thereof. Transition metal chelates and their preparation processes are known in the prior art.
EXAMPLES
In the examples described below, all parts and percentages, unless indicated otherwise, are by weight. Unless indicated otherwise, the examples below are carried out at a pressure of the surrounding atmosphere, that is to say approximately at 1000 hPa, and at room temperature, that is to say at approximately 20° C., or at a temperature that establishes itself when the reactants are combined at room temperature without additional heating or cooling. In the following, all viscosities relate to the dynamic viscosity at a temperature of 20° C. and a shear of 1 s −1 . The examples which follow explain the invention without implying any limitation. All the examples show the total composition of the crosslinked products, irrespective of whether they are formulated as one- or two-component compositions.
The following abbreviations are used:
Cat. platinum catalyst Ex. example No. number PDMS polydimethylsiloxane % by weight corresponds to percent by weight Shore A/D hardness according to DIN 53505 TPR tear propagation resistance according to ASTM D624-B-94 in N/mm Visco dynamic viscosity, shear rate d EB elongation at break according to DIN 53504-85S1 in % TS tear strength according to DIN 53504-85S1 in N/mm 2
Example 1
Silicone Elastomer Composition 1
5% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
5% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 110,000 g/mol
16% by weight of a linear SiH comb crosslinker with a hydrogen content of 0.75% by weight having a mean molecular weight of 3000 g/mol
74% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 1 mmol/g
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 1.6
Example 2
Silicone Elastomer Composition 2
8% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
5% by weight of a vinyl-containing, linear PDMS having lateral vinyl groups and a molecular weight of 30,000 g/mol
6% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 110,000 g/mol
18% by weight of a linear SiH comb crosslinker with a hydrogen content of 1.15% by weight having a mean molecular weight of 3000 g/mol
63% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 1 mmol/g
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 3.4
Example 3
Silicone Elastomer Composition 3
7% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
6% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 110,000 g/mol
22% by weight of a linear SiH comb crosslinker with a hydrogen content of 1.15% by weight having a mean molecular weight of 3000 g/mol
65% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 1 mmol/g
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 4.0
Example 4
Silicone Elastomer Composition 4
5% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
5% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 110,000 g/mol
24% by weight of a linear SiH comb crosslinker with a hydrogen content of 1.15% by weight having a mean molecular weight of 3000 g/mol
66% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 0.8 mmol/g
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 4.8
Example 5
Silicone Elastomer Composition 5
8% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
11% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 16,000 g/mol
4% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 110,000 g/mol
6% by weight of a linear SiH comb crosslinker with a hydrogen content of 1.15% by weight having a mean molecular weight of 3000 g/mol
71% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 0.8 mmol/g
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 0.9
Example C6
Silicone Elastomer Composition 6 (Comparison Example)
20% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 8000 g/mol
20% by weight of a vinyl-terminated linear PDMS having a mean molecular weight of 16,000 g/mol
10% by weight of a linear SiH comb crosslinker with a hydrogen content of 1.15% by weight having a mean molecular weight of 3000 g/mol
50% by weight of a branched vinyl-group-containing silicone resin having a mean molar mass of 4000 g/mol and a content of aliphatically unsaturated groups of 0.7
10 ppm of platinum catalyst, based on the metal
The ratio Si—H groups to aliphatically unsaturated groups is: 2.6
The results of the measurements of the mechanical strength of the crosslinked silicone rubbers are given in Table 1. The Shore D hardness was determined on a sample 6 mm thick, which had been crosslinked for one hour at 200° C. for that purpose.
TABLE 1
according to
Shore D
TPR
ET
TS
the invention
Ex. 1
50
5
7
5
yes
Ex. 2
35
7
9
4
yes
Ex. 3
40
8
6
4
yes
Ex. 4
38
8
8
4
yes
Ex. 5
30
10
20
3
yes
Ex. C6
20
2
4
3
no
Table 2 shows the results of the viscosity determination for the ratio of the dynamic viscosity of the examples at shear rates of 1 s −1 and 100 s −1 and a temperature of 20° C.
TABLE 2
3-point flexural
Visco d = 1/Visco d = 100
modulus
Ex. 1
1.04
150
Ex. 2
1.03
110
Ex. 3
1.03
130
Ex. 4
1.02
120
Ex. 5
1.02
80
Ex. C6*
1.02
20
*not according to the invention | Addition curing silicone elastomers of high Shore D hardness are grindable and polishable, and are particularly useful as temporary adhesives in the processing of semiconductor wafers. | 2 |
BACKGROUND
[0001] Outdoor barbecue cooking is a popular method of preparing food throughout the world. Barbecue grills come in myriad sizes, shapes, styles, and fuel sources. For example, grills can be round, square, rectangular, tall, short, fixed-in-place, cart mounted, portable, light, heavy, and so on. Similarly, grills can be fueled by burning wood, charcoal, LP (liquid propane), butane, and/or natural gas, electrical elements, etc.
[0002] Equally vast are the varieties of foods that can be and are cooked on barbecue grills. Meats, fish, poultry, vegetables, fruits, breads, as well as fully prepared dishes, such as casseroles, can all be prepared over hot coals, gas burners, and the like. The variety of cooking means and foods to cook are virtually endless, limited only by the skill and creativity of the chef.
[0003] A relatively recent addition to the line-up of foodstuffs suitable for grilling is pizza. Pizza, often called pizza pie, comes in a variety of forms; i.e., thin crust, thick crust, deep dish, and so on; and can also contain a wide variety of ingredients. In general; however, pizza comprises a base layer of bread-type, cracker, or doughy crust, a layer of sauce, e.g. tomato sauce, cheese, and from there, virtually any edible item that is used as a topping. When made and ready to be cooked, a pizza, in general, is relatively soft and flexible, thus requiring a hard, flat surface for cooking.
[0004] When cooked on a barbecue grill, a substantially solid, heat conducting base, termed a pizza stone, or like expedient, is used for supporting the pizza within the barbecue grill, where a typical support surface is a wire cooking grate. Whatever is used for the supporting base, it is normally a conductor of heat in order to facilitate cooking, sturdy enough to withstand the elevated temperatures associated with grilling, and possessing of a hard, flat, surface, so as to facilitate the placement and removal of the pizza when cooked.
[0005] U.S. Patent Application Publication No. US2011/0214662A1 to Contarino Jr. details an accessory that is used to convert a common barbecue grill, such as a kettle style grill, to an oven-type enclosure for grilling pizza and other foods that are not particularly suited to being cooked on a cooking grate, or being cooked on a barbecue grill itself.
[0006] The application teaches a cylindrical insert, round in the example so as to follow the shape of the kettle grill, open at the top and bottom, and designed to fit between the firebox and the hood or lid of the grill. The insert is of a gauge substantial enough to withstand the high temperature of grilling and to support the weight of the grill hood. A window is formed in the side of the insert and used for inserting and withdrawing foods cooked in the grill. A ceramic stone or like means is placed over the cooking grate to support the pizza or other foods. This application is incorporated by reference in its entirety.
[0007] While the conversion device performs well for its intended use, the present application teaches improvements that have been designed to further enhance the utility of the barbecue grill as a cooking device.
SUMMARY
[0008] The present application teaches a locking insert and a modified cooking grate assembly for use with a grill according to the Contarino, Jr. application or with other barbecue grills. The insert is mounted on the firebox and receives and supports the insert with the window, the cooking grate, the cooking stone, and the grill hood. The cooking grate includes elongated handles and integral feet for supporting the grate on a stable surface upon its removal from the grill. The assembly may also be used with other conventional grills that do not use the insert with the window.
[0009] Various additional objects and advantages of the present locking insert and modified grate will become evident from the description hereinbelow, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is an exploded, perspective view of the present locking insert and modified cooking grate, illustrating their relative positions in a kettle-type grill;
[0011] FIG. 2 is a partial, exploded, perspective view showing the locking insert, grate, and circular insert with the window;
[0012] FIG. 3 is a partial, cross-sectional view showing the assembled condition of the locking insert and grate;
[0013] FIG. 4 is a partial, exploded, perspective view illustrating the assembly in working form; and
[0014] FIG. 5 is a partial, cross-sectional view showing the grill assembled without the insert having the window.
DETAILED DESCRIPTION
[0015] Referring now more specifically to the drawings, and to FIG. 1 in particular, numeral 10 designates generally a kettle grill, shown here in exploded format. The kettle grill has a firebowl 12 and a hood 14 and is mounted for portability on cart 16 . Inside the firebowl is a coal grate 18 that supports whatever combustible material is used for cooking, i.e. charcoal briquettes, wood chunks, etc. The firebowl can also contain alternative heat sources such as a gas burner or burners, electric elements, and the like.
[0016] In the Contarino, Jr. application, insert 20 with its window 22 is mounted on the firebowl 12 , supported thereon by the upper rim 28 of the firebowl; or it is mounted inside the firebowl, supported by the original equipment cooking grate (not shown). The pizza stone 24 is mounted in the firebowl, either on the original equipment lugs (not shown) that normally support the cooking grate, or on the original grate itself.
[0017] As discussed in the Contarino, Jr. application, the cooking fuel, e.g. charcoal, is piled near the rear of the firebowl. The combination of the localized fuel, the shape of the kettle enclosure, and the vents in the firebowl and hood, generate a draft and thus, a tremendous amount of heat. Temperatures upwards of 600-700° F. and higher are common and necessary for successfully grilling pizza. However, the factors that generate the extreme heat also rapidly consume the fuel. In order to grill multiple pizzas, or other foods, it is necessary to replenish the fuel supply. In order to replenish the fuel in the Contarino, Jr. device, the hood, pizza stone, and cooking rack must be removed and replaced, individually, and in sequential order. This is, of course, complicated by the extreme temperatures.
[0018] To address this issue, the present Applicants have devised a novel solution. Referring again to FIG. 1 , firebowl 12 is modified with the addition of L-shaped tabs 26 , disposed inside the firebowl below the upper rim 28 . The circular insert 20 is removed and replaced by the present locking insert 40 . While the description references a locking insert, it is to be understood that the locking insert is a solid walled insert designed to mate with the firebowl and, as such, will be made in the shape of the firebowl, e.g. round, square, rectangular, etc. The cooking grate will then be similarly shaped and any such variations are considered to be within the scope of the present disclosure.
[0019] The locking insert 40 includes at least one, and in the embodiment shown, a plurality of C-shaped brackets 42 . The lower ends of brackets 42 are secured to tabs 26 with screws, bolts 44 and nuts 46 , (as shown in FIG. 5 ), rivets, or some other type of fastener. The lower, outer rim of the insert 40 is flared outwardly to encircle and cover the upper rim of the firebowl, providing a substantially sealed engagement therewith. The locking insert can be permanently, or, at least semi-permanently, attached to the firebowl 12 , as shown in FIG. 3 , effectively making the firebowl deeper and facilitating the draft effect which helps to achieve the elevated temperatures needed to grill pizzas or other foods. The upper ends of the C-shaped brackets extend inwardly from ring 40 to form horizontal supports 47 , which are disposed generally parallel to the base or ground, for use as described hereinbelow.
[0020] Insert 40 also includes at least one, and in the embodiment shown, a plurality of slots 48 , which are formed in the upper rim 50 of insert 40 . In this embodiment, four such slots 48 are provided, generally opposite one another in the lengthwise, or side-to-side, direction of the firebowl. The horizontal supports 47 are configured such that the top surface of each support is disposed in substantially the same horizontal plane as the bottoms of the slots 48 .
[0021] In the Contarino, Jr. device, the original equipment grill surface, i.e. a cooking grate, is discussed in paragraph 0031 as being mounted on supports 105, shown in FIG. 4B. The OE grill surface is not illustrated, but in grills of this type, the grill surface is supported in the interior of the firebowl and is completely covered by the grill hood. This arrangement facilitates the generally sealed environment of a kettle-type grill, which utilizes the restriction of influent oxygen to control flare-ups. Without a cooking surface in place, the supports 105 are used to mount the pizza stone, typically a heavy, round, ceramic or stone element on which the pizza is cooked.
[0022] In the present device, modified cooking grate 52 is provided, as shown in FIGS. 1-5 . Referring to FIG. 2 , the grate can comprise a circular element having a succession of closely spaced wire rods that are used either to support food being cooked over the heat source or, as shown in FIG. 3 , the pizza stone 24 . While shown as a circular, wire grate, the grate can be made in different shapes, generally corresponding to the shape of the firebowl and hood, and with many different materials that can withstand the heat used for cooking food thereon, such as steel, aluminum, ceramics, and the like. The cooking grate can also be cast iron, aluminum bars, ceramic rods, or other suitable material. The configuration of the grate can also take various forms, using circular elements, elongated bars, flat surfaces, rectangular surfaces, and the like. Cooking grate 52 is modified using at least one, and in some embodiments, a plurality of elongated, lengthwise, horizontal bars 54 that underlie and support the food support rods 56 . The bars 54 are extended radially outwardly from the grate 52 on each side, and converge on each side thereof to where they terminate in grate handles 58 .
[0023] When the grate is placed over the locking insert 40 , the outer ends of bars 54 are received in the slots 48 in the upper rim of insert 40 . This arrangement locks the grate in place against rotating, and also signals to the user that the grate is correctly seated with the handles 58 disposed outwardly of the firebowl. Localized portions of the food support rods are received on top of supports 47 , further ensuring a stably mounted surface. In addition, at least one, and in this embodiment, a plurality of rods 56 are bent downwardly to form V-shaped supports 60 , below the cooking grate 52 . These supports 60 serve as feet to suspend the grate 52 over another supporting surface, as described more fully hereinbelow.
[0024] Referring again to FIG. 2 , in order to convert the insert 20 of Contarino, Jr. to be usable with the present locking insert and modified cooking grate, the insert 20 is modified to include at least one, and in this embodiment, a plurality of downwardly facing slots 70 , formed in the bottom rim 72 of insert 20 . The bottom rim 72 is flared outwardly to fit over the upper rim 50 of the locking ring 40 . The downwardly facing slots 70 fit over the grate bars 54 , as shown in FIG. 4 , where the various elements are shown assembled. The combination of the grate bars 54 and the complementary-formed slots 48 and 70 , serve to help seal what would otherwise be an unobstructed pathway for the ingress of air and the egress of heat, each with its own possibly deleterious effect on the cooking process.
[0025] As discussed hereinabove, the design of the Contarino, Jr. device makes it effective for achieving the high temperatures required to successfully grill pizzas, but also requires that the fuel be replenished for grilling multiple pizzas or other foods due to the fact that the draft effect created by the deep firebowl, the vents in the firebowl and hood, and the open window in the insert 20 , rapidly consumes fuel. Referring to FIG. 4 , one of the beneficial effects of the present modifications is illustrated. When it becomes necessary to replenish the fuel, the user grasps the extended handles 58 and lifts the cooking grate, the pizza stone, and the grill hood off of the locking ring as a single unit. The integrity of the unit is maintained by the engagement of the grate bars 54 with the slots 70 , formed in the modified circular insert 20 . The now separated upper portion of the grill can be then placed on any suitable supporting surface, resting on the V-shaped supports 60 . This provides direct access to the firebowl for adding more fuel, i.e. charcoal, wood chunks for flavoring, etc. After adding the fuel, the entire upper portion is replaced on the locking insert, the reception of the grate bars 54 in the slots 48 indicating to the user that the upper portion is securely seated and locked in place for further use. Exact registering of the bars 54 with slots 48 is not a requirement during the replacement of the upper assembly as the bars 54 , upon making resting contact with the upper rim 50 of the locking insert, support the assembly while a slight rotation of the assembly in one direction or the other will result in registry of the bars with the slots. As the seating is a positive engagement that can be felt even if not seen, given the environment, the user is assured that the grate, stone, and hood have been securely and safely re-positioned in a defined orientation over the firebowl.
[0026] While discussed above with relation to the Contarino, Jr. application, the present locking insert and modified cooking grate assembly can also be used with virtually any grill type of virtually any shape, e.g. kettle-type grills, rectangular or square grills, hibachi-type grills, etc. As shown in FIG. 5 , the locking insert 40 is installed on a typical kettle-type grill firebowl 12 . The grate 52 is installed thereon, the bars 54 of the grate being received in the slots 48 of ring 40 . Food to be cooked is placed on the grate and the hood 14 is placed over ring 40 . The ring is sized to fit just inside the outer rim of the hood, providing a substantially sealed cooking environment while adding the benefit of the deepened firebowl and increased draft effect. For a grill that is not circular, the locking “insert” becomes a locking “spacer”, serving to space the hood farther up from its normal position on top of the firebowl. The cooking grate is similarly modified to conform to the shape of the grill, while providing extended handles that extend beyond the outer perimeter of the grill proper, and bars that lock into slots formed in the locking spacer.
[0027] While an embodiment of a locking insert and modified cooking grate has been shown and described in detail herein, various additional changes and modifications may be made without departing from the scope of the present disclosure. | For use with a barbecue grill, a locking insert mounted to the firebowl of the grill and having a slot or slots formed in its upper rim. A cooking grate having a bar or bars underlying the cooking surface is disposed over the insert, the bars mating with the slots to secure the grate in a defined position. The grate has laterally extending handles for lifting the grate and the grill hood off of the insert for replenishing spent fuel. | 0 |
CROSS REFERENCE TO RELATED APPLICATION
This application is a divisional of U.S. patent application Ser. No. 11/081,909, filed Mar. 16, 2005, now abandoned which in turn is a divisional of U.S. patent application Ser. No. 09/299,388, filed Apr. 27, 1999, now U.S. Pat. No. 6,923,979, granted Aug. 2, 2005.
BACKGROUND OF THE INVENTION
This invention is directed towards the deposition of small (usually fractional gram) masses on a generally electrically non-conductive substrate. One of the most common methods for accomplishing the goal is practiced by manufacturers of photocopiers and electrophotographic electronic printers. This involves causing charged toner particles to migrate with an electric field to a charged area on a photoreceptor, so-called electrostatic deposition. While electrostatic deposition has been proposed for packaging powdered drugs (see U.S. Pat. Nos. 5,669,973 and 5,714,007 to Pletcher), electrostatic deposition is limited by the amount of mass that can be deposited in a given area.
This limitation is intrinsic to electrostatic deposition technology and is determined by the combination of the amount of charge that can be placed on the photoreceptor and the charge to mass ratio of the toner particles. The mass that can be deposited in an area of a substrate is limited to the charge in the area divided by the charge to mass ratio of the particles being deposited. The maximum amount of charge that can be deposited in an area of a substrate is determined by the substrate electrical properties, the electrical and breakdown properties of the air or gas over it, and by the properties of mechanism used for charging the substrate. Likewise, the minimum charge to mass ratio of particles (which determines the maximum mass that can be deposited) is determined by the charging mechanism. However, as the charge to mass ratio is decreased, the variation in the charge to mass ratio increases even to the point where some particles may be oppositely charged relative to the desired charge on the particles. This variation prevents the reliable deposition of a controlled mass on the substrate. Furthermore, low charge to mass ratio particles limit the overall speed of deposition because the force of a particle, which sets the particle velocity, from an electrostatic field is proportional to the charge carried by the particle. For these reasons, higher charge to mass ratio particles are generally preferred.
Packaged pharmaceutical doses, in the range of 15 to 6000 μg are employed in dry powder inhalers for pulmonary drug delivery. A mean particle diameter of between 0.5 and 6.0 μm is necessary to provide effective deposition within the lung. It is important that the dose be metered to an accuracy of +/−5%. A production volume of several hundred thousand per hour is required to minimize production costs. High speed weighing machines are generally limited to dose sizes over about 5,000 μg and thus require the active pharmaceutical be diluted with an excipient, such as lactose powder, to increase the total measured mass. This approach is subject to limitations in mixing uniformity and the aspiration of extraneous matter. Hence, electrostatic deposition of such pharmaceutical powders is highly desirable.
U.S. Pat. No. 3,997,323, issued to Pressman et al, describes an apparatus for electrostatic printing comprising a corona and electrode ion source, an aerosolized liquid ink particles that are charged by the ions from the ion source, a multi-layered aperture interposed between the ion source and the aerosolized ink for modulating the flow of ions (and hence the charge of the ink particles) according to the pattern to be printed. The charged ink particles are accelerated in the direction of the print receiving medium. This patent discusses the advantages in the usage of liquid ink particles as opposed to dry powder particles in the aerosol. However, from this discussion it is apparent, aside from the disadvantages, that dry powder particles may also be used. Furthermore, the charge to mass ratios achieved from using an ion source for charging the powder particles are much higher than those generally achieved using triboelectric charging (commonly used in photocopies and detailed by Pletcher et al in U.S. Pat. No. 5,714,007), thereby overcoming the speed issue discussed above. Such printers have been commercially marketed and sold. However, an apparatus for depositing powder on a dielectric (i.e. a powder carrying package) using the Pressman approach also suffers from the above described maximum amount of powder that can be deposited on the dielectric. This is because during the deposition process, charge from both the ions and the charged particles accumulates on the dielectric, ultimately resulting in an electric field that prevents any further deposition. In other words, the amount of material that can be deposited on the dielectric packaging material is limited by the amount of charge that can be displaced across it which is determined by the capacitance of the dielectric and the maximum voltage that can be developed across it.
SUMMARY OF THE INVENTION
The above disadvantages are overcome in the present invention by providing an alternating electric field for depositing particles onto a dielectric substrate. More particularly, the present invention comprises a method and apparatus for depositing particles from an aerosol onto a dielectric substrate wherein the method comprises and the apparatus embodies the following steps: charging the aerosol particles, positioning them in a deposition zone proximate to the dielectric, and applying an alternating field to the deposition zone by which the aerosol particles are removed from the aerosol and deposited on the dielectric substrate thus forming a deposit. The alternating field provides the means to deposit charged particles and/or ions such that the accumulation of charge on the dielectric substrate does not prevent further deposition of particles thus enabling electrostatic deposition of a deposit with relatively high mass.
In one embodiment of the invention, the particles are alternately charged in opposite polarities and deposited on the substrate with the alternating electric field, thus preventing charge accumulation on the dielectric substrate.
In a second embodiment, an ion source is provided in the deposition zone to provide ions of both polarities for charging the particles. The alternating field determines which polarity of ions is extracted from the ion source. These extracted ions may be used for charging the particles and/or discharging the deposited particles on the dielectric substrate.
In a third embodiment substantially all of the particles are removed from the aerosol. In this embodiment, the mass of the deposit is controlled by measuring the mass flow into the deposition zone and controlling the deposition time to accumulate the desired mass of deposit.
In yet another embodiment, the mass of the deposit is determined by measuring the mass flow both into the deposition zone and immediately downstream thereof, and the difference being the amount deposited.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing, and other advantages of the present invention will become apparent from the following description taken together with the accompanying drawings in which:
FIG. 1 depicts a schematic cross section of a deposition apparatus made in accordance with the present invention;
FIG. 2 illustrates voltage differences in the deposition apparatus of FIG. 1 ;
FIG. 3 depicts an article made in accordance with the present invention; and
FIGS. 4 to 7 depict schematic views of various preferred embodiments of the present invention.
DETAILED DESCRIPTION
The present invention provides a method and apparatus for depositing a relatively large mass of material upon a dielectric substrate and the resulting deposition product. The general apparatus for carrying out this deposition is shown in FIG. 1 and includes a first electrode 5 , a dielectric substrate 1 closely proximate to or in contact with a second electrode 3 , also herein referred to as a deposition electrode. The volume between the dielectric substrate 1 and the first electrode 5 comprises a deposition zone into which aerosol particles are introduced. This is indicated by the horizontal arrow of FIG. 1 . An alternating electric field (the deposition field), indicated by the vertical arrow in FIG. 1 is created within the deposition zone by first electrode 5 , second electrode 3 in combination with an alternating voltage source, shown in FIG. 1 as comprising batteries 9 and 11 and switch 7 wherein the polarity of the field generating voltage is determined by the position of switch 7 . However, any suitable means for generating an alternating voltage is contemplated to be within the scope of the invention. Charged particles from the aerosol within the deposition zone are electrostatically attracted to the substrate 1 thereby forming a deposit 15 as shown in FIG. 2 . The deposit is incrementally formed from groups of particles deposited from each cycle of the alternating field thereby forming a deposit with a relatively larger mass than is possible if a static electric field were to be used. The process of forming the deposit may be terminated by removal of the alternating field. The completed deposit is shown in FIG. 3 as deposited on the dielectric substrate 1 .
The aerosol particles may comprise a dry powder or droplets of a liquid. In one particular embodiment of this invention, the particles comprise a pharmaceutical, for example, albuterol. The pharmaceutical deposits made from deposited pharmaceutical particles may, for example, form a dosage used in a dry powder inhaler. In a second embodiment of this invention, the particles comprise a carrier coated with a biologically active agent. An example of a bioactive agent coated carrier is a gold particle (the carrier) coated by fragments of DNA (the bioactive agent). Such particles are used for gene therapy. The prior examples are intended to exemplify the applications of the invention, and not intended to limit the scope of it.
The aerosol gas may comprise air or any other suitable gas or gas mixture. For some applications where it is desired to control precisely the environment to which the particles are exposed, and/or to control ion emission characteristics (discussed subsequently), pure nitrogen, or nearly pure nitrogen mixed with a small percentage of another gas, e.g. carbon dioxide, is preferred.
Basic components of an aerosol generator include means for continuously metering particles, and means for dispersing the particles to form an aerosol. A number of aerosol generators have been described in the literature and are commercially available. The most common method of dispersing a dry powder to form an aerosol is to feed the powder into a high velocity air stream. Shear forces then break up agglomerated particles. One common powder feed method employs a suction force generated when an air stream is expanded through a venturi to lift particles from a slowly moving substrate. Powder particles are then deagglomerated by the strong shear force encountered as they pass through the venturi. Other methods include fluidized beds containing relatively large balls together with a chain powder feed to the bed, sucking powder from interstices into a metering gear feed, using a metering blade to scrape compacted powder into a high velocity air stream, and feeding compacted powder into a rotating brush that carries powder into a high velocity air stream. A Krypton 85 radioactive source may be introduced into the aerosol stream to equilibrate any residual charge on the powder. Alpha particles from the source provide a bipolar source of ions that are attracted to charged powder resulting in the formation of a weakly charged bipolar powder cloud.
Non-invasive aerosol concentration (and mass density for aerosols of known particle size and specific density) may be determined optically by using right angle scattering, optical absorption, phase-doppler anemometry, or near forward scattering. A few commercially available instruments permit the simultaneous determination of both concentration and particle size distribution.
Particles may be charged within or outside of the deposition zone. One contemplated method of charging particles is triboelectric charging. Triboelectric charging occurs when the particles are made to come in contact with dissimilar materials and may be used with the particles are from a dry powder. Triboelectric charging is well known and widely used as a means to charge toner particles in photocopying and electrophotographic electronic printing processes. Generally, triboelectric charging of particles takes place outside of the deposition zone. A parameter that characterizes the efficacy of particle charging is the charge-to-mass ratio of particles. This parameter is important as it determines the amount of force that can be applied to the particle from an electric field, and therefore, the maximum velocity that particles can achieve during deposition. This, in turn, sets an upper bound to the deposition rate that can be achieved. Charge-to-mass ratios of 1 μC to 50 μC per gram are achievable when triboelectrically charging 1 μm to 10 μm diameter particles. Such charge-to-mass ratios are documented for pharmaceuticals by Pletcher et al in U.S. Pat. Nos. 5,714,007. However, other particle charging methods may achieve charge-to-mass ratios at least ten times greater than is possible with triboelectric charging. Accordingly, it is preferred to use such a method to maximize the velocity of the particles when under influence of the deposition field and the rate at which it is possible to form the deposit.
Generally these methods for applying higher amounts of charge to the particles utilize an ion source to generate an abundance of ions of both or either positive and negative polarities. Some of the negative polarity ions may be electrons. As particles from the aerosol pass in front of the ion source (the charging zone), ions of one polarity are accelerated away from the ion source by an electric field through which the particles travel. Ions that impact the particles attach to the particles. Ions continue to impact the particles until the local electric fields from the ions attached to the particles generate a local electric field of sufficient magnitude to repel the oncoming ions. FIGS. 5 and 6 illustrate two approaches for generating charging ions as well as the means for providing an accelerating field.
In FIG. 5 ions are generated using corona wire 35 . Ions are accelerated through an open mesh screen 39 from an electric field created between open mesh screen 39 and electrode 25 . Housing 37 may be slightly pressurized to prevent the migration of aerosol particles into the corona cavity. Alternatively, the corona source may consist of one or more corona points at the location of corona wire 35 . Aerosol enters the charging zone through channel 23 . Particles are charged by corona generated ions that pass through the apertures of screen 39 . Such a particle charging method is known. A derivative of this method is described by Pressman et al in U.S. Pat. No. 3,977,323. As shown in FIG. 5 , electrode 25 is the previously described deposition electrode and open mesh screen is the first electrode of the previously described deposition zone. Likewise, substrate 33 is the previously described dielectric substrate. Thus, in this exemplary configuration, the charging zone and deposition zone are the same and the particles are simultaneously charged and made to deposit. A particle trajectory is shown by path 41 .
An alternate particle charging method using an ion source employs a silent electric discharge (SED) charge generator. The construction and operation of this class of device is described by D. Landheer and E. B. Devitts, Photographic Science and Engineering, 27, No. 5, 189-192, September/October, 1993 and also in U.S. Pat. Nos. 4,379,969, 4,514,781, 4,734,722, 4,626,876 and 4,875,060. In the exemplary implementation illustrated in FIG. 6 , a cylindrical glass core 43 supports four glass coated tungsten wires 45 equally spaced about its surface. The assembly is closely wound with a fine wire 47 in the form of a spiral. A typical generator unit, available from Delphax Systems, Canton, Mass., consists of a 1 cm diameter Pyrex glass rod supporting four glass clad 0.018 cm diameter tungsten wires. The assembly is spiral wound with 0.005 cm diameter tungsten wire at a pitch of about 40 turns per cm. Only one glass coated tungsten wire is activated at any time. The other three wires are spares that may be rotated into the active position if the original active wire becomes contaminated. In FIG. 6 , the active wire is that wire closest to the opening in channel 23 . Ions and electrons are generated in the region adjacent the glass coated wire when a potential of about 2300 VACpp at a frequency of about 120 KHz is applied between the tungsten wire core and the spiral wound tungsten wire. Ions and electrons are withdrawn from the active region by an electric field created between spiral winding 47 and electrode 25 . As in FIG. 5 , in the exemplary configuration of FIGS. 6 and 7 , the aerosol particles are simultaneously charged and made to deposit.
Other ion sources exist that may be suitable for charging particles. For example, it is possible to generate ions with X-rays or other ionizing radiation (e.g. from a radioactive source). When particles are charged with an ion source, any means for making available ions of both or either positive and negative polarity ions is meant to be within the scope of the invention.
Another means for charging particles particularly applicable to liquid droplets is described by Kelly in U.S. Pat. No. 4,255,777. In this approach, charged droplets are formed by an electrostatic atomizing device. Although, the charge-to-mass ratio of such particles cited by Kelly is not as high as can be achieved when charging particles with an ion source, it is comparable to that achievable by triboelectric charging and may be both preferable in some applications of the invention and is, in any case, suitable for use with the present invention.
The above cited configurations are not meant to imply any limitations in configuration. Rather they are meant to serve as examples of possible configurations contemplated by the invention. Therefore, for example, although particle charging with ion sources is shown and discussed wherein particles are charged within the deposition zone, charging of particles with ion sources outside of the deposition zone is also contemplated. All possible combinations of system configuration made possible by the present disclosure are contemplated to be within the scope of the invention.
The alternating deposition field preferably has a frequency between 1 Hz and 10 KHz, and most preferably, frequency between 10 Hz and 1000 Hz, and a magnitude of between 1 KV/cm and 10 KV/cm. Other frequencies and magnitudes are possible, depending upon the system configuration. For example, a higher deposition field magnitude is possible, generally up to 30 KV/cm—the breakdown potential of air and other gases, but not preferred because it may lead to unexpected sparking. Lower deposition field magnitudes are not preferred because the velocity of the aerosol particles in response to the applied field becomes too low. Likewise, an alternating frequency below 1 Hz generally is not preferred for most applications because it is anticipated that charge buildup on the dielectric substrate may substantially diminish the magnitude of the deposition field over periods of a second or more. However, there may be applications where this is not the case. Frequencies of 10 KHz and higher generally are not preferred because it is believed that the charged particles will not have sufficient time to travel through the deposition zone and form the deposition. However, for systems with very small deposition zones, this may not be a factor.
The waveform of the deposition field preferably is rectangular. However, it has been found that triangular and sinusoidal waveforms also are effective in forming deposits, although generally less so. The waveform has a duty cycle, which is defined in terms of a preferred field direction. The duty cycle is the percentage of time that the deposition field is in the preferred field direction. The preferred field direction either may be positive or negative with respect to the deposition electrode depending upon the characteristics of a particular system configuration. The duty cycle preferably is greater than 50% and most preferably 90%. The preferred field direction is that which maximizes the deposition rate.
As previously described, the deposition field is formed between a first electrode and a second, deposition electrode, The first electrode may or may not be an element of an ion emitter. In some configurations of the invention use of an ion emitter in the deposition zone is advantageous in that it helps to discharge the deposited charged particles thereby preventing the buildup of a field from the deposited charged particles that repels the further deposition of particles from the aerosol. This is particularly advantageous when the duty cycle is greater than 50%. Of course, an ion emitter is required in the deposition zone if the aerosol particles are to be charged within the deposition zone. However, it is also possible to control the charging of the particles, synchronously with or asynchronously to the alternation of the deposition field such that the buildup of a particle repelling field from the deposit is minimized.
The dielectric substrate is closely proximate to and preferably in contact with the deposition electrode. By closely proximate is meant that the separation between the dielectric substrate and the deposition electrode is less than the thickness of the dielectric substrate. In this way, the charged aerosol particles are directed to land on the dielectric substrate in an area determined by the contact or closely proximate area of the deposition electrode. Thus, it is possible to control the location and size of the deposit.
The substrate for the deposit may consist of a dielectric material, such as vinyl film, or an electrically conducting material such as aluminum foil. As previously mentioned, as unipolar charged powder is deposited upon the surface of a dielectric, a large electrical potential is formed which generates an electric field that opposes the deposition field and deposition is thus self-limiting at rather low masses. If unipolar charged powder is deposited on the surface of an electrical conductor, then again a surface potential will be built up but of a lower magnitude than that of a corresponding insulating substrate. The ratio of the surface voltage of a deposit on an insulating layer to that of a deposit on the surface of a conducting layer is roughly equal to ratio of the relative thickness of the dielectric plus the thickness of the deposited powder and the thickness of the deposited powder layer. The use of alternating deposition to form bipolar layers through the use of ac aerosol charging and ac deposition field allows larger masses to be deposited onto the surfaces of conductors.
The dielectric substrate may be any material and have any structure suitable to its other functions. For example, it may be a packaging medium, such as a tablet, capsule or tubule, or the blister of a plastic or metal foil blister package. The dielectric substrate may also be a pharmaceutical carrier, for example, a pill or capsule. It may be any edible material, including chocolate. Alternatively, it may be simply a carrier of the deposit for carrying it to another location for further processing.
We have found with the present invention that it is possible to deposit substantially all of the aerosol particles that pass through the deposition zone under conditions where the flow rate of the aerosol is below a maximum. This maximum flow rate is determined primarily by the magnitude of the deposition field, the charge-to-mass ratio of the charged particles, and their diameters. The capability to deposit substantially all of the aerosol particles has been demonstrated for relatively large mass deposits, much larger than is possible using prior art systems that electrostatically create deposits. For example, we have deposited several milligrams of lactose power into a blister of a blister pack of 6 mm diameter. A particular advantage of the present invention is that there are no limits related to charge-to-mass ratio of the charged particles nor the amount of charge laid down on a substrate as there are with prior art systems. The use of an alternating deposition field enables deposition of charge of either polarity on the combination of substrate and deposit, whether the charge is carried by ions or charged particles. The net deposited charge may be therefore neutralized if necessary. As such, the limits to the mass of the deposit become mechanical in nature rather than electrical.
The ability to deposit substantially all of the aerosol particles that pass through the deposition zone provides a new method for controlling the mass of the deposit. In this method the mass flow of the aerosol particles that pass into and out of the deposition zone is measured over time by means of sensors 60 , 62 located upstream and downstream of the deposition zone. The results could be recorded for manufacturing control records and adjustments in flow rate, etc., made as need be to maintain a desired deposition amount. As previously mentioned there are various known means for measuring the velocity of an aerosol. In combination, these means enable the measurement of the mass flow rate. The integration of the mass flow rate over time gives the total mass. Accordingly, the mass of a deposit may be controlled by measuring the mass flow of aerosol particles into the deposition zone and upon reaching a desired deposit mass, removing the presence of the alternating deposition field. In circumstances wherein a portion of the total aerosol is not deposited as it passes through the deposition zone, a second measuring instrument may be positioned immediately after the deposition zone. The difference between the two measurements represents the total mass deposited from the aerosol as it passes the deposition zone. The deposit may be controlled by removing the presence of the alternating deposition field as described previously. Even in cases wherein substantially all of the aerosol particles are deposited in the deposition area, the existence of a second measuring instrument provides confirmation of the actual mass deposited, and is of particular interest in applications where the reliability of the mass deposited is of commercial interest such as pharmaceutical dosages. The mass of deposits formed by the present invention is relatively larger than deposits that can be formed with prior art methods that electrostatically create deposits. On the other hand, they may be much smaller than masses conveniently created using prior art methods that mechanically weigh or otherwise mechanically measure or control the mass. As such, the present invention provides a unique means to address a hitherto unaddressed need.
The details of the invention may be further examined by considering FIG. 4 . Here, an aerosol generator 17 forms an air borne particle dispersion that is carried by enclosed channel 19 to aerosol concentration monitoring station 21 . Channel 23 then carries the aerosol through a region where charging device 31 charges the powder. An electrostatic field is provided between the charging device 31 and deposition electrode 25 . Deposition electrode 25 corresponds to electrode 3 shown in FIG. 1 . A dielectric substrate 27 shown here as a blister pack pocket that collects charged particles deflected by the electrostatic field. A second concentration monitoring station 29 is employed to determine how much of the particles have been removed from the aerosol. Under conditions whereby essentially all of the particles are removed from the air stream, this second concentration monitor may not be required. The air stream then moves into collector 30 . This collector might consist of a filter or an electrostatic precipitator or both. Alternately, the air may be recirculated through the aerosol generator.
EXAMPLE
A filling device was set up according to the schematic of FIG. 6 . The channel was fabricated of ¼-inch thick polycarbonate sheet. The channel width was 40-mm and its height was 6-mm. A blister pack pocket, formed of 6-mil polyvinyl chloride, having a depth of 4-mm and a diameter of 6-mm was supported on a circular electrode 25 having a diameter of 4-mm.
The charge source, consisting of glass core rod 43 , spiral wire electrode 47 and four glass coated wire 45 spaced at intervals around the periphery of the core rod, was obtained from Delphax Systems, Canton, MA. Delphax customers employ these rods in discharging (erasing) latent images on Delphax high-speed printer drums.
Spiral winding 47 was maintained at ground potential and glass coated tungsten wire 45 was excited using 2300 volt peak-to-peak ac at a frequency of 120 kHz. A Trek high voltage amplifier was employed to provide square wave switching of deposition electrode 25 at a frequency of 35 Hertz. The output voltage was switched between +5 kV and −5 kV. The duty cycle was set so that negative charges were extracted for 10% of the square wave period leaving positive charge extraction to occur over 90% of the duty cycle.
An aerosol consisting of lactose powder, having a particle size in the range of about 3 to about 7 microns, was suspended in a flowing stream of nitrogen gas. The lactose was aerosolized by the turbulent action of pressurized nitrogen in a Wright Dust Feed aerosolizer manufactured by BGI Inc., Waltham, Mass. The aerosol concentration was about 1 microgram/cm 3 and the channel flow velocity was adjusted to 30 cm/sec.
Charging and deposition potentials were applied for a period of two minutes during aerosol flow. A well-defined mass of powder, measured and found to be 1 mg, was formed at the bottom of the blister pack pocket. No powder deposition was found at the blister pack walls or on the bottom of the channel.
Subsequent experimental runs established that the mass deposited was proportional to the deposition time over the time intervals of ½ to 5 minutes.
With the present invention, it is also possible to multiplex the operation of two or more deposition zones served from a single aerosol source by configuring deposition zones along the aerosol path and selectively applying an alternating deposition field at one deposition zone at a time. Aerosol particles passing into a deposition zone where no alternating deposition field exists simply pass through the deposition zone whereupon they can pass into a next deposition zone.
Although various embodiments which incorporate the teachings of the present invention have been shown and described in detail herein, many other varied embodiments that still incorporate these teachings may be made without departing from the spirit and scope of the present invention. For example, the aerosol particles may comprise carrier particles which may comprise inert substrates including biocompatible metal particles coated with a bioactive agent. | A method for depositing controlled quantity of particles on a substrate comprises providing aerosolized particles in a deposition zone having first and second electrodes, and creating an electrostatic field between the first electrode and the second electrode to create a pool of ions at the first electrode, charging particles within the deposition zone with the ions, and moving the particles towards and depositing the particles onto the substrate. In order to prevent excessive charge build up on the substrate, the electrostatic field is periodically reversed. | 1 |
CROSS REFERENCE TO RELATED APPLICATION
Not Applicable
TECHNICAL FIELD
This invention relates to an apparatus for clearing debris. In particular, the device is for clearing materials such as manure out from under a fence row of a feed lot.
BACKGROUND ART
A problem commonly encountered by cattle feed lot operators is the removal of material such as manure from under a fence row. The problem of removal of such material is difficult since fences encompassing feed lots are often constructed in great lengths, and require a large expenditure of time and effort to maintain. Fences encompassing feed lots are typically constructed of steel. The removal of materials such as manure from around and under a typical feed lot fence is necessitated by the fact that manure is corrosive to a metal fence.
Currently, a common method of removing materials such as manure from under a feed lot fence includes driving a tractor or other vehicle having a front mounted device, such as a blade or other device, perpendicular to the fence row to push out material from under the fence. This step must be repeated numerous times to remove material from under a length of fence. After material has been pushed out from under a fence, a separate vehicle may then scoop up the material for removal.
A disadvantage of this method of removing material from under a fence row is that it is extremely time consuming to repeatedly maneuver a vehicle perpendicular to a section of fence, drive forward to push out the material, and then back out the vehicle before aligning with another section of fence.
It is therefore desirable to utilize a device that will enable a vehicle to drive parallel to a fence row and facilitate the removal of material from under a fence. It is additionally desirable to utilize a device that is rugged in construction and is capable of removing materials having substantial mass, such as manure, dirt or other materials.
SUMMARY OF THE INVENTION
It is therefore an object of the invention to provide a device that is capable of clearing materials out from under a fence row while being mounted to a vehicle traveling parallel to the fence row.
It is a further object of the invention to provide a device capable of removing substantially heavy materials such as dirt or manure from under a fence row.
It is a further object of the invention to provide a rotating wheel having rigid teeth mounted thereon wherein the wheel is adjustable in horizontal and vertical directions.
It is an additional object of the invention to provide a method for clearing materials from under a fence row that is substantially less time consuming than currently practiced methods.
The apparatus of the invention includes a mounting structure for affixing to a vehicle such as a Case model 1838, which is commonly known as a skid loader. Pivotally mounted to the mounting structure is an arm that extends forward of the vehicle and preferably pivots to one side of the vehicle. Rotatably mounted to a distal end of the arm is a wheel. A mover, such as a hydraulic cylinder, is affixed to the mounting structure and the arm for selectively pivoting the arm and wheel either in front of or to a side of the vehicle. The wheel has a plurality of rigid teeth extending from its perimeter for engaging materials such as manure or dirt and for removing the material from under a fence. Examples of other uses for the invention include removing dirt away from barbed wire fences, removing dirt away from buildings, throwing dirt up against a building to maintain a drainage grade, leveling ground in restricted areas as well as open spaces, defining sharp and accurate vertical cuts for curbs, railroad ties, etc, positioning rock and soil back on trails to help prevent erosion, replacing gravel around oil tank overflow dikes, maintaining alleys or other dirt roads, cutting drainage around culverts and bridges, filling sprinkler wheel tracks, cutting water drainage trenches, clearing sagebrush and for forestry and horticulture purposes, including cutting cedar trees for removal from the ground. Preferably the wheel is driven by a reversible motor of sufficient power to throw material approximately ten feet away from the fence where it may be easily collected thereafter.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevation view of the apparatus of the invention affixed to a vehicle shown removing materials from under a typical feed lot fence.
FIG. 2 is a top view of the vehicle and apparatus wherein the arm of the apparatus is shown in a side or fence line engaging position and is also shown in a forward most position in phantom lines.
FIG. 3 is a top view of the invention.
FIG. 4 is a side view of the invention showing the apparatus in a lower position. A raised position is shown in phantom lines.
FIG. 5 is a top view of the invention showing the arm in a side or fence line engaging position. Additionally, the arm is shown in a forward most position in phantom lines.
FIG. 6 is a side view of the apparatus of the invention.
FIG. 7 is a bottom view of the wheel of the invention.
FIG. 8 is a side view of the motor and wheel assembly of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to FIG. 1, designated generally 10 is the apparatus of the invention. Apparatus 10 is shown mounted on vehicle 12. Preferably, vehicle 12 is a skid loader such as Model 1838 manufactured by Case. Skid loaders are desirable since they have raisable stingers or arms 14 which permit vertical adjustment of apparatus 10. However, other types of vehicles may be utilized effectively with apparatus 10 including tractors or other vehicles. Apparatus 10 is shown removing material from under fence 16 in FIG. 1.
Referring now to FIG. 2, mounting structure 18 is affixed to raisable arms 14 of vehicle 12. In the preferred embodiment, mounting structure 18 is a steel plate of 1/2 inch thickness, which is 18 inches high by 48 inches wide. However, other materials and dimensions for mounting structure 18 may be utilized. Pivotally mounted to mounting structure 18 is arm 20. Arm 20 is pivotally mounted to mounting structure 18 by arm mount 22. In the preferred embodiment, arm mount 22 is constructed of three 3/4 inch×4 inch strap irons that are welded to mounting structure 18. Preferably, the strap irons of arm mount 22 have a 2 inch hole for accommodating pin 24, which is 2 inches in diameter. In the preferred embodiment, the strap irons of arm mount 22 have 1/2 inch walled bushing stock positioned therein for engaging pin 24.
In the preferred embodiment, arm 20 is 5 feet long and is constructed of 4 inch square steel tubing. Rotatably mounted on distal end 26 of arm 20 is wheel 28. Affixed to wheel 28 is a plurality of rigid shanks or teeth 30. Teeth 30 may be subsoil shanks, bull tongues, paddles, chisel blades, slicers or other suitable protuberances. Affixed to mounting structure 18 is a mover for selectively pivoting arm 20. The mover may be a hydraulic cylinder 32 or other device for pivoting arm 20 including electric or gasoline powered motors, other piston-cylinder devices, a chain drive or other devices. In the preferred embodiment, hydraulic cylinder 32 is affixed to mounting structure 18 by mounting structure pivot 34. Preferably, hydraulic cylinder 32 is affixed to arm 20 by arm pivot 36. In a preferred embodiment, shield 38 is affixed to arm 20 to prevent materials such as dirt, rocks or manure from being thrown at an operator of vehicle 12.
Referring now to FIG. 3, shown is a more detailed top view of the apparatus 10. Wheel 28 is shown mounted proximate distal end 26 of arm 20. A plurality of strap iron segments 40 are preferably welded to upper surface 42 of wheel 28. Additionally, gussets 44 are preferably welded at right angles to strap iron segments to reinforce strap iron segments 40. Gussets 44 are preferably 2 inches×2 inches×1/2 inch. In the preferred embodiment, teeth 30 are removably affixed to strap iron segments 40 by means of nuts and bolts 48. Teeth 30 have carbide tips 50 to increase the service life of teeth 30. It is desirable for teeth 30 to be removably attached to strap iron segments 40 so that teeth 30 may be easily replaced when they wear out.
Motor 52 is preferably mounted above wheel 28 for rotating wheel 28 and teeth 30. Preferably, motor 52 is of sufficient power to rotate wheel 28 at 500-600 rpm. Additionally, motor 28 should be powerful enough to dig out debris and throw the debris approximately 10-12 feet. A preferred motor for use with the invention is a hydraulic orbital motor. In one embodiment, a grater blade may be provided on the bottom of arm 20 for scraping debris into a uniform longitudinal pile for facilitating easy clean up by a scooping vehicle.
Referring now to FIG. 4, shown is a side view of apparatus 10. Shown in phantom lines is apparatus 10 in a raised position. Additionally, shown in phantom lines is raisable arm 14 of vehicle 12. In addition to having raisable arm 14, a preferred vehicle has hydraulic cylinder 53 for tilting mounting structure 18 at a desired angle. It is desirable to mount apparatus 10 on a vehicle having a raisable arm 14 so that apparatus 10 may be selectively vertically adjustable. The ability to vertically adjust apparatus 10 aids in the removal of debris found on or near uneven ground that may be encountered in the field.
In the preferred embodiment, motor 52 engages wheel shaft 54 by means of a double sprocket arrangement wherein one sprocket is affixed to wheel shaft 54 and a second sprocket is affixed to motor shaft 56. Preferably, the sprockets affixed to wheel shaft 54 and motor shaft 56 are 16 teeth sprockets connected by double chain 58. Preferably double chain 58 is a No. 60 double chain. To prevent damage to motor 52, wheel 28 is affixed to wheel shaft 54 by means of shear bolt 60. In preferred embodiment, shear bolt 60 is a 5/8" shear bolt.
Visible in FIG. 4 is auxiliary arm 62. Auxiliary arm 62 is provided to add additional strength to arm 20 of apparatus 10. Auxiliary arm 62 is preferably 2 feet in length. Arm 20 is provided with downward bend 63 so that teeth 30 of wheel 28 more readily engage the ground. Without bend 63, rotating wheel 28 operates in a plane substantially parallel to the surface of the ground. In the preferred embodiment, downward bend 63 is a 5 degree bend positioned 12" from distel end 26 of arm 20.
Referring now to FIG. 5, shown is arm 20 of apparatus 10 in a side or fence engaging position. Arm 20 is further shown in a forward position with phantom lines. Hydraulic cylinder 32 is provided to selectively pivot arm 20 to a desired location. Preferably, hydraulic cylinder 32 is a 3 inch diameter cylinder having a 20 inch stroke. In the preferred embodiment, hydraulic arm pivot 36 is 25" away from pin 24, thereby allowing for an approximately 90 degree swing of arm 20.
Referring now to FIGS. 6-8, a side view, a bottom view and a detailed side view of wheel 28 is shown. Strap iron segments 40 are positioned on both upper surface 42 and lower surface 64 of wheel 28. In the preferred embodiment, four segments of strap iron 40 are welded at right angles to upper surface 42 and four pieces of strap iron 40 are welded to lower surface 64 of wheel 28. The resulting assembly allows for teeth 30 to be affixed to strap iron segments 40 at 45 degree intervals. By affixing teeth 30 to both upper surface 42 and lower surface 64 of wheel 28, an effective cutting area is doubled in width. Upper row 65 and a lower row 66 of teeth 30 each engage material to be removed rather than a single row of teeth.
Wheel shaft 54 is guided by an upper shaft guide 67 and lower wheel shaft guide 68. Wheel shaft 54 is shown in FIG. 8 affixed to wheel mount plate 70. Motor mount plate 72 is provided to support motor 52.
In the preferred embodiment, hydraulic solenoid valves are electrically controlled for operating apparatus 10. Preferably one system is provided for facilitating control of arm 20 and a separate system is provided to control hydraulic motor 52. In the preferred embodiment, a dead switch is provided for the operator, which must be depressed to maintain rotation of wheel 28. It should be understood, however, that other means of controlling apparatus 10 may be provided within the scope of the invention.
In practice, apparatus 10 is affixed to vehicle 12. Vehicle 12 is driven parallel to a fence row and arm 20 is selectively pivoted by hydraulic cylinder 32 to position wheel 28 under a fence or to position wheel 28 in front of vehicle 12 to avoid impacting teeth 30 on a fence post or other obstacle. Wheel 28 may be vertically adjusted via raisable arms 14 if vehicle 12 is equipped with raisable arms 14. Wheel 28 may also be horizontally adjusted by hydraulic cylinder 32. Therefore, an operator may easily position wheel 28 to effectively clear material out from under a fence row with teeth 30 on rotating wheel 28.
The invention has significant advantages. The invention allows an operator to clear out materials from below a fence in a greatly reduced amount of time. The ability to maneuver a vehicle parallel to a fence line eliminates significant vehicle maneuvering and should allow an operator to complete a fence clearing job with less effort.
While the invention has been shown in only one of its forms, it should be apparent to those skilled in the art that the invention is not so limited but is susceptible to various changes without departing from the scope of the invention. For example although the arm is shown controlled by hydraulic cylinder, other means may be used to position the arm. Additionally, although a hydraulic motor is shown powering the rotation of the wheel, other types of motors or methods of impairing rotation to wheel 28 may be utilized. | A method and apparatus for clearing debris is disclosed. More particularly, a method and apparatus for clearing manure and other material from under a feedlot fence row is disclosed. The apparatus is preferably mounted to a vehicle such as a skid loader. The apparatus consists of a mounting structure for affixing to a vehicle, a pivotally mounted arm affixed to the mounting structure, and a motor driven wheel rotatably mounted proximate a distal end of the arm. The wheel has a plurality of teeth or shanks extending therefrom for digging out debris from under a fence row and throwing the debris away from the fence. In practice, an operator may drive a vehicle parallel to a fence row and selectively pivot the wheel in and out between fence posts to clear manure out from under the fence. | 0 |
GOVERNMENTAL INTEREST
The Government has rights in this invention pursuant to Contract No. DAAA21-89-C-0013 awarded by the U.S. Army.
The invention described herein was made under a contract with the Government and may be used and licensed by or for the Government.
FIELD OF USE
This invention describes the direct functionalization of nitrocubanes via irradiation in the presence of an oxalyl halide.
BACKGROUND OF THE INVENTION
Considerable effort in recent years has been directed toward the synthesis of polynitrocubanes because of the potential use of this class of energetic materials as explosives, propellants, fuels and binders (Chemistry of Energetic Materials; Ed., G. A. Olah; D. R. Squire; Academic Press, Inc., San Diego, Cal., 1991. Also see Carbocyclic Cage Compounds; Ed., E. J. Osawa; O. Yonemitsu; VCH Publishers, Inc., New York, N.Y. 1992). The compact structures of cage molecules result in high densities, and the introduction of NO 2 groups further enhances the density. The strain energy present in the cubane skeleton (>166 kcal/mol) is an added bonus to its performance. Furthermore, preliminary results with polynitrocubanes indicate that such compounds are thermally very stable and are also very insensitive energetic materials. Consequently, it is of interest to introduce functional groups on the cubane skeleton which can be converted to nitro group or other active functionalities.
Direct functionalization of nitrocubanes, while an attractive approach, has not heretofore been realized. Cationic or anionic reactions, due to the activity of the nitro groups give either decomposed products or recovered starting materials. We report here an efficient direction functionalization of a nitrocubanes molecule by its irradiation in a solution of oxalyl halide (for a related case see Wiberg, K. B.; 10 th Annual Working Group Meeting, Jun. 3-6, 1992, Kiamesha Lake, N.Y. For much simpler cases see Wiberg, K. G.; Williams, Jr., V. Z.; J. Org. Chem., 1970, 35, 369; Appliquist, D. E.; Saski, T.; J. Org. Chem.; 1978, 43, 2399). This new and potentially powerful synthetic development will greatly shorten the number of steps necessary to obtain nitrocubane derivatives which are otherwise difficult to synthesize.
SUMMARY OF THE INVENTION
A solution of 1,4-dinitrocubane (Eaton, P. E.; et al; J. Org. Chem.; 1984, 49, 185; Eaton, P. E.; Wicks, G. E.; J. Org. Chem.; 1988, 53, 5353) in oxalyl chloride was irradiated under a sunlamp for 12 h at room temperature. After removing oxalyl chloride under reduced pressure, the reaction mixture was hydrolyzed and partioned between ethyl acetate and 5% aqueous NaOH. From the organic phase was isolated 2-chloro-1,4-dinitrocubane, 3, and 2,5-dichloro-1,4-dinitrocubane, 4. After acidification of the alkaline layer with HCl and extraction with ethyl acetate, 2-carboxy-1,4-dinitrocubane, 5, was obtained in 68% yield. ##STR1##
The structures of 3,4 and 5 were confirmed by NMR spectrometry. Furthermore, Compound 5 was converted to the corresponding 2-carbomethoxy-1,4-dinitrocubane 6 by esterification using MeOH, and the molecular structure of 6 was confirmed by X-ray crystallographic analysis.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following section describes specific experimental procedures used for the synthesis:
A mixture of 1,4-dinitrocubane, 1, (388 mg, 2.0 mmol) in oxalyl chloride (50 mL) was photolyzed under a sunlamp for 18 h at room temperature. Oxalyl chloride was removed on a rotary evaporator and the solid residue was partioned between EtOAc (40 mL) and NaOH solution (5%, 30 mL). After stirring for 3 h, the organic phase was separated, washed with brine, dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was chromatographed on silica gel using hexane/CH 2 Cl 2 (1:1) to give 2-chloro-1,4-dinitrocubane 3, m.p. 145°-147° C.; 1 H NMR (CDCl 3 ); δ4.84 (m, 2H); 4.71 (m, 3H); and 2,5-dichloro-1,4-dinitrocubane, 4, m/p. 188°-190° C.; 1 H NMR (CDCl 3 ); δ4.90 (dd, 2H); 4.78 (dd, 2H).
The alkaline layer was acidified with HCl (10%) and organic materials were extracted with EtOAc (2×30 mL). The organic phase was washed with brine, dried over Na 2 SO 4 , and concentrated via rotary evaporator to give 400 mg or a crude product which was triturated with hexane/acetone 10:1, (5.0 mL) to give 2-carboxy-1,4-dinitrocubane, 5, m.p. 187°-189(Dec)° C.; 1 H NMR (acetone -d 6 ); δ4.96 (m,2H); 4.74 (m,3H).
Compound 5 (100 mg, 0.4 mmol) was stirred with MeOH (20 mL) and MeSO 3 H (4 drops) at reflux overnight. The reaction mixture was concentrated and then dissolved in ethyl acetate (20 mL). The solution was washed with aqueous Na 2 CO 3 (5%), then brine, dried over anhydrous Na 2 SO 4 and concentrated. The residue was triturated with ether/hexane (1:1) to give 2-carbomethoxy-1,4-dinitrocubane 6 m.p.=165° C.; 1 H NMR (CDCl 3 ), δ4.92 (M,2H); 4.62 (m, 3H), 3,80 (s, 3H).
In another experiment, the solid residue from the reaction of 1,4-dinitrocubane (100 mg) and oxalyl chloride (20 mL) under a sunlamp (vide supra) was treated with methanol (20 mL) for 4h at room temperature. The excess methanol was evaporated and the residue was dissolved in ethyl acetate (20 mL). The organic layer was washed with 5% aqueous Na 2 CO 3 and then brine. After drying over Na 2 SO 4 and then concentration, the crude produce was chromatographed on silica gel using hexane/CH 2 Cl 2 (1:1) to give compounds 3,4, and 6. | An efficient direct functionalization of nitrocubanes has been achieved by irradiation of a solution in an oxalyl halide to yield halogenated and halocarbonylated derivatives of nitrocubanes. | 2 |
BACKGROUND OF THE INVENTION
This invention relates to new and useful improvements in electric dry shavers and in particular to a drive assembly for a movable inner cutter of the shaver cutter head assembly.
In electric dry shavers it is well-known to provide a cutter head assembly whereby a movable inner cutter is held in spring-biased engagement with a stationary outer cutter whereupon in movement of the inner cutter facial hairs which are combed into the cutter head through openings in the outer cutter are sheared.
In certain electric dry shavers the outer cutter comprises a thin metallic foil which is maintained in a bowed or arcuate configuration conforming to the arcuate shape of inner cutter bars. The cutter bars engage the under surface of the foil and is spring urged into contact with the foil. In some shavers of this type the movable inner cutter is held captive within a hairpocket section provided in a recessed portion of the shaver. The hairpocket is adapted for mounting and dismounting as an assembled unit over a motor driven oscillator arm which projects from the motor compartment of the shaver housing. In other shavers of this type the cutter foil is carried by a removable or hinged hairpocket and the inner cutter is secured to the motor oscillator arm. In these shavers the hairpocket may be removed or pivoted away from the casing without disturbing the inner cutter and access thereto is gained without interfering with the positioning of the outer cutter foil.
In these shavers various means have been provided in the past for mounting the inner cutter on the oscillator arm. Although these means have met with varying degrees of success, certain problems have been encountered in providing means for permitting ready detachment of the inner cutter assembly without interfering with the spring biasing means for the inner cutter. Further means must usually be included in such an arrangement for supporting the inner cutter for linear movement upon operation of the motor.
It is an object of the present invention to provide a novel cutter drive arrangement for an electric dry shaver.
Another object is to provide novel means for mounting a movable inner cutter in an electric dry shaver in a manner whereby it may be readily detached from the motor driven oscillator arm when desired.
Another object is to provide novel interlocking means for securely holding the inner cutter in position on a motor driven oscillator arm and which interlocking means include means for readily releasing the inner cutter from the oscillator arm.
Still another object is to provide a cutter drive means which provides for omnidirectional movement of the inner cutter without interfering with the positioning of an outer cutter foil.
SUMMARY OF THE INVENTION
The present invention contemplates a novel cutter drive assembly for an electric dry shaver. One embodiment of the cutter drive assembly includes a rectangular-shaped driven plate member for supporting the inner cutter blades of a cutter head assembly. The plate is disposed over a motor driven oscillator arm and interlocking means are provided on the oscillator arm and drive plate. Spring means are located on the drive arm which engage the under surface of the driven plate to urge the plate into cutting cooperation with an outer cutter foil mounted on a support frame hinged to the hairpocket section of the electric dry shaver. The interlocking means further include means for releasing the cutter drive plate from the drive arm without releasing the spring means therefrom.
The above and other objects and advantages of the present invention will appear more fully hereinafter from the consideration of the detailed description which follows taken together with the accompanying drawing wherein one embodiment of the invention is illustrated.
DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a perspective view of an electric dry shaver which incorporates one embodiment of the present invention;
FIG. 2 is an exploded view of portions of the inner cutter supporting plate and drive means therefor;
FIG. 3 is a cross-sectional view taken through the upper portion of the electric dry shaver of FIG. 1;
FIG. 4 is an end view of the upper portion of the shaver of FIG. 3 with parts broken away to show the inner cutter assembly in an intermediate position prior to mounting on the motor driven oscillator arm;
FIG. 5 is a view simlar to FIG. 4 showing the inner cutter assembly in mounted position with the outer cutter pivoted to open position; and
FIG. 6 is a perspective view of another embodiment of the inner cutter supporting plate.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings for a more detailed description of the present invention, an electric dry shaver incorporating one embodiment thereof is generally indicated by reference numeral 10 in FIG. 1. Electric dry shaver 10 is of a generally usual structure and includes a premolded main casing section 11 in which is housed an electric motor (partially shown at 13 in FIG. 3) for operating a cutter head assembly generally indicated by the reference numeral 14 (FIGS. 1 and 3) upon operation of on/off switch 16. Switch 16 controls power in a usual manner to either an external power outlet or internal battery circuit.
Cutter head assembly 14 includes an outer cutter foil 17 mounted on a rectangular frame 18 disposed over a recessed hairpocket portion 19 of shaver 10 provided between end walls 20 and 22 which project upwardly from main casing 11. Foil supporting frame 18 includes end walls 23 and 24 (FIG. 1) and front and rear walls 25 and 26 (FIG. 2). Frame 18 is pivotally mounted to end pieces 20-22 as by hinge means indicated in broken lines at 27 in FIG. 3. Through releases of suitable latch means (not shown) controlled by button 28.
Outer cutter foil 17 is made by a thin flexible metallic material as suitably formed for example by an electroforming process and includes two perforated bowed portions 29-30 having hair reception slots 31. Bowed portions 29-30 are separated by a bar member 32 extending centrally of foil supporting frame 18 and are maintained in arcuate configuration by the urging of spring-biased inner cutter assembly (generally indicated by the reference numeral 33) in a manner to be hereinafter explained in detail.
Inner cutter assembly 33 comprises two spaced and parallel rows of arcuate cutter blades 34 carried by frame members 36 such as for example disclosed in U.S. Pat. No. 3,858,461 which issued on Jan. 7, 1975 to R. J. Tolmie entitled "Shaver Inner Cutter". Frame members 36 are mounted on a rectangular-shaped driven plate 38 by means of depending posts 40 press-fitted into openings 41 in plate 38 (FIGS. 2 and 3) which is formed from a premolded plastic material.
Cutter drive means comprise an oscillator arm 43 (FIG. 3) extending from main casing 11 and which arm 43 is reciprocated by motor 13 in a usual manner. In mounted position of cutter head assembly 14 on shaver 10 (FIG. 3) drive arm 43 is located within an H-shaped drive slot portion 44 of driven plate 38. The tip of arm 43 is provided with spaced inclined projections 45 which are adapted to rest on ledge portions 47 formed on the walls of slot 44 in an open position of outer cutter frame 18 (FIG. 5).
In order to bias inner cutter assembly 32 into engagement with outer cutter foil 17 an inverted conical spring 49 is disposed about drive arm 43 and is held in position thereon by a circular-shaped metallic cap member 50. Cap 50 is mounted over spring 49 on drive arm 43 by means of an enlarged opening 51 therein having cut out portions 52 (FIG. 2) conforming to projections 45 on arm 43. In mounting cap 50 cutout portions 52 are aligned with ears 43 and cap 50 is pressed down on arm 43 and rotated slightly to position cutouts 52 clear of projections 45. In this position (FIG. 5) release of cap 50 cause a spring 49 to lock cap 50 against projection 45.
In closed position of frame 18 relative to hairpocket 19 (FIG. 3) inner cutter assembly 32 is pressed downwardly on spring 49 and projection 45 are raised clear of ledges 47 as drive arm 43 engages the walls of slot 44 in position to drive inner cutter assembly 32.
If it is desired to remove inner cutter assembly 32 from drive arm 43 from the position shown in FIG. 3 then frame 18 is first pivoted to an open position as seen in FIG. 5 whereat spring 49 urges inner cutter assembly upwardly until cap 50 engages ears 45 on drive arm 43. Inner cutter head assembly 32 is then pressed downwardly manually on both cap 50 and spring 49 in the direction of arrow A (FIG. 5) and then slid in the direction of arrow B until projections 45 of arm 43 are moved clear of ledges 47 to the enlarged rear area 53 of slot 44 to the position shown in FIG. 4. In this position inner cutter assembly 32 is readily released from drive arm 43 since the enlarged area 53 permits the plate to pass over projection 45 on arm 43.
In released position of inner cutter 32 cap 50 and spring 49 are held captive on arm 43 by the engagement of projections 45 with cap 50 (FIG. 2).
If it is desired to remount inner cutter assembly 32 to drive arm 43 then a reverse procedure is followed by simply placing opening 53 of slot 44 of plate 38 on drive arm 43 and pressing downward and sliding the inner cutter assembly 32 in the direction opposite to arrow B until ears 45 are located in recessed ledge portions 47. Inner cutter assembly 32 is then released to allow the spring action of coil spring 49 to maintain cap 50 and drive arm 43 locked to plate 38 in the manner previously described. It will be appreciated that by providing ears 45 with inclined undersurfaces 55 allows for easier insertion of slot 44 onto arm 43. In addition as seen in FIG. 5 in open position of frame 18 inner cutter assembly 32 is held at angle relative thereto so as not to interfere with the pivotal movement of the frame.
In mounted position inner cutter assembly 32 is adjacent for omnidirectional movement about arm 43. In engagement with outer cutter foil 17 cutter 32 is thereby provided with increased freedom of movement increasing the efficiency of the shaving operation.
In FIG. 6 is shown another embodiment of the drive plate designated at 58. In this embodiment the H-shaped drive slot 59 is formed by spaced bars 50-61 adjacent openings 52-63. In this manner as drive arm 43 drives plate 58 a desired frequency of vibration is established by the flexing of bars 60-61 which reduces the vibrations transmitted to casing 11 in operation of shaver 10.
It will be apparent from the foregoing description that the novel drive assembly and mounting means therefore has many advantages in use. One advantage is that a relatively uncomplex structure is provided for mounting the inner cutter assembly to the drive arm. The assembly may be easily removed from the drive arm without disturbing the spring biasing means or other mechanisims within shaver 10.
Although two embodiments of the present invention have been illustrated and described in detail, it is to be expressly undertood that the invention is not limited thereto. Various changes can be made in the design and arrangement of parts without departing from the spirit and scope of the invention as the same will now be understood by those skilled in the art. | A drive assembly for a movable cutter of an electric dry shaver and which assembly includes a driven member detachably mounted on a motor operated oscillator arm. The driven member includes a rectangular plate having means supporting a plurality of cutter bars in engagement with the under surface of an outer cutter. The plate is supported on the oscillator arm by a spring urged cap member which is disposed over the oscillator arm and causes the inner cutter to be placed in cutting cooperation with the outer cutter. | 1 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of Invention
[0002] The present invention relates to the field of mouth guards and jaw-strengthening devices.
[0003] 2. Description of Related Art
[0004] Humans have the need for a strong jaw for athletics, in addition to appearance. Toned jaw muscles help tighten the facial skin and define the jawline. Jaw muscles also impact the ability eat harder foods without discomfort or strain. Jaw exercises may also help with temporomandibular joint (TMJ) dysfunction. The TMJ is surrounded by a series of muscles that control the movement of the lower jaw relative to the upper jaw. On closing, the masseter, anterior and middle temporalis, medial pterygoid, and superior head lateral pterygoid muscles are activated. To open the joint again, the inferior head of lateral pterygoid, anterior digastric and mylohyoid muscles play a part.
[0005] There have been many devices created to strengthen the jaw, from rubber inserts that are pressed on with the teeth in order to strengthen the closing of the TMJ, to springs and other resistance attached to orthodontics, to strengthen the opening of the TMJ. Typically the latter are used in conjunction with alignment rods to retrain the movement of the upper and lower jaw relative to one another, to improve orthodontic treatment and jaw alignment over time. Resistance means such as springs may be present between the upper and lower jaw such that compressive force is required to close the jaw, strengthening the closing muscles.
[0006] There are drawbacks in the prior art, however, as springs and other metal components may cause harm to the inside of the user's mouth, and alignment rods require braces to be installed on the teeth. Many of the resistance means are set, such that the amount of resistance is not variable.
[0007] Based on the foregoing, there is a need in the art for a jaw strengthening device that has no exposed components which may injure the mouth, and which may be inserted and removed as desired in order to perform jaw strengthening exercises. Furthermore, the ability to vary the resistance has the benefit of allowing the user to increase the intensity of the exercise.
SUMMARY OF THE INVENTION
[0008] A jaw-strengthening device has a first receiver configured to receive a row of teeth having first and second molar sections, the first receiver having a first air chamber within the receiver positioned in a first molar section, a second air chamber within the receiver positioned in a second molar section, and an egress valve, configured to permit egress of air and prevent ingress of air, in communication with the first and second air chambers, a second receiver configured to receive a second row of teeth, the second receiver having a third air chamber within the receiver positioned in a first molar section, a fourth air chamber within the receiver positioned in a second molar section, and an ingress valve, configured to permit ingress of air and prevent egress of air, in communication with the third and fourth air chambers, wherein the first and third air chambers are in communication, and wherein the second and fourth air chambers are in communication.
[0009] In an embodiment, the device has a lip guard positioned on an outside of the ingress valve, configured to retain a lip and prevent the lip from closing the ingress valve. It may also have a lip guard positioned on an outside of the egress valve, configured to retain a lip and prevent the lip from closing the egress valve. In an embodiment, the egress valve has a plurality of resistance settings wherein the egress air is restricted more for a higher resistance, and restricted less for a lower resistance. The egress valve may have a plurality of holes configured to permit egress of air from the egress valve and a slider configured to selectively cover the holes.
[0010] The upper and lower receivers may terminate in rear terminals, wherein the upper and lower receivers are connected at each side at the rear terminals, and air channels pass through the terminals. The air chambers may be resilient and open when no force is applied thereto. The air chambers may form bladders to temporarily retain air. The first and second receivers are molded to fit the rows of teeth. Finally, spring hinges may connect the rear terminals of the first and second receivers, wherein the spring hinge is configured to provide resistance.
[0011] 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
[0012] For a more complete understanding of the present invention, the objects and advantages thereof, reference is now made to the ensuing descriptions taken in connection with the accompanying drawings briefly described as follows.
[0013] FIG. 1 is a perspective view of the jaw-strengthening device, according to an embodiment of the present invention;
[0014] FIG. 2 is a view of the jaw-strengthening device positioned within the mouth, according to an embodiment of the present invention;
[0015] FIG. 3 is a side elevation view of the jaw-strengthening device in an open position, according to an embodiment of the present invention;
[0016] FIG. 4 is a side elevation view of the jaw-strengthening device in a closed position, according to an embodiment of the present invention;
[0017] FIG. 5 is a top plan view of the jaw-strengthening device, according to an embodiment of the present invention;
[0018] FIG. 6 is a front elevation view of the jaw-strengthening device in a closed position, according to an embodiment of the present invention;
[0019] FIG. 7 is a detail view of the air ingress and egress valves of the jaw-strengthening device, according to an embodiment of the present invention.
[0020] FIG. 8 is a side elevation view of the jaw-strengthening device in an open position, according to an embodiment of the present invention;
[0021] FIG. 9 is a side elevation view of the jaw-strengthening device in an open position, according to an embodiment of the present invention;
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0022] Preferred embodiments of the present invention and their advantages may be understood by referring to FIGS. 1-7 , wherein like reference numerals refer to like elements.
[0023] With reference to FIG. 1 , the jaw-strengthening device has an appearance similar to a mouth guard, and is adapted to be fitted within the mouth. An upper jaw receiver 5 is generally semicircular, terminating at an open rear with a terminal 8 on each side, and has an upper groove 6 (shown in FIG. 5 ) on the top to accommodate the teeth of the upper jaw. The lower jaw receiver 10 is generally semicircular, has an open rear comprising lower terminals 12 , and has a lower groove 11 (not shown) on the bottom to accommodate the lower teeth. The upper and lower jaw receivers 5 , 10 have sections generally corresponding to the teeth that are enclosed, namely an incisor section 14 in the front, a canine section 16 and a molar section 18 near the terminals 8 , 12 . The upper and lower jaw receivers 5 , 10 are connected to each other at the terminals by a hinge 20 on each side. In an embodiment, the hinge is an extension of the material of the upper and lower jaw receivers. In another embodiment, the hinge has a spring hinge 22 biasing the strengthener into an open position, wherein a force is required to compress the spring hinge 22 and close the strengthener between the teeth.
[0024] Intermediate each of the canine section 16 and the terminals 8 , 12 of the upper and lower receivers 5 , 10 , generally coinciding with the molar section 18 of a row of teeth, are compressible upper air chambers 25 on the upper receiver 5 and lower air chambers 30 on the lower receiver 10 . Within the air chambers are bladders 24 , 29 (shown in FIG. 3 ) that retain air. The lower air chambers 30 of the lower receiver are in communication with an lower air channel 26 (shown in FIG. 3 ) that passes from the lower air chamber 30 through the canine section 16 of each side of the lower receiver 10 and terminates with an air ingress valve 32 , a one-way valve that permits the ingress, but not egress, of air. The upper receiver 5 has upper air chambers 25 in communication with an upper air channel 27 (shown in FIG. 3 ) through the canine section 16 of the upper receiver 5 and terminating in an air egress valve 34 , a one-way valve that permits egress, but not ingress, of air. The upper air chambers and lower air chambers are in communication by a terminal air channel 28 (shown in FIG. 3 ) passing through the hinge at the rear. The air channels are resilient to withstand the compressive forces of the jaw as the air chambers are compressed, in order to prevent the air channels from collapsing.
[0025] Other configurations of air chambers may be used. In an embodiment, air chambers are only present either on the upper receiver or on the lower receiver, but not both, wherein the ingress and egress valves are both on the same receiver. In another embodiment, the ingress valve 32 is on the upper receiver 5 and the egress valve 34 is on the lower receiver 10 . In another embodiment, the upper receiver 5 or lower receiver 10 has both the ingress and egress valves 32 , 34 thereon. So as to prevent the lips from blocking the ingress valve 32 , a further lip groove for accommodating the lip may be present below the ingress valve to retain the lower lip and prevent the lip from obstructing the ingress valve. A similar lip groove may be present above the egress valve, but this is not critical as the egress valve will not be substantially blocked by being covered by the lip due to the exiting air flow.
[0026] The air chambers have resilience such that they return to an open or inflated position if no force is applied. Depending on the strength of the rubber used, there may be a significant mechanical compression resistance of air chambers as they are compressed in the form of distortion of the air chamber material itself. The rubber composition may be varied to provide greater or less resistance and durability. A harder durometer rubber will provide greater resistance and durability than a softer durometer rubber.
[0027] In one embodiment the egress valve has a fixed resistance. In another embodiment the egress valve 34 has variable resistance, such that the air exits the air chamber faster or slower thus decreasing or increasing the resistance, respectively. In an example the adjustable egress valve 34 has a slider 38 and a number of egress ports 36 , each sized to permit a certain air flow, wherein the slider rests in a track 40 over the ports 36 and may be slid across to cover all, some or none of the ports thereby varying the resistance of the egress.
[0028] The upper 5 and lower receivers 10 may be formed for a particular person's mouth or bite to custom fit the teeth, and may be made of a heat-deformable plastic or rubber to effect a molding to the bite, or from other non-toxic materials known in the art to take and hold a mold of the teeth.
[0029] With reference to FIG. 2 , the jaw-strengthening device is shown within the mouth, wherein the upper and lower grooves (not shown) fit over the upper and lower teeth, respectively, and the ingress valve 32 and egress valve 34 are unblocked by the lips that rest underneath the ingress valve 32 and above the egress valve 34 . In another embodiment, the ingress 32 and egress valves 34 are flush with the front of the upper 5 and lower receivers to permit the user to close his or her mouth.
[0030] With reference to FIG. 3 , the jaw-strengthening device is shown in an open position, wherein the mouth of the wearer is open. In this position, the resilient upper bladder 24 and lower bladder 29 expand to their open size, producing an area of low pressure within the bladders 24 , 29 . The ingress valve 32 draws air in along airflow marked A and through the lower channel 26 as the lower bladder 29 expands, and through the terminal channel 28 as the upper bladder 29 expands. The draw of the expanding bladders 24 , 29 pushes aside a flapper (not shown) within the valve 32 to fill the chambers and equalize the pressure. The flapper (not shown) prevents the egress of air through the ingress valve 32 . Despite a low pressure within the bladders 24 , 29 , no air ingresses through the one-way egress valve 34 . The spring hinge 22 is open in this position. The ingress and egress valves are one-way valves and may be selected from a number of designs known to those skilled in the art.
[0031] With reference to FIG. 4 , the jaw-strengthening device is shown in a closed position, wherein the mouth of the wearer is closed. In this position, the upper and lower chambers are compressed and the bladders 24 , 29 therein are compressed. The air in the system passes from the lower bladder 29 , through the terminal channel 28 , into the upper bladder 24 , through the upper channel 27 and egresses through the egress valve 34 , along the airflow marked B. The egress valve provides varying resistance to the outflow of air, wherein the resistance is either preset or is adjustable through a mechanism such as a slide 38 and a series of ports 36 . The spring hinge 22 is compressed in this position.
[0032] With reference to FIGS. 5 and 6 , a top view of the upper receiver 5 is shown, with a groove 6 for retaining the teeth running along the top. The upper bladders 5 on each side are shown in stippled lines, along with terminal channels 28 and upper channels 27 . The egress valve 34 is shown in cutaway view wherein the upper channels 27 are connected to the valve opening 40 , which communicates with the environment through a plurality of egress ports 36 , which may be selectively blocked by slider 38 .
[0033] With reference to FIG. 7 , the valves 32 , 34 are shown in detail view, and the slider 38 has been positioned over two of the four ports 36 in this embodiment increasing the resistance of air exiting the system as the jaw is clenched. The slider 38 moves within a track (not shown) and may be slid to block all ports 36 to increase resistance or leave all ports open to reduce resistance.
[0034] In an embodiment, the jaw-strengthening device is shown in an open position, wherein a piston 50 is shown biasing the device in the open position. One or more pistons are attached to the jaw-strengthening device such that force is required to overcome the biasing force of the piston to transition the device into the closed position. The placement of the piston 50 is shown wherein a single piston is towards the front of the device near the valves 32 , 34 in FIG. 8 or a plurality of pistons are positioned near the mid-section or hinge section as in FIG. 9 . In an alternative embodiment, one or more pistons 50 are used in combination with the spring hinge 22 .
[0035] The jaw strengthener has the benefit of increasing fellatio performance and endurance, rehabilitating the jaw and corresponding muscles after a trauma such as a broken jaw/surgery or other injury, allowing musicians such as saxophone players to play longer with more comfortability, and decrease susceptibility to knock outs for fighters and athletes.
[0036] The invention has been described herein using specific embodiments for the purposes of illustration only. It will be readily apparent to one of ordinary skill in the art, however, that the principles of the invention can be embodied in other ways. Therefore, the invention should not be regarded as being limited in scope to the specific embodiments disclosed herein, but instead as being fully commensurate in scope with the following claims. | A jaw-strengthening device has a first receiver configured to receive a row of teeth having first and second molar sections, the first receiver having a first air chamber within the receiver positioned in a first molar section, a second air chamber within the receiver positioned in a second molar section, and an egress valve, configured to permit egress of air and prevent ingress of air, in communication with the first and second air chambers, a second receiver configured to receive a second row of teeth, the second receiver having a third air chamber within the receiver positioned in a first molar section, a fourth air chamber within the receiver positioned in a second molar section, and an ingress valve in communication with the third and fourth air chambers, wherein the first and third air chambers, and separately the second and fourth air chambers, are in communication. | 0 |
BACKGROUND OF THE INVENTION
This application is a continuation-in-part application of U.S. patent application Ser. No. 08/785,994, filed Jan. 21, 1997, now U.S. Pat. No. 5,819,961.
This invention relates to a device for hanging clothing, and more particularly, to a collapsible and foldable valet which results in a streamline, narrow, flush configuration.
There are numerous garment supporters or racks in the prior art. Such devices are disclosed in U.S. Pat. Nos. 984,591; 1,075,395; 1,176,563; and 1,525,701. However, nothing in the prior art teaches the structure of the present invention whereby a valet may be collapsed and folded into the present unique, reduced collapsed configuration while at the same time providing a hanger extension when in the extended position. The prior art generally does not teach providing additional support beneath any outstretched member; thus, the weight of clothing hung from the racks of the prior art often results in the collapse or deformation of the rack. The clothing hung from the prior art racks often becomes twisted and wrinkled, thereby defeating a principal purpose of such racks.
The present invention solves the problems of the prior art by providing a hanger lifting arm which supports the outstretched hanger member when the valet is in use.
SUMMARY OF THE INVENTION
A mountable valet has a housing with a longitudinal channel for receiving a hanger arm and a supporting or lifting arm in a flush or flat profile. An elongated slot in the hanger arm slidably secures a first end of the lifting arm while the second end is held by a pivot pin within the channel. A notch in the bottom edge of the arm receives the pivot pin when the hanger is in the collapsed position.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a front, right side perspective view of the invention in the folded or collapsed position.
FIG. 2 illustrates a front, right side perspective view of the invention in the open or extended position.
FIG. 2A illustrates a side elevation view of the invention in the extended position in an alternative valet style.
FIG. 3 shows a front elevation view of the mounting bracket of the present invention.
FIG. 4 shows a side elevation view of the mounting bracket of the present invention taken along Line A--A of FIG. 3.
FIG. 5 is a front elevation view of the hanger member of the present invention.
FIG. 6 is a side elevation view of the hanger member of the present invention.
FIG. 7 is a front elevation view of the support arm of the present invention.
FIG. 8 is a side elevation view of the support arm of the present invention.
FIG. 9 is a side elevation view of a longer hanger arm of the present invention.
FIG. 10 is a side plan view of the longer arm within a housing.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 illustrates the present invention in a folded or collapsed position. The wall mounted valet (10) has a decorative mounting housing (12) which has a longitudinal area (A) and a face (14). A retraction slot (16) extends vertically along the longitudinal axis of the housing (12) and has grasping notches (18A and 18B) along opposite edges of the slot (16). The grasping notches may be moved to the lower section of the bracket as shown in FIG. 2.
A hanger arm member (20) is pivotally attached inside slot (16) at pivot (22) at a top end of the hanger arm (20). Along a top edge (24) of hanger arm (20) are a multiplicity of ramped shoulders (26). At the end opposite the pivot (22) is a bulbous tab (23) which functions both as a means for grasping and lifting the hanger arm (20) and as an end stop for items affixed to the hanger.
As FIG. 6 shows in more detail, the hanger arm member (20) is provided with a slide slot (28) extending from the pivot (22) to the knob (23). A short "L" shaped section is provided in slot (28) at a 78° angle to the vertical to accept the support arm (30) in a locked open position as shown in FIG. 2.
FIG. 2 illustrates the present invention (10) in the open, extended, or raised position with hanger arm member (20) extending outwardly and upwardly from the face (14) of the bracket (12). It may be understood that individual hangered items (not shown) may be placed along the top edge (24) of the hanger and be held by the ramped shoulders (26).
FIG. 2A illustrates the valet hanger arm (20) on a different type of mount (100). Support lifting arm (30) and the ramped shoulders (26) on the top edge (24) of the arm (20) support the hangers in position. The valet is shown in the extended position. The lifting arm (30) is pivotally attached at a first end (33) to the upper sleeve (96) and at a second end (32) to beneath the approximate mid-point of the hanger arm (20). Hanging arm (20) and lifting arm (30) are positioned within a channel (16) and lie parallel to and against the vertical support member (92) when the sleeve (96) is in the collapsed position.
FIG. 3 shows a front elevation view of the mounting bracket (12). Slot (16) extends vertically along the face (14). Grasping notches (18A and 18B) may be seen on opposite sides of slot (16). Nipples (19A and 19B) are formed into the bracket (12) to hold pivot pin (21A) which pivotally supports support arm (30) at support pivot opening (33). The upper end of hanger member (20) is pivotally held in slot (16) at pivot (22) by a pin (21B) passing through member (20) and pivotal between shoulders (34A and 34B) on the bracket (12).
Bracket (12) may be mounted to a wall through openings (36), or other suitable means, using various types of fasteners.
FIG. 4 shows the details of the bracket profile. The recessed slot (16) enables the hanger (20) and support arm (30) to be recessed within the bracket in the folded condition. This yields a smooth flat or flush profile.
FIGS. 5-8 illustrate the construction details of the hanger member (20) and the support arm (30). Of particular importance is the sliding slot (28) with the "L" shaped end (29) angled at 78° from the vertical which enables the hanger to be "locked" in the extended position. A small pin (not shown) passes through the opening (32) in the upper end (40) of arm (30) and into slot (28) to lift and support the hanger (20).
FIG. 9 illustrates another embodiment in which the hanger arm (20A) has an additional length. Slot (28) is provided with lock (29). Along the bottom edge (98) of arm (20A) is a notch (99) which receives pivot pin (21A). This allows the arm (20A) to lie flush in the channel (16) when the longer hanger arm (20A) is used.
FIG. 10 illustrates the valet (10) in the collapsed position with pivot pin (21A) received into notch (19) of arm (20A).
Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limited sense. Various modifications of the disclosed embodiments, as well as alternative embodiments of the inventions will become apparent to persons skilled in the art upon the reference to the description of the invention. It is, therefore, contemplated that this disclosure and the attached drawings will cover such modifications that fall within the scope of the invention. | A flush, mountable valet having a hanger arm and a support arm. The hanger arm and support arm are retained within a longitudinal channel extending the length of the valet housing. A flat or flush profile is achieved. | 0 |
This application claims the benefit of U.S. Ser. No. 60/076,677, filed Mar. 3, 1998.
FIELD OF THE INVENTION
The field of the invention is generally related to pharmaceutical agents useful in treating graft-versus-host disease (GVHD) in patients that have received allogenic bone marrow transplants.
BACKGROUND OF THE INVENTION
Organ transplantation is now used with great success to improve the quality of human life. Substantial progress has been made in using kidneys, hearts, and livers from unrelated individuals. However, transplantation of hematopoietic stem cells from an unrelated (or allogeneic) donor is a more complicated endeavor. Here multipotent stem cells which have the capacity to regenerate all the blood-forming elements and the immune system are harvested from bone marrow or peripheral blood from one individual are transferred to another. However, histocompatibility differences between donor and recipient results in a higher incidence of transplant-related complications, and has limited the use of this procedure (Forman et al., Blackwell Scientific Publications , 1994).
It is unfortunate that only few individuals are candidates for allogeneic hematopoietic stem cell transplantation at the present time because the spectrum of diseases treatable by this procedure has steadily increased. These diseases now include hematologic malignancies such as the acute or chronic leukemias, multiple myeloma, myelodysplastic syndromes; lymphomas; and the severe anemias such as aplastic anemia or thalassemia.
Allogeneic stem cell transplantation begins with treatment of the recipient with a highly immunosuppressive conditioning regimen. This is most commonly accomplished with high doses of chemotherapy and radiation which effectively kill all the blood forming elements of the bone marrow. Besides preparing the recipient bone marrow for donor stem cell transplantation, the conditioning regimen serves to kill much of the malignancy that remains in the body. The period of time between the completion of the conditioning regimen, and engraftment of the donor stem cells is the most dangerous for the recipient. It is during this time that the patient is completely immunocompromised and susceptible to a host of life-threatening infections. This vulnerability persists until the grafted donor stem cells proliferate and differentiate into the needed white blood cells and immune cells needed to combat infections.
Moreover, donor stem cell preparations generally contain immune cells called T lymphocytes. Unless the donor stem cells originate from an identical twin the transferred T cells turn against the recipient's tissues and trigger a deadly ailment called graft versus host disease (or GVHD). This is because the donor T lymphocytes recognize histocompatibility antigens of the recipient as foreign and respond by causing multi-organ dysfunction and destruction.
Current techniques of immunosuppression have made allogeneic stem cell transplantation from a related, histocompatible (HLA-matched) donor much safer than it once was. Allogeneic stem cell transplantation from an unrelated, HLA-matched donor is commonly complicated by serious, often fatal GVHD. The threat of GVHD is even higher when the stem cell donor is HLA mismatched.
Since only 30% of patients in need of allogeneic stem cells will have a sibling with identical histocompatibility antigens (Dupont, B., Immunol Reviews 157:12, 1997), there is a great need to make HLA-matched unrelated, and HLA-mismatched transplantation a safer procedure. There have been two principal approaches to resolving this problem. The first has been to deplete the graft of contaminating T lymphocytes and the second has been to inactivate the T cells so they cannot attack the recipient.
In the 1970's it became evident that ex-vivo removal of mature T lymphocytes from a bone marrow graft prior to transplantation dramatically decreased or prevented GVHD in animals receiving marrow grafts across major histocompatibility barriers (Rodt, H. J. Immunol 4:25-29, 1974; and 4 Vallera et al., Transplantation 31:218-222, 1981). However, with T cell depletion the incidence of graft failure, graft rejection, relapse of leukemia, and viral-induced lympho-proliferative disease markedly increased (Martin et al. Blood 66:664-672, 1985; 6 Patterson et al. Br J Hematol 63:221-230, 1986; Goldman et al. Ann Intem Med 108:806-814, 1988; and Lucas et al. Blood 87:2594-2603, 1996). Thus, the transplantation of donor T cells on the stem cells has beneficial as well as deleterious effects. One needs the facilitating effect of the T cells on the engraftement of stem cells and the now well recognized graft-versus-tumor effects, but not graft-versus host disease.
Several approaches have been used to decrease T cell activation. These include: 1) in vivo immunosuppressive effects of drugs such as FK506 and rapamycin (Blazar et al. J. Immunol 153:1836-1846, 1994; Dupont et al. J. Immunol 144:251-258, 1990; Morris, Ann NY Acad Sci 685:68-72. 1993; and Blazar et al. J Immunol 151:5726-5741, 1993); 2) the in vivo targeting of GVHD-reactive T cells using intact and F(ab′)2 fragments of monoclonal antibodies(mAb)reactive against T cell determinants or mAb linked to toxins (Gratama et al. Amj Kidney Dis 11:149-152, 1984; Hiruma et al. Blood 79:3050-3058, 1992; Anasetti et al. Transplantation 54:844-851, 1992; Martin et al. Bone Marrow Transplant 3:437-444, 1989); 3) inhibition of T cell signaling via either IL-2/cytokine receptor interactions (Herve et al. Blood 76:2639-2640, 1990) or the inhibition of T cell activation through blockade of co-stimulatory or adhesogenic signals (Boussiotis et al. J Exp Med 178:1753-1763, 1993; Gribben et al. Blood 97:4887-4893, 1996; and Blazar et al. Immunol Rev 157:79-90, 1997); 4) the shifting of the balance between acute GVHD-inducing T helper-type 1 T cells to anti-inflammatory T helper-type 2 T cells via the cytokine milieu in which these cells are generated (Krenger et al. Transplantation 58:1251-1257, 1994; Blazar et al. Blood 88:247, 1996, abstract; Krenger et al. J Immunol 153:585-593. 1995; Fowler et al. Blood 84:3540-3549, 1994); 5) the regulation of alloreactive T cell activation by treatment with peptide analogs which affect either T cell receptor/major histocompatibility complex (MHC) interactions, class II MHC/CD4 interactions, or class I MHC/CD8 interactions (Townsend and Korngold (unpublished data)); and 6) the use of gene therapy to halt the attack of donated cells on the recipient's tissues (Bonini et al. Science 276:1719-24, 1997).
There is suggestive evidence that the T lymphocytes from non-identical donors can become tolerant to the recipient's tissues. Unlike patients who receive solid organ allografts for whom life-long immunosuppressive therapy is needed to control chronic rejection, there is evidence of immunologic tolerance with stem cell allografts. The majority of these patients can be withdrawn from immune suppression without further evidence of GVHD (Storb et al. Blood 80:560-561, 1992; and Sullivan et al. Semin Hematol 28:250-259, 1992).
Immunologic tolerance is a specific state of non-responsiveness to an antigen. Immunologic tolerance generally involves more than the absence of an immune response; this state is an adaptive response of the immune system, one meeting the criteria of antigen specificity and memory that are the hallmarks of any immune response. Tolerance develops more easily in fetal and neonatal animals than in adults, suggesting that immature T and B cells are more susceptible to the induction of tolerance. Moreover, studies have suggested that T cells and B cells differ in their susceptibility to tolerance induction. Induction of tolerance, generally, can be by clonal deletion or clonal anergy. In clonal deletion, immature lymphocytes are eliminated during maturation. In clonal anergy, mature lymphocytes present in the peripheral lymphoid organs become functionally inactivated.
Following antigenic challenge stimulation, T cells generally are stimulated to either promote antibody production or cell-mediated immunity. However, they can also be stimulated to inhibit these immune responses instead. T cells with these down-regulatory properties are called “suppressor cells”.
Although it is known that T suppressor cells produce cytokines such as transforming growth factor beta (TGF-beta), interleukin 4 (IL-4) or interleukin (IL-10) with immunosuppressive effects, until recently the mechanisms responsible for the generation of these regulatory cells have been poorly understood. It was generally believed that CD4+ T cells induce CD8− T cells to develop down-regulatory activity and that interleukin 2 (IL-2) produced by CD4+ cells mediates this effect. Although most immunologists agree that IL-2 has an important role in the development of T suppressor cells, whether this cytokine works directly or indirectly is controversial (Via et al. International Immunol 5:565-572, 1993; Fast, J Immunol 149:1510-1515, 1992; Hirohata et al. J Immunol 142:3104-3112, 1989; Taylor, Advances Exp Med Biol 319:125-135, 1992; and Kinter et al., Proc. Nati. Acad. Sci. USA 92:10985-10989,1995). Recently, IL-2 has been shown to induce CD8+ cells to suppress HIV replication in CD4−T cells by a non-lytic mechanism. This effect is cytokine mediated, but the specific cytokine with this effect has not been identified (Barker et al. J Immunol 156 : 4476 - 83 , 1996 ; and Kinter et al. Proc Nat Acad Sci USA 99:10985-9 1995).
A model using human peripheral blood lymphocytes to study T cell/B cell interactions in the absence of other accessory cells has been developed (Hirokawa et al. J. Immunol . 149:1859-1866, 19??). With this model it was found that CD4+ T cells by themselves generally lacked the capacity to induce CD8+ T cells to become potent suppressor cells. The combination of CD8+ T cells and NK cells, however, induced strong suppressive activity (Gray et al. J Exp Med 180:1937-1942, 1994). It was then demonstrated that the contribution of NK cells was to produce TGF-beta in its active form. It was then reported that a small non-immunosuppressive concentration (10-100 pg/ml) of this cytokine served as a co-factor for the generation of strong suppressive effects on IgG and IgM production (Gray et al. J Exp Med 180:1937-1942, 1994). Further, it was demonstrated that NK cells are the principal lymphocyte source of TGF-beta (Gray et al. J Immunol, 160:2248-2254, 1998).
TGF-beta is a multifunctional family of cytokines important in tissue repair, inflammation and immunoregulation (Border et al. J Clin Invest 90:1-7, 1992; and Sporn et al. J Cell Biol 105:1039-1045, 1987). TGF-beta is unlike most other cytokines in that the protein released is biologically inactive and unable to bind to specific receptors (Massague, Cell 69:1067-1070, 1992). The conversion of latent to active TGF-beta is the critical step which determines the biological effects of this cytokine.
There is some evidence that NK cell-derived TGF-beta has a role in the prevention of GVHD. Whereas the transfer of stem cells from one strain of mice to another histocompatibility mismatched strain resulted in death of all recipients from GVHD within 19 days, the simultaneous transfer of NK cells from the donor animals completely prevented this consequence. All the recipient mice survived indefinitely. This therapeutic effect, however, was completely blocked by antagonizing the effects of TGF-beta by the administration of a neutralizing antibody (Murphy et al. Immunol Rev 157:167-176, 1997 ).
It is very likely, therefore, that the mechanism whereby NK cell-derived TGF-beta prevented GVHD is similar to that described by Horwitz et al. in the down-regulation of antibody production. In each case NK cell-derived TGF-beta was responsible for the generation of suppressor lymphocytes that blocked these respective immune responses. The mouse study is of particular interest since the histocompatibility differences between genetically disparate inbred mice strains would mirror that of unrelated human donors. A modification of this strategy, therefore might overcome GVHD in mismatched humans.
Anti-CD2 monoclonal antibodies and other constructs that bind to the CD2 co-receptor have been shown to be immunosupressive. It has now been demonstrated that at least one mechanism to explain this immunosuppressive effect is by inducing the production of TGF-beta (Gray et al. J Immunol , 160:2248-2254, 1998).
One strategy to prevent GVHD would be to isolate and transfer NK cells along with the stem cells. Another would be to treat the immunocompromised recipient who has received allogeneic stem cells with TGF-beta, anti-CD2 monoclonal antibodies, IL-2 or a combination of these cytokines. The first strategy would be difficult because NK cells comprise only 10 to 20% of total lymphocytes so that it would be difficult to harvest a sufficient number of cells for transfer. The second strategy is limited by numerous effects on different body tissues and are not very safe to deliver to a patient systemically. What is needed, therefore, is a way to induce mammalian cells to suppress the development of GVHD ex vivo.
SUMMARY OF THE INVENTION
In accordance with the objects outlined above, the present invention provides methods for inducing T cell tolerance in a sample of ex vivo peripheral blood mononuclear cells (PBMCs) comprising adding a suppressive composition to the cells. The suppressive composition can be IL-10, TGF-β, or a mixture.
In an additional aspect, the present invention provides methods for treating donor cells to ameliorate graft versus host disease in a recipient patient. The methods comprise removing peripheral blood mononuclear cells (PBMC) from a donor, and treating the cells with a suppressive composition for a time sufficient to induce T cell tolerance. The cells are then introducing to a recipient patient. The PBMCs can be enriched for CD8+ cells, if desired. The methods may additionally comprising adding the treated cells to donor stem cells prior to introduction into the patient.
In an additional aspect, the invention provides kits for the treatment of donor cells comprising a cell treatment container adapted to receive cells from a donor and at least one dose of a suppressive composition. The kits may additionally comprising written instructions and reagents. The cell treatment container may comprise a sampling port to enable the removal of a fraction of the cells for analysis, and an exit port adapted to enable transport at least a portion of the cells to a recipient patient.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and 1B depict that TGF-β can upregulate expression of CD40 Ligand (CD40L) on T cells. Purified T cells were stimulated with PMA (20 ng/ml) and ionomycin (5 μM) in the presence or absence of TGF-β. After 6 hours the cells were stained with anti-CD40L antibodies. In the absence of TGF-β, there were 30% positive cells (solid line, panel A). With 100 pg/ml of TGF-β, 66% of the cells were positive (solid line, panel B). The dotted line in both panenis is the reactivity of a control antibody.
FIGS. 2A, 2 B, 2 C and 2 D depict that TGF-β increases TNF-α expression by CD8+ cells. Purified CD8+ cells were stimulated for 24 hours with Con A (5 pg/ml) + TGF-β (10 pg/ml)+ IL-2 (10 U). During the last 6 hours, monensin (2 μM) was also present to prevent cytokine release. The cells were first stained with anti-CD69 to distinguish the activated cells. Then the cells were fixed (4% paraformaldhyde), permeabilized (0.1% saponin) and stained with anti-TNF-α antibodies.
FIGS. 3A and 3B depict TGF-β, enhances IL-2 expression by T cells. Purified T cells were stimulated in the presence or absence of TGF-β (1 ng/ml). In the absence of TGF-β, 36% of the cells were positive (panel A, solid line) whereas with TGF-β, 53% were positive (panel B, solid line).
FIGS. 4A, 4 B and 4 C depict that TGF-β can enhance or inhibit cytotoxic activity. In panels A and B, purified T cells were cultured with irradiated allogenic stimulator cells in the presence or absence of the indicated cytokines. After 48 hours, the cells were washed and after a further 3 days, assayed for cytotoxic activity against 31 Cr-labelled stimulator ConA blasts. In panel C, purified CD8+ cells were cultured with irradiated allogenic cells in the presence or absence of TGF-β(10 pg/ml) or IL-12 (100 U). After 48 hours, the cells were washed and added to autologous T cells and irradiated allogenic cells. After 5 days of culture, cytotoxic activity was determined using 31 Cr-labelled stimulator ConA blasts as target cells.
DETAILED DESCRIPTION OF THE INVENTION
The present invention allows for the transfer of histoincompatible stem cells to humans with a variety of malignant or hereditary diseases using a method to prevent life-threatening graft-versus-host disease. This is accomplished by treatment of donor cells with a combination of mitogens and cytokines ex-vivo. The particular advantage of this procedure is that it avoids the removal of donor T cells which facilitate stem cell engraftment and that have the potential to attack any remaining malignant cells. Once a state of tolerance between donor and host has been achieved, non-conditioned donor T cells can be transferred to maximize the beneficial graft-versus-tumor immune response.
This strategy is unlike almost all other treatment modalities currently in use. These cytokines and mitogens described would have severe toxic side effects if administered in vivo. The ex-vivo protocol described avoids these side effects. The ability to successfully engraft histoincompatible stem cells for treatment of life-threatening diseases would be a milestone in medicine.
In addition, a further advantage of the present invention is that it may avoid or minimize the very toxic immunosuppressive medicines that must be given to the recipient to prevent GVHD. These medicines also block the ability of the donor-derived lymphocytes which repopulate the immune system of the recipient from becoming “educated” to their new host. Therefore, it is difficult to stop the immunosuppressive drugs, unless an alternative treatment such as the present invention is used.
The strategy of the present invention is to suppress GVHD by both suppressing T cell activation and inducing a tolerant state in the donor cells, which prevents the donor cells from attacking recipient cells. Surprisingly, the methods outlined herein result in not only the suppression of the treated cells but additionally induces them to prevent other donor cells from killing recipient cells as well, i.e. they become tolerant. That is, the methods outlined herein not only decrease the capacity of the donor's cells to attack the recipient's cells, but induces some of the donor's cells to assume a surveillance role and prevent other donor cells from mounting an immune attack against the recipient host. The net result is for the donor lymphocytes to be tolerant to the histocompatibility antigens of the recipient, but does not impair the ability of the new lymphocytes to attack tumor cells.
Another significant potential advantage of this strategy is a low probability of serious adverse side effects. Since only trace amounts of suppressive compositions such as cytokines will be returned to the patient, there should be minimal toxicity.
Accordingly, the present invention is drawn to methods of treating donor cells for transplantation into a recipient that comprise removing peripheral blood mononuclear cells (PBMCs) from the donor and treating the cells with a composition that is on one hand suppressive, but on the other hand generates surveillance cells to prevent an immune attack.
The present invention shows that the treatment of the donor cells by a suppressive composition blocks an immune attack against the recipient's cells. Without being bound by theory, it appears that there are several ways the methods of the invention may work. First of all, the donor cells are activated to become tolerant to the recipient's cells. Secondly, the donor CD8+ cells get activated to become regulatory cells, to prevent other donor cells from killing recipient cells. These results lead to amelioration of a GVH response. Without being bound by theory, it appears that the inhibition of cytotoxic activity may occur as a result of the effects TGF-β on the cells; as depicted in the figures, the addition of TGF-β causes the upregulation of CD40L on T cells, increases TNF-α expression by CD8+ cells, and enhances IL-2 expression.
Thus, in a preferred embodiment, the present invention induces tolerance in the donor cells to recipient tissue, thus avoiding GVHD, by treating them with a suppressive composition ex vivo.
Accordingly, the present invention provides methods of treating donor cells to induce or establish tolerance to recipient cells prior to transplantation into a recipient patient to decrease or eliminate a graft-versus-host response. By “T cell tolerance” herein is meant immune non-responsiveness to the recipient, i.e. a tolerance to the histocompatibility antigens of the recipient. Without being bound by theory, this may be due to anergy or death of the T cells. Preferably, the T cells retain the ability to recognize other antigens as foreign, to facilitate tumor killing and general immunological responses to foreign antigens.
Using the methods outlined herein, a GVH response is suppressed or treated. By “treating” GVHD herein is meant that at least one symptom of the GVHD is ameliorated by the methods outlined herein. This may be evaluated in a number of ways, including both objective and subjective factors on the part of the patient as is known in the art. For example, GVHD generally exhibits a skin rash, an abnormality in liver function studies, fever, general symptoms including fatigue, anemia, etc.
By “patient” herein is meant a mammalian subject to be treated, with human patients being preferred. In some cases, the methods of the invention find use in experimental animals and in the development of animal models for disease, including, but not limited to, rodents including mice, rats, and hamsters; and primates.
The methods provide for the removal of blood cells from a patient. In general, peripheral blood mononuclear cells (PBMCs) are taken from a patient using standard techniques. By “peripheral blood mononuclear cells” or “PBMCs” herein is meant lymphocytes (including T-cells, B-cells, NK cells, etc.) and monocytes. As outlined more fully below, it appears that the main effect of the suppressive composition is to enable CD8+ T cells to become tolerant. Accordingly, the PBMC population should comprise CD8+ T cells. Preferably, only PBMCs are taken, either leaving or returning red blood cells and polymorphonuclear leudocytes to the patient. This is done as is known in the art, for example using leukophoresis techniques. In general, a 5 to 7 liter leukophoresis step is done, which essentially removes PBMCs from a patient, returning the remaining blood components. Collection of the cell sample is preferably done in the presence of an anticoagulant such as heparin, as is known in the art.
In general, the sample comprising the PBMCs can be pretreated in a wide variety of ways. Generally, once collected, the cells can be additionally concentrated, if this was not done simultaneously with collection or to further purify and/or concentrate the cells. The cells may be washed, counted, and resuspended in buffer.
The PBMCs are generally concentrated for treatment, using standard techniques in the art. In a preferred embodiment, the leukophoresis collection step results a concentrated sample of PBMCs, in a sterile leukopak, that may contain reagents or doses of the suppressive composition, as is more fully outlined below. Generally, an additional concentration/purification step is done, such as FicollHypaque density gradient centrifugation as is known in the art.
In a preferred embodiment, the PBMCs are then washed to remove serum proteins and soluble blood components, such as autoantibodies, inhibitors, etc., using techniques well known in the art. Generally, this involves addition of physiological media or buffer, followed by centrifugation. This may be repeated as necessary. They can be resuspended in physiological media, preferably AIM-V serum free medium (Life Technologies) (since serum contains significant amounts of inhibitors of TGF-β) although buffers such as Hanks balanced salt solution (HBBS) or physiological buffered saline (PBS) can also be used.
Generally, the cells are then counted; in general from 1×10 9 to 2×10 9 white blood cells are collected from a 5-7 liter leukophoresis step. These cells are brought up roughly 200 mls of buffer or media.
In a preferred embodiment, the PBMCs may be enriched for one or more cell types. For example, the PBMCs may be enriched for CD8+ T cells, CD4+ T cells or, in the case of stem cell isolation as is more fully described below, CD34+ stem cells. This is done as is known in the art, as described in Gray et al. (1998), J. Immunol . 160:2248, hereby incorporated by reference. Generally, this is done using commercially available immunoabsorbent columns, or using research procedures (the PBMCs are added to a nylon wool column and the eluted, nonadherent cells are treated with antibodies to CD4, CD16, CD11b, and CD74, followed by treatment with immunomagnetic beads, leaving a population enriched for CD8+ T cells). In one embodiment, cell populations are enriched for CD8+ cells, as these appear to be the cells most useful in the methods of the invention. However, one advantage of using PBMCs is that other cell types within the PBMC population produce IL-10, thus decreasing or even eliminating the requirement of the suppressive composition comprising IL-10.
Once the cells have undergone any necessary pretreatment, the cells are treated with a suppressive composition. By “treated” in this context herein is meant that the cells are incubated with the suppressive composition for a time period sufficient to result in T cell tolerance, particularly when transplanted into the recipient patient. The incubation will generally be under physiological temperature.
By “suppressive composition” or “tolerance composition” is meant a composition that can induce T cell tolerance. Generally, these compositions are cytokines. Suitable suppressive compositions include, but are not limited to, IL-10, IL-2 and TGF-β. A preferred suppressive composition is a mixture of IL-10 and TGF-β.
The concentration of the suppressive composition will vary on the identity of the composition, but will generally be at physiologic concentration, i.e. the concentration required to give the desired effect, i.e. an enhancement of specific types of regulatory cells. In a preferred embodiment, TFG-β is used in the suppressive composition. By “transforming growth factor -β ” or “TGF-β” herein is meant any one of the family of the TGF-βs, including the three isoforms TGF-β1, TGF-β2, and TGF-β3; see Massague, (1980), J. Ann. Rev. Cell Biol 6:597. Lymphocytes and monocytes produce the β1 isoform of this cytokine (Kehrl et al. (1991), Int J Cell Cloning 9:438-450). The TFG- 0 can be any form of TFG-β that is active on the mammalian cells being treated. In humans, recombinant TFG-β is currently preferred. A human TGF-β2 can be purchased from Genzyme Pharmaceuticals, Farmington, Mass. In general, the concentration of TGF-β used ranges from about 2 picograms/ml of cell suspension to about 2 nanograms, with from about 10 pg to about 500 pg being preferred, and from about 50 pg to about 150 pg being especially preferred, and 100 pg being ideal.
In a preferred embodiment, IL-10 is used in the suppressive composition. The IL-10 can be any form of IL-10 that is active on the mammalian cells being treated. In humans, recombinant IL-10 is currently preferred. Recombinant human IL-10 can be purchased. In general, the concentration of IL-10 used ranges from about 1 U/ml of cell suspension to about 100, with from about 5 to about 50 being preferred, and with 10 U/ml being especially preferred.
In a preferred embodiment, IL-2 is used as the suppressive composition. The IL-2 can be any form of IL-2 that is active on the mammalian cells being treated. In humans, recombinant IL-2 is currently preferred. Recombinant human IL-2 can be purchased from Cetus, Emeryville, Calif. In general, the concentration of IL-2 used ranges from about 1 Unit/ml of cell suspension to about 100 U/ml, with from about 5 U/ml to about 25 U/ml being preferred, and with 10 U/ml being especially preferred. In a preferred embodiment, IL-2 is not used alone.
In a preferred embodiment, TGF-β can be used alone as the suppressive composition. Alternate preferred embodiments utilize IL-10 alone, combinations of TGF-β, IL-10 and IL-2, with the most preferred embodiment utilizing a mixture of TGF-β and IL-10.
The suppressive composition is incubated with the donor cells and a population of irradiated PMBC recipient cells (harvested as outlined above). The recipient cells are irradiated so that they cannot attack the donor cells, but will stimulate the donor cells to become tolerant to the recipient cells. The incubation occurs for a period of time sufficient to cause an effect, generally from 4 hours to 96 hours, although both shorter and longer time periods are possible.
In one embodiment, treatment of the donor cells with the suppressive composition is followed by immediate transplantation into the recipient patient, generally after the cells have been washed to remove the suppressive composition.
In a preferred embodiment, a second step is done. In this embodiment, after the donor cells have been conditioned or treated with the suppressive composition, they may be frozen or otherwise stored. Then a second step comprising obtaining a population of donor hematopoietic stem cells from aspirated bone marrow or PBMCs. Stem cells comprise a very small percentage of the white blood cells in blood, and are isolated as is known in the art, for example as described in U.S. Pat. Nos. 5,635,387 and 4,865,204, both of which are incorporated by reference in their entirety, or harvested using commercial systems such as those sold by Nexell. As outlined above, CD34+ stem cells can be concentrated using affinity columns; the eluted cells are a mixture of CD34+ stem cells and lymphocytes. The contaminating lymphocytes are generally be removed using known techniques such as staining with monoclonal antibodies and removal using conventional negative selection procedures.
Once the CD34+ stem cells have been isolated, they may be mixed with the donor cells previously treated with the suppressive composition and immediated introduced into the recipient patient.
In one embodiment, the cells are treated for a period of time, washed to remove the suppressive composition, and may additionally reincubated. The cells are preferably washed as outlined herein to remove the suppressive composition. Further incubations for testing or evaluation may also be done, ranging in time from a few hours to several days. If evaluation of any cellular characteristics prior to introduction to a patient is desirable, the cells may be incubated for several days to several weeks to expand numbers of suppressor cells.
Once the cells have been treated, they may be evaluated or tested prior to transplantation into the patient. For example, a sample may be removed to do: sterility testing; gram staining, microbiological studies; LAL studies; mycoplasma studies; flow cytometry to identify cell types; functional studies, etc. Similarly, these and other lymphocyte studies may be done both before and after treatment. A preferred analysis is a test using labeled recipient cells; incubating the treated tolerant donor cells with a labeled population of the recipient cells will verify that the donor cells are tolerant and won't kill the recipient cells.
In a preferred embodiment, the treatment results in the conditioning of the T cells to become non-responsive to histocompatibility antigens of the recipient so that GVHD is prevented.
In a preferred embodiment, prior to transplantation, the amount of total or active TGF-β can also be tested. As noted herein, TGF-β is made as a latent precursor that is activated post-translationally.
After the cell treatment, the donor cells are transplanted into the recipient patient. The MHC class I and class II profiles of both the donor and the recipient are determined. Preferably, a non-related donor is found that preferably matches the recipients HLA antigens, but may mismatch at one or more loci if a matched donor cannot be identified. The recipient patient has generally undergone bone marrow ablation, such as a high dose chemotherapy treatment, with or without total body irradiation.
The donor cells are transplanted into the recipient patient. This is generally done as is known in the art, and usually comprises injecting or introducing the treated cells into the patient as will be appreciated by those in the art. This may be done via intravascular administration, including intravenous or intraarterial administration, intraperitoneal administration, etc. For example, the cells may be placed in a 50 mol Fenwall infusion bag by injection using sterile syringes or other sterile transfer mechanisms. The cells can then be immediately infused via IV administration over a period of time, such as 15 minutes, into a free flow IV line into the patient. In some embodiments, additional reagents such as buffers or salts may be added as well.
After reintroducing the cells into the patient, the effect of the treatment may be evaluated, if desired, as is generally outlined above and known in the art.
The treatment may be repeated as needed or required. After a period of time, the leukemic cells may reappear. Because the donor lymphocytes are now tolerant to the recipient's cells, the patient now receives a transfusion of unconditioned donor lymphocytes which recognize the leukemic cells as foreign and kill these cells.
In a preferred embodiment, the invention further provides kits for the practice of the methods of the invention, i.e., the incubation of the cells with the suppressive compositions. The kit may have a number of components. The kit comprises a cell treatment container that is adapted to receive cells from a donor. The container should be sterile. In some embodiments, the cell treatment container is used for collection of the cells, for example it is adaptable to be hooked up to a leukophoresis machine using an inlet port. In other embodiments, a separate cell collection container may be used.
The form and composition of the cell treatment container may vary, as will be appreciated by those in the art. Generally, the container may be in a number of different forms, including a flexible bag, similar to an IV bag, or a rigid container similar to a cell culture vessel. It may be configured to allow stirring. Generally, the composition of the container will be any suitable, biologically inert material, such as glass or plastic, including polypropylene, polyethylene, etc. The cell treatment container may have one or more inlet or outlet ports, for the introduction or removal of cells, reagents, suppressive compositions, etc. For example, the container may comprise a sampling port for the removal of a fraction of the cells for analysis prior to introduction into the recipient patient. Similarly, the container may comprise an exit port to allow introduction of the cells into the recipient patient; for example, the container may comprise an adapter for attachment to an IV setup.
The kit further comprises at least one dose of a suppressive composition. “Dose” in this context means an amount of the suppressive composition such as cytokines, that is sufficient to cause an effect. In some cases, multiple doses may be included. In one embodiment, the dose may be added to the cell treatment container using a port; alternatively, in a preferred embodiment, the dose is already present in the cell treatment container. In a preferred embodiment, the dose is in a lyophilized form for stability, that can be reconstituted using the cell media, or other reagents.
In some embodiments, the kit may additionally comprise at least one reagent, including buffers, salts, media, proteins, drugs, etc. For example, mitogens can be included.
In some embodiments, the kit may additional comprise written instructions for using the kits.
The following examples serve to more fully describe the manner of using the above-described invention, as well as to set forth the best modes contemplated for carrying out various aspects of the invention. It is understood that these examples in no way serve to limit the true scope of this invention, but rather are presented for illustrative purposes. All references cited herein are incorporated by reference in their entirety.
EXAMPLES
Example 1
Donor Lymphocyte ex vivo Treatment to Prevent an Immune Attack Against Blood Cells from an Unrelated Recipient
A blood sample from a donor was obtained and lymphocytes prepared by density gradient centrifugation. T cells were prepared using a conventional negative selection procedure. These T cells were conditioned to prevent them from attacking the recipient cells. For this conditioning, the CD8+ T cells were mixed with irradiated stimulator cells from the recipient. The stimulator cells were derived from T cell-depleted blood cells from the recipient. The mixture of donor T cells and recipient stimulator cells were cultured for 48 hours with different concentrations of one or more cytokines. In this example the cytokines were TGF-β and IL-10. This procedure abolished the potential of the donor T cells to kill recipient cells, in FIG. 4 B.
To test the ability of the donor T cells to recognize and kill recipient blood cells, the donor T cells were cultured with irradiated stimulator cells for 5 days. Then the donor cells were cultured for 4 hours with a sample of recipient radiolabeled blood cells. When the recipient's cells are killed they release radioisotope into the culture medium. By determining the amount of radioisotope released, one can calculate the percentage of cells killed. In the standard cytotoxicity assay shown in FIG. 1, donor cells were cultured with labeled recipient cells in 30 to 1, 15 to 1, and 7.5 to 1 ratios. These combinations of donor and recipient cells are called effector to target ratios. Killing is indicated by the various symbols. As expected, maximum killing was seen at the highest effector to target cell ratio. In panel A, the open circles shows that if 30 donor cells were mixed with 1 recipient cell, 40 percent of the recipient cells were killed. When donor T cells were conditioned with very small concentrations of TGF-β(0.01 or 0.1 nanograms per ml), they had no effect on killing. However, if the T cells were treated with 1 nanogram per ml of TGF-β, the killing of recipient cells decreased by 50 percent. Panel B shows that if the T cells were treated with IL-10, killing also decreased by 50%. If the T cells had been conditioned with both IL-10 and TGF-β at 1 nanogram per ml, these cells completed blocked the killing of recipient cells; killing was almost undetectable. Various combinations of mitogens, cytokines, and monoclonal antibodies can be used to make T cells non-responsive.
Example 2
CD8+ T Cells from the Donor Conditioned ex vivo to Prevent other Donors T Cells from Mounting an Attack Against Blood Cells from an Unrelated Recipient
A blood sample from a donor was obtained and lymphocites prepared. CD8+ T cells were mixed with irradiated stimulator cells of the recipient and either TGF-β(picograms per ml) or IL-12 100 U/ml. IL-12 is known to enhance the ability of CD8+ T cells to develop the capacity to kill. Here IL-12 was used to show that a given population of CD8+ cells can be induced to kill or to block killing depending upon how they are activated. Other CD8 + cells were cultured in culture medium only as a control (CD8med).
The CD8+ T cells, the stimulator cells and the cytokines were cultured for 48 hours and the cytokines were removed from the cultures by washing. This procedure not only abolished the potential of the TGF-β, conditioned CD8+ cells to kill the recipient cells, but also induced them to prevent other donor T cells from killing the recipient cells (FIG. 4 C).
To enable the donor T cells to recognize and kill recipient blood cells, the donor cells were cultured with irradiated stimulator cells for five days. Then the donor cells were cultured for 4 hours with a sample of recipient radiolabeled blood cells. The open circles show the level of donor cells of recipient cells when no CD8+ cells were added. At a 30:1 effector to target cell ration, 30% of the recipient's cells were killed. If CD8+ cells that had been cultured for 48 hours without cytokines were added, there was no change in the killing (CD8+ +Med, solid circles). If the CD8+ cells had been conditioned with TGF-β, killing was suppressed by about 50%. However, the CD8+ T cells conditioned with TGF-β not only did not kill, but the decreased levels of cytotoxicity indicate that they blocked the ability of other T cells to kill blood cells of the recipient.
Example 3
Treating a Patient with Chronic Myelocytic Leukemia with the Stem Cells from a Histoincompatible Donor: Tolerization with Mitogens
The harvested PBMC of the donor are placed in a sterile container in HBBS as in Example 1. The cells are then incubated with mitogens to induce lymphocytes to become non-responsive to histocompatibility antigens of the recipient. In this case the cells are incubated with physiological concentrations of concanavalin A (Con A) for 4 to 72 hours using standard incubation techniques. The concentration of Con A used can range from about 0.01 to about 10 micrograms/ml with 1 microgram/ml being presently preferred. Alternatively, SEB may be used as the mitogen at concentrations of 0.001 to 100 ng/ml.
The incubation of the mononuclear cells in the mitogen solution increases the population of T suppressor cells. These cells, when transferred to the recipient, will enable the stem cells to engraft without causing GVHD. Although it is not known how the mitogens work, it is believed to induce the production of TGF-beta by certain mononuclear cells in preparation, and the TGF-beta acts on T cells to become suppressor cells.
After the cells have been incubated with the mitogens, the cells are washed with HBBS to remove any mitogens that are in the solution. The cells are suspended in 200-500 ml of HBBS, mixed with the stem cells and administered to a patient with CML who has been treated with myeloablative agents to prepare the stem cells for engraftment.
Once the donor hematopoietic cells lymphocites engraft in the recipient, and the patient again becomes healthy and free of leukemic cells. If the leukemic cells recur, the patient receives a transfusion of donor lymphocites and the leukemic cells again disappear.
Example 4
Treating a Patient with Chronic Myelocytic Leukemia with the Stem Cells from a Histoincompatible Donor: Tolerization with Anti-CD2 Monoclonal Antibodies
The harvested enriched stem cell preparation of the donor are placed in a sterile container in HBBS as in Example 1. The cells are then incubated with anti-CD2 monoclonal antibodies to induce lymphocytes to become non-responsive to histocompatibility antigens of the recipient. In this case, the cells are incubated with anti-CD2 monoclonal antibodies for 4 to 72 hours using standard incubation techniques. The concentration of anti-CD2 monoclonal antibodies are 10 ng/ml to 10 ug/ml. Optionally, 1-1000 units of IL-2 can be added.
The incubation of the mononuclear cells in the anti-CD2 solution increases the population of T suppressor cells. These cells, when transferred to the recipient will enable the stem cells to engraft without causing GVHD. It is believed that incubation with anti-CD2 monoclonal antibodies induces the production of TGF-beta by certain monuclear cells in preparation, and the TGF-beta acts on T cells to become suppressor cells.
After the cells have been incubated with the anti-CD2 monoclonal antibodies, the cells are washed with HBBS to remove antibodies that are in the solution. The cells are suspended in 200-500 ml of HBBS mixed with the stem cells harvested previously and administered to a patient with CML who has been treated with myeloblative agents to prepare the stem cells for engraftment.
Once the donor hematopoietic cells lymphocytes engraft in the recipient, and the patient again becomes healthy and free of leukemic cells. If the leukemic cells recur, the patient receives a transfusion of donor lymphocytes and the leukemic cells again disappear.
Example 5
Treating a Patient with Chronic Myelocytic Leukemia with the Stem Cells from a Histoincompatible Donor: Tolerization with Mitogens and Cytokines
The harvested PBMC of the donor are placed in a sterile container HBBS as in Example 1. The cells are then incubated with cytokines and mitogens to induce lymphocytes to become non-responsive to histocompatibility antigens of the recipient. In this case the cells are incubated with physiological concentrations of Con A or SEB, IL-2 or IL-10 and TGF-beta for 4 to 72 hours using standard incubation techniques.
After the cells have been incubated with the cytokines and mitogens, the cells are washed with HBBS to remove any cytokine and mitogen that are in the solution. The cells are suspended in 200-500 ml of HBBS mixed with the stem cells and administered to a patient with CML who has been treated with myeloabative agents to prepare the stem cells for engraftment.
Once the donor hematopoietic cells and lymphocytes engraft in recipient and the patient again becomes healthy and free of leukemic cells. If the leukemic cells recur, the patient receives a transfusion of donor lymphocytes and the leukemic cells again disappear.
Example 6
Treating a Patient with Chronic Myelocytic Leukemia with the Stem Cells from a Histoincompatible Donor; Tolerization with a Mitogen and Cytokine
The harvested PBMC of the donor are placed in a sterile container in HBBS as in Example 1. The cells are then incubated with a cytokine and a mitogen to induce lymphocytes to become non-responsive to histocompatibility antigens of the recipient. In this case the cells are incubated with physiological concentrations of ConA, and IL-2 for 4 to 72 hours using standard incubation techniques. In another case, SEB could be used.
After the cells have been incubated with the cytokines and mitogens, the cells are washed with HBBS to remove any cytokine and mitogen that are in the solution. The cells are suspended in 200-500 ml of HBBS mixed with stem cells and administered to a patient with CML who has been treated with myeloablative agents to prepare the stem cells for engraftment.
Example 7
Treating a Patient with Chronic Myelocytic Leukemia who has Developed GVHD Following the Stem Cell Transplant
In the instance that the initial procedure to prevent early or late GVHD following the stem cell transplant is not successful, this event will be managed BY transfer of a larger number of donor T cells that have been conditioned to become suppressor cells. Approximately 1×10 9 PBMCs obtained by leukopheresis are concentrated in a sterile leukopak; in Hanks balanced salt solution (HBBS). The PMMCs or separated CD8+ T cells (or the specific suppressor cell precursor subset CD8+CD45RA+C27+) prepared by immunoaffinity columns will be treated with antiCD2 monoclonal antibodies and/or mitogens and/or cytokines described above to condition them to become suppressor cells.
After incubation with the cytokines or mitogens for a period of time ranging from 4 hours to 72 hours, the cells are washed to remove the cytokines or mitogens and then are transferred to the recipient. These conditioned T cells migrate to lymphoid organs and suppress the GVHD.
Besides chronic myelocytic leukemia, other hematologic malignancies such as acute and chronic leukemias, lymphomas, solid tumors such as breast carcinoma or renal cell carcinoma among a few, and non-malignant diseases such as severe anemias (thalassemia, sickle cell anemia) can be treated with mismatched allogeneic stem cells.
Another aspect of this invention is a kit to perform the cell incubation with the cytokines. The kit comprises a sterile incubating container with the appropriate concentration of cytokines preloaded within the container. In one embodiment of the kit, the cytokines are present in lyophilized form in the container. The container is preferably a bag, similar to an IV bag. The lyophilized cytokines are reconstituted with HBBS and then the cells are injected into the container and thoroughly mixed and incubated. In another embodiment of the invention the cytokines are already in solution within the container and all that has to be done is the injection of washed stem cell preparation and incubation. | The field of the invention is generally related to pharmaceutical agents useful in treating graft-versus-host disease (GVHD) in patients that have received allogenic bone marrow transplants. | 2 |
FIELD
[0001] The present application is directed to the field of patient ventilators. More specifically, the present application is directed to ventilator circuit integrity detection.
BACKGROUND
[0002] It is desirable that, prior to the start or restart of ventilation to a patient requiring respiration assistance, that the integrity of the circuit be validated. This includes that the circuit is intact, connected, and the right patient interface component is attached. This will assure that the ventilator delivers the appropriate set of breathing gases without gas leakage. It is also advantageous that a humidifier and bacteria filter be attached to ensure gases breathed by the patient are humidified and cross contamination is prevented. In volume controlled ventilation, some gas volumes delivered by the ventilator is absorbed in a compliant breathing circuit, or circuit component such as a humidifier, filters, HME, resulting in less tidal volume delivered to the patient. Breathing circuits come in different lengths with correspondingly different compliance values. Present methods to compensate gas volume losses is to inject a known gas volume and measure the total circuit compliance prior to the start of ventilation, or enter the type of circuit elements with their compliances or predefined compliances summing them together to obtain the total compliance. These are tedious and require additional steps by the user to enter the right information, enter the total circuit compliance and compensate for the volumes not delivered to the patient.
[0003] Current solutions detect circuit disconnects by detecting gas leakage or failure to pressurize the breathing circuit during ventilation. A common approach to detect disconnects in other industries is to provide a parallel loop back connection to test the integrity of the connected circuit. Loop-back connection can be done via electrical, pneumatic or optical leads that run the length of the breathing circuit. A weakness in this solution is it does not report what is connected and where. The introduction of electrical wires, tubes or optical fiber glass running along the gas flow passage of the breathing circuit components can be costly and intrusive. Another weakness, particularly in anesthesia ventilation, is the failure to detect reconnection of the breathing circuit. A test procedure must be conducted prior to start of ventilation to compute total compliance and resistance to provide compensation for compliance and resistance losses. This is time consuming and has to be added to the user workflow.
SUMMARY
[0004] The above-mentioned shortcomings, disadvantages and problems are addressed herein which will be understood by reading and understanding the following specification.
[0005] The system and method of the present application automates the integrity check of the breathing system and informs the ventilator to deliver the compensated gas volume, and alert the user if a vital component of breathing circuit is absent or not fully connected. The present application utilizes an open RFID tag on a first point of connection and a conducting ring on the second point of connection such that when a circuit connection is made, the open RFID tag becomes active and provides an RFID reader with data regarding the circuit connection.
[0006] In one aspect of the present application, a ventilator breathing circuit comprises a plurality of circuit connections, each of the plurality of circuit connections including a first conduit and a second conduit, a radio frequency identification (RFID) reader, an open RFID tag affixed to any of the first conduits, a conducting ring affixed to the second conduit corresponding to the first conduit having the open RFID tag, such that when the first conduit and the second conduit are connected, the open RFID tag is activated and sends a set of data to the RFID reader, wherein the set of data includes information about the circuit connection.
[0007] In another aspect of the present application, a method of monitoring the integrity of a ventilator breathing circuit, the method comprises identifying a circuit connection of a ventilator breathing circuit, fashioning a first conduit of the circuit connection with an open RFID tag, fashioning a second conduit of the circuit connection with a conducting ring, connecting the first and second conduits of the identified circuit connection, thus activating the open RFID tag, receiving a set of data from the identified circuit connection, and analyzing the set of data from the identified circuit connection, optimizing the ventilation delivery based on the analysis, and displaying the analysis and the optimization for a user.
[0008] In another aspect of the present application, a non-transitory computer-readable medium includes instructions that, when executed on a computing system, cause the computing system to receive a set of data from a circuit connection wherein an open RFID tag is activated by a conducting ring when a connection is made between a first and second conduit, analyze the set of data from the circuit connection, optimize a delivery of the ventilator based on the analysis, and display the analysis and the optimization for a user.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIGS. 1 a and b are schematic illustrations of a circuit connection and network in accordance with an exemplary embodiment of the present application;
[0010] FIG. 2 is a schematic illustration of a breathing circuit illustrating an embodiment of the present application;
[0011] FIG. 3 is a schematic illustration of a breathing circuit illustrating an embodiment of the present application;
[0012] FIG. 4 is a flow chart illustrating an exemplary method in accordance with an embodiment of the present application; and
[0013] FIG. 5 is a block diagram illustrating an embodiment of the system of the present application.
DETAILED DESCRIPTION
[0014] In the present description, certain terms have been used for brevity, clearness and understanding. No unnecessary limitations are to be applied therefrom beyond the requirement of the prior art because such terms are used for descriptive purposes only and are intended to be broadly construed. The different systems and methods described herein may be used alone or in combination with other systems and methods. Various equivalents, alternatives and modifications are possible within the scope of the appended claims. Each limitation in the appended claims is intended to invoke interpretation under 35 U.S.C. §112, sixth paragraph, only if the terms “means for” or “step for” are explicitly recited in the respective limitation.
[0015] In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration specific embodiments that may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the embodiments, and it is to be understood that other embodiments may be utilized and that logical, mechanical, electrical and other changes may be made without departing from the scope of the embodiments. The following detailed description is, therefore, not to be taken as limiting the scope of the invention.
[0016] Referring to FIG. 1 a , 1 b and 2 , the system and method of the present application makes use of open radio frequency identification (RFID) tags 25 located at the opening of circuit components 135 to detect the connection of two breathing circuit components 135 or any circuit connection 10 . In one embodiment, an open RFID circuit tag 25 (having an open lead to the antenna wire or the RFID chip) is utilized such that the RFID chip in the open RFID tag 25 is not communicating when the circuit connection 10 is open, such as is illustrated in FIG. 1 a . When connected, the open lead of the open RFID tag 25 connects with a conducting ring 20 to complete the electrical connection, thus resulting in an active RFID tag 27 , as illustrated in FIG. 1 b . Once connected, the active RFID tag 27 behaves as a conventional RFID tag and may be energized by an RFID reader to send and receive signals to communicate their presence and data to an RFID reader 30 as an active connection 10 and to report properties, if any. Properties can include device type such as bacteria filter, number of connecting ports or circuit connections 10 , connecting location, physical property of the component, such as compliance and flow resistance, that are relevant to safe and optimal ventilation delivery. Simultaneous reporting of active RFID tags 27 can provide the location and sequence of the circuit connections 10 . This helps to map the topology of active portions of the breathing circuit 100 ( FIG. 2 ). Since only active circuit connections 10 are energized and can communicate with the RFID reader 30 , only active circuit connections 10 can report to the RFID reader 30 . The RFID reader 30 is typically located proximal to the ventilator 150 and/or electronically connected with the ventilator 150 computing system 300 . The RFID reader 30 detects the presence of active RFID tags 27 and reads all the circuit connections 10 that are actively connected together. It then forwards the results to the computing system 300 that confirms the breathing circuit 100 is intact, the required circuit components 135 such as a filter or HME are present, and the physical properties of the breathing circuit 100 , for example, total resistance and compliance of each component present to yield the total resistance and compliance of the breathing circuit. An alarm is raised if a critical safety component 135 , for example a bacteria filter 135 is not actively connected to the breathing circuit 100 prior to start of ventilation. The controller 300 can be programmed to deny the start of ventilation until a critical circuit component 135 is connected or the denial overridden by the user. During ventilation delivery, the ventilator 150 uses the aggregated physical makeup of the circuit components 135 to adjust tidal volume delivery to compensate for gas volumes retained in the circuit components 135 (resulting in compliant volumes losses, dead spaces and other issues) that is not delivered to the patient. Similar compensation can be provided to compensate for flow resistance in the gas passage of the breathing circuit 100 . Additional information can be gleaned from computing frequency, duration of active use of a connected circuit components 135 , such as to replace a circuit component 135 .
[0017] Referring back to FIG. 1 a , a circuit connection 10 of the present application is illustrated in an unconnected position. In other words, the two breathing circuit conduits 15 are not connected to one another, leaving the open RFID tag 25 in a non-energized state that does not allow the open RFID tag 25 to transmit a set of data to the RFID reader 30 . As discussed previously, the open RFID tag 25 includes information regarding the breathing circuit conduit 15 that it is connected to, such as but not limited to, the location of the breathing circuit conduit 15 in the breathing circuit 100 and the particular circuit component 135 that the breathing circuit conduit 15 may be associated with or connected to. The conducting ring 20 is configured on the opposite breathing circuit conduit 15 , and when the circuit connection 10 is in a connected position as shown in FIG. 1 b , the conducting ring 20 completes the circuit so that the active RFID tag 27 is able to transmit a set of data to the RFID reader 30 .
[0018] As discussed previously, the RFID reader 30 may be configured proximate to the breathing circuit 100 , and the ventilator 150 , and/or connected through a network 40 or hardwired to a computing system 300 as further illustrated in FIG. 1 b , and further described below with respect to FIG. 5 .
[0019] Referring now to FIG. 2 , an embodiment of a breathing circuit 100 of the present application is illustrated. Here, a ventilator 150 including an expiratory port 140 and an inspiratory port 145 are connected with breathing circuit conduits 15 to any one of a patient interface component 105 in order to provide ventilation to a patient (not shown). The ventilator 150 further includes an RFID reader 30 as discussed above, but it should be noted that not all ventilators will have such an RFID reader 30 . The breathing circuit 100 also includes various circuit components 135 , in this case a bacteria filter is illustrated but should not limit the present application to such a filter. Any other appropriate filters or devices that belong in breathing circuits 100 may be connected through the breathing circuit 100 such as, but not limited to, heat moisture exchanges, active humidifiers and nebulizers. The breathing circuit 100 also includes an expiratory limb 115 and an inspiratory limb 130 , as well as a y-piece 155 , as is well known in the art. The patient interface components 105 may include any patient interface components known in the art, and illustrated are an endotracheal tube 110 , a facemask 120 , and a laryngeal mask 125 .
[0020] Still referring to FIG. 2 , in this embodiment the inspiratory limb 130 and expiratory limb 115 are configured with conducting rings 20 on the ends of the limbs 115 , 130 in close proximity to the ventilator 150 . Furthermore, the y-piece 155 includes both a conducting ring 20 and an open RFID tag 25 on the breathing circuit conduit 15 portion to be connected with any of the patient interface components 105 . Each of the patient interface components 105 is configured with a conducting ring and open RFID tag 25 . The circuit component 135 , in this case a bacteria filter, includes a conducting ring 20 on the end proximate to the expiratory port 140 of the ventilator 150 , and an open RFID tag 25 on the end configured proximate to the expiratory limb 115 . The expiratory port 140 and the inspiratory port 145 both include open RFID tags 25 .
[0021] Still referring to FIG. 2 , when each connection is made in this embodiment, and the open RFID tags 25 become active RFID tags 27 ( FIG. 1 b ), thus energized by the completion of the RFID tag 27 circuit with a conducting ring 20 , the active RFID tags 27 will communicate with the RFID reader 30 in order to provide a set of data to the RFID reader 30 that includes its device type, its properties, number of connecting parts, location of the active RFID tag 27 , a status that the active RFID tag 27 is indeed connected, and further whether the active RFID tag 27 is associated with any circuit component 135 . For example, when the y-piece 155 is connected to the endotracheal tube 110 , the active RFID tag 27 on the y-piece 155 will transfer a set of data to the RFID reader 30 that indicates that the y-piece 155 is connected. The endotracheal tube 110 will also send a signal from its active RFID tag 27 that it is further connected. A user will then know that the endotracheal tube 110 is connected to the y-piece 155 , and that that portion of the breathing circuit 100 has an acceptable integrity. It should first be noted that the Applicant has illustrated the breathing circuit 100 in FIG. 2 (and in FIG. 3 ) to show all of the open RFID tags 25 and conducting rings 20 in an unconnected state for clarity. Again for clarity, these connections have only been shown in FIG. 1 b . It should be assumed that the breathing circuit 100 of FIGS. 2 and 3 , when connected, will include circuit connections 10 in every location where circuit connections 10 are to be made. Of course, some circuit connections 10 in the breathing circuit 100 of FIGS. 2 and 3 will include two conducting rings 20 and two active RFID tags 27 in the instances where each breathing circuit conduit 15 includes an open RFID tag 25 and a conducting ring 20 .
[0022] It should be further noted that in this embodiment, the ends of the expiratory and inspiratory limbs 115 , 130 proximate to the ventilator 150 do not include open RFID tags 25 , and only conducting rings 20 . In this case, only the position and connectivity of the circuit component 135 (bacteria filter), expiratory port 140 and inspiratory port 145 will be transmitted to the RFID reader 30 when all of these circuit connections 10 are made. When the number of available open RFID tags 25 before connection of the breathing circuit 100 matches the number of active RFID tags 27 after the breathing circuit 100 is connected, then the breathing circuit 100 is completed and connected. After connection, the active RFID tags 27 continue to communicate with the RFID reader 30 . Any subsequent circuit connection 10 disconnect may be recognized by the RFID reader 30 when a previously active RFID tag 27 fails to continue to report and deliver a set of data to the RFID reader 30 during any given read cycle.
[0023] Referring now to FIG. 3 of the present application, an additional embodiment showing both open RFID tags 25 and conducting rings 20 on each and every connection point 16 of the breathing circuit 100 is illustrated. For ease of description, only the pertinent portions of FIG. 3 have been labeled with numerals, and it can be assumed that those components not labeled in FIG. 3 have the same number as its corresponding component in FIG. 2 . Here, as an example, the inspiratory limb 130 includes an open RFID tag 25 and a conducting ring 20 , as does the inspiratory port 145 . When this circuit connection 10 is made, both the inspiratory limb 130 RFID tag 25 and the inspiratory port 145 open RFID tag 25 will become active RFID tags 27 and send a set of data reflecting the conduit 15 , conduit location of the circuit component 135 , and location and connectivity of each of the inspiratory limb 130 and inspiratory port 145 to the RFID reader 30 . This embodiment, by way of including an open RFID tag 25 and conducting ring 20 , at each and every connection point in the breathing circuit 100 , ensures the highest level of integrity and tracking of the breathing circuit 100 that is possible. Of course, a user may be able to customize the breathing circuit 100 solution by including open RFID tags 25 and conducting rings 20 on those connection points. One advantage of knowing the pairing of all of the circuit component 135 conduits 15 and the location for each circuit component 135 conduit 15 , the arrangement of the entire breathing circuit 100 can be mapped out via the connected sequence of the circuit connections 10 .
[0024] Referring now to FIG. 4 , a method 200 of the present application is illustrated in the flowchart. In step 205 , a user identifies a circuit connection of a breathing circuit, and in step 210 a first conduit of the identified circuit connection is fashioned with an open RFID tag. In step 215 , a second conduit of the identified circuit connection is fashioned with a conducting ring. If there are additional circuit connections to be identified in step 220 , then the method 200 returns to step 205 and such circuit connections are identified. If all of the circuit connections are identified at step 220 , then the first and second conduits of each of the identified circuit connections are connected at step 225 . Once these circuit connections are made, the open RFID tags become active, and a set of data is received from each of the identified circuit connections from the active RFID tags in step 230 . This is achieved by the conducting ring completing the open RFID tag as described above, and allowing the now active RFID tag to energize and send the set of data to the RFID reader. In step 235 , the set of data from each of the identified circuit connections is analyzed, optimizing the ventilator 150 delivery based on the analysis, and the data is displayed along with the analysis and the optimization for a user. During step 235 , alerts and/or reports may be provided to the user, and the user may manipulate the analysis such as with an override or turning off alarms, amending or closing the analysis accordingly.
[0025] FIG. 5 is a system diagram of an exemplary embodiment of a computing system 300 as may be used to implement embodiments of the method 200 , or in carrying out embodiments of portions of the breathing circuit 100 . The computing system 300 includes a processing system 306 , storage system 304 , software 302 , communication interface 308 , and a user interface 310 . The processing system 306 loads and executes software 302 from the storage system 304 , including a software module 330 . When executed by the computing system 300 , software module 330 directs the processing system to operate as described herein in further detail in accordance with the method 200 , or a portion thereof. It should be noted that the computing system 300 may be configured in a number of locations proximate or remote from the breathing circuit 100 . For example, the computing system 300 may be included in the ventilator 150 in the RFID reader 30 , and/or in any user workstation proximate to the ventilator 150 or remote in a practitioner's station, care station, or other computer station.
[0026] Although the computing system 300 as depicted in FIG. 5 includes one application module 330 in the present example, it is to be understood that one or more modules could provide the same operations or that exemplary embodiments of the method 200 may be carried out by a plurality of modules 330 . Similarly, while the description as provided herein refers to a computing system 300 and a processing system 306 , it is to be recognized that implementations of such system can be performed by using one or more processors 306 , which may be communicatively connected, and such implementations are considered with be within the scope of the description. Exemplarily, such implementations may be used in carrying out embodiments of the system 100 depicted in FIGS. 2 and 3 .
[0027] Referring back to FIG. 5 , the processing system 306 can comprise a microprocessor or other circuitry that retrieves and executes software 302 from storage system 304 . Processing system 306 can be implemented within a single processing device but can also be distributed across multiple processing devices or sub-systems that cooperate in executing programming instructions. Examples of processing system 306 includes general purpose central processing units, application specific processor, and logic devices, as well as any other type of processing device, combinations of processing device, or variations thereof. The storage system 304 can include any storage media readable by the processing system 306 and capable of storing the software 302 . The storage system 304 can include volatile and non-volatile, removable and non-removable media implemented in any method of technology for storage of information such as computer readable instructions, data structures, program modules or other data. Storage system 304 can be implemented as a single storage device but may also be implemented across multiple storage devices or sub-systems. Storage system 304 can further include additional elements, such as a controller capable of communicating with the processing system 306 .
[0028] Examples of storage media include random access memory, read only memory, magnetic disc, optical discs, flash memory, virtual and non-virtual memory, magnetic sets, magnetic tape, magnetic disc storage or other magnetic storage devices or any other medium which can be used to store the desired information and that may be accessed by an instruction execution system, as well as any combination or variation thereof, or any other type of storage medium. In some implementations, the storage media can be a non-transitory storage media. It should be understood that in no case is the storage media propagated signal.
[0029] User interface 310 can include a mouse, a keyboard, a voice input device, a touch input device for receiving a gesture from a user, a motion input device for detecting non-touch gestures, and other motions by a user, and other comparable input devices and associated processing elements capable of receiving user input from a user. User interface 310 can also include output devices such as a video display or a graphical display that can display an interface associated with embodiments of the systems and methods as disclosed herein. Speakers, printers, haptic devices, and other types of output devices may also be included in the user interface 310 . The user interface 310 is configured to receive user inputs 340 which in non-limiting embodiments may be irregularity user preferences as disclosed in further detail herein. It is also understood that embodiments of the user interface 310 can include a graphical display that presents the reports or alerts as described in further detail herein.
[0030] As has been described in further detail herein, the communication interface 308 is configured to receive RFID data 320 . The RFID data 320 , as described previously, may include the location of the circuit connection 10 , the confirmation that a connection has indeed occurred, and any circuit component 135 that the corresponding active RFID tag 27 may be associated with. The computing system 300 processes the RFID data 320 according to the software 302 and as described in detail herein to produce reports and alerts 350 which may be pushed to one or more users through the user interface 310 . The reports 250 may include any analysis conducted by the computing system including reports 350 on optimizing the ventilation delivery as described above. Further as described herein, the computing system 300 can output alerts, and/or report 350 to the user, and may further accept user input 340 , such as but not limited to, setting off of alerts, modifications of the reports, and other administration of the alerts and data. It is the user interface 310 , including the alert and reports 350 provided to the user and the user input 340 that allows response to a detection of a lapse in integrity of the breathing circuit 100 and may provide an alarm if a critical component is absence, or denies start of patient ventilation until a critical component is added or the denial is overridden by a user.
[0031] As described earlier, knowing the pairing of all the circuit components 135 and circuit connections 10 and the circuit connection 10 location of each circuit component 135 , the arrangement of the entire breathing circuit 100 and circuit connections 10 can map out via the connected sequence of the paired active RFID tags 27 and rings 20 . Along with the property of the circuit components 135 , the fluid property of the breathing circuit 100 arrangement can be derived. For example, reading that the expiratory port 140 is connected to filter 135 , that in turn is connected to the expiratory limb 115 and connected to an endotracheal tube 120 , and knowing the flow resistance of each of the segments of the circuit elements 135 , fluid resistance in the expiration limb 115 of the breathing circuit 100 can be computed and compensate the work of expired breathing by appropriately adjusting the ventilator 150 pressure during expiration in the control of the ventilation delivery. Likewise, in another example, knowing that an LMA 125 and filter 135 is connected to the common limb of the Y-piece 155 will help to determine the dead space ventilation contributed by the breathing circuit 100 . The computing system 300 can therefore instruct the ventilator 150 to then compensate the increased dead space by correspondingly increasing the delivered tidal volume. In yet another compensation, the compliance of the connected circuit components 135 can be summed according to its serial or parallel connection to the gas flow path to compute the gas volume loss in the breathing circuit 100 and not delivered to the patient. To clarify, the computing system, in executing the method 200 , may be able to instruct the ventilator 150 to correct integrity issues in the breathing circuit 100 found by the method 200 .
[0032] While the invention has been described with reference to preferred embodiments, those skilled in the art will appreciate that certain substitutions, alterations and omissions may be made to the embodiments without departing from the spirit of the invention. Accordingly, the foregoing description is meant to be exemplary only, and should not limit the scope of the invention as set forth in the following claims.
[0033] In the foregoing description, certain terms have been used for brevity, clearness, and understanding. No unnecessary limitations are to be inferred therefrom beyond the requirement of the prior art because such terms are used for descriptive purposes and are intended to be broadly construed. The different configurations, systems, and method steps described herein may be used alone or in combination with other configurations, systems and method steps. It is to be expected that various equivalents, alternatives and modifications are possible within the scope of the appended claims. | The system and method of the present application automates the integrity check of the breathing system and informs the ventilator to deliver the compensated gas volume, and alert the user if a vital component of breathing circuit is absent or not fully connected. The present application utilizes an open RFID tag on a first point of connection and a conducting ring on the second point of connection such that when a circuit connection is made, the open RFID tag becomes active and provides an RFID reader with data regarding the circuit connection. | 0 |
BACKGROUND OF THE INVENTION
The invention relates to flotation devices for supporting a person in water.
In particular, the invention sets out to provide a flotation device for supporting a person partly immersed in water so that the device may be used safely by persons unable otherwise to support themselves in the water through not knowing how to swim or through infirmity or physical disability. The flotation device according to the invention has general application as a water sporting device, for amusement, but may also be useful for teaching and therapeutic purposes.
SUMMARY OF THE INVENTION
According to the invention, a flotation device for supporting a person in water comprises an elongate frame including at least one body-support member, and front and rear float assemblies mounted on the frame, at least one of said float assemblies comprising two float elements spaced apart transversely of the elongate frame, the float elements being so disposed that, when the device is floating in the water, the body-support member is below water level.
Thus, in use, the person using the device and being supported by the body-support member has the benefit and experience of being partly immersed in water but at the same time has the advantage of being safely supported. In particular, the provision of the transversely spaced float elements provides lateral stability to the device.
The two transversely spaced float elements are preferably separately formed and are connected to the elongate frame by rear mounting elements, although they could also comprise portions of a single, larger float element. The front float assembly may comprise a single float element disposed on the longitudinal axis of the frame and may be connected to the frame by a front mounting element.
Each float element may comprise a body of buoyant material connected to said mounting elements. For example the buoyant material may comprise cross-linked closed cell polyethylene foam.
Each mounting element may be shaped to define an aperture into which said body of buoyant material is received. For example, the mounting element may be bent into a loop to define said aperture.
The body of buoyant material may include a portion of reduced cross-sectional area between two portions of greater cross-sectional area, whereby the buoyant material may be retained in the aperture by forcing it through the aperture until the portion of reduced cross-sectional area is disposed within the aperture.
The body-support member may comprise a substantially flat panel on which a person may sit or lie. It may further comprise an additional panel disposed at an angle to the first panel for use as a back rest by a person sitting on the first said panel.
The front and/or rear mounting elements are preferably adjustably mounted on the elongate frame whereby the positions of the float elements may be adjusted with respect to one another and to the body-support member. Preferably the rear mounting elements are adjustable so as to bring the rear float elements closer to or further from the body-support member so as to adjust the distance below water level of the body-support when the device is floating. Preferably the rear mounting elements are also adjustable so as to move the rear float elements toward or away from one another.
The device may incorporate laterally extending hand grips in addition to the aforesaid body-support member.
In a version of the device usable by two people, the elongate frame includes two body-support members symmetrically disposed on either side of the central longitudinal axis of the frame.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a flotation device according to the invention,
FIG. 2 is a similar view of the device of FIG. 1, showing an alternative arrangement of the components of the device, and
FIG. 3 is a perspective view of a modified form of the device, suitable for use by two people.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In each of the embodiments, the device comprises a main elongate frame, and front and rear float mounting elements, formed from aluminium tubing the open ends of the tubing, where appropriate, being plugged with polypropylene end caps.
In the embodiment of FIGS. 1 and 2, the main frame 10 is in the form of an elongated U, the limbs 11 of the U extending rearwardly and having a triangular seat panel 12 mounted across the rear ends thereof. The rear mounting elements 13 are bolted to the rear ends of the limbs respectively, and extend upwardly at right angles thereto and then downwardly away from one another. The free ends of the mounting elements are bent to form horizontally flattened loops 14. A panel 15 of cross-linked closed cell polyethylene foam is wedged through each of the flattened loops 14 to form one of the rear float elements. A back rest in the form of a further triangular metal panel 16 is secured to the parallel portions of the mounting elements extending at right angles to the frame, and a horizontal stay 17 is bolted between the upper ends of the mounting elements 13.
Secured to the front closed end of the U-shaped frame 10 by a bolted clamp 18a is a front mounting element 18 also bent from aluminium tubing to provide two spaced parallel forwardly and downwardly extending arms terminating in a horizontally flattened loop 19 which extends transversely of the axis of the frame 10. A further panel 20 of polyethylene foam is received in the flattened loop 19 to form the front float element. The rear ends of the arms of the front mounting element are bent laterally outwardly away from one another to form hand grips or foot rests 21.
The panels of foam forming the float elements 15 and 20 are rounded at the front and taper rearwardly and are formed partway along their longitudinal sides with notches 22 so as to define a central area of reduced cross-section. Each panel may thus be retained in its associated loop by forcing the panel through the loop until the aluminum tubing snaps into the notches.
The connection between the front mounting element and the frame 10 is adjustable. The clamp 18a may be loosened so that the front mounting element may be slid forwardly or rearwardly with respect to the frame, and the clamp 18a then re-tightened.
In use, the floats 15, 20 rest at the surface of the water and the seat 12 and back rest 16 are disposed below water level so that a person sitting on the seat is partly immersed in the water. The device may then be propelled forward or backwards by use of the hands and/or feet, or by use of oars or a paddle, or by a sail (not shown) carried by a mast mounted at the forward end of the main frame 10. The device may also be used for surfing. Due to the lateral spacing of the rear float elements, and the low positioning of its centre of gravity, the device is very stable even in rough water thus making it easy to get on to or off the device.
Where a lesser degree of immersion in the water is required, the horizontal stay 17 connecting the rear mounting elements 13 may be replaced by a longer horizontal stay 23, as shown in FIG. 2. In the arrangement shown in that figure, the rear mounting elements 13 are interchanged and swung outwardly and downwardly so as to lower the rear float elements 15 with respect to the seat 12 so that, in use, the seat is a shorter distance below water level. In this case the back rest 16 is removed to permit the swinging apart of the rear mounting elements 13.
FIG. 3 shows an alternative form of flotation device in accordance with the invention, suitable for use by two people at the same time.
In this arrangement the main elongate frame 24 is formed from a single length of aluminium tubing bent so as to provide a front horizontally flattened loop 25, laterally extending U-shaped hand grips or foot rests 26, rear U-shaped laterally extending seat supports 27 and rear upwardly and laterally extending mounting elements 28 formed with rear horizontally flattened loops 29.
An elongate U-shaped strengthening member 30, also formed from aluminium tubing, overlies the longitudinal portions of the main frame 24 and extends from a point to the rear of the seat supports 27 to a point forwardly of the hand grips or foot rests 26. The strengthening member 30 is bolted to the main frame at its rear end by bolts 31 and is also clamped thereto by spaced clamps 32, 33 and 34.
Triangular seat panels 35 are mounted on the seat supports 27 and triangular back rest panels 36 are mounted on the rear mounting elements 28 and on a horizontal stay 37 extending between them.
Two panels of cross-linked closed cell polyethylene foam, similar to the panels 15 and 20 of the FIG. 1 arrangement are wedged into the flattened loop 25 to form a front float element 38, and three panels of foam are wedged into each of the loops 29 to form rear float elements 39.
The flotation device may be used by two people, one occupying each seat, in similar fashion to the single seat version shown in FIG. 1. Since the people sitting on the device are partly immersed in the water, most of their weight is supported by the water and consequently there is little tendency for the device to list if there should be a disparity in weight between the two people using it.
The device may also be used with a sail and for this purpose there is provided a front clamp 40 from which extends upwardly a socket 41 to receive the lower end of a mast (not shown). A keet 42 is formed on the lower part of the clamp 40 and may be connected at its rearward end to the clamp 33. Any suitable form of sail may be carried by the mast, there being provided, in conventional fashion, a rearwardly extending swinging boom having its rearward end a mainsheet controlled by one of the people using the device.
To provide the necessary control of the device when used with a sail, there is provided a rudder 43 pivotally mounted on a clamp 44 connecting the rear mounting elements 28. The rudder is controlled by a tiller 45 projecting forwardly between the two seats 35 for use by either person on the device.
A further keel plate 46 may be mounted beneath the seats for additional stability, and may conveniently be mounted on the clamps 44 and 32.
It will be appreciated that in any of the arrangements described above the device may be easily broken down into its component parts for transport and storage by releasing the various clamps holding the component parts together. | A flotation device for supporting a person in water comprises an elongate tubular frame including at least one body-support member, and front and rear float assemblies mounted on the frame. The rear float assembly comprises two float elements spaced apart transversely of the elongate frame, and the float elements are so disposed that, when the device is floating in the water, the body-support member is below water level, so that a person using the device is partly in the water. | 1 |
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application No. 60/489,199 filed on Jul. 22, 2003.
BACKGROUND OF THE INVENTION
[0002] Sudden infant death syndrome (SIDS) is a sudden and unexpected death of an apparently healthy infant whose death remains unexplained after further medical investigation. SIDS is not acknowledged as a disease, nor has it been diagnosed for a living baby. However, many SIDS deaths have been documented where an infant has been sleeping face down. A face down infant is considered by many experts in the field of infant mortality to be a high risk position for a SIDS attributed death because a face down position may lead to periods of apnea (stoppage of breathing). While infants may be resuscitated during a period of apnea, most SIDS events occur at night when the infant's caregiver is sleeping.
[0003] Attempts have been made to identify a SIDS event and provide a technological solution to early detection. Once such example, U.S. Pat. No. 4,350,166, APNEA DETECTOR, attempts to identify potential SIDS risks by the detection of long wave infrared radiation typical of carbon dioxide emitted from a breathing infant. However, this type of detector merely identifies that an infant has stopped breathing, which is too late to prevent the SIDS event from occurring. Furthermore, infant body heat can skew the detection of infrared radiation. Another such example is U.S. Pat. No. 6,492,634, OPTICAL MONITOR FOR SUDDEN INFANT DEATH SYNDROME, where a monitor tracks the movement of a laser beam or light emitting diode projected onto an infant. This device again merely tracks the breathing patterns of the infant and will only initiate an alarm if the infant has stopped breathing as indicated by the movement or lack of movement of the laser beam. Therefore, it would be desirable to provide a SIDS detection device capable of detecting high risk movement of an infant prior to any disruption in the infant's breathing pattern.
SUMMARY OF THE INVENTION
[0004] A method of detecting high risk movements of an infant relating to sudden death syndrome is disclosed. A reference image of an infant is signaled to a controller a location of a first plurality of pixels. The location of the plurality of pixels is stored in the controller generating for a reference image. A second electronic image of the infant is signaled to the controller a location of a second plurality of pixels. The second electronic image is compared to the first electronic image by determining the correlation between the first plurality of pixels to the second plurality of pixels for identifying high risk movements of the infant prior to an apnea event occurring.
[0005] The present inventive method of detecting high risk movements of an infant provides the ability to generate and transmit a distress signal prior to adverse breathing patterns developed in the infant. Unlike prior art detection systems, which identify problems with the infant based upon breathing irregularities, a caregiver now has the ability to interact with an infant before any breathing irregularities put the infant at risk. As previously stated, infants are believed to be at risk when sleeping on their front side. The inventive concept provides the ability to detect if an infant has rolled completely over even onto the infant's side while sleeping. In the event an infant rolls over or onto his/her side, a distress signal is generated and transmitted notifying the caregiver to take action prior to a sleep apnea event occurring.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] Other advantages of the present invention will be readily appreciated as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings wherein:
[0007] FIG. 1 shows a schematic view of a sleeping infant associated with the inventive sudden infant death syndrome detection system; and
[0008] FIG. 2 shows a flow diagram of the logic pattern used by the inventive sudden infant death syndrome method.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0009] Referring to FIG. 1 , a preferred embodiment of the present assembly is generally shown at 10 . The assembly 10 interacts with a sleeping surface, or a crib 12 , upon which an infant 14 sleeps.
[0010] A vision system or a camera 16 is placed above the infant 14 and provided with a view of, preferably, the entire infant 14 . The camera 16 is preferably mounted to a wall 18 , but may optionally be mounted to the crib 12 if necessary. More than one camera 16 is alternatively used to further enhance the image of the infant that is generated. As will be discussed further below, the camera 16 generates sequential images of the infant and transmits those images to a processor 20 . The camera 16 is preferably hard wired to the processor 20 . However, in an alternate embodiment, the camera includes an RF or equivalent transmitter and signals a remote processor 20 with the image of the infant 14 being generated.
[0011] Technological advances and cameras 16 have produced high resolution images capable of generating a significant number of pixels from a received image. By transmitting the image to a processor, the camera 16 enables the processor 20 to record and detect through computer algorithms minor changes in sequential images transmitted by the camera 18 .
[0012] Cameras 16 capable of generating the high resolution images that provide a high number of pixels include charge coupled cameras, high dynamic range cameras, active pixel cameras, and complementary metal oxides semi-conductor cameras and their equivalents. Each of these cameras provide the high resolution necessary to generate the plurality of pixels required for the processor 20 to measure variations in pixels between sequentially generated images. It may be necessary to provide an infrared transmitter 22 to enhance the image of the infant 14 generated by the camera 16 . The infrared transmitter 22 is particularly relevant when a satisfactory amount of light is not available such as, for example, during night time. Alternatively, a camera 16 capable of detecting electromagnetic radiation also produces sufficient resolution.
[0013] The processor 20 is electronically connected to a remote signaling device 24 for when a high risk movement of the infant is determined by the processor 20 as will be explained further below. The signaling device 24 is alternatively hard wired to the processor 20 or receives a signal from the processor 20 through an RF or equivalent transmission. Preferably, a plurality of signaling devices 24 are spaced around a residence so that the infant's 14 caregiver is always within range of the signaling device 24 . The signaling device 24 is alternatively an optical or sound transmitting device capable of notifying the infant's 14 caregiver of a high risk movement of the infant as detected by the processor 20 as desired.
[0014] Initially, a reference image is first generated that provides a base point for the processor 20 to begin its analysis of the infant's 14 movement. Various techniques are available to generate a reference image 26 that provides the necessary pixels required to conduct a computer algorithm required to analyze the movements of the infant 14 .
[0015] A first alternative to generating the reference image 26 makes use of a doll or test dummy having the size and characteristics of an infant at the age where SIDS is known to be a risk. The camera 16 takes an image of the doll's face, and preferably body, when a doll is positioned as though sleeping on its back. Various features are identifiable by the processor 20 through the high resolution of pixels generated by the camera 16 , such as, for example, eyes, nose, mouth, and chest of the infant.
[0016] An alternative to using a doll or dummy to generate a reference image 26 is to use the infant 14 as intended to be monitored by the assembly 10 . In this case, additional reference images can be generated as the infant 14 grows providing an even more accurate analysis of the infant's sleeping pattern and potential for high risk movements.
[0017] An alternative reference image to the infant's 14 front is to generate a reference image of the infant's 14 side by detecting features, such as, the infant's 14 profile, ears, and shoulder. In this case, the infant 14 has already made a movement toward sleeping on his/her stomach which is regarded as the highest risk sleeping position related to SIDS. In any event, the reference image is stored in the processor 20 thereby generating a plurality of pixels necessary for the analysis and detection of the infant's 14 high risk movements.
[0018] As shown in FIG. 2 , a second electronic image 28 of the infant is generated once the infant has been placed in the crib 12 for sleep. The camera 16 signals the processor 20 the location of a second plurality of pixels corresponding to the infant's 14 sleeping position.
[0019] The second plurality of pixels corresponding to the second image 28 is compared by the processor 20 against the reference image 26 by way of a computer algorithm as set forth in block 30 using statistical analysis to determine the correlation between the second image 28 and the reference image 26 . For example, if the second image 28 includes the characteristics of the infant 14 identified in the reference image 26 , the processor 20 will signal the camera 16 to continue to sequentially relay images of the sleeping infant 14 over a period of time to monitor the infant's sleeping pattern set forth in block 32 . Alternatively, if the reference image 26 is made of the side of the infant 14 , the second image 28 is compared against features such as, for example, the infant's 14 profile, ear, or shoulder.
[0020] When the processor 20 determines the infant 14 has moved to a high risk position, either face down or on the infant's 14 side, an alarm situation is identified 34 , and a distress signal 30 is generated and transmitted 36 to the plurality of remote locations 24 notifying the infant's 14 caregiver. In the event that the processor 20 does not determine the infant has performed a high risk movement, the camera 16 continues to generate sequential images, from which the processor 20 compares against the reference image 26 . Preferably, the camera 16 generates an image in just a fraction of a second where the camera can also detect symptoms such as rapid eye blinking, erratic breathing, jerking movements, and the like, each of which trigger a distress signal 36 to the infant's 14 caregiver.
[0021] The invention has been described in an illustrative manner, and it is to be understood that the terminology which has been used is intended to be in the nature of words of description rather than of limitation.
[0022] Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, wherein reference numerals are merely for convenience and are not to be in any way limiting, the invention may be practiced otherwise than as specifically described. | A method of detecting high risk movements of an infant relating to Sudden Infant Death Syndrome includes generating a reference image of an infant by signaling a controller a location of a first plurality of pixels. The first plurality of pixels are stored in a controller generating a reference image. A second electronic image of the infant is generating a second plurality of pixels that are signaled to the controller. The controller compares the second electronic image to the first electronic image by determining a correlation between the first plurality of pixels to the second plurality of pixels for determining if the infant has made a high risk movement. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of and claims priority to U.S. application Ser. No. 10/647,765, filed Aug. 25, 2003 and issued as U.S. Pat. No. 6,823,979 on Nov. 30, 2004, which is a divisional of U.S. application Ser. No. 09/813,478, filed Mar. 21, 2001 and issued as U.S. Pat. No. 6,648,120 on Nov. 18, 2003), which is a continuation-in-part of U.S. application Ser. No. 09/081,223, filed May 19, 1998 and issued as U.S. Pat. No. 6,231,036 on May 15, 2001. The disclosure of these applications are hereby incorporated herein by reference in their entirety for all purposes.
FIELD OF THE DISCLOSURE
The present invention relates generally to clamping devices, and more specifically to a device that clamps a workpiece for processing.
BACKGROUND
Polyvinyl tubing is commonly used for many purposes, including by way of example rather than limitation, fencing, decking, lawn furniture, etc. In such applications, it is often required that the polyvinyl tubing be processed in one or more ways. For example, in many applications holes or slots must be cut into one or more of the sidewalls in order to accommodate mounting hardware or other associated components, or to otherwise permit a portion of one piece of tubing to be inserted into a portion of another piece of tubing. In other applications, such as polyvinyl decking systems, it may desirable to cut grooves into one surface of the tubing in order to create a non-slip surface.
The processing of such components often involves the use of a drill or router which is guided by a template or by a computerized control system. In such a process, the workpiece (e.g., a piece of tubing or some other piece of stock) must be secured in a predetermined location, with the workpiece being aligned and centered. Moreover, in order to ensure processing efficiencies, the workpiece must be quickly inserted and clamped prior to processing, and must further be quickly removed after processing. There exists a continuing need for improved clamping devices.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary view in perspective of a process machine for processing elongated articles, such as polyvinyl tubing, incorporating a clamping mechanism made pursuant to the teachings of the present invention;
FIG. 2 is an exploded view of the apparatus illustrated in FIG. 1 ;
FIG. 3 is a fragmentary top plan view of the apparatus illustrated in FIG. 1 and illustrating a workpiece illustrated being conveyed onto the device;
FIG. 4 is a view similar to FIG. 3 , but illustrating the workpiece installed in the apparatus and with the clamping members engaging the workpiece to hold the workpiece in place for processing;
FIG. 5 is a cross-sectional view taken substantially along line 5 — 5 of FIG. 1 ;
FIG. 6 is a view similar to FIG. 5 , but illustrating the manner in which the device can be adjusted to accommodate a workpiece of a smaller size than the workpiece illustrated in FIG. 5 ;
FIG. 7 is a fragmentary view in perspective of a clamping device assembled in accordance with the teachings of a second preferred embodiment of the invention;
FIG. 8 is an end elevational view taken along line 8 — 8 of FIG. 7 ;
FIG. 9 is a top plan view of the clamping device illustrated in FIG. 7 ;
FIG. 10 is a side elevational view of the device shown in FIGS. 7–9 ;
FIG. 11 is a fragmentary view in perspective of a clamping device assembled in accordance with the teachings of a third preferred embodiment of the invention;
FIG. 12 is an end elevational view taken along line 12 — 12 of FIG. 11 ;
FIG. 13 is a top plan view of the clamping device illustrated in FIG. 11 ;
FIG. 14 is a side elevational view of the device shown in FIGS. 11–13 ;
FIG. 15 is a fragmentary view in perspective of a clamping device assembled in accordance with the teachings of a fourth preferred embodiment of the invention;
FIG. 16 is an end elevational view taken along line 16 — 16 of FIG. 15 ;
FIG. 17 is a top plan view of the clamping device illustrated in FIG. 15 ,
FIG. 18 is a side elevational view of the device shown in FIGS. 15–17 ;
FIG. 19 is an enlarged fragmentary cross-sectional view taken along line 19 — 19 of FIG. 18 ;
FIG. 20 is a fragmentary view in perspective of a clamping device assembled in accordance with the teachings of a fifth preferred embodiment of the invention;
FIG. 21 is an end elevational view taken along line 21 — 21 of FIG. 20 ;
FIG. 22 is a top plan view of the clamping device illustrated in FIG. 20 ; and
FIG. 23 is a side elevational view of the device shown in FIGS. 20–22 ;
DETAILED DESCRIPTION
The following description of the disclosed embodiment is not intended to limit the scope of the invention to the precise form or forms detailed herein. Instead, the following description is intended to be illustrative of the principles of the invention so that others may follow its teachings.
Referring now to the drawings, a machine 10 for cutting openings in the side walls of an elongated workpiece 12 ( FIG. 3 ) includes a fixed support or table generally indicated by the numeral 14 , which includes a pair of longitudinal side frame members 16 , and a pair of transversely extending upper end frame members 18 which interconnect the side frame members 16 . Legs 20 extend downwardly from each end of both side frame members 16 . A lower transverse member 22 interconnects the legs 20 on each end of the machine 10 . Levelers 24 extend downwardly from each end of both lower transverse members 22 . A pair of elevators 26 are installed on each of the lower transverse members 22 and consist of an outer member 28 and an inner member 30 which extends from, and retracts into, the outer member 28 . The inner member 30 extends through the corresponding upper end frame member 18 . The elevators 26 may be operated manually, such as by a crank, pneumatically, or in any other manner.
A conveyor generally indicated by the numeral 32 is supported along the center line defined by the side frame members 16 by the elevators 26 . The conveyor 32 includes a pair of side frame members 34 which extend substantially parallel to the side frame members 16 of the fixed support or table 14 . Conveyor 32 further includes transverse end members 36 which are secured to the inner members 30 of elevators 26 . Accordingly, by operation of the elevators 26 , the conveyor 32 may be raised and lowered relative to the fixed support or table 14 . Conventional rollers 38 extends between the side members 34 and are journaled for rotation relative thereto. It will be noted that in the disclosed embodiment intermittent gaps 39 are provided between sets of the rollers 38 in which the spacing between rollers is substantially greater than the normal spacing between the rollers 38 .
A clamping and holding mechanism assembled in accordance with a first preferred embodiment of the invention is generally indicated by the numeral 40 . The clamping and holding mechanism 40 includes a pair of longitudinally extending, transversely spaced clamping members 42 which extend generally parallel to the side frame members 16 . A shaft 44 is mounted between a pair of extensions 46 extending upwardly from the end frame member 18 on one end of the support or table 14 . Glides 48 are mounted on one end of each of the clamping members 42 and are slidably engaged with the shaft 44 , to thereby restrain the clamping members 42 to movement transverse to the conveyor 32 and restraining the clamping members 42 against longitudinal movement. The clamping members 42 are actuated by camming members generally indicated by the numeral 50 .
As shown in FIG. 2 , each of the camming members 50 includes an axle 52 which is rotatably supported in a corresponding one of a number of cross members 54 which extend between the side frame members 16 intermediate the end frame members 18 . A radially extending plate 56 is mounted for rotation with each axle 52 on the end thereof that projects above the cross members 54 . A crank arm 58 is mounted for rotation with some of the axles 52 and is mounted on the end thereof extending below the cross members 54 . Each of the crank arms 58 is operated by a pneumatic actuator 60 which extends between each crank arm 58 and a bracket 62 mounted on one of the side frame members 16 . Alternatively, the actuators 60 may be attached directly to an end of the plate 56 . In order to reduce the number of actuators 60 , one or more tie rods 64 may be pivotally connected between a corresponding end of adjacent plates 56 , so that rotation of any of the plates 56 will be transferred to rotate all of the other plates 56 in the same direction. Arms 66 are rigidly mounted adjacent opposite ends each of the plates 56 and extend upwardly therefrom. Each of the arms 66 engage a corresponding one of the clamping members 42 .
Accordingly, when the pneumatic actuators 60 are operated to turn the crank arm 58 in the counterclockwise direction (viewed from above), the plates 56 will be rotated in the same direction and, because the arms 66 are rigidly connected to the plates 56 but pivotal and slidable relative to the clamping members 42 , the clamping members 42 will move transversely toward the center line of the conveyor 32 . In the disclosed embodiment, longitudinal movement of the clamping members 42 is prevented by virtue of the glides 48 slidably mounted on the shaft 44 . When the pneumatic actuators are operated to rotate the crank arms 58 and plates 56 in the clockwise direction, the clamping members 42 are spread apart. One of the clamping members 42 carries a spring loaded pin 68 ( FIGS. 3 and 4 ) that is urged outwardly from the inner edge of the clamping member to engage an end of the workpiece 12 as most clearly illustrated in FIG. 4 , to thereby locate the workpiece in a predetermined position relative to the machine 10 when the work piece is processed as will hereinafter be explained.
A router carriage generally indicated by the numeral 70 includes a bridge 72 having opposite ends 74 which are provided with glides 76 to slidably engage a corresponding one of rails 78 which are mounted on the side frame members 16 and extend upwardly therefrom. Accordingly, the bridge 72 may slide along the side frame members 16 between the ends of the table or export 12 . The height of the bridge is established by a number of uprights 80 50 that transverse portions 82 clear the conveyor 32 and the clamping members 42 . Shafts 84 extend between corresponding pairs of the uprights 80 substantially parallel to the side frame members 16 . A router support 86 is slidably mounted on the shafts 84 for movement longitudinally along the conveyor 32 . The router support 86 carries a pair of transversely extending shafts 88 which slidably engage the router 90 to guide the router for movement transverse to the conveyor 32 . Accordingly, by sliding relative to the shafts 84 and 88 , the router 90 can be positioned at any point along the upper side of the workpiece 12 when the workpiece 12 is installed in the machine 10 and engaged by the clamping members 42 . The router 90 is guided by a conventional follower arm 92 which traces on the pattern 96 incorporated within a template 94 , in a manner well known to those skilled in the art. Necessary electrical connections to the router 90 are made by electrical wiring extending through a clamp 98 attached to the carriage 70 .
In operation, the workpiece 12 is placed upon the rollers 38 from the right hand end of the machine 10 (viewing FIGS. 1–4 ). The workpiece 12 is supported by the rollers 38 , and the operator may easily push the workpiece 12 into the machine 10 until the end of the workpiece 12 engages the pin 68 to locate the workpiece relative to the machine 10 . The height of the conveyor 32 may be adjusted by operation of the elevators 26 to bring the workpiece 12 to the proper height where it may be engaged by the router 90 and in which the end of the workpiece will engage the spring loaded pin 68 . For example, in FIG. 5 , a relatively large cross section workpiece is being processed, so such that the elevators 26 are used to lower the conveyor 32 . In FIG. 6 a smaller cross section workpiece is illustrated in which the conveyor 32 has been raised to properly position the workpiece 12 relative to the router 90 .
After the workpiece 12 has been installed in the machine 10 , the pneumatic actuators 60 are operated to rotate the camming members 50 . Since the axle 52 of each camming member 50 is located along the centerline of the machine 10 , rotation of the camming members 50 in the counterclockwise direction (viewed from above) causes the clamping members 42 to move towards the center line of the conveyor 32 , each clamping member 42 moving towards the center line from opposite directions. Accordingly one of the clamping members 42 will engage the side of the workpiece before the other clamping member 42 engages the other side of the workpiece, unless the workpiece is aligned along the center line. The work piece will be moved transversely as the clamping members 42 close against opposite sides of the workpiece, thereby aligning the center line of the workpiece along the center line of the machine 10 .
Processing of the workpiece using the router 90 may then begin. The carriage 70 is moved manually along the tracks 78 along the template 96 , which extends along the side of the machine. After the follower arm 92 is installed in the pattern 96 defined in the template 94 , operation of the router 90 is initiated to cut the desired apertures in the workpiece 12 . Accordingly, the carriage 70 is moved manually along the workpiece to cut successive apertures or other features into the workpiece 12 . Of course, it is within the scope for the invention to use the clamping mechanism with more automated types of machines, in which the router or equivalent cutting or processing device is indexed by numerical control along the length of the workpiece. It is also obviously within the scope of the invention to provide other types of processing of the workpiece other than by router, and processing of different types of workpieces, such as shafts, elongated metal parts, etc.
Referring now to FIGS. 7 through 10 , a clamping and holding device assembled in accordance with the teachings of a second embodiment of the invention is shown and is referred to by the reference numeral 140 . It will be understood that the clamping and holding device 140 may be suitably mounted to any suitable frame or support, such as, for example, the table 14 discussed above with respect to the first embodiment. In the disclosed embodiment, the clamping and holding mechanism 140 may be mounted to one or more of the cross members 54 (shown in fragment in FIGS. 7 , 8 and 10 ) of the table 14 . The clamping and holding device 140 includes a pair of elongated clamp rails 142 a , 142 b which function to engage the work piece 12 in a manner similar to that discussed above with respect to the first disclosed embodiment. It will be noted that the clamp rails 142 a , 142 b are disposed on opposite sides of a path along which the workpiece 12 proceeds, with the path being indicated in FIG. 7 by the reference character A. The clamp rails 142 a , 142 b are engaged by a plurality of clamp members 144 which are spaced apart along the path A.
Referring now to FIG. 8 , each of the clamp members 144 includes a pair of uprights 146 a , 146 b , each of which has an upper end 146 c which engages an adjacent one of the clamp rails 142 a , 142 b . Each of the uprights 146 a , 146 b also includes a lower end 146 d . The lower ends 146 d of the uprights 146 a , 146 b are mounted to a cross member 148 , and the cross member 148 is mounted to an axle 152 . The axle 152 is mounted to the cross member 54 (discussed above with respect to the first embodiment and shown in fragment in FIGS. 7 , 8 and 10 ) 50 as to be pivotable about its longitudinal axis. In the disclosed embodiment, the axle 152 is pivotably mounted to the cross member 54 by a pair of journaled supports 154 . A lower end 156 of the axle 152 extends below the lower support 154 , and a lever arm 158 is mounted to the lower end 156 of the axle 152 and extends laterally therefrom. Alternatively, the axle 152 may be suitably mounted to a single journaled support 154 . Further, the lever arm may extend from a central portion or an upper portion of the axle 152 . Also, it will be noted when viewing FIG. 7 that not all of the clamp members 144 need include a lever arm 158 . However, for each of the clamp members 144 including the lever arm 158 , an actuator 160 is provided, each of which is connected to one of the lever arms 158 and also to a fixed support (not shown), such as a fixed portion of the table 14 . Alternatively, the actuator 160 may be connected directly to the cross member 148 . It will be understood that a number of different mechanisms may be employed to pivot the clamp members 144 , such as, by way of example and not limitation, a gear mechanism or a suitable linkage mechanism. The operation of the actuators 160 is controlled by a controller 161 (illustrated schematically in FIG. 10 ). It will be understood that the actuators 160 (or any of the actuators discussed herein with respect to any of the disclosed embodiments) may be any suitable commercially available actuators, such as pneumatic actuators, hydraulic actuators, air over oil actuators, electric linear actuators, servo motors, stepper motors, or any other type of powered actuators.
Referring now to FIGS. 7 and 9 , the upper end 146 c of each of the uprights 146 a , 146 b may be pivotably connected to its corresponding clamp rail 142 a , 142 b , respectively, by a pivot 162 . By virtue of the pivots 162 , in response to rotation of the cross members 148 in the clockwise direction caused by the extension of the actuator 160 , the clamp rail 142 a will move to the left when viewing FIG. 9 , while the clamp rail 142 b will move to the right when viewing FIG. 9 . It will be understood of course that the clamp rails 142 a and 142 b will also move inwardly toward a workstation disposed along the path A. When the operation of the actuator 160 is reversed, the clamp rails 142 a and 142 b will move in the opposite directions and away from the path A. As an alternative, the upper ends 146 c of the uprights 146 a and 146 b may pivotably and slidably engage their corresponding clamp rails 142 a , 142 b . In such an alternative situation, each of the clamp rails 142 a and 142 b would be provided with a guide, such as the guides 48 which engage a transverse shaft 44 in a manner similar to that discussed above with respect to the first disclosed embodiment and which arrangement is shown in FIGS. 1 , 2 and 3 . It will be understood that in such an alternative arrangement the guides 48 engaging the shaft 44 will prevent longitudinal movement of the clamp rails 142 a , 142 b , such that they will move inward and outward in a manner similar to the movement of the rails 42 in the first embodiment.
In operation, the workpiece 12 proceeds along the path A supported by a suitable conveyor, such as the conveyor 32 discussed above with respect to the first disclosed embodiment. Once the workpiece 12 has reached the desired location, which is typically defined when the leading end of the workpiece 12 comes into contact with the spring loaded pin 68 (discussed above with respect to the first disclosed embodiment) or any other suitable stop (not shown), the actuators 160 are activated. Viewing FIG. 9 , when the actuators 160 are extended, each of the clamp members 144 will pivot about its respective axle 152 in a generally clockwise direction when viewed from above. Again, the pivoting action of the clamp members 144 is provided by the actuators 160 engaging the lever arm 158 on selected ones of the clamp members 144 . The rotation of the clamp members 144 causes the clamp rails 142 a and 142 b to move closer to the center line of the path A, such that the inward edges of the clamp rails 142 a , 142 b will come into contact with the side edges of the workpiece 12 , thus centering and clamping the workpiece 12 at the desired workstation. The processing operations such as the drilling of holes, the cutting of grooves, or other operations, are then carried out using the router 90 or other required tools in the manner discussed in greater detail above with respect to the first disclosed embodiment.
When the processing of the workpiece 12 is complete, the actuators 160 are retracted, which once again moves the rails 142 a and 142 b outwardly and away from the workpiece 12 , thus permitting the workpiece 12 to be conveyed off the machine 10 . Another workpiece may then be processed in a similar manner.
Referring now to FIGS. 11 through 14 , a clamping and holding device assembled in accordance With the teachings of a third embodiment of the invention is shown and is referred to by the reference numeral 240 . The clamping and holding device 240 may be suitably mounted to any suitable frame or support, such as the table 14 discussed above with respect to the first embodiment. The clamping and holding mechanism 240 may be mounted to one or more of the cross members 54 (shown in fragment in FIG. 11 ) of the table 14 . The clamping and holding device 240 includes an elongated link arm 242 which interconnects a plurality of clamp members 244 which are spaced apart along the path A.
Referring now to FIG. 12 , each of the clamp members 244 includes a pair of uprights 246 a , 246 b , each of which has an upper end 246 c . Each of the uprights 246 a , 246 b also includes a lower end 246 d . The lower ends 246 d of the uprights 246 a , 246 b are mounted to a cross member 248 , and each of the cross member 248 is mounted to an axle 252 . The axle 252 is mounted to the cross member 54 so as to be pivotable about its longitudinal axis. In the disclosed embodiment, the axle 252 is pivotably mounted to the cross member 54 by a pair of journaled supports 254 . The link arm 242 is mounted to each of the clamp members 244 , such that the rotational movement of all of the clamp members 244 about their respective axes will be synchronized (i.e., they will all move in unison). In the disclosed embodiment the link arm 244 is mounted to the cross members 248 . Alternatively, the link arm 242 may be mounted to the uprights 246 a or 246 b . A number of actuators 260 are provided, each of which is connected to the link arm 242 . Alternatively, the actuators 260 may be mounted to a lever arm (not shown) or other suitable mechanism engaging the axle 252 , or the actuators 260 may be mounted directly to the clamp members 244 in order to rotate the clamp members 244 . The operation of the actuators 260 is controlled by a controller 261 (illustrated schematically in FIG. 14 ).
In operation, the workpiece 12 proceeds along the path A supported by a suitable conveyor, such as the conveyor 32 discussed above with respect to the first disclosed embodiment. Once the workpiece 12 has reached the desired location, which again may be defined when the leading end of the workpiece 12 comes into contact with the spring loaded pin 68 (discussed above with respect to the first disclosed embodiment) or any other suitable stop (not shown), the actuators 260 are activated by the controller 261 . Viewing FIG. 13 , when the actuators 260 are extended, each of the clamp members 244 will pivot about its respective axle 252 in a generally clockwise direction when viewed from above. The pivoting action of the clamp members 244 is synchronized by the link arm 242 . The rotation of the clamp members 244 causes the uprights 246 a , 246 b to move closer to the center line of the path A, such that the inward portions of the uprights 246 a , 246 b will come into contact with the side edges of the workpiece 12 , thus centering and clamping the workpiece 12 at the desired workstation. Once again, the processing operations such as the drilling of holes, the cutting of grooves, or other operations, are then carried out using the router 90 or other required tools in the manner discussed in greater detail above with respect to the first disclosed embodiment.
Referring now to FIGS. 15 through 19 , a clamping and holding device assembled in accordance with the teachings of a fourth embodiment of the invention is shown and is referred to by the reference numeral 340 . The clamping and holding device 340 may be suitably mounted to any suitable frame or support, such as the table 14 discussed above with respect to the first embodiment. The clamping and holding mechanism 340 may be mounted to one or more of the cross members 54 (shown in fragment in FIG. 15 ) of the table 14 . The clamping and holding device 340 includes a plurality of counter-pivoting clamp members 344 and a plurality of counter-pivoting clamp members 345 , all of which are spaced apart along the path A.
Each of the clamp members 344 includes a first clamp 344 a and a second clamp 344 b , which counter-rotate relative to each other about a common pivot axis 347 . The clamp 344 a includes a pair of uprights 344 c mounted to a common cross member 348 a , while the clamp 344 b includes a pair of uprights 344 d mounted to a common cross member 348 b . The uprights 344 d are both pivotably mounted to the cross member 348 b , and are both operatively connected to a drive motor 349 by a drive belt 351 .
Referring now to FIG. 19 , the clamp 344 a is mounted to a hollow pivot axle 352 which is rotatably mounted within a pair of journaled supports 354 s . The clamp 344 b is mounted to a pivot axle 355 which is rotatably received within the hollow pivot axle 352 . Each of the axles 352 a and 352 b includes a lever 358 a , 358 b , respectively, which extends outwardly. An actuator 360 a engages the lever 358 a , while an actuator 360 b engages the lever 358 b . The clamps 344 are similar in all respects to the clamps 345 , except for the omission of the rotatable uprights and the motors 349 .
In operation, the workpiece 12 proceeds along the path A. The workpiece may supported by a suitable conveyor, such as the conveyor 32 discussed above with respect to the first disclosed embodiment. However, forward motion of the workpiece 12 along the path A is caused by rotation of the uprights 344 d in response to operation of the motors 349 . Accordingly, the conveyor 32 need not include a separate driving mechanism. Still further, the conveyor 32 may be dispensed with in its entirety, with the functions of supporting the workpiece 12 being performed solely by the clamps 344 a and 344 b , and the function of moving the workpiece 12 along the path A being performed solely by the rotating uprights 344 d on the clamps 344 b.
Once the workpiece 12 has reached the desired location, which again may be defined when the leading end of the workpiece 12 comes into contact with the spring loaded pin 68 (discussed above with respect to the first disclosed embodiment) or any other suitable stop (not shown), the actuators 360 a and 360 b are activated. Viewing FIG. 17 , operation of the actuators 360 a and 360 b will cause the uprights 344 c of the clamp 344 a and the uprights 344 d of the clamp 344 b to move inwardly in unison toward the path A, thus engaging, centering and holding the workpiece 12 at the work station. The counter-rotating pivoting action of the clamps 344 a and 344 b is synchronized by synchronizing the operation of the actuators 360 a and 360 b using any suitable control system (not shown) which control system would be within the ability of one skilled in the art. Once again, the processing operations such as the drilling of holes, the cutting of grooves, or other operations, are then carried out using the router 90 or other required tools in the manner discussed in greater detail above with respect to the previous embodiments.
Referring now to FIGS. 20 through 23 , the clamping and holding device 340 is shown in which the clamp members 344 described above are eliminated, and instead only the clamp members 345 are employed. It will be understood that in such a situation the conveyor 32 discussed above with respect to the first disclosed embodiment, or any other suitable conveyor, must still be employed. In all other respects, the alternative arrangement of FIGS. 20 through 23 is essentially the same as that outlined above with respect to FIGS. 15 through 19 .
Those skilled in the art will appreciate that, although the teachings of the invention have been illustrated in connection with certain embodiments there is no intent to limit the invention to such embodiments, On the contrary, the intention of this application is to cover all modifications and embodiments fairly falling within the scope of the appended claims either literally or under the doctrine of equivalents. | A device for receiving and processing an elongated workpiece that proceeds along a path is disclosed. The device comprises a plurality of clevis-shaped members, each clevis-shaped member being pivotable about a vertical axis and having a pair of spaced apart upwardly extending posts. The clevis-shaped members are spaced apart relative to the path, and the posts of each clevis-shaped member defining therebetween a centered workstation disposed along the path. At least one actuator is provided, with the actuator operatively engaging each of the clevis-shaped members such that the each clevis-shaped member will pivot about its vertical axis. Accordingly, in response to operation of the actuators the posts of each of the clevis-shaped members shift in unison to center and clamp the workpiece at the workstation. | 1 |
BACKGROUND OF THE INVENTION
I. Field of the Invention
This invention relates generally to hunting decoys and, more particularly, to a drive system for providing animation to such decoys.
II. Discussion of the Prior Art
Hunters frequently employ decoys when hunting game animals. For example, when hunting water fowl, a hunter will commonly set out a plurality of decoys in a pattern typical of that assumed by live birds so that the setting will appear natural to the species being hunted when viewed from a distance. The decoys are designed to resemble the water fowl species being hunted and, generally speaking, most decoys either sit stationary on land (as in the case of geese) or are anchored so as to float as a group on water as with ducks. For the most part, such decoys do not have movable parts.
The prior art does include decoys which are not totally immovable. For example, the U.S. Pat. No. 5,636,466 to Davis illustrates a goose decoy containing a radio controlled motor for causing the decoy's wing appendages to flap and for the decoy to move from a sitting position to a standing position. The Hazlett U.S. Pat. No. 4,845,873 patent describes a duck decoy incorporating an electric motor coupled to wing appendages for producing a flapping motion thereof. Various other patents have been granted in the past that incorporate either an electric motor or a string mechanism manipulated by the hunter to produce animation, such as wing and/or head movement.
When it is considered that electric motor drive systems for use in decoys generally deploy DC motors powered by batteries and that it is desirable that such batteries will provide sufficient current to power the appendages for prolonged periods of time, e.g. 12 hours at a stretch, it is imperative that the drive system be highly efficient and minimize torque demand on the motor. The present invention provides such a drive system.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided an apparatus for animating a hunting decoy where the decoy is of the type having a hollow body and an appendage that is adapted to be moved relative to the hollow body. The drive system includes a mounting block affixed to a portion of the hollow body of the decoy and which projects inwardly into an interior of the hollow body. An electric motor and associated gear reduction box is attached to the mounting block and the gear reduction box has an output shaft supporting an eccentrically disposed drive shaft, which is journaled for rotation by suitable bearings in a connector block. When the motor is energized, the connector block follows an orbital circular path. A pair of wheel members are also journaled for rotation about bearings surrounding cylindrical posts affixed to the mounting block and a flat, flexible, spring member is used to link the connector block to a peripheral surface of the first and second wheels such that the wheels are made to oscillate with reciprocating motion through a predetermined arc as the connector block traverses its circular orbit. In accordance with one embodiment of the invention, means are provided for coupling appendages of the decoy to the pair of wheels, thereby imparting a swinging motion to the appendages when the motor is energized.
In the preferred embodiment, the appendages may be wings on a water fowl decoy and the weight of the wings are counter-balanced by the spring action provided by the flexible link member, which greatly reduces the output torque requirements necessary to drive the orbiting connector block. With the drive system of the present invention applied to a Canadian goose decoy whose wing appendages are each two feet in length, the wing tips were allowed to move up and down approximately 23 inches and required only about 0.595 in lbs. of torque on the motor to do so. Using a 9 volt transistor radio battery, the device was made to operate continuously for a period of 25 hours in a wind-free environment. By incorporating a remotely controlled switch for coupling the battery output to the motor, intermittent operation can be achieved, prolonging still further the life of the battery used in powering the appendage drive system.
DESCRIPTION OF THE DRAWINGS
The foregoing features, objects and advantages of the invention will become apparent to those skilled in the art from the following detailed description of a preferred embodiment, especially when considered in conjunction with the accompanying drawings in which like numerals in the several views refer to corresponding parts.
FIG. 1 is a perspective view of a hunting decoy having movable wing appendages;
FIG. 2 is a side elevational view of a hunting decoy incorporating the improved drive system of the present invention;
FIG. 3 is a cross-sectional view taken through the hollow body along line 3--3 in FIG. 1 showing a front view of the drive system; and
FIG. 4 is a side view of the drive system of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to the perspective view of FIG. 1, the hunting decoy is here shown as a Canadian goose. However, it is to be understood that the present invention can be applied to other hunting decoys, such as ducks and other water fowl or even to larger animals, such as deer, where it is desired to provide a degree of animation to the decoy. The goose decoy is indicated generally by numeral 10 and it is shown in a standing disposition with a body 12 supported by legs 14. First and second fabric wings 16 and 18 are affixed to mounting pegs 20 and 22, which project outwardly through a slot 24 formed in the back portion of the hollow, molded body 12 just behind the neck.
The wings 16 and 18 each include a lightweight, elongated, graphite stiffening spar 26 extending through a tubular hem 28 formed along one edge of the fabric 30, preferably Tyvek®, comprising the wing. The wing is curved along its opposite edge to simulate the shape of a goose wing and the wing fabric is secured to the body 12 proximate the tail thereof by means of snaps as at 32.
As will be explained in greater detail hereinbelow, the lightweight graphite stiffening ribs 26 of the wings connect to the mounting pegs 20 and 22 which are driven so as to move in a coordinated wig-wag fashion, either continuously or intermittently, to provide a more realistic appearance to live geese flying over the site where the decoys are placed by the hunter.
Referring next to the side elevation of FIG. 2, a portion of the body 12 and wing 16 are broken away to reveal the positioning of the motor drive system of the present invention within the hollow body cavity of the decoy. A generally rectangular access panel 34 is provided in the decoy's back and fastened thereto by screws as at 35 is a generally rectangular mounting block 36 having a curved upper edge to conform to the curvature of the access panel 34 and the decoy's back surface at the location of the access opening. An electric, battery-operated DC motor 38 with an integral gear reduction box 39 is attached to the mounting block 36 by four stand-offs and screws as at 40. With no limitation intended, the motor 38 may comprise a Type CLL, 4 watt DC motor sold by Maxon Precision Motors, Inc. of Burlingame, Calif. The gear reduction box used with this motor provides a 100:1 reduction ratio. This motor provides adequate output torque with a relatively low current drain and is capable of being powered by a standard 9 volt transistor radio battery having a 0.5 ampere-hour rating.
As can best be seen in FIG. 4, the gear reduction box 39 has an output shaft 42 supporting an eccentric 44 disposed within a circular bore 46 formed in the mounting block 36. The eccentric 44, in turn, has a drive shaft 48 on which a connector block 50 is journaled by bearings 52.
Also affixed to the mounting block 36 is a spring clip 54 for releasibly holding a DC battery 56 therein. The battery leads 58 are connected in series with an ON-OFF switch 60 mounted on the cover panel 34 (FIG. 3) and to terminals 62 on the motor 38. It is also contemplated that a radio-controlled ON-OFF switch module 64 may be provided whereby the drive may be turned on and off by a hunter located in a blind a predetermined distance from the animated decoy of the present invention.
Referring to FIG. 3, two wheels 66 and 68 are journaled for rotation on the mounting block 36. More specifically, bolts 70 pass through ball bearings 72 seated in the wheels 66 and 68 with the bolts passing through tubular spacers 74 (FIG. 4) and the mounting block 36 and are secured by nuts 76. The mounting pegs 20 and 22 are affixed to the front face surface of the wheels 66 and 68 and, as mentioned above, the pegs pass through slots 24 formed between the access cover panel 34 and the edge of the opening in the decoy's hollow body in which the cover panel 34 is adapted to fit.
The wheel 66 has a resilient, flat spring link member 78 affixed to its periphery by a screw 80 and the strip 78 extends downward into a slot 82 formed in a top portion of connector block 50. Likewise, a flat spring link member 84 is connected by a screw 86 to the periphery of the wheel 68 and the opposite end of this link member 84 also fits into the slot 82 in the connector block 50. Positioned between the spring-like flexible link members 78 and 84 is a generally rigid divider strip 88. The lower ends of the flexible link members 78 and 84 as well as the divider strip 88 are held in the slot 82 in the top of the connector block 50 by means of a rivet 90. The link members 78 and 84 may comprise spring steel, but preferably are fabricated from a suitable polymer, such as PEEK, having a thickness of about 0.787 mils. The divider member 88 may be a copper beryllium alloy or other suitable, relatively inflexible metal or polymer.
Having described the constructional features of the drive system of the present invention in detail, consideration will next be given its mode of operation.
OPERATION
When the manual switch 60 or the radio-controlled switch 64 is actuated to its ON position, current is delivered from the battery 56 to the motor, causing the output shaft 42 of the gear reduction 39 to rotate. Rotation of the shaft 42, in turn, causes the eccentric 44 to orbit within the circular bore 46 in the mounting block 36 causing the connector block 50 to also trace an orbital path as the eccentric shaft 48 rotates within the bearing 52. As the connector block rises and falls in traversing its orbital path, the flexible link members 78 and 84 joining the connector block 50 to the peripheral surface of the wheels 66 and 68 imparts an oscillating rotational movement of these wheels through a predetermined arc. The divider 88 operates to control the extent of bending of the flexible link members, reducing any tendency of the link members to fail through fatigue.
As the wheels 66 and 68 oscillate, the outer ends of the wing mounting pegs 20 and 22 sweep through a predetermined arc of about 23 inches in length and impart a flapping motion to the wings 16 and 18 (FIG. 1). With the type of motor and gear reduction box identified herein, the wings are made to flap at a rate of about 30 cycles per minute with a fresh battery. It is found that the weight of the wings is counter-balanced by the spring force provided by the flexible link members as they wrap about the periphery of the wheels during the orbital movement of the connector block 50. This greatly conserves the current that has to be drawn from the battery to provide the necessary torque needed to displace the wings. In fact, the drive system described was able to flap the wings for a period of 151/2 hours with a drop in flapping frequency of about 20 percent and a drop in voltage of only 1.5 volts, i.e., from 9 volts to 71/2 volts.
In a comparison test between the drive system of the present invention using PEET leaf spring elements as the connecting rod and a drive system using a standard style connecting rod coupled between the eccentric shaft and the wheels 66 and 68, the average current draw per cycle was decreased by 1/3 using the present invention.
This invention has been described herein in considerable detail in order to comply with the patent statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use such specialized components as are required. However, it is to be understood that the invention can be carried out by specifically different equipment and devices, and that various modifications, both as to the equipment and operating procedures, can be accomplished without departing from the scope of the invention itself. For example, in applying the drive system of the present invention to a deer decoy, the ear appendages and/or the tail of the decoy can be made to twitch back and forth in a realistic manner. | A drive system for animating a hunting decoy is designed to fit within the decoy's hollow body and provide movement to appendages, such as wings, on the decoy. The drive system comprises a battery-operated DC motor for imparting reciprocal movement of mounting pegs on which the appendages are affixed. The oscillating, reciprocating motion is provided by an eccentric that is coupled through flexible leaf spring links to the periphery of first and second wheels that are journaled for rotation on parallel axes. The leaf spring linkages function to counter-balance the weight of the appendages, reducing current drain on the motor. | 0 |
BACKGROUND OF THE INVENTION
[0001] The invention relates to a method for supplying animals kept in restricted compartments with feed by means of at least one dispensing unit which is arranged movably along the restricted compartments, is connected to a control center and has at least one dispensing element, and also to an apparatus therefor.
[0002] Animals which are kept in individual or group stalls are intended to be fed automatically several times per day. This applies, for example, to calves which are to be supplied with milk 3-4 times in the first 14 days. In the case of liquid feed, such as milk, the feed is intended to be delivered either in buckets in the stalls, or else the individual stalls are assigned automatic drinkers or suction teats connected to automatic drinkers. An example of such a system is described in DE 10 2008 050 715.6.
[0003] What is referred to as a mobile milk dispenser is also known, from DE 10 2006 044 721, with which milk is passed from stall to stall where it is transferred into corresponding dispensing units, for example into buckets. This is extremely time-consuming.
[0004] DE 36 09 387 A1 discloses an apparatus in which a supporting and guide rail which runs along the stall arrangement and is arranged above the front side of the stalls is provided. A traveling trolley which has a supporting extension arm moving along the steel passageway is arranged movably on said supporting and guide rail. The traveling trolley is moved from stall to stall, with liquid feed and/or water being delivered into corresponding receiving containers. The entire system requires a very large amount of space and is suitable only for supplying one row of stalls.
[0005] DE 36 13 887 A1 discloses a device for supplying animals with a liquid feed which is removable from an automatic drinker and is suppliable to a suction point via a hose line. Said suction point moves along a guide rail, but this can take place only very close to the stalls or in the latter themselves so that the animals come to the teat.
[0006] The present invention is based on the object of developing a method and an apparatus of the type mentioned above, with which a large number of animals in a large number of stalls can be supplied with feed several times per day with feed in a time-saving manner without said system having a substantial interfering effect on the entire operation.
SUMMARY OF THE INVENTION
[0007] The foregoing object is achieved by compartments having group animals and compartments for individual animals being jointly supplied with feed by a control center.
[0008] In this connection, it is possible, for example—but in a non-limiting manner—for the control center to be assigned in a stationary manner to the compartments having group animals and for the dispensing unit to be assigned movably to the compartments having individual animals. In this case, the control center can be arranged so as to be accessible between a plurality of compartments and from said compartments such that the corresponding dispensing elements are also reachable by a multiplicity of animals. By contrast, the movable dispensing elements themselves reach a multiplicity of animals kept individually.
[0009] The object is also achieved in that opposite compartments are jointly supplied with feed by a control center; also in this connection, it is possible, for example—but in a non-limiting manner—for the control center to be assigned to the compartments in a stationary manner and for the dispensing unit to be assigned thereto in a movable manner. The corresponding dispensing elements themselves reach a multiplicity of animals.
[0010] Conceivable control centers for feed include especially automatic drinkers, but also stores or the like which serve to prepare or temporarily store the feed. The direct connection to a milking robot is also conceivable, and therefore, for example, a specific calf can directly drink the milk from its own mother.
[0011] The dispensing elements for young animals will primarily be teats. However, the invention also includes other dispensing elements, such as drinking dishes, troughs, buckets or the like.
[0012] Of course, the entire system contains a corresponding means of detecting the feed quantity. This is undertaken, for example, via a hose pump, a flow sensor with flow measurement or the like, wherein the corresponding quantity is then also assigned again to the individual animal. For this purpose, for example, the teat or the stall can be assigned an identification system having, for example, a known RFID antenna, as a result of which the drinking animal is identified, the consumption is documented and is optionally restricted. If a container is carried along, for example in the intermediate container, a pair of scales which determines a corresponding stock of feed can also be arranged here. Therefore, measurements in the dispensing element, for example in the bucket, are also possible. The buckets are filled on the outward trip and checked on the return trip. A plurality of possibilities are conceivable here and are intended to be covered by the invention.
[0013] Furthermore, in a preferred exemplary embodiment of the invention, it is intended to check the animals. This can be carried out in multiple ways. Firstly, a camera can photograph the corresponding drinking animal. The camera can also determine the activity of the animal and, for example, can emit an alarm signal if the activity falls short of a certain level. The photo can also be used, for example, to draw a conclusion about the weight and the appearance and therefore about the condition of the animal. Video sequences showing the behavior of the animals can also be compiled.
[0014] Health parameters can also be derived via the suction speed, and also via the time which an animal requires in order to start sucking after the teat has been brought into its position. Alarm signals can also be emitted if certain values are fallen short of, especially if the entire quantity of feed has not been retrieved. It is determined, for example, how long the animal needs until it arrives at the teat or whether it remains lying down and does not stand up. A temperature measurement can also be undertaken at the teat itself.
[0015] The disinfecting of the teat is especially also of great importance. The dispensing element can preferably even be provided with a “teat turret”, thus giving rise to the possibility of providing each animal with its own teat which is only used by the animal, or of cleaning the individual teats after use before said teats are used for the following animal.
[0016] The temperature of the feed should be influenced especially when keeping animals in the open air. For example, it is conceivable to heat the feed before the dispensing element. For this purpose, the teat, the dispensing unit, the tube system and/or an intermediate container are assigned corresponding insulating means and/or heating means which keep the feed at a necessary temperature.
[0017] A lock system is preferably also intended to be provided and is used to indicate to the animal the possibility of feed intake. For example, this may be an acoustic or optical signal, in particular a light during darkness. Also here, there are again many options which are intended to be covered by the invention.
[0018] The invention also includes an apparatus for supplying animals kept in restricted compartments with feed by means of at least one dispensing unit which is arranged movably along the restricted compartments and has a dispensing element, wherein a distance between dispensing element and the restricted compartment is changeable.
[0019] This means that the position of the teat with respect to the animal is now changeable and, secondly, said teat can be removed again from the remaining working region if, for example, said working region is required for other purposes. In this case, it is of secondary importance how said extension arm and the changing of the distance between dispensing element and the restricted compartment are configured technically. It is conceived of merely by way of example to design the extension arm as a bar, at the two ends of which a respective teat is arranged. The bar can be extended horizontally in relation to the dispensing unit sometimes more to the left and sometimes more to the right such that said bar can supply left rows of stalls and also right rows of stalls with feed by the rail. It is also conceivable for the extension arm to be designed to be telescopic such that it can be extended and retracted again on one or both sides of the dispensing unit.
[0020] Another possibility consists in designing the extension arm to be pivotable or rotatable through approx. 180° with respect to the dispensing unit such that sometimes a stall of the left row of stalls and sometimes a stall of the right row of stalls can be supplied with feed, but that, on the other hand, if the space between the rows of stalls is intended to be used, the extension arm is positioned vertically and is therefore out of the way.
[0021] Of course, two or more extendable or pivotable extension arms on the right and/or on the left, which can then also be assigned a plurality of pumps for the feed, are also conceivable.
[0022] The pivoting out or extension can be undertaken by motor; telescoping is also conceivable, in particular, pneumatically or hydraulically. However, purely mechanical deflecting means are also possible, for example via corresponding slotted guides or types of disk controllers or the like. All this is intended to be covered by the inventive concept.
[0023] The dispensing unit itself is preferably connected directly to a control center, for example to a corresponding automatic drinker or similar preparation station for the feed, a storage container, milking robot, etc. For example, a suction tube which is carried along during the movement of the dispensing unit can serve for this purpose. So that longer distances can also be spanned, a pump which assists the drinking can also be switched on in the suction tube. This can be controlled by a corresponding suction sensor.
[0024] It is also conceivable for the dispensing unit to be assigned an intermediate container, preferably with a plurality of chambers for different types of feed, said intermediate container being movable together with the dispensing unit. Said intermediate container is then connected to the corresponding preparation station or can be filled at the preparation station.
[0025] In a further exemplary embodiment of the invention, it is possible to fill, for example, water buckets in the stalls with water via a second system. For this purpose, a separate system can be provided, but integration into the existing system is also possible by corresponding valves being used to produce a connection to the intermediate container/automatic drinker for advancing feed and, as an alternative thereto, a connection to a water source. A similar procedure is also undertaken for cleaning the entire system and in particular the teats. The tube line and also the teats can be rinsed by means of water or a cleaning agent.
[0026] The manner in which the rail is configured and where the latter is arranged is intended likewise to be of secondary importance. It is conceivable, for example, for the rail itself to be incorporated into a roof structure such that the rail itself does not have any interfering effect whatsoever. The dispensing unit then hangs from the rail into the stall aisle and is arranged on the rail itself so as to be movable as customary.
[0027] By means of the overall arrangement, keeping animals which are younger than 14 days individually can be automated. If said animals then come into the group, they are already familiar with the automatic drinker. The automatic drinker is better utilized, since the rail system is “controlled” from the mixer thereof. However, the subsequent feeding in combination with a normal automatic drinker when keeping older animals in groups is also advantageous.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Further advantages, features and details of the invention emerge from the description below of preferred exemplary embodiments and with reference to the drawing, in which
[0029] FIG. 1 shows a schematic illustration of a part of an apparatus according to the invention for supplying animals kept in restricted compartments with feed, in the use position;
[0030] FIG. 2 shows an enlarged side view of another exemplary embodiment of a dispensing unit on a rail;
[0031] FIG. 3 shows a schematic illustration of another exemplary embodiment of a part of an apparatus according to the invention for supplying animals kept in restricted compartments with feed, in the use position.
DETAILED DESCRIPTION
[0032] According to FIG. 1 , 1 identifies a row of stalls in which animals (not shown specifically) which are kept for rearing or fattening are located. In the present exemplary embodiment, two rows of stalls are arranged approximately parallel to each other, wherein a rail 3 runs in a corresponding stall aisle 2 . A dispensing unit 4 for a feed is located movably on the rail 3 . Said feed is prepared in a control center 5 and is supplied via a line 6 or a tube, pipe or the like either directly to the dispensing unit 4 or to an intermediate container 7 connected in between. If an intermediate container 7 is provided, said intermediate container can likewise be movable on the rail 3 . Of course, the intermediate container can also be integrated in the dispensing unit.
[0033] According to the invention, the dispensing unit 4 is assigned an extension arm 8 on which respective teats 9 . 1 and 9 . 2 are located on both sides of the dispensing unit 4 . Said extension arm 8 is arranged in the dispensing unit 4 so as to be displaceable or telescopic horizontally along the double arrow X such that a distance a between teat and stall 1 is changeable. It is indicated by dashed lines in FIG. 1 that the teat 9 . 1 was brought up close to the stall 1 . 1 into a previous use position such that the animal or animals kept in stall 1 . 1 can drink. The current use position of the dispensing unit 4 , in which the teat 9 . 2 is extended toward stall 1 . 2 such that the animals located in stall 1 . 2 can drink, is then illustrated by solid lines. The entire operation is monitored by an identification system 10 .
[0034] According to FIG. 2 , it is indicated that, instead of a telescopic extension arm 8 , a pivotable extension arm 8 . 1 can also be assigned to the dispensing unit 4 , said extension arm being able to be pivoted from the left to the right corresponding to the double arrow Y. In this manner, feed can be administered sometimes to the animals of the row of stalls on the left side and sometimes to animals in the row of stalls on the right side, or else in an alternating manner.
[0035] The line 6 can also be assigned a valve 11 with which it is possible to produce a connection to the control center 5 and a connection to a water supply means 12 . It is therefore firstly also possible to rinse the line 6 and/or the teats 9 . 1 and 9 . 2 , but secondly also to fill, for example, water points in the individual stalls 1 , wherein then a corresponding dispensing element is provided instead of the teats or next to the teats.
[0036] The present invention functions as follows:
[0037] The dispensing unit 4 is connected via the tube 6 either directly to the control center 5 or via the intermediate container 7 to the control center 5 , wherein, in the latter case, a connection between container 7 and control center 5 can also be eliminated, but then the intermediate container 7 is filled at intervals.
[0038] Depending on requirements, the dispensing unit 4 is moved along the rail 3 and supplies the individual stalls 1 with feed. In this case, likewise depending on requirements, the extension arm 8 is extended to the left or right with respect to the dispensing unit 4 and therefore the particular teat 9 . 1 or 9 . 2 is arranged in the vicinity of the animal to be fed. However, part of the stall aisle 2 always remains free and can be walked along by the user irrespective of the feeding.
[0039] Of course, this feeding option is also possible with the pivotable extension arm 8 . 1 according to FIG. 2 . The latter also has the advantage that, if it is not required, it can be placed vertically such that the user can pass on both sides of the rails without being disturbed by the extension arm, or, for example, dung or the like can be transported away.
[0040] Furthermore, cleaning of the entire supply system up to and including the teats 9 . 1 and 9 . 2 is then possible via the water supply means 12 . However, the water supply means 12 also provides the option of filling water buckets present in the individual stalls 1 with water for the animals. The operation is then similar as for feeding the animals, but then a different dispensing element than the teat is used and, for example, the extension arm 8 is extended in a targeted manner such that the corresponding dispensing unit is located above the water bucket. This is possible without difficulty by control technology.
[0041] According to FIG. 3 , it is also conceivable to supply not only individual animals kept in compartments but also animals kept in groups with feed. For this purpose, larger stalls 1 . 3 , 1 . 4 are connected to the control center 5 . | In a method for supplying animals kept in restricted compartments ( 1 to 1.4 ) with feed by at least one dispensing unit ( 4 ) which is arranged movably along the restricted compartments, is connected to a control center ( 5 ) and has at least one dispensing element ( 9.1, 9.2 ), compartments ( 1.1 ) having group animals and compartments ( 1.2 ) for individual animals are intended to be jointly supplied with feed by a control center ( 5 ). | 0 |
[0001] This application claims priority to U.S. Provisional Application Ser. No. 61/191,423 filed Sep. 9, 2008, the content of which is incorporated by reference.
BACKGROUND
[0002] Many people have some form of physical handicap which limits their mobility, and who require some form of mechanical aid or assistance for their movement. In many cases, the physical infirmity is not so severe as to require a wheelchair or similar device for mobility; many times, the handicapped person has limited use of his or her legs, and can get around reasonably well with the use of one or more crutches, canes, a walker, etc. In some instances, a person may require only a single cane, at least for some limited mobility.
[0003] In recent years, the number of persons who might require the assistance of a cane while walking has increased significantly. Such increase is due primarily to the gradual overall aging of the population, which in turn can be attributed in large degree to significant advances in medicine and generally improved living conditions. However, such medical advances have also allowed younger individuals suffering from particular maladies or who are partially incapacitated as a result of an accident or other happening, which persons might otherwise be incapable of walking or moving around at all, to regain at least some of their mobility more quickly than in the past with the assistance of a device such as a cane.
[0004] Although canes can be enormously effective in aiding one's mobility by partially transferring the user's weight from the legs to the arms as well as by steadying such person, in effect providing three legs rather than only two, most cane users also find that it is desirable to have a means for quickly and effectively temporarily storing such cane when it is not in use. For example, during times when the user is sitting down or in a resting position, the cane is not required to be used, but preferably should be stored within easy reach of the user for convenient retrieval when such cane is again required for use. However, often there is no convenient or practical place to store or rest the cane within easy reaching distance. If the cane is placed temporarily aside, older users not only may forget where it was placed, but the cane may be precariously placed, and when an attempt is made to recover it, frequently it will be just out of reach or may have been knocked down or over or may have slid to the floor where it can itself constitute a tripping hazard. In addition, many cane users do not have the ability, vision, or range of motion to easily walk, bend, or otherwise move to recover a cane which may have been resting against a wall and fallen to the floor, whereupon it may have become a tripping hazard or danger itself, not only to the user, but to others. Not infrequently, the cane user himself or herself may knock over a standing cane and then have difficulty in recovering it, or even be unable to recover it, from the floor. On the other hand, a cane user often does not wish to hold the cane when it is not required, as he or she wishes to have his or her hands free to perform other tasks, such as preparing food, opening medicine bottles, eating, writing, using the telephone, or sometimes the cane owner simply wants to rest without having to grasp the cane.
[0005] While various approaches have been attempted and frequently adopted for either holding a cane nearby the user or in a vertical position or both, there are also a wide variety of sizes, shapes, styles and other structural differences between canes. Often, a user will have several different canes, each having slightly different dimensions. For example, while most canes have a generally rounded shaft, others may have a generally oval or even square or rectangular shape. There is also a wide variance in the types of handles among different canes, as well as differences in the diameters of the shafts of canes. Thus, any holding device for canes must be able to be used on a variety of differently dimensioned canes. Such device should preferably also be able to hold the cane clear of the floor while standing and relatively close to the owner and more or less upright when sitting in order to prevent a tripping hazard.
[0006] U.S. Pat. No. 6,997,362 discloses a cane holding device for temporarily holding a cane in close proximity to the body of the user comprising a cane engaging member having at least two interconnected apertures for holding canes of different shapes and sizes, and a lanyard securable around the neck of the user for holding the cane engaging member. The material from which the cane holder is formed is resilient to allow a cane to be pressed from one aperture or orifice in the cane holder to another.
SUMMARY
[0007] 1. An accessory to provide a user with hands-free placement of a cane, comprising:
a. a hook including
i. a curved body to be mounted on the cane and below a cane handle, and ii. a tip adapted to be received in a pocket or a pouch affiliated with the user to provide hands-free operation; and
b. a cane interface pad positioned between the curved body and the cane.
[0012] 2. The accessory of claim 1 , comprising a foot pad at the tip.
[0013] 3. The accessory of claim 2 , wherein the foot pad comprises rubber.
[0014] 4. The accessory of claim 2 , wherein the foot pad comprises acrylic tape.
[0015] 5. The accessory of claim 1 , wherein the pocket comprises a pant pocket or a shirt pocket.
[0016] 6. The accessory of claim 1 , wherein the pocket comprises a pocket on a purse.
[0017] 7. The accessory of claim 1 , wherein the cane interface pad comprises a tape.
[0018] 8. The accessory of claim 7 , wherein the cane interface pad is installed on the cane to keep the cane from touching the ground during hands-free placement.
[0019] 9. An accessory to provide a user with hands-free placement of a cane, comprising:
a. a hook including
i. a curved body to be mounted on the cane and below a cane handle, and ii. a tip adapted to be received in a pocket on the user to provide hands-free operation; iii. a foot pad at the tip to provide traction when the tip is positioned on a flat surface; and
b. a cane interface pad positioned between the curved body and the cane.
[0025] 10. The accessory of claim 9 , wherein the foot pad comprises rubber.
[0026] 11. The accessory of claim 9 , wherein the foot pad comprises acrylic tape.
[0027] 12. The accessory of claim 9 , wherein the pocket comprises a pant pocket or a shirt pocket.
[0028] 13. The accessory of claim 9 , wherein the pocket comprises a pocket on a purse.
[0029] 14. The accessory of claim 9 , wherein the cane interface pad comprises a tape.
[0030] 15. The accessory of claim 9 , wherein the cane interface pad is installed on the cane to keep the cane from touching the ground during hands-free placement.
[0031] 16. A method for providing hands-free operation with a cane accessory including a hook, a curved body, a tip adapted to be placed in a pocket or pouch, and a cane interface pad, the method comprising:
a. determining a position of the cane interface pad so that cane hook is not dragging on the ground while at pocket height during installation; b. adjusting the position so that the cane bottom clears table height or rest room height; c. mounting the cane interface pad below a cane handle at the position between the curved body and the cane; and d. placing the tip in the pocket or pouch to provide hands-free operation.
[0036] 17. The method of claim 16 , comprising testing the hook in different locations for individual tastes.
[0037] 18. The method of claim 16 , comprising forming a foot pad at the tip bottom to provide traction.
[0038] 19. The method of claim 16 , comprising permanently mounting the cane hook in the predetermined position.
[0039] 20. The method of claim 16 , comprising painting the cane accessory to match the cane color.
[0040] 21. (TO BE UPDATED ONCE FINALIZED)
[0041] Advantages of the cane hook may include one or more of the following. The cane hook can hang from the user's pocket or purse when the user needs to be hands-free. The acrylic cane hook allows the user to become hands free when needed, for example when shopping, on the phone, loading groceries or whenever two hands are needed. The cane will always be within reach! The cane hook is perfect for left or right handed users. The cane hook also provides a sanitary and safer option for the user's hands. The cane handle is insulated and does not touch potentially grimy surfaces, since the cane hook is mounted below the handle. A rubber tip allows the cane to hang from a table or a flat surface while the user is seated. The quick mounting pad or tape allows the user to experiment where to place the cane hook since everyone's pockets or tables have a different height.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] The foregoing aspects and many of the attendant advantages of this invention will be more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:
[0043] FIG. 1A shows a top view of a first cane holder embodiment.
[0044] FIG. 1B shows a side view of a first cane holder embodiment.
[0045] FIG. 1C shows a front view of a first cane holder embodiment.
[0046] FIG. 2A and FIG. 2B show top views of a second cane holder embodiment.
[0047] FIG. 2C shows a side view of a second cane holder embodiment.
DESCRIPTION
[0048] The following detailed description is of the best mode or modes of the invention presently contemplated. Such description is not intended to be understood in a limiting sense, but to be an example of the invention presented solely for illustration thereof, and by reference to which in connection with the following description and the accompanying drawings one skilled in the art may be advised of the advantages and construction of the invention.
[0049] FIG. 1A shows a top view of a first cane holder embodiment, while FIG. 18 shows a side view of a first cane holder embodiment and FIG. 1C shows a front view of a first cane holder embodiment. In one embodiment, the cane 100 is cylindrical. The cane holder of FIGS. 1A-1C is adapted to be secured to a cane 100 through an interface pad 110 . The other side of the cane holder pad 110 is attached to a body 132 with a curved hook 130 . The concave curvature of the body of the hook body allows the cane hook to be easily mounted on any cane. The cane hook is an accessory that fits virtually all canes.
[0050] At one end of the hook 130 is a recessed region 136 which is adapted to support a hook foot pad 138 . In one embodiment, the foot pad 138 is an acrylic tape on the top of the cane hook that provides traction on slippery surfaces such as glass. In another embodiment, the foot pad 138 can be rubber or other suitable elastic substances that provide a connecting surface, which allows the foot pad to affix firmly to the cane 100 through the hook 130 and provide a better supporting effect. Due to the elasticity of the foot pad and its contact against an outer supporting surface, an anti-skid effect of the foot pad is improved and the foot pad is capable of absorbing the deformation so as to ensure stability when using the cane 100 .
[0051] During installation, the user locates the appropriate location for the cane holder pad 110 on the cane 100 and the cane hook body 132 . Preferably, the bottom of the cane 100 is not touching or dragging on the ground when the hook is hooked on a pocket or a recess to free the user's hand. This can be done by testing the hook in different locations for individual tastes. The user should set the height so the cane hook is not dragging on the ground while at pocket height. The user should set the location of the cane holder pad 110 such that the cane 100 clears table and rest room heights as well. During the installation, the acrylic tape does not solidify and allows relocation as long as it is kept clean. Once the location is determined, the user can then use a clear cement or high strength glue to permanently mount the handy cane hook in the desired location.
[0052] In one embodiment, the cane hook 130 is clear acrylic. In other embodiment, the cane hook 130 can be painted to match cane color if desired.
[0053] FIG. 2A shows a cross-sectional top view of a second cane holder embodiment. In this embodiment, a hook 230 is securely connected to a cane 200 through a tape or pad 210 . The tip of the hook has a foot pad 238 that can be a material to provide traction for surfaces such as glass or plastic, among others. FIG. 2B shows another top view of a second cane holder embodiment.
[0054] FIG. 2C shows a side view of a second cane holder embodiment. As shown in FIG. 2C , the foot pad 238 is secured to the tip of the hook 230 with a recess 236 which is filled with the same material as the foot pad 238 . In one embodiment, the tip of the hook 230 is immersed in a rubber or similar elastic material and after the immersion, the rubber fills the recess 236 and forms a seal on the outside of the tip at the same time. Also, the body of the cane hook is curved so that when the body is placed against the pad 210 and the cane 200 , the pad 210 securely affixes the bottom of the cane hook to the curved surface of the cane.
[0055] As indicated above, the cane holder of the invention is not only utilitarian and practical but also can be decorative. For example, the plastic holder itself can be formed from various colors of plastic not only in solid colors, but because of the shape of the holder of mixtures of colors such as swirls, multi-colors, and the like. In addition, the lanyard can be made in various decorator fabric designs and colors including color coordination with the outfit of the user.
[0056] While the present invention has been described at some length and with some particularity with respect to the several described embodiments, it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment, but it is to be construed with references to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and, therefore, to effectively encompass the intended scope of the invention. | An accessory to provide a user with hands-free placement of a cane includes a hook with a curved body to be mounted on the cane and below a cane handle, and a tip adapted to be received in a pocket or a pouch affiliated with the user to provide hands-free operation; and a cane interface pad positioned between the curved body and the cane. | 0 |
STATEMENT OF GOVERNMENT INTEREST
The U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of N00019-02-C-3003 awarded by the United States Navy.
BACKGROUND
The present invention relates to devices used to adhesively bond gas turbine components. Gas turbine components can have very intricate geometries that sometimes require composite pieces to be adhered together in order to form the gas turbine component. In order to cure the adhesive, a desired pressure needs to be applied to the composite pieces. Elevated temperatures also may be used in order to cure the adhesive.
Fixturing devices using mechanical tooling are often used to apply pressure to composite materials in order to cure an adhesive under desired conditions. However, in some applications, this curing process sometimes requires applying a specific, known pressure to the composite materials. Such devices may not be designed to adequately accommodate the temperatures needed to thermally cure the particular adhesive. Additionally, these fixturing devices may be bulky and cumbersome to use, and may be too large to use in certain applications.
BRIEF SUMMARY OF THE INVENTION
The present invention relates to a pressure application device for curing an adhesive on a component, particularly components of complex geometries. The device comprises a pair of jaws, at least one spring recessed into a cavity defined within the first jaw, and a cap. A first end of a spring partially extends into the cavity and a second end of the spring contacts the cap. When force is applied to the cap, the cap transmits the force through the spring to the first jaw. In order to limit the separation of the cap from the first jaw, a retainer is used. Besides curing the adhesive with pressure, the pressure application device can be placed into an oven to thermally cure the adhesive.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded perspective view of a fan inlet case.
FIG. 2 is a top view of a pressure application device.
FIG. 3 is a side view of the pressure application device.
FIG. 4 is a front view of the pressure application device.
FIG. 5 is a perspective view of a disassembled portion of the pressure application device.
FIGS. 6A-6C are cross-sectional views of alternative spring arrangements for use with the pressure application device.
FIGS. 7A and 7B are cross-sectional views of the pressure application device and a workpiece before and after application of force.
DETAILED DESCRIPTION
As shown in FIG. 1 , a fan inlet case 10 has an outer hub 12 , an inner hub 14 , and a plurality of struts 16 extending therebetween. Struts 16 can each be covered with a fairing 18 having an inside surface 22 and an outside surface 24 . Each strut 16 has an outer surface 26 . Inside surface 22 of fairing 18 is attached to outside surface 24 of strut 16 using an adhesive 28 , such as an adhesive of the type described in commonly-assigned U.S. application Ser. No. 11/494,830. Generally, in order for adhesive 28 to cure, it must be subjected to pressure and heat. Furthermore, the strict geometric limitations of fan inlet case 10 make it difficult to apply pressure to fairing 18 in order for adhesive 28 to cure and secure fairing 18 to strut 16 .
As shown in FIG. 2 , pressure application device 30 includes clamps 32 and 34 , a first jaw 36 , a second jaw 38 , and a cap 40 . First jaw 36 and second jaw 38 apply pressure to the workpiece, in particular fairing 18 . In order for the first jaw 36 and second jaw 38 to apply pressure to the workpiece, a force applicator applies force to cap 40 . The force applicator can be a mechanical device, such as vices and clamps, or hydraulic or pneumatic devices (e.g., pressure cylinders). In the illustrated embodiment, clamps 32 and 34 are each threadably-adjustable cantilever C-clamps. Clamps 32 and 34 are positioned on cap 40 and second jaw 38 to apply a force to cap 40 . When this force is applied to cap 40 , cap 40 transmits the force through a spring mechanism (shown in FIG. 5 and described in detail later in this description) located between cap 40 and first jaw 38 to apply a controlled amount of pressure to the workpiece. The force transmitted to first jaw 38 is a function of the distance cap 40 moves toward first jaw 38 and the spring constant of the spring mechanism.
First jaw 36 has a front side 46 and a back side 48 , and second jaw 38 has a front side 52 and a back side 54 . First jaw 36 and second jaw 38 are configured so that pressure application device 30 can fit within the tight geometrical restrictions of mounting locations of a component, such as fan inlet case 10 , when the adjacent struts are occupied by clamps. In order to meet these geometrical restrictions, the overall width of first jaw 36 (measured between front side 46 and back side 48 ) can be between about 0.64 cm (0.25 inch) and 2.54 cm (1 inches). Portions of first jaw 36 and second jaw 38 can be tapered as shown in the illustrated embodiment to reduce widths in selected areas, in order to further accommodate placement of device 30 in geometrically restricted areas (e.g., between struts 16 near inner hub 14 of inlet case 10 ). First jaw 36 can be made from stainless steel, titanium, aluminum or other metallic materials. In the present embodiment, first jaw 36 and second jaw 38 are substantially rectangular members, although depending on the desired pressure profile they can have various other shapes.
Front sides 46 , 52 of jaws 36 , 38 each form a clamping surface. Front sides 46 , 52 can include a layer of material, such as an elastomer, silicone or other polymer, to create a soft face in order to not damage fairing 18 or other workpieces when pressure is applied.
In the illustrated embodiment, first jaw 36 is connected to second jaw 38 by support pieces 56 , 58 and shoulder bolts 62 , 64 , 66 , 68 . Support pieces 56 , 58 each have holes 72 , 74 , 76 , 78 where shoulder bolts 62 , 64 , 66 , 68 are inserted. Holes 72 , 74 , 76 , 78 are elongated slots so that the spacing between first jaw 36 and second jaw 38 can be regulated. Support pieces 56 , 58 can have notches 82 , 84 to allow the workpiece to be inserted between first jaw 36 and second jaw 38 with enough clearance.
Cap 40 surrounds first jaw 36 . In the illustrated embodiment, cap 40 is positioned between support piece 56 and support piece 58 . As shown in FIG. 3 , cap 40 is a C-shaped or U-shaped cap that covers back side 48 of first jaw 36 . A first end 86 of clamp 32 is adjacent cap 40 and a second end 88 of clamp 32 is adjacent the back side 54 of second jaw 38 . First jaw 36 is connected to second jaw 38 by support pieces 56 , 58 and shoulder bolts 62 , 64 , 66 , 68 . When pressure is to be applied to the workpiece, clamps 32 , 34 apply a force to cap 40 and to back side 54 of second jaw 38 . When this force is applied to cap 40 , cap 40 transmits the force through a spring mechanism (shown in FIG. 5 and described in detail later in this description) located between cap 40 and first jaw 38 to apply a controlled amount of pressure to the workpiece. As this force is applied to cap 40 , first jaw 36 moves relative to second jaw 38 . The movement of first jaw 36 relative to second jaw 38 is controlled by support pieces 56 , 58 .
As shown in FIG. 4 , pressure device 30 also has retainers 90 , 91 that are comprised of alignment rods 92 , 94 and disc members 96 , 98 . Each disc member 96 , 98 is positioned onto an end of each alignment rod 92 , 94 . Disc members 96 , 98 and alignment rods 92 , 94 could be a single piece, such as a bolt or other fasteners. However, disc members 96 , 98 can also be adjustable along alignment rods 92 , 94 . For example, disc members 96 , 98 can be threaded rings (e.g., nuts) and alignment rods can be threaded rods (e.g., bolts). Retainers 90 , 91 limit separation of cap 40 from first jaw 36 . Furthermore, when no force is applied to cap 40 , cap 40 abuts disc members 96 , 98 of retainers 90 , 91 .
As shown in FIG. 5 , each pressure transferring assembly is comprised of clamp 34 , first jaw 36 , cap 40 , alignment rod 94 , disc member 98 , and spring 102 . Spring 102 can comprise a plurality of springs that can be arranged in series, in parallel or in combinations thereof to achieve various pressure profiles. Springs 102 can be disc springs, coil springs, leaf springs, or other types of springs. In the illustrated embodiment, springs 102 are disc springs, which have a relatively low profile that helps reduce the overall thickness of the device 30 . First jaw 36 has cavity 104 , and springs 102 are inserted into cavity 104 . By recessing springs 102 inside cavity 104 , the overall thickness of pressure device 30 is significantly reduced. Cap 40 has a hole 106 , and alignment rod 94 is inserted through hole 106 and into cavity 104 . When inserted into cavity 104 , alignment rod 94 is surrounded by spring 102 . First jaw 36 also has a hole 108 wherein the shoulder bolt 68 can be inserted through the hole 78 in the support piece 58 and secured in first jaw 36 .
FIGS. 6A-6C are cross-sectional views of alternative spring arrangements for use with the pressure application device 30 . As shown in FIG. 6A , a first disc spring 102 a provides a maximum spring travel x and a maximum spring force y. Value of the maximum spring travel x and maximum spring force y are a function of mechanical properties of the spring 102 a , and a suitable commercially-available disc springs can be selected to match the values desired for a particular application. If a first disc spring 102 a is put in series with a second disc spring 102 b both having identical spring properties, as shown in FIG. 6B , the maximum spring travel x will remain essentially constant while the maximum spring force will be 2y. However, if first disc spring 102 a is put in parallel with second disc spring 102 b , as shown in FIG. 6C , the maximum spring travel will be 2x, while the maximum spring force will remain y. Therefore, depending on how springs 102 are arranged inside cavity 104 , different amounts of force can be applied to first jaw 36 and thus different amounts of pressure can be applied to fairing 18 in order to cure adhesive 28 . Additional disc springs 102 can be utilized together in serial and/or parallel in order to achieve desired travel and force parameters. The use of springs allows a regulation of applied force, as explained further below.
FIGS. 7A and 7B are cross-sectional views of the pressure application device 30 and a portion of the inlet case 10 before and after application of force, respectively. As shown in FIG. 7A , when pressure assemblies of the pressure application device 30 are at rest and no force is applied to cap 40 , cap 40 rests against disc member 98 . When force is applied to cap 40 , as shown in FIG. 7B , gap 110 is created. Gap 110 is measurable and can be calibrated to the force applied to front side 46 of first jaw 36 . Thus, a specific, known amount of force can be transferred to fairing 18 in order to cure adhesive 28 and adhere fairing 18 to strut 16 . If disc member 98 is fixed on alignment rod 94 , gap 110 may be adjusted by using a new disc member 98 and a new alignment rod 94 or if threaded, by adjusting the length of the alignment rod 94 . If disc member 98 is adjustable on alignment rod 94 , gap 110 may be calibrated by adjusting disc member 98 relative to the cap 40 when it is at rest. Besides calibrating gap 110 , the force applied to the front side 46 of first jaw 36 can also be adjusted by changing the arrangement of springs 102 depending on the desired pressure profile as discussed previously. By combining springs 102 in various combinations of series and parallel arrangements, a desired maximum force can be applied and a known spring travel can be used to determine a desired size of gap 110 .
Pressure application device 30 can have more than two pressure transferring assemblies located along first jaw 36 . As mentioned earlier, a pressure transferring assembly comprises clamp 34 , first jaw 36 , cap 40 , retainer 90 , and spring 102 . Pressure application device 30 can also have multiple caps 40 along first jaw 36 , each cap 40 having at least two pressure transferring assemblies.
In one embodiment, pressure application device 30 is configured to apply a maximum pressure between about 0 N/mm 2 (0 psi) and 6.90 N/mm 2 (1000 psi) to a surface (e.g., to the fairing 18 ), preferably between about 0.345 N/mm 2 (50 psi) and 1.38 N/mm 2 (200 psi). Pressure application device 30 also can operate during the thermal cure cycle of the adhesive 28 at temperatures between about −17.8° C. (0° F.) and 232° C. (450° F.), preferably between room temperature (about 22° C. (72° F.)) and about 148° C. (350° F.), but could operate at temperatures greater than about 232° C. (450° F.) with a limited life.
It is possible to place pressure application device 30 into an oven (not shown) or other high temperature environment along with components being adhered (e.g., fan inlet case 10 ) in order to simultaneously apply pressure and heat to cure adhesive 28 . Simple mechanical clamps alone, like prior art C-clamps, would generally not provide precise, controllable levels of force when placed in a high temperature environment, but rather would tend to vary the applied force due to thermal expansion of the clamps and/or workpiece. Moreover, the use of force sensing equipment in a high temperature environment like an oven would be difficult, and sensing equipment that could survive the high temperature environment tends to be cost-prohibitive. Pressure application device 30 utilizes springs 102 to regulate applied force while still allowing consistent performance in high temperature environments and a relatively compact overall size.
Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. For example, the particular type and arrangement of springs used to regulate applied force can vary as desired for particular applications. | The present invention relates to a pressure application device for curing an adhesive on a component, particularly components of complex geometries. The device comprises a pair of jaws, at least one spring recessed into a cavity defined within the first jaw, and a cap. A first end of a spring partially extends into the cavity and a second end of the spring contacts the cap. When force is applied to the cap, the cap transmits the force through the spring to the first jaw. In order to limit the separation of the cap from the first jaw, a retainer is used. | 1 |
The invention relates to a photoetching process for making surgical needles that has particular applicability to the simultaneous manufacture of large numbers of surgical needles, to a sheet made by said process containing a plurality of surgical needles, and to certain surgical needles that can be made by said process.
BACKGROUND OF THE INVENTION
Surgical needles are made, one at a time, by a multi-step process involving considerable time, labor, and precision machinery. A brief outline of a typical process for making surgical needles is the following:
Stainless steel wire of the appropriate diameter is straightened and cut to the desired length to form a blank. One end of the blank is die-formed and/or ground to produce a cutting edge or point. The other end is either drilled to form a hollow receptacle for a surgical suture, or it is stamped to form a channel for swaging the suture. The point is sharpened, and the needle is bent. As a rule, the final steps are a heat treatment to temper the needle, that is, to increase the hardness without imparting brittleness, and a polishing process. After this, sutures are attached to the needles by any of several means. One additional feature of the prior art process for making surgical needles is that the shape of the needle is limited by what can be done to a piece of wire. As will be apparent below, this invention provides a process that can be used to make any shape that can be drawn in two dimensions.
This multi-step process is acceptable for the production; of relatively large surgical needles, but with the advent of microsurgery and the need for ever smaller surgical needles, the process has proven to be quite inefficient for the production of small needles having diameters of, e.g., from one to three mils because of the large amount of skilled labor and precision machinery required in handling such small needles individually throughout the various steps of the process leading to attachment of sutures and final inspection.
This invention provides a process that is particularly well adapted to the efficient simultaneous production of large numbers of small size surgical needles.
BRIEF SUMMARY OF THE INVENTION
The process of the invention comprises the steps of: (a) coating at least one side of a metal sheet with a light sensitive photoresist; (b) exposing the photoresist with light in the image of a plurality of surgical needles (the dimensions of the image are modified to compensate for lateral etching during the etching step, as will be explained below); (c) removing the unexposed photoresist, to thereby leave in place on the metal sheet hardened photoresist in the image of a plurality of surgical needles; (d) exposing the product of step (c) to an etchant to remove metal not protected by said hardened photoresist, to thereby form a plurality of surgical needles.
The invention also provides a metal sheet containing a plurality of surgical needles.
THE PRIOR ART
Heath, in U.S. Pat. No. 2,735,763, discloses a photoetching process for making small parts from a sheet of thin metal which will not withstand any mechanical working.
Jacks et al., in U.S. Pat. No. 3,358,363, discloses a photoetching process for making fuse elements.
Snyder, in U.S. Pat. No. 3,816,273, discloses a photoetching process for making wire.
Poler, in U.S. Pat. No. 4,080,709, discloses a photoetching process for making the mounting structure for an intra-ocular lens.
Dinardo, in U.S. Pat. No. 4,282,311, and James, in U.S. Pat. No. 4,284,712, disclose a photoetching process for making flyleads for video disc styli.
BRIEF DESCRITION OF THE DRAWINGS
FIG. 1 is a top plan view of a metal sheet containing a plurality of surgical needles produced by the process of the invention;
FIG. 2 is an enlargement of a portion of the sheet of FIG. 1;
FIG. 3 is an enlarged perspective view of a surgical needle made by the process of the invention;
FIG. 4 is a perspective view of the needle of FIG. 3 attached to a surgical suture;
FIG. 5 is an enlarged plan view of a photomask of the image of a single surgical needle that can be used in carrying out the process of the invention;
FIG. 6 is an enlarged plan view of a second photomask of the image of a single surgical needle that can be used in carrying out the process of the invention;
FIG. 7 is an enlarged view of a portion of FIG. 5;
FIG. 8 is an enlarged perspective view of the suture attachment end of the needle of FIG. 3;
FIG. 9 is a cross-sectional view taken along line 9--9 of FIG. 8, and additionally showing a suture attached to the needle;
FIG. 10 is an enlarged view of a portion of FIG. 2;
FIG. 11 is a cross-sectional elevation taken along line 11--11 of FIG. 10; and
FIG. 12 is an enlargement of a portion of FIG. 5.
DETAILED DESCRIPTION OF THE INVENTION
The first step in the process of the invention is to coat at least one side of a metal sheet with a light sensitive photoresist material. The metal sheet that is used can be selected so as to possess all of the strength, hardness, toughness, and grain structure, in the sheet form that the metal will need in the form of a surgical needle. This is one advantage over the current multi-step process for producing surgical needles, in which one step is usually a heat treatment step to develop optimum properties. Any metal or alloy that can be obtained in thin sheet form can be used, provided that it has the requisite properties of strength, hardness, etc. For instance, a tensile strength of at least about 300,000 psi, a Rockwell C hardness of at least 45, and ductility so that the needle can be bent up to about 90° and then straightened without breaking, are desirable. The metals that can be used include stainless steel, specifically, 320 stainless steel and Gin 5 and Gin 6 razor blade grade stainless steel, and molybdenum. Gin 6 stainless steel is preferred. The metal sheet will usually have a thickness of from about one to about ten mils.
The photoresist compositions used are known in the art. For instance, they are discussed in "Photo-Resist Materials and Processes" by William DeForest, McGraw-Hill 1975, and a wide variety of photoresist compositions are available commercially. The metal sheet can be coated with the photoresist by any convenient method, such as dip coating, spraying, and the like. In a preferred aspect of the invention, both sides of the sheet are coated with the photoresist and the needle images are formed on both sides. (In any event, the second side must be coated with either a photoresist or a protective coating.) In a typical coating process, the metal sheet is thoroughly cleaned, rinsed, dipped in dilute aqueous acid, e.g., 10% HCl, rinsed again, dried, and then coated. Since the photoresist compositions are sensitive to light, the coating should be carried out under "safe light" conditions, e.g., under yellow or orange light, or in the dark. After coating, the coated metal sheet is baked at a moderately elevated temperature for a few minutes, e.g., at about 80° C. for about 10 minutes, to dry the coating. After the coated sheet has cooled, it is then exposed to light in the image of a plurality of surgical needles, shaped to compensate for lateral etching of metal during the etching step, a principle that is well understood in the art. This is done by first covering the coated sheet with a negative or first photomask containing an image of the needles. An illustrative enlarged negative or first photomask of a single surgical needle is shown as 14 in FIG. 5 (it will be discussed in more detail) below. In a preferred aspect of the invention, the coated reverse side of the metal sheet is then covered with a second photomask that is the mirror image of the first photomask 14 and in perfect register therewith, and then exposed to light. An illustrative enlarged second photomask of a single surgical needle is shown as 16 in FIG. 6. As will be explained in more detail below, the said second photomask 16 may differ in certain details from the said first photomask 14. The light source used to expose the photoresist is rich in ultraviolet radiation. A carbon-arc light is preferred, but mercury-vapor lamps or ultraviolet rich fluorescent lights may also be used. Typical exposure times are within the range of a few seconds to several minutes, depending upon the nature and power of the light source, the distance of the light from the photoresist, and the sensitivity of the photoresist. The instructions of the manufacturer of the photoresist should be followed in this respect.
After exposure, the photoresist is rinsed in a suitable commercially available "developer" formulated for the particular photoresist being used, to remove the unexposed photoresist. After rinsing, the sheet with the photoresist coating in the form of surgical needles may be baked at, e.g., 120° to 260° C. for 5 to 10 minutes to further harden the remaining photoresist coating. The next step is to etch away the unwanted metal in an etching solution. Typical etching solutions include 36- to 42- degrees Baume aqueous ferric chloride, an aqueous mixture of ferric chloride and HCl, or a mixture of aqueous hydrochloric acid and nitric acid, or the like. Such etching solutions are known in the art, as is their use in a photoetching process. After the etching step, there remains the desired surgical needles, which are removed from the etching solution, washed, and dried. The developed and hardened photoresist is then removed by dissolving away with a suitable commercially available stripper formulated for the photoresist being used. A detailed discussion of the application of the above process to a specific surgical needle design follows.
A surgical needle to be produced by the process of the invention is shown as 12 in FIG. 3. The needle includes a shank 18, a point 20, and a suture attachment end 22. In this design, the suture attachment end 22 includes a channel 24 by which a suture 26 may be attached, as is explained in more detail below. The first step in using the process of the invention to produce this needle 12 is to make a precision black drawing of the needle 12 several hundred times larger than the required finished size. This drawing is then optically reduced to the required size, and an exposure is made near the corner of a sheet of high resolution film. The film is moved laterally by a precision stepping device and a second exposure is made. This is repeated until a row of exposures across the film is completed. The stepping device moves the film upward by one row's width, and a second row of exposures is made. This process is repeated until the entire film area is covered. The film is then developed to produce a negative or photomask of the images of the needles.
FIG. 1 shows a sheet 28 containing a plurality of surgical needles 12 attached at their suture attachment ends 22 to continuous base rows 30 that extend the width of the sheet 28. An enlargement of a portion of the sheet 28 showing one needle 12 is shown in FIG. 2. An enlargement of a photomask 14 corresponding to this needle 12 is shown in FIG. 5. The dimensions of the image 12a of the needle in the photomask are modified to allow for lateral etching of the metal during the etching step. The photomask image of a particular part will be referred to by the same reference number, with the addition of an "a" to the number. Thus, the photomask image of the needle 12 is referred to by the reference number 12a.
As a first approximation, the metal will be etched laterally about the same distance as vertically. Thus, in the preferred situation wherein the metal sheet is etched from both sides, lateral undercutting equal to approximately one-half the thickness of the sheet should be allowed for in the photomask. The image 20a of the needle's point in the photomask preferably does not come to a point, but rather is preferably blunted as is shown in FIG. 5. Lateral etching will cause a point to be formed. This is shown schematically in FIG. 7, which is an enlargement of the image 20a of the needle's point. The arrows show the direction of lateral etching of the metal so that, after the etching step, the point of the needle will have the configuration shown in dashed lines in FIG. 7. (If the needle's point were pointed in the photomask, after etching, the point would probably be rounded rather than sharply pointed, as a result of the lateral etching.)
For ease of handling the needles produced by the process of the invention, it is preferred to produce the needles such that they are attached by a breakable connection to the metal sheet from which they are etched. By so doing, the needles can be kept separated and in order until they are ready for further processing. One way to do this is illustrated in the drawings (see, especially, FIGS. 1, 2, 5, and 6). The sheet 28 shown in FIG. 1 has the needles 12 attached to base rows 30 that extend all the way across the sheet. To assist in the removal of the individual needles 12 from the base rows 30, a transverse groove 32 may be made at the point of attachment of the needle 12 to the base row 30. (See FIGS. 10, 11 and 12.) In the photomask 14, the groove 32 is provided for by a transverse line 32a, in one of the two photomasks only, at the point of attachment to the base row 30a.
Referring now to FIGS. 5, 6, 8, and 9, the suture attachment end 22 includes a channel 24 for use in attaching the needle to a suture 26. In the embodiment shown, the channel 24 is a bilevel channel in which the first half 34 of the channel is offset longitudinally from the second half 36, as is shown clearly in FIGS. 8 and 9. The two halves of the channel are etched equally from both sides of the metal sheet so that each has a depth of about one half the thickness of the sheet. Where the two halves 34, 36 overlap, a hole 38 is produced so that the two halves 34, 36 communicate with each other. A suture 26 is attached by filling both halves 34, 36 with an adhesive material (not shown) such as an epoxy glue while the second half 36 is lying on a flat surface, and then inserting the end of a suture 26 through the hole 38 between the two halves, 34, 36 as is shown in FIG. 9. The epoxy resin is hardened at room temperature, and then given a final cure in an oven at moderately elevated temperatures, such as 40° to 60° C. The photomask images 34a, 36a, of the two halves of the channel are thin lines, as is shown in FIGS. 5 and 6, to allow for the lateral etching that will occur during the etching process. The "bilevel" channel described here has several advantageous properties. First, it serves to hold the suture securely in place while the adhesive sets, and, second, it helps to prevent the suture from being pulled out of the channel by a lateral force.
The needles 12 may be detached from the sheet 28 before attaching to a suture 26. This can be done by grasping a single needle 12 with forceps and flexing it at the break-off groove 32. Alternatively, all needles in a single row can be detached simultaneously by cutting both ends of the base row 30, removing it from the sheet 28, and then pressing the row of needles lightly on to an adhesive surface. Flexing the base row 30 upwards will cause it to break off at the break-off grooves 32, leaving the needles precisely spaced and securely held on the adhesive surface in an ideal position for suture attachment.
After the etching step and after removal of the hardened photosist, if desired, entire sheets of needles may be electropolished using conventional electropolishing methods to smooth off rough edges, polish the surfaces, and improve the shape of the needle points by reducing or eliminating undesirable projections, and by sharpening the edge. This is another advantage of the invention, since hundreds, and perhaps thousands, of needles can be electropolished simultaneously in a few minutes.
A typical electropolishing bath is an aqueous sulfuric, phosphoric, and glycolic acid bath. Polishing times of about 30 seconds at ten volts and 90° C. are typical.
The invention has been described and claimed in terms of a dry positive photoresist technique, that is, the hardened photoresist on the metal sheet is in the image of the part that is to be made. It is theoretically possible to use a wet photoresist or a negative photoresist technique in carrying out the process of the invention, although to do so would be awkward and uneconomical. | Surgical needles are produced by a process which comprises the steps of:
(a) coating at least one side of a metal sheet with a light sensitive photoresist;
(b) exposing the photoresist with light in the image of a plurality of surgical needles, each needle having a pointed end and a suture attachment end;
(c) removing the unexposed photoresist, to thereby leave in place on the metal sheet hardened photoresist in the image of a plurality of surgical needles;
(d) exposing the product of step (c) to an etchant to remove metal not protected by said hardened photoresist, to thereby form a plurality of surgical needles. | 0 |
FIELD OF THE INVENTION
The present invention relates generally to lead systems for arrhythmia control devices, and more specifically to an endocardial defibrillation lead having a mechanism that can be used both for septal fixation of the defibrillation electrode and for pacing and sensing.
BACKGROUND OF THE INVENTION
The use of electrical signals to stimulate or steady heart rhythm (pacing) or to restore heart rhythm when the muscle fibers of the heart undergo very rapid irregular contractions, which result in very little pumping of blood (defibrillation), is a well accepted, lifesaving medical technique. Implantable cardioverter/defibrillator devices have been under development since at least the 1960's. The term cardioverter is used to mean a device for the correction of ventricular tachycardia (abnormally rapid heart rate of about 100-240 beats per minute) by discharging electrical energy into the heart. The term defibrillation is used to refer to high voltage shocks which terminate fibrillation (a rapid, chaotic heart rhythm resulting in no effective pumping of blood.) Implanted defibrillation is normally accomplished by passing a current between at least a pair of internally placed electrodes. The electrode arrangement may include an endocardial lead which is transvenously positioned within the heart of the patient so that one defibrillation electrode is within the right ventricle (RV). The other electrode, in the form of a flexible, substantially planar patch, is positioned outside the heart, either subcutaneously or within the thoracic cavity next to the left ventricle. Alternatively, the housing of the defibrillator may be used as an electrode. In other systems an electrode is positioned transvenously within the superior vena cava (SVC). The SVC electrode may be used in place of or in addition to the patch electrode. Electrical current is supplied to the electrodes by a battery powered pulse generator implanted under the skin of the patient, either in the abdominal or pectoral region. Improving the conductance path between the patch electrode (or device housing or SVC electrode) and the right ventricular electrode results in reduced energy required per defibrillation pulse and this may increase the lifetime of the system or allow for the use of smaller batteries.
For purposes of defibrillation, it is desirable to maximize the contact of the defibrillation electrode with the heart wall, preferably the septum between the right and left ventricles. Such intimate contact with the heart tissue makes defibrillation more effective by lowering the defibrillation threshold (DFT).
One prior art technique for positioning one or more defibrillation electrodes near the septum has used a lead system which includes a plurality of flexible electrodes which, when released, laterally expand into positions which bear resiliently against the surrounding heart walls. See U.S. Pat. No. 5,010,894 to Edhag and U.S. Pat. No. 4,998,975 to Cohen et al. These systems however, are somewhat complex and may be difficult to remove after chronic use. Additionally, the systems do not allow significant control in the placement of the electrodes.
A number of techniques have been developed for fixation of the distal end of transvenous endocardial leads within the heart of a patient. One such endocardial electrode is described in U.S. Pat. No. 3,902,501 to Citron et al. which uses a plurality of pliant fixation tines which extend at an acute angle to the lead body from the distal tip of the lead. When the lead is extended into the right ventricle, the tines act as an anchor catching in the trabeculae of the heart wall. Over time, the growth of tissue around the tines will further act to secure the lead tip in place. Another common prior art technique for lead fixation uses a helical or "screw" tip fixation device which extends from the distal tip of the lead body. A stylet or other mechanical means extending through the lead body is used to rotate the screw tip to cause it to bore into the heart tissue. Another fixation technique for a pacemaker lead is disclosed in U.S. Pat. No. 4,858,623 to Bradshaw et al. A rigid hook for engaging tissue is pivotally fastened to the lead in the vicinity of the electrode. The tip of the hook is normally resiliently urged into a recess in the lead adjacent to the electrode. A mechanism is coupled to the lead to permit the normal bias on the hook tip to be overcome to cause the hook to extend outward from the electrode. Each of these techniques is used to affix the distal tip of the lead body to the tissue of a patient's heart. However, with each of these prior art techniques, the positioning of the lead body is not accurately controlled, if at all.
Many of the prior art fixation techniques have been developed for use with pacemaker leads. With standard pacemaker leads, positioning of the distal tip of the lead is all that is required since the lead body is simply an insulated connector. Endocardial defibrillation leads, however, include a defibrillation electrode which extends along the lead body. Typically, the defibrillation electrode of such prior art leads is fixated chronically by fibrosis or not at all and its placement is not accurately controlled at the time of implant.
Additionally, most RV defibrillation leads also include a pacing electrode at the distal tip. In most patients, the lead is generally positioned with the pacing electrode as close to the RV apex as possible, resulting in pacing pulses delivered to the apex. Recent literature shows that hemodynamics could be improved by pacing from the intraventricular septum instead of the RV apex. See for example Karpawich et al., "Septal His-Purkinje Ventricular Pacing in Canines: A New Endocardial Electrode Approach," PACE 1992; 15:2011 and "Ventricular Pacing Site Does Make a Difference: Improved Left Ventricular Function with Septal Pacing," PACE 1994; 17: 820.
It is a first object of the invention to provide a transvenous defibrillation lead for use with an implantable cardioverter/defibrillator which allows precise defibrillation electrode placement in intimate contact with the intraventricular septum.
It is a second objective of the invention to provide a defibrillation lead having a pacing electrode that delivers pacing pulses to the septum.
It is a third objective to meet the first two objectives without unnecessarily complicating the lead structure, thereby maintaining small size and good reliability.
It is a fourth objective to provide a defibrillation lead having two ventricular sensing sites for tachyarrhythmia discrimination.
SUMMARY OF THE INVENTION
The present invention provides a novel transvenous lead system which allows precise placement and maintenance of the defibrillation electrode and pacing electrode along the intraventricular septum. This is accomplished by providing a securable septal pacing electrode spaced along the length of the lead body for securing the defibrillation electrode to the septum between the fight and left ventricle. The lead system includes a lead body with a proximal end for connection to an implantable cardioverter/defibrillator and a distal end for transvenous insertion into the right ventricle of a patient's heart. As with most standard RV defibrillation leads, the distal tip of the lead is typically positioned in the apex of the fight ventricle, and may include fixation means such as a screw tip or tines. A defibrillation electrode begins near the distal tip and rims back along the length of the lead body. A securable septal pacing electrode is spaced along this portion of the lead body between the apex and the tricuspid valve. In addition to pacing, the "securable septal pacing electrode" may also be used for sensing. In one embodiment, the securable septal pacing electrode comprises a hook which is rotated out from the lead body for deployment and then counter rotated to pierce myocardial tissue and cause the lead body to be secured against the septum. The hook is initially in a retracted position within a recess in the lead body to provide ease of insertion of the lead body through a vein into the heart. The hook may have either a circular or elliptical or other appropriate cross section. This embodiment facilitates explant of the lead system since the hook may be rotated out of the septum and then back into the recess for removal. The lead body includes a septal pacing conductor which extends along a portion of the lead body parallel to the central lumen of the lead. A fixation stylet may be inserted through the lumen of the septal pacing conductor during implant and used to rotate the hook first away from the lead body and then into the heart tissue.
In an alternative embodiment of the invention, a guiding catheter is used for placement of the lead, thereby shielding venous tissue from potential damage caused by the securable septal pacing electrode during implant. This shielding may alternatively be accomplished by encapsulating the septal pacing electrode in a material such as mannitol which harmlessly dissolves following exposure to body fluids.
BRIEF DESCRIPTION OF THE DRAWINGS
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 drawings in which:
FIG. 1 shows a sectional view of a heart having a transvenous lead according to the invention inserted therein;
FIG. 2 shows a sectional view of a heart having an alternative embodiment of a transvenous lead according to the invention inserted therein;
FIG. 3 shows a cross-sectional view of a portion of the lead shown in FIG. 1;
FIG. 4A shows a cross-sectional view of the lead of the invention along section 4--4 of FIG. 3;
FIG. 4B shows the cross-section of FIG. 4A with the hook deployed in the septum;
FIG. 5 is a diagrammatic representation of a bowing stylet used in positioning the lead of the invention; and
FIG. 6 is a cross-sectional view of a septal pacing electrode of an alternative embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
An endocardial lead system according to the invention will now be described with reference to FIGS. 1-6. An endocardial lead 20 shown in FIG. 1 includes a defibrillation electrode 22 proximal of the distal end of the lead and extending along the lead body, and a pacing/sensing electrode 28 positioned in the region of the defibrillation electrode and secured to the patient's intraventricular septum. The proximal end of lead 20 is connected to an implanted cardioverter/defibrillator (not shown) of known construction. The distal tip may include a pacing/sensing tip electrode 24, and tines 26 to aid in fixation of the distal end within the apex of the patient's heart. In an alternative equally preferred embodiment, the distal fixation device may include a helical screw tip, which may or may not be electrically active for pacing/sensing. In another alternative embodiment, the tip may include no fixation device and/or no distal pacing tip electrode at all. Without a distal fixation device, the distal tip is retained in the apex region of the right ventricle by fixation of the lead body in the vicinity of the defibrillation electrode 22 to the ventricular septum wall 30 as described below with respect to FIGS. 2-5. Defibrillation electrode 22 of lead 20 may be used in conjunction with a subcutaneous (SQ) patch electrode or defibrillator housing electrode (not shown) for defibrillation. In addition to or instead of the SQ electrode, a superior vena cava (SVC) electrode may be used, and may be located on lead 20 or may be on a separate lead. Septal pacing electrode 28 may be used to pace the ventricles as needed, and will provide improved hemodynamics as compared with the typical method of pacing at the apex from a tip electrode such as electrode 24. Either electrodes 28 and 22 (or SQ), or electrodes 24 and 22 (or SQ), may be paired for sensing. As another alternative, both pairs may be used to discriminate between various arrhythmias, using the techniques of one or more of the following U.S. Patents, which are incorporated herein by reference in their entirety: 4,354,497 to Kahn; 4,790,317 to Davies; and 4,799,493 to DuFault.
FIG. 2 shows an endocardial lead 21 having a defibrillation electrode 22 proximal of the distal end of the lead and extending along the lead body, and a pacing/sensing electrode 28 positioned just proximal of defibrillation electrode 22 and secured to the patient's intraventricular septum. The lead body has a curve 48 imparted to it to aid in positioning defibrillation electrode 22 against septum 30. During implant, the lead is stiffened with a stylet, straightening curve 48 for insertion through an introducer sheath and through a vein. Upon removal of the stylet, or insertion or a less stiff stylet, the lead body resumes its curved shape to guide defibrillation electrode 22 and septal pacing electrode 28 toward septum 30. The distal tip is shown with a helical screw tip 25, which may be electrically active for pacing/sensing, may be active for defibrillation, such as described in U.S. Pat. No. 5,374,287 to Rubin, or may be electrically inactive.
It should be noted that the steps of positioning the distal tip in the apex, positioning the defibrillation electrode against the septum, securing the distal tip to the apex, and securing the septal pacing electrode to the septum can occur in various orders. The most options in step order are available if both pacing electrodes are extendable and retractable and do not require rotation of the entire lead to engage the tissue.
Septal pacing electrode 28 may be used to pace the ventricles as needed, and will provide improved hemodynamics as compared with the typical method of pacing at the apex from a tip electrode such as electrode 24. Either electrodes 28 and 22 or electrodes 25 and 22 may be paired for sensing. As another alternative, both pairs may be used to discriminate between various arrhythmias, using the techniques as described with respect to FIG. 1 above.
Also included on lead 21 are two atrial sensing electrodes 47, preferably located 10.5 to 17 centimeters from the distal end of the lead. Sensing from the pair of atrial electrodes 47 (or from atrial electrodes on a separate lead), from electrode 28 paired with either electrode 22 or a SQ electrode (not shown), and from electrode 25 paired with either electrode 22 or a SQ electrode, may provide the necessary signals to discriminate between various arrhythmias, using the technique of the U.S. Pat. No. 4,577,634 to Gessman, which is incorporated herein by reference in it's entirety. The invention would be practiced by substituting the septal electrode 28 for Gessman's low right atrial electrode.
FIG. 3 shows a portion of the lead 20 in cross-section which includes the defibrillation electrode 22 in the form of a conductive coil wound around the periphery of the lead body. The coil may be of the type assigned in U.S. Pat. No. 5,439,485, which is assigned to the assignee of the present application and is incorporated herein by reference. Other known electrode configurations may also be used. Coil 22 is connected to a lead conductor (not shown) at at least one point, preferably its distal end. A pacing hook 28 is positioned in the region of the defibrillation electrode, preferably four to ten centimeters from the distal end of the lead. Pacing hook 28 may have various cross sectional geometries including circular to provide a cylindrical hook body and rectangular to provide a flat, ribbon body. In either case, the hook is tapered to a sharp point at its tip. The ribbon configuration provides flexibility along the longitudinal extent of the lead and rigidity in the transverse plane. Pacing hook 28 pivots on a pin 32 which is mounted in a fixation ring 34 within a recess 36. Pacing hook 28 is typically a biocompatible metal such as platinum/iridium. Fixation ring 34 is preferably non-conductive, such as ceramic, acetal, or parylene coated MP35N. A septal pacing conductor 45 extends through lumen 38, which lies along lead 20 parallel to and spaced from a lead central lumen 39. The proximal end of septal pacing conductor 45 is electrically coupled to a lead connector (not shown) for connection to a pulse generator. The distal end of conductor 45 is electrically coupled to pin 32, which is in turn electrically coupled to pacing hook 28. Lumen 38 may have a seal at its distal end to prevent intrusion of body fluids. Central lumen 39 is shown including apical pacing conductor coil 41 which is electrically coupled to apical pacing electrode 24 (shown in FIG. 1 ).
During implantation of the lead, hook 28 is retracted within recess 36 which extends around the periphery of fixation ring 34 as shown in FIGS. 3 and 4A. Once the distal end of lead 20 has been positioned within the right ventricle with the defibrillation electrode 22 proximate the septum 30, hook 28 is deployed by rotating it away from the lead body. This is accomplished using a fixation stylet which is inserted through lumen 38. The stylet has a slot head at its distal end which interfaces with a slot 40 in the head of pin 32. Alternatively, conductor 45 may be stiff enough to transmit torque to pin 32 without insertion of a stylet; this stiffness may be imparted to conductor 45 by filling it or binding it with polyurethane or a polytetrafluoroethylene or the like. After the hook 28 is deployed away from fixation ring 34, it may be rotated in the opposite direction to pierce the myocardial tissue of the septum 30 to securely fix the defibrillation electrode 22 against the septum as shown in FIG. 4B. A depth of about one to three millimeters is sufficient to ensure fixation without any significant damage to the heart tissue. Attachment in this manner allows for later removal in the event this is so desired. The implanting surgeon will position the lead and actuate the fixation mechanism prior to tunneling the remainder of the lead to the pulse generator implanted in either the abdominal or pectoral region.
In some embodiments of the invention, the hook may extend out from the lead body during implantation. In this case, as described above, the hook is flexible in the direction of the lead axis and is stiff in the transverse plane. This reduces the potential for damage of the blood vessels or heart valve during an implant or explant surgical procedure. Additionally, the lead can be rotated or "sptm" in the reverse direction of the hook by the surgeon as the lead is being inserted to prevent the hook from catching on tissue. In such embodiment, the hook may be covered with a biocompatible material which is soluble in body fluids in a manner such as is described in U.S. Pat. No. 4,827,940 to Mayer et al., which patent is incorporated herein by reference. Mannitol or other sugars may be used. In this manner, the hook has a smooth coating during insertion of the lead thereby protecting the vein through which the lead is deployed. During and following insertion of the lead, the coating begins to dissolve and expose the hook for the fixation step. Alternatively, the fixation mechanism may be shielded during the implantation procedure by using an insertion catheter in a known manner.
FIG. 5 is a diagrammatic representation of a double, bowing stylet which may be used to flex the electrode against the septum. Pulling on one arm 42 of the stylet and pushing on the other arm 44 causes the pair to bow a sufficient amount to position the defibrillation electrode. Use of this technique for steerable guide wires is known in the art. Alternatively, a stylet may be shaped with an appropriate curvature or bend and then inserted into the central lumen of the lead body to position the fixation mechanism against the septum. Another technique for achieving the desired lead curvature is disclosed in U.S. Pat. No. 4,677,990 to Neubauer, which patent is incorporated herein by reference. A thread is anchored distally of the area of curvature and extends within the central lumen to the area of curvature. There the thread exits the central lumen and extends along the inside of an outer insulating sheath. The thread then reenters the central lumen and extends to the proximal end. By pulling on the thread, the lead is caused to curve in the area where the thread runs outside the central lumen.
In another alternative embodiment of the invention, a fixation device such as the one disclosed in U.S. Pat. No. 4,233,992 to Bisping, which patent is incorporated herein by reference, may be used to secure the defibrillation electrode to the septum. The fixation mechanism includes a spiral-shaped sharp fixing hook which may be provided with a spring winding. The hook is released once the lead body is in place and the spring action causes the hook to pierce the septum and fix the electrode thereto. As an alternative to using a spring to actuate the fixation hook, a stylet may be used to torque the spiral and "screw" it into the septum.
Another alternative embodiment of the invention is illustrated in cross section in FIG. 6. Instead of the pivoting pacing hook 28 shown in FIG. 3, which is not movable in the axial direction with respect to the lead body, FIG. 6 shows a septal pacing electrode 29 that is axially movable. In FIG. 6, electrode 29 is shown as a barb; it may alternatively be a rotatable hook or helix which may be extended and retracted. As shown in FIG. 6, extendable/retractable pacing barb (or hook or helix) electrode 29 is positioned in a recess 31 during implantation. Once defibrillation electrode 22 is positioned against septum 30, pacing electrode 29 is pushed out of recess 31 and pierces septum 30. A conductor 45 is electrically coupled to electrode 29 and may be used to push it out of recess 31; alternatively, a stylet (not shown) through conductor 45 may be used to extend electrode 29 (and to rotate electrode 29 in the case of a hook or helix). Conductor 45 may be insulated with a material 46 such as parylene, polyimide, or polytetrafluoroethylene. A double bowing stylet may be used to assist in positioning the defibrillation electrode 22 against the septum. Additionally, an insertion catheter or soluble coating may be used to shield the fixation mechanism during implantation as described above.
It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that structures and methods within the scope of these claims and their equivalents be covered thereby. | A lead system for use with an implantable pacemaker/cardioverter/defibrillator. The lead system includes a securable pace/sense electrode positioned between the distal tip of the lead and the tricuspid valve. The distal tip of the lead is positioned at the apex of the right ventricle and may or may not be secured there by a second fixation means such as a screw tip or tines. The securable pace/sense electrode allows the defibrillation electrode to be accurately positioned by the patient's surgeon and maintained in intimate contact with the septum wall of the patient's heart, thereby reducing defibrillation thresholds; it provides a sense signal from the region of the His bundle or AV node, which can be used with other electrodes to distinguish between various arrhythmias; and it provides more physiologic pacing leading to greater cardiac output. | 0 |
STATEMENT OF GOVERNMENT INTEREST
The invention described herein may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor.
BACKGROUND OF THE INVENTION
The present invention generally relates to a gas mixture for use in an aerostat. More particularly the gas mixture utilizes two substances one of which condenses at an altitude to reduce the weight of the air displaced causing the aerostat to float at a constant altitude.
Present aerostat technology dictates the use of bottled helium and a strong envelope so that the balloon would have constant volume and would support considerable super pressure at the hovering altitude.
SUMMARY OF THE INVENTION
It is therefore a general object of the invention to disclose an improved mixture of gases for use in an aerostat. It is an additional object that an aerostat containing the mixture of gases be particularly suitable for underwater launch from a submarine.
This is accomplished in accordance with the present invention by providing a mixture of gases in which both the gases, n-hexane and ammonia are suitable to be launched underwater in the liquid state and to assume the gaseous state upon surfacing in the water. This would enable an unmanned aerostat to carry many kinds of instrumentation.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph of altitude vs. mole fraction of n-hexane in ammonia to lift 1 kilogram; and
FIG. 2 is a pressure-temperature graph comparing saturated n-hexane and ammonia to standard atmospheric conditions over a range of altitudes.
DESCRIPTION OF THE PREFERRED EMBODIMENT
An aerostat may be filled with a mixture of two components, one of which condenses at a predetermined altitude to reduce the weight of air displaced and thereby float at a constant altitude. It is required that the condensing component at its partial pressure in the mixture condense at the temperature corresponding to the desired altitude. Thus, for an aerostat to float at 5 km in the U.S. Standard Atmosphere (1962) the temperature is -17° C. and the pressure is 540 mbars, the condensing gas should be saturated.
In Table 1 below several hydrocarbons are shown. Both ammonia and helium are shown as lifting gases since neither reacts with the hydrocarbons. Ammonia and hydrocarbons are both reducing agents, and helium is inert. Since the aerostat may be submarine launched, ammonia is preferred. Ammonia becomes liquid at shallow ocean depths of about 55 meters, making for convenient packaging. The important results tabulated in Table 1 include the volume of the gas mixture, V in cubic meters; the takeoff load, L 0 in kilograms; the buoyancy margin, B; the average molecular weight of the binary gas, M x ; and the lifting load with the substance condensed, L 1 in kilograms. Of the candidates listed n-hexane combined with ammonia appears to be the best. It has adequate buoyancy margin in a reasonable size.
The data for helium instead of ammonia as the lifting gas shows cyclopentane to be the best substance. This mixture will not condense at any ocean depth and is not particularly suitable for submarine launch. It is, however, a very safe mixture.
Table 2 below shows the altitude, temperature, pressure and density of the U.S. Standard Atmosphere (1962). For each temperature is computed the saturation pressure of n-hexane. Each saturation pressure has been divided by the corresponding atmospheric pressure to yield the mole fraction of n-hexane which would result in saturation at that temperature and pressure. Also computed and tabulated are the molecular weight of the mixture, M x ; and the volume of mixture required to lift one kilogram at sea level, V. The essential results are plotted in FIG. 1. Stable altitudes between 1.5 and 6 km can be obtained by varying the proportions of n-hexane and ammonia.
TABLE 1__________________________________________________________________________ Partial pressure at -17° C. when Mole M.sub.s saturated Fraction Lifting Avg. V L.sub.1 L.sub.0Substance Formula Mole wt psia/molar of substance Gas M.W. m.sup.3 kg kg B__________________________________________________________________________n-hexane C.sub.6 H.sub.14 86.17 .32/22.1 .0409 Ammonia 19.858 2.595 .870 .935 .070 Helium 7.36 1.09 .941 .971 .0302,3 dimethyl C.sub.6 H.sub.14 86.17 .6/41.4 .0767 Ammonia 22.333 3.563 .665 .833 .201butane Helium 10.30 1.27 .883 .942 .062cyclopentane C.sub.5 H.sub.10 70.13 .82/56.5 .1046 Ammonia 22.584 3.703 .525 .763 .237 Helium 10.917 1.31 .832 .916 .084n-pentane C.sub.5 H.sub.12 72.15 1.5/103.4 .1915 Ammonia 27.585 17.081 -3.007 -1.003 Helium 17.05 1.98 .534 .767 .304__________________________________________________________________________
TABLE 2__________________________________________________________________________U.S. STANDARD ATMOSPHERE Saturated Psat C.sub.6 H.sub.14 C.sub.6 H.sub.14 andAlt. Temp. Press. Density n-hexane Mole NH.sub.3 vkm ° K. ° C. mbar kg/m.sup.3 mbar Fraction M.sub.x m.sup.3__________________________________________________________________________0 288.1 15 1013. 1.225 141.1 .139 26.66 10.231 281.6 8.5 899. 1.112 100.6 .112 24.77 5.6252 275.1 2.0 795. 1.007 70.5 .089 23.16 4.073 268.7 -4.5 701. 9.092 48.6 .069 21.83 3.314 262.2 -11.0 617. 8.194 32.9 .053 20.72 2.875 255.7 -17.5 540. 7.364 21.87 .040 19.83 2.596 249.2 -24.0 472. 6.601 14.22 .030 19.11 2.407 242.7 -30.5 411. 5.900 9.03 .022 18.55 2.278 236.2 -36.9 357. 5.258 5.60 0.0157 18.12 2.18__________________________________________________________________________
The following calculations are for determining the essential characteristics of binary gases in a constant altitude aerostat:
M W.sub.avg =M.sub.x =M.sub.L (1-x)+M.sub.s x
where
M w avg =M x =average molecular weight of combined lifting gas and substance
M l =molecular weight of lifting gas
M s =molecular weight of substance
x=mole fraction of substance when combined with lifting gas.
To lift load L with both the lifting gas and the substance vaporized ##EQU1## where d A =density of the atmosphere
M a =molecular weight of atmosphere
With the substance condensed to a negligible volume and the lifting gas as gaseous form, we can lift a lesser load, L, ##EQU2##
So that the buoyancy margin is the fraction ##EQU3## depending on the state of the condensing substance P mbar =68.95 P sia
x=(P mbar /540)
M l =m.w.
for H e , M.W.=4.00
For NH 3 , M.W.=17.03
Line of sight range to horizon from altitude H(km)=113 √H
For zero buoyance in water using the n-hexane-ammonia composition, the following relationship must hold: ##EQU4## When the expression is unity d L (max) is determined. d L (max)=4.36 gm/cm 3 (sp.gr.=4.25), payload density
Where
mole vol=22.414 m 3 /kg
d s =density liquid n-hexane=0.6603
d N =density liquid ammonia=0.817
Envelope capacity should be ##EQU5## to avoid burst at 5 km altitude. Solar heating will raise the internal temperature and raise the altitude of the aerostat.
Properties
C 6 h 14 b.p.=68.95° c.
______________________________________temp range, t A B______________________________________-50 to -10° C. 35167 8.399-10 to +90° C. 31679 7.724______________________________________
where ##EQU6## and P mbar =1.3332 P mm Hg P is the saturation pressure at temperature T=t+273
A and B are constants in the Antoine equation
So that
______________________________________ ##STR1## Total pressure whent °C. P.sub.mbar mole fraction = .0408______________________________________-50 1.94 47.5-40 4.37 107.-30 9.23 226.-20 18.36 449.6-17.2 22.05 540.-10 34.67 849.090 61.39 1502.+10 100.52 2463.______________________________________
This data is plotted in FIG. 2.
For NH 3 B.P.=-33.35° C.
P sat vs t° C. is given below
______________________________________t° C. P.sub.mm Hg P.sub.mbar______________________________________-77 47.8 63.7-62 143.8 191.7-50 307. 409.3-41 510.3 680.3-35 699.1 932.0-20 1427. 1902. (= 8.8 meters)+10 4612. 6149. (= 50.7 m)______________________________________
This data is plotted in FIG. 2.
Proportions of mixture
For mole fraction, x, hexane=0.0408
and mole fraction (1=x) ammonia=0.9592
vol liquid 0.0408 moles hexane
V h =x M hex /d hex
V h =m hex /d hex =5.32 ml
vol gas ammonia
22.4 liters×0.9592=21.49 liters
which will lift ##EQU7##
Therefore, add 0.64 ml of hexane for each gram lift from pure ammonia. Adding more will reduce the hovering altitude as shown in FIG. 1
The described mixture is suitable for use in a aerostat enabling the aerostat to raise a communication buoy from a submarine, transport meteorological instruments and radar false targets.
It will be understood that various changes in details, materials, steps and arrangement of parts, which have been herein described and illustrated in order to explain the nature of the invention, may be made by those skilled in the art within the principle and scope of the invention as expressed in the appended claims. | A balloon filled with a gas mixture of ammonia and n-hexane will stay at aonstant altitude due to condensation at altitude of the n-hexane. Since both components are liquid below about 50 meters in the ocean and together with the load are buoyant, the aerostat may be submarine launched and rise to the surface at which point the ammonia and n-hexane evaporate and take the balloon and load to its preset altitude. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is in the field of construction tool implements. More particularly, the present invention is a tool which is designed to assist a worker in hammering nails into a desired surface area; namely in holding a multiplicity of nails in areas where it is difficult for the worker to effectively hold the nails by hand during the process of hammering the nail into the desired surface such as wood, in acting as a shield so that the hammer will hit the tool instead of the surface such as wood if the worker misses the nail on his strike, and in acting as a finishing nail setter to tap a fine finishing nail slightly below the surface of fine wood.
2. Description of the Prior Art
The prior art contains several patents which disclose tools that are designed to hold a nail or a fastener for hammering into a wooden surface and also are designed to act as a shield to prevent the blow of the hammer accidentally striking the wooden surface if the nail should be missed on a strike. However, all of these prior art designs have several disadvantages and none of them disclose the novel design, application and combination of the present invention.
U.S. Pat. No. 3,682,213 issued to Litz discloses a Nail Placing Implement whose principal function is to assist in the placement of a plurality of nails at desired spaced intervals. The nail holding section is of a sandwich type construction which provides a straight edge that contains a plurality of equally spaced openings for purposes of holding a nail. The design of the tool is of an awkward elongated construction which would make it difficult to use in small, hard to reach areas. The holes through which the nails are placed are of a U-shaped design, from which a nail could easily fall out if the tool was being used to hammer nails into a ceiling or at a substantially elevated area. Since the nails are retained along one lengthwise edge, the tool's use as a shield is at best marginal.
U.S. Pat. No. 4,079,764 issued to Hayes also discloses a Decorative Nail Spacing Tool. Once again, the primary object of this tool is to provide even spacing for hammering in a multiplicity of nails at the same time. The planar surface wherein the nails are held is very small and therefore the effectiveness of the tool as a nail shield is at best marginal. The openings where each nail is held are wide V-shaped grooves. This tool is therefore really only effective for holding the nail while hammering downward on a horizontal surface. The tool could not effectively hold the nails for hammering on a vertical or ceiling surface.
U.S. Pat. No. 3,060,442 issued to Tomek discloses a Nail Holder Tool which is designed to specifically hold a single nail. The tool is very narrow and is totally ineffective for use as a shield. The tool is also capable of holding only one nail at a time.
U.S. Pat. No. 2,716,750 issued to Biblis is applicable for holding a fastener but would be ineffective for holding a nail since the tool is composed of a multiplicity of circular openings which are adequate for generally holding a fastener but are too large and rigid for holding a nail. The tool could not be used to grip a nail when hammering in either a vertical direction or upward against a ceiling.
U.S. Pat. No. 874,613 issued to McColm for a Nail Holder and Set discloses a tool which can carry a multiplicity of nails but again is only effective for hammering downward on a horizontal surface. The tool does not effectively grip the nail for hammering on a vertical surface or on a ceiling surface. The tool is also awkwardly designed and could not be easily fit into inaccessible areas.
Overall, the prior art patents do not disclose a tool which could be effectively used in inaccessible areas while at the same time providing a nail holder that can hold a multiplicity of nails for hammering in a vertical direction against a ceiling or for hammering against a vertical surface and at the same time acting as an effective shield to protect the surface being hammered on. Additionally, none of these patents disclose a tool which can also be used as a finishing nail set to hammer a fine finishing nail slightly below the surface of wood.
SUMMARY OF THE PRESENT INVENTION
The present invention relates to a tool which can be used to securely hold a multiplicity of nails for hammering into a vertical wall or against a ceiling in addition to hammering nails downward against a horizontal surface. The same tool can also be effectively used as a shield to protect the surface being hammered against a blow from the hammer if the worker should miss the nail. Additionally, the same tool can be used as a finishing nail set and is useful in this application for both left-handed and right-handed people.
It has been discovered, according to the present invention, that if a nail holder is made of flexible material which contains a multiplicity of narrow V-grooves along its outer edge, the grooves can effectively hold a nail for hammering purposes in any direction, including a straight vertically upward direction.
It has been further discovered, according to the present invention, that if the narrow grooves extend into an opening well within the inner area of the tool, the tool can be effectively used as a shield to protect the surface while the nail is being hammered into it after the nail has been started into the surface by being held within the narrow V-groove portion of the tool.
It has additionally been discovered, according to the present invention, that if the tool is designed to accommodate a pair of headed metal shafts which each taper to a point at one end, these shafts can be used as a finishing nail set to hammer a fine finishing nail into a wooden surface.
It has also been discovered, according to the present invention, that if the surface which holds the nails is of U-shaped design which then extends into a handle portion that is substantially elevated above the plane of the nail holding portion, the tool can be easily fit into inaccessible areas.
It is therefore an object of the present invention to provide a tool for holding a multiplicity of nails such that the nails can be effectively held regardless of which direction they are being hammered.
It is another object of the present invention to provide a tool which can also be used as an effective nail shield in addition to holding the nail.
It is a further object of the present invention to provide a tool which can also be used as a finishing nail set to hammer in fine finishing nails.
It is an additional object of the present invention to provide a tool which can easily be fit into inaccessible areas while being used to start a nail into the area, then act as a shield to protect the area while the nail is being hammered in, and also occassionally used as a nail set to hammer in finishing nails below the surface.
Further novel features and other objects of the present invention will become apparent from the following detailed description, discussion and the appended claims, taken in conjunction with the drawings.
DRAWING SUMMARY
Referring particularly to the drawings for the purpose of illustration only and not limitation there is illustrated:
FIG. 1 is a perspective view of the present invention looking from the right.
FIG. 2 is a perspective view of the present invention upside down looking from the right, with an optional reinforcing member shown in phantom.
FIG. 3 is a cross-sectional view taken along line 3--3 of FIG. 1.
FIG. 4 is a cross-sectional view taken along line 4--4 of FIG. 1.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference to the drawings of the invention in detail and more particularly to FIG. 1, there is shown at 10 the preferred embodiment of the Combination Nail Holder, Nail Shield and Nail Finishing Set, hereinafter called the present invention or the tool, interchangeably.
The body of the present invention is made of one piece construction but has three distinct sections; a substantially horizontally disposed planar gripping body member 20, a thick mid-body member 40 located at the rear section of said gripping body 20, and a handle section 60 extending from the rear of the thick mid-body member 40.
In the preferred embodiment, the gripping body 20 is in a substantially U-shaped configuration, as shown in FIGS. 1 and 2, with the curved portion of the U forming the forward edge of the tool 10. Alternatively, the configuration of the gripping body member 10 could be rectangular. The gripping body 20 has a substantially flat lower surface 22 which is placed over the surface of an object into which a nail will be hammered.
The outer edge 26 of the gripping body 20 contains a multiplicity of nail receiving and gripping grooves 28. Each nail receiving and gripping groove 28 is a very narrow V-shaped wedge which extends inward from the edge of the gripping body 20 and also extends through the entire thickness of the gripping body 20. The present invention 10 is made of flexible material such as rubber which therefore permits the very narrow V-shaped groove 28 to receive a significant variety of nails of varying thicknesses and lengths. In the preferred embodiment as shown in FIGS. 1 and 2, there is one larger receiving and gripping groove 28 which extends from the front of the tool inwards and two smaller nail receiving and gripping grooves 28 on either side of the gripping body 20. It is within the spirit and scope of the present invention to have any number of such nail receiving and gripping grooves 28 extending inwardly from various portions of the outer edge of the gripping body 20.
The apex or innermost portion of the nail receiving groove 28 terminates in and extends into an opening 30 which is of generally circular configuration and also extends through the entire thickness of the gripping body 20. In this design, a nail can be held in the nail receiving and gripping groove 28, the lower surface 22 of the gripping body 20 is placed against the surface into which the nail will be hammered, and then the nail is started into the wood or other surface by hammering on it while it is being held in the receiving and gripping groove 28. After it has started into the surface, the nail is slid along the length of the groove 28 until it enters the opening 30. The upper surface 24 of the gripping body 20 contains a recessed area 32 around the opening 30. This serves to provide a target for the worker who can then aim at the nail head and use the recessed area 32 as a guide for accuracy as well as a shield to protect the wood or other surface if the worker should miss the nail on his strike with the hammer. In the preferred embodiment 10 shown in FIGS. 1 and 2, there is only one large opening 30 which extends from the main groove 28 at the front of the tool 10 and the grooves 28 on the sides are merely there to hold additional nails. It is within the spirit and scope of the present invention to have a multiplicity of such large grooves and large openings so that several can be used to act as hammering guides and shields while the nail is hammered into the surface.
The rear portion of the gripping body 20 extends into a thicker upwardly extending mid-body portion 40. The mid-body member 40 extends transversely from the upper surface 24 of the gripping body 20, as more clearly shown in FIG. 2. The portion of the gripping body 20 beneath the mid-body portion 40 is recessed inwards on each side to form right and left cavities 34 and 36 respectively. As shown in greater detail in FIG. 3, the mid-body portion 40 contains two longitudinal substantially cylindrical cavities which extend through the entire height of the mid-body portion 40. Each cylindrical cavity, 42 and 44 respectively, accommodates a headed, sustantially cylindrical tapering shaft 46 and 52 respectively. Cylindrical shaft 46 contains a head portion 47, an elongated tapering body portion 48 and a tip 49. Cylindrical shaft 52 contais a head portion 53, and elongated tapering body portion 54 and a tip 55. Each head, 47 and 53 respectively, rests on the upper surface 56 of the mid-body portion 40. Each shaft portion, 48 and 54 respectively, extends through a respective cavity, 42 and 44. Each tip portion 49 and 55 respectively, protrudes through the bottom of the mid-body portion 40 and into cavities 34 and 36 respectively.
These headed substantially cylindrical tapering shafts 46 and 52 respectively are finishing nail sets which are used to hammer a fine finishing nail slightly below the surface of fine wood. A finishing nail is started in the receiving and gripping groove 28, is hammered into the wood by being slid into the opening 30 and hammered most of the way in, and then the tool 10 is removed and the tip 49 or 55 of shaft 46 or 52 is placed over the nail and the hammer is used to tap the head portion, 47 or 53 to gently tap the finishing nail slightly below the surface of the wood. The purpose of two such shafts is to accommodate a left-handed or a right-handed user or to accommodate a particular application if only one of the areas of the tool 10 is accessible to such hammering. Each shaft 46 and 52 is made of metal such as steel.
The third section of the tool 10 is the handle 60 which extends substantially perpendicular to the rear surface 50 of the mid-body portion 40. For ease of gripping, the handle 60 is substantially cylindrical and has a slightly textured surface 62. Other shapes for the handle 60 are also within the spirit and scope of the present invention. Since the entire tool 10 is formed out of flexible material such as rubber, it is preferable to have a reinforcing member in the handle 60 to stiffen it and make the tool 10 easier to grip. A reinforcing member 64 such as a wooden dowel or metal rod is therefore cast into the handle section 60, as shown in FIG. 4.
In some applications, it may be desirable to also stiffen the gripping body 20 as well as the rest of the tool 10. In such an alternative embodiment, a reinforcing member 56 can be cast into the tool 10 as shown in phantom in FIG. 2, such that the reinforcing member 56 extends within the body of the tool 10 and adjacent the outer edge of each section, and goes around and does not interfere with any groove 28 or hole 30 or cylindrical opening 46 or 52.
The present invention 10 therefore provides a very useful combination nail holder, nail shield and nail finishing set, all in one compact design. Since the tool 10 is made of flexible material such as rubber, it can very easily be fit into difficult to reach areas. The design of the very narrow V-grooves 28 into flexible and resilient material such as rubber permits the worker to use the tool 10 to hold any multiplicity of sizes of nails in any desired direction whatsoever, including holding nails for hammering against a vertical wall or hammering straight upward against a ceiling. The compact design of having left and right nail sets permits the worker to use the tool to also hold and start fine finishing nails, hammer them well into the fine wood, and then tap them in with the finishing set. The left and right nail sets makes the tool useful for either left-handed or right-handed workers. The multiplicty of receiving and gripping grooves 28 enable a worker to grip several nails at the same time so the worker can hammer in one after the other. This is especially useful when the worker is working in an area where accessibility is difficult.
The tool 10 can be of any variety of sizes, and is not confined to one set of dimensions. In one example, a common construction wood is a 2×4, which is in fact 15/8 inches high and 31/2 inches wide. The present invention can be designed such that the gripping body 20 is 15/8 inches wide and 31/2 inches long from front to back. This allows it to fit perfectly either over the height or the width of a 2×4 to thereby completely shield the wood while the worker is hammering the nail in. By using a tool 10 of these dimensions, the tool 10 can also be used as a measuring device to indicate how many 2×4s will fit in a given area. The lengths of 31/2 inches can be used to measure the number of widths of 2×4s which can be accommodated in a given area. The widths of 15/8 inches can be used to measure the number of heights of 2×4s which can be accommodated in a given area. To complete the sample specification, the height of the mid-body member 40 can be 11/2 inches and the handle 60 can be 1 inch in diameter and 4 inches long. With these dimensions, the tool 10 can easily be fit into the tool pouch or nail bag or a construction worker.
The tool 10 can be molded out of rubber or other comparable flexible and resilient material. The tool can further have the stiffening members previously described cast into the rubber, either in just the handle member or throughout the tool as previously described.
Of course, the present invention is not intended to be restricted to any particular form or arrangement, or any specific embodiment disclosed herein, or any specific use, since the same may be modified in various particulars or relations without departing from the spirit or scope of the claimed invention hereinabove shown and described of which the apparatus shown is intended only for illustration and for disclosure of an operative embodiment, not to show all of the various forms of modification in which the invention might be embodied.
The invention has been described in considerable detail in order to comply with the patent laws by providing a full public disclosure of at least one of its forms. However, such detailed description is not intended in any way to limit the broad features or principles of the invention, or the scope of the patent monopoly to be granted. | The present invention relates to a tool which can be used to securely hold a multiplicity of nails for hammering into a vertical wall or against a ceiling in addition to hammering nails downward against a horizontal surface. The same tool can also be effectively used as a shield to protect the surface being hammered against a blow from the hammer if the worker should miss the nail. Additionally, the same tool can be used as a finishing nail set and is useful in this application for both left-handed and right-handed people. | 1 |
RELATED INFORMATION
[0001] This application is a continuation of U.S. application Ser. No. 12/035,247 filed on Feb. 21, 2008 which is a continuation of U.S. application Ser. No. 10/786,699 filed on Feb. 24, 2004, which is a continuation of U.S. application Ser. No. 09/869,923 filed on Oct. 15, 2001. The priority of the prior application is expressly claimed, and the disclosure of this application is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to heart assist devices, systems and methods.
BACKGROUND OF THE INVENTION
[0003] Currently the only real options for improvement of end-stage heart failure are medical therapy, left ventricular assist devices (LVADs) and transplantation. ACE (Angiotensin Converting Enzyme) inhibitors unload the heart and prolong survival. LVADs pump blood and significantly improve life style and survival, but are complicated to implant, maintain and remove, with relatively high complications relating to bleeding, infection, thromboembolism, and device malfunction.
[0004] The transplant rate has stabilised at approximately 2,300 per year in the USA, being limited by organ availability. Transplantation achieves a 75% five year survival rate and a 65% ten year survival rate with significant improvements in functional class.
[0005] The number of people awaiting heart transplantation is steadily increasing and they are a sicker group, with increasing numbers requiring hospitalisation, intravenous ionotropes, short-term percutaneous trans-femoral intra-aortic balloon pumping and/or LVAD implantation.
[0006] The Institute of Medicine has estimated that by the year 2010, up to 70,000 patients will be candidates for permanent mechanical circulatory support systems.
[0007] Over the last ten years, LVADs have been well proven to save lives, acting as bridges to transplantation for critically ill patients. Recently, LVADs have been considered as alternatives to transplantation, and very recently, have been explanted in a few patients who have shown recovery. This latest realisation is starting to gather a lot of interest as researchers focus on recovery of the failing heart. LVADs totally unload the left ventricle and many believe that the heart will then recover. Moreover there is evidence beyond the few patients in whom devices have been removed that there is reversal in markers of heart failure. On the other hand, others have described an increase in myocardial fibrosis which raises a question of whether the heart is being unloaded too much.
[0008] The intra-aortic balloon pump (IABP) was first proposed ill the 1960s as a method of partial support for the acutely failing heart, for example, after heart surgery or heart attack. It was built as a long thin catheter [10-14 Fr] with an elongated balloon at its tip [volume 30-40 ml]. The balloon was inserted via the femoral artery and inflated and deflated in counter-pulsation with the heart beat. Inflation in diastole causes a diastolic pressure augmentation and increases coronary artery blood flow and deflating in systole (triggered by the R wave of the ECG) reduces the afterload, or the pressure head against which the left ventricle has to eject blood. Early investigators determined that the best and most efficient balloon position was closest to the heart, i.e., in the ascending aorta. However, in recent times, the balloon is positioned via the femoral artery in the descending aorta for short term (1-10 days) use. There is substantial proof beyond doubt that counterpulsation works very well in the short-term to assist hearts to recover when drugs (ionotropes etc.) are insufficient or inappropriate to support the cardiovascular system.
[0009] Intra-aortic balloon heart pumps operating in counterpulsation assist the heart function. When inflated, the balloon propels blood peripherally from within the aorta to improve blood circulation in the patient. Moreover, more blood is forced into the coronary arteries to help nourish and strengthen the heart muscle. However, the balloon comes into direct contact with the blood flowing into the aorta, which can cause damage to the blood cells and there is a risk of thromboembolism. In addition, current intra-aortic balloon pump systems are inflated by means of a tube passing through the body, the tube connecting the balloon to an external compressor. The opening for the tube to enter the body provides a possible site of infection or other injury. The tube is typically inserted into a groin vessel, the femoral artery, and there is a high risk of associated leg complications. Further, the patient is bedridden and cannot mobilize. Additionally, the use of a gas to inflate the balloon is not an entirely safe operation since any leakage of gas from the balloon into the blood stream could cause an air embolus.
[0010] Aortic compression (periaortic diastolic compression) has been described as a means to increase coronary blood flow. For example, U.S. Pat. No. 4,583,523 describes an implantable heart assist device including an elongated assembly extending transversely between the ribs of a patient from the rib cage to the aorta of the heart to be assisted. The assembly includes an aorta compressing device at the front end and a mounting device at the rear end thereof to support the device from the ribs of the patient. A motive device actuates and deactivates the compressing device alternatively to help pump blood through the aorta in a counterpulsation mode of operation. Although this device has advantages for many applications, it does require relatively complicated surgery to implant/explant the device, particularly in regard to the need to mount the device including its motive means, to the ribs of the patient. Moreover the mounting arrangement and motive means of the device have to be positioned outside the rib cage, making the presence of the device more noticeable to the patient. There is also substantial risk of infection With the device coming through the skin. Furthermore, because the device is attached/mounted to the ribs, there may be shear stresses on the aorta as the rib cage moves with inspiration/expiration. These stresses may cause untoward damage of the aorta.
[0011] U.S. Pat. No. 4,979,936 discloses an autologous biologic pump in the form of an apparatus using skeletal muscle formed into a pouch which then surrounds a collapsible, shape-retaining bladder. The bladder is connected to a second bladder enclosed in a sheath around a portion of the aorta. The bladders are filled with a fluid such that when the skeletal muscle contracts in response to an electrical stimulation, the fluid is forced from the first bladder into the second bladder sheathed around the aorta, expanding that second bladder and forcing the aorta to compress. Although this approach may be useful in some circumstances, it is doubtful that it is suitable for long term in that the muscle function would probably degrade over time. Furthermore, the muscle has to be “trained” for many weeks before the device can be relied on to assist blood circulation.
[0012] WO 99/04833 discloses a cardiac ventricle aid device which is implanted in the abdominal cavity with an aorta sleeve tube placed on, or inserted in, the descending aorta. A disadvantage of the disclosed device is it has a separate actuator and compliance chamber and its implantation is thus complicated. Another disadvantage is it is difficult to securely mount the device components to a structure in the abdominal cavity that is capable of supporting its weight. A further disadvantage is a number of vertebral arteries stem from the descending aorta which can be damaged during the implantation of the device.
[0013] It would be desirable to have a heart assist device that could be quickly and totally implanted in a relatively easy manner and with minimum trauma to the patient and to allow ambulation with low risk of complications. Also desirable would be a heart assist device that allows partial unloading of the heart longterm, augmenting the cardiac output of the native heart, and possibly allowing substantial recovery of the heart so that the device could be weaned. Moreover, it would be desirable for such a device to have no blood contacting surfaces, and not require cardiopulmonary bypass to implant the device. In a small proportion of patients however there will exist aortic disease making a periaortic device unsuitable. In these patients it would be desirable to be able to apply the same aortic counterpulsation, but with a device that replaces the ascending aorta. Such a device would require cardiopulmonary bypass and would be blood contacting, but has the same advantages of allowing partial unloading of the heart longterm, augmenting the cardiac output of the native heart, and possibly allowing substantial recovery of the heart so that the device could be weaned.
[0014] It is an object of the present invention to satisfy one or more of the above desirable criteria.
SUMMARY OF THE INVENTION
[0015] In a first aspect, the present invention provides a heart assist device adapted for implantation into a patient, the device including
[0016] a) an aortic compression means adapted, when actuated, to compress an aorta of a patient;
[0017] b) a fluid reservoir; and
[0018] c) a pump means adapted to pump a fluid from the fluid reservoir to the aortic compression means so as to actuate the aortic compression means at least partly in counterpulsation with the patient's heart,
[0019] wherein the fluid reservoir is adapted to be wholly positioned within the chest is cavity of the patient.
[0020] In a second aspect, the present invention provides a heart assist device adapted for implantation into a patient the device including:
[0021] a) an aortic compression means adapted, when actuated, to compress the ascending aorta of a patient;
[0022] b) a liquid reservoir;
[0023] c) a pump means adapted to pump a liquid from the liquid reservoir to the aortic compression means so as to actuate the compression means, wherein the liquid reservoir and the aortic compression means are adapted to be positioned in close juxtaposition with one another within the chest cavity of the patient.
[0024] In a third aspect, the present invention provides an aortic compression means for use in a heart assist device, the aortic compression means including:
[0025] a) an elastic inflatable cuff adapted to be placed about the ascending aorta of a patient; and
[0026] b) a flexible, substantially inelastic, sheath adapted to extend around the cuff and at least assist in retaining it in position on the aorta.
[0027] In a fourth aspect the present invention provides a heart assist device including:
[0028] a) an aortic compression means adapted to be placed around the ascending aorta of a patient; and
[0029] b) an actuation means to periodically actuate the aortic compression means in at least partial counterpulsation with the heart,
[0030] wherein the aortic compression means and the actuation means are placed wholly within the chest activity of the patient.
[0031] In a fifth aspect, the present invention provides a heart assist device adapted for implantation wholly into a bodily cavity of a patient the device including:
[0032] a) an aortic compression means adapted, when actuated, to compress an aorta of a patient;
[0033] b) a housing with an exterior surface;
[0034] c) a fluid reservoir in the housing, the fluid reservoir having a flexible exterior surface forming part of the housing exterior surface; and
[0035] d) a pump means adapted to pump a fluid from the fluid reservoir to the aortic compression means so as to actuate the aortic compression means at least partly in counterpulsation with the patient's heart,
[0036] wherein the fluid reservoir flexible exterior surface is adapted to expand during aortic compression and constrict in the absence of aortic compression and is further adapted to be positioned substantially adjacent a flexible organ in the patient's bodily cavity.
[0037] Preferably, the bodily cavity is the thoracic cavity and the organ is the lung.
[0038] In a sixth aspect the present invention provides a heart assist device adapted for implantation into a patient, the device including:
[0039] a) an elastic inflatable cuff adapted, when inflated, to compress an aorta of a patient;
[0040] b) a fluid reservoir;
[0041] c) a means for pumping a fluid from the fluid reservoir to the cuff so as to inflate the aortic compression means at least partly in counterpulsation with the patient's heart; and
[0042] d) a means for adjusting the volume of fluid in the cuff in the absence of aortic compression.
[0043] In a seventh aspect, the present invention provides a human or animal having a heart assist device according to any one of the preceding aspects of the invention implanted therein.
[0044] In a further aspect, the present invention provides an implantable system for assisting the functioning of the heart of a subject, the system including:
[0045] an implantable device for assisting the functioning of the heart of a subject, including:
[0046] means for externally engaging and compressing the aorta;
[0047] motive means responsive to control signal(s) for actuating and deactivating the compressing means cyclically to help blood pump through the aorta, wherein the compressing means and the motive means are fully implantable within the thoracic cavity of the subject and wherein the compressing means and/or motive means include means to adapted for attachment to the aorta and/or surrounding tissue within the thoracic cavity of the subject;
[0048] sensing means adapted for sensing the heart and generating sensing signals;
[0049] control means responsive to the sensing signals for generating the control signal(s); and
[0050] a power source for providing power to the motive means.
[0051] The device of the invention may operate in countersynchronisation to the heart (counterpulsation).
[0052] An advantage of the device and system of the present invention is that the risk of limb ischemia associated with conventional IAB systems is avoided because there is no blood contact with the device whatsoever. Patient ambulation is also possible. Additionally the implantation technique used for the device of the invention is less invasive than those required for other devices. In particular, compared to the arrangement taught in U.S. Pat. No. 4,583,523, the device of the present invention provides a better outcome in term of reduced risk of infection, cosmesis and ease of implant and explant. A further advantage of the device and system of the present invention is that there is little risk to die patient in the event of device failure. The device has the great advantage of being able to be weaned and turned off in the event of cardiac recovery. This is simply not possible with known LVADs. Furthermore if the heart shows signs of relapsing back into failure, the device can be switched back on.
[0053] The compressing means of the device of the present invention preferably includes a preshaped balloon cuff for wrapping around a portion of the aorta. Preferably, the balloon is configured longitudinally to fit the curve, that of a circular or oval arc, of the ascending aorta. In a particularly preferred form of the device of the present invention, the cross-section of the cuff is C-shaped, allowing wrapping of the cuff with some overlap around the aorta. Preferably, the cuff is shaped such that it does concentrically compress the length of enclosed aorta and spreads the compression forces evenly, reducing any wear or fatigue on any one part of the aorta. The balloon cuff is enclosed within a flexible and non-elastic outer sleeve. The sleeve has an elongated “tongue” on one arm of the C-shaped cuff and this is passed around the aorta to be secured by suturing or other means on the outer aspect of the other arm of the C-shaped cuff. This arrangement stops the balloon inflation force from going outwards. Furthermore, the preshaped cuff and flexible sleeve arc particularly designed to create a snug fit and low profile on the aorta, to reduce damage to the aorta and surrounding structures, and to create maximum efficiency of the device.
[0054] In a preferred form of the invention, the device is adapted for compression of the ascending aorta. An upper mid-line sternotomy provides easy surgical access to the ascending aorta and has the further advantage of not being very painful for the patient. A minimum incision is required in this procedure. In this mode of use of the device of the invention, the compressing means is preferably adapted to squeeze approximately 15-25 ml of blood from the ascending aorta in each compression cycle.
[0055] The cuff has a single inlet/outlet port for the fluid to move to inflate/deflate the balloon. The fluid used is preferably liquid, such as water or saline, as this is noncompressible and less likely to leak compared to gas. Furthermore, using a liquid allows a fully implantable device so that the patient can mobilize easily. The port and connecting tube to the motive means is of sufficient diameter and length to allow rapid emptying and filling of the cuff without generating too high compression pressures. The fluid must move within 0.15 sec for effective counterpulsation action. The compressive force emptying the cuff is the force exerted by the compressed aorta. This approximately 100 mmHg. A tube lumen of approximately 1 to 1.5 cm with a length of 3 to 8 cm allows 17 to 25 ml fluid to pass down a gradient of 100 mmHg in less than 0.15 sec. The compressive force filling the cuff is generated by the motive means, and this pressure gradient is approximately the same ie the motive means generates approximately 200 mmHg to allow the fluid to shift into the cuff in less than 0.15 sec.
[0056] The port more preferably has a trumpet-shaped or flanged opening into the cuff to spread the fluid more evenly into the balloon during inflation and to assist more rapid deflation. There may be a diffuser mounted within the lumen of the port to reduce the fluid force on the balloon cuff during inflation.
[0057] Preferably, the motive means drives the fluid via a fluid filled sac contained within the motive means. The motive means of the device of the invention may be any means that is capable of cyclically compressing and decompressing the fluid sac. The motive means may be a mechanical or an electromechanical device. The motive means may be an electric motor/cam arrangement. The motive means may include spring mounted arms driven by a pulse of power to hinged solenoids or the like to drive the pressure plates towards each other and thereby compress the aorta. An example of a suitable motive means is an adaptation of the solenoid actuator described in U.S. Pat. No. 4,457,673, the relevant disclosure of which is incorporated herein by reference. The motive means may also be based on that used in the Novacor N100 Left Ventricular Assist System.
[0058] The motive means is preferably enclosed in an air-tight housing. The housing may have a flexible portion that allows for the fluid shift from the motive means—the flexible portion is presented toward the lung tissue and can thus move back and forth. More particularly the motive means is fully implanted within the thoracic cavity and a pressure compliance membrane “interfaces” with the lung surface. Alternatively the housing may be rigid and when the motive means is activated and the fluid sac compressed, a small vacuum is created within the housing. This vacuum has the advantage of increasing the pressure gradient for subsequent emptying of the cuff, to make emptying more rapid. The level of vacuum could be adjusted by accessing a transcutaneous gas reservoir linked to the housing. A final alternative is to have a external gas line from the motive means to allow gas exhaust, eliminating the need for a compliance chamber, but introducing a percutaneous line that has an increased risk of infection.
[0059] The motive means may be designed so that in the event of failure, it automatically goes into “off” with the fluid sac filled so that the aorta is not compressed, thus minimising risk to the patient.
[0060] The motive means may include or be associated with means for detecting speed and completeness of cuff filling and emptying, and of monitoring the fluid pressure within the connector tube, means for measuring arterial blood pressure or flow. The motive means may also act to record the ECG, having electrodes positioned on the housing or as separate wires attached to body tissues.
[0061] The means adapted for attachment to the aorta and/or surrounding tissue of the subject may be any suitable means. For example, the attachment means may be adapted for suturing and/or gluing the compressing means or motive means to the aorta or the surrounding tissue within the chest cavity. The attachment means may be suturing tabs. The attachment means may be apertures allowing ingrowth of tissue and/or surface portions adapted to promote tissue growth into or onto the compressing means and/or the motive means so as to hold the device in position relative to the aorta. For example, the cuff may have a plurality of holes through which the cuff may be sutured to the aorta. The cuff may also have hole or slits to accommodate coronary artery bypass grafts to the ascending aorta. The motive means will sit within the chest cavity, preferably the right thoracic cavity, between the mediastinum and the right lung.
[0062] The sensor means may be means detecting a selected physiological event associated with heartbeat. The sensor means may be any means for producing an ECG. Means for detecting the action potentials of the cardiac muscles, for example electrodes, are well known to those skilled in the art and will not be described in detail here.
[0063] The control means may be any means capable of providing an output to actuate the motive means in response to signal(s) providing the sensor means.
[0064] The control means may provide signals to the motor means to countersynchronise compression of the aorta with the heart beat to provide counterpulsation, for example, aorta compression may commence with aortic valve closure (ventricular diastole), whilst aorta release occurs just prior to contraction/ejection (ventricular systole).
[0065] The power means may be an internal and/or external battery, or TET (transcutaneous electronic transfer).
[0066] De-activation of the compressing means may be timed to the R wave of the ECG and may be adapted for adjustment either manually or automatically. The dicrotic notch on the arterial pressure wave may provide the signal for actuation of the compressing means.
[0067] In yet a further aspect, the present invention provides a method for improving blood circulation in a subject, the method including implanting a device in accordance with the invention fully within the thoracic cavity of a subject, actuating the compressing means periodically in synchrony with the diastole period to compress the aorta; and alternating the period of actuation with periods of deactivation of the compressing means thereby allowing the aorta to return to its uncompressed shape.
[0068] The system and device of the invention allow relief/recovery from chronic heart failure whilst allowing the subject to move around freely without being constrained by a large external pumping device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0069] Preferred embodiments of the invention will now be described, by way of examples only, with reference to the accompanying drawings in which:
[0070] FIG. 1 a is a schematic drawing of a first embodiment of a heart assist device according to the invention implanted in the thoracic cavity of a subject;
[0071] FIG. 1 b is an enlarged view of the device shown in FIG. 1 a;
[0072] FIG. 2 a is an enlarged perspective detailed view of the device shown in FIG. 1 a;
[0073] FIG. 2 b is a partial top view of the device shown in FIG. 1 a;
[0074] FIG. 3 is top view of a second embodiment of a heart assist device according to the invention;
[0075] FIG. 4 is a top view of a third embodiment of a heart assist device according to the invention;
[0076] FIG. 5 a is a top view of a fourth embodiment of a heart assist device according to the invention;
[0077] FIG. 5 b is a perspective view of the device shown in FIG. 5 a;
[0078] FIG. 6 is a block diagram of an embodiment of a cardiac assist system according to the invention;
[0079] FIG. 7 is a side view of an embodiment of an inflatable cuff;
[0080] FIG. 8 is a rear view of the cuff shown in FIG. 7 ;
[0081] FIG. 9 a is a top view of the cuff shown in FIG. 7 ;
[0082] FIG. 9 b is a top view of the cuff shown in FIG. 7 after application of an external sheath;
[0083] FIG. 10 is a front view of the cuff shown in FIG. 7 ;
[0084] FIG. 11 is a fifth embodiment of a heart assist device according to the invention;
[0085] FIG. 12 is a schematic side view of a sixth embodiment of a heart assist device according to the invention;
[0086] FIG. 13 is a schematic side view of an seventh embodiment of a heart assist device according to the invention;
[0087] FIG. 14 is an indication of an electrical cardiograph (ECG) readout, heart diastolic pressure (Pr.) and power supply (Po) for the device shown in FIG. 13 ;
[0088] FIG. 15 is a schematic side view of an eighth embodiment of a heart assist device according to the invention;
[0089] FIG. 16 is an exploded view of the pump housing of the device shown in FIG. 15 ;
[0090] FIG. 17 is a schematic cross sectional view of a ninth embodiment of a heart assist device according to the invention; and
[0091] FIG. 18 is a schematic view of a tenth embodiment of a heart assist device according to the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0092] FIG. 1 a to 2 b are schematic drawings showings a first embodiment of a heart assist device 10 in accordance with the invention. The device 10 is suitable for complete implantation in the thoracic cavity of a subject 99 adjacent the ascending portion of the aorta 15 , as shown. The device 10 includes an aortic compression means in the form of a hinged solenoid 2 (see FIGS. 2 a and 2 b ) in a housing 12 . The solenoid 2 is driven by pulses of electrical power from a controller/battery 14 to actuate wedge-shaped compression plates 4 via arms 3 . The wedge-shaped plates 4 surround the ascending portion of the aorta 15 . When the plates 4 are actuated they approach each other and that part of the aorta 15 between the plates 4 is compressed. The plates 4 have a plurality of holes 6 that provide means for suturing the plates to the aorta 15 and permitting ingrowth of tissue therethrough.
[0093] FIGS. 2 a and 2 b are detailed schematic drawings of the solenoid 2 which show that it includes two arcuate plates 26 hinged at 8 . The plates 26 are shown in the de-activated (resting) position in FIG. 2 a and are shown in the actuated position in FIG. 2 b compressing the aorta 15 . The plates 26 are soft form moulded and are actuated by the hinged solenoid 4 via arms 23 .
[0094] FIGS. 3 to 5 b are schematic drawings of second to fourth embodiments of heart assist devices in accordance with the present invention.
[0095] In the second embodiment shown in FIG. 3 , the compression plates 34 are actuated via arms 33 , with each of the arms 33 being acted on by a respective rod solenoid 38 acting through springs 37 between the rod solenoid 38 and the respective arm 33 .
[0096] In the third embodiment shown in FIG. 4 , solenoids 48 act on deformable nitinol plates 44 connected together at either end 47 to encircle the aorta 15 .
[0097] In the fourth embodiment shown in FIGS. 5 a and 5 b , wedge-shaped plates 54 are connected together at one end 57 and each plate is actuated by solenoids 58 acting through arms 53 . As best shown in FIG. 5 b , the wedge-shaped plates 54 effectively conform to the shape of the ascending aorta 15 .
[0098] FIG. 6 is a block diagram of an embodiment of a cardiac assist system constructed in accordance with the invention suitable for use with, for example, the cardiac assist device 10 .
[0099] Initiation of the compression of the aorta 15 by the compression plates 4 is accomplished by energisation of the solenoid 2 . This energisation is under the control of a control means 100 which activates the solenoid 2 of the motive means 1 in response to signals received from an ECG monitor 102 or systemic arterial blood pressure 103 or the like. The ECG monitor 102 and/or the control means 1 are preferably implanted but may be on the body of the subject 99 .
[0100] In operation, de-activation of the compression plates 4 draws them apart and effectively unloads the left ventricle by allowing the aorta 15 to return to its usual circular shape. The expansion of the aorta 15 between the de-activated plates causes a pressure drop in the aorta 15 , facilitating left ventricle ejection (ie unloading of the heart). After the heart has finished ejecting blood into the aorta 15 and the aortic valve closes, the plates 4 are activated to move them towards each other and compress the aorta 15 and thereby squeeze blood out of the volume of the aorta 15 compressed by the compression plates 4 and augment the diastolic pressure. Coronary artery blood flow to the left ventricle occurs predominantly in diastole so compression of the aorta 11 also augments coronary blood flow.
[0101] FIGS. 7 to 10 show an aortic compression means in the form of a flexible hollow inflatable cuff 60 . The cuff 60 is curved along its length so as to substantially replicate the curve of the aorta 15 adjacent thereto. The cuff 60 is shown in its de-activated (uninflated) state in FIG. 9 a , and has two free ends 61 and 62 which are adapted to overlap when the cuff 60 is placed around the aorta. As best shown in FIG. 10 , the cuff 60 is retained adjacent the aorta after implantation by suturing the two free ends together at 63 . This also ensures that the cuff 60 is a snug fit around the aorta, when the aorta is in its usual circular shape.
[0102] Further, as best shown in FIG. 9 b , a substantially inelastic, flexible sheath 65 is also preferably placed around the cuff 60 . The sheath 65 assists in retaining the cuff 60 adjacent the aorta and inwardly concentrates the compression forces generated by inflation of the cuff 60 , as indicated by arrows 66 . The sheath 65 can also have free ends sutured together to retain it and the cuff 60 adjacent the aorta in addition to, or in place of, the cuff sutures 63 . The sheath 65 is preferably made from DACRON (Trade Mark), KEVLAR (Trade Mark), TEFLON (Trade Mari), GORE-TEX (Trade Mark), polyurethane or other flexible inelastic bio-compatible materials. The sheath 65 is preferably glued, fused or otherwise bonded to the cuff 60 .
[0103] The cuff 60 also has a single inlet/outlet port 64 for the introduction of fluid to inflate the cuff 60 and thereby compress the aorta and the removal of fluid for the deflation of the cuff and relaxing of the aorta. The fluid is preferably water or an isotonic solution of salt or other low-viscosity, non-toxic liquid.
[0104] The fluid is actively pumped into the cuff 60 for inflation into the shape indicated in phantom in FIG. 9 b . The cuff 60 can be actively deflated by suctioning the fluid from the cuff 60 . Alternatively, the cuff 60 can be passively deflated by the blood pressure of the constricted aorta re-expanding and returning the cuff 60 to the state shown in FIG. 9 a , which ejects the fluid from the cuff 60 . It is preferable to actively deflate the cuff 60 as it gives better presystolic unloading of the heart and counteracts any high intrathoracic pressures, such as when the subject coughs. In either case, the natural resilience of the cuff 60 also assists in deflation by biasing the cuff 60 to the shape shown in FIG. 9 b.
[0105] In another embodiment of heart assist device (not shown), the compression plates 4 are used to squeeze the cuff 60 . This embodiment can be configured to operate in two ways. Firstly, the plates 4 can provide a larger aortic compression and the cuff 60 a smaller aortic compression, either simultaneously or one after the other. This reduces the fluid requirements of the cuff 60 . Secondly, the cuff 60 can be set at a fixed inflation and provide a cushion between the plates 4 and the aorta.
[0106] In other embodiments of cuff (not shown), the sheath is integrally formed with the cuff, preferably by moulding, or in the form of flexible, inelastic fibres embedded in the cuff.
[0107] FIGS. 11 to 18 are schematic drawings of fifth to tenth embodiments of heart assist devices in accordance with the present invention that utilise the cuff 60 shown in FIGS. 7 to 10 .
[0108] In the fifth embodiment shown in FIG. 11 , the cuff 60 is closely coupled to a fluid-filled air-tight housing 70 that has therein a pump, in the form of rotatable impeller 71 and a pair of valves 72 and 73 for directing the flow of the impeller 71 . The housing also includes an inlet/outlet 76 in fluid communication with the inlet/outlet port 64 of the cuff 60 . A fluid reservoir is also provided in the housing 70 in the form of an internal portion 74 of the volume of the housing 70 , as is a pressure compliance means, in the form of a substantially flexible portion of 75 of the housing 70 .
[0109] In operation, energisation of the impeller 71 with the valves 72 and 73 in the position shown in FIG. 11 causes fluid to be actively withdrawn from the cuff 60 , which allow the aorta to return to its usual circular shape. This fluid is pumped into the internal portion 74 of the housing 70 and causes the flexible portion 75 to expand to the position shown in FIG. 11 . When the valves 71 and 73 are in the positions shown in phantom in FIG. 11 and the impeller 71 is energised, the fluid in the portion 74 is pumped into the cuff 60 to expand same and to compress the aorta. The removal of fluid from the portion 74 causes the flexible portion 75 to retract to the position shown in the phantom in FIG. 11 . As with earlier embodiments, the control of the impeller and valves is in response to signals received from an ECG monitor or systemic arterial blood pressure or the like.
[0110] In the sixth embodiment shown in FIG. 12 , the device has only a single valve 76 . The aorta is compressed by positioning the valve 76 as shown in FIG. 12 and energising the impeller 71 . When the valve 76 is moved to the position shown in phantom in FIG. 2 and impeller is de-energised the expanding aorta passively ejects the fluid back into the portion 74 of the housing 71 and causes the flexible portion 75 to expand to the position shown in phantom.
[0111] In the seventh embodiment shown in FIG. 13 , the impeller 71 is driven in one direction to cause fluid flow in the direction indicated by the arrow to deflate the cuff 60 and expand the flexible portion 75 . Reversing the direction of the impeller 71 causes the flexible portion 75 to retract to the position shown in phantom as fluid is displaced into the cuff 60 to inflate same. This embodiment requires variable power control to the motor driving the impeller 71 and a plot of the motor power requirements (Po) relative to the subject's electro cardiograph reading (ECG) and aortic pressure (Pr.) are shown in FIG. 14 .
[0112] In the eighth embodiment shown in FIGS. 15 and 16 , the housing 71 has a rigid upper portion 71 a and a partially rigid lower portion 71 b that includes the flexible portion 75 . A motor 77 is mounted in the lower portion 71 b that drives a pair of rollers 78 , each positioned on an end of a common shaft 79 . The housing portion 71 b also has a pair of upstanding guide posts 80 which are slidably received in corresponding holes in a swash plate 81 . The swash plate 81 has a pair of cam formations 82 on its underside. A fluid-filled sac 83 is positioned between the swash plate 81 and the housing portion 71 a . The interior of the sac 83 is in fluid communication with the interior of the cuff 60 . Power is supplied to the motor 77 through line 84 .
[0113] In operation, the motor 77 is energised to rotate the rollers 78 , which ride along the cam formations 82 to drive the swash plate 81 upwards to compress the sac 83 and eject the fluid therein into the cuff 60 to inflate same. When the rollers 78 have passed the cams 82 the swash plate 81 returns to its original position and the expanding aorta passively ejects the fluid back into the sac 83 . In an alternative embodiment (not shown), the rollers 78 are linked to the earn formations 82 to drive the swash plate 81 up and down and thereby actively inflate and actively deflate the cuff 60 . As a further alternative, (not shown) a stepper motor(s) can be used to drive the swash plate.
[0114] In the ninth embodiment shown in FIG. 17 , the housing 71 has a fluid filled sac 83 positioned between a pair of compression plates 84 which are hinged at 85 and driven by a solenoid 86 . Energising the solenoid 86 brines the plates 84 together to squeeze the sac 83 and force the liquid therein into the cuff 60 to inflate same. De-energising the solenoid 86 draws the plates 84 apart and the expanding aorta passively ejects the fluid back into the sac 83 . As with earlier embodiments as the sac 83 inflates the flexible portion 75 of the housing 71 expands to accommodate the increase in pressure in the housing 71 .
[0115] In the tenth embodiment shown in FIG. 18 , the heart assist device includes a liquid pressure adjustment means, in the form of remote reservoir 90 , connected between the cuff 60 and the reservoir 74 . Liquid can be added to the heart assist device, via the remote reservoir 90 , to adjust the liquid retained in the (de-activated) cuff 60 and thereby adjust the pressure therein. This allows the size of the cuff 60 to be adjusted to compensate for changes in the size of the aorta and/or the amount of aortic compression to be adjusted to, for example, wean the patient from the heart assist device. When the reservoir is positioned near the skin, its volume can be adjusted by using a needle to inject or withdraw liquid. When the reservoir is positioned near the heart assist device, its volume can be adjusted by adding or withdrawing liquid via a transcutaneous tube. The pressure in the reservoir 90 can also be sensed and automatically adjusted so as to maintain a predetermined pressure.
[0116] It will be appreciated that the system and device of the present invention, in their preferred forms, are designed to be simple with no blood contact and a much lower morbidity risk compared to LVADs. The device and system allows the heart to remain totally un-instrumented, and the device, by effective counterpulsation in the aorta, augments the cardiac output up to 15-20%. All natural blood pathways are maintained. Pulsatile blood flow is also maintained. The patient is able to ambulate and there is no risk of leg ischaemia.
[0117] The present invention provides for long term relief and/or stabilization/of or recovery from chronic heart failure. Moreover the present invention may be a suitable bridging device for transplantation.
[0118] The device and system of the above-described embodiments improve cardiac work efficiency by reducing the afterload (pressure/resistance to flow which the heart has to overcome to eject blood) during systole (ejection phase), by augmenting diastolic aortic blood pressure to maintain a greater mean arterial pressure, and by increasing left ventricular coronary artery blood flow during diastole.
[0119] The preferred embodiments of the heart assist device compress the ascending aorta. This is advantageous as the ascending aorta is less prone to disease than the descending aorta and, being closer to the heart, provides improved pumping efficiency and thus a smaller heart assist device.
[0120] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. For example, although the invention has been described in specific reference to compression of the aorta, the devices, systems and methods of the present invention can equally be used for the compression of the pulmonary artery to effectively act as a right ventrical assist device, and the present invention extends to this alternative aspect. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. | An apparatus and method for use in assisting a human heart are disclosed. The apparatus comprises an aortic compression means which may be fully implanatable, a fluid reservoir and a pump means adapted to pump a fluid from the reservoir to the aortic compression means so as to actuate the aortic compression means at least partly in counterpulsation with the patient's heart. In addition, the device is adapted to be wholly positioned within the right chest cavity of the patient. The aortic compression means of the device may be curved along its length so as to substantially replicate the curve of the ascending aorta. | 0 |
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. filed Nov. 2, 2009, and incorporates the prior application in its entirety.
TECHNICAL FIELD
[0002] The present invention relates to the field of exercise monitoring, more particularly to an apparatus and method for monitoring pressure generation while strengthening core muscles.
BACKGROUND
[0003] Back pain is one of the most common medical problems, affecting eight of ten people at some point during their lives. About 25% of Americans are affected by back pain each year. They spend more time at the doctor's office for back pain than for any other medical condition except high blood pressure and diabetes (which are directly related to obesity). Unfortunately, the expected improvements in patient health have not been achieved through the current services and procedures, resulting in a dramatically increased use of narcotics, injections and surgery over the past decade. More money is spent treating neck and back pain than almost any other medical condition, and most neck and back pain is preventable. There are more than 15 million outpatient physician visits for back pain alone in a given year in the US. Even though only a fraction of people with back pain are good candidates for surgery, complicated spine operations are on the rise. Complicated surgeries can result in unwanted scarring that gives rise to more pain; repeat surgeries are at 20%.
[0004] Back and neck problems are the second leading cause of disability and the leading cause of job-related disability, costing the US more than USD50 billion each year.
[0005] About a half a billion dollars a year is spent on the sale of exercise equipment through infomercials and USD 207 million of that is for abdominal machines alone. However, none of these machines provide detailed instructions on how to properly activate “core” muscles. When the deep inner core muscles are not activated properly, strain is placed on the spine and can results in injuries and/or pain.
[0006] Currently there is a subjective measure of core muscle activation that is used universally in physical therapy: The clinician places a hand between the lower back and the floor or table while instructing the patient to continue to apply pressure or “squeeze” the back into the clinician's hand and maintain that position while performing various exercise motions. This is labor intensive for the clinician. When the patient exercises unsupervised, she quickly forgets the fine points of such exercise and returns to improper activation, discomfort and inadequate physical performance.
[0007] A device used in some physical therapy clinics for treatment of low back pain is a blood pressure cuff, but that has the following limitations: 1) too short a hose which causes the body to twist and cause an inaccurate reading while performing exercises, 2) an extra hose that gets in the way, 3) too small print on the gauge to read the biofeedback data on, in addition to also being in units of mmHg and no indicators of the ideal range to reach throughout exercise, 4) dependence on clinician to place the air filled sac of the blood pressure cuff in the correct part of the body to get a accurate biofeedback, 5) too much error in feedback because the blood pressure cuff requires someone to manually pump air into the sac, and 6) manual pumping producing variable amounts of air and variable results, and 7) mishandling the bulb valve decreasing pressure.
[0008] There recently has been introduced a device called the ‘Stabilizer’ that works like a blood pressure cuff that has earlier been utilized as an objective biofeedback when the transverse abdominals are activated during physical therapy sessions (U.S. Pat. No. 5,338,276). This new device apparently depends on the clinician to correctly place the device on the body, the air sac seems too large and causes distortion of body position, and the biofeedback is given in units of mmHg, without a clear guide to desired pressure, although a new model has red lines to indicate a range).
SUMMARY OF THE INVENTION
[0009] In accordance with the present invention, an exemplary apparatus for monitoring pressure generation needed for proper abdominal strengthening is disclosed. The apparatus has a stretchable belt with a first end, second end, a first side, a second side, inside surface, outside surface. The first and second ends have fasteners to attach the belt around the customer's waist, and the fasteners are so arranged as to accommodate a variety of waist sizes. The first side has a small opening; and the belt has a wider portion in the middle formed by wider surfaces of the fabric, the wider portion forming a pocket with an exit at the small opening. The pocket accommodates a finable sac containing gas-filled foam. A manometer attaches to the sac via a tube that passes out through the small opening, the manometer displaying data on pressure changes as the customer uses the belt.
[0010] Optionally the center of the wider portion of the apparatus has a marker to align substantially with an athlete's spine. The marker is painted, sewn, silk screened or glued onto the belt. The belt is formed from Neoprene® polychloroprene or other material with similar characteristics.
[0011] The two surfaces of the belt comprise two at least attached pieces of Neoprene®. The tube connecting the foam sac and the manometer is sufficiently long for the person wearing the belt to see the manometer while exercising and without twisting. Such a tube is at least 30 inches long. Alternatively, the tube is between 28 and 45 inches long.
[0012] The tube passes from the sac through the belt to a side hole for exiting the belt.
[0013] The manometer has a face with demarcated directions and pressure units. Alternatively, the small opening for the tube is lengthened to the width of the sac, thereby permitting removal of the sac assembly. The fasteners are Velcro® hooks and loops, hooks and eyes, buttons, snaps, etc.
[0014] In another embodiment, the monitoring apparatus has a) a stretchable belt formed from a single piece of Neoprene® with a first end, second end, a first side, a second side, inside surface, outside surface; b) the first and second ends having fasteners to attach the belt to the athlete's waist, the fasteners being so arranged as to accommodate a variety of waist sizes; c) a pocket sized to contain a sac filled with compressible foam, the pocket having an inner surface and an outer surface, the inner surface being attached to the outside belt material of the belt, so that the foam sac is compressed against the back in use, the pocket further having an upper edge; and d) a manometer attached to the sac via a tube that passes out through the open upper edge of the pocket, the manometer representing data on pressure changes as improper activation, initiation of activation, and proper and consistent activation of transverse abdominals, as the customer uses the belt.
[0015] The apparatus also has a marker to align substantially with an athlete's spine. This marker is painted, silk screened, sewn or glued onto the belt. The apparatus can have two surfaces of the belt comprise two attached pieces of Neoprene® material. The tube connecting the foam sac and the manometer is sufficiently long for the person wearing the belt to see the face of the manometer while exercising and without twisting or having to torque their neck. The tube is about 28-45 inches long.
[0016] The apparatus' fasteners can be Velcro® hooks and loops, Velcro hooks alone on the fabric, hooks and eyes, buttons, or snaps.
[0017] In another embodiment, there is provided a method of monitoring to maintain the proper pressure of the abdominal muscles during exercise. The first step is providing an apparatus including a stretchable, two-layered belt with a wide middle portion for encapsulating a foam sac, the foam sac being attached to a tube whose other end attaches to a manometer, either end of the belt having fasteners, and the middle of the belt having a marker for centering the foam air sacover the spine; putting on the belt by pulling the belt around the midsection;
attaching the fasteners for a snug fit; checking to assure that the center marker is over the spine and optionally rearranging the belt until the belt is so positioned; positioning the body of the customer to perform an exercise involving the transversal abdominals or the multifidi; Positioning the manometer so that the customer can see the manometer face without turning the face from the midline; beginning the exercise; and watching the manometer face and adjusting the exercise performance until the manometer face indicates proper and consistent activation of muscles.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] For a further understanding of the objects and advantages of the present invention, reference should be made to the following detailed description, taken in conjunction with the accompanying drawing, in which like parts are given like reference numbers and wherein:
[0023] FIG. 1 is an overview of the monitoring apparatus;
[0024] FIG. 2 is a schematic of the monitoring apparatus, showing the Velcro® ends and the central compressible foam sac;
[0025] FIG. 3 shows a variation on the design and assembly of the belt.
[0026] FIG. 4 shows another variation on the design; and
[0027] FIG. 5 shows another variation on the design and assembly of the belt.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0028] As an athletic trainer and strength coach, I found my athletes and patients were not retaining the proper activation of their abdominals throughout various movements and exercise. Like most therapists I would tell them to push my hand into the ground with their back. I grew to realize that they would not maintain that amount of activation when I removed my hand, so I needed to develop another method of teaching proper abdominal muscle activation.
[0029] I remembered my professor in grad school teaching us to use a blood pressure cuff and watch the pressure dial to make sure athletes maintain the contraction throughout “dead bug” exercise or while lowering their shoulders back to the ground following a “mini crunch.” However, I observed several problems with this device. First, the hose was not long enough for the athlete to stay in position and observe the dial. If the athlete were to see the dial, he would have to twist and get inaccurate readings and less benefit. Second, the blood pressure has two hoses and an air bulb which confuses the customer and gets in the way of exercising. Third, the apparatus needed to be repositioned for each exercise. Fourth, there was frequent error in feedback, because we clinicians had no way of standardizing the amount of starting air volume in the blood pressure cuff. Also, the effectiveness of blood pressure cuff depends on the clinician properly placing the air-filled sac to get an accurate reading. Finally, there was no way for the customer to set up a hands-free view of the pressure gauge.
[0030] Taking into account these problems with the current device, I developed my own design. I set about making an apparatus that is more efficient, operable by the customer, and easy to put on correctly. When going through the thought process of designing my own apparatus, I realized there is no reason to show the pressure units (so I can use a different manometer), and I realized that constant air volume and a closed system were crucial to the effectiveness of the apparatus. I invented a way to eliminate the bulb for pumping air into the air sac with a separate hose. Also, I needed a belt to go with this so the customer could move between multiple exercises without having to reset the apparatus under the back properly. Since I have patients of all different sizes, I needed an adjustable belt. And since activation of the abdominals can result in expanding the abdomen, I sought a material for the belt with more elasticity than typical nylon belts used in physical therapy in addition to material that can be properly cleaned between uses.
[0031] In an exemplary embodiment of the present invention, as shown in FIG. 1 , my exercise monitoring apparatus 10 has an expandable waist belt 20 , a polyurethane bladder that contains air-filled, compressible foam (not shown) a rubber hose 30 , and a manometer 40 . This apparatus when placed correctly around the waist and lower back provided an objective biofeedback for the activation of the abdominal and core muscles, throughout various exercises.
[0032] The biofeedback was enabled by the use of a manometer 40 attached to the single hose 30 extending from the foam-filled sac that is embedded in a wider section 50 of the waist belt 20 . As the transverse abdominals and multifidi were activated appropriately during various exercises, the pressure in the foam filled sac increased and was read on the aneroid dial 60 . The pressure increased with correct activation of the abdominals in combination with movement of the upper torso, upper extremity, and/or the lower extremity. There are many advantages in both the design and the utilization of this biofeedback product and concept. The potential advantages are: 1) independence from a clinician to utilize this apparatus correctly which allows for a broader range of people able to utilize this apparatus and concept of training their “core”, 2) chronic back pain decreased, 3) more effective physical therapy for those patients that are trying physical therapy to either put off the need for surgery or as their last resort prior to surgery in many parts of the body (i.e. shoulder, back, knee, hip); 4) the design of the waist belt allowed for consistency of proper placement with each use; 5) the design of the belt with markers indicating proper placement and the long hose allowed persons to be independent from their clinician, strength coach, personal trainer, etc; 6) prevention of acute and chronic injuries (i.e. knee, back, hip, shoulder) due to proper and effective “core” training; and 7) the long hose with a hands-free stand allowed the patient to perform exercises without moving their body in improper ways when attempting to read the dial for feedback during exercises.
[0033] FIG. 2 shows more details of the monitoring apparatus 10 . As shown, the belt 10 is approximately 42 inches long. In the middle of the belt 10 is the wider section 50 that holds the foam-filled sac 70 . To assure proper placement, the sac 70 is shown stitched in place. At either end of the belt 10 are hooks and loop strips of Velcro® 80 and 90. Alternately, the Velcro hooks grasp the Neoprene material alone. Strip 90 is shown as about 12 inches in length and to allows ample adjustment of the belt length. Between strip 90 and the wider portion 50 of the belt 10 is shown a sewn channel 100 in the belt. The rubber hose (not shown) exits the sac 70 , travels through the channel 100 and exits the belt (not shown) adjacent the strip 90 .
[0034] The monitoring apparatus is preferably made from two pieces of Neoprene® that are sewn or glued together. A sac is filled with gas-filled foam and is closed except for an opening to attach the proximal end of a rubber hose. A pocket is partially formed in the middle of the belt and is sewn shut around the sac, except for a small opening for the rubber hose that is then placed in the belt and a channel is sewn around it. A manometer is attached to the distal end of the hose. Nylon tabs are sewn to one end of the belt and to the upper and lower centers of the wider portion of the belt. Lastly, Velcro® hooks are attached to one end of the belt and Velcro loops attached to the other end.
[0035] To use the monitoring apparatus, the customer places the belt at the waist with the central tabs substantially aligned with the spine. The customer stretches and overlaps the ends of the belt and presses the Velcro hooks into the Velcro loops to firmly attach the monitoring apparatus. The rubber hose and manometer hang from the side of the belt. The customer positions herself for the exercise and places the manometer where she can see the face of the manometer, optionally clipped on a holder/stand. The customer begins a series of core strengthening exercises and glances at the manometer, which initially indicates improper activation of transverse abdominals. With harder work, the manometer indicates initiation of activation, and finally the manometer indicates proper and consistent activation of transverse abdominals and other core muscles.
Materials for an Exemplary Embodiment
[0036] The hose is made of biocompatible material, including but not limited to rubber.
[0037] The manometer is available from a variety of manufacturers, including but not limited to American Diagnostic Corporation. The face of the manometer need not be limited to numbers in terms of mmHg or torr. In fact, these numbers are not very meaningful to most customers and their significance is quickly forgotten. Preferably the face of the manometer is designed to show the preferred pressure range. Other areas of the face can optionally have encouraging words and color-coded ranges.
[0038] The material of the belt can be made of any material that is somewhat stretchy but has the strength to hold the foam sac in place. Preferred materials are rubber and synthetic rubber, such as NEOPRENE® polychloroprene.
[0039] The belt can be fastened by any of a variety of fasteners, including but not limited to Velcro® hooks and loops, hooks and eyes, buttons and buttonholes, and Velcro® hooks grasping the belt material.
[0040] The sac can be made from a flexible, air-proof material such as vinyl or polyurethane. The compressible foam is preferably made of polyethylene open-cell foam. Other materials can be substituted, provided they have the same features, including but not limited to polyurethane foam.
[0041] The monitoring apparatus is preferably made from two pieces of Neoprene® that are sewn or glued together. Initially a polyurethane sac is filled with gas-filled polyethylene foam. A pocket is partially formed in the middle wider section of the belt and is sewn shut around the sac, except for a small opening for the rubber hose that is then placed in the belt and a channel is sewn around it. An opening is formed in the side of the belt for the hose to exit and a manometer is attached to the distal end of the hose. Nylon tabs are added to one end of the belt and to the upper and lower centers of the wider portion of the belt. Lastly, Velcro® hooks are attached to one end of the belt and Velcro loops attached to the other end.
[0042] To use the monitoring apparatus, the customer places the belt at the waist with the central tabs substantially aligned with the spine. The customer stretches the ends of the belt to overlap and presses the Velcro loops into the Velcro hooks to firmly attach the monitoring apparatus. The rubber hose and manometer hang from the side of the belt. The customer positions herself for the exercise and places the manometer where she can see the face of the manometer, optionally on a holder. The customer begins a series of core strengthening exercises and glances at the manometer, which initially indicates improper activation of transverse abdominals. With harder work, the manometer indicates initiation of activation, and finally the manometer indicates proper and consistent activation of transverse abdominals and core muscles.
Example 1
[0043] A waist belt is made of washable Neoprene® material, in the preferred embodiment, or any elastic type of material that can expand and fit snugly around the body when wrapped around the waist. Waist belt is 42″-55″ long with the capability to fit most adult waist sizes. For fastening the belt, a strip of Velcro® loops is placed along the belt's left end and a strip of Velcro® hooks is placed on the inside of the right end. Vertical markers are placed on the belt to indicate proper placement when belt is wrapped around waist. These can be sewn on the belt (loops) or can be silk screened, painted, or glued on the belt. The waist belt also has a pocket that holds the foam sac made of a same material as the belt.
[0044] The hose exits from the pocket through a hole in the exterior surface of the Neoprene® belt on a side. The rubber hose is preferably 39″ long and ¼″ diameter, and it is securely fastened to a manometer to ensure an accurate representation of pressure produced in the auto-inflate air sac during exercise.
[0045] The hose exits the pocket and weaves through a tunnel on the Neoprene® belt to ensure manometer and hose are easy to reach.
[0046] The pocket is made of similar material as the belt, is sewn on the Neoprene® belt in the middle of the inner side of the belt designed as followed: The pocket is sewn on to the waist belt on all 4 sides to secure the foam sac. There is a 0.25″ hole cut out of the exterior surface of belt inside the top left corner of the pocket to allow the hose to exit the pocket. The single chambered sealed polyurethane pouch has open-celled foam embedded inside with a 1 cm diameter of space between the lateral edges of the foam and the edge of pouch as well as:
[0047] The proximal end of the rubber hose inserts into the air sac through top left corner and is sealed to ensure no leakage of air around the hose attachment. The rubber hose is then threaded through a channel between the inside and outside pieces of Neoprene® and out the side of the belt as it sits on the customer's waist. Channeling the rubber hose to the side keeps it out of the way of the exercise. The length of the rubber hose is preferably greater than 30 inches or in a range of about 28 to 45 inches. These lengths were chosen to permit the customer to view the manometer face without substantially turning the face from the midline. Substantial turning impedes proper balanced exercising.
[0048] The thickness of the open-celled foam affords a set amount of air volume in air sac at all times. The foam is approximately ¼″-1″ inch thick, with the thickness being adjusted for the resistance of the foam. Foam thickness can be adjusted, depending on its resistance to compression and the effect achieved. As pressure on the air-filled sac increases, the preferred embodiment's manometer attached to the rubber hose displays an increase of pressure.
[0049] The manometer's face plate is large for ease of reading by customers of all ages that utilize this product. The diameter is equal to or greater than 2″. The gauge can be any practical shape, such as ovoid, rectangular and other multi-sided structures. The manometer has an indicator needle in front of a multi-color display, such as red, yellow, and green. This is designed to provide biofeedback that customers understand. Red indicates improper activation of transverse abdominals, yellow indicates initiation of activation, and green indicates proper and consistent activation of transverse abdominals and core muscles. These colors can be easily seen so the customer need not substantially turn the head to monitor status.
[0050] In another embodiment, the biofeedback is also indicated by a noise that sounds if the pressure is not in the “green area” of the manometer during exercises.
[0051] A hands-free metal stand is an optional part of this invention as a separate embodiment on which the manometer is seated. This allows the apparatus to be hands-free and aids the ability to perform the exercises properly.
[0052] In another embodiment the hands-free metal stand connects to a large body-size padding for the person to lie on when performing exercises.
[0053] In another embodiment the hands-free metal stand is designed as a north-pole magnetic stand to allow the south-pole magnetic manometer to be held on with magnetic forces.
Clinical Examples
[0054] I worked with Client #1, a non-athletic patient who had undergone more than three years of physical therapy for her back pain. She had been taught many times by physical therapists to activate her transverse abdominis with the method of pushing the back into the hand of the therapist while lying supine. But when I repeatedly used the inventive apparatus, she was able to see the “objective” feedback of how much more she needed to activate her abs for the necessary effect. She very quickly became pain free in her lumbar spine during exercise and activities of daily living. In addition, she became able to lift and move more weight and to perform longer cardio exercise. She lost two inches from her waist within first month of use.
[0055] Client #2 had been treated by a chiropractor for back pain for almost one year. After using the monitoring apparatus for two weeks of training, she was able to reduce the rate of chiropractic visits. After eight sessions, the individual reported no longer needing any chiropractic visits.
[0056] Client #3 was an elite football player who needed to rapidly increase his upper body strength and increase his speed so he could participate in the NFL combine. Using the monitoring apparatus to activate his abdominals correctly, his bench pressing increased 50 lbs and his 40 yd time decreased by 0.03 sec in three weeks, with no other change in his strength and conditioning routine.
[0057] Client #4 was a runner with repetitive knee injury causing pain. She learned how to activate her abs with the monitoring apparatus and had a noticeably tighter abdomen and a significant increase pelvic stability and lower body strength after four weeks of use. Knee pain was completely gone within the first two weeks, because her center of gravity was moved backward and the harmful anterior force was removed from knees.
[0058] Client #5 was four months post pregnancy, with a loose abdomen. Within 7 visits, she lost most of her baby belly fat and gained abdominal and back muscles she never realized she had
[0059] Client #6 was a 63-year-old male who had severe low back pain. Three spinal surgeons told him spinal surgery was his only option. He decided to try the monitoring apparatus as one last opportunity to heal prior to going into surgery. In less than three months of using the monitoring apparatus, his back pain was gone, and surgery was no longer needed. Now with no back pain, he works out intensely and lifts double the amount of weight he had been able to lift in the last five years.
[0060] Where the apparatus and procedures described herein for the monitoring apparatus, there may be additional modifications to provide a commercially viable apparatus. As can be seen from the drawing figures and from the description, each embodiment and method of the inventive apparatus and method in accordance with the present invention solves a problem by addressing the need for an improved apparatus to enable athletes and others to properly exercise and build up their abdominal and “core” to avoid injuries and improve strength and physical prowess.
[0061] Although specific embodiments have been illustrated and described herein, those of ordinary skill in the art will appreciate that any arrangement calculated to achieve same purposes can be substituted for the specific embodiments or exemplary methods shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments of the invention. It is to be understood that the above description has been made in an illustrative fashion, and not a restrictive one. Combinations of the above embodiments, and other embodiments not specifically described herein will be apparent to those of skill in the art upon reviewing the above description. The scope of various embodiments of the invention includes any other applications in which the above structures and methods are used. Therefore, the scope of various embodiments of the invention should be determined with reference to the appended claims, along with the full range of equivalents to which such claims are entitled.
[0062] In the foregoing description, if various features are grouped together in a single embodiment for the purpose of streamlining the disclosure, this method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments of the invention require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus the following claims, and such other claims as may later be added, are hereby incorporated into the description of the embodiments of the invention, with each claim standing on its own as a separate preferred embodiment. | An exercise monitoring apparatus for measuring proper abdominal strengthening affords a customer an improved method for developing better abdominal muscles to treat back pain, avoid injuries and improve physical performance. The exercise apparatus has a stretchable belt with first and second ends having fasteners to attach the belt to the athlete's waist, the fasteners accommodating a variety of waist sizes. The belt has a wider middle portion formed by wider surfaces of the fabric, the wider portion forming a pocket with an exit at a small opening. The pocket accommodates an airtight sac containing gas-filled, compressible foam. A manometer is attached to the sac via a tube that passes through the small opening around the sac, and the manometer displays data on pressure changes as the customer uses the belt. | 0 |
BACKGROUND OF THE INVENTION
[0001] Embodiments relate generally to the field of ophthalmic surgery and more particularly to instruments and methods for removing cataracts.
[0002] The human eye in its simplest terms functions to provide vision by transmitting light through a clear outer portion called the cornea, and focusing the image by way of the lens onto the retina. The quality of the focused image depends on many factors including the size and shape of the eye, and the transparency of the cornea and lens.
[0003] When age, disease, trauma, etc. causes the lens to become less transparent, vision deteriorates because of the diminished light which can be transmitted to the retina. This deficiency in the lens of the eye is medically known as a cataract. A generally accepted treatment for this condition is surgical removal and replacement of the lens with an artificial intraocular lens (IOL).
SUMMARY OF THE INVENTION
[0004] Embodiments described herein provide instruments for infusion and aspiration during eye surgery.
[0005] One embodiment provides an instrument including an infusion sleeve, an aspiration tube, and an infusion/aspiration tip. The infusion sleeve can include a body which defines an infusion channel. The aspiration tube can be positioned in the infusion channel and can define an aspiration channel. The infusion/aspiration tip can couple to and conform to the distal end of the aspiration tube. The infusion/aspiration tip can seal a gap between the infusion sleeve and the aspiration tube. Furthermore, in some embodiments, the infusion/aspiration tip can include a flange with a profile (e.g., a tapered portion) corresponding to a profile of the infusion sleeve. In some embodiments, the infusion sleeve and the infusion/aspiration tip can be keyed such that the infusion sleeve directs fluid in one direction and the infusion/aspiration tip aspirates material from another direction. The infusion and aspiration directions can be perpendicular to each other. The aspiration channel of the infusion/aspiration tip can extend distally beyond the aspiration port. In some embodiments, the infusion/aspiration tip can extend proximally to a point adjacent to an infusion port of the sleeve.
[0006] One embodiment provides a single use, disposable component for use with an ophthalmic surgical instrument. The instrument can include an infusion sleeve comprising an elongated body defining an infusion channel and having a proximal end, a distal end, and a longitudinal axis along the length of the elongated body whereas the component can include an aspiration tube and an infusion/aspiration tip. The aspiration tube can define an aspiration channel and can have a proximal end and a distal end. When the disposable component is in the instrument, the aspiration tube can be positioned in the infusion channel. The infusion/aspiration tip can couple to and conform to the distal end of the aspiration tube.
[0007] In some embodiments, when the disposable component is coupled to the instrument, a gap can exist between the distal end of the infusion sleeve and the distal end of the aspiration tube. The infusion/aspiration tip can seal the gap when the disposable component is coupled to the instrument. The infusion/aspiration tip can define an aspiration port oriented to draw material from the environment from a direction which is perpendicular to the longitudinal axis of the disposable component and perpendicular to the direction in which an infusion port of the infusion sleeve directs infusion fluid when the disposable component is coupled to the instrument. In some embodiments, when the disposable component is coupled to the instrument, the infusion/aspiration tip can extend in a direction along the longitudinal axis to a point adjacent to the infusion port.
[0008] Embodiments provide instruments which reduce patient trauma during cataract extraction and other ophthalmic procedures. More particularly, embodiments provide instruments which reduce, if not eliminate, the possibility of tears in capsular bags due to micro burrs on various instruments. Embodiments provide inexpensive and disposable aspiration tubes for ophthalmic instruments. In some embodiments, leakage of infusion fluid between the infusion sleeve and the infusion/aspiration tip can be eliminated or greatly reduced. Embodiments eliminate the need to clean aspiration tubes and infusion/aspiration tips of various ophthalmic surgical instruments following surgery.
BRIEF DESCRIPTION OF THE FIGURES
[0009] A more complete understanding of the present invention and the advantages thereof may be acquired by referring to the following description, taken in conjunction with the accompanying drawings in which like reference numbers indicate like features.
[0010] FIG. 1 is a cross sectional view of an eye undergoing ophthalmic surgery.
[0011] FIG. 2 is a perspective view of one embodiment of an ophthalmic surgical instrument.
[0012] FIG. 3 is a cross sectional view of one embodiment of an ophthalmic surgical instrument.
[0013] FIG. 4 is a diagrammatic representation of an embodiment of a curved ophthalmic instrument.
[0014] FIG. 5 is a diagrammatic representation of an embodiment of a bent ophthalmic instrument.
DETAILED DESCRIPTION
[0015] Preferred embodiments are illustrated in the FIGURES, like numerals generally being used to refer to like and corresponding parts of the various drawings.
[0016] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, process, article, or apparatus that comprises a list of elements is not necessarily limited only those elements but may include other elements not expressly listed or inherent to such process, process, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present). A is false (or not present) and B is true (or present), and both A and B are true (or present).
[0017] Additionally, any examples or illustrations given herein are not to be regarded in any way as restrictions on, limits to, or express definitions of, any term or terms with which they are utilized. Instead these examples or illustrations are to be regarded as being described with respect to one particular embodiment and as illustrative only. Those of ordinary skill in the art will appreciate that any term or terms with which these examples or illustrations are utilized will encompass other embodiments which may or may not be given therewith or elsewhere in the specification and all such embodiments are intended to be included within the scope of that term or terms. Language designating such nonlimiting examples and illustrations includes, but is not limited to: “for example”, “for instance”, “e.g.”, “in one embodiment”.
[0018] Previously, to remove a lens from an eye, surgical personnel sometimes used an ophthalmic instrument with an infusion sleeve and an aspiration tube therein. Surgical personnel also used a sleeve made of silicon and having a hole therein for aspirating fluid. Surgical personnel slipped the sleeve over the aspiration tube and then used the instrument for ophthalmic surgery. The sleeves, though, were often difficult to use. For instance, the sleeves could tear thereby making it necessary to remove and replace the damaged sleeve. In addition, once on the aspiration tube, these sleeves could slip off of the aspiration tube making its replacement on the aspiration tube necessary. Moreover, because these sleeves only partially filled the space between the aspiration tube and the infusion tube, some infusion fluid could leak out of the distal end of the instrument and move in a forward direction and into the eye. This condition can be undesirable because surgical personnel typically prefer that the instrument direct the infusion fluid perpendicularly from the instrument while aspirating material longitudinally from the distal end of the instrument.
[0019] With reference now to FIG. 1 , a cross sectional view of eye 10 undergoing ophthalmic surgery is illustrated. The procedure illustrated could be a cataract extraction. Eye 10 includes sclera 12 , optic nerve 14 , retina 16 , lens 18 , capsular bag 19 , iris 20 , cornea 22 , and pupil 24 . Normally, lens 18 focuses light passing through cornea 22 and pupil 24 on to retina 16 . Retina 16 converts light to nerve impulses which retina 16 sends along optic nerve 14 to the brain. Iris 20 regulates the amount of light passing through pupil 24 and lens 18 thereby allowing eye 10 to adapt to varying levels of light. Capsular bag 19 holds lens 18 in place and is transparent so that light may pass through it. Thus, the nerve impulses traveling along optic nerve 14 correspond to scenes visible to eye 10 .
[0020] However, various diseases, conditions, injuries, etc. can cause lens 18 to become clouded, translucent, etc. to the point that it might be desirable to extract lens 18 from eye 10 . In such situations, the affected patient can be said to have a “cataract.” Often, when lens 18 is removed from eye 10 (i.e., the cataract is extracted), surgical personnel replace lens 18 with an artificial lens, thereby restoring sight to the affected patient. Alcon Laboratories, Inc. (of Fort Worth, Tex.) provides exemplary artificial lenses such as the AcrySof® intraocular lenses. To remove lens 18 , surgical personnel sometimes use instrument 100 . As illustrated by FIG. 1 , instrument 100 can include elongated infusion sleeve 102 , infusion/aspiration tip 104 , and handpiece 113 . Ophthalmic tubing 115 can be connected to instrument 100 at handpiece 113 and can supply infusion fluid from an infusion/aspiration machine to instrument 100 and return material aspirated from eye 10 to the infusion/aspiration machine. Handpiece 113 can provide communication channels between ophthalmic tubing 115 and infusion sleeve 102 and infusion/aspiration tip 104 . Additionally, handpiece 113 can couple with infusion sleeve 102 and indirectly with infusion/aspiration tip 104 (via one or more internal components) thereby holding these components 102 and 104 in fixed operational relationship to each other.
[0021] To extract the cataract, surgical personnel can make an incision in cornea 22 and capsular bag 19 . Through the incision, surgical personnel can insert infusion/aspiration tip 104 of instrument 100 into lens 18 . Using instrument 100 , surgical personnel can direct infusion fluid from infusion/aspiration tip 104 into lens 18 thereby causing lens 18 to disintegrate. Infusion/aspiration tip 104 can draw the infusion fluid, cortical material, and portions of disintegrated lens 18 from capsular bag 19 . At some time, surgical personnel can withdraw instrument 100 from eye 10 , insert an artificial lens into capsular bag 19 of eye 10 , and close the incision.
[0022] Previously, during such procedures, micro burrs on surfaces of previously available instruments would catch on, and tear, capsular bag 19 . Furthermore, forward leakage of infusion fluid from previously available instruments could interfere with aspiration of material from capsular bag 19 . Forward leakage can reduce the efficiency of various surgical techniques and increase the time necessary for performing such techniques. Embodiments of instrument 100 , though, can have a smooth, relatively micro burr-free, surfaces. Thus, embodiments of instrument 100 can reduce, if not eliminate, capsular bag 19 tears caused by micro burrs while increasing the speed and efficiency of various ophthalmic techniques.
[0023] FIG. 2 further illustrates instrument 100 including infusion sleeve 102 , infusion/aspiration tip 104 , infusion port 106 , aspiration tube 108 , aspiration port 110 , distal end 112 of infusion sleeve 102 , flange 114 of infusion/aspiration tip 104 , proximal end 116 of infusion/aspiration tip 104 , tapered portion 118 of infusion/aspiration tip 104 , distal end 120 of infusion/aspiration tip 104 , and longitudinal axis 122 of instrument 100 . Aspiration tube 108 can fit coaxially within infusion sleeve 102 and both can couple to handpiece 113 (see FIG. 1 ) at their respective proximal ends. Handpiece 113 can provide communication paths from ophthalmic tubing 115 (see FIG. 1 ) to and from, respectively, infusion sleeve 102 and aspiration tube 108 . Thus, infusion fluid can be directed distally through infusion sleeve 102 and out through infusion port 106 in a direction perpendicular to longitudinal axis 122 . Aspiration port 110 of infusion/aspiration tip 104 can draw material from its environment (for instance, lens 18 of FIG. 1 ) for return to, for example, an infusion/aspiration machine via aspiration tube 108 . The direction from which aspiration port 110 can draw material can be perpendicular to the direction in which infusion port 106 directs fluid.
[0024] FIG. 3 illustrates a cross sectional view of one embodiment of instrument 100 . Furthermore, FIG. 3 illustrates infusion sleeve 102 ; infusion channel 103 ; irrigation/aspiration tip 104 ; aspiration channel 105 ; infusion port 106 ; aspiration tube 108 ; aspiration channel 109 ; aspiration aperture 110 ; distal end 112 of infusion sleeve 102 ; flange 114 ; proximal end 116 of infusion/aspiration tip 104 ; tapered portion 118 ; distal end 120 of infusion/aspiration tip 104 ; longitudinal axis 122 ; and distal end 124 of aspiration tube 108 . More particularly, FIG. 3 illustrates infusion/aspiration tip 104 being coupled to and conforming to distal end 124 of aspiration tube 108 . In some embodiments, infusion/aspiration tip 104 can be overmolded onto aspiration tube 108 . Aspiration channel 105 of infusion/aspiration tip 104 can align with and correspond to aspiration channel 109 of aspiration tube 108 . In some embodiments, aspiration channel 105 of infusion/aspiration tip 104 can extend distally beyond aspiration port 110 . Aspiration channel 105 of infusion/aspiration tip 104 can communicate with aspiration port 110 thereby allowing instrument 100 to aspirate material generally adjacent to infusion/aspiration tip 104 through aspiration port 110 , aspiration channel 105 of infusion/aspiration tip 104 , and aspiration channel 109 of aspiration tube 108 (and then through ophthalmic tubing 115 for disposal). From aspiration channel 109 of aspiration tube 108 , aspirated material can be returned to an infusion/aspiration machine (or other system for disposal) via ophthalmic tubing 115 (see FIG. 1 ).
[0025] Flange 114 of infusion/aspiration tip 104 can abut distal end 112 of infusion sleeve 102 and can seal infusion channel 103 against leakage from distal end 112 of infusion sleeve 102 . Infusion/aspiration tip 104 can extend into infusion channel 103 some distance thereby also sealing against the internal walls of infusion sleeve 102 . Furthermore, infusion/aspiration tip 104 can extend into infusion sleeve 102 to a point adjacent to a portion of infusion port 106 thereby blocking flow through infusion channel 103 and directing infusion fluid out through infusion port 106 . In some embodiments, the interior surface of infusion sleeve 102 can taper away from infusion/aspiration tip 104 in the vicinity of infusion port 106 , thereby allowing flow through infusion port 106 passed infusion/aspiration tip 104 . In some embodiments, infusion/aspiration tip 104 can be retained in infusion sleeve 102 by friction between infusion/aspiration tip 104 and the internal walls of infusion sleeve 102 despite pressure within infusion channel 103 . For instance, infusion/aspiration tip 104 and infusion sleeve 102 can be shaped and dimensioned to create an interference fit when infusion/aspiration tip 104 is inserted into infusion sleeve 102 . Alternatively, some clearance can exist between infusion/aspiration tip 104 and infusion sleeve 102 . In some embodiments, infusion/aspiration tip 104 can be indirectly coupled to handpiece 113 (see FIG. 1 ) by aspiration tube 108 , thereby allowing it to remain in infusion sleeve 102 despite pressure therein. The indirect coupling of infusion/aspiration tip 104 and handpiece 113 can hold infusion/aspiration tip 104 against distal end 112 of infusion sleeve 102 thereby creating a seal between these two components 104 and 102 . Thus, infusion/aspiration tip 104 can prevent leakage of infusion fluid from infusion sleeve 102 in a direction along longitudinal axis 122 .
[0026] FIG. 3 also illustrates infusion/aspiration tip 104 including tapered portion 118 . Tapered portion 118 can have a diameter at proximal end 116 of infusion/aspiration tip 104 which is about the same as the diameter of distal end 112 of infusion sleeve 102 . Thus, the profile of infusion/aspiration tip 104 can correspond to the profile of infusion sleeve 102 . Tapered portion 118 can taper to another, smaller diameter some distance from proximal end 116 of infusion/aspiration tip 104 . Thus, the interface between infusion/aspiration tip 104 and infusion sleeve 102 , can be smooth and offer little or no resistance to inserting instrument 100 into eye 10 (see FIG. 1 ). From the distal end of tapered portion 118 , the surface of infusion/aspiration tip 104 can be parallel to longitudinal axis 122 from approximately tapered portion 118 to approximately the distal edge of aspiration port 110 .
[0027] Infusion/aspiration tip 104 can be formed from various plastics, elastomers, etc. while infusion sleeve 102 and aspiration tube 108 can be formed from stainless steel, titanium, or any other biocompatible material. In some embodiments, infusion/aspiration tip 104 is made from a plastic material such as Makrolon(® 2558 (which is available from Bayer MaterialScience L.L.C. of Pittsburg, Pa.). Thus, infusion/aspiration tip 104 can have a smooth surface free of sharp edges, micro burrs, etc. Accordingly, infusion/aspiration tips 104 of various embodiments can avoid tearing capsular bag 19 , thereby speeding patient recovery and reducing patient discomfort associated with certain ophthalmic surgical procedures.
[0028] Moreover, instrument 100 can be quickly assembled by surgical personnel. Instrument 100 can be assembled by sliding aspiration tube 108 (with infusion/aspiration tip 104 overmolded thereon) into infusion sleeve 102 . As infusion/aspiration tip 104 approaches distal end 112 of infusion sleeve 102 , surgical personnel can align infusion/aspiration tip 104 and distal end 112 of infusion sleeve 102 . Surgical personnel can push infusion/aspiration tip 104 into infusion channel 103 thereby sealing distal end 112 of infusion sleeve 102 . Surgical personnel can, when desired, connect infusion sleeve 102 and aspiration tube 108 to handpiece 113 , ophthalmic tubing 115 , etc. (see FIG. 1 ).
[0029] Surgical personnel can navigate instrument 100 to the vicinity of eye 10 and begin to insert distal end 120 of infusion/aspiration tip 104 into an incision therein. As infusion/aspiration tip 104 enters eye 10 , smooth surfaces of infusion/aspiration tip 104 can distract tissues it encounters without tearing capsular bag 19 or otherwise traumatizing eye 10 . As surgical personnel advance instrument 100 into eye 10 , tapered portion 118 can also distract tissues without tearing capsular bag 19 or otherwise traumatizing eye 10 . Surgical personnel can therefore manipulate instrument 100 to extract cataracts and other tissues as may be desired. When desired, surgical personnel can withdraw instrument 100 from eye 10 .
[0030] Surgical personnel can disassemble instrument 100 and dispose of infusion/aspiration tip 104 and aspiration tube 108 . Infusion/aspiration tip 104 and aspiration tube 108 can be relatively inexpensive to manufacture thereby allowing such single uses of infusion/aspiration tip 104 and aspiration tube 108 . Thus, embodiments can alleviate surgical personnel from the need to clean and sterilize infusion/aspiration tip 104 and aspiration tube 108 following various surgical procedures. Moreover, because infusion/aspiration tip 104 and aspiration tube 108 can be pre-sterilized, the need for surgical personnel to clean and sterilize infusion/aspiration tip 104 and aspiration tube 108 (including any crevice that might exist between infusion sleeve 102 and infusion/aspiration tip 104 ) prior to certain ophthalmic surgical procedures can be alleviated by various embodiments.
[0031] In the previous embodiments, the surgical instrument has a generally straight profile. In FIG. 4 , one the other hand, surgical instrument 300 can have a curved profile. In FIG. 4 , instrument 300 can include aspiration sleeve 302 , infusion/aspiration tip 304 , and an attachment portion 306 for attachment to a hand piece. The radius of curvature of aspiration tube 302 can be selected to be extend the entire length of aspiration tube 302 or a portion of the length. One or more sections of aspiration tube 302 can remain straight when the tube is curved. As shown in FIG. 5 , the curved section may be relatively small and have a small radius, while the remainder of aspiration tube 302 remains straight to give the instrument a bent appearance. For example a straight portion can run from attachment portion 306 to the curved section and another straight portion can run from the curved section to infusion/aspiration tip 304 . In other embodiments, a bent profile can be achieved using a non-curved interface between straight sections.
[0032] While the disclosure has been described with reference to particular embodiments, it should be understood that the embodiments are illustrative and that the scope of the invention is not limited to these embodiments. Many variations, modifications, additions and improvements to the embodiments described above are possible. It is contemplated that these variations, modifications, additions and improvements fall within the scope of the invention as detailed in the following claims. | Embodiments described herein provide ophthalmic surgical instruments. One embodiment provides an instrument including an infusion sleeve, aspiration tube, and infusion/aspiration tip. The sleeve can include a body defining an infusion channel. The tube can be in the infusion channel and define an aspiration channel. The tip can conform to the distal end of the tube. The tip can seal a gap between the sleeve and tube and can include a flange with a profile (e.g., a tapered portion) corresponding to the profile of the sleeve. The sleeve and tip can be keyed such that the sleeve directs fluid in one direction and the tip draws fluid perpendicularly from that direction. The tip's aspiration channel can extend distally beyond its aspiration port. The tip can extend to a point adjacent to an infusion port of the sleeve. A disposable component (including an aspiration tube and infusion/aspiration tip) for use with instruments is provided. | 0 |
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
This patent application is not the direct outgrowth of federally sponsored research.
BACKGROUND OF THE INVENTION
The invention is in the field of chemical reactor design, applied to the conversion of a solid (usually in the form of a slurry) to soluble products, which are subject to decomposition. The objective of the design is to obtain high conversion of the solids while maintaining low decomposition of the soluble product(s). Of particular interest in this application is the hydrolysis of cellulose and hemicellulose in the solid to form sugars. The solid may be a form of biomass, such as wood, or a product derived from biomass, such as paper. The cellulose and hemicellulose in biomass can be hydrolyzed using an acid or base catalyst to form sugars, which are soluble and subject to decomposition. In some cases it is desired to convert the hemicellulose while leaving the cellulose largely untouched, so that the cellulose can be subsequently converted to sugars using enzyme catalysts. This partial hydrolysis is often referred to as pretreatment or prehydrolysis.
Many reactor configurations have been considered in the published literature for the hydrolysis of biomass to sugars. The U.S. WWII effort to build a commercial reactor used a percolation reactor (Katzen, ISAF XIII, International Symposium on Alcohol Fuels Stockholm, Sweden, Jul. 3-7, 2000) 1 in which an acid solution was applied to a bed of wood chips, and the sugar containing solution was withdrawn from the bottom of the reactor. Recently this type of reactor has been referred to as a ‘flow-through’ reactor since the liquid flows through a bed of solids.
1 These refer to the citation numbers given in the Information Disclosure forms.
Grethlein, U.S. Pat. No. 4,237,226 2 , discloses the use of a continuous co-current plug-flow reactor for the pre-hydrolysis of biomass.
Converse et al., U.S. Pat. No. 4,556,430 3 , discloses the use of a non-aqueous immiscible carrier fluid in a continuous plug flow reactor in order to convey the solids and, at the same time, increase the sugar concentration in the aqueous phase.
Wright et al., U.S. Pat. No. 4,615,742 4 discloses the use of a series of fixed-bed flow-through reactors in which the liquid flow is switched so as to approximate counter-current flow.
Converse et al., U.S. Pat. No. 4,818,295 5 discloses the use of a cyclone reactor in order to obtain counter-current flow between the solids and the liquid.
None of the above patents, and many others that teach methods of hydrolyzing cellulose and hemicellulose, make use of a cross-flow pattern. The patents referenced in this paragraph do speak of cross-current flow pattern. Torget et al., U.S. Pat. Nos. 5,424,417 6 ; 5,503,996 7 ; and 5,705,369 8 discloses the use of a flow-through reactor for the prehydrolysis if lignocellulosic material. Specific to the current application the patent states. “the lignocellulose solids may be stationary, travel in a counter-current or cross-current fashion. . . . One can perform a solid-liquid separation in the flow-through system by using a screw-like device to cause the separation continuously during or at the end of prehydrolysis. Important to the process is the movement and removal of fluid during the prehydrolysis to separate soluble products as they are released from the solid lignocellulosic residue.” (col. 6, lines 47-57, U.S. Pat. No. 5,503,996) 7 Furthermore it states: “such a reactor would have lignocellulosic material driven through the reactor while fluid is passed through the material, typically in a counter-current or cross-current manner. . . . Alternatively, the lignocellulosic substrate may be driven laterally while fluid is applied on top and allowed to percolate down to be removed at the bottom.” (col. 6, line 66-col. 7, line 10, U.S. Pat. No. 5,503,996) 7 The same statement can be found in the other two patents cited above, as well. O. Bobleter and H. Binder, German Patent No. DE 3225074 14 , include, without comment on implimentation, the crossflow of water to solubilize and remove hemicellulose and portions of the lignin; it does not include the use of an acid catalyst nor the conversion of cellulose.
The current application uses these principles but differs from the patents cited above in the following aspects: 1) a unique geometry for effecting cross flow is described, 2) it is not limited to prehydrolysis, and 3) a computer simulation, employing cross-flow reactor
Recently the desirability of forcible expression of the liquid in a so-called ‘shrinking-bed’ reactor has been analyzed and demonstrated (Pettersson et al., 22nd Symp. on biotech, for fuels and chemicals, Gatlinburg, Tenn. May 7-11, 2000 Poster 3-48 9 ; Lee et al, Biores. Tech. 71, 29-39, 2000 10 ; Torget et al., Ind. Eng. Chem. Res., 39, 2817-2815, 2000 11 ).
Torget et al., U.S. Pat. No. 6,022,419 12 , discloses the use of a continous shrinking-bed flow-through reactor for the hydrolysis and fractionation of lignocellulosic biomass. The patent states that “the invention consists of a series co-current, counter-current or single pass, isolated stages . . . ” No mention is made of cross-current flow or withdrawal of the excess liquid in the radical direction.
BRIEF SUMMARY OF THE INVENTION
The present invention is a reactor system for converting solids to soluble products which are subject to decomposition. An example is the conversion of biomass to such products, and includes the conversion of hemicellulosic, cellulosic and lignocellulosic substances to sugars. The term biomass, as used herein, means substances that are produced by photosynthesis, and includes hemicellulosic, cellulosic and lignocellulosic substances, both natural and processed, as well as natural or manufactured organic materials more broadly. Emphasis in the following discussion is placed on producing sugars for biomass, but the invention is broader, and is applicable to the conversion of any solid to liquid products which themselves are subject to decomposition.
The essence of the invention is that liquid, containing products from the reacting solids, is squeezed from the slurry by a compressive force and removed from the reacting zone by passage through an outer porous wall. This is done in order to minimize the residence time of the soluble products in the reactor, and thereby, minimize their decomposition. The liquid product stream may be thermally or chemically quenched as it is withdrawn to prevent further chemical reaction. The direction in which the exiting liquid moves is approximately perpendicular to the direction in which the slurry moves.
Liquid, possibly containing acid or base, may, or may not, be admitted into the reactor through the porous wall of the inner tube to aid in the washing of soluble product through the outer wall of the reactor. This liquid may assist in the temperature control of the reacting solids and may be mixed with steam. It may also contain chemicals such as a mineral acid to affect the reaction.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic representation of one configuration of the reactor. The slurry is fed into annulus A at position 1 . Liquid or steam may be forced into tube C at position 2 and from tube C through a porous wall E into annulus A. The slurry is compressed by an auger, or other means, so a to squeeze water out of the slurry as it proceeds through annulus A. Liquid from the slurry flows through porous wall D into annulus B where the reaction is quenched. Liquid products exit through 3 ; remaining slurry exits through 4 . It may be desirable to add a liquid containing chemicals at 5 in order to chemically quench the reaction.
FIG. 2 shows a variation of FIG. 1 in which tube C has been removed, creating tube A and leaving annulus B. Slurry enters A at 1 and is forced through tube A. As it reacts, some of the solids are converted to liquids. The excess liquids are forced through the porous wall D into annulus B. Liquid products exit through 3 ; remaining slurry exits through 4 . It may be desirable to add a liquid containing chemicals at 5 in order to chemically quench the reaction.
FIG. 3 shows a variation of FIG. 1 in which wall D has non-porous as well as porous sections, and annulus B has a partition so the various soluble products, such as xylose and glucose, can be separated. One product would be withdrawn through 5 and the other through 3 . It may be desirable to add a liquid containing chemicals at 6 in order to chemically quench the reaction.
DETAILED DESCRIPTION OF THE INVENTION
In FIG. 1 there is shown a system for producing a product, such as sugars, from a two phase mixture, typically a liquid-solid mixture, which introduced to the system at 1 , at the entrance of Annulus A. This slurry of biomass chips is conveyed horizontally through Annulus A by a auger, or some other means, through a restriction at 4 . The auger, if employed, fits tightly against the inside of Porous Wall D, and scrapes the wall as it turns, thus removing solids from the wall. Liquid is introduced at 2 , at the entrance of Tube C, at a pressure higher than the pressure in Annulus A. Thus, this liquid flows through Porous Wall E into Annulus A. The liquid entering at 2 may be preheated; its temperature may be controlled as it flows through Tub C by heaters or steam injector(s) placed inside Tube C. Thus the temperature of the liquid in C can be caused to increase as it flows through the reactor; since some of this liquid flows through Wall E, the temperature of the slurry in A can also be increased as it flows through the reactor. The liquid entering at 2 may also contain catalysts, e.g., an acid, solvents, or other chemicals, thereby affecting the chemical composition and the reaction(s) in A.
The slurry entering at 1 may contain a catalyst, such as sulfuric acid and it may be preheated. As the slurry flows through Annulus A, a portion of the solids is liquefied. Due to the compression of the slurry, some of the liquid in Annulus A is forced into Annulus B. This transfers some of the soluble products from Annulus A to Annulus B. This removal of soluble products, such as sugars, from A to B is furthered by the liquid entering A from C. In addition to temperature control, the introduction of liquid, from C into A, provides a means for quickly removing the soluble products from the slurry, where they are formed, in a radical direction which is much shorter than the axial dimension of the reactor. This is done in order to minimize the decomposition of desirable soluble products formed in the reaction. This movement of the liquid in the radial direction in order to reduce the residence time of the soluble products, is a principal feature of the invention.
Annulus B is maintained at a lower pressure than Annulus A; hence, some of the liquid entering Annulus B from A, flashes, reducing the temperature abruptly and quenching the reactions. This flashing also increases the concentration of soluble products in the liquid in B. It may be desirable to feed liquid containing chemicals into B at 5 ; for example, it may be desirable to add a base in this stream in order to neutralize an acid catalyst present in the liquid coming from A. In the application of this system to the hydrolysis of biomass, the liquid in B contains soluble sugars. In the case where it is desirable to separate sugars formed from the hemicellulose from those formed from cellulose, at higher temperatures further down the reactor, partitions are be placed in Annulus B, as shown in FIG. 3, to at least partially separate the two products streams. This is just one example of how the system could be used to separate various products, such as proteins in addition to carbohydrates, in the refining of biomass.
A tendency of Porous Wall D to plug up with solids could be partially offset by the scraping action of the auger, if used. It could also be offset by periodically increasing the pressure in Annulus B for a brief period of time which would back-flush the porous wall, D.
In order to further the solids washing action of the liquid entering A from C, the auger may be shaped to cause regions where the liquid fraction in the slurry increases, followed by regions where it is again decreased in order to squeeze out the liquid which contains the soluble product.
Soluble products exit the reactor at 3 , or, in the case that partitions are installed in Annulus B, at various points from Annulus B. The remaining solids exit from 4 .
This reactor system could also be modified to use different liquids at different points in the reactor by installing partitions in Tube C. It would thus be quite generally useful in the refining of wood. If delignifying solvents were used, the remaining solids (e.g., paper pulp) would be a valuable product.
Extension I
Tube C contains a partition so that at least the initial portion can be filled with steam rather than a liquid. In this case steam flows through the porous wall, E, and condenses in Annulus A. This has the advantage in that the high latent heat of the steam conveys much more heat into A per kg of added fluid; hence, for a given temperature increase, the dilution of the material in A would be much less. Hence the concentration of the soluble product would be greater. In some cases it may be desirable to fill the entire of Tube C with steam.
Extension II
As shown in FIG. 2 there is only one annular region, B. The liquid that flows into Annulus B is that expressed due to the liquefying reaction and the compression of the solids in A . Unlike in FIG. 1, this liquid is not diluted by liquid being added to C. This would increase the concentration of the soluble product, but at the expense of yield since the soluble product would no longer be washed from the solids that remain in A. The simulated performance of this configuration is presented in Example 5 below.
Extension III
Combined counter-current and radial flows. By introducing liquid near the outlet of Annulus A and making part of the wall, D, non-porous it would be possible to have counter-current flow in the right and end of Annulus A. This flow could then be withdrawn at the upper portion of the reactor where a porous outer wall would be used in Annulus A. This could be combined with a non-porous section in the upper portion of Annulus A to permit withdrawal of the soluble products at the desired region. As shown in FIG. 3 the use of alternating sections of porous and non-porous sections of the outer wall of Annulus A would allow separate product streams to be withdrawn; hence biomass might be fractionated into a number of products (e.g., lignin, glucose, xylose, proteins). FIG. 3 is drawn to demonstrate the withdrawal of two product streams; the concept could be extended to more than two product streams, or only one, if desired.
Extension IV
To control the flow rate between Annulus A and B, a second porous pipe section is installed so that it covers the porous section in the outer wall of Annulus A. When rotated so that the pores (holes) match up, the flow is greater; when rotated so that there is a mismatch so that the hole in one is blocked, at least partially, by the solid portion in the other, the flow is reduced.
Extension V
The fluid fed through tube C into annulus A is immiscible with water. This would still produce a high yield since the sugar is swept from the annulus A into annulus B where the reaction is quenched. However, this modification would also produce a high concentration since the sugars would be extracted into the aqueous portion and would not be diluted. This principle was patented in the context of a co-current plug flow reactor (U.S. Pat. No. 4,556,430). Here it is extended to a cross-current radial flow reactor.
EXAMPLES
The following is based on computer simulations. The corresponding theory is presented in an unpublished paper, Simulation of a Cross-Flow Shrinking-Bed Reactor for the Hydrolysis of Lignocellulosics by A. O. Converse, which is attached 13 .
In all simulations the biomass composition was: 41% glucan, 5% fast glucan (which is converted instantaneously) 24% xylan and 30% inerts, and the values for the ‘kinetic constants’ are computed from the following equations: (C a is in weight % acid.)
Cellulose to glucose (Grethlein and Converse, 1982) k c = 5.39 e22 * C a 1.55 * exp ( - 47100 1.987 * T ) hr - 1 = 461 at 240 ° C . and 1 % acid
Glucose to hmf (Grethlein and Converse, 1982) k g = 2.38 e11 * C a 0.569 * exp ( - 21000 1.987 * T ) hr - 1 = 268 at 240 ° C . and 1 % acid
Hemicellulose to xylose (Kwarteng, 1983; and Converse et al., 1989) k h = 3.74 e15 * C a 1.17 * exp ( - 27827 1.987 * T ) hr - 1 = 5 , 220 at 240 ° C . and 1 % acid
Xylose to furfural (Kwarteng, 1983; and Converse et al., 1989) k x = 1.40 e14 * C a 0.688 * exp ( - 27130 1.987 * T ) hr - 1 = 385 at 240 ° C . and 1 % acid
Dissolution of half of the inserts:
k I =300 (a dummy value)
Simulation Results
Example 1
The plug flow results in Table 1 are typical of what has been predicted and obtained. Values close to 60% yield require 1% acid and 260° C. These results are presented here to provide a check on the simulation program, and for comparison with Table 2. The concentrations presented in Table 1 are those that exist when the corresponding yield is maximum. They both could not be obtained in a single plug-flow reactor.
Example 2
Simulations of an ideal cross flow reactor are presented in Table 2. Through out Table 2 the flow of liquid per unit reactor length from Tube C to Annulus A is given by Rww*(Cg+Cx). Table 2a presents results at 240° C. At this temperature and the indicated flow rate, the reactor is short, 0.1 m. As the cross-flow wash rate, Rww, is increased, the sugar yield increases but the sugar concentration decreases, as expected. The results are sensitive to the ratio of occluded water to solids, Rws. All the runs show reasonably high concentrations and yields in excess of 80%.
Example 3
Table 2b presents results at 200° C. At this temperature and the indicated flow rate, the reactor is 3 m. In run 8 the yields are good but the concentrations are low because the washing rate per unit reactor length is still high and the reactor is 30 times longer than in Table 2a. As shown in Run 9, the concentrations can be increased but still fall short of what is desired, while the yields fall below what is desired.
Example 4
Table 2c presents results at 200° C. in a short, 0.3 m, reactor, as might be the case in a pretreatment reactor. Only the xylose results are shown because most of the glucan has been remains unconverted. Comparison with Row 1 in Table 1 indicates that the cross flow reactor can obtain a higher yield than the plug flow reactor but at a lower concentration.
Example 5
Table 2d presents the results when there is no wash water introduced, but free liquid (i.e. not occluded) is able to escape through the outer porous wall. The yields and concentrations in Table 2d are at the position where the combined yield, of glucose or xylose in the sidestream and in the main axial flow are at their combined maximum values for each of the two sugars. Compared to the plug flow reactor (Table 1) both the yields and concentrations are higher. This comparison clearly demonstrates the advantage of a ‘shrinking-bed’ reactor in which excess liquid is removed as soon as possible
TABLE 1
Simulation Results for Plug Flow - Glucose and Xylose from Mixed Hardwood
(Rws = ratio of occluded water to solids in the slurry)
Concentration, g/L
Length
Temp
Acid
Maximum Yield, %
at Max. Yield
m
C.
%
Rws
Glucose
Xylose
G
X
Program
3
200
1
2
12
77
25
90
CFR28
3
200
1
10
13
80
6.6
21
″
0.3
240
1
2
44
78
85
89
″
0.3
240
1
10
46
81
22
21
″
0.1
260
1
2
63
79
117
87
″
0.1
260
1
10
65
81
31
21
″
Table 2 Simulation Results for Cross Flow—Glucose and Xylose from Mixed Hardwood
TABLE 2a
(Reactor length, L = 0.1 m.)
Rww
T
Yg
Yx
C gss
C xss
C gss +
Run #
m 2 h −1
Rws
° C.
%
%
g/L
g/L
C xss
Program
Date
1
3000
2
240
86
89
36
35
71
CFR26
Dec. 27, 2000
2
″
3
″
83
87
31
30
61
″
″
3
″
1
″
88
91
47
45
92
″
″
4
2000
2
″
83
87
43
42
85
″
″
5
4000
″
″
87
90
32
31
62
″
″
6
″
1
″
89
92
41
39
80
″
″
7
400
2
″
69
73
76
75
151
″
″
(Inlet solids flow, M s (0) = 1000 kg/hr.; Cross-section area, A = 0.1 m 2 ; Density, ρ = 1000 kg/m 3 ; Acid concentration, C a = 1%)
(Rww = wash water addition constant, m 2 h −1 (The flow of liquid per unit reactor length from Tube C to Annulus A is given by Rww*(Cg + Cx)); Rws = ratio of occluded water to solids in the slurry; Yg = glucose yield, % ; Yx = xylose yield, %; Cgss = concentration of glucose in the product withdrawn from
#Annulus B at position 3, g/L; Cxss = concentration of xylose at the same location; Cgss + Cxss = total sugar concentration, g/L.
TABLE 2b
(Reactor length, L = 3.0 m.)
Rww
Yg
Yx
C gss
C xss
C gss +
Run #
m 2 h −1
Rws
T
° C.
%
%
g/L
C xss
Program
Date
8
4000
2
200
83
96
5.7
6.1
12
CFR27
Dec. 29, 2000
9
400
″
″
60
87
14.7
19.6
24
″
″
TABLE 2c
(Reactor length, L = 0.3 m.)
Rww
Yg
Yx
C gss
C xss
C gss +
Run #
m 2 h −1
Rws
T
° C.
%
%
g/L
g/L
Program
Date
10
4000
2
200
96
24
CFR27
Dec. 29, 2000
11
400
″
″
85
67
″
″
(M s (0) = 1000 kg/hr., A = 0.1 m 2 , L = 0.3 m, T = 200° C., ρ = 1000 kg/m 3 , C a = 1)
TABLE 2d
(Rww, wash liquid rate = 0)
T
Ygo
Lgo
Cgo
Yxo
Lxo
Cxo
Run #
Rws
° C.
%
m
g/L
%
m
g/L
Program
Date
12
2
240
55
0.037
137
79
0.0104
204
CFR30
Jan. 22, 2001
13
10
240
62
0.148
30
83
0.0412
42
″
″
14
2
260
77
0.0087
191
81
0.0036
208
″
″
15
10
260
83
0.0343
40
84
0.0142
42
″
″
(Lgo = reactor length at which the sum of glucose in Annulus A and the glucose in Annulus B is maximum; Lxo = reactor length at which the sum of xylose in Annulus A and the xylose in Annulus B is maximum; Cgo = concentration of glucose in the mixture of the two streams at Lgo, g/L; Cxo = concentration of xylose in the
#mixture of the two streams at Lxo, g/L | A process is described for the production of decomposable soluble products from a slurry of solids in which the slurry is convey axially through the reactor and excess liquid is removed radially through the walls of the reactor. The primary example is the hydrolysis of lignocellulosic biomass to form sugars, usually using an acid catalyst. In one variation of the process liquid and possibly steam are added through the inner wall of the reactor to provide additional flow in the radial direction and to control the temperature. Pressures are maintained such that the product stream is thermally quenched due to partial flashing as it leaves the reactor. | 2 |
FIELD OF THE INVENTION
The present invention relates to a polyoxyalkylene derivative having a carboxyl group and hydroxy groups useful for producing an aqueous polyurethane resin and as a modifier for various kinds of polymers, a method of producing the polyoxyalkylene derivative, and a polyurethane resin using the polyoxyalkylene derivative.
BACKGROUND OF THE INVENTION
Recently, from the view points of the dangerousness of an inflammation, an explosion, etc., the toxicity to human being, the occurrence of environmental pollution, etc., caused by organic solvents, the tendency of using aqueous resins in place of organic solvent type resins conventionally used has been increased. In particular, in regard to aqueous polyurethane resins, polymers having characteristic excellent properties are obtained by reacting many isocyanate compounds and polyol compounds each having different structures together with a chain-lengthening agent from soft elastomers to hard plastics, various investigations for obtaining aqueous polyurethane resins have been proceeded in a wide field of coating materials, adhesives, impregnants, etc.
As aqueous polyurethane resins, anion type resins, cation type resins, and nonion type resins are known but from the points of the stability with the passage of time, the physical properties thereof, the miscible stability with other emulsions or various kinds of pigments, etc., a self-emulsifying aqueous polyurethane having a carboxyl group introduced into the polyurethane resin skeleton has been watched with keen interest.
An ordinary method of introducing a carboxyl group into a polyurethane resin is practiced by reacting a polyol compound with an excessive amount of a polyisocyanate compound to synthesize an isocyanate group-terminated prepolymer and then reacting the prepolymer with a compound having at least one carboxyl group and two active hydrogen atoms capable of reacting with isocyanate groups in the molecule.
As a compound for introducing a carboxyl group into a polyurethane skeleton, the compounds described in D. Dieterich, Progress in Organic Coatings, 4, 281-340 (1981), etc., are known but these compounds have the problems that they all have a high melting point, the solubility thereof in polyurethane resins and organic solvents being used for polyurethane resins is poor, and the introduction of a carboxyl group into the resin skeleton is not easy.
As a compound capable of relatively easily introducing a carboxyl group into the polyurethane resin skeleton in conventionally known compounds, there is 2,2'-dimethylolpropionic acid but the compound has a high melting point and since the solubility of the compound in polyurethane resins and organic solvents is poor, it is required to use an organic solvent having a high polarity such as N-methyl-2-pyrrolidone in the case of using the foregoing compound. However, it is difficult to remove N-methyl-2-pyrrolidone, etc., which is a water-soluble high boiling solvent, from an aqueous polyurethane resin and hence there is a problem that the aqueous polyurethane resin obtained by the method is used in the state of containing the organic solvent.
SUMMARY OF THE INVENTION
The present invention has been made under these circumstances.
A first object of the present invention is to provide a polyoxyalkylene derivative which can easily introduce a carboxyl group into a polyurethane resin skeleton, etc., has a low melting point or is in a liquid state at normal temperature, and contains at least one carboxyl group and hydroxy groups in the molecule.
A second object of the present invention is to provide a method of producing the foregoing polyoxyalkylene derivative.
A third object of the present invention is to provide a carboxyl group-containing polyurethane resin particularly suitable for producing an aqueous polyurethane resin, comprising the foregoing polyoxyalkylene derivative, a polyisocyanate compound, and, if necessary, a polyol compound and a chain-lengthening agent.
As the result of various investigations for attaining the objects described above, the inventors have discovered that a novel polyoxyalkylene derivative having a carboxyl group and hydroxy groups is synthesized by addition-polymerizing a cyclic ether to the hydroxy group of a compound having a carboxylic acid alkyl ester and hydroxy groups to synthesize a polyoxyalkylene derivative having a carboxylic acid alkyl ester and hydroxy groups and then hydrolyzing the carboxylic acid alkyl ester of the polyoxyalkylene derivative, and have accomplished the present invention based on the discovery.
That is, the present invention is as follows.
1. A polyoxyalkylene derivative having a carboxyl group and hydroxy groups represented by formula (I): ##STR2## wherein R 1 represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms; R 2 represents an alkylene group having from 1 to 6 carbon atoms or an arylene group having from 6 to 8 carbon atoms; A represents an alkylene group having from 4 to 7 carbon atoms; B represents an alkylene group having from 2 to 6 carbon atoms; l represents from 0 to 2; m represents 0.1 to 35; n represents from 0.1 to 50; and 0.5<(m+n)<50.
2. A method of producing the foregoing polyoxyalkylene derivative having a carboxyl group and hydroxy groups by addition-polymerizing a 5-membered cyclic ether and a 3- or 4-membered cyclic ether to a compound having a carboxylic acid alkyl ester group and hydroxy groups represented by formula (II) using a Lewis acid to synthesize a polyoxyalkylene derivative having a carboxylic acid alkyl ester group and hydroxy groups, and then hydrolyzing the polyoxyalkylene derivative in the presence of a base or an acid: ##STR3## wherein R represents an alkyl group having from 1 to 8 carbon atoms; R 1 represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms; R 2 represents an alkylene group having from 1 to 6 carbon atoms or an arylene group having from 6 to 8 carbon atoms; and l represents an integer of from 0 to 2.
3. A carboxyl group-containing polyurethane resin comprising the foregoing polyoxyalkylene derivative having a carboxyl group and hydroxy groups, a polyisocyanate compound, and, if necessary, a polyol compound and a chain-lengthening agent.
DETAILED DESCRIPTION OF THE INVENTION
Then, the present invention is described in detail.
The polyoxyalkylene derivative represented by formula (I) is a mixture of the compounds which are different in the number of the --(AO)-- moiety and the number of the --(BO)-- moiety. The numerals m and n in formula (I) mean an average of the number of --(AO)-- and an average of the number of --(BO)--, respectively. The numerals m and n are calculated using the average molecular weight obtained by gel permeation chromatography and the information of NMR analysis.
R 1 preferably represents CH 3 --, R 2 preferably represents --CH 2 --, A preferably represents --CH 2 CH 2 CH 2 CH 2 -- or ##STR4## B preferably represents ##STR5## l preferably represents zero, m preferably represents 1 to 15, and n preferably represents 0.5 to 5.
The compound having a carboxylic acid alkyl ester and hydroxy groups being used in the present invention is the compound shown by following formula (II): ##STR6## wherein R represents an alkyl group having from 1 to 8 carbon atoms; R 1 represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms; R 2 represents an alkylene group having from 1 to 6 carbon atoms or an arylene group having from 6 to 8 carbon atoms; and l represents an integer of from 0 to 2.
As specific examples of the compound represented by formula (II), there are the alkyl esters having from 1 to 8 carbon atoms of a compound having one carboxyl group and two hydroxy groups, such as 2,2-bis(hydroxymethyl)propionic acid, 4,4-bis(4-hydroxyphenyl)valeric acid, bis(4-hydroxyphenyl)acetic acid, etc.
As the Lewis acid being used in the present invention, there are metal halides or non-metal halides, such as boron trifluoride, phosphorus pentafluoride, antimony pentafluoride, antimony pentachloride, aluminum chloride, ferric chloride, titanium tetrachloride, tin tetrachloride, lithium hexafluorophosphate, etc.; solid acids such as silicon dioxide, titanium dioxide, zirconium dioxide, aluminum oxide, etc., the solid acids obtained by adding the foregoing halides to the foregoing solid acids; and complexes of boron trifluoride, antimony pentafluoride, etc., and a chain or cyclic ether such as dimethyl ether, diethyl ether, tetrahydrofuran (THF), etc. Among them, a complex of boron trifluoride and THF is particularly preferred.
As the 3- or 4-membered cyclic ether compound being used in the present invention, there are 3-membered cyclic alkylene oxides such as ethylene oxide, 1,2-propylene oxide, 1,2-butylene oxide, 2,3-butylene oxide, epichlorohydrin, etc., and 4-membered cyclic alkylene oxides such as 1,3-propylene oxide, 1,3-butylene oxide, 2-methyl-1,3-epoxypropane, 2,2-dimethyl-1,3-epoxypropane, etc. Among them, ethylene oxide and propylene oxide are particularly preferred.
These Lewis acids can be used singly or as a mixture thereof.
As the 5-membered cyclic ether compound being used in the present invention, there are tetrahydrofuran, 3-methyltetrahydrofuran, 3-ethyltetrahydrofuran, 2-methyltetrahydrofuran, etc.
In the case of practicing the present invention, the kinds and the amounts of the compound having a carboxylic acid alkyl ester group and hydroxy groups, the cyclic ether compound, and the catalyst to be used must be selected according to the molecular structure and the molecular weight of the desired polyoxyalkylene derivative.
In the case of addition polymerizing a 5-membered cyclic ether to the hydroxy group, since the addition polymerization does not proceed using a Lewis acid alone, the addition polymerization is practiced by adding a 5-membered cyclic ether to the compound having a carboxylic acid alkyl ester group and hydroxy groups to dissolve the compound, then adding a Lewis acid to the solution, and gradually adding dropwise a 3- or 4-membered cyclic ether to the mixed solution to carry out the reaction. As to the amount ratio of each component to the hydroxy group of the compound of formula (II), the amount of the Lewis acid is generally from 0.01 to 2 moles, preferably from 0.04 to 0.5 moles, and the amount of the 3- or 4-membered cyclic ether is generally from 0.5 to 50 moles and preferably from 1 to 10 moles, per mole of the hydroxyl group. The amount of the 5-membered cyclic ether is determined by the relation with the amount of the 3- or 4-membered cyclic ether, but is usually used in an excessive amount since the 5-membered cyclic ether serves as a solvent, and the unreacted ether is recovered after the polymerization reaction for reuse.
When it is necessary to improve the solubility of the product, an inert organic solvent such as toluene, xylene, diethyl ether, dibutyl ether, etc., may be used.
The reaction is carried out generally at a temperature of from -20° C. to 60° C., and preferably from 0° C. to 40° C. It is preferred that the reaction is carried out under a substantially water free condition, e.g., under a dry nitrogen gas stream. The reaction is generally conducted from 1 to 15 hours in the foregoing temperature range and then from 2 to 6 hours at a temperature range of from 0° C. to 10° C.
The polymerization finished liquid is neutralized with an aqueous solution of an alkali such as sodium hydroxide, potassium hydroxide, sodium hydrogencarbonate, etc., and after removing the unreacted cyclic ether by distillation, etc., the aqueous layer containing the catalyst decomposition products is separated. When the neutralization of the solid acid, etc., is unnecessary, after separating the catalyst component by subjecting the polymerization finished liquid to an adsorption filtration as it is, the unreacted cyclic ether is recovered. The organic layer containing a polymer produced is purified by a known method such as water washing, an adsorption, a filtration, etc., to provide the polyoxyalkylene derivative having a carboxylic acid alkyl ester group and hydroxy groups.
The polyoxyalkylene derivative having a carboxyl group and hydroxy groups of the present invention is obtained by adding an aqueous solution of an alkali such as sodium hydroxide, potassium hydroxide, etc., to the polyoxyalkylene derivative having a carboxylic acid alkyl ester group and hydroxy groups obtained by the method described above and carrying out the hydrolysis reaction (saponification reaction). The hydrolysis reaction is efficiently carried out at a temperature of from 60° C. to 100° C., using an alkali at least in the equimolar amount to the carboxylic acid alkyl ester group, and if necessary, adding a water-soluble solvent such as a lower alcohol (e.g., ethanol) and THF. The hydrolysis reaction can be also practiced in the presence of an acid catalyst such as hydrochloric acid, sulfuric acid, a solid acid, etc.
There is no particular restriction on the polyisocyanate compound being used in the present invention and there are aliphatic, aromatic, and cyclic diisocyanate compounds such as tolylene diisocyante, 4,4'-diphenylmethane diisocyanate, 3,3'-dimethyldiphenylmethane-4,4'-diisocyanate, p-phenylene diisocyanate, 1,5-naphthalene diisocyanate, m-xylene diisocyanate, tetramethylxylene diisocyanate, 1,6-hexamethylene diisocyanate, 1,4-tetramethylene diisocyanate, trimethylhexamethylene diisocyanate, 1,3-bisiisocyanate methylcyclohexane, 4,4'-dicyclohexylmethane diisocyanate, 1,4-bisisocyanate methylcyclohexane, etc.
Any conventionally known polyol may be used in combination with the polyoxyalkylene derivative of formula (I) for the production of the polyurethane resin according to the present invention, and the examples thereof include polyether polyols such as polyoxypropylene polyol, polyoxytetramethylene glycol, etc.; polyester polyols such as polybutylene adipate polyol, polyhexamethylene adipate polyol, polycaprolactone polyol, polyhexamethylene carbonate, etc.
As the chain-lengthening agent being used in the present invention, there are glycols such as ethylene glycol, butanediol, etc.; diamine compounds such as ethylenediamine, isophoronediamine, hydrazine, etc.
The production of the aqueous polyurethane resin using the polyoxyalkylene derivative having a carboxyl group and hydroxy groups of the present invention is described below.
That is, by reacting a conventionally known polyol and an excessive amount of a polyisocyanate compound in the presence or absence of a solvent, an isocyanate group-terminated prepolymer is synthesized and then by reacting the prepolymer and the polyoxyalkylene derivative having a carboxyl group and hydroxy groups of the present invention, an isocyanate group-terminated prepolymer having a carboxyl group is synthesized. Then, the aqueous polyurethane resin of the present invention is synthesized by mechanically dispersing and emulsifying the prepolymer in deionized water containing an inorganic base such as sodium hydroxide, etc., or an organic base such as triethylamine, tributylamine, dimethylethanolamine, morpholine, etc., and, if necessary, a chain-lengthening agent such as ethylenediamine, isophoronediamine, etc.
In other method, the aqueous polyurethane resin can be also synthesized by polymerizing the isocyanate group-terminated prepolymer having a carboxyl group with the foregoing chain-lengthening agent such as ethylenediamine, etc., and after making the carboxyl group of the polymer to a salt thereof with an organic base such as triethylamine, etc., and mechanically dispersing and emulsifying the polymer in deionized water.
In the preparation of the aqueous polyurethane resin, the polyoxyalkylene derivative of formula (I), the other polyols, the polyisocyanate compound, and a chain-lengthening agent are generally added in an equivalent ratio of from 0.02 to 0.50, from 0 to 0.50, from 0.50 to 0.67, and from 0 to 0.50, respectively.
The polyoxyalkylene derivative having a carboxyl group and hydroxy groups of the present invention is in a liquid state at normal temperature or has a low melting point and since the polyoxyalkylene derivative can be reacted with the isocyanate group-terminated prepolymer without using solvent, in addition to the foregoing aqueous polyurethane resin, carboxyl group-containing polyurethane resins can be easily produced using the polyoxyalkylene derivative having a carboxyl group and hydroxy groups of the present invention by the methods of producing conventionally known polyurethane resins, and the polyurethane resins can be used as solvent-type adhesives and solventless-type thermoplastic urethane ionomers.
Then, the following examples are intended to illustrate the present invention practically but not to limit the invention in any way. In addition, all parts and percentages in these examples, unless otherwise indicated, are by weight.
In these examples, the hydroxyl value is the value measured by a pyridine-acetic anhydride method. The gel permeation chromatography (GPC) was practiced using a high-speed chromatography (manufactured by TOSOH CORPORATION) under the conditions of using TSK-G2500HX/G4000HX as the column and tetrahydrofuran as the solvent. The number average molecular weight by GPC was calculated by the calibration curve obtained by a commercially available polyethylene glycol standard reagent. Also, the 1H-NMR analysis and the 13C-NMR analysis were carried out by GSX-400 and FT-HNR (manufactured by JEOL Ltd.).
EXAMPLE 1
In a four neck 500 ml flask equipped with a stirrer, a thermometer, and a silica gel tube, the inside atmosphere of which was replaced with a nitrogen gas, were placed 57 parts of 2,2-dimethylolpropionic acid n-butyl ester and 144.2 parts of tetrahydrofuran. The mixture was stirred under cooling by an ice-cooling bath, 7.0 parts of boron trifluoride tetrahydrofuran complex was added thereto, and then 58.1 parts of propylene oxide was gradually added to the mixture by a dropping funnel over a period of 2 hours at a temperature of from 5° C. to 10° C. Thereafter, after carrying out the polymerization reaction for 4 hours at a temperature of from 5° to 10° C., 320 parts of an aqueous solution of 10% sodium carbonate was added to the reaction system to stop the polymerization.
Then, a distillation apparatus was set to the flask and unreacted tetrahydrofuran was distilled off by heating. After allowing to cool and stand the reaction mixture to form an upper organic layer and a lower aqueous layer, the lower aqueous layer was removed. Then, 200 parts of toluene and 100 parts of water were added to the organic layer and after raising the temperature thereof to 60° C., the mixture was stirred to wash the organic layer, and then allowed to cool and stand to form an upper organic layer and a lower aqueous layer, and the lower aqueous layer was removed. Further, water washing was conducted by adding 150 parts of water to the remaining organic layer and stirring the mixture at 60° C., allowed to stand to form an upper organic layer and a lower aqueous layer, and removing the lower aqueous layer, and the same water washing was repeated further three times. Then, toluene was distilled off from the organic layer under reduced pressure at 100° C. to provide 199 parts of a colorless transparent polymer which was in a liquid state at normal temperature.
The hydroxyl value (mgKOH/g) of the polymer was 151, the acid value thereof was 0.8, and the results of the GPC analysis and the NMR analysis showed that the 2,2-dimethylolpropionic acid n-butyl ester used as the raw material had been vanished and the polymer obtained was a tetrahydrofuran-propylene oxide-added copolymerized polyol having an average molecular weight of 738.
EXAMPLE 2
In a one liter four neck flask equipped with a stirrer, a thermometer, and a condenser were placed 150 parts of the copolymerized polyol synthesized in Example 1, 150 parts of toluene, 50 parts of tetrahydrofuran, and 200 parts of an aqueous solution of 30% sodium hydroxide and the hydrolysis was carried out with a hot water bath of 80° C. for 3 hours. After allowing to cool, the reaction mixture was neutralized using 4N hydrochloric acid, and after allowing to cool and allowing to stand the mixture to form an upper organic layer and a lower aqueous layer, the lower aqueous layer was removed. Further, water washing was conducted by adding 100 parts of water to the remaining organic layer and stirring the mixture at 60° C. for 20 minutes, allowed to stand to form an upper organic layer and a lower aqueous layer, and removing the lower aqueous layer, and the same water washing was repeated further three times. Toluene and tetrahydrofuran were removed under reduced pressure from the resulting organic layer to provide 121.5 parts of a transparent polymer which was in a liquid state having a viscosity of 1260 cps/22° C. at normal temperature.
The acid value of the polymer was 69, the hydroxyl value thereof was 137, and the average molecular weight by the GPC analysis was 817. Also, the result of the NMR analysis showed that the polymer had added thereto 3.1 moles of tetrahydrofuran and 2.1 moles of propylene oxide per one equivalent of the hydroxyl group of 2,2-dimethylolpropionic acid. The resulting polymer is a compound represented by formula (I) where R 1 =CH 3 --, R 2 =--CH 2 --, A=--CH 2 CH 2 CH 2 CH 2 -- ##STR7## m=3.1 and n=2.1.
EXAMPLE 3
In a 500 ml four neck flask equipped with a stirrer, a thermometer, and a silica gel tube were placed 152.1 parts of polyhexamethylene carbonate diol having a hydroxyl value of 54.2 (N-960R, trade name, made by Nippon Polyurethane Industry Co., Ltd.) and 28.7 parts of hexamethylene diisocyanate (HDI, trade name, made by Nippon Polyurethane Industry Co., Ltd.), after carrying out the reaction for 5 hours at 85° C. under a nitrogen gas stream, 39.9 parts of the polyoxyalkylene derivative having an acid value of 69 and a hydroxyl value of 137 synthesized in Example 2 was added to the mixture, and the reaction was carried out for 5 hours at 85° C. to provide an isocyanate group-terminated prepolymer having a carboxyl group.
Then, to the prepolymer were added 4.9 parts of an acetone solution containing 10% by weight hydrazine monohydrate and 150 parts of acetone and after carrying out the reaction for one hour at 40° C., 5.9 parts of triethylamine was added to the reaction mixture followed by stirring for 10 minutes at 40° C. to form the salt. Then, 360 parts of the prepolyer was forcibly emulsified in 250 parts of water under stirring in a homo-mixer. After distilling off acetone in the polyurethane emulsion obtained under heat and reduced pressure, the polyurethane emulsion aged for 5 days.
The polyurethane emulsion obtained was an emulsion having 36.5% by weight solid components, a viscosity of 3800 cps/20° C., and pH 7.5 and showing a good mechanical stability.
A film of about 200 μm in thickness was formed using the polyurethane emulsion at room temperature and heat-treated at 80° C. for 30 minutes. The tensile properties of the film were measured under two conditions, 1) at a normal state (20° C., 65% RH) and 2) after water immersion (the measurement was conducted by immersing the film in water (20° C., 24 hours), taking it out, and immediately the measurement was conducted at 20° C.). The obtained results are shown in Table below.
The tensile properties were measured using Tensilon UTM-III-100 (trade name, manufactured by Orienteck K.K.) at a tensile speed 500 mm/minute.
TABLE______________________________________ Tensile Properties 100% 300% TensileMeasured Modulus Modulus Strength ElongationCondition (kgf/cm.sup.2) (kgf/cm.sup.2) (kgf/cm.sup.2) (%)______________________________________Normal State 19 44 311 800Water 20 64 305 680Immersion______________________________________
COMPARATIVE EXAMPLE 1
The same reaction as in Example 3 was carried out except that 2,2-dimethylolpropionic acid was used in place of the polyoxyalkylene derivative of the present invention, and 152.1 parts of polyhexamethylene carbonate, 26.8 parts of hexamethylene diisocyanate, and 5.5 parts of dimethylolpropionic acid were used such that the ratio of idocyanate group/hydroxy group of the raw materials constituting the polyurethane resin and the carboxylic acid content in the polyurethane resin were same as those in Example 3. As the result thereof, a part of dimethylolpropionic acid was dissolved but the greater part thereof was not dissolved.
When the prepolymer obtained was forcibly emulsified in water using a homo-mixer, a good polyurethane emulsion was not obtained.
The polyoxyalkylene derivative of the present invention is an oligomer having a carboxyl group and hydroxy groups as different functional groups and has a low melting point or is in a liquid state at normal temperature, and the polyoxyalkylene derivative can be used as a hydrophilic property imparting agent and a modifier for polymers.
The carboxyl group-containing polyurethane of the present invention can be suitable used for producing, in particular, an aqueous polyurethane resin and the aqueous polyurethane resin has an excellent stability and excellent mechanical properties and can be used as coating materials, adhesives, binders, etc.
While the invention has been described in detail with reference to specific embodiments, it will be apparent to one skilled in the art that various changes and modifications can be made to the invention without departing from its spirit and scope. | Disclosed is a polyoxyalkylene derivative which is useful for a carboxyl group-containing polyurethane resin, can easily introduce a carboxyl group into a polyurethane resin skeleton, and has a low melting point or is in a liquid state at normal temperature. The polyoxyalkylene derivative is represented by formula (I): ##STR1## wherein R 1 represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms; R 2 represents an alkylene group having from 1 to 6 carbon atoms or an arylene group having from 6 to 8 carbon atoms; A represents an alkylene group having from 4 to 7 carbon atoms; B represents an alkylene group having from 2 to 6 carbon atoms; l represents from 0 to 2; m represents from 0.1 to 35; n represents from 0.1 to 50; and 0.5<(m+n)<50. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 09/428,990, filed Oct. 29, 1999, now U.S. Pat. No. 6,701,176 B1, which claims the benefit of U.S. Provisional Patent Application No. 60/106,965, filed Nov. 4, 1998. The aforementioned applications are hereby incorporated herein by reference in their entireties.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates in general to ablation and electrophysiologic diagnostic and therapeutic procedures, and in particular to systems and methods for guiding and providing visualization during such procedures.
2. Related Art
Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are of great concern in contemporary cardiology. They represent the most frequently encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, remain therapeutic challenges.
Atrial fibrillation affects a larger population than ventricular tachyarrhythmias, with a prevalence of approximately 0.5% in patients 50-59 years old, incrementing to 8.8% in patients in their 80's. Framingham data indicate that the age-adjusted prevalence has increased substantially over the last 30 years, with over 2 million people in the United States affected. Atrial fibrillation usually accompanies disorders such as coronary heart disease, cardiomyopathies, and the postoperative state, but occurs in the absence of any recognized abnormality in 10% of cases. Although it may not carry the inherent lethality of a ventricular tachyarrhythmia, it does have a mortality twice that of control subjects. Symptoms which occur during atrial fibrillation result from the often rapid irregular heart rate and the loss of atrio-ventricular (AV) synchrony. These symptoms, side effects of drugs, and most importantly, thromboembolic complications in the brain (leading to approximately 75,000 strokes per year), make atrial fibrillation a formidable challenge.
Two strategies have been used for medically managing patients with atrial fibrillations. The first involves rate control and anticoagulation, and the second involves attempts to restore and maintain sinus rhythm. The optimal approach is uncertain. In the majority of patients, attempts are made to restore sinus rhythm with electrical or pharmacologic cardioversion. Current data suggest anticoagulation is needed for 3 to 4 weeks prior to and 2 to 4 weeks following cardioversion to prevent embolization associated with the cardioversion. It remains controversial whether chronic antiarrhythmic therapy should be used once sinus rhythm is restored. Overall, pharmacologic, therapy is successful in maintaining sinus rhythm in 30 to 50% of patients over one to two years of follow-up. A major disadvantage of antiarrhythmic therapy is the induction of sustained, and sometimes lethal, arrhythmias (proarrhythmia) in up to 10% of patients.
If sinus rhythm cannot be maintained, several approaches are used to control the ventricular response to atrial fibrillation. Pharmacologic agents which slow conduction through the AV node are first tried. When pharmacologic approaches to rate control fail, or result in significant side effects, ablation of the AV node, and placement of a permanent pacemaker is sometimes considered. The substantial incidence of thromboembolic strokes makes chronic anticoagulation important, but bleeding complications are not unusual, and anticoagulation cannot be used in all patients. Medical management of atrial fibrillation, therefore, is inadequate.
In addition to medical management approaches, surgical therapy of atrial fibrillation has also been performed. The surgical-maze procedure, developed by Cox, is an approach for suppressing atrial fibrillation while maintaining atrial functions. This procedure involves creating multiple linear incisions in the left and right atria. These surgical incisions create lines of conduction block which compartmentalize the atrium into distinct segments that remain in communication with the sinus node. By reducing the mass of atrial tissue in each segment, a sufficient mass of atrial tissue no longer exists to sustain the multiple reentrant rotors, which are the basis for atrial fibrillation. Surgical approaches to the treatment of atrial fibrillation result in an efficacy of >95% and a low incidence of complications. Despite these encouraging results, this procedure has not gained widespread acceptance because of the long duration of recovery and risks associated with cardiac surgery.
Invasive studies of the electrical activities of the heart (electrophysiologic studies) have also been used in the diagnosis and therapy of arrhythmias, and many arrhythmias can be cured by selective destruction of critical electrical pathways with radiofrequency (RF) catheter ablation. Recently, electrophysiologists have attempted to replicate the maze procedure using radio-frequency catheter ablation, where heating destroys myocardium. The procedure is arduous, requiring general anesthesia and procedure durations often greater than 12 hours, with exposure to x-rays for over 2 hours. Some patients have sustained cerebrovascular accidents.
One of the main limitations of the procedure is the difficulty associated with creating and confirming the presence of continuous linear lesions in the atrium. If the linear lesions have gaps, then activation can pass through the gap and complete a reentrant circuit, thereby sustaining atrial fibrillation or flutter. This difficulty contributes significantly to the long procedure durations discussed above.
Creating and confirming continuous linear lesions could be facilitated by improved techniques for imaging lesions created in the atria. Such an imaging technique may allow the procedure to be based purely on anatomic findings.
The major technology for guiding placement of a catheter is x-ray fluoroscopy. For electrophysiologic studies and ablation, frame rates of 7-15/sec are generally used which allows an operator to see x-ray-derived shadows of the catheters inside the body. Since x-rays traverse the body from one side to the other, all of the structures that are traversed by the x-ray beam contribute to the image. The image, therefore is a superposition of shadows from the entire thickness of the body. Using one projection, therefore, it is only possible to know the position of the catheter perpendicular to the direction of the beam. In order to gain information about the position of the catheter parallel to the beam, it is necessary to use a second beam that is offset at some angle from the original beam, or to move the original beam to another angular position. Since x-ray shadows are the superposition of contributions from many structures, and since the discrimination of different soft tissues is not great, it is often very difficult to determine exactly where the catheter is within the heart. In addition, the borders of the heart are generally not accurately defined, so it is generally not possible to know if the catheter has penetrated the wall of the heart.
Intracardiac ultrasound has been used to overcome deficiencies in identifying soft tissue structures. With ultrasound it is possible to determine exactly where the walls of the heart are with respect to a catheter and the ultrasound probe, but the ultrasound probe is mobile, so there can be doubt where the absolute position of the probe is with respect to the heart. Neither x-ray fluoroscopy nor intracardiac ultrasound have the ability to accurately and reproducibly identify areas of the heart that have been ablated.
A system known as “non-fluoroscopic electroanatomic mapping” (U.S. Pat. No. 5,391,199 to Ben-Haim), was developed to allow more accurate positioning of catheters within the heart. That system uses weak magnetic fields and a calibrated magnetic field detector to track the location of a catheter in 3-space. The system can mark the position of a catheter, but the system relies on having the heart not moving with respect to a marker on the body. The system does not obviate the need for initial placement using x-ray fluoroscopy, and cannot directly image ablated tissue.
Magnetic Resonance Imaging (MRI) is a known imaging technique which uses high-strength magnetic and electric fields to image the body. A strong static magnetic field (between the magnet poles in this example) orients the magnetic moments of the hydrogen nuclei. RF time-varying magnetic field pulses change the spatial orientation of the magnetic moments of the nuclei. To exert a significant torque on the moment, the frequency of the magnetic field must be equal to the frequency of precession of the magnetic moment of the nuclei about the direction of the static magnetic field. This frequency of precession is a natural, or resonance, frequency of the system (hence Magnetic Resonance Imaging). The time-varying gradient magnetic field is used for spatial encoding of the signals from the tissue. The magnitude of the gradient field is a linear function of the space coordinates in the magnet. As a result of the addition of the static and gradient magnetic fields, the total local magnetic field and, thus, the local resonance frequency, becomes a linear function of position. Thus, imaging tissues in any plane can be accomplished because the location of each volume element is known in three-dimensional space.
MRI is generally considered a safe technique, since no x-rays are used and the electromagnetic fields do not, by themselves, cause tissue damage.
While MRI may provide the visual guidance necessary for creating and confirming linear lesions, it has been assumed that electrical wires implanted in a patient can act as antennas to pick up radio-frequency energy in an MR system and conduct that energy to the patient, thereby causing tissue injury.
Magnetic resonance imaging has been used to guide procedures in which RF energy is applied to non-contractile organs such as the brain, liver and kidneys to ablate tumors. However, these systems are not suitable for use in the heart.
U.S. Pat. No. 5,323,778 to Kandarpa et al. discloses a method and apparatus for magnetic resonance imaging and tissue heating. There is no provision in the disclosed probe for measuring electrical signals; and, it is unclear how much resolution the probe provides.
OBJECTS AND SUMMARY OF THE INVENTION
It is therefore an object of the invention to provide an improved system and method for guiding and/or providing visualization during electrophysiologic procedures.
It is a further object of the invention to provide a system and method for guiding or visualizing ablation procedures which is suitable for use in the heart and other structures.
It is a further object of the invention to provide a system and method for imaging ablation lesions with increased resolution and reliability.
The invention provides a system and method for using magnetic resonance imaging to increase the safety and accuracy of electrophysiologic procedures. The system in its preferred embodiment provides an invasive combined electrophysiology and imaging antenna catheter which includes an RF antenna for receiving magnetic resonance signals and diagnostic electrodes for receiving electrical potentials. The combined electrophysiology and imaging antenna catheter is used in combination with a magnetic resonance imaging scanner to guide and provide visualization during electrophysiologic diagnostic or therapeutic procedures. The invention is particularly applicable to catheter ablation of atrial and ventricular arrhythmias. In embodiments which are useful for catheter ablation, the combined electrophysiology and imaging antenna catheter may further include an ablation tip, and such embodiment may be used as an intracardiac device to both deliver energy to selected areas of tissue and visualize the resulting ablation lesions, thereby greatly simplifying production of continuous linear lesions. Additionally, the ablation electrode can be used as an active tracking device that receives signal from the body coil excitation. Gradient echoes are then generated along three orthogonal axes to frequency encode the location of the coil and thus provide the three-dimensional space coordinates of the electrode tip. These numeric coordinates can then be used to control the imaging plane of the scanner, thereby allowing accurate imaging slices to be automatically prescribed though the anatomic target for RF therapy. The invention further includes embodiments useful for guiding electrophysiologic diagnostic and therapeutic procedures other than ablation. Imaging of ablation lesions may be further enhanced by use of MR contrast agents. The antenna utilized in the combined electrophysiology and imaging catheter for receiving MR signals is preferably of the coaxial or “loopless” type that utilizes a helical whip. High-resolution images from the antenna may be combined with low-resolution images from surface coils of the MR scanner to produce a composite image. The invention further provides a system for eliminating the pickup of RF energy in which intracardiac wires are detuned, by for example low-pass filters, so that they become very inefficient antennas. An RF filtering system is provided for suppressing the MR imaging signal while not attenuating the RF ablative current. Steering means may be provided for steering the invasive catheter under MR guidance. Lastly, the invention provides a method and system for acquisition of high-density electroanatomic data using a specially designed multi-electrode catheter and the MRI scanner. This will be achieved by using an active tracking system that allows the location of each electrode to be determined.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing and other objects, features, and advantages of the invention will be apparent from the following more particular description of preferred embodiments as illustrated in the accompanying drawings, in which reference characters refer to the same parts throughout the various views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating principles of the invention.
FIG. 1 shows a schematic view of a combined electrophysiology and imaging antenna catheter in accordance with a preferred embodiment of the invention.
FIG. 2 shows a cross-sectional detail view of a tip portion of combined electrophysiology and imaging antenna catheter in accordance with a preferred embodiment of the invention.
FIG. 3 shows a block diagram illustrating the operation of an MRI scanner system which may be used in connection with the system and method of the invention.
FIG. 4 illustrates a schematic block diagram showing an example of radiofrequency filters which may be used in accordance with the invention.
FIG. 5 shows a graphic representation of electrical signals measured from a catheter in accordance with the invention during MR imaging.
FIG. 6 shows a high-level block diagram illustrating an ablation system incorporating radio-frequency filters in accordance with a preferred embodiment of the invention.
FIG. 7 shows three-dimensional reconstructions of MR images from planar sections.
DETAILED DESCRIPTION
The invention in its preferred embodiment uses MR imaging to allow catheters to be placed without radiation, and provides very accurate localization of catheter tips in 3-dimensional space. With current MRI scanners, resolution is limited by the distance the RF coil is from the volume of tissue being imaged. RF from any particular imaging volume is picked up by the surface coil. The gradients select a volume inside the body for imaging, but the coil outside the body picks up the signal from the volume. The farther the surface coil is from the imaging volume, the more noise will be present.
In accordance with a preferred embodiment of the invention, an intracardiac receiving coil/antenna is used so that the receiving coil/antenna is closer to the imaging volume (lesions), thereby reducing noise, increasing signal, and improving resolution where it is needed most.
In a first embodiment of the invention, MRI is used to facilitate catheter ablation of atrial fibrillation by guiding creation of continuous linear ablation lesions and confirming that a complete linear lesion has been created (line of block). The visualization of areas of ablation may allow a reduction in the number of lesions needed, and may also reduce the number of recurrences, by more accurately ablating the arrhythmias.
FIGS. 1 and 2 show schematic and detail views, respectively, of a combined electrophysiology and imaging antenna catheter in accordance with a preferred embodiment of the invention. The device of the invention is used in combination with an MRI scanner such that RF energy can be delivered to selected areas of tissue, the tissue imaged with an invasive (e.g., intracardiac) antenna, and RF lesions or other targets can be visualized in both high and low resolution modes. MRI allows visualization of lesions in the ventricle with the use of surface coils, and in the atria with surface coils and/or the intracardiac catheter-antenna. With these catheter antennae, the image can be aligned perpendicular to the catheter, such that the best resolution will be at site of the lesion. This lesion visualization can be used for (1) precise titration of therapy, (2) the ability to test the length and depth of lesions from new ablation-energy sources, and (3) accurate assessment of the success of making lines of ablation.
In addition to catheter-antenna, high-resolution imaging can also be done with receivers that contain loops that are placed inside the body. These loops may be fixed in size or may be expandable once placed in the body to increase their surface area.
MRI can also be used in accordance with the invention to guide other procedures. In cardiology, accurate anatomic information, combined with electrical measurements, allows improved study of the pathophysiology of arrhythmias, stunning, remodeling, and tachycardia-induced myopathy. Outside of cardiology, it has already been demonstrated that biopsies of liver, kidney, adrenal gland, neck masses, and lymph nodes could all be done safely and accurately with MR-guidance. With extensions of the biopsy technique, MRI-guided ablation of tumors such as metastatic liver disease, brain tumors, and prostate cancer, may allow treatment with less morbidity and less cost than conventional open surgery.
FIG. 1 shows a schematic diagram of the device 1 of the invention and FIG. 2 shows a detail view of a tip portion 15 of the device. The system of the invention preferably comprises a combined electrophysiology and imaging antenna catheter 1 which is used in conjunction with an MRI scanner such that visualization can be performed simultaneously with delivery of RF energy to selected areas of tissue for ablation. In embodiments designed for cardiac ablation applications, the length of the invasive portion of the device is preferably at least 1200 millimeters long so that the tip can be placed into the heart from the femoral artery or vein. The diameter of the device is approximately 2.5 mm.
The device preferably includes between one and three diagnostic electrodes 11 for receiving electrical potentials, e.g., intracardiac potentials, in connection with electrophysiological procedures and testing. In embodiments useful for ablation applications, the device further includes an ablation tip 13 . The electrodes 11 are preferably fabricated from platinum or gold. The tip portion 15 of the device is deflectable by a steering wire 5 , preferably of titanium construction, that is inside a low-friction sheath, preferably of Teflon construction. The steering wire 5 connects to a steering knob 7 and moves toward or away from the tip when the steering knob 7 is rotated, deflecting the tip in the appropriate direction. A connector 9 is used to interconnect the antenna 3 with receiver or scanner circuitry, which is discussed in further detail below, and is also used to connect the electrodes 11 to external electronic devices.
The device of the invention includes an antenna portion 19 , which may be of various suitable designs. In the preferred embodiment, a flexible, helical whip coaxial loopless antenna is used. Such an antenna can be made by removing a section of the shield from an antenna coaxial cable, so as to form a ‘whip’ with the center conductor. To avoid direct biofluid contact with conductive components of the catheter it will be covered with a non-conductive dielectric material. Addition of insulation to the antenna, however, increases the whip length required for optimal image quality to a length that prohibitively large for in vivo use. Incorporating a helical whip in the loopless antenna design overcomes this limitation by allowing up to 10 times the electrical length to be achieved in the same physical length as a straight conductor whip. In addition to these electromagnetic advantages, the helical antenna whip also improves the mechanical properties of the device and thereby greatly improve intravascular and intracardiac navigation of the catheter without kinking, folding or mechanical failure of the whip. The flexible helical whip has guidewire properties and thus reduces the risks of vascular or cardiac perforation. The length of helical whip can be varied to help in tuning the antenna to the optimal impedance and in optimizing the signal-to-noise ratio. Further details regarding the structure and design of suitable loopless antennas can be found in U.S. Pat. No. 5,928,145, issued Jul. 27, 1999, the entire disclosure of which is incorporated herein by reference.
Since loops can receive more signal in a given imaging volume, an antenna incorporating a loop may provide an improved signal-to-noise ratio, resulting in clearer images. A loop can be formed, where the antenna whip 21 is connected to the antenna body 19 via a miniature capacitor. A balloon can be incorporated into the catheter, and the loop can be attached to the surface of the balloon. When the balloon is inflated, the loop will expand.
In embodiments of the invention wherein a coaxial loopless antenna is utilized, a helical whip portion 21 of the flexible antenna protrudes from the distal tip to complete the dipole antenna. The whip portion 21 is coated with an insulating layer and its tip 23 can be exposed and formed into a “J” to help prevent the whip from perforating internal physiological structures. The antenna whip portion 21 should be insulated from the ablation tip.
When the device of the invention is used for intracardiac ablation procedures, tissue is imaged with the antenna and RF lesions can be visualized in both high and low resolution modes. As is discussed in detail below, the images may be enhanced with MRI contrast, such as gadolinium. Software can be provided for optimally visualizing the lesions, and for allowing the operator to change viewing perspective in near-real time.
As is set forth above embodiments of the invention which are useful for ablation procedures preferably include an ablation tip 13 . As an alternative to the preferred embodiment wherein the active element of the antenna runs within the catheter in a coaxial fashion, the RF ablation element in the ablation tip may be designed to serve both as an RF ablation transmitter and as a receiver coil for MR imaging. In such embodiments, a switching device can be used to switch the catheter between imaging and ablation modes. When not in ablation mode, the ablation electrode, and the other electrodes on the catheter, can be used to measure electrical signals.
Another embodiment of the combined antenna and RF probe device is the use of untuned RF electrodes as tracking devices. Single or multiple RF electrodes may serve as small RF coils that receive signal from the body coil excitation and then are frequency encoded in three orthogonal planes. These three space numeric coordinates can then be used to automatically control the imaging plane of the scanner, allowing optimal imaging of the target region for RF therapy. Additionally, as the electrodes can also acquire bioelectric signals, electrode location data allows the generation of true electroanatomic data.
For most applications, the impedance of the imaging antenna must match the impedance of the input amplifier. With an ordinary 64 MHz input amplifier, this impedance is 50 Ohms. A number of matching networks are possible, the simplest being a series capacitor of an appropriate value. A network analyzer can be used to allow optimal matching of different antenna designs. To customize matching to an individual patient, the network analyzer can be automated and incorporated into the matching network to automatically tune the matching network after the antenna has been placed into the patient.
The catheter antenna device of the invention in accordance with its preferred embodiment is constructed so as to be fully MRI-compatible. Specifically, its design and materials are selected such that (1) the image is not significantly distorted by the device; (2) the MRI electromagnetic fields do not alter the normal functioning of the device; (3) cardiac arrhythmias are not produced by the device, and (4) no damage to the tissue is produced by radio-frequency energy received from the MRI scanner. The presence of even small amounts of magnetic material in the imaging fields can produce substantial amounts of image distortion. This distortion is caused by perturbation of the imaging magnetic field. The most distortion is caused by ferromagnetic materials (iron, nickel, cobalt). Little if any distortion is produced by materials that do not become significantly magnetized (low magnetic susceptibility) by the MRI magnetic field. Metals which do not produce significant magnetization include copper, gold, platinum and aluminum. Many plastics and synthetic fibers are entirely non-magnetic and do not distort the images.
FIG. 3 shows a block diagram illustrating the operation of an MRI scanner system which may be used in connection with the system and method of the invention. A magnet is provided for creating the magnetic field necessary for inducing magnetic resonance. Within the magnet are gradient coils for producing a gradient in the static magnetic field in three orthogonal directions. Within the gradient coils is an RF coil. The RF coil produces the magnetic field necessary to rotate the spins of the protons by 90° or 180°. The RF coil also detects the signal from the spins within the body. A computer is provided for controlling all components in the imager. The RF components under control of the computer are the RF frequency source and pulse programmer. The source produces a sine wave of the desired frequency. The pulse programmer shapes the RF pulses, and the RF amplifier increases the pulse power up to the kilo-watt range. The computer also controls the gradient pulse programmer which sets the shape and amplitude of each of the three gradient fields. The gradient amplifier increases the power of the gradient pulses to a level sufficient to drive the gradient coils.
The invention in accordance with a preferred embodiment further includes filter means and shielding for protecting electronic equipment (e.g., the MR scanner) from RF produced by the ablation system, for protecting the ablation and measuring system from RF produced by the MR scanner, and for allowing measurement of the relevant electrical signals. Without adequate radio-frequency filters, the electronics attached to the catheter may malfunction during imaging. FIG. 4 illustrates a schematic block diagram showing an example of radio-frequency filters which may be used in accordance with the invention. Low-pass filters using 1 microHenry inductors made without magnetic materials, and 220 picoFarad capacitors, have optimal attenuation of the 64 MHz radio-frequency energy present in the 1.5 Tesla MR scanner. A number of filter topologies were tested, and the two stage filter shown in FIG. 4 had the best results. A separate two-stage filter (L 1 , L 3 , C 1 , C 3 ; and L 2 , L 4 , C 2 , C 4 ), is preferably placed in each wire to the catheter. These filters can reduce the 15-32 volts of radio-frequency pickup down to a few millivolts and cause no problems with the electronics.
The output of the RF filters can be applied to a series of active filters. The active filters may comprise, e.g., a sixth order, Chebyshev (1 dB ripple), low-pass filter (50-300 Hz corner); then a second order, Chebyshev (1 dB ripple), high-pass filter (3-50 Hz corner); and then a 60 Hz notch filter. These filters limit the signal bandwidth, and substantially reduce gradient-field-induced noise—see FIG. 5( c ), discussed below. The gradient field noise was not rejected by the RF filters. This filter arrangement is used in the catheter-intracardiac electrogram measuring circuit. The circuit for ablation does not incorporate the active filters, since while the RF filtering system is designed to suppress the 64 MHz imaging signal. It does not attenuate the RF ablative current, since the radio frequency of the ablation system is 200-800 kHz, and the corner for the lowpass RF filters is 1-10 MHz. The ablation circuit does not need the lower-frequency filters, since that circuit is not being used to measure electrograms.
FIG. 5 shows a graphic representation of electrical signals measured from a catheter in accordance with the invention during MR imaging. FIG. 5( a ) shows the signals measured from a catheter without the use of RF filters; it can be seen that the ECG is obscured by noise (32 volts peak-to-peak). FIG. 5( b ) shows such signals wherein RF filters are used; it can be seen that nearly all radio-frequency interference is removed and an ECG signal is now apparent. The pairs of vertical lines are artifacts from the gradient fields. FIG. 5( c ) shows such signals wherein active RF filters are used; it can be seen that most of the gradient artifact is also suppressed.
FIG. 6 shows a high-level block diagram illustrating an ablation system incorporating the filters described above. The RF Generator may comprise, e.g., a standard clinically approved ablation unit, such as those commercially available from Medtronic, having an RF output frequency of 482.6±5 kHz and an output of 50 W into a 50-250 Ω load. The output frequency from the RF generator is directed to the ablation catheter through two filter assemblies (low pass, 2 MHz corner). Both filter assemblies are fully shielded and are connected by fully shielded cable. The ECG amplifiers incorporate the active filters as described above. The dispersive ground electrode consists of a large conductive-adhesive pad that is attached to the skin of the animal to complete the circuit. The defibrillator (identified as “defib” in FIG. 8 ) may comprise a standard defibrillator used in ablation procedures.
It is important that the location of the tip of the catheter can be accurately determined. A number of modes of localization can be used. Because the catheter is a receiver it can be used to directly image the tissue around it. This image can be viewed on its own at high resolution, or, it can be viewed at low resolution as an overlay on a large field-of-view “scout” image obtained with an auxiliary coil outside the body. The location of the catheter in the body can be tracked by the bright line of signal moving in the scout image. The scout image can be updated at an interval set by the user to compensate for patient motion. An interactive control will allow the physician to “zoom in” towards the bright catheter, finally resulting in a high resolution image around the catheter tip. The “zoom” function can be achieved with interactive control of the imaging gradients.
A composite “medium resolution” resolution image can be used to construct a three-dimensional map of the areas in the heart that have undergone ablation. These areas will be marked by elevated T2 values, or decreased T1 values during Gd infusion. A composite three-dimensional rendering of the heart can be updated after each ablation and displayed with an appropriate rendering technique.
The guidance of the catheter tip to the next site of ablation, or to fill in a previous ablation line can be assisted using the MR images. This assistance can be entirely passive, in that the physician uses the images to manipulate the catheter, or automatic tracking and feedback could assist that physician to steer the catheter.
The lesions may be visualized using standard imaging techniques. It may be necessary to MR contrast to enhance the lesions to allow adequate visualization to occur. One such enhancement method uses gadolinium-DTPA, but other suitable contrast agent could be used. The rationale underlying the utilization of gadolinium-DTPA based contrast agents to enhance signal intensity in atrial or ventricular myocardium injured by RF during therapeutic ablation is based on the following observations: 1) Gadolinium-DTPA exerts its signal enhancing effect by interacting with water protons and inducing a shorter relaxation time in response to any given radio-frequency stimulus. This effect creates the image contrast necessary to allow distinction in relation to regions unaffected by contrast. 2) Gadolinium-DTPA is a large molecule which cannot penetrate the uninjured cell membrane and is therefore restricted to the extracellular space in uninjured myocardium. After the RF burn, the injured membrane allows penetration of the contrast agent thus increasing significantly the volume of distribution for the contrast agent and resulting in a ‘brighter’ voxel of tissue on T1 weighted images. 3) This difference in voxel content of water protons potentially exposed to the gadolinium-DTPA molecule creates the possibility of distinguishing injured from non-injured tissue with greater spatial resolution than in non-enhanced images.
Gadolinium-DTPA can be injected prior to the RF ablation protocol to enhance injured myocardium as the lesions are produced. The agent takes 5-10 minutes to equilibrate between extracellular and intracellular spaces and a few hours to be eliminated through the kidneys. The agent is routinely used in brain MRI studies to highlight areas of inflammation and in cardiac MR studies to delineate myocardial regions injured by prolonged ischemia. Gadolinium-DTPA has an appropriate safety profile and except for occasional nausea, does not cause side effects leading to discomfort or complications in patients.
Imaging of ablated lesions may be further enhanced by use of thermal imaging techniques. Thermal imaging can be accomplished by using phase differences in MR signals.
Three-dimensional image reconstruction can be performed using the system and method of the invention. FIG. 7 shows three-dimensional reconstructions of MR images from planar sections. In particular, FIG. 7 shows three-dimensional reconstructions of images during activation of the left ventricle from a right ventricular pacing site. In FIG. 7 , the white areas show the spread of mechanical activation as the wave of electrical activation spreads across the left ventricle from the right ventricular 5 pacing site. Similar image processing techniques can be used for visualizing ablated areas.
The advantages of the system and method for MR-guided electrophysiology in accordance with the invention will now be discussed in further detail.
Recent advances in MRI technology enable frame rates higher than 10/sec. This exceeds the frame rate often used in current pulsed x-ray fluoroscopy systems. When the depth dimension of the MRI slice is set as large as the body depth, the resulting 2-dimensional image sequence can serve as an effective substitute for x-ray fluoroscopy. The system can thus facilitate catheter placement for EP study with real-time imaging, without the need for ionizing radiation. Catheters used in this system must be composed entirely of non-ferromagnetic materials, so as not to perturb the electromagnetic gradient field required for distortion-free MR imaging.
MRI allows for precise localization of object elements in three-dimensional space. Catheter tip position within the heart can thus be determined accurately and precisely, and can then be displayed superimposed on anatomically accurate reconstructions of cardiac architecture. This functionality is not possible with x-ray fluoroscopy.
Electrical activation timing information obtained via an EP mapping catheter, when combined with catheter localization information, enables accurate color-coded activation maps. This capability is most useful in determining the site of origin of an atrial or ventricular tachycardia.
Activation maps can be superimposed on anatomically accurate reconstructions of cardiac structure. Spatially accurate voltage data, however, requires knowledge of the location of each electrode in contract with the myocardium. This can be achieved by using high-density basket catheter electrodes in conjunction with active tracking RF coils. Each untuned electrode is capable of receiving signal, which in turn, provides the 3-space coordinates of each electrode. Electrical data originating from each known electrode position allows generation of activation and voltage maps on true anatomic structures. This provides significant advantages beyond the capabilities of the non-fluoroscopic electroanatomic mapping system noted above, since that system does not provide accurate anatomic information, again without additional hardware.
An imaging antenna can be incorporated into a steerable mapping/ablation catheter, enabling high-resolution imaging in the region near the catheter tip. The image obtained with this antenna has a similar radius of view as that with intracardiac ultrasound, but with far greater resolution. Furthermore, this high-resolution image is obtained without the need for placement of an additional catheter, as is required with intracardiac ultrasound.
High-resolution images derived from the internal antenna can be combined with lower-resolution wide-field images obtained with the external coil into a single image. This composite image will display the entire cardiac cross section with enhanced resolution in the area of greatest interest
When the ablation/imaging catheter is used for the delivery of ablative radio-frequency energy, the high-resolution image obtained via this catheter enables visualization of the lesion and of lesion growth. It may also be possible to visualize lesions with surface coils alone, if the tissue is thick enough.
Directional orientation, as well as location, of the catheter tip can be determined in three-dimensional space. The high-resolution image data obtained via the internal antenna can be displayed in any plane, and in particular, in the plane orthogonal to the catheter. Since the image is obtained with the same catheter that is delivering the ablative energy, the orthogonal-plane image is guaranteed to display the lesion at its maximal radius, without the need to manipulate a second (imaging) catheter into alignment with the ablation catheter. Lesion size will thus not be underestimated as often occurs with intracardiac ultrasound. In the latter case, the imaging catheter differs from the ablation catheter. It is therefore not necessarily imaging at the same level as the ablation catheter tip, and is not necessarily parallel to the ablation catheter so the image plane is oblique to the lesion equator.
MR is an imaging modality that can be tuned to characterize tissue physiology as well as structure. This enables imaging of lesions by virtue of changes in structure and cell function that occur with fulguration. Injection of gadolinium further enhances the MR image contrast between healthy and ablated myocardium. Intracardiac ultrasound, on the other hand, enables visualization of lesions only to the extent that tissue echogenicity is altered.
Because the MRI-guided EP system of the invention combines two-dimensional real-time image sequences, accurate three-dimensional catheter tip localization for activation mapping, and the ability to “see” myocardial tissue and lesion growth, it offers the best features of x-ray fluoroscopy, the non-fluoroscopic electroanatomic mapping system, and intracardiac ultrasound all at once without ionizing radiation, extra venipunctures, or excessively expensive catheters.
High-resolution visualization of ablative lesions by the internal MR antenna allows for documentation of whether or not RF application resulted in successful lesion development and of where lesions have and have not yet been made. This facilitates efficient catheter placement so that RF is applied only to tissue not previously ablated.
The high-resolution images obtained with the internal MR antenna enables visualization of the relatively thin atrial wall. This structure may not be well visualized by the external MR coil due to lack of adequate resolution. If the atrial wall or other anatomical structures to be visualized have thick enough walls, which does occur, adequate visualization may be obtained with surface coils alone.
The combination of the high-resolution visualization and images discussed above makes high-resolution MRI guidance ideal for visualization and verification of ablative lesion lines, particularly in atrial tissue. This is useful for ablation of the reentrant circuit in typical atrial flutter and is crucial for successful ablation of atrial fibrillation. Investigators have shown that atrial fibrillation can be eliminated with multiple lines of ablative lesions placed in the right and left atria to emulate the surgical maze procedure. Failures of the ‘percutaneous maze’ procedure have resulted primarily from incomplete lesion lines. MRI guidance should allow rapid confirmation of lesion line continuity and avoidance of unnecessary repetition of RF application where tissue has already been successfully ablated.
The MRI-guided catheter ablation system offers advantages in ablation of ischemic and idiopathic ventricular tachycardias, ectopic atrial tachycardias, atrial flutter, and atrial fibrillation. Unlike AV node reentry and accessory pathway mediated tachycardia, these other arrhythmias have lower ablation success rates and longer ablation procedure durations, primarily due to difficulties in accurate activation mapping or confirmation of lesion development with conventional equipment. Procedure durations and risk of complications should thus be reduced substantially with the MRI-guided catheter ablation system.
While the invention has been particularly shown and described with reference to a preferred embodiment 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. | A method of performing brain therapy may include placing a subject in a main magnetic field, introducing into the subject's brain a combination imaging and therapeutic probe, the probe including a magnetic resonance imaging antenna and an electrical energy application element, acquiring a first magnetic resonance image from the antenna of the combination probe, acquiring a second magnetic resonance image from a surface coil, combining the first and second magnetic resonance images to produce a composite image, positioning the combination probe within the brain with guidance from at least one of the images, and delivering electrical energy to the brain from the electrical energy application element of the combination probe thus positioned. | 0 |
TECHNICAL FIELD
[0001] The invention relates to a method and to an apparatus for folding together an inflatable airbag jacket of an airbag module for motor vehicles.
BACKGROUND OF THE INVENTION
[0002] Airbag modules for vehicle airbags are manufactured in large quantities. One therefore attempts to simplify and speed up the manufacture of the airbag modules, which includes the folding together of the airbag jacket.
[0003] The problem (object) of the invention is to create a possibility of manufacturing airbag modules for motor vehicles as rapidly and simply as possible, with it being desirable for this possibility also to be given in particular for side airbag arrangements in which the airbag deploys downwardly in the manner of a curtain along a vehicle side wall in the vehicle in the event of an accident.
SUMMARY OF THE INVENTION
[0004] This object is satisfied by the features of the method claim 1 and in particular in that the at least partly spread out airbag jacket is arranged in at least one folding pocket and a folding volume of the folding pocket which contains the airbag jacket is reduced in size.
[0005] In accordance with the invention the airbag jacket is folded together or gathered by means of the folding pocket in that the folding volume, that is, that region of the folding pocket in which the airbag jacket is arranged, is reduced in size. An essential advantage of the invention consists in that the folded together airbag jacket is still arranged within the folding pocket at the end of the folding process. The folding of the airbag can thus be secured through the folding pocket which surrounds the folded together airbag jacket.
[0006] At the same time the folding pocket serves as a cover which protects the folded together airbag jacket. Thus no further measures are required for the securing of the folding and for the protection of the folded airbag jacket. The folding pocket with the folded together airbag jacket which is arranged in it can be mounted in a vehicle as an airbag module or as constituent of the airbag module.
[0007] Through the folding method in accordance with the invention consequently the folding together of the airbag jacket and thus the manufacture of airbag modules is considerably simplified and speeded up.
[0008] A further advantage of the folding of the airbag jacket in accordance with the invention in a folding pocket consists in that the danger of damage to the airbag jacket is a minimum, since the airbag jacket comes in contact exclusively with the folding pocket and a direct contact with other objects is avoided.
[0009] Advantageous is also that the folding volume of the folding pocket can in principle be brought to any size as small as desired. Through reducing the size of the folding volume a minimum packing size of the folded together or gathered airbag jacket can therefore be achieved.
[0010] In principle the folding method in accordance with the invention can be used for the manufacture of any desired packing shapes of the folded together airbag jacket. In accordance with a particularly preferred exemplary embodiment of the invention the airbag jacket is folded together to form an elongate packing shape.
[0011] Through this the folding method in accordance with the invention can be used in the manufacture of side airbag arrangements, the airbag of which deploys in the manner of a curtain in the event of an accident.
[0012] The side airbag arrangements can comprise at least one gas tube which is provided with a gas outlet opening and which extends at least region-wise through the airbag jacket. Through fixing the gas tube the airbag jacket can be fixed region-wise, so that the airbag jacket can be pressed against the fixed gas tube through moving the folding pocket relative to the gas tube. The gas tube thus serves as a support or holding member for the airbag jacket.
[0013] This folding possibility is in principle also given in other support or holding members which are provided at airbag modules, which are fixed through suitable means and against which the airbag jacket is pressed by means of the folding pocket through reduction of the folding volume.
[0014] In accordance with a further preferred exemplary embodiment of the invention at least one material layer is laid around the airbag jacket for forming the folding pocket.
[0015] In this the folding pocket can be formed in a particularly simple way by a single material layer, which is e.g. first spread out and onto which the at least partly spread out airbag jacket is then placed. Through folding over of the region of the material layer which is not covered by the airbag jacket the folding pocket then arises, between the side walls of which the airbag jacket is arranged in a planar manner.
[0016] In principle a hanging folding pocket with substantially vertical side walls, between which the airbag jacket is hung, can also be provided in accordance with the invention. Through drawing upwards of at least one side wall of the folding pocket the airbag jacket is then moved in the direction of a fixed region of the airbag jacket and e.g. pressed against a gas tube which fixes the airbag jacket.
[0017] In accordance with a further preferred embodiment of the invention the folding volume is reduced in size at least substantially without folding the folding pocket.
[0018] Through this it is ensured that the airbag jacket is always surrounded by a substantially fold-free jacket both during the folding together and in the finally folded together state. An interlocking of the folding pocket and the airbag jacket is thus reliably avoided.
[0019] In this it is preferred for the volume reduction to take place through moving the folding pocket, in particular through drawing at the folding pocket, in a direction which extends approximately parallel to the plane of spreading out of the airbag jacket. For this, preferably one side wall of the folding pocket is fixed and the folding volume is reduced in size through drawing at another, in particular at the oppositely lying, side wall of the folding pocket.
[0020] In accordance with a further preferred exemplary embodiment of the invention the reduction of the folding volume takes place within a folding space, through which the packing size of the airbag jacket is limited during the folding together in directions which deviate from a folding direction, in particular approximately perpendicular to the folding direction.
[0021] Through folding together of the airbag jacket within a folding space of this kind it is automatically ensured that a maximum size of the package formed by the folded together airbag jacket, which can be set through the choice of the dimensions of the folding space, is not exceeded. The folding principle in accordance with the invention, in which the airbag jacket is folded together or gathered by means of the folding pocket, is in principle independent of the size of the folding space and requires in particular—apart from the material thickness of the airbag jacket and of the folding pocket—no minimum dimensions of the folding space, so that airbag jacket packages of in principle any desired size can be produced through adjusting the folding space dimensions.
[0022] Furthermore, it is preferred for the reduction of the folding volume to take place between two limiting surfaces which extend at least substantially parallel and which are formed in particular at plate-shaped limiting members.
[0023] The folding space can e.g. be formed by two plates which extend in parallel, so that the airbag jacket is folded together between the two plates. The reduction of the folding volume of the folding pocket and thus the folding of the airbag jacket takes place in a folding direction which lies in a plane which extends approximately parallel to the plates. Perpendicularly to this folding direction the dimensions of the airbag jacket package which arises during the folding together are limited through the plates to the plate spacing.
[0024] In accordance with a further preferred embodiment of the invention the folding pocket is closed after the folding together of the airbag jacket to the final packing size. In particular through connection, preferably welding and/or sewing, of oppositely lying side walls of the folding pocket.
[0025] Through this the folding pocket forms a protective envelope which surrounds the folded together airbag jacket and which on the one hand secures the folded package produced in that it prevents an unfolding or relaxation of Me airbag jacket, and which on the other hand protects the airbag jacket from external influences. Additional measures for securing the folding or for protecting the airbag jacket respectively can therefore be dispensed with.
[0026] The object of the invention is also satisfied through the features of the apparatus claim 13 and in particular in that the apparatus comprises at least one folding pocket for the reception of the at least partly spread out airbag jacket and an actuation device by means of which a folding volume of the folding pocket which contains the airbag jacket can be reduced in size.
[0027] The folding pocket is preferably manufactured of a textile and/or fabric material, for example of nylon.
[0028] Through this, ideal flexibility and stability properties can be imparted to the folding pocket.
[0029] In accordance with a further preferred embodiment of the invention the folding pocket is provided with at least one preferably line-shaped or strip-shaped tear-open region.
[0030] The folding pocket can thereby serve as a cover or envelope for the folded together airbag jacket in the state of being mounted in a vehicle, which tears open during the inflation of the airbag at the tear-open region which is provided for this purpose in order to enable the deployment of the airbag jacket.
[0031] In accordance with a further preferred exemplary embodiment of the invention a fixing device for the airbag jacket is provided, which is preferably arranged outside a folding space for the folding pocket.
[0032] The fixing of the airbag jacket enables the folding pocket to be moved relative to the fixed region of the airbag jacket and the airbag jacket to be folded together or gathered respectively by means of the folding pocket in the direction of the fixed region of the airbag jacket.
[0033] In this it is preferred for the fixing device to be formed for the fixing of a support member of the airbag module, to which the airbag jacket is connected.
[0034] In this the airbag jacket can be pressed together between the folding pocket and the support member in that the airbag jacket is for example drawn or gathered respectively against the support member through drawing at the folding pocket.
[0035] The support member can be the gas tube of an airbag module for a side airbag arrangement, which extends at least region-wise within the airbag jacket.
[0036] The gas tube which serves for the inflation of the airbag and which is preferably provided with a plurality of gas outlet openings serves here at the same time as an abutment for the airbag jacket which is pressed together or gathered respectively by means of the folding pocket.
[0037] The folding apparatus in accordance with the invention can be designed in such a manner that at the end of the folding process the gas tube is arranged within the folding pocket together with the folded together airbag jacket. Thus at the end of the folding process a module is present which is ready for installation and which can be installed in a vehicle as an airbag module or as a constituent of the airbag module.
[0038] In accordance with a further preferred exemplary embodiment of the invention the folding apparatus is subdivided into a plurality of sections, which can preferably be displaced relative to one another. The subdivision into a plurality of sections enables a specific packing shape of the folded together airbag jacket to be intentionally realized which is predetermined through the manner of the arrangement of the sections. Through the preferred displaceablity of the sections, different packing shapes of the folded together airbag jacket can be achieved with one folding apparatus.
[0039] In particular for forming differently curved elongate packing shapes the fixing or clamping device respectively which is provided for fixing the airbag jacket or a gas tube of the airbag jacket respectively can be designed to be displaceable.
[0040] An airbag module which comprises the folded together airbag jacket and which is a constituent of a side airbag arrangement can thereby be intentionally adapted to the respective use or vehicle type.
[0041] Further preferred embodiments of the invention are also set forth in the subordinate claims, the description and the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] The invention will be described in the following in an exemplary manner with reference to the drawings. Shown are:
[0043] [0043]FIGS. 1 a - 1 c are, in each case in a sectioned side view, of different phases of a folding of an airbag jacket which is carried out in accordance with the invention;
[0044] [0044]FIG. 1 d is a section along line A-A of FIG. 1 c;
[0045] [0045]FIG. 2 is a plan view of a portion of the folding apparatus; and
[0046] [0046]FIG. 3 is a plan view of the entire folding apparatus, which is subdivided into a plurality of sections.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0047] The invention will be described in the following using as an example an airbag for a side airbag arrangement which comprises an airbag jacket 12 and a cylindrical gas tube 18 which passes through the airbag jacket 12 and which is provided with a plurality of gas outlet openings 18 a.
[0048] The folding apparatus comprises two plates 27 , 28 , which extend parallel to one another in the horizontal direction in the operating position in accordance with FIGS. 1 a - 1 d. The plates 27 , 28 bound a folding space 22 of small height in comparison with the extension of the plates 27 , 28 . The folding space 22 can be opened and closed through pivoting the upper plate 27 in manner indicated by the arrow in FIG. 1 a . Furthermore, the plates 27 , 28 can be moved relative to one another in such a manner that the plate spacing, i.e. the height of the folding space 22 , can be adjusted continuously.
[0049] Furthermore, the folding apparatus comprises a material layer 14 which consists of a fabric material which is for example manufactured of nylon. At the beginning of the folding process the material layer 14 is spread out on the lower plate 28 with the upper plate 27 being pivoted upwards and is pushed at an edge region onto holding pins 36 which are distributedly arranged along the gas tube 18 .
[0050] Then the spread out airbag jacket 12 with the plugged in gas tube 18 is laid onto the material layer 14 , which is fixed by means of the holding pins 36 . Then the region of the material layer 14 which is not covered by the airbag jacket 12 is folded over and laid onto the airbag jacket 12 .
[0051] The airbag jacket 12 is thereby arranged in a folding pocket which is formed by the material layer 14 and is located within a folding volume 16 of the folding pocket 14 which is bounded on the one side by the gas tube 18 , on the opposite side by the base 14 c of the folding pocket 14 and by the opposite side walls 14 a, 14 b of the folding pocket 14 .
[0052] Then the folding space 22 is closed by pivoting the upper plate 27 downward.
[0053] Prior to the folding together of the airbag jacket 12 the gas tube 18 which is arranged outside the folding space 22 in the region of a longitudinal side of the plate arrangement 27 , 28 is fixed by means of clamping devices which are not illustrated in FIGS. 1 a - d. The clamping devices will be discussed in more detail in the following in connection with FIGS. 2 and 3.
[0054] The upper side wall 14 b of the folding pocket 14 is connected outside the folding space 22 to a merely schematically illustrated actuation device 24 . For this the side wall 14 b is clamped in between two clamping jaws 24 a, 24 b of the actuation device 24 . The means for coupling the folding pocket 14 or the upper side wall 14 b of the folding pocket 14 respectively to the actuation device 24 can in principle be designed in any desired manner.
[0055] The actuation apparatus 24 can be moved approximately perpendicular to the longitudinal extent of the gas tube 18 in a drawing direction Z in a plane which is parallel to the plates 27 , 28 and thus parallel to the plane of the spreading out of the airbag jacket 12 . The actual folding process begins through moving the drawing or actuation device 24 respectively, through which the upper side wall 14 b of the folding pocket 14 is drawn out from the folding space 22 and thus the folding volume 16 of the folding pocket 14 which contains the airbag jacket 12 is reduced in size.
[0056] As can be seen in particular in FIG. 1 b , which illustrates an intermediate state of the folding process, the reduction of the folding volume 16 takes place without folding the folding pocket 14 . The regions of the side walls 14 a, 14 b of the folding pocket 14 which are located in the folding space 22 between the two plates 27 , 28 extend parallel to the plates 27 , 28 during the folding process.
[0057] As a result of the reduction of the folding volume 16 through drawing at the upper side wall 14 b of the folding pocket 14 the airbag jacket 12 is pressed together between the base 14 c of the folding pocket 14 and the gas tube 18 . This process can also be designated as gathering, pressing, squashing, crumpling or creasing together.
[0058] The folding of the airbag jacket 12 which thereby develops is illustrated in FIGS. 1 b and 1 c as a substantially regular, accordion-like folding. In principle the manner of the folding is subject to chance, and in this folding method a completely irregular folding of the airbag jacket 12 or one having both regular and irregular portions can also develop.
[0059] The extent perpendicular to the drawing or folding direction Z respectively of the airbag jacket package which arises during the folding is limited by the height of the folding space 22 and thus by the spacing of the two plates 27 , 28 . In this exemplary embodiment the plate spacing is approximately equal to the outer diameter of the gas tube 18 .
[0060] [0060]FIG. 1 c shows the finally folded together state, in which the airbag jacket 12 is folded together or drawn together to the desired final packing size. When this state has been reached the two side walls 14 a , 14 b of the folding pocket 14 are connected to one another between the gas tube 18 and the holding pins 36 on the side of the gas tube 18 which faces away from the airbag jacket package. This connection can for example be realized through ultrasonic welding or sewing.
[0061] Through this closing of the folding pocket 14 the airbag jacket 12 is fixed in its finally folded together state, so that it can not relax and unfold by itself. In addition the folded together airbag jacket 12 is arranged ready to mount in a cover or envelope which is formed by the folding pocket 14 at the end of the folding process.
[0062] After the opening of the folding space 22 through pivoting the upper plate 27 upwards, the constructional group consisting of the gas tube 18 , the folded together airbag jacket 12 and the folding pocket 14 can be removed from the folding apparatus.
[0063] In accordance with the invention in this exemplary embodiment the material layer 14 thus becomes a folding pocket 14 in the preparation of the folding process and becomes a constituent of the airbag module which forms a cover or envelope of the airbag jacket 12 through the folding process.
[0064] A substantial advantage of the invention consists in that a maximum packing density of the folded together airbag jacket 12 and thus a minimum packing size can be achieved in the above described manner of the folding. The more tightly the folding pocket 14 is drawn together by means of the actuation device 24 , the greater will be the final packing density.
[0065] The packing size in the drawing direction Z can consequently be set through the length of the drawing path which is traveled by the actuation device 24 in this drawing direction Z, whereas the dimensions of the airbag jacket packing perpendicular to the drawing direction Z can be predetermined through the spacing of the plates 27 , 28 .
[0066] In particular FIG. 1 d shows that a line-shaped tear-open region 26 which extends parallel to the gas tube 18 and which is formed as a tear-open seam is provided in the region of the material layer 14 , which forms the base 14 c of the folding pocket 14 when the airbag jacket 12 is finally folded together.
[0067] The tear-open seam 26 is designed in such a manner that it tears open in the event of an accident through inflation of the airbag jacket 12 by means of the gas tube 18 in order to enable a free unfolding of the airbag jacket 12 .
[0068] [0068]FIG. 2 shows a plan view of a portion of the folding apparatus in accordance with the invention without the upper plate 27 prior to the forming of the folding pocket. The material layer 14 which later forms the folding pocket is spread out on the lower plate 28 , whereas the airbag jacket 12 , through which the gas tube 18 passes, lies on the material layer 14 in the spread out state. Clamping devices 32 for fixing the gas tube 18 are arranged laterally to the plate 28 . Furthermore, the holding pins 36 which serve for fixing the material layer 14 are illustrated.
[0069] The fixing means 32 and 36 for the gas tube 18 or the folding pocket 14 respectively can in principle be designed in any desired manner.
[0070] In FIG. 2 only a partial section of the gas tube 18 , of the airbag jacket 12 and of the material layer 14 which later forms the folding pocket is in each case illustrated. As FIG. 3 shows, the folding apparatus in accordance with the invention is subdivided into a plurality of sections 34 , which comprise four plate arrangements 27 , 28 in the illustrated exemplary embodiment. The plate arrangements 27 , 28 are arranged adjacently to one another in accordance with the curvature of the gas tube 18 . The gas tube 18 is connected with one end to a gas generator 38 , which is also designated as an inflator.
[0071] The material layer 14 , which is not illustrated in FIG. 3, can extend over the full length of the airbag jacket 12 or comprise a plurality of sections which are arranged one after the other along the gas tube 18 .
[0072] The clamping devices 32 of the folding apparatus in accordance with the invention which serve for fixing the gas tube 18 are mutually displaceable, just as the plates 27 , 28 , which are in each case arranged between two clamping devices 32 , so that the folding apparatus can be used in conjunction with gas tubes 18 of any desired curvature. Thus through the invention elongate packing shapes of the folded together airbag jacket 12 of any desired curvature can be achieved. | The invention relates to a method for folding together an inflatable airbag jacket of an airbag module for motor vehicles, in which the at least partly spread out airbag jacket is arranged in at least one folding pocket and a folding volume of the folding pocket which contains the airbag jacket is reduced in size. The invention also relates to a folding apparatus. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention:
This invention relates to compositions of specific nutrients to facilitate the adapation of skeletal muscle to programs of strenuous exercise. In particular, the invention is directed to novel combinations of certain amino acids which exert beneficial effects on the metabolism (especially protein synthesis) of skeletal muscle. The specific field of application of these amino acids is in exercise training, with a training diet providing:
1. an improved, novel mixture of certain nutrients to maximize protein synthesis in skeletal muscle; and
2. nutrients to "spare" the liver which is metabolically stressed on behalf of skeletal muscle as a result of exercise.
2. Description of the Prior Art:
Athletes who participate in sports at any level--amateur or professional--strive to bring their bodies to a physical state which is optimal for the sport or activity of interest. One factor which enables athletes to participate effectively is a high degree of development of the aerobic capacity and/or strength of skeletal muscle.
Both aerobic capacity and strength--especially the latter--is a function of training and of muscle mass. These in turn require net synthesis of proteins in the muscle. Strenuous exercise is an effective stimulus for protein synthesis. However, muscle requires a large array of nutrients, including amino acids (which are derived from protein) for protein synthesis. These nutrient substrates can be supplied by ingesting diets which provide the necessary amounts of protein (the source of amino acids), calories and other nutrients.
The desire to attain, in a rapid manner, the maximum degree of skeletal muscle adaptation to exercise has led some athletes to resort to the use of drugs. Such drugs, particularly steroids, are known to "force" muscle growth (protein synthesis) to degrees greater than can be achieved by exercise and diet alone. The use of such drugs is both illegal and dangerous.
Thus, it is desirable to apply training programs which employ a combination of specific exercise technique and diet. This is the only known and accepted manner for stimulation of the protein synthesis required for skeletal muscle adaptation. Many nutrients must be supplemented to athletes in training. This invention is directed at specific amino acids to be supplemented to such training diets.
Nearly all amino acids, both essential (indispensible) and non-essential (dispensible) are required by cells as substrates (i.e., raw materials) for protein synthesis. However, the critical feature of this invention is the specific application of certain amino acids (carnitine, glutamine, isoleucine, leucine and valine), which are known to exert net stimulatory effects on protein synthesis in skeletal muscle and liver.
Nine amino acids are known to be essential nutrients in the diet of healthy adults. Three of these essential amino acids are isoleucine, leucine and valine; they are termed the "branched amino acids" or "branched-chain amino acids" (BAA) because they share a specific type of chemical structure. For over a decade the BAA--and leucine in particular--have been known to stimulate protein synthesis in at least some skeletal muscles. The BAA produce this effect in liver as well.
The relationship between the BAA and skeletal muscle is even more intimate, a fact which is significant to this invention. Certain metabolic reactions involving the BAA occur in many organs. Since skeletal muscle mass in toto is greater than any other organ, the reactions of BAA in muscle are thus of quantitative significance.
It is well known that skeletal muscle is the primary site for the initial step in the catabolism of the BAA. Catabolism is the metabolic breaking down of the BAA resulting in energy production, and is often termed "oxidation" or "burning".
The first metabolic reaction in oxidative catabolism of BAA is "transamination" (enzymatic transfer of the alpha-amino group to another molecule) resulting in the formation of a branched keto acid (BKA) and a different amino acid (see FIGURE). The BKA can either accept an amino group, thus becoming a BAA again; or be further and irreversibly catabolized for calories. The BKA are so catabolized to a lesser extent within muscle cells. The major quantity of BKA is exported from muscle via the blood to other organs (such as liver and kidney) where they are catabolized or re-aminated.
It is well known that strenuous exercise increases the oxidation ("burning") of BAA. In fact, it has been shown that trained muscle, while in the resting (non-exercising state), also oxidizes more BAA than non-trained muscle. Further, it has been shown that the BAA burned by skeletal muscle during exercise is derived from muscle protein which is degraded during exercise, as well as from BAA delivered to the muscle in the bloodstream. The major source, during exercise, of the blood-borne BAA is the liver.
Thus, it is known that exercise causes transient periods (which extend beyond the actual exercise) wherein the normal balance in skeletal muscle of protein synthesis and degradation has been tipped toward a net, or relative, increase in protein degradation. That is, strenuous exercise cuases muscle to burn up a portion of its protein structure.
The reason for this increased "burning" of protein, especially BAA, is not clear. Some have suggested that this process reflects a "clean up" of damage caused by exercise-induced ischemia. Others suggest that increased protein oxidation contributes to the increased caloric demand of exercise. However, it has been clearly shown that the quantitative contribution of protein oxidation to the increased energy needs of exercise is quite small. Nevertheless, oxidation of BAA may be significant in view of the fact that their oxidation generates the amino acids alanine and glutamine, which can be transported from muscle to be used as fuels elsewhere. Alanine is carried, via the blood, to the liver where it contributes to the formation of glucose, the latter being the preferred fuel of the brain. Glutamine is a known fuel for the kidney and intestine. Whatever the reason, it appears that increased oxidation of protein and BAA during exercise is obligatory.
One of the functions for the oxidation of BAA in exercising muscle is, in effect, to remove lactate from muscle. It is well known that strenuously exercising muscle burns glucose in a largely anaerobic manner, resulting in the generation of lactate. (Lactate is derived directly from pyruvate.) Build up of lactate in muscle is associated with muscle fatigue, and is considered to be undesirable.
The drawing FIGURE shows that the amino groups of the BAA are transferred via intermediate reactions, to pyruvate, resulting in the formation of alanine. Alanine is exported to the liver to participate in glucose synthesis. That pyruvate which is thus involved in alanine synthesis is not converted to lactate. Therefore, BAA oxidation serves, in effect, to modulate lactate accumulation in muscle.
In addition, protons H + from catabolic reactions must be eliminated, so as to remove any risk of a drop in pH. The proton is removed from muscle by combining (in the form of ammonium--NH + 4 ) with glutamate to form glutamine. When taken up by the kidney, NH 30 4 (and hence H + ) is removed and excreted via the acid urine.
SUMMARY OF THE INVENTION
In summary, the object of the present invention is to provide diet supplements which comprise BAA (and other amino acids as discussed below) in order to promote muscle adaptation (to strenuous exercise) via the following mechanisms:
1. to "spare" muscle protein and especially muscle BAA by providing the very substrate which is being utilized at the expense of muscle mass as well as of liver protein.
2. to stimulate muscle and liver protein synthesis, which is a function of at least leucine, apart from the role of BAA as substrates for protein synthesis.
3. to contribute amino groups for the synthesis of alanine and glutamine, both of which are involved in gluconeogenesis.
4. to encourage metabolism of pyruvate to alanine, rather than to lactate.
5. to encourage proton efflux from muscle (via glutamine), so as to maintain intramuscular pH at optimum.
A further observation concerns the BAA and the liver. It is known that during strenuous exercise in man the liver suffers a net loss of the BAA; the skeletal muscle concomitantly takes up BAA from the blood. Thus, the increased burning of BAA in muscle seems to cause a "drain" on the BAA stored in liver protein. Further, it has been noted that the rate of protein breakdown in the liver can be partly reversed by amino acids--in particular glutamine. In particular, it was noted that an increased amount of glutamine ws exported from the liver during exercise, which may be related to the effect of this amino acid on protein synthesis. Glutamine is, therefore, included in this invention, to provide the liver with that amino acid which is known to encourage protein synthesis, in the proper metabolic environment. The liver, being central to numerous metabolic functions, may in fact be the key to adaptation to exercise.
The last amino acid to be part of this invention is carnitine. (While not all authorities will agree with designating carnitine an amino acid, it is so designated here; its chemical designation is: 3-hydroxy-4-N-trimethylaminobutyrate.) This amino acid is synthesized in the body from two other (essential) amino acids (lysine and methionine). Carnitine is known to be required for the oxidation of fat for calories, and that fat is a major fuel for skeletal muscle during exercise.
It is known as well that carnitine metabolism increases during exercise training. Further, carnitine has been shown to protect against the toxic effects of ammonia. Ammonia is generated during catabolism of amino acids, such as occurs during strenuous exercise, and is toxic. The ready removal of ammonia from muscle is thus desirable.
It is only recently known that carnitine may be important in the oxidation of the BAA in muscle. Also, a study of patients with coronary-artery disease showed that those patients who received oral supplements of carnitine did significantly better on exercise tests.
The present invention employs carnitine to optimize skeletal muscle function in relation to oxidation of fatty acids for calories; to the oxidation of BAA for the effects summarized above; and to enhance the removal of toxic ammonia.
Heretofore, conventional diets for "sports" or for exercise programs have employed supplements of whole protein, without consideration of the possible applications of the pharmacologic properties of specific components (amino acids) of the proteins. What is needed is a dietary supplement which provides the best metabolic milieu to permit and encourage protein synthesis in skeletal muscle and in liver.
Accordingly, it is an object of this invention to supply an amino acid supplement which is directed at optimizing protein synthesis in skeletal muscle and in liver.
The objects of the invention are realized by a careful selection of specific amino acids to be added to whole protein and other nutrients, so as to achieve a diet which is enriched with specific amino acids (carnitine, glutamine, isoleucine, leucine and valine), in order to maximize protein synthesis in skeletal muscle.
BRIEF DESCRIPTION OF THE DRAWING
The sole FIGURE of the drawing is a simplified diagram which illustrates interrelationships of protein and amino acids within muscle cells.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The compositions of this invention are defined by the following L-amino acids in the cited ranges (expressed in grams of each amino and per 100 grams of whole protein).
______________________________________ Grams per 100 gramsAmino Acid whole protein______________________________________L-carnitine from 0.3 to 2.0L-glutamine from 10.0 to 30.0L-isoleucine from 15.0 to 40.0L-leucine from 20.0 to 45.0L-valine from 15.0 to 40.0______________________________________
The amino acids used in practicing this invention are preferably pure, and in the crystalline form. They should be in the L-form, rather than the D-form. The amino acids are preferred to be in the free form, rather than as salts or derivatives; however, the salts and derivatives may be employed if those forms enable superior formulation with other nutrients as described below. The keto- (or oxo-) forms of the amino acids may also be employed.
The composition is suitable for oral intake. Total daily intake of the supplement may vary as needed, but generally will not exceed 30% of the individual's usual protein intake. The supplement should be composed of the appropriate amino acids in conjunction with other nutrients, including whole protein, vitamins, minerals, all of which may be combined with the amino acid composition of the invention prior to administration, or supplied through ordinary dietary sources.
The ranges of the amino acid proportions recited above, the concentrations of ingested amino acid-containing diet supplements, the amount of amino acids ingested per day, and the rate of ingestion of amino acids or supplements containing them may all be varied to refine the adaptive responsiveness of the individual in training.
The effectiveness of the dietary program which utilizes these amino acid supplements may be assessed by well-known measures of aerobic training and of skeletal muscle function, during and following the exercise period. Suitable examples of functional efficacy include the following: time to onset of muscle or overall fatigue, intensity of effort, pulse rate, oxygen consumption, strength testing (by dynamometry), and mid-arm muscle circumference. Other assessment criteria will be apparent to the ordinary artisan.
The relative proportions of the amino acids are preferably within 20% of the ranges recited above. The proportions of the BAA (isoleucine, leucine and valine) should be approximately 50% (w:w) of the whole protein portion of the diet supplement.
The concentration of nutrients should be such that osmolality of the supplement, as ingested, be not greater than 400 m Osm/kg of water; this will avoid subjecting the intestine to "osmotic shock" during a period of reduced hemoperfusion. One unit of supplement would contain approximately 10% of the individual's usual daily intake of protein. Three units would be ingested in roughly the following schedule. One unit to be consumed slowly (over 10-15 minutes) beginning 45 to 30 minutes prior to the onset of strenuous exercise. A second unit to be consumed in small amounts during most of the exercise period. The third unit to be ingested slowly (over 10-15 minutes) within 30 to 60 minutes after exercise ceases.
The above manner of spreading out intake of the supplements serves two purposes: 1. it avoids intestinal distress by allowing only small volumes of fluids and nutrients to enter the intesting during exercise; and 2. it encourages a steady input of nutrients into the bloodstream during the entire "peri-exercise period" (i.e., before, during and after exercise), since this is when the nutrients will be most needed and used for their unique effects.
The invention will be more fully understood by reference to the following example.
EXAMPLE 1
This example demonstrates the formulation and use of the diet supplement which contain the AA composition of this invention.
The formulation of one unit consists of the following amounts of nutrients per 400 ml of water:
______________________________________Nutrient Quantity______________________________________Amino AcidsL-carnitine 0.025 gr.L-glutamine 0.05 gr.L-isoleucine 0.625 gr.L-leucine 0.85 gr.L-valine 0.625 gr.ProteinCasein, soy protein, 2.5 gr.lactalbumin, or anycombination thereof.CarbohydratesCorn syrup solids; sucrose 25.0 gr.FatsSunflower oil; soybean oil 5.5 gr.(1:1, vol.:vol.)Medium-chain triglycerides 6.0 gr.Vitamins (10% RDA)Vitamin C 6.0 mg.Folic acid 35 microgramVitamin B1 1.0 mg.Vitamin B2 1.2 mg.Niacin 1.7 mg.Vitamin B6 0.15 mg.Biotin 15 microgramCholine 5.0 mg.Vitamin B12 1.0 microgramPantothenate 0.2 mg.MineralsSodium 60 mg.Magnesium 20 mg.Potassium 200 mg.Calcium 50 mg.Phosphate 75 mg.Chloride 350 mg.______________________________________
The volume of water should be adjusted to keep the osmolality between 300 and 600 m Osm/kg, preferably towards the low end of this range.
Three supplement units are taken as described above. The total intake is carefully recorded. Depending on the exercise regime appropriate to a given sport, relevant parameters of efficacy are monitored during and following the exercise period. Dietary supplements should be dosed according to the needs of the athlete.
This invention is intended only as a supplement; the diet composition suggested should not be used as the sole or major source of nutrition on a daily basis. It should also not be ingested by individuals not undergoing exercise programs. | A combination of amino acids (carnitine, glutamine, isoleucine, leucine and valine) provide diet supplements which employ branched amino acids (BAA) to promote muscle adaptation to strenuous exercise. The diet supplements provide the BAA substrate which is utilized at the expense of muscle mass as well as liver protein, stimulate muscle and liver protein synthesis, contribute amino groups for the synthesis of alanine and glutamine, encourage metabolism of pyruvate to alanine, rather than to lactate, and encourage proton efflux from muscle (via glutamine). | 0 |
BACKGROUND OF THE INVENTION
The field of the invention is systems for analyzing athletic performance and body mechanics of a subject, for example, those body mechanics of a pitcher who is being trained to pitch a baseball.
U.S. Pat. No. 4,830,369 teaches a baseball pitching practice target which includes a plurality of panel members disposed side-by-side to form a target area and a support frame which independently supports the panel members. Each panel has a designated segment portion of the target area. The target area includes a central strike zone area which is delimited by some of the panel members. A plurality of normally-open electrical contact are associated with each panel and are closable upon the application of an impact force on an outer surface of its associated panel. A display device identifies which panel has been subjected to an impact force. A visual display identifies the panel having been impacted and also provides a numerical read-out of a total numerical value with each of the panels having independent numerical values.
U.S. Pat. No. 4,629,188 teaches a baseball target device which includes a target that is adjustable in height and length to simulate the strike zones of different size batters. The baseball target device utilizes a base to which a telescopically adjustable vertical frame is attached, wherein the frame supports an adjustable spring-loaded window shade device. The shade of this device hangs down from the frame and its unrolled portion defines a "strike zone" for the pitcher. A picture of a crouched catcher and umpire is imprinted on the shade to give the target a realistic effect. The pitcher may adjust the target to the size of the strike zone for a particular batter by adjusting the telescopic frame to the height of the batter's shoulder and then adjusting the target shade to the batter's knee, thus creating a target whose size and location simulates the exact strike zone for that particular batter.
U.S. Pat. No. 5,064,194 teaches an apparatus for practicing pitching of baseballs to enable a user to improve pitching accuracy and to indicate pitched balls delivered within a strike zone.
U.S. Pat. No. 4,955,607 teaches a double loop device for practicing spot pitching which simulates actual game conditions.
U.S. Pat. No. 4,781,376 teaches a life-like training device for pitchers which has a target including a catcher figure and separate batter figure. Both the catcher figure and batter figure are adjustable in height to simulate different sized batters from Little League to adult size. The batter figure can be supported as a left or right handed batter and is pivotable as well as adjustable in distance from the catcher to simulate different batter box positions. A catcher's mitt target is supported on the catcher figure in different positions for different pitches and has an alarm in the pocket of the mitt to indicate an on-target pitch.
U.S. Pat. No. 4,563,005 teaches an apparatus for detecting and computing the location of a baseball as it is pitched over a plate in which infrared receivers are disposed at corner locations on opposite sides of a target zone which is aligned with the plate. First and second arrays of infrared emitters are mounted on opposite sides of the target zone for transmitting infrared light pulses to the opposite corner receivers. The infrared emitters are sequentially energized and transmit infrared pulse signals having relatively short durations in a scan cycle. Digital data words representative of the reception and nonreception by the receivers of the optical pulse signals are generated during each pulse interval of the scan cycle. Computer circuitry calculates the coordinates of the baseball within the target zone as a function of predetermined angular data retrieved computer memory. The computer memory is preprogrammed with a table of angular data corresponding to each receiver data word and the particular emitter pulse interval in which it occurs.
U.S. Pat. No. 4,545,576 teaches a baseball-strike indicator and trajectory analyzer which computes the trajectory of a moving object by remote, non-interfering sensors. The apparatus is able to compute the trajectory of a pitched baseball throughout its flight, including the trajectory of the baseball as it passes in the vicinity of a three-dimensional strike zone. The apparatus includes two pairs of video cameras, an alignment mechanism, video-storage device, a digitizer, a computer, output devices and an operator's console. The baseball-strike indicator and trajectory analyzer is required to identify the baseball, compute its position in three dimensions as a function of time, compute the speed of the baseball and its trajectory, and present the output via computer graphics to present the viewer with essentially any desired view of the pitched baseball.
U.S. Pat. No. 4,657,250 teaches a pitching practice apparatus which includes a frontal mechanical strike zone target at which the pitcher aims the ball and which contains yielding elements enabling the ball to pass rearwardly through a photoelectric sensing plane having sensing beams on two orthogonal axes. The photoelectric sensing arrangement precisely locates the position of the ball in the strike zone horizontally and vertically.
U.S. Pat. No. 5,138,322 teaches an apparatus for continuously and precisely measuring the positions of a tennis ball in motion in a predefined three-dimensional region. The apparatus transmit multiple radar signals from a first, second and third antenna devices into the predefined three-dimensional region. Multiple return signals are sensed and are compared with the transmitted signals to determine phases of the return signal to thereby obtain ranges of the object.
U.S. Pat. No. 4,858,922 teaches an apparatus for determining the velocity and path of travel of a ball which includes a pair of velocity sensing devices which are are disposed on opposite sides of the proposed path of travel of a ball. The electromagnetic energy beams from the sensing devices are directed at acute angles to the proposed path of travel. Velocity signals which are generated by the two sensing devices are averaged and converted to visible messages concerning the speed of the ball and its likely distance of travel had its flight not been interrupted.
U.S. Pat. No. 4,673,183 teaches a golf playing arrangement which includes a fairway, a tee area at one end of the fairway, a plurality of radar ground surveillance units located on the fairway at a successively greater distance from the tee area, a central processor, a video display and a putting green adjacent the tee area. Each ground surveillance unit detects golf balls moving on the ground in a predetermined circular area. The central processor calculates and the computer terminal visually displays the distance of the unit furthest from the tee area which detects a golf ball moving therethrough, and the sum of a succession of such distances.
U.S. Pat. No. 4,979,745 teaches an apparatus for practicing a golf swing includes a processor, a transmitter-receiver and a relay. The transmitter-receiver is stationarily arranged on the ground. The relay is attached to the golf club in or near to the head thereof. The transmitter-receiver includes an infrared light emitter and a pair of receivers. The relay includes a receiver for receiving the light from the emitter of the transmitter-receiver and a infrared ray emitter for emitting a ray toward the pair of receivers of the transmitter-receiver. The processor processes the light received by the pair of receivers separately, for detecting a change in intensity at time elapses for calculating the direction of the swing, and the timing of a maximum intensity for obtaining the head speed.
U.S. Pat. No. 4,898,389 teaches a golf training device which detachably coupled to the head of any golf club in order to give a golfer an exact indication of the point of impact of the face of a golf club with a golf ball. The training device includes a housing which supports at least one impact sensitive transducer, an electronic circuit and a display system. The impact sensitive transducer generates an electric signal upon impact. The electronic circuit determines if the transducer has received an impact. The display system is responsive to the electronic circuit and signals if the transducer has received an impact. There is a mechanism for connecting and disconnecting the training device to a golf club head. When attached to the head of a club, with the transducer on the face of the club, and swung into contact with a golf ball, the transducer generates an electrical signal which is transmitted to the electronic circuit which processes the electrical signal and transmit it to the display system which indicates the point of contact of the club face with the golf ball.
U.S. Pat. No. 4,708,343 teaches a baseball practice apparatus which includes a vertically extending panel having a plurality of selectively operable lights which generate focused light beams directed forward from the panel. A player swings a bat having a light reflecting surface which will intercept and cause the light beams to be reflected back towards the panel. On the panel there is an array of spaced light sensors. One of the light sensors detects the reflected light. A visual indication is provides the simulated result of the swing, for example, a "line drive" or a "fly ball". A foregoing visual display is provided in response to which a light, or lights, were illuminated to simulate a pitched ball and which a sensor senses reflected light from the bat A "curve", a "sinker" or other pitch is simulated by actuating selected lights in a predetermined sequence.
U.S. Pat. No. 4,515,365 teaches an apparatus for measuring and analyzing the swing of a baseball player. The apparatus includes devices for emitting a plurality of spaced light beams projected in directions to be intersected by the swing plane of a bat and a corresponding plurality of light receiving elements arranged to receive light beams reflected from the bat. Signals received by the light receiving elements are collected and supplied to a processing apparatus and the results of this processing are displayed on a display which provides indication of angle, speed and level of the swing. The information may also be provided to a printer. The apparatus indicates whether the swing is performed normally and if it deviates from normal indicates the error involved.
U.S. Pat. No. 4,977,896 teaches an array of magnetic and/or electrical sensors external which measures signals produced by brain activity. Each sensor of the array of magnetic and/or electrical sensors is external to but proximate to either the head or other portion of the body of a subject. The measurements which are obtained simultaneously from all of the sensors are combined in a manner to permit selective measurement of the electrical activity from a specified location within the body, or alternatively, to permit the location in the body producing a particular type of response to be identified. The instantaneous measurement of each sensor is scaled by a weighting coefficient for that sensor, and the products added over all of the sensors. The weighting coefficients are calculated from a mathematical model of the brain that includes information on the shape of the potential source, the extent or type of source activity, the electrical and magnetic properties of the media, and the locations and orientations of the sources and the sensors.
SUMMARY OF INVENTION
The present invention is directed to a system for training a pitcher to pitch a baseball. The system includes a plurality of position detectors, a processor, a display and a target to which the pitcher pitches the baseball.
In a first aspect of the invention each position detector is disposed in the path of flight of the pitched baseball.
In a second aspect of the invention each position detector is a locating array which has at least one ultrasonic transmitter and at least three ultrasonic receivers.
In a third aspect of the invention each position detector includes an ultrasonic transmitter and an ultrasonic receiver coupled to either a catcher or a coach for computing the speed of a pitched baseball.
In a fourth aspect of the invention a smart plate includes a plate, at least one optical transmitter and at least one optical receiver both of which are disposed inside the peripheral edge of the plate for detecting the time dependent position in a two-dimensional space of the pitched baseball as it overpasses the first smart plate.
In a fifth aspect of the invention the smart plate also includes at least one ultrasonic transmitter and at least one ultrasonic receiver coupled to the top surface of the plate for detecting the time dependent height of the pitched baseball as it overpasses the first smart plate.
In a sixth aspect of the invention a second smart plate has a plate, at least one ultrasonic transmitter and at least three ultrasonic receivers all of which are coupled to the top surface of the plate for detecting the time dependent position in a three-dimensional space of a pitched baseball as it overpasses the second smart plate.
In a seventh aspect of the invention a plurality of locating arrays are disposed around a pitcher who is wearing a plurality of ultrasonic transmitters for analyzing his pitching mechanics.
In an eighth aspect of the invention a catcher's mitt is a movable target to which a pitcher pitches a baseball and a movement detector coupled to the catcher's mitt so that the movement detector measures the distance which a catcher moves his mitt from its initial target position to the position required for catching the pitched baseball.
Other aspects and many of the attendant advantages will be more readily appreciated as the same becomes better understood by reference to the following detailed description and considered in connection with the accompanying drawing in which like reference symbols designate like parts throughout the figures.
The features of the present invention which are believed to be novel are set forth with particularity in the appended claims.
DESCRIPTION OF THE INVENTION
FIG. 1 is a schematic diagram of a pitcher, a catcher who is wearing a wrist speedgun and automatic target unit, a system for training the pitcher to pitch a baseball including a plurality of locating arrays disposed both along the path of flight of the baseball and around the pitcher, a smart plate, a processor which is coupled to the locating arrays and a display according to the first embodiment.
FIG. 2 is a perspective drawing of one of the locating arrays of FIG. 1 which includes one ultrasonic transmitter and three ultrasonic receivers.
FIG. 3 is a block diagram of the locating array of FIG. 2.
FIG. 4 is front elevational view of the processor and the display of FIG. 1.
FIG. 5 is a block diagram of the processor and the display of FIG. 1 and a user interface, an acquisition and processing device and a memory module.
FIG. 6 is a schematic diagram of the smart plate and the catcher wearing the wrist speedgun and automatic target unit of FIG. 1.
FIG. 7 is a perspective of the wrist speedgun and automatic target unit of FIG. 1.
FIG. 8 is a partial front elevational view of the wrist speedgun and automatic target unit of FIG. 1.
FIG. 9 is a block diagram of the wrist speedgun and automatic target unit of FIG. 1.
FIG. 10 is a front elevational view of a wrist speedgun and accuracy unit with a detachable transducer unit according to the second embodiment.
FIG. 11 is a side elevational view of the wrist speedgun and accuracy unit of FIG. 10.
FIG. 12 is top plan view of the detachable transducer unit of the wrist speedgun and accuracy unit of FIG. 10.
FIG. 13 is a front elevational view of a hand-held speedgun according to the third embodiment.
FIG. 14 is a side elevational view of the hand-held speedgun of FIG. 13.
FIG. 15 is a schematic diagram of a pitcher who has a plurality of transmitters which are applied to various parts of his body according to the fourth embodiment.
FIG. 16 is a schematic diagram of a batter who has a plurality of transmitters which are applied to various parts of his body and his bat according to the fifth embodiment.
FIG. 17 is a schematic diagram of a golfer who has a plurality of transmitters which are applied to various parts of his body and his bat according to the sixth embodiment.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1 in conjunction with FIG. 2 a system 10 for training a pitcher to pitch a baseball includes a plurality of ball position detectors 11, a processor 12 and a display 13 and a target 14 to which the pitcher pitches the baseball. Measuring the time dependent three-dimensional trajectory of the pitched baseball in flight inherently provides three-dimensional velocity information. Accuracy is also determined from ball trajectory for the case where accuracy is measured with respect to a fixed target such as either a baseball plate or a static target such as a backstop with a visible target pattern. The processor 12 may also control and measure accuracy with respect to an electro-mechanical target such as an array of lights, a moving picture, or a series of impact-actuated panels. The processor 12 has the ability to modify the target which is presented to the pitcher and measure pitching accuracy autonomously within a training session.
Each ball position detector 11 is disposed in the flight path of a pitched baseball. The processor 12 is coupled to the ball position detectors 11. The display 13 is coupled to the processor 12. The target 14 is coupled to the processor 12. The target 14, the ball position detectors 11 and the processor 12 operate together to determine the speed, the accuracy and the trajectory of the pitched baseball. Each ball position detector 11 is a locating array which includes an elongated housing 15, an ultrasonic transmitter 16 and three non-collinear ultrasonic receivers 17, 18 and 19. The transmitter 16 and the three ultrasonic receivers 17, 18 and 19 operate together to determine the three-dimensional position of the pitched baseball as it flies within the field of view of the ball position detector 11. Each ball position detector 11 is usually placed on the ground between the pitcher and the target and is oriented at right angles to a straight line drawn from the pitcher to the catcher. A plurality of ball position detectors 11 are used under control of the processor 12 to track the pitched baseball over its flight path.
The processor 12 initiates the transmission of a signal from the ultrasonic transmitter 16. The signal is reflected from the baseball and returns to the ultrasonic receivers 17, 18 and 19. Based on the delay time between the time of transmission and the time at which the echoes are received by ultrasonic receivers 17, 18 and 19 the position of the pitched baseball at the time of reflection is determined. The plurality of ball position detectors 11 each of which is under the control of the processor 12 produces a series of multiple transmit and receive cycles which the processor 12 uses to determine the three-dimensional position of the pitched baseball in flight.
In the preferred embodiment each ball position detector 11 includes an elongated housing 15, an ultrasonic transmitter 16, a first ultrasonic receiver 17, a second ultrasonic receiver 18 and a third ultrasonic receiver 19. The elongated housing 15 has a first end 20 and a second end 21. The ultrasonic transmitter 16 is coupled to the elongated housing 15 between the first and second ends 20 and 21 thereof and is disposed at a first vertical level. The first ultrasonic receiver 17 is coupled to the elongated housing 15 between the first and second ends 20 and 21 and is disposed at the first vertical level. The second ultrasonic receiver 18 is coupled to the elongated housing 15 at the first end 20 thereof. The third ultrasonic receiver 19 is coupled to the elongated housing 15 at the second end 21 thereof. The second and third ultrasonic receivers 18 and 19 are disposed at a second vertical level which is different than the first vertical level so that the first, second and third ultrasonic receivers 17, 18 and 19 are non-collinear thereby forming a locating array. The non-collinear arrangement is necessary to provide unique ball position calculations to be made from the three echo distances. A locating array's field of coverage (the three dimensional space in which the locating array can measure the position of the baseball) can be optimally maximized using either or both of the following techniques: a) by using additional (more than three) ultrasonic transducer elements, and b) by optimizing the angular coverage and sensitivity of each ultrasonic transducer element within the locating array. This is accomplished by forming each tranducer element out of a pluality of sub-elements which are geometicalluy and electrically coordinated.
Referring to FIG. 3 in conjunction with FIG. 2 the ultrasonic transmitter 16 and the first ultrasonic receiver 17 includes a control logic circuit 22, a pulse counter 23, a drive circuit 24, a coupling circuit 25, a transducer 26 or plurality of transducers, a tuned amplifier 27 and a latch 28. The coupling circuit 25 couples the drive circuit 24 to the transducer 26. The drive circuit 24 drives the transducer 26. The coupling circuit 25 is coupled to the latch 28 through the tuned amplifier 27. The latch 28 is coupled to the control logic circuit 22. The processor 12 provides a send signal to the ultrasonic transmitter 16. Based on this signal the control logic circuit 22 triggers the pulse counter 23. The pulse counter produces a series of pulses of appropriate frequency, duty cycle, and duration. The transducer 26 is driven with this temporal signal at the appropriate voltage and impedance which are provided by the drive circuit 24 and coupling circuit 25. After the echo return signal returns from the pitched baseball the transducer 26 receives the echo return signal and couples it to the tuned amplifier 27 through the coupling circuit 25. The tuned amplifier 27 conditions this echo return signal and based on magnitude and duration criteria produces a digital signal to the latch 28. The latch 28 responds by triggering the control logic circuit 22 which in turn responds by sending the echo return signal to the processor 12. Subsequent echo return signals are similarly processed.
Each of the second and third ultrasonic receivers 18 and 19 includes a control logic circuit 22, a coupling circuit 25, a tuned amplifier 27 and a latch 28. The coupling circuit 25 is coupled to the latch 28 through the tuned amplifier 27. The latch 28 is coupled to the control logic circuit 22. These elements operate in processing a received echo return signal in the same manner as described above.
Referring to FIG. 4 in conjunction with FIG. 1 and FIG. 5 a processor unit 30 includes sixteen bit echo timers 31 which are used to measure the duration of echoes to each receiver in the system 10, an event timer 32 which provides a master timing clock for the system 10, an RS-232 interface module 33 which allows the processor unit 30 to communicate with other computers, a crystal 34 which provides microprocessor timing, a microprocessor 35 which controls the system 10 and processes data, a random access memory 36, a non-volatile memory 37 which allows data to be held between training sessions, a memory card interface module 38 and a user memory card 39 which contains user specific data and may be retained by a specific user between training sessions. The sixteen bit echo timer 31, the event timer 32 and the RS-232 interface module 33 are coupled to the microprocessor 35. The random access memory 36 and the non-volatile memory 37 are coupled to the microprocessor 35. The user memory card interface module 38 is coupled to the microprocessor 35 and the user memory card 39. The display unit 40 includes an interface logic module 41, user interface buttons 42 on a key pad, a display driver 43 and a display 44. The display 44 displays information to the user and allows for the user to control the processor unit 30 and the entire system via the user interface buttons 42 on the key pad. The display driver 43 is coupled to the microprocessor 35. The display 44 is coupled to the display driver 43. The interface logic module 41 is coupled to the microprocessor 35. The user interface buttons 42 are coupled to the interface logic module 41.
Referring to FIG. 6 in conjunction with FIG. 1 the system 10 also includes a smart plate 110 for detecting the time dependent position in a three-dimensional flight path of the pitched baseball in order to call balls and strikes based on the location of pitched baseball as it overflies the smart plate 110. The first smart plate 110 includes a plate 111 having a peripheral edge 112 and a top surface 113, a plurality of optical transmitters 114 and a plurality of optical receivers 115. The optical transmitters 114 are disposed inside the peripheral edge 112 of the plate 111. The optical receivers 115 are disposed inside the peripheral edge 112 of the plate 111. The optical transmitters 114 and optical receivers 115 operate together with the processor 12 to detect the time dependent position in a two-dimensional space of a pitched baseball as it overpasses the smart plate 110. Each of the optical transmitters 114 projects a narrow beam of light in a vertical direction above the smart plate 110. As the pitched baseball passes over one of the peripheral edge of the smart plate 110 the beam of light is reflected from the baseball back to the smart plate 110 and is detected by the optical receivers 115. The smart plate 110 communicates this signal to the processor 12 which determines based on this signal that the pitched baseball has passed over some portion of the smart plate 110 thereby satisfying the two-dimensional criteria of a called strike. In order to measure the vertical height of the pitched baseball as it passes over the smart plate 110 the smart plate 110 also includes an ultrasonic transmitter 116 and at least one ultrasonic receiver 117. The ultrasonic transmitter 116 is coupled to the top surface 113 of the plate 111 and the processor 12. The ultrasonic receiver 117 is coupled to the top surface 113 of plate 111 and the processor 12. The ultrasonic transmitter 116 and the ultrasonic receiver(s) 117 operate together to detect the time dependent height of the pitched baseball as it overpasses the smart plate 110. The processor 12 controls the echo location process as performed by the ultrasonic transmitter 116 and the ultrasonic receiver 117. The two-dimensional information which the optical transmitters 114 and the optical receivers 115 provide and the height information which the ultrasonic transmitter 116 and the ultrasonic receiver(s) 117 provide allow for strikes to be called based on a user defined a three-dimensional strike zone. The processor 12 processes the two-dimensional information and the height information and provides the result on the display 13.
The smart plate 110 may also include an ultrasonic locating array for calling strikes and measuring the trajectory of the pitched baseball as it overflies the smart plate 110. The smart plate 110 also includes at least one ultrasonic transmitter 116 and at least three non-collinear ultrasonic receivers 117. The ultrasonic transmitter 116 and the three non-collinear ultrasonic receivers 117 are disposed inside the peripheral edge 112 of the plate 111. The ultrasonic transmitter 116 and the three non-collinear ultrasonic receivers 117 operate together to detect the time dependent position in a three-dimensional space of a pitched baseball as it overpasses the smart plate 110. The principle of operation of the smart plate 110 is same as that of the position detector 11. The ultrasonic transmitter 116 sends an ultrasound signal angled towards the incoming pitched baseball. The ultrasonic receivers 117 receive the ultrasonic echoes from the incoming pitched baseball and sends this information to the processor 12 which processes the information in order to determine the time dependent position in a three-dimensional space of the pitched baseball as it overpasses the smart plate 110. The three-dimensional information which the ultrasonic transmitters 116 and the ultrasonic receivers 117 provide allows for balls and strikes to be called based on a user defined three-dimensional strike zone. The processor 12 processes the three-dimensional information and provides the result on the display 13.
Referring to FIG. 7 in conjunction with FIG. 1, FIG. 2, FIG. 8 and FIG. 9 a wrist accuracy unit and speedgun 210 includes a housing 211, a plurality of ultrasonic transmitters 212 and an ultrasonic transmitter/receiver 213, a control panel 214, a processor 221 and a display 216. The housing 211 is coupled to a catcher's wrist adjacent to his mitt. The ultrasonic transmitters 212 and the ultrasonic transmitter/receiver 213 are coupled to the processor 221. The display 216 is coupled to the processor 221. The wrist accuracy unit and speedgun 210 not only provides a measurement of pitch accuracy in terms of the difference between the position of the catcher's mitt as the catcher present the target to the pitcher and position of the baseball when it arrives in the catcher's mitt, but provides a measurement of speed of the pitched baseball as it approaches and reaches the catcher's mitt.
Referring to FIG. 9 in conjunction with FIG. 7 and FIG. 8 the wrist accuracy unit and speedgun 210 also includes a wireless transceiver 218, ultrasonic transmitters 212, an ultrasonic transmitter/reciever 213, a control panel 214, a central processor 221 with random access memory 222, a beeper 223 which is coupled to the display 216, a battery 224, a ball impact detection circuit 225, a ball impact detection conditioning circuit 226 and non-volatile memory 227. The control panel 214 is coupled to the central processor 221. The central processor 221 is coupled to the display 216. The ball impact detection circuit 225 is coupled to the ball impact detection conditioning circuit 226. The ball impact detection conditioning circuit 226 is coupled to the central processor 221. The wireless transceiver 218 is coupled to the central processor 221. The ultrasonic transmitters 212 and the ultrasonic transmitter/receiver 213 are coupled to the central processor 221.
When the catcher wears the wrist accuracy unit and speedgun 210 on his wrist adjacent to his mitt the display 216 faces him while the ultrasonic transmitters 212 and the ultrasonic transmitter/receiver 213 face the incoming baseball. The catcher operates the wrist accuracy unit and speedgun 210.
Before presenting a target to the pitcher he activates the wrist accuracy unit and speedgun 210 by means of buttons 220 on the control panel 214 in order to measure and record the position of the pitching target, namely his mitt. The location of the wrist accuracy unit and speedgun 210 is measured by the transmission of consecutive signals from the ultrasonic transmitters 212. Concurrent with each of these signals a radio pulse is sent by the wireless transceiver 218. The combination of the locating array 11 which is positioned several feet in front of the catcher on the ground in a measured and known location and the processor 12 uses the radio pulse and signals from the ultrasonic transmitters 212 to determine the three-dimensional position of the wrist accuracy unit and speedgun 210 and hence the position of the pitching target, namely the catcher's mitt. When two ultrasonic transmitters 212 are used in order to allow measurement of both location and rotation of the wrist, a more accurate determination of the position of the mitt's pocket, which is the precise target and in which the pitched baseball lands, is able to be determined. After the pitcher pitches the baseball the ultrasonic transmitter/receiver 213 determines the speed of the pitched baseball as it approaches the mitt. The central processor 221 controls the ultrasonic transmitters 212 and the ultrasonic transmitter/receiver 213 and extrapolates the time of impact. At the time of ball impact the ultrasonic transmitters 212 send another set of radio-frequency and ultrasonic signals to the locating array 11. The processor 12 calculates the after catch position of the mitt and transmits this information to the wrist accuracy unit and speedgun 210. This information along with the speed of the pitched baseball is displayed by the central processor 221 to the catcher on the display 216. The ball impact detection circuit 225 includes either an accelerometer or a microphone for detecting either mechanical movement or sound which the arriving pitched baseball produces. The ball impact detection circuit 225 alternately or supplementally can be used to determine the time of the arrival of the pitched baseball. The ball impact conditioning circuit 226 conditions this signal and communicates it the central processor 221.
The ball impact detection circuit 225 may include three accelerometers which may also be used as an alternative means to determine the movement of the mitt from the time the target is presented to when the pitched baseball arrives by integrating the three-dimensional acceleration signals within the central processor 221. To facilitate this accelorometric movement detection scheme the ball impact conditioning circuit 226 should include an analog to digital converter.
The ultrasonic transmitter/receiver 213 operates to measure velocity of the pitched baseball by one of two methods. The first method is to measure distance to the baseball with respect to time. Each distance measurment is made by measuring the time delay between the time of transmission of a signal and reception of the echo returning from the pitched baseball. The second method is to evaluate the Doppler frequency shift of the echo with respect to the transmitted signal.
Referring to FIG. 10 in conjunction with FIG. 9, FIG. 11 and FIG. 12 a wrist speedgun and accuracy unit 310 includes a housing 311, an ultrasonic transmitter/receiver unit 312, a housing 313, a processor 221 and a display 314. The housing 311 may be strapped to the wrist. The functional block diagram of the wrist speedgun and automatic target unit 310 is the same as the functional block diagram of the wrist accuracy unit and speedgun 210 in FIG. 9. The housing 311 may be strapped to the wrist. The measurement of both the baseball velocity and the mitt position for use in making the accuracy measurement is accomplished with the ultrasonic transmitter/receiver unit 312. The wrist speedgun and automatic target unit 310 is used by removing the ultrasonic transmitter/receiver unit 312 therefrom and clipping it to the catcher's mitt. The ultrasonic transmitter/receiver unit 312 is mounted on a ball and socket joint 315 so that it can be adjusted to point in the direction of the incoming pitched baseball.
The two functions of the ultrasonic transmitter/receiver unit 312 are 1) the measurement of the velocity of the pitched baseball as it approaches the catcher's mitt; and 2) the transmission of an ultrasonic signal before and after the pitch which allows the determination of pitch accuracy. The second wrist speedgun and automatic target unit 310 performs both of these functions in the same manner as the wrist speedgun and automatic target unit 210. Because the ultrasonic transducer is positioned on the catcher's mitt directly a single transducer is adequate to provide both the measurement of the baseball velocity and the determination of the mitt location.
Referring to FIG. 13 in conjunction with FIG. 9 and FIG. 14 a hand-held speed gun 410 includes a housing 411, an ultrasonic transmitter/receiver unit 412, a display 414 and a belt-clip 415. The hand-held speed gun 410 also includes processing electronics and a wireless transmitter/receiver and operates in the similar manner as the wrist speedgun and automatic target unit 210 operates by measuring the distance with respect to time or alternatively by measuring the Doppler shift of the echo. The hand-held speed gun 410 is small enough to be able to fit in a shirt pocket.
Referring to FIG. 15 in conjunction with FIG. 1, FIG. 2, FIG. 4 and FIG. 5 the system 10 is also used to measure the motions of the pitcher's body as he delivers a baseball pitch in order to determine and analyze the pitching mechanics of the pitcher. The system 10 further includes a plurality of ultrasonic transmitters 511 and a plurality of locating arrays 512 which are disposed around the pitcher. The ultrasonic transmitters 511 are disposed on the body of the pitcher and are placed at various critical poistion of his body, generally at his hands, his elbow joints, his shoulder joints, his ankle joints, his knee joint and both sides of his head. Each locating array 512 includes at least three non-collinear ultrasonic receivers and is similar to the locating array 11. The locating arrays 512 are disposed around the pitcher in measured and known positions and operates in the same manner as the locating arrays 11. The processor 12 is coupled to the ultrasonic transmitters 511 and the ultrasonic receivers of the locating arrays 512. The display 13 is coupled to the processor 12. The signals from the ultrasonic transmitters 511 may be multiplexed in either time or frequency.
At the start of a training session the ultrasonic transmitters 511 are coupled to the processor 12 and programmed thereby. Each ultrasonic transmitter 511 is identified and placed at a certain body position and programmed with timing and/or frequency information. This information is the time at which the individual ultrasonic transmitter 511 will send its signal and/or the frequency at which it will transmit. During the pitching session the locating arrays 512 receive a sequence of signals from the ultrasonic transmitters 511 which are located on the body of the pitcher. The transmitters 511 may either fire in sequence being identified according to their assigned order within that sequence or fire together being identified according to their assigned frequency. Based on these signals the processor 12 calculates the three-dimensional position of each signal and accordingly the position of that body point over time. This information is processed and presented to the user of the system 10 as either data or graphics, for example a representational picture of the pitcher's body. The ultrasonic transmitters 511 may be either augmented with or replaced by either a plurality of three-dimensional accelerometers or a plurality of optical transmitters. The locating arrays would then include a plurality of optical receivers configured as additional position detectors 11.
Referring to FIG. 16 in conjunction with FIG. 15 and FIG. 17 the system 10 may be used to measure the motions of the body of either a batter or a golfer as he swings either a bat or a club in order to determine and analyze the his body mechanics.
The system 10 includes a plurality of transmitters disposed on the body of the subject and at least one determinator of positions of the transmitters adjacent to the subject. When the transmitters are optical the determinator of positions includes at least one two dimensional array of optical sensors. When the transmitters are ultrasonic the determinator of positions includes at least three non-collinear ultrasonic receivers. The system 10 may also be used for determining and analyzing body mechanics of a subject undergoing either a medical diagnosis or rehabilitation.
From the foregoing it can be seen that a system for training a pitcher to pitch a baseball has been described. It should be noted that the sketches are not drawn to scale and that distance of and between the figures are not to be considered significant. Accordingly it is intended that the foregoing disclosure and showing made in the drawing shall be considered only as an illustration of the principle of the present invention. | A system for training a pitcher to pitch a baseball includes a plurality of emitting body markers worn by the pitchers, a plurality of position detectors for measuring both the position of the emitting body markers and the position of the pitched baseball, a target, a processor and a display. The processor is coupled to the emitting body markers, the position detectors and the target. The pitcher pitches the baseball to the target. The display is coupled to the processor. Each position detector is a locating array which has at least one ultrasonic transmitter and at least three non-collinear ultrasonic receivers. The locating array is disposed in the path of flight of the pitched baseball and and is used to determine the speed and the trajectory of the pitched baseball. The position of the emitting body markers are measured either optically or ultrasonically over a period of time so as to enable the analysis of the pitcher's body mechanics. The body mechanics analysis is also applicable to the golf, tennis, other sports and medical diagnostics. | 0 |
BRIEF SUMMARY OF THE INVENTION
In the past, many different types and kinds of devices have been employed for the purpose of catching fish. In this regard, special types of fishing rods have been employed to facilitate the setting of the fishhook in a positive manner so as to facilitate the catching of the fish. For example, reference may be made to the following U.S. Pat. Nos. 3,943,650 and 3,956,845. While such devices have been satisfactory for some applications, it would be highly desirable to have a simple and relatively inexpensive device which may be attached to a conventional fishing rod or pole to facilitate the setting of the fishhook during a fishing operation. In this regard, it would be highly desirable to have a device which would be readily attached to a fishing rod or pole and used to pull on a fishing line in an abrupt manner when the fish pulls on the line so as to set automatically the hook in the fish's mouth. Alternatively, the attachment need not be used on certain occasions, if desired.
Therefore, it is the principal object of the present invention to provide a new and improved attachment for fishing rods or the like, which fishing attachment is relatively inexpensive to manufacture and facilitates in the setting of the fishhook.
Briefly, the above and further objects are realized by providing a new and improved fishing device adapted to be attached to a fishing rod and having an inner tube telescoping within and axially aligned with an outer tube which is adapted to be attached to the fishing rod in parallel disposition thereto. A hook device is mounted on the inner tube and is adapted to be attached releasably to the fishing line. A main spring device urges resiliently the tubes to an initial position, and a latching device fixes releasably the tubes in a set position against the force of the main spring and frees the two tubes relative to one another in response to a force applied to the hook device via the fishing line so that the tubes return abruptly under the force of the spring device to their initial position, thereby jerking on the fishing line to set the fishhook in place to catch a fish. The main spring is in the form of a pair of coil springs interconnected threadably end-to-end so that the overall length of the main spring may be adjusted for storage purposes.
BRIEF DESCRIPTION OF DRAWINGS
Other objects and advantages of the present invention relating to the adjustable spring feature as well as others will become apparent to those skilled in the art when considered in connection with the accompanying drawings, wherein:
FIG. 1 is a pictorial side elevational view of the fishing device, which is constructed in accordance with the present invention and which is shown attached to a fishing device prepared to set automatically the hook during a fishing operation;
FIG. 2 is a greatly enlarged fragmentary cross-sectional elevational view of the device of FIG. 1;
FIG. 3 is a fragmentary reduced-scale elevational view of the front portion of the device of FIG. 2 illustrating it in an intermediate position moving from its set position after a pulling force is applied to the fishing line;
FIG. 4 is a reduced-scale cross-sectional elevational view of the rear portion of the device of FIG. 2;
FIG. 5 is a cross-sectional reduced-scale elevational view of the device of FIG. 2 illustrating it in its final position after the device has been released by the pulling force applied to the fishing line; and
FIG. 6 is a developmental view of the cam mechanism of the rear portion of the device of FIG. 2.
DETAILED DESCRIPTION
Referring now to the drawings, and more particularly to FIGS. 1 and 2 thereof, there is shown a new and improved fishing device 10, which is constructed in accordance with the present invention, and which is shown attached to a pole 11 of a fishing rod 12 having a handle 14 with a reel 16 mounted thereon. A fishing line 18 is mounted on the reel 16 and extends through a series of eyelets 20 on the pole 11 and terminates at a fishhook 22, which is adapted to be baited for fishing purposes. The device 10 generally comprises an outer tube 24 which is fixed to the pole 11 by a pair of clamps 26 and 28 to position the outer tube 24 in a parallel disposition on the upper portion of the pole 11. An inner tube 31 is disposed within the outer tube 24 in an axially aligned slidable manner. As best seen in FIGS. 2 and 5 of the drawings, a main spring 33 comprising a pair of axially aligned coil springs 33A and 33B threadably engaging one another as best seen in FIG. 5 of the drawings to form one long spring urges resiliently the inner and outer tubes to the position as shown in FIG. 5 of the drawings. The two-piece main spring enables the overall length of the unit to be adjustable for storage purposes as hereinafter described in greater detail. A latch member 35 is mounted for radially slidable movement on the inner tube 31 to engage a chamferred shoulder 37 at the end of an internal groove 39 of the outer tube 24 to fix releasably the inner tube 31 within the outer tube 24 in a set position as best seen in FIG. 2 of the drawings against the force of the main spring 33 to prepare the device 10 for catching a fish. A hook assembly 41 mounted on the forward end position of the inner tube 31 is adapted to receive an intermediate portion of the fishing line 18 to pull abruptly the fishing line rearwardly within the outer tube 24 when the latch member 35 releases the inner tube 31 relative to the outer tube as hereinafter described in greater detail when a pulling force is exerted on the fishing line 18. A latch spring 43 cooperates with an adjustment knob 45 mounted externally of the hook assembly 41 to enable the adjustment of the amount of tension required to release the latch member 35 as hereinafter described in greater detail. A push button 47 is reciprocatively mounted at the rear end portion of the inner tube 31 for causing the fishing line 18 to be free from the hook assembly 41 as hereinafter described in greater detail and for turning off a buzzer 49 energized by a pair of batteries 50 and 52, so that, when the latch 35 is released, the buzzer 45 generates an attention-attracting signal and the push button 47 may be pushed inwardly to turn off the buzzer 49 and release the line 18 from the hook assembly 41, to enable the reel 16 to be operated for pulling in the fish.
Considering now the outer tube 24 in greater detail with particular reference to FIGS. 1, 2 and 3 of the drawings, the outer tube 24 generally comprises a tubular body portion 54 having a cup-shaped front member 56 fixedly connected thereto by any convenient technique such as by a threadable engagement (not shown) or other suitable technique. A large opening 58 in the front member 56 permits a portion of the hook assembly 41 to extend therethrough when the device 10 is disposed in its set position as shown in FIG. 2 of the drawing. A smaller opening 60 in the front member 56 receives the adjustment knob 45 when the device 10 is disposed in its set position as shown in FIG. 2 of the drawings. A rear opening 62 in a rear end wall 63 receives the inner tube 31 in a slidable manner to enable the inner and outer tubes to the axially aligned with one another in a telescoping manner.
An integral internal tube 64 extends rearwardly from the front member 56 terminating near the rear edge of the rear opening 62 and is spaced radially from the inner tube 31 to receive the main spring 33 therebetween, which extends between the front member 56 and the inner surface of the inner tube 31.
The main spring 33 normally biases the inner and outer tubes to assume their overall maximum length with the inner tube 31 extending rearwardly from the rear opening 62 of the outer tube 24 as shown in FIG. 5 of the drawings. In that position, the overall length of the main spring 33 is substantially the same as the overall length of the inner and outer tubes. In order to store the device 10 with the inner tube 31 disposed within the outer tube 24, as shown in FIG. 2 of the drawings, without causing the main spring 33 to remain under tension for long periods of time, the coil springs 33A and 33B are threadably interengaged as shown in FIG. 5 of the drawings with their opposite ends fixed to the respective outer and inner tubes. As a result, in order to shorten the overall length of the inner and outer tubes of the device 10, the inner tube 31 may be rotated about its central axis to thread its coil spring 33B along the other coil spring 33A of the outer tube 24, whereby the inner tube 31 can then be moved axially within the interior of the outer tube 24 until the inner tube 31 is disposed in the position shown in FIG. 2 of the drawings, and the two springs 33A and 33B are completely interengaged threadably and are relaxed for storage purposes. In order to prepare the device 10 for use after a storage period, the inner tube 31 may be rotated again about its central longitudinal axis in an opposite direction to back the inner tube 31 out of the outer tube 24 and, at the same time, back the coil spring 33B out of the other coil spring 33A until only the last few coil turns interengage threadably one another as shown in FIG. 5 of the drawings.
Considering now the inner tube 31 in greater detail with references to FIGS. 2, 3 and 5 of the drawings, the inner tube 31 generally comprises a tubular body portion 66 which is generally circular in cross section throughout its length to enable it to be inserted within the outer tube 24 which is also generally circular in cross section throughout its length. An external annular flange 68 of the tubular body portion 66 is disposed near but spaced from the front end portion of the tubular body portion 66 and is adapted to engage an internal forwardly facing annular flange 69 at the rear wall 63 of the outer tube 24 to limit the rearward axial movement of the inner tube 31 relative to the outer tube 24 as best seen in FIG. 5 of the drawings. During a forward axial movement of the inner tube 31 relative to the outer tube 24, a rearwardly facing annular shoulder 70 of the outer tube 24 serves as a stop member to engage the annular flange 68 of the inner tube 24 or limiting the forward movement thereof as best seen in FIG. 2 of the drawings.
A cup-shaped rear member 72 is fixed to the tubular body portion 66 by any convenient technique such as a threadable engagement (not shown) and extends rearwardly from the outer tube 24 when the inner tube 31 is disposed therewithin as shown in FIG. 2 of the drawings. A reduced diameter portion 74 of the tubular body portion 66 enables the fingers of the users to grasp the outer tube 24 immediately in front of an external annular flange 75 of the cup-shaped member 72 for grasping the inner tube 31 and pushing it axially within the outer tube 24 until the inner tube is disposed within the outer tube as shown in FIG. 2 of the drawings.
A rear opening 76 in the cup-shaped rear member 72 reciprocatively receives the push button 47 which extends outwardly therefrom.
An inner concentric block 78 of the tubular body portion 66 is integral with and extends from an internal annular shoulder 79 of the tubular body portion 66 extending from the reduced diameter portion 74 at the rear end thereof and terminating at the front end portion thereof in a thick front wall 81, behind which is disposed a hook assembly compartment 83. A compartment 85 is disposed to the rear of the hook assembly compartment 83 for confining the batteries 50 and 52 in end-to-end axial alignment with the buzzer 49 disposed in axial alignment in front of the battery 50, as best seen in FIG. 2 of the drawings. A latch compartment 87 and the tubular body portion 66 confines the latch member 35, and a small compartment 89 communicating with the larger compartment 87 receives a coil spring 91 which urges resiliently the latch member 35 radially outwardly, as best seen in FIG. 2 of the drawings.
In order to permit the attention-attracting sound signal produced by the buzzer 49 to exit the device 10, when a fish has tripped the device 10 and the inner tube 31 has snapped rearwardly to the position as shown in FIG. 5 of the drawings, a series of radially expending perforations or openings 92A extend through the tubular body 66 in alignment with openings or perforations 92B extending radially through the inner concentric block 78 into communication with the buzzer and battery compartment 85 as best seen in FIGS. 2 and 5 of the drawings. For the purpose of permitting the attention-attracting sound to exit the device 10, when it is disposed in its set position as shown in FIG. 2 of the drawings, when a fish merely nibbles on the bait carried by the hook 22 to momentarily sound the buzzer 49 as hereinafter described in greater detail, a series of radially extending openings 93A in the internal tube 64 are aligned with the openings 92A and with a series of openings 93B extending radially in the tubular body portion 54 of the outer tube 24.
Considering now the hook assembly 41 in greater detail with particular reference to FIGS. 2, 3 and 5 of the drawings, the hook assembly 41 includes a hollow tubular member 94 having at its front end portion a rounded nose 95 and extending through an opening 97 in the thick front wall 81 of the tubular body portion 66. A block 99 is slidably mounted within the tubular member 94 and has an elongated tail member 100 extending rearwardly therefrom through an opening 101 and the tubular body portion 66 communicating with the latch compartment 87, and from there an opening 102 in the latch member 35 terminating in a cut-out portion 104 which extends through an opening or passage 106 and into a compartment 107 when the device 10 is disposed in its set position as shown in FIG. 2 of the drawings. When the latch member 35 moves into engagement with the cut-out rear portion 104 of the tail 100 as a force is applied to the fishing line 18 by a fish pulling on the hook 22, the slidable block 99 is pulled forwardly within the compartment 83, as shown in solid lines in FIG. 3 and as indicated in FIG. 2 in the broken line showing of the knob at 45A. A corner cam surface 35A of the latch member 35 cooperates with the shoulder 37 at the end of the internal group 39, under the force of the compressed main spring 33, to move the latch member 35 radially inwardly until it engages the cut-out portion 104 as shown in FIG. 3 of the drawings. In order to facilitate this camming action, a rounded corner or camming surface 108 at the transition between the main portion of the tail member 100 and the cut-out narrow portion 104 mates or cooperates with a corresponding rounded corner portion or camming surface 110 opposite the corner 35A of the latch member 35 at the forward upper end portion of the opening 102 therein. Once the cam member 35 moves out of the groove 39, the inner tube 31 is free of the outer tube 24, and the inner tube 31 snaps rearwardly under the force of the spring 33 until the external annular flange 68 at the rear end of the inner tube 31 engages the internal forwardly facing annular flange 69 of the outer tube 24 in the position as illustrated in FIG. 5 of the drawings.
In order to retain loosely the fishing line 18 to the inner tube 31 to pull the line abruptly rearwardly into the outer tube 24, as shown in FIG. 5 of the drawings, for setting the hook 22 in the mouth of a fish, a hook 111 is disposed within the tubular member 94 opposite an open slot or opening 112 to retain the fishing line 18 within the slot 112. A boss 113A fixed to the shank portion of the hook 111 projects forwardly from a slidable block 113 mounted at the rear of the compartment 83 and is integral therewith to provide a seat for a return spring 115 surrounding the shank portion of the spring 111 between the block 113 and an internal annular shoulder 117 of the hollow tubular member 94. As a result, when the block 113 moves forwardly to advance the hook 111 until the front distal end portion 111A thereof is moved to a position forwardly of the slot 112, the fishing line 18 is free therefrom. In this regard, after the hook 22 is set in the mouth of the fish and the block 113 is pulled forwardly by the fishing line 18 until the distal end portion 111A of the hook 111 is disposed forwardly of the slot 112 so that the fishing line 118 can then slide forwardly out of the open slot 112 and over the upper portion of the tubular member 94. As a result, the fish pulls the fishing line out of the interior of the outer tube 24 to enable the user to operate the fishing reel 16 to pull in the fish. It should be noted that the fishing rod 12 is used independently of the device 10 once the hook 22 is set in the mouth of the fish, and if desired, the fishing rod may be used entirely in a conventional manner without employing the device 10, since the fishing line 18 is completely free and independent of the device 10.
After the hook 111 is moved to a forward position, the return spring 115 snaps the block 113 and thus the hook 111 to their rearward most position with the block 113 disposed in engagement with the sliding block 99 as shown in FIG. 2.
In order to control the movement of the hook 111, the push button 47 causes a cam mechanism 119 to move axially forwardly against the force of a conical coil spring 122 disposed between the cam mechanism 119 and the rear end portion of the battery 52 for the purpose of causing the hook 111 to move forwardly to free the fishing line 18. In this regard, a ring 124 disposed forwardly of and engaging the cam mechanism 119 is pushed forwardly by the mechanism 119 to turn push axially forwardly a rod 126 disposed within a passage 128 in the tubular body portion 66. A rod 130 is engaged by and pushed axially forwardly by the front distal end portion of the rod 126, the rod 130 being connected fixedly to the slidable block 113, which in turn moves the hook 111 forwardly. An opening 132 extending transversely through the latch member 35 receives the rod 130 when the latch 35 is disposed in its set position as shown in FIG. 2 of the drawings. An opening 134 in the slidable block 99 receives the intermediate or shank portion of the rod 130 and is disposed in alignment with the opening 132 when the latch member 35 is disposed in its latch position (FIG. 2). In this regard, after the inner tube 31 is moved to the set position as shown in FIG. 2 of the drawings, the push button 47 is pressed inwardly by the thumb of the user until the push button 47 is disposed in its inner most position with the spring 122 fully compressed. By doing this, and retaining the pressure against the button 47, the ring 124 moves forwardly axially as a result of the force supplied to it by the cam mechanism 119. The ring 124 then pushes in turn the rod 126 forwardly, and the forward end of the rod 126 pushes in turn the rod 132. As a result, the block 113 and the hook 111 fixed thereto move forwardly until the forward distal end portion 111A of the hook 111 clears the slot 112. At this point, the thumb of the user continues to apply the pressure to the push button 47 to hold it fully depressed until the fishing line 18 is slipped through the upper open end portion of the slot 112 to insert the fishing line down into the slot 112. Thereafter, the pressure is released on the push button 47 and the spring 122 then causes the push button to retract fully outwardly until it reaches the position as shown in FIG. 2, as hereinafter more fully described, in its fully retracted position shown in FIG. 2, the button 47 and the cam mechanism 119 prepare the buzzer to be actuated when a pulling force is applied to the line 18. By thus relieving the pressure applied to the rod 126 and 130, the return spring 115 forces the slidable block 113 and its hook 111 backwardly until the block 113 engages the block 99 to cause the distal end portion 111A of the hook 111 to move through and thus close the upper end portion of the slot 112 to retain loosely the fishing line 18 in the slot 112.
After a fish pulls on the fish line 18 to release the latch member 35 and thus to cause the inner tube 31 to snap rearwardly to the position as shown in FIG. 5 of the drawing, the fishing line 18 is thus pulled rearwardly within the outer tube 24, since the rear end portion of the fishing line is retained within the fishing reel 16. Since the fishing line is trapped loosely within the slot 112, the forward end portion of the fishing line is then pulled rearwardly abruptly to set the hook 22 in the mouth of a fish. In order to free in a quick convenient manner the fishing line 18 from the tubular member 94 so that the fishing line 18 can be reeled in, the push button 47 is once again pushed inwardly to a fully depressed position against the force of the spring 122 to enable the hook 111 to move forwardly within the hollow tubular member 94 for freeing the fishing line from the open slot 112. In this regard, once the distal end portion 111A of the hook 111 moves forwardly to a position for clearing the slot 112, the pulling force exerted by the fish on the front end portion of the fishing line 18 pulls the line 18 out of the slot 112 over its open upper end portion thereof and thus out of the interior of the outer tube 24. In this regard, it should be noted that the slot 112 is inclined downwardly and rearwardly at an angle such that the fishing line 18 can be readily pulled along the edge of the slot 112 upwardly and out of the slot 112 in a convenient manner without snagging the line 18, whereby the line 18 can be quickly released from the hook assembly 41 and the user can commence reeling in the fish. Once the line 18 is free of the hook assembly 41, the pressure is released from the button 47 to permit it to snap back to the partially retracted position as shown in FIG. 4 of the drawings under the control of the cam mechanism 119 as more fully described hereinafter in greater detail. By depressing the button 47 to free the line 18, the buzzer 49 is turned off as hereinafter described in greater detail.
Once the inner tube 31 has snapped back into the released position as shown in FIG. 5 of the drawings, and when the button 47 is depressed to release the fishing line 18 from the hook assembly 41, it should be noted that the latch member 35 is resting on the cut-out portion 104 of the tail member 100, in which position the opening 132 is no longer in alignment with the push rod 126. For this reason, a second opening 138 extending through the latch member 35 has an L-shaped push rod 139 reciprocatively mounted therein. When the latch member 35 is disposed in the position illustrated in FIG. 5 of the drawings, the distal end portion of the rod 126 is disposed opposite the rear end upstanding portion of the push rod 139. Thus, when the latch 35 is disposed in the position as illustrated in FIG. 5 of the drawings, the rod 130 fixed to the slidable block 113 is disposed out of the opening 132 as well as the opening 138, since it was necessary to enable the latch member 35 to move radially inwardly into engagement with the cut-out portion 104. The L-shaped push rod 139 thus serves as an extension or connecting link between the rod 126 and the rod 130 when the latch member 35 is disposed in its release position as illustrated in FIG. 5 of the drawings. As best seen in FIG. 2 of the drawings, the rear upstanding portion 139A of the push rod 139 is adapted to engage an internal shoulder 140 at the forward end portion of the opening 138.
Considering now the tension adjustment for the device 10, a forwardly projecting boss 141 integrally connected to the sliding block 99 serves to seat one end of the coil spring 43 which surrounds a threaded rod 142 journaled for rotation within the hook assembly compartment 83, the rod 142 being disposed in a parallel-spaced manner with the tubular member 94. An annular bearing 143 surrounds the rod 142 at the forward end portion thereof near an opening 144 in the fixed wall 81, the rod 142 extending through the opening 144 and having its forward distal end portion terminating in the adjustment knob 45. A nut 145 is threadably engaged by the rod 142 so that, when the knob 45 is grasped by the fingers of the user and rotated so that the rod 142 rotates about its axis, the nut 145 moves rearwardly from the position as illustrated in FIG. 2 of the drawings to compress the spring 43. By compressing the coil spring 43, the pressure exerted by the spring 43 on the slidable block 99 to urge it resiliently rearwardly relative to the thick front wall 81 may be adjusted. In this regard, when a fish pulls on the fishing line 18, the tubular member 94 and the block 99 fixed to it are pulled forwardly within the compartment 83 against the force of the adjustment spring 43. By increasing the tension on the spring 43, a greater pulling force acting on the fishing line 18 is required to trip the latch member 35. Consequently, by reducing the tension on the spring 43, a more gentle pulling force on the fishing line can trip the latch member 35.
Considering now the buzzer 49 in greater detail, with particular reference to FIGS. 2, 3, 4 and 5 of the drawings, a coil spring 147 is disposed in and axially aligned with the compartment 107 in the tubular body portion 66, the rear end portion of the spring 147 engaging the terminal 148 of the buzzer 49 to electrically contact it. A post 149 is integrally connected to and extends rearwardly from a slidably mounted electrical contact 151, the plane of which extends transversely across the compartment 107 to move into electrical engagement with an annular electrical contact 153 fixed to the tubular body portion 66 at the front entrance to the compartment 107 to complete an electrical circuit to energize the buzzer 49, the electrical circuit including the buzzer 49, the coil spring 147, the contact 151, the contact 153, a conductor 155, extending within a passageway 157 in the body portion 66, an annular electrical contact 159 disposed within the rear cup-shaped member 72 surrounding the push button 47, an annular electrical contact 160 surrounding the push button 47 within the interior of the cup-shaped member 72 fixed to the cam mechanism 119, the cam mechanism 119, the coil spring 122, and the two batteries 50 and 52. In this regard, when the user initially depresses the push button 47 to enable the fishing line 18 to be secured to the hook assembly 41, the push button 47 is subsequently released and it is urged outwardly to its further most position by means of the spring 122 and the cam mechanism 119 to close the contacts 159 and 160 as shown in FIG. 2 of the drawings. In this position, the device 10 is prepared for generating the attention-attracting signal by the buzzer 49, since the contacts 151 and 153 need only to be closed to complete the electrical circuit to the buzzer 49. It should be noted at this point that, should a fish only pull momentarily on the fishing line 18, the contact 151 and 153 will engage electrically one another only momentarily to generate a short beeping sound to alert the user that a fish is beginning to nibble at the bait. However, such a momentary pull on the fishing line would not be sufficient to release the latch member 35. Once a sufficient pulling force is applied to the latch member 35 to release it so that the inner tube 31 snaps rearwardly to the position as illustrated in FIG. 5 of the drawings, the contacts 151 and 153 remain closed to complete the circuit to the buzzer 49 to sound a constant buzzing signal to alert the user that a fish has now been caught by the hook 22.
Once the attention-attracting signal is sounded, the user again depresses the button 47 to release the fishing line 18, and once the line 18 is released, the button 47 is permitted to snap back to the position as illustrated in FIG. 4 of the drawings. In that position, the spring 122 and the cam mechanism 119 cause the button 47 to extend outwardly to a substantially lesser extent as the position shown in FIG. 2 of the drawings, whereby the contacts 159 and 160 remain spaced apart to open the circuit to the buzzer 49 until such time as the push button 47 is depressed to once again attach releasably the fishing line to the hook assembly 41.
Considering now the camming mechanism 119 in greater detail, with particular reference to FIGS. 2, 4 and 6 of the drawings, the camming mechanism 119 is similar in design to a conventional well-known camming mechanism and push-button assembly (not shown) of a ball point pen for advancing and retracting ink writing cartridges. In this regard, a serrated edge 162 of a forward rim 163 (FIGS. 2 and 4) carrying a series of radial projections 164 at the serrated edge 162 cooperates with a cam member 165 (FIGS. 2 and 4) which has a series of widely spaced apart radially extending cam projections 166 having inclined camming surfaces to mate with the serrated camming edge 162. A rearwardly extending integral hub 171 (FIGS. 2 and 4) of the cam member 165 is disposed freely rotatably within the hollow interior of the button 47 so that the cam member 165 is free to rotate within the button 47 whereby each time the button 47 is pressed inwardly, the cam member 165 rotates about its axis and is indexed to the next position in a similar manner as well-known ball point pen camming mechanisms.
A series of alternating longer grooves 173 and shorter grooves 175 in the inside surface of the cup-shaped rear member 72 are adapted to receive alternatingly the mating projections 164 and 166. In this regard, when the button 47 is depressed, for example as shown in phantom lines in FIG. 6, the cam member 165 is pushed axially inwardly with its projections 166 disposed in the longer slots 173. In this position, the button 47 is then partly retracted only as shown in FIG. 4 of the drawings. When the button 47 is subsequently depressed and then released, the cam member 165 rotates about its axis and is advanced to the next position by means of the serrated edge 162 of the button 47, whereby, as indicated in FIG. 6 of the drawings, the projections 164 and 166 enter the short grooves 175 to cause the button 47 to remain in its fully retracted position as shown in FIG. 2 of the drawings. | A fishing device adapted to be attached to a fishing rod having a fishing line connected at one of its ends to the rod and at its other end to a fishhook includes an inner tube telescoping within and axially aligned with an outer tube which is adapted to be attached to the fishing rod in parallel disposition thereto. A hook device is mounted on the inner tube and is adapted to be attached releasably to the fishing line. A main spring device urges resiliently the tube to an initial position, and a latching device fixes releasably the tubes in a set position against the force of the main spring and frees the two tubes relative to one another in response to a force applied to the hook device via the fishing line so that the tubes return abruptly under the force of the main spring to their initial position, thereby jerking on the fishing line to set the fishhook in place to catch a fish. The main spring includes a pair of first and second coil springs threadably interconnected in axial alignment with the first coil spring disposed within and fixed to the outer tube and with the second coil spring being disposed within and fixed to the inner tube, whereby the overall length of the main spring device may be adjusted by threadably advancing forwardly or backing out of one of the first and second coil springs relative to the other one of the first and second coil springs. The hook device includes a tubular member having a backwardly inclined slot therein and having a spring loaded hook mounted on a block slidably mounted therein for receiving loosely an intermediate portion of the fishing line extending into the interior of the tubular member within the slot so that a push rod can move slidably within the block to move the hook to a position out of alignment with the slot to enable the intermediate portion of the fishing line to be inserted into the slot and subsequently thereto when the force is applied to the line, to release the line from the fishing device. A buzzer is provided to provide an attention attracting signal when a fish exerts a force on the fishline. A cam mechanism both releases the hook device and sets the buzzer in preparation for catching the fish. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
(Not Applicable)
STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT
(Not Applicable)
BACKGROUND OF THE INVENTION
The present invention relates generally to baby wipes warmers, and more particularly to an improved baby wipes warmer having a liquid tank located therewithin which provides heated liquid vapors to the baby wipes for maintaining moisture and coloration of the baby wipes.
Baby wipes have been marketed in the United States for many years. Essentially, baby wipes are small pre-moistened paper or synthetic (non-woven) towelettes and are typically available in packages to the consuming public. They are primarily used to cleanse the skin of infants and small children. The wipe-fluid content for these pre-moistened wipes is generally comprised of cleansers, lotions and preservatives.
A few years after the baby wipes were introduced into the marketplace, various products for warming the wipes were made available to the public. Such products have been devised to comfort the baby wipe users from the inherent “chill” given off by the contact of the moistened wipes. For example, it is now a common practice for parents to employ the use of warm baby wipes on their children.
These warming products are generally electric operated and come in two distinct styles. One is an “electric blanket” style which is sized to wrap around the external surfaces of a plastic baby wipes container. The other is a self-contained plastic “appliance” style which warms the accommodated baby wipes with its internally positioned heating element. Though such currently known and available baby wipes warming products achieve their primary objective of warming baby wipes, they possess certain deficiencies which detract from their overall utility.
Perhaps the two greatest deficiencies of the prior art baby wipes warming products are the inabilities to sustain the moisture content and coloration of the baby wipes. More specifically, drying of the baby wipes occurs due to heating of their moisture which accelerates dehydration. Further, discoloration of the same appears to be inevitable because of a reaction of various chemicals in the wipes to heating. As such, even though these existing products may adequately warm the baby wipes, they cannot, however, seem to avoid the undesirable effects of dehydration and discoloration when warming them.
Thus, there exists a substantial need in the industry, and in the infant products manufacturing business in particular, for a baby wipes warming product that can effectively provide warmth to the baby wipes without dehydrating and/or discoloring them. Further, there exists a need for a baby wipes warming product which can achieve these objectives in a user-friendly and time-efficient manner.
BRIEF SUMMARY OF THE INVENTION
The present invention specifically addresses and overcomes the above-described deficiencies of prior art baby wipes warming products by providing an improved baby wipes warmer that can warm baby wipes while substantially maintaining their original moisture content and coloration. Briefly, in order to accomplish such objectives, the present baby wipes warmer may utilize a heatable liquid tank assembly which can provide liquid vapors to the baby wipes through its at least one vapor aperture, Alternatively, the present baby wipes warmer may use an elevated support surface such as a suspension tray in lieu of the tank assembly in which the baby wipes supported thereon can be heated while sustaining their moisture and color through vapors rising from the heated liquid pool disposed thereunderneath. These as well as other features of the present invention will be discussed in more detail infra.
In accordance with a first preferred embodiment of the present invention, there is provided a baby wipes warmer for warming baby wipes while substantially maintaining their original moisture content and coloration. Such warmer comprises a housing with a pivotally engaged lid member that can open and close relative thereto. A liquid tank assembly is disposed within the housing in such a way that its upper tank surface is vertically surrounded by the housing's interior-side housing wall and horizontally closed off by the lid member. In this respect, an inside compartment is defined which can be selectively accessed by opening and closing the lid member.
The liquid tank assembly is preferably fabricated from any heat conducting material such as metal (e.g., aluminum). The tank assembly comprises a liquid compartment which is formed between its upper and lower tank surfaces. The liquid compartment is used to hold any liquid that can produce vapors when heated such as water. By heating the liquid compartment, a portion of the liquid may change its physical state and flow into the inside compartment as vapors which helps to maintain the original moisture content and coloration of the baby wipes placed thereat. To allow the rising vapors to seep into the inside compartment from the liquid compartment, at least one vapor aperture is formed through the upper tank surface.
A heating element is disposed within the housing relative to the lower tank surface for the purpose of heating the liquid. The heating element may be located in various positions to achieve such purpose. For example, the heating element can be placed within the liquid compartment itself adjacent the lower tank surface to substantially extend thereabout. However, the heating element can also be placed outside the liquid compartment and still provide the requisite heat to the lower tank surface by being adjacent thereto. It is specifically contemplated herein that any types of heating element such as an electrically powered heating pad may be used.
In the first preferred embodiment, the upper tank surface is characterized by a generally flat support surface used for supporting the baby wipes thereon. This surface may be defined to be a part of the upper tank surface itself. In the alternative, however, the support surface can be formed by a suspension tray which is removably engaged upon a sponge material that extends through an exposed opening defined on the upper tank surface. If the latter configuration is used, the vapor aperture(s) of the upper tank surface is formed by the sponge itself as its inherent characteristics would allow the vapors to gradually flow therethrough. Moreover, a ridge may be formed around both types of support surfaces for confining the baby wipes within the physical boundary set thereby.
Further in the first preferred embodiment of the present invention, there may be provided a liquid reservoir which is set in fluid communication with the liquid compartment. The liquid reservoir may be disposed within the housing adjacent the liquid tank assembly, or alternatively mounted to an exterior of the housing. To establish fluid communication, any elongated and hollowed structure such as a conduit may be used to provide a flow channel between the reservoir and the liquid compartment. As will be demonstrated below, the liquid reservoir ensures that the liquid within the liquid compartment is always sustained at a certain level sufficient to provide adequate evaporation.
In accordance with a second preferred embodiment of the present invention, there is provided a baby wipes warmer which utilizes an elevated support surface such as a suspension tray in lieu of the tank assembly. The support surface is disposed within an inside compartment which is collectively formed by the interior-side housing wall and the upper housing wall. More specifically, the interior-side housing wall defines a generally flattened interior compartment surface used for placing the support surface thereon above the liquid level contained within the inside compartment. By doing so, the baby wipes accommodated thereon can be heated while sustaining their moisture and color through vapors rising from the heated liquid pool disposed underneath.
In accordance with a third preferred embodiment of the present invention, a liquid tank assembly in the form of an elongated central channel is embedded laterally along the flattened interior compartment surface. This assembly forming the elongated central channel includes a sponge material therewithin so that it may draw liquid out of the reservoir by capillarity. Similar to the first embodied baby wipes warmer, its upper tank surface comprises at least one vapor aperture which allows liquid vapor to travel therethrough.
In illustrating the operation for all embodied baby wipes warmers, a stack of baby wipes may be placed within the inside compartment simply by opening and then closing the lid member. The liquid contained within the baby wipes warmer should be checked to ensure that there is sufficient quantity, i.e., water level present. This can be accomplished by checking the liquid reservoir (for the first and third embodiments) or the liquid level within the inside compartment itself (for the second embodiment). Thereafter, the baby wipes warmer may be plugged into an electrical outlet in order to activate the heating element (if not already done). By following this easy-to-follow procedure, portions of the liquid can transition into vapors when sufficiently heated which then travel upwardly through the vapor aperture(s) to contact the baby wipes so that they may be maintained in constant moisturized condition and coloration.
BRIEF DESCRIPTION OF THE DRAWINGS
These as well as other features of the present invention will become more apparent upon reference to the drawings wherein:
FIG. 1 is a perspective view of a baby wipes warmer constructed in accordance with a first preferred embodiment of the present invention and illustrating a stack of baby wipes positioned within its inside compartment;
FIG. 2 is an exploded perspective view of the baby wipes warmer of FIG. 1 and illustrating a liquid reservoir which is exteriorly mountable to its exterior-side housing wall;
FIG. 3 is a cross-sectional view of the baby wipes warmer of FIG. 1 and illustrating a heating element disposed between its water tank assembly and base member;
FIG. 3A is a plan view of the water tank assembly of FIG. 3 and illustrating a plurality of vapor apertures which are formed through its upper tank surface;
FIG. 4 is a cross-sectional view of the baby wipes warmer of FIG. 1 and illustrating a heating element immersed in a quantity of liquid contained within its water tank assembly;
FIG. 5 is a cross-sectional view of the baby wipes warmer of FIG. 1 and illustrating a suspension tray which is placed upon a sponge extending through an exposed opening of its water tank assembly;
FIG. 6 is a cross-sectional view of a baby wipes warmer constructed in accordance with a second preferred embodiment of the present invention and illustrating a suspension tray which is placed directly over a quantity of liquid contained within its inside compartment; and
FIG. 7 is a cross-sectional view of a baby wipes warmer constructed in accordance with a third preferred embodiment of the present invention and illustrating a sponge disposed within its water tank assembly which is in the form of a laterally extending central water channel.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the drawings wherein the showings are for purposes of illustrating preferred embodiments of the present invention only, and not for purposes of limiting the same, FIG. 1 prospectively illustrates a baby wipes warmer 10 constructed in accordance with a first preferred embodiment of the present invention. As indicated above, the baby wipes warmer 10 is adapted to warm a stack of baby wipes 12 accommodated therein while maintaining the wipes 12 in a substantially moisturized condition and with their original coloration (i.e., white). Those of ordinary skill in the art will recognize that the baby wipes warmer 10 may be formed to have a variety of external housing shapes, configurations, geometries, sizes and textures other than for that shown in the provided figures.
Referring more particularly to FIGS. 1 and 2, the baby wipes warmer 10 comprises a housing 14 . This housing 14 may be fabricated from any rigid material, but plastic polymer is preferred. The housing 14 is formed having a main body member 16 and a base member 18 . More particularly, the body member 16 is peripherally defined by an exterior-side housing wall 20 with a base end 22 that engages onto the base member 18 . The base member 18 is contemplated to be used for supporting the baby wipes warmer 10 on any provided surface (e.g., desktop, floor, night stand, etc.) and may optionally include a plurality of adjustable foot pads 24 for this purpose.
The housing 14 of the present baby wipes warmer 10 comprises a pivotally engaged top lid member 26 which is capable of opening and closing relative to the housing 14 . The lid member 26 may open and close utilizing any conventional methods such as using a door spring 28 , for example. When such lid member 26 is closed with respect to the housing 14 , it becomes an upper housing wall as it encloses the interior of the housing 14 from the outside. On the other hand, the opening of the lid member 26 allows access to an inside compartment 30 of the housing which will be discussed in more detail below. By accessing the inside compartment 30 , a stack of baby wipes 12 (layered or inter-folded stack) may be inserted and individually withdrawn for use.
Referring now to FIGS. 2 and 3, a liquid tank assembly 32 is provided within the housing 14 . More specifically, the liquid tank assembly 32 is located between the body and base members 16 , 18 when they are engaged to each other in the manner described above. Upon such placement, the upper tank surface 34 of the tank assembly 32 collectively forms the inside compartment 30 . with the interior-side housing wall 36 and the lid member 26 of the housing 14 . To describe this aspect in more detail, the upper tank surface 34 becomes vertically surrounded as the tank end 38 of the interior-side housing wall 36 is rested against the upper tank peripheral edge 40 thereof. The upper tank surface 34 is then horizontally closed off by the top lid member 26 forming the closed position. By such structural interaction, the requisite inside compartment 30 may be formed.
Although FIG. 2 illustrates the liquid tank assembly 32 to be generally rectangular in configuration, it is expressly stated herein that the tank assembly 32 may be configured in other ways without deviating from its operational capabilities.
The liquid tank assembly 32 defines a lower tank surface 42 which is positioned beneath the upper tank surface 34 towards the base member 18 . The upper and lower tank surfaces 34 , 42 are connected to each other by a surrounding side tank surface 44 to thereby form a liquid compartment 46 within the tank assembly 32 . This liquid compartment 46 is used for holding any liquid 48 that can evaporate when sufficiently heated and thus produce vapors 49 which are able to moisturize. A type of liquid 48 which is exemplary of this nature is water. However, the use of any fluids which may safely moisturize the baby wipes 12 are foreseeable.
Because the contained liquid 48 must evaporate upon sufficient heating, the liquid tank assembly 32 should therefore be made from any material that is capable of rising in temperature in reaction to heating. It is preferred that the tank assembly 32 is fabricated from a heat-conducting material such as metal. More preferably, aluminum would be desirable for fabricating the tank assembly 32 as it reacts very well to heating.
As shown in FIGS. 3 and 3A, the upper tank surface 34 includes a plurality of vapor apertures 50 extending therethrough which provide fluid communication between the inside and liquid compartments 30 , 46 . The vapor apertures 50 allow the vapors 49 to pass through from the liquid compartment 46 to the inside compartment 30 so as to heat the wipes and maintain the baby wipes 12 in a constant moisturized condition and coloration. Preferably, the vapor apertures 50 are formed within the support surface 52 which is surrounded by a ridge 54 formed therearound. The support surface 52 is primarily used for accommodating the baby wipes 12 in which the surrounding ridge 54 confines them in place to prevent side-to-side movement.
Referring now to FIG. 5 only, an alternative embodiment of the support surface 52 is depicted. In this embodiment, the upper tank surface 34 may instead define an exposed opening 56 between the ridge 54 . A support surface 52 may be disposed within this opening 56 in a manner as to extend substantially thereabout. Any structure providing a horizontal flat surface can be defined as the support surface 52 such as a suspension tray, for example. Preferably, a sponge material 58 extending through the exposed opening 56 from the liquid compartment 46 is used to removably secure the support surface 52 in place. The sponge 58 is preferred for this purpose as its naturally formed pores may simulate the vapor apertures 50 thereby permitting the vapors 49 to seep therethrough.
Referring now to FIGS. 3-5, a heating element 60 is provided within the housing 14 relative to the lower tank surface 42 . As noted above, the purpose of the heating element 60 is to heat the tank assembly 32 so that portions of liquid 48 are changed into vapors 49 . The heating element 60 may be disposed in various positions to achieve this purpose. One position is to locate the heating element 60 within the liquid compartment 46 so that it is immersed in liquid 48 to substantially extend adjacent the lower tank surface 42 (best shown in FIG. 4 ). The heating element 60 may also be positioned outside the liquid compartment 48 to extend adjacent the lower tank surface 42 (best shown in FIGS. 3 and 5 ). Although the. use of various heaters is contemplated, it is preferred that an electrically powered heating pad is utilized.
Referring now back to FIGS. 1 and 2, a liquid reservoir 62 may optionally be incorporated into the present baby wipes warmer 10 . However, the use of the liquid reservoir 62 is not mandatory as the liquid level within the liquid compartment 46 may be manually refilled. The liquid reservoir 62 is in fluid communication with the liquid compartment 46 . By such communication, the reservoir 62 can provide additional liquid to the liquid compartment 46 when needed. The additional liquid may be provided manually by operation of a valve device which may open and close the liquid flow into the liquid compartment 46 . The liquid reservoir 62 includes a refill cap 64 preferably fabricated from a rubber material for selectively accessing its interior.
Similar to the heating element 60 , the liquid reservoir 62 may also be located in multiple positions. For example, it can be disposed within the housing 14 adjacent the liquid tank assembly 32 (shown in FIG. 7 ). Alternatively, the liquid reservoir 62 may be exteriorly mounted to the exterior-side housing wall 20 (shown in FIG. 1 ). Irrespective of its positioning, the important concept to be derived is that the reservoir 62 fluid communicates with the liquid compartment 46 for providing additional liquid 48 thereto when needed. To establish fluid communication, any elongated and tubular structure 66 such as a conduit may be used to form a reservoir channel 66 between the reservoir 62 and the liquid compartment 46 . In this respect, the liquid reservoir 62 ensures that the liquid 48 within the liquid compartment 46 is always kept at a certain level which is sufficient to provide adequate evaporation.
FIG. 6 illustrates a baby wipes warmer 70 which is constructed in accordance with a second preferred embodiment. The second embodied baby wipes warmer 70 is substantially identical to the first embodiment with one major distinction. More specifically, the baby wipes warmer 70 of the second embodiment eliminates the use of the liquid tank assembly 32 . Rather, its interior-side housing wall 72 is adapted to define a substantially flattened interior compartment surface 74 which extends generally parallel to the base member 18 . By merely closing the top lid member (not shown), an inside compartment 78 is formed. A quantity of liquid 80 is directly contained within this compartment 78 .
A support surface 82 which is defined by a suspension tray 84 is disposed within the inside compartment 78 . However, it should be noted that the support surface 82 is positioned above the pool of liquid 80 as it must accommodate the baby wipes 12 thereon. The support surface 82 may be engaged upon the interior compartment surface 74 through any known process such as bonding or fastening. By utilizing this arrangement, the baby wipes 12 are adequately heated while sustaining their moisture and color through vapors 86 rising from the heated liquid pool 80 disposed immediately underneath the support surface 82 .
FIG. 7 shows a baby wipes warmer 90 which is made in accordance with a third preferred embodiment of the present invention. This warmer 90 is substantially identical to the first embodied baby wipes warmer 10 except that its liquid tank assembly 92 is fabricated in the form of an elongated central channel and is embedded laterally along the interior compartment surface 94 . This elongated central channel serving as the liquid tank assembly 92 includes a sponge 96 within its liquid compartment 98 . The sponge 96 operates to draw the liquid 100 out of the adjacently located liquid reservoir 102 by capillarity. Similar to the tank assembly 32 of the first embodiment, its upper tank surface 104 includes a plurality of vapor holes 106 which allow the liquid 100 to evaporate therethrough.
The operation of the first embodied baby wipes warmer 10 is described herein which is simultaneously representative for operations of the second and third embodied baby wipes warmers 70 , 90 . First, a stack of baby wipes 12 to be warmed is placed within the inside compartment 30 simply by opening and then closing the lid member 26 . The liquid 48 contained within the baby wipes warmer 10 should be checked to ensure that there is sufficient level present for adequate evaporation. This can be accomplished by visually checking the liquid reservoir (for the first and third embodiments) or the liquid level within the inside compartment itself (for the second embodiment). Thereafter, the baby wipes warmer 10 should be plugged into an electrical outlet (not shown) in order to activate the heating element 60 (if not already done). By following this easy-to-follow procedure, portions of the liquid 48 can transition into vapors 49 when sufficiently heated which are then provided to the baby wipes 12 so that they may be maintained in constant moisturized condition and coloration.
Additional modifications and improvements of the present invention may also be apparent to those of ordinary skill in the art. Thus, the particular combination of parts described and illustrated herein is intended to represent only certain embodiments of the present invention, and is not intended to serve as limitations of alternative devices within the spirit and scope of the invention. | There is provided a baby wipes warmer comprising a housing which defines an upper housing wall. It also comprises a liquid tank assembly that has an upper tank surface defining at least one vapor aperture therethrough. The tank assembly is disposed within the housing in a manner as to form an inside compartment between the upper housing wall and the upper tank surface. The warmer further comprises a heating element which is disposed within the housing to provide heat to the tank assembly. In this regard, a portion of liquid within the tank assembly transitions into vapors when heated by the heating element and flow to the inside compartment through the vapor aperture(s). By providing the vapors, the moisture and coloration of the baby wipes supported therein can be maintained while warming them. | 0 |
CROSS REFERENCE TO THE RELATED APPLICATION
This is a continuation-in-part application of Application Ser. No. 870,824 filed on June 5, 1986, now abandoned.
FIELD OF THE INVENTION
This invention relates to an austenitic-martensitic stainless steel which is suitable to be used as a material for parts and elements, in which high strength, high toughness, high ductility and corrosion resistance are required, such as thin leaf spring, thin plate coil, cutlery, cutting tool body, etc., and which is especially suitable as a material for parts in which high strength and high ductility are required.
BACKGROUND OF THE INVENTION
For manufacturing the above-mentioned parts and elements, martensitic stainless steels, work-hardenable austenitic stainless steels, precipitation-hardenable stainless steels, etc. have conventionally been used.
Martensitic stainless steels are hardened by quenching from the austenitic state at an elevated temperature to cause martensitic transformation. Steels of SUS 410, 410J, 420J1, 420J2, 440A, 440B, 440C, etc. are typical examples of these steels, which have conventionally been used. Although these steels are low in strength and toughness in the annealed state, considerably high strength and toughness are attained by quenching and tempering. Therefore, these steels are widely used as inexpensive materials.
However, as martensitic stainless steels are not satisfactory for use in which high corrosion resistance is required, in such a field, work-hardenable austenitic stainless steels are used. These steels are Cr-Ni austenitic steels which are in the metastable state at ordinary temperatures and are hardened by cold rolling. The hardened steels are of two phases consisting of austenitie and martensite and therefore excellent in strength and ductility and also excellent in corrosion resistance. Typical examples of these steels are SUS 301, 304, etc. The strength of these steels depends upon the degree of cold working as stipulated in JIS G4313 and intensive cold working is required in order to attain high strength.
Precipitation-hardenable stainless steels contain precipitation-hardening elements and are hardened by heat-treatment, and therefore afford articles of good shape. Therefore, these steels are employed when shape requirements of products are strict and corrosion resistance is an important factor.
Typical examples of these steels are SUS 630, which contains Cu, and SUS 631, which contains Al. The former is hardened by solution treatment followed by aging during which a Cu-rich phase is precipitated. But the hardness thereof is 140 kgf/mm 2 at the highest. The latter is hardened by first subjecting to solution treatment, then transforming tbe metastable austenite phase partly or wholly to the martensite phase by cold working, for instance, and thereafter precipitating a Ni 3 Al intermetallic compound by aging. This can provide considerably high strength materials.
As a method for transforming the austenite phase of SUS 631 to martensite phase and then aging it, treatments such as TH 1050, RH 950, CH, etc. can be resorted to. But the strength attained by the former two treatments is 130 kgf/mm 2 at the highest, while a strength as high as 190 kgf/mm 2 can be attained by the CH treatment. In the CH treatment, the steel is first subjected to cold working to convert the austenite phase to the austenite-martensite two phases as in the case of work-hardenable stainless steels, and is thereafter subjected to aging. The strength after the cold working is around 150 kgf/mm 2 , depending on the degree of cold working. But the above-mentioned high strength is attained by precipitation of the Ni 3 Al intermetallic compound when the steel is age-hardened.
Of the above-described stainless steels, martensitic stainless steels must be subjected to quenching and tempering in order to attain strength and toughness. The heat treatments are troublesome. In quenching, materials are heated to a high temperature (950°-1100° C.), wherefrom they are quenched. Rapid mertensitic transformation deteriorate shape of treated articles. In order to prevent such trouble, a special heat treatment such as press-quenching is required.
In the case of austenitic stainless steels, high degree cold working is required in order to attain high strength. But if high strength is attained, ductility is sacrificed, and the shape of sheet products and strip products is often deteriorated.
Further, in the case of precipitation-hardenable stainless steels, SUS 630 does not attain high strength, and SUS 631 often devlops surface roughness and is impaired in toughness and ductility because the steel contains 0.75-1.50% Al which has a strong affinity for oxygen and nitrogen, and alumina type inclusions are formed during the steel-making and coagulated inclusions of AlN are formed when the steel is cast.
Japanese Laid-open Patent Publication No. 52-007317 disclose a steel substantially contained in % by weight, C: ≦0.02%, S: ≦1.00%, Mn: ≦2.00%, P: ≦0.040%, S: ≦0.003%, Ni: 5.00-8.50%, Cr: 16.00-21.00%, Cu: 0.50-4.00%, N: <0.20%, O: ≦0.015% and the balance being Fe and unavoidable impurities. This steel is for compression forming and, therefore work-hardenability and formation of martensite are restricted by reducing C content, increasing N and adding Cu and reducing Si. That is, hardness of the resulting products are not satisfactory.
Japanese Laid-Open Patent Publication No. 56-077364 discloses a steel comprising, by weight C: ≦0.15%, N: ≦0.15%, Si: 0≦1.5%, Mn: 0.5-2.0%, Ni: 5.0-9.0%, Cr: 13.0-20.0%, Cu: 1.0-4.0%, and the balance being Fe and unavoidable impurities and having the Md.sub.(30) (°C.) value of -30°-80° C., said Md.sub.(30) (°C.) being defined as ##EQU1##
The Md.sub.(30) (°C.) is the temperature at which 30% cold-worked super-cooled austenite transforms into martensite of 50% and represents austenite stability (instability). This steel is intended for a spring material as well as the present invention. However, this steel is not satisfactory in the balance of strength and elongation. This is because the Mn content is rather high, the Si content is rather low and S is not restricted.
U.S. Pat. No. 4,378,246 by the inventors including two of the inventors of the present invention discloses a martensitic precipitation-hardening type stainless steel for spring comprising in % by weight more than 0.03% but not more than 0.08% of C, 0.3 to 2.5% of Si, not more than 4.0% of Mn, 5.0 to 9.0% of Ni, 12.0 to 17.0% of Cr, 0.1 to 2.5% of Cu, 0.2 to 1.0% of Ti and not more than 1.0% of Al, the balance being Fe and having a specifically defined restricted austenite stability A' of less than 42, said A' being defined as ##EQU2## having a specifically defined Cr equivalent/Ni equivalent ratio of not more than 2.7, said ratio being defined as ##EQU3## and further having a specifically defined hardness increase by aging ΔHv of between 120 and 210, said ΔHv being defined as ##EQU4## This steel is genuinely martensitic precipitation-hardenable steel. The fact is represented by the A' value less than 42, the rather high Mn content and addition of precipitate-forming elements such as Ti and Al. The A' value is an index which represents existence of the residual austenite after solution treatment. When this value is less than 42, the steel is simply martensitic.
It is not that ductility is not considered as the upper limit of ΔHv is somewhat restricted. However, ductility of this steel is not sufficient.
DISCLOSURE OF THE INVENTION
The present invention intends to provide a new steel material of a type different from the above-described. That is, this invention provides a stainless steel which has good workability and is hardened by work-hardening of austenite and formation of minute work-induced martensite and further hardened by aging, probably strain aging accompanied by some precipitaion.
This invention provides a high strength stainless steel essentially consisting of not more than 0.10% C., more than 1.5% and not more than 2.95% Si, less than 0.5% Mn, not less than 4.0% and not more than 8.0% Ni, not less than 12.0% and not more than 18.0% Cr, not less than 0.5% and not more than 3.5% Cu, not more than 0.15% N and not more than 0.004% S, wherein the total content of C and N is more than 0.10%, the balance being Fe and incidental impurities including up to 0.020% Al and up to 0.020% Ti, and the A' value as defined below is 50-150 and the Md(N) as defined below is 35-95. ##EQU5##
The steel of this invention contains Si, which is a martensite inducer and martensite strengthener, in a larger amount of more than 1.5% and not more than 2.95% than the conventional steel; and it contains C and N, which are martensite phase strengtheners, in an amount of not less than 0.10% in total. Therefore, the martensite phase is easily induced from the metastable austenite after the solution treatment by light cold working because of the presence of the high level of Si; and the thus induced martensite phase is hardened by Si, C and N and thus products of good shape, high strength and high ductility can be obtained. And as a precipitation hardening element, Cu, which acts synergistically with Si and with which there is no risk of inclusion formation, is added, and aging is additionally carried out, and thus a higher strength is attained. Therefore, the steel of this invention can be used as a work-hardenable stainless steel which is superior to the conventional steel in strength and ductility an also can be used as a precipitation-hardenable stainless steel.
Now the reason why the composition is defined as stated above is explained.
C is an austenite former and is effective for inhibiting formation of δ-ferrite at high temperature and strengthening the martensite phase induced by cold working. But the solution limit of C is restricted because of high Si content in the steel of this invention. Therefore, a high carbon content will cause deposition of chromium carbides at grain boundaries, which will induce abatement of ductility and resistance to intergranular corrosion. Therefore, the C content is limited to 0.10%.
Si is used usually as a deoxidizer. For this purpose, the Si content is not more than 1.0% as seen in work-hardenable austenitic stainless steels such as SUS 301, 304, etc., and precipitation hardenable stainless steel such as SUS 631. In the case of the steel of this invention, however, Si is contained in a higher amount than this, that is, more than 1.5%, so that the martensite phase is easily induced in cold working, that is, it is induced even by slight cold working and the formation thereof is promoted and the ratio of martensite phase to austenite phase is enhanced. The formed martensite is not only strengthened but it is dissolved in the remaining austenite phase to harden it and thus the hardness after working is enhanced. Also, in aging Si increases the aging effect in combination with Cu. As stated above, Si has many effects. In order to make Si exhibit such effects, Si must be contained in an amount of more than 1.5%, higher than the conventional content range. But if it exceeds about 3.0%, it induces high temperature cracking and causes some problems in manufacturing. More than 1.5% and not more than 2.95% is a suitable content.
Mn is an element which controls the stability of the austenite phase. The content is determined by taking into consideration the balance with the other elements. In the steel of the present invention, a higher content of Mn will cause abatement of ductility and also causes some problems when the steel is used. For this reason the Mn content is limited to 0.5%, rather remarkably lower than the conventional range.
Ni is an essential element for the formation of an austenite phase at both high temperatures and room temperature. In the case of the steel of this invention, metastable austenite must exist at room temperature and must be transformed into martensite phase by cold working. For this purpose, with less than 4.0% Ni, a large amount of δ-ferrite is formed at a higher temperature and the austenite phase becomes rather unstable than metastable at room temperature. On the other hand, with more than 8.0% Ni, the martensite phase is not easily induced by cold working. Therefore the Ni content is selected as 4.0-8.0%.
Cr is an essential element for obtaining corrosion resistance. In order to provide the steel with desired corrosion resistance, not less than 12% of Cr is required. But Cr is a ferrite former. If a higher amount of Cr is contained, a large amount of δ-ferrite is formed at high temperatures. Therefore, a correspondingly larger amount of austenite former elements (C, N, Ni, Mn, Cu, etc.) must be contained to inhibit formation of the δ-ferrite. And if large amounts of the austenite formers are contained, the austenite is in turn stabilized at room temperature and the steel is not hardened by cold working and aging. As such, the upper limit of the Cr content is defined as 18.0%.
Cu hardens the steel in aging in combination with Si. With too small an amount, the effect thereof is not remarkable and if too large an amount thereof is contained, it causes cracking. The proper amount is estimated as 0.5-3.5%.
N is an austenite former and is very effective for hardening both austenite phase and martensite phase. However, if N is contained in high amounts, it may cause blow holes when the steel is cast. Therefore, the N content is limited to not more than 0.15%.
S forms MnS in the presence of Mn, and brings about abatement of ductility and therefore it is an especially deleterious element in the steel of this invention. The upper limit thereof is restricted to 0.004% in order to avoid abatement of ductility.
C and N have similar effects and are interchangeable. Although the respective upper limits for these elements are as defined above, the total amount of these two elements must be not less than 0.10% to utilize their effect.
In addition to the above-mentioned elements, a slight residual amount of Al and Ti, which are used as deoxidizers, Ca and REM's (rare earth metals) which are used as desulfurizer, etc. and incidental inevitable impurities such as P are permitted to be present in the steel of the present invention. The steel of this invention is allowed to contain not more than 0.020% of Al, not more than 0.020% of Ti, although these elements are undesirable because they form non-metallic inclusions which impair ductility. Not more than 0.040% of P, not more than 0.01% of Ca and not more than 0.02% of REM's are allowed.
Preferably, the high strength stainless steel of this invention contains not more than 0.08% C, more than 1.5% and not more than 2.95% Si, less than 0.46% Mn, not less than 4.5% and not more than 7.5% Ni, not less than 14.0% and not more than 17.0% Cr, not less than 0.8% and not more than 3.0% Cu, not more than 0.13% N and not more than 0.0035% S.
More preferably, the high strength stainless steel of this invention contains not more than 0.075% C, more than 1.5% and not more than 2.95% Si, less than 0.42% Mn, not less than 5.50% and not more than 7.30% Ni, not less than 14.5% and not more than 16.5% Cr, not less than 1.00% and not more than 2.65% Cu, not more than 0.125% N and not more than 0.003% S.
In any case, the total content of C and N should be not less than 0.10%.
The above-mentioned A' value as defined in the same way as in U.S. Pat. No. 4,378,246 must be more than 42. In the present invention the A' value is calculated with the Ti and Al contents as 0.02% respectively. The A' value as defined above is simply referred to in order to distinguish the steel of the present invention from that of U.S. Pat. No. 4,378,246, although the thus defined A' value is not inherently applicable to the steel of the present invention.
The Md(N) is an index which represents austenite stability at room temperature (25° C.). The smaller this value, the more stable the austenite. Therefore, as the value is larger, more martensite is formed. If this value is less than 35, the resulting age-hardened steel material is insufficient in hardness. When this value exceeds 95, the resulting steel material is insufficient in ductility.
BRIEF EXPLANATION OF THE DRAWINGS
The invention will now be described by way of working examples with reference to the attached drawings.
FIG. 1 shows the relation between tensile strength and elongation of the steels of this invention (hereinafter called "inventive steels"), conventional steels and comparative steels in the cold-rolled state and age-hardened state. The circle, square and triangle symbols denote respectively the inventive steels, conventional steels and comparative steels. Blank symbols denote the cold-rolled state and solid black ones the age-hardened state. The solid line, broken line and one-dot chain line indicate respectively the data distributions of the inventive steels, conventional steels and comparative steels.
FIG. 2 shows the relation between tensile strength and elongation of Inventive Steel H1 and Comparative Steel e.
FIG. 3 is a graph representing the relation between the amount of the work-induced martensite and the Md(N) value of inventive steels and similar steels.
FIG. 4 is a graph representing the relation between the ratio of notch tensile strength (NTS)/tensile strength (TS) and the Md(N) value of inventive steels and similar steels.
FIG. 5 is a graph representing the relation between the ΔHv value and the Md(N) of the invention steels and similar steels.
DETAILED DESCRIPTION OF THE INVENTION
Inventive steels (H1-H4), conventional steels (A-C) and comparative steels (a-f) of the compositions as shown in Table 1 were prepared and hot-rolled by the usual method, and they were cold-rolled with varied degrees of reduction to form high strength cold-rolled steel sheet samples. The calculated A' values and Md(N) values are indicated in Table 1. A' values were calculated with the Ti and Al contents as 0.02% respectively. The amount of the martensite induced by cold working (α), hardness, tensile strength and elongation of the thus made steel sheet samples were measured. Then these high strength cold-rolled steel sheets were age-hardened, and hardness, tensile strength and elongation were measured. The results are shown in Table 2, wherein the difference in the hardness before and after aging (ΔHv) is also indicated. Of the results as shown in Table 2, the relation between tensile strength and elongation is shown in FIG. 1. Further, the relation between tensile strength and elongation of Inventive Steel H1 and Comparative Steel e, which is close to the inventive steels in properties in the cold-rolled state is shown in FIG. 2.
As is apparent from Table 2, the amounts of the induced martensite (α) of the inventive steels are larger than those of the conventional steels at the same reduction, since martensite is more easily induced by cold rolling in the inventive steels. In the inventive steels, more martensite is produced with less reduction.
As is apparent from FIG. 1, the inventive steels have a higher tensile strength and elongation than the conventional and comparative steels, both in the cold-rolled state and in the aged state, and show a remarkable increase in tensile strength by aging. That is to say, the inventive steels are superior to conventional work-hardenable austenitic stainless steels and precipitation-hardenable stainless steels in tensile strength and elongation both when they are used in the cold-rolled state and when they are used in the aged state. As the degree of cold-rolling can be reduced, good shape can be attained.
It will be apparent from a comparison of Table 1 and Table 2 that greater values of ΔHv are obtained in steels in which Si and Cu co-exist. It is understood that the age-hardening is caused by the synergistic action of Si and Cu.
It is apparent from FIG. 2 that Comparative Steel e which contains higher amounts of Mn and S is inferior to the inventive steels in elongation at the strength level after age-hardening. It is understood that ductility is inferior when the steel contains Mn and S in higher amounts.
TABLE 1__________________________________________________________________________ Elements (%) C Si Mn S Ni Cr N Cu Al Remarks Ms (°C.) Md (N) A' value__________________________________________________________________________InventiveSteelsH1 0.028 2.67 0.46 0.002 6.50 15.88 0.103 1.75 -- -61.6 73 62.3H2 0.059 2.72 0.42 0.001 6.56 15.97 0.099 1.74 -- -114.0 56 88.8H3 0.075 2.49 0.22 0.002 5.93 15.80 0.125 2.43 -- -125.4 43 102.0H4 0.042 2.18 0.36 0.002 5.85 15.10 0.098 2.65 -- 12.6 74 73.7ConventionalSteelsA 0.105 0.52 1.05 0.004 7.09 16.82 0.025 0.05 -- SUS301 -95.1 66.7 128.0B 0.120 0.50 1.13 0.006 7.54 17.50 0.015 0.07 -- " -161.23 38.8 141.7C 0.085 0.41 0.57 0.005 7.39 16.72 0.011 0.05 1.18 SUS631 -33.5 83.7 110.2ComparativeSteelsa 0.013 2.69 0.30 0.008 9.91 12.01 0.016 1.70 -- 66.1 93.97 50.5b 0.027 2.01 0.42 0.005 7.96 14.93 0.061 0.91 -- -19.9 91.3 61.1c 0.104 0.28 1.00 0.007 6.59 16.07 0.017 1.79 -- -9.9 49.0 127.6d 0.063 0.22 1.00 0.006 6.60 15.68 0.062 1.80 -- 0.7 62.7 92.5e 0.074 2.78 1.47 0.008 5.59 15.43 0.061 1.92 -- -30.6 68.8 101.1f 0.071 2.83 2.10 0.002 7.91 13.40 0.086 0.03 -- -146.8 80.9 98.7__________________________________________________________________________
TABLE 2__________________________________________________________________________ As rolled As aged 400° C. × 1 hr Sample Reduction α H'dness T.S. El. H'dness T.S. El. No. (%) (%) Hv (10) (kg/mm.sup.2) (%) Hv (10) (kg/mm.sup.2) (%) ΔHv__________________________________________________________________________Inventive H1 40 63.0 455 154 6.7 547 185 3.2 92steels 45 68.5 469 163 5.0 568 200 2.5 99 50 72.0 488 169 4.0 589 206 2.1 101 55 74.5 500 175 3.1 599 220 1.7 96 H2 40 63.5 481 167 6.1 580 196 3.1 99 45 64.5 502 175 4.4 601 208 2.3 99 50 67.0 520 183 4.0 612 219 2.0 92 55 69.5 534 191 3.4 628 225 1.6 94 H3 45 43.5 469 162 5.9 571 196 3.0 102 50 49.0 490 170 5.0 595 205 2.1 105 55 54.0 511 178 4.1 619 219 1.7 108 H4 45 45.5 428 147 7.2 526 178 3.1 98 50 51.5 440 151 6.3 541 180 2.6 101 55 57.3 456 159 4.4 551 187 2.0 95Conventional A 45 39.5 440 149 6.7 467 155 3.5 27steels 50 43.5 451 155 5.1 490 163 2.4 39 55 47.0 465 162 4.5 503 171 1.5 38 B 55 32.5 464 161 4.5 506 178 1.8 40 60 45.0 504 177 2.4 544 194 1.4 40 C* 45 44.5 420 143 7.0 520 182 1.7 100 50 49.0 445 153 5.6 549 189 1.2 104 55 58.0 451 159 4.6 558 195 1.1 107Comparative a 50 43.0 379 127 4.3 476 160 2.1 95Steels 60 55.5 410 136 2.9 506 171 1.0 96 b 50 56.0 415 140 5.2 482 164 2.8 67 60 65.0 441 149 3.1 507 172 1.4 66 c 50 60.5 473 165 4.4 514 180 2.0 43 60 69.0 500 183 1.9 542 195 1.6 42 d 50 67.0 444 157 2.6 503 174 2.3 59 60 76.0 459 172 2.0 516 182 1.5 57 e 40 48.0 459 160 5.6 549 188 1.8 90 45 50.5 473 162 5.0 558 194 1.7 85 50 55.5 486 167 4.0 580 202 1.5 94 55 59.5 499 173 3.3 592 212 1.2 93 f 50 46.5 447 149 4.8 500 170 2.1 53 60 54.0 479 161 2.7 528 180 0.9 49__________________________________________________________________________ *Conventional Steel C was aged at 480° C. for 1 hour.
Incidentally, ΔHv values of Conventional Steel C and Comparative steel a are high. But tensile strength in the cold-rolled state of these steels is not high and therefore the increase in tensile strength by aging is not so large. The high ΔHv value of Comparative Steel C is based on precipitation of the intermetallic compound Ni 3 Al.
For the sake of comparison, we reproduce Table 1 of U.S. Pat. No. 4,378,246 here as Table 3 in which Ms(°C.) values and Md(N) values are incorporated.
As seen in Table 1 and 3, the Md(N) values of the steels % U.S. Pat. No. 4,378,246 are more than 100, while those of the present invention are 43-74 in the indicated working examples.
Further, we carried out the following experiment. Steels of the present invention and those of similar compositions, which are indicated in Table 4, were prepared in the same manner as described above and the cold-rolled sheets were subjected to aging at 400° C. for 1 hour and mechanical properties were measured. The results are illustrated in FIGS. 3, 4 and 5.
FIG. 3 shows the relation between the Md(N) value and the amount of martensite formed from austenite. As seen there, the two are in the linearly proportional relation.
FIG. 4 shows the relation between the Md(N) value and the NTS (notch tensile strength)/TS (tensile strength) ratio. Said ratio is an index of toughness. FIG. 4 tells that when Md(N) exceeds 95, said ratio precipitously drops.
TABLE 3__________________________________________________________________________ A' Cr equ. Hv Md Specimen No. C Si Mn Ni Cr Cu Ti Al N value Ni equ. Value Ms (N)egree.C.)__________________________________________________________________________Steels of 1 0.033 1.45 0.31 7.40 14.90 1.00 0.34 0.020 0.015 39.83 2.32 162 101.5 115U.S. Pat. No. 2 0.047 0.65 1.00 6.70 14.50 0.51 0.32 0.45 0.009 39.57 2.42 188 146.8 1364,378,246 3 0.034 1.52 0.29 7.01 14.77 0.61 0.28 0.025 0.015 39.46 2.45 146 127.8 137 4 0.048 1.51 0.30 7.10 14.52 1.70 0.26 0.018 0.013 41.31 2.28 156 112.7 104 5 0.032 1.53 0.31 7.07 14.55 0.51 0.49 0.030 0.010 38.37 2.51 195 144.0 143 6 0.044 1.53 0.30 7.21 14.70 0.70 0.43 0.020 0.008 39.37 2.44 179 112.9 128 7 0.045 0.34 2.50 6.21 14.50 0.30 0.95 0.021 0.012 38.55 2.32 205 133.7 120 8 0.064 1.55 0.30 7.10 14.75 0.90 0.47 0.024 0.012 40.01 2.49 177 76.9 113 9 0.065 1.45 0.29 6.71 14.58 0.62 0.26 0.022 0.011 41.24 2.50 123 111.0 132 10 0.034 1.49 0.32 7.45 15.05 1.30 0.41 0.020 0.012 39.96 2.33 187 94.1 105Control 11 0.075 1.53 0.52 7.70 15.00 0.50 0.29 0.024 0.012 42.70 2.25 124 4.7 95.9 12 0.063 0.96 0.32 6.50 14.43 0.52 0.22 0.018 0.009 41.51 2.43 87 149.4 143.6 13 0.035 1.50 0.32 7.10 14.70 0.55 0.70 0.024 0.012 38.27 2.61 232 128.1 137.3 14 0.036 1.49 0.32 7.44 14.94 1.08 0.57 0.020 0.009 39.38 2.41 217 100.9 112.2 15 0.010 1.54 0.33 7.51 14.81 1.09 0.31 0.028 0.014 38.86 2.27 180 135.4 124.2 16 0.006 1.59 0.35 7.66 14.89 0.95 0.41 0.028 0.013 38.66 2.30 204 129.1 125.1 17 0.010 1.08 0.28 7.63 15.03 1.07 0.33 0.020 0.010 39.03 2.20 159 140.0 121.4 18 0.007 1.55 0.32 7.49 14.93 1.08 0.36 0.026 0.018 38.68 2.32 188 130.0 123.5 19 0.010 1.54 0.30 7.30 14.97 1.05 0.48 0.021 0.011 38.50 2.44 215 147.5 128.9 A (SUS301) 0.096 0.51 1.04 6.96 16.72 0.06 -- 0.020 0.010 not not not -42.3 80.3 calc'd calc'd calc'd B (17-7PH) 0.071 0.44 0.51 7.24 16.73 0.08 0.09 1.18 0.021 not not not -16.9 91.5 calc'd calc'd calc'd__________________________________________________________________________
TABLE 4__________________________________________________________________________ Amount of NTS/ A'Sp. No C Si Mn S Ni Cr Cu N Md(N) ΔHv Martensite TS Ms (°C.) Value Remarkes__________________________________________________________________________1 0.060 1.22 0.32 0.002 6.53 16.46 1.79 0.062 63 74 55 1.07 -27.6 89.8 X2 0.062 2.32 0.92 0.003 5.23 15.48 1.81 0.055 97 108 87 1.00 +50 90.0 X3 0.030 1.41 0.20 0.002 6.56 16.52 1.79 0.112 63 81 58 1.07 -66 64.4 X4 0.060 2.64 0.43 0.003 7.66 15.86 1.64 0.086 38 78 43 1.10 -54.7 90.6 O5 0.059 2.72 0.42 0.001 6.56 15.97 1.74 0.099 56 92 58 1.12 -114 88.8 H2 O6 0.073 2.54 0.53 0.003 5.35 15.13 1.71 0.054 103 105 95 0.80 +47.9 99.0 O7 0.106 2.58 1.04 0.004 6.96 16.30 1.79 0.019 30 48 29 1.12 -114 129.7 X8 0.028 2.67 0.46 0.003 6.50 15.88 1.75 0.103 73 101 72 1.10 -61.6 62.3 H1 O9 0.073 2.77 1.04 0.007 5.41 15.60 1.94 0.056 78 95 65 1.05 -2.1 99.9 X10 0.065 1.42 0.35 0.003 7.32 16.20 0.98 0.096 56 64 47 1.08 -136.6 94.1 X11 0.075 2.49 0.22 0.002 5.93 15.80 2.43 0.125 43 105 40 1.08 -125.4 102.0 H3 O12 0.037 2.01 0.42 0.005 7.96 15.30 0.91 0.061 80 67 76 1.05 -51.9 70.4 O13 0.066 2.83 1.54 0.008 6.12 16.64 2.07 0.110 21.5 45 20 1.10 -185.4 75.7 X14 0.074 2.78 1.47 0.008 5.56 15.43 1.92 0.061 69.5 99 56 1.00 -28.8 101.1 E X__________________________________________________________________________ O: invention steel, X: similar steel
FIG. 5 shows the relation between ΔHv and Md(N). FIG. 5 tells that under the Md(N) value of 35, the hardness increased by aging is insufficient. From the results shown in FIGS. 3, 4 and 5, it is understood that when the Md(N) value is between 35 and 95, the aged steel materials have good combination of hardness and ductility.
As has been described above, the steel of this invention is superior to known work-hardenable austenitic stainless steels and precipitation hardenable stainless steels in strength and ductility. The amounts of Mn, S, Ti, and Al, which form undesirable non-metallic inclusions, are carefully restricted and controlled, and in their stead, Cu, which does not produce undesirable inclusions, is added in a proper amount. This does not impair good surface smoothness, which is a characteristic of stainless steels. The steel is inexpensive since it does not contain no expensive elements. | There is disclosed a high strength stainless steel consisting essentially of not more than 0.10% C., more than 1.5% and not more than 2.95% Si, less than 0.5% Mn, not less than 4.0% and not more than 8.0% Ni, not less than 12.0% and not more than 18.0% Cr, not less than 0.5% and not more than 3.5% Cu, not more than 0.15% N and not more than 0.004% S, wherein the total content of C and N is not less than 0.10%, the balance is Fe and incidental impurities, said steel satisfies the relations A'>42, and 35<Md(N)<95, wherein A'=17×(C % / Ti %)+0.70×(Mn %)+1 x-(Ni %)+0.60×(Cr %)+0.76 (Cu %)-0.063×(Al %) and Md(N)=580-520 (C %)-2 (Si %)-16 (Mn %)-16 (Cr %)-23 (Ni %)-300 (N %)-26 (Cu %). This steel is inexpensive and can be provided with high strength and high ductility by cold working and aging. | 2 |
BACKGROUND
The present invention relates generally to mobile gaming and, more particularly, to a method for updating a multiplayer game session on a mobile device.
The widespread availability of mobile communication devices, such as cellular telephones, personal digital assistants, and laptop computers, has lead to increasing demand for mobile game applications. In the past, most mobile game applications comprised single player applications that were pre-installed or downloaded into the memory of the mobile device. Many mobile devices have limited capabilities, such as small displays and limited memory. Further, many mobile devices may connect over communication links characterized by limited bandwidth and intermittent connectivity. These limitations make it difficult to implement multi-player games on mobile devices.
SUMMARY
The present invention relates generally to multi-player games designed to be played on mobile devices. The multi-player game may comprise a plurality of game stages or game scenarios that can be stored as game data objects at a game data object server connected to a communication network. The game data can be downloaded one at a time to the mobile devices to update a game session on the mobile devices. Because the game applications are executed independently on each of the mobile devices, the mobile devices do not have to remain connected to the network to continue playing the game. A mobile device involved in a multiplayer game may connect to the game server, download a game scenario, and disconnect while the scenario is played on the mobile device. When a game update is required, the mobile device can reconnect to the game server to request a game update.
One aspect of the present invention includes a method for updating a game session on a mobile device. The method comprises detecting a game event during a game session, sending an update request to a game data object server responsive to the game event, receiving a game data object from the game data server responsive to the update request, and updating the game session with the game data object. The update request preferably includes an event identifier associated with the game event and the identity of one or more game participants. The game data object server may select a game data object based on the event identifier and/or the game participants identified in the update request. The game data object is sent to all participants in the game and contains information for a new game stage or new game scenario.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an exemplary communication network for online gaming.
FIG. 2 illustrates an exemplary method of updating a game session on a mobile device.
FIG. 3 illustrates an exemplary mobile device for playing multiplayer games.
FIG. 4 illustrates an exemplary game data object server.
DETAILED DESCRIPTION
The present invention is described below in the context of a data communications network 10 , shown in FIG. 1 . Data communications network 10 provides networking capabilities for a plurality of mobile devices 100 , which may comprise cellular telephones, personal digital assistants, laptop computers, or personal game devices. The data communications network 10 enables mobile device users to participate in multiplayer games. It should be appreciated, however, that the present invention is not limited to any specific type of data communications network or access technology.
The data communication network 10 comprises a mobile communication network 20 having one or more base stations or wireless access points 22 for communicating with mobile devices 100 . The mobile communication network 20 provides packet data services to mobile devices 100 as is known in the art and may operate according to any conventional standard, such as GSM, WCDMA, WiFi, WiMAX, and LTE standards. Mobile communication network 20 connects to a Packet Data Network (PDN) 30 . PDN 30 comprises a packet-switched network that implements conventional protocols, such as the suite of Internet protocols. The PDN 30 may comprise a public or private network, and may be a wide area or local area network. The Internet is one well-known example of a PDN 30 . Mobile devices 100 may also connect to the PDN 30 .
A game data object (GDO) server 50 connects to the mobile communication network 20 and/or PDN 30 and is accessible to the mobile devices 100 via the mobile communication network 20 and/or PDN 30 . The GDO server 50 provides online gaming services to mobile devices 100 and may function as a game server. In one exemplary embodiment, the mobile devices 100 may have a game client installed for interacting with the GDO server 50 . In other embodiments, the GDO server 50 may push game applications to the mobile devices 100 to enable players to play games with their mobile devices 100 .
The GDO server 50 enables two or more players to engage in a multiplayer game without the need to remain connected to the network for the duration of the game session. The game may be embodied in a series of GDOs that are pushed to the user one at a time. Each GDO may represent a distinct game stage or game scenario. As described in more detail below, the mobile devices 100 may connect to the GDO server 50 to download a GDO containing a game stage. When the GDO is downloaded, the mobile device 100 can disconnect from the game server 50 while the game stage is played. When the game stage is completed, the mobile device 100 can reconnect to the GDO server 50 and request a new game stage.
The GDOs may contain state information that updates a game application executing on the players' mobile devices 100 . When predetermined game events defined by a game stage or game scenario occur, the game client on the player's mobile device 100 sends an update request to the GDO server 50 . In response to the update request, the GDO server 50 sends a new GDO containing a new game stage to the game players.
FIG. 2 illustrates an exemplary method 200 for updating a game session according to one embodiment of the invention. To simplify the description, it is assumed that there are two game players, denoted herein as Player A and Player B. Those skilled in the art will appreciate, however, that the principals may be easily extended to three or more players.
The GDO server 50 may allow the players to create customized game stages or game scenarios that are unique to the particular players. Before beginning a gaming session, Player A and Player B may optionally log into the GDO server 50 to create or define one or more game stages or game scenarios (block 202 ). For example, the GDO server 50 may allow game players to define one or more events that may occur during a game stage, define characters in the game, define objects that appear in the game, and define rewards and penalties. The game stages or scenarios created by the players are stored as GDOs by the GDO server 50 (block 204 ).
When the players are ready to begin playing the game, the players establish a gaming session (block 206 ). At the start of the game session, a GDO corresponding to the first game stage is sent to each of the players. During the course of the game, the occurrence of certain predetermined game events defined by the game scenario will trigger the game application on the mobile device 100 to request an update from the GDO server 50 . When a game event is detected requiring an update of the game session (block 208 ), the mobile device 100 connects to the GDO server 50 and sends an update request (block 210 ). The update request includes an event identifier to identify the game event that triggered the update request, and a player identifier that identifies at least one other game player. For example, if Player A's game client detects the game event, Player A's game client sends an update request including the identity of Player B. Conversely, if the Player B's game client detects the game event, the Player B's game client sends the update request including the identity of Player A. In response to the update request, the GDO server 50 sends a new GDO corresponding to a new game stage to both players (block 212 ). When the new GDO is received by the mobile device 50 (block 214 ), the game session is updated (block 216 ).
The game events that trigger game updates may comprise composite events. A composite event is an event having two or more components. For example, the game context may require a game player to move around in a real-world environment. The movement of the player in the real-world environment may be reflected in the virtual game environment. In this example, the game context may require the player to move to a predetermined location and perform some predetermined action. Thus, the composite game event comprises moving to location x and performing action y.
FIG. 3 illustrates an exemplary mobile device 100 for online gaming The mobile device 100 comprises a game processor 102 , memory 104 , a communication interface 106 , and a user interface 108 . The game processor 102 may comprise one or more microprocessors, microcontrollers, hardware circuits, and/or a combination thereof, for executing game applications and for communicating with the GDO server 50 . Memory 104 stores data and programs needed by the game processor 52 . Memory 104 may comprise one or more discrete memory devices, such as random access memory, read-only memory, and flash memory. Communications interface 106 connects the mobile device to the communication network 10 . The communication interface 106 may comprise, for example, a cellular transceiver, WiFi transceiver, an Ethernet interface, cable modem, or DSL interface. The user interface 108 may comprise a display for viewing game information and one or more input devices, such a keypad, joystick, etc for receiving user input. The mobile device 100 may further include a GPS receiver 110 for determining the location of the mobile device 100 . Alternatively, the players' mobile device 100 may determine its location using triangulation techniques as is known in the art.
FIG. 4 illustrates an exemplary GDO server 50 . The GDO server 50 comprises a game processor 52 , memory 54 , communication interface 56 , and a mass storage device 60 . The data processor 52 may comprise one or more microprocessors, microcontrollers, hardware circuits, and/or a combination thereof. Memory 54 stores data and programs needed by the data processor 52 . Memory 54 may comprise one or more discrete memory devices, such as random access memory, read-only memory, and flash memory. Communications interface 56 connects the GDO server 50 to the packet data network 30 or mobile communication network 20 . The communication interface 56 may comprise, for example, an Ethernet interface, cable modem, or DSL interface. The GDO server 50 receives update requests and sends GDO objects to players via the communication interface 56 . The mass storage device 60 , such as a magnetic or optical disk drive, stores game data objects.
The present invention may, of course, be carried out in other specific ways than those herein set forth without departing from the spirit and essential characteristics of the invention. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, and all changes coming within the meaning and equivalency range of the appended claims are intended to be embraced therein. | A method for updating a game session comprises detecting a game event during a game session, sending an update request to a game data object server responsive to the game event, receiving a game data object from the game data server responsive to the update request, and updating the game session with the game data object. The update request preferably includes an event identifier associated with the game event and the identity of at least one game participant. Based on the player and event identified in the update request, the game data object server selects a corresponding game data object and sends the game data object to each of the players. | 0 |
[0001] This application claims priority to U.S. Provisional Application Ser. No. 60/924,032, filed May 24, 2007, the entirety of which is hereby incorporated by reference.
FIELD
[0002] This disclosure relates generally to porous keratin constructs and their various uses in different methods of wound healing. More particularly, the present disclosure relates to a porous keratin construct to enhance wound healing and which may be used as, for example, a pad applied directly on a wound or as a spacer or interface used in vacuum induced healing of open wounds.
BACKGROUND
[0003] Chronic wounds can be caused by a variety of events, including surgery, prolonged bed rest, and traumatic injuries. Partial thickness wounds can include second degree burns, abrasions, and skin graft donor sites. Healing of these wounds can be problematic, especially in cases of diabetes mellitus or chronic immune disorders. Full thickness wounds have no skin remaining, and can be the result of trauma, diabetes (e.g., leg ulcers), and venous stasis disease, which can cause full thickness ulcers of the lower extremities. Full thickness wounds tend to heal very slowly. Proper wound care technique, including the use of wound dressings, is extremely important to successful chronic wound management. Chronic wounds affect an estimated four million people a year, resulting in health care costs in the billions of dollars.
[0004] The wound healing process involves a complex series of biological interactions at the cellular level, which can be grouped into three phases: hemostasis and inflammation, granulation tissue formation and re-epithelization, and remodeling. Keratinocytes (epidermal cells that manufacture and contain keratin) migrate from wound edges to cover the wound. Growth factors such as transforming growth factor-β (TGF-β) play a critical role in stimulating the migration process. The migration occurs optimally under the cover of a moist layer.
[0005] Keratins have been found to be necessary for the re-epithelization phase of the wound healing process. Keratins are major structural proteins of all epithelial cell types and appear to play a major role in wound healing.
[0006] Although not ideal for chronic wounds, several wound dressings are currently on the market, including occlusive dressings, non-adherent wound dressings and dressings in the form of sheets, foams, powders and gels. However, these wound dressings are not optimal and face several problems. For example, many existing wound dressings fail to manage exudates while still providing a beneficial material (such as keratin) to wounds. Additionally, wound dressings comprising layers of protein on synthetic foam tend to prevent uptake of exudates because the protein layers tend to ingress into the foam. Finally, existing wound dressings do not prevent oxidative stress associated with highly exuding wounds. Accordingly, a wound dressing suitable to be placed directly into a wound that addresses some or all of these issues is desirable.
[0007] Additionally, certain severe wounds require treatment that goes beyond merely placing a wound dressing directly on to the wound in order to achieve effective healing. As is well known to those of ordinary skill in the art, closure of surface wounds involves the inward migration of epithelial and subcutaneous tissue adjacent the wound. This migration is ordinarily assisted through the inflammatory process, whereby blood flow is increased and various functional cell types are activated. Through the inflammatory process, blood flow through damaged or broken vessels is stopped by capillary level occlusion; thereafter, cleanup and rebuilding operations may begin. Unfortunately, this process is hampered when a wound is large or has become infected. In such wounds, a zone of stasis (i.e., an area in which localized swelling of tissue restricts the flow of blood to the tissues) forms near the surface of the wound.
[0008] Without sufficient blood flow, the epithelial and subcutaneous tissues surrounding the wound not only receive diminished oxygen and nutrients, but are also less able to successfully fight bacterial infection and thus are less able to naturally close the wound. In the past, such difficult wounds were addressed only through the use of sutures or staples. Although still widely practiced and often effective, such mechanical closure techniques suffer a major disadvantage in that they produce tension on the skin tissue adjacent the wound. In particular, the tensile force required in order to achieve closure using sutures or staples may cause very high localized stresses at the suture or staple insertion point. These stresses commonly result in the rupture of the tissue at the insertion points, which can eventually cause wound dehiscence and additional tissue loss.
[0009] Additionally, some wounds harden and inflame to such a degree due to infection that closure by stapling or suturing is not feasible. Wounds not reparable by suturing or stapling generally require prolonged hospitalization, with its attendant high cost, and major surgical procedures, such as grafts of surrounding tissues. Examples of wounds not readily treatable with staples or suturing include large, deep, open wounds; decubitus ulcers; ulcers resulting from chronic osteomyelitis; and partial thickness burns that subsequently develop into full thickness burns.
[0010] One such alternative method of treating these types of wounds is vacuum induced healing. Vacuum induced healing of open wounds has recently been popularized by Kinetic Concepts, Inc. of San Antonio, Tex., by its commercially available V.A.C.® product line. The vacuum induced healing process has been described in U.S. Pat. No. 4,969,880 issued on Nov. 13, 1990 to Zarnierowski, as well as its continuations and continuations in part, U.S. Pat. No. 5,100,396, issued on Mar. 31, 1992, U.S. Pat. No. 5,261,893, issued Nov. 16, 1993, and U.S. Pat. No. 5,527,293, issued Jun. 18, 1996, the disclosures of which are incorporated herein by this reference. Further improvements and modifications of the vacuum induced healing process are also described in U.S. Pat. No. 6,071,267, issued on Jun. 6, 2000 to Zamierowski and U.S. Pat. Nos. 5,636,643 and 5,645,081 issued to Argenta et al. on Jun. 10, 1997 and Jul. 8, 1997 respectively, the disclosures of which are incorporated by reference as though fully set forth herein.
[0011] As a result of the shortcomings of mechanical closure devices described above, methods and apparatus for draining wounds by applying continuous negative pressure have been developed. When applied over a sufficient area of the wound, such negative pressures have been found to promote the migration toward the wound of epithelial and subcutaneous tissues. In practice, the application to a wound of negative gauge pressure, commercialized by KCl Licensing, Inc., San Antonio, Tex., under the designation “Vacuum Assisted Closure” (or “V.A.C.®”) therapy, typically involves the mechanical-like contraction of the wound with simultaneous removal of excess fluid. In this manner, V.A.C.® therapy augments the body's natural inflammatory process while alleviating many of the known intrinsic side effects, such as the production of edema caused by increased blood flow absent the necessary vascular structure for proper venous return.
[0012] While V.A.C.® therapy has been highly successful in the promotion of wound closure, healing many wounds previously thought largely untreatable, some difficulty remains. Because the very nature of V.A.C.® therapy dictates an atmospherically sealed wound site, the therapy must often be performed to the exclusion of other beneficial, and therefore desirable, wound treatment modalities. One of these hitherto excluded modalities is the encouragement of cell growth by the provision of an in situ cell growth-enhancing matrix.
[0013] Additional difficulty remains in the frequent changing of the wound dressing. As the wound closes, binding of cellular tissue to the wound dressing may occur. Use of traditional V.A.C.® therapy necessitates regular changing of the dressing. Dressing changes can result in some tissue damage at the wound site if cellular tissue has grown excessively into the dressing.
[0014] U.S. Pat. No. 7,070,584, issued Jul. 4, 2006, discloses using a fused-fibrous ceramic, a bioabsorbable polymer or cell growth enhancing matrix or scaffolding in a V.A.C.® environment.
[0015] Accordingly, an object of the embodiments disclosed herein is to provide a wound dressing that effectively serves as a wound dressing for placement directly on to the wound and which provides keratin to the wound to promote healing.
[0016] A further object of the embodiments disclosed herein is to provide a wound dressing for placement into the wound that manages exudates, is bioabsorbable and reduces oxidative stress.
[0017] Another object of the embodiments disclosed herein is to provide an improved wound dressing for vacuum induced healing therapy, which overcomes the problems and limitations of the prior art.
[0018] An additional object of the embodiments disclosed herein is to allow for controlled application of growth factors or other healing factors, which could be embedded in the dressing or introduced into the dressing through a port or other connector fitting.
[0019] Still another object of the embodiments disclosed herein is to provide a fully and/or partially bioabsorbable wound dressing that minimizes disruption of the wound site during dressing changes.
[0020] A yet further object of the embodiments disclosed herein is to provide such a dressing that is economical and disposable, but also safe for general patient use.
SUMMARY
[0021] In accordance with the foregoing objects, the present disclosure generally comprises a porous keratin construct for insertion substantially into the wound site. The porous keratin construct may be placed directly in the wound and optionally maintained in the wound through the use of, for example, a bandage, or may be used in conjunction with, for example, vacuum assisted closure as described in greater detail below.
[0022] In a first embodiment, the pad is a foamed solidified keratin protein material. The keratin protein is preferably S-sulfonated protein, oxidized keratin protein or reduced keratin protein. The keratin protein may also be keratin protein fractions, such as intermediate filament keratin protein, high-sulfur keratin protein or high-glycine-high-tryosine keratin protein. The keratin protein or protein fractions may be intact or hydrolysed.
[0023] In another embodiment, the pad comprises a conventional foam pad, such as a foam pad made of polyurethane or polyvinylalcohol, and a layer of porous keratin protein on the foam pad adjacent the wound, such that upon removal of the pad during dressing changes, the keratin protein is either left behind or has already bioabsorbed into the wound, leaving the wound site undisturbed. The porous keratin protein layer may be S-sulfonated protein, oxidized keratin protein or reduced keratin protein. The keratin protein adjacent the wound may also be a keratin protein fraction, such as intermediate filament keratin protein, high-sulfur keratin protein or high-glycine-high-tryosine keratin protein. The keratin protein or protein fraction may also be intact or hydrolysed.
[0024] In still another embodiment, either pad as described above is used as part of an assembly for vacuum assisted closure. In addition to the pad, the assembly may include a wound drape for enclosing the porous keratin construct or keratin construct and synthetic foam construct at the wound site. The keratin construct (with or without synthetic foam), comprised of a foamed solidified material having relatively few open cells in contact with the areas upon which cell growth is to be encouraged so as to avoid unwanted adhesions but having sufficiently numerous open cells so that drainage and vacuum assisted therapy may continue unimpaired, may be placed in the wound and encapsulated by the wound drape. Utilization of keratin in the pad enables the pad to remain in place during the healing process. As cell growth continues, the keratin material is absorbed, and there is no need to remove the pad. The assembly may also include a vacuum source for application of negative pressure to the area under the wound drape and promotion of fluid drainage. The wound drape forms an airtight seal over the wound site to prevent vacuum leakage.
[0025] Spaces in the porous keratin material create small volume areas that provide an excellent environment to enhance cell growth, and thus further the process envisioned by the healing process. Accordingly, cell growth enhancement therapy may be conveniently combined with existing vacuum assisted therapies, without loss of performance and without inconvenience or overly increased cost.
[0026] In still another embodiment, a method for treating wounds employing the construct described above is disclosed. The keratin construct may be placed in a wound and subsequently encapsulated by a wound drape. The wound drape may be placed in fluid communication with a vacuum source, and negative pressure may be applied to the area encapsulated by the wound drape.
[0027] The type of wound which may be treated by the above described embodiments is not limited and may include, for example, soft tissue wounds or bone defects.
[0028] Finally, many other features, objects and advantages of the present disclosure will be apparent to those of ordinary skill in the relevant arts, especially in light of the foregoing discussions and the following drawing and exemplary detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] These and other features and advantages of the disclosure will now be described with reference to the drawings of certain preferred embodiments, which are intended to illustrate and not to limit the disclosure, and wherein like reference numbers refer to like components, and in which:
[0030] FIG. 1 shows, in partially cut away perspective view, a first embodiment of the present disclosure as applied to a mammalian wound site wherein a porous keratin pad is used in a vacuum assisted wound care environment;
[0031] FIG. 2 shows, in partially cut away perspective view, a second embodiment of the present disclosure as applied to a mammalian wound site wherein the porous keratin layer is used with a conventional foam pad in a vacuum assisted wound care environment.
DETAILED DESCRIPTION
[0032] Although those of ordinary skill in the art will readily recognize many alternative embodiments, especially in light of the illustrations provided herein, this detailed description is exemplary of the preferred embodiment of the present disclosure, the scope of which is limited only by the claims that may be drawn hereto.
[0033] The present disclosure is directed to a biocompatible wound dressing which may be used by, for example, maintaining the wound dressing directly in the wound or in conjunction with negative pressure or vacuum assisted wound therapy. The term “wound” as used herein, while not limited, may include burns, incisional wounds, excisional wounds, ulcers, traumatic wounds, bone defects and chronic open wounds. As used herein, the term “construct,” while not limited, may include foams, screens, pads and blocks. The term “conventional pad,” while not limited, may include polyurethane (PU) or polyvinylalcohol (PVA) foam pads commonly used with vacuum assisted therapy.
[0034] In a first embodiment, a porous keratin construct is used in wound healing.
[0035] Keratin is a family of proteins characterized by a high degree of the amino acid cystine, which imparts a high degree of crosslinking to keratin proteins through disulfide links. Keratin proteins are present in a wide range of biological tissue, performing a structural role in skin, hair and other materials. Keratins extracted from hair have been shown to be a valuable component in wound dressings. Specifically, keratins have been found to be necessary for the re-epithelization phase of the wound healing process. Accordingly, a keratin construct used in negative pressure therapy will further promote wound healing and absorb into the wound, thus reducing the occurrence of traumatizing wounds when changing dressings or discontinuing use of negative pressure therapy.
[0036] The keratin protein of the present disclosure may be chemically modified. One such process involves chemically modifying keratin to form S-sulfonated keratin as described in U.S. Pat. No. 7,148,327, issued Dec. 12, 2006, incorporated herein by reference.
[0037] In one aspect, the keratin used in this disclosure is S-sulfonated keratin protein. S-sulfonated keratin refers to keratin protein that undergoes a process wherein the disulfide bonds between cystine amino acid in keratin protein are reversibly modified to create polar functional groups that allow for controlled re-introduction of the natural disulfide crosslinks originally present in the keratin protein. S-sulfonated keratins have cysteine/cystine present predominantly in the form of S-sulfocysteine. This highly polar group imparts a degree of solubility to proteins. Whilst being stable in solution, the S-sulfo group is a liable cysteine derivative, highly reactive towards thiols, such as cysteine, and other reducing agents. Reaction with reducing agents leads to conversion of the S-sulfo cysteine group back to cystine. S-sulfo cysteine is chemically different from cysteic acid, although both groups contain the SO 3 − group. Cysteic acid is produced irreversibly by the oxidation of cysteine or cystine and once formed cannot form disulfide crosslinks back to cysteine. S-sulfocysteine is reactive towards cysteine and readily forms disulfide crosslinks In the case of S-sulfonated keratin protein, the conversion of the S-sulfonate form to the crosslinked disulfide form may be accomplished through application of reducing conditions, for example, by applying a thiol. S-sulfonated keratin protein may be prepared by a variety of methods, including those described in U.S. Pat. No. 7,148,327, issued Dec. 12, 2006, incorporated herein by reference.
[0038] The mechanism for modifying the cystine disulfide bond to cysteine S-sulfonate is summarized as follows, wherein K is keratin:
[0000] K-S-S-K→2K-S-SO 3 −
[0039] The mechanism for reforming the crosslinks may be summarized as follows, wherein K is keratin and R is a reducing agent:
[0000] K-S-SO 3 − +R-S − →K-S-S-R+SO 3 2−
[0000] K-S-S-R+R-S − →K-S-+R-S-S-R
[0000] K-S-SO 3 − +R-S − →K-S-S-K+SO 3 2−
[0040] The keratin protein may be a keratin protein fraction. Keratin protein fractions are distinct groups from within the keratin protein family, and include intermediate filament proteins, high sulfur proteins and high glycine-tyrosine proteins.
[0041] Intermediate filament proteins are described in detail by Orwin et al. ( Structure and Biochemistry of Mammalian Hard Keratin , Electron Microscopy Reviews, 4, 47, 1991) and also referred to as low sulfur proteins by Gillespie (Biochemistry and physiology of the skin, vol. 1, Ed. Goldsmith Oxford University Press, London, 1983, pp. 475-510). Key characteristics of intermediate filament protein family are molecular weight in the range 40-60 kD and a cysteine content (measured as half cystine) of around 4%.
[0042] The high sulfur protein family is also well described by Orwin and Gillespie in the same publications reference above. This protein family has a large degree of heterogeity, but can be characterized as having a molecular weight in the range 10-30 kD and a cysteine content of greater than 10%. A subset of this family is the ultrahigh sulfur proteins, which can have a cysteine content of up to 34%.
[0043] The high glycine-tryosine protein family is also well described by Orwin and Gillespie in the same publications referenced above. This family is also referred to as the high tyrosine proteins and has characteristics of a molecular weight less than 10 kD, a tyrosine content typically greater than 10% and a glycine content typically greater than 20%.
[0044] For the purpose of this disclosure, a “keratin protein fraction” is a purified form of keratin that contains predominantly, although not entirely, one distinct protein group as described above.
[0045] The keratin protein or protein fraction may also be intact. The term intact refers to proteins that have not been significantly hydrolysed, with hydrolysis being defined as the cleavage of bonds through the addition of water. Gillespie considers intact to refer to proteins in the keratinized polymeric state and further refers to polypeptide subunits which complex to form intact keratin in wool and hair. For purposes of this disclosure, intact refers to the polypeptide subunits described in Gillespie. These are equivalent to the keratin proteins in their native form without the disulfide crosslinks formed through the process of keratinization.
[0046] Intact keratin proteins and keratin protein fractions are discussed in greater detail in co-pending, co-owned U.S. patent application Ser. No. 10/583,445, filed Jun. 19, 2006 and of which the entire application is hereby incorporated by reference.
[0047] The keratin may also be oxidized keratin. Oxidized keratins are produced as a result of exposing insoluble keratins to oxidizing agents, resulting in the conversion of cystine to cysteic acid and the keratin being converted to a soluble form. As a result of this, oxidized keratins are suitable for use in wound healing as disclosed herein.
[0048] The keratin may also be reduced keratin. Reduced keratins are produced as a result of exposing insoluble keratins to reducing agents, such as thiols, phosphines or other similar reducing agents. This converts the cystine present to cysteine or an alternative derivative, cleaving the crosslinks and converting the insoluble keratin into a soluble form. In this form, reduced keratins are soluble and suitable for use in wound healing as described herein.
[0049] In yet another alternate embodiment of the present disclosure, a conventional foam pad (e.g., a polyurethane foam or a polyvinylalcohol foam) further comprises a porous keratin protein growth-enhancing matrix layer facing towards a wound site. In this configuration, removal of the basic foam pad during dressing changes enables at least part of the porous keratin protein material to be left in the wound, thus leaving the wound site undisturbed. Furthermore, because the keratin is or comprises a material that is both bioabsorable and capable of promoting wound healing, the porous keratin further enhances negative pressure wound therapy when used for that purpose.
[0050] As with the previous embodiments, keratin protein may be S-sulfonated keratin protein, reduced keratin protein or oxidized keratin protein. The keratin protein may be a keratin protein fraction such as intermediate filament keratin protein, high sulfur keratin protein and high glycine-tyrosine keratin protein. The keratin protein or keratin protein fraction may be hydrolysed or intact.
[0051] Methods of making the porous keratin construct and keratin layer described above are set forth in commonly-owned, co-pending U.S. application Ser. No. 12/000,292, filed Dec. 11, 2007, the entirety of which is hereby incorporated by reference.
[0052] Referring now to the figures, a construct as described above and used in conjunction with known negative pressure therapy is shown in FIG. 1 . Assemblies for use in negative pressure therapy generally comprise a porous keratin construct 11 for insertion substantially into the wound site 12 , a wound drape 13 forming a sealing enclosure over the construct 11 at the wound site 12 and a vacuum source. According to one embodiment of the disclosure, the wound site is a soft tissue wound bed or a bone defect. The porous construct 11 may be made of or substantially comprise a solid, porous keratin protein. The porous keratin protein may be keratin protein fractions, intact and/or hydrolysed as discussed in greater detail above. In an alternate aspect of the embodiment, the porous construct 11 may be comprised of multiple, distinct layers of porous keratin. The layers may be separated from one another upon removal of the construct 11 from the wound so as to leave behind some layers.
[0053] After insertion of the keratin construct 11 into the wound site 12 and sealing with the wound drape 13 , the wound drape 13 may be placed in fluid communication with a vacuum source and a negative pressure may be applied to the area encapsulated by the wound drape 13 . Negative pressure is applied for promotion of fluid drainage in accordance with conventional procedures. The wound drape 13 may be placed in fluid communication, via a plastic or like material hose 15 , with a vacuum source, which may comprise a canister safely placed under vacuum through fluid communication, via an interposed hydrophobic membrane filter, with a vacuum pump. The wound drape 13 , which preferably may comprise an elastomeric material at least peripherally covered with a pressure sensitive, acrylic adhesive for sealing application over the wound site 12 , is air tight so as to allow for negative pressure in the area enclosed by the wound drape 13 . In one aspect, the construct 11 may also include perforations to reduce any pressure drop or impedance to exudate flow.
[0054] According to another embodiment of the instant disclosure and as illustrated in FIG. 2 , a conventional foam pad 17 is modified to include a keratin layer 14 , whereby a desired porous cell growth-enhancing construct that may be directed into and about the wound site 12 is provided. The keratin layer 14 may be, keratin protein fractions, hydrolysed and/or intact as described in greater detail above. The conventional pad 17 may be comprised of several distinct layers of conventional foam pads stacked on top of one another. Similarly, the keratin layer 14 may be comprised of several distinct layers of keratin layers stacked on top of one another.
[0055] After insertion of the foam pad 17 and keratin layer 14 into the wound site 12 and sealing with the wound drape 13 , the wound drape 13 is placed in fluid communication with a vacuum source for promotion of fluid drainage in accordance with known procedures. The porous keratin layer 14 may cover the entire surface of the foam pad or only a portion thereof to suit specific wound care needs.
EXAMPLE I
[0056] S-sulfonated keratin protein is formed into a porous pad. The general principles of known vacuum assisted wound therapy are followed with the pad in contact with the wound. During the expected duty cycle of the pad, the pad is partially or totally absorbed by the growing cells, so that there is less need to replace the pad and disturb the wound site.
EXAMPLE II
[0057] A conventional foam pad used in vacuum assisted wound therapy is selected. A S-sulfonated keratin protein growth-enhancing porous layer is applied to a portion of the bottom thereof intended to face a wound site. The general principles of vacuum assisted wound therapy are followed, with the keratin layer containing pad substituted for a conventional pad. During the expected duty cycle of the pad, the keratin layer is absorbed by the growing cells, so that when the basic foam pad is removed, the keratin layer has been partially or totally absorbed, and the growing cells are not disturbed.
EXAMPLE III
[0058] A porous solid pad formed of S-sulfonated keratin protein is selected. The pad is placed directly in a wound. The pad is secured on the wound by use of bandage or other securable means. During the expected duty cycle of the pad, the pad is absorbed by the growing cells, so that there is no need to replace the pad and disturb the wound site.
EXAMPLE IV
[0059] A polymer foam or other conventional foam pad is selected. A solid porous S-sulfonated keratin protein growth-enhancing layer is applied to a portion of the bottom thereof intended to face a wound site. The composite pad is secured on the wound by use of bandage. During the expected duty cycle of the pad, the keratin layer is absorbed by the growing cells, so that when the pad is removed, the layer had been absorbed, and the growing cells are not disturbed.
EXAMPLE V
In Vitro Performance of Keratin Constructs
[0060] Using a bench top simulation rig, it was established that fluid could be drawn, at typical flow rates which prevail in highly exuding wounds, through a porous keratin construct or multiple layers of such constructs placed between a conventional polyurethane dressing and a wound surface without causing excessive pressure drop across the construct(s). Thus, it was demonstrated that said construct or constructs could be used adjacent to the polyurethane construct when administering negative pressure wound therapy without excessive loss of vacuum at the wound surface.
[0061] Further, when simulated wound fluid (Trypsin) was drawn through the porous keratin construct, it caused the construct to biodegrade, as is expected from experience with such constructs in wounds, and this reduced the pressure drop across the construct. This demonstrated that the biodegradation of the construct, which would be expected to occur in vivo, does not cause the construct to create an excessive pressure drop or loss of vacuum at the wound surface.
[0062] Still further, when simulated wound fluid (Trypsin) was drawn through multiple porous keratin constructs, the lowest construct (i.e., in direct contact with the wound upon first application) was observed to biodegrade first and there was a significant period of time when the lowest construct biodegraded but the upper porous keratin construct remained intact. This demonstrated that by using multiple porous keratin constructs in the wound bed under the conventional polyurethane construct, the benefits of a bioresorbable construct can be obtained whilst the upper construct remains intact and provides an interface to the conventional polyurethane construct and would prevent any tissue in-growth into the conventional polyurethane construct.
EXAMPLE VI
In Vivo Performance of Keratin Constructs
[0063] A clinical evaluation was performed on the use of a keratin construct as an adjunct to negative pressure wound therapy. In a series of cases of wound patients who would ordinarily receive negative pressure therapy, negative pressure wound therapy was administered using standard commercially available equipment involving a polyurethane foam and a vacuum pump typically set to 125-150 mmHg continuous negative pressure. In each case, pain at dressing change was evaluated prior to study commencement and again at each dressing change. Pain at dressing change typically occurs due to disruption of healing tissue as a result of in-growth into the polyurethane foam.
[0064] On commencement of the evaluation, keratin constructs were perforated with multiple 5 mm off-set incisions and hydrated in saline for approximately 3 minutes. These constructs were then placed under the polyurethane foam (i.e. at the wound interface), and negative pressure therapy continued in the normal manner. Dressing changes occurred typically 3 times per week. In several cases pain at dressing change was rated as 10 out of 10 prior to the study. By the third dressing change this had reduced to 0 out of 10, indicating a substantial reduction in pain at dressing change as a result of the keratin construct interface. Visual examination of the polyurethane foam indicated substantially less tissue in-growth following use of the keratin construct. In addition, exudate flows were reported as normal.
[0065] While the foregoing description is exemplary of the preferred embodiment of the present disclosure, those of ordinary skill in the relevant arts will recognize the many variations, alterations, modifications, substitutions and the like are readily possible, especially in light of this description and the accompanying drawings. In any case, because the scope of the present disclosure is much broader than any particular embodiment, the foregoing detailed description should not be construed as a limitation of the scope of the present disclosure, which is limited only by the claims that are drawn hereto. | A porous keratin construct for use in wound healing is disclosed. The porous keratin construct may be used standing alone or in combination with a synthetic foam backing layer. Either the porous keratin construct or the porous keratin construct and synthetic foam combination may be used in a wound therapy such as negative pressure wound therapy. An assembly for use in negative pressure wound therapy may comprise a porous keratin construct or porous keratin construct and synthetic foam combination, a wound drape to encapsulate the wound and the porous keratin construct or porous keratin construct and synthetic foam combination, and a vacuum source in fluid communication with the wound drape to apply a negative pressure to the area encapsulated by the wound drape | 0 |
BACKGROUND
[0001] 1. Technical Field
[0002] The present invention relates to an improved apparatus to seal the sides of the nip area at the sides of opposing sheeter rollers generally mounted parallel to each other. An improved seal prevents doughy material from penetrating into crevices of the apparatus according to the prior art as doughy material is compressed into a sheet. Specifically, this invention uses improved materials and configurations to create a new side seal for a sheeting apparatus.
[0003] 2. Description of Related Art
[0004] With reference to FIG. 1 , in a conventional dough sheeter, opposing rollers 110 are separated by a small gap or nip 102 . Doughy material 104 is fed into the nip 102 above opposing rollers 110 and passes through the nip 102 to form a sheet 106 . It is normally necessary to place a seal at the ends of opposing sheeter rollers to prevent leakage of doughy material from the sides of opposing rollers 110 . Leakage results in loss of valuable product as well as thinning of the dough sheet near the edges.
[0005] FIG. 2 shows an overhead view of conventional side seals. With reference to FIG. 2 , side seals 210 are typically made of a plastic or other low-friction material, and are pressed against the ends of sheeting rollers 110 by mechanical means including, but not limited to, screws 204 attached to a sheeter housing 206 . Such side seals 210 press with a force greater than the pressure created by the sheeting process. There are several drawbacks to conventional arrangements including seal leakage, seal wear due to pressurized contact, and poor accessibility for seal replacement.
[0006] FIG. 3 a is a cross-sectional drawing of a portion of a prior art side seal. Such a side seal according to the prior art consists of a side seal bracket 320 of arbitrary shape made of metal or other stiff material, a shim 312 also made of a metal or other stiff material, and a plastic sealing piece 308 . FIG. 3 a shows such a portion of a side seal after newly assembled and before operation of a sheeting apparatus. The shim 312 is held in place by one or more screws 314 .
[0007] Often, manual adjustment of the side seal is required to obtain the desired distance between the plastic sealing piece 308 and the sheeting rollers 512 , 514 . Generally, the shims 312 and screws 314 must be manually adjusted to bring the sealing pieces 308 within about 0.05 inches (1.27 mm) to 0.07 inches (1.78 mm) of the side surface of the sheeting rollers 512 , 514 along the length of the sealing piece 308 . According to some embodiments of the prior art, such adjustment may require up to twelve hours of manual adjustment each time the seals are replaced. According to the prior art, side seals wear out within about one month of continuous sheeting operation.
[0008] With reference to FIG. 3 a, when the side seal is assembled, the shim 312 and plastic sealing piece 308 are tightly abutted to each other, and the plastic sealing piece 308 is uniform having no wear. FIG. 3 b is a similar cross-sectional drawing showing the same pieces of a side seal after having been subjected to approximately one month of continuous operation and wear. Over time, doughy material 104 is forced into the interface between the plastic sealing piece 308 and the metal shim 312 by the operating or sheeting pressure generated by opposing sheeting rollers 512 , 514 . As seen in FIG. 3 b, repeated penetration of doughy material 104 between the sealing piece 308 and the metal shim 312 has forced the plastic sealing piece 308 to bulge outward toward the sheeting rollers 110 . This has caused the plastic sealing piece 308 to wear away and to be replaced by doughy material 104 although still maintaining a relatively flat outer surface 402 . Over time, the thickness of the plastic sealing piece 308 remains thicker near the attaching screw 310 . If the plastic sealing piece 308 is not replaced, the side seal eventually becomes ineffective.
[0009] Consequently, a need exists for an improved apparatus to provide for more effective sealing of the sides of a dough sheeter and less waste of doughy material. A need exists to eliminate the required manual adjustment necessary to replace plastic sealing pieces. A need exists for an apparatus that allows for easier, faster installation of replacement side sealing pieces. A further need exists to eliminate plastic sealing material from entering sheeted dough as the plastic sealing piece is worn away during sheeting operation. Additionally, a need exists to reduce the frequency of replacing worn plastic sealing pieces.
SUMMARY OF THE INVENTION
[0010] The proposed invention comprises an improved end seal for a sheeting apparatus. A sealing material is formed into a more effective surface to prevent doughy material from leaving the sheeting nip. In one embodiment, an improved end seal provides an improved wiping and sealing function. Such an improved seal also reduces wear by preventing doughy material from being forced into the seal assembly, thus reducing the frequency of seal replacement. Such an improved seal reduces the amount of installation time and amount of error associated with manual adjustment ordinarily required to replace end seals. Additional features and benefits of the present invention will become apparent in the following written detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The novel features believed characteristic of the invention are set forth in the appended claims. The invention itself, however, as well as a preferred mode of use, further objectives and advantages thereof, will be best understood by reference to the following detailed description of illustrative embodiments when read in conjunction with the accompanying drawings, wherein:
[0012] FIG. 1 is a drawing showing a cross-sectional side view of a pair of opposing sheeting rollers;
[0013] FIG. 2 is a drawing showing an overhead cross-sectional view of a sheeting apparatus according to the prior art wherein side seals are mounted to the sheeter housing;
[0014] FIG. 3 a is a drawing of a cross-sectional view of a portion of a freshly installed side seal, and FIG. 3 b illustrates a typical side seal after substantial wear and approximately one month of continuous operation;
[0015] FIG. 4 is a partial cross-sectional view of a preferred embodiment of a roller-mounted side seal according to the present invention;
[0016] FIG. 5 is a drawing of one roller and one section of a roller-mounted side seal according to the present invention as seen from the side of a sheeting apparatus; and
[0017] FIG. 5 a is a drawing showing a close-up view of a bracket used to mount a side seal on the roller shown in FIG. 5 .
REFERENCE NUMERALS
[0000]
102 nip
104 doughy material
106 dough sheet
110 opposing sheeting rollers
204 screws
206 sheeter housing
210 side seals
306 bracket mounting screw
308 plastic sealing piece
310 seal attaching screw
312 shim
314 set screw
316 seal distance
320 side seal bracket
402 flat outer surface in FIG. 3 b, mating contour in FIG. 4
400 sealing element
402 mating contour
404 roller lip
406 groove
408 back surface
410 bracket lip
512 first sheeting roller according to a prior art apparatus
514 opposing sheeting roller according to a prior art apparatus
500 improved sealing bracket
502 seal mounting hole
504 bracket mounting hole
612 first sheeting roller
614 opposing sheeting roller
DETAILED DESCRIPTION
[0046] While the invention is described below with respect to a preferred embodiment, other embodiments are possible. The concepts disclosed herein apply to other systems for producing sheeted products.
[0047] The primary objective of this invention is to provide an apparatus which provides improved sealing of the sides of the nip area of a dough sheeting apparatus. In one embodiment, a side seal is made such that after it is mounted in place, the side seal lightly or nearly contacts the side edge of the sheeting rollers. In such an embodiment, no shim 312 is required. One or more shims, however, may be used, depending on the specific application. One or more plastic sealing pieces are attached to a bracket by screws or other mechanical means. Such a side seal is mounted to a housing or other member adjacent to the nip region of the sheeting rollers.
[0048] With reference to FIG. 4 , according to a preferred embodiment of the invention, side seals are mounted on the sides of a first sheeting roller 612 , across the sheeter nip 102 , and overlap an opposing sheeting roller 614 . With reference to FIG. 4 , FIG. 5 , and FIG. 5 a, a sealing element 400 is attached with attaching screws 310 through seal mounting holes 502 to an improved sealing bracket 500 . An improved sealing bracket 500 has a bracket lip 410 on the edge of a sealing bracket 500 which tightly holds a sealing element 400 in place. In one embodiment, a sealing element 400 is formed with a mating contour 402 that coordinates with a bracket lip 410 along the edge of a sealing bracket 500 , which contributes to maintaining tightly in place the sealing element 400 . A bracket lip 410 on an improved sealing bracket 500 holds a sealing element 400 along the entire circumference of a sheeter roller and is not held solely by mounting screws 310 . Such an arrangement of pieces reduces wear to a seal element 400 by reducing the possibility that dough is forced into the seal assembly such that replacement of a seal element 400 is only necessary about every few years instead of about once per month. In another embodiment, screws 310 are not used to attach a sealing element 400 because of the presence of a bracket lip 410 of an improved sealing bracket 500 .
[0049] In another embodiment, an improved sealing bracket 500 or sealing element 400 is formed such that there is no need for a shim 312 along the back surface 408 of the sealing element 400 . Such sealing element 400 eliminates a necessity in the prior art to manually adjust the distance 316 between a sealing piece 308 and the side surface of an opposing sheeting roller 614 by the addition of one or more shims 312 . With fewer pieces, replacement of side seals takes less time translating into more time of actual sheeter operation. In one embodiment, replacement of side seals takes about two hours.
[0050] In another embodiment, a sealing element 400 is formed such that when the sealing element 400 and the improved sealing bracket 500 are installed, the distance 316 between the sealing element 400 and the side of an opposing roller 614 is from about 0.05 inches (1.27 mm) to 0.07 inches (1.78 mm). As a reference, the size of the sheeter nip 102 during operation is typically in the range from about 0.008 inches (0.20 mm) to 0.012 inches (0.30 mm). Other sizes of sheeter nip 102 are possible, and other distances between the sealing element 400 and the side of an opposing roller 614 are possible.
[0051] In one embodiment, a sealing element 400 is made of an elastomeric material. Alternatively, a sealing element is made of Delrin®, or Teflon®, two commercially available materials. In another embodiment, a sealing element is made of ultra high molecular weight polyethylene (UHMWP). UHMWP has long molecular chains, is durable and versatile, and is used in many industries. UHMWP, Delrin®, Teflon®, and elastomeric materials have desirable attributes such as a high abrasion resistance, a low coefficient of friction, and unparalleled impact resistance.
[0052] In one embodiment, a sealing element 400 is formed such that it fits in an improved sealing bracket 500 and fits tightly against the most proximal portion of a side surface of a first sheeting roller 612 . The side surface may form part of a roller lip 404 . A sealing element 400 is preferably formed with a groove 406 such that the sealing element 400 is held tightly around a roller lip 404 of the first sheeting roller 612 . This improvement avoids gaps and crevices between a plastic sealing piece 308 , any shims 312 , and a first sheeting roller 612 . Such improvement prevents doughy material 104 from being forced into such areas while the doughy material 104 is under operating sheeting pressure.
[0053] In one embodiment, a sealing element 400 is pressed firmly against the side of a first sheeting roller 612 by a screw 306 . In other embodiments of the invention, other types of fasteners may be used. Doughy material under sheeting pressure is thereby further prevented from infiltrating crevices between attached parts. With such improved features, a sealing element 400 more effectively performs wiping and sealing functions along the sides of an opposing sheeting roller 614 during the operation of the sheeting apparatus.
[0054] With reference to FIG. 5 and FIG. 5 a , side seals are mounted piecewise around the circumference of a first sheeting roller 612 . In one embodiment, twelve pieces or sealing brackets 500 are used to apply a complete side seal which covers the entire circumference of one side of a sheeting roller 612 . A side seal can be joined to each side of the first sheeting roller 612 , and thus the sheeter nip 102 can be sealed on both sides. In FIG. 5 a, each improved side seal bracket 500 is attached to a first sheeting roller 612 by screws (not shown) placed in bracket mounting holes 504 along one side of an improved side seal bracket 500 .
[0055] While the invention has been particularly shown and described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention. | An improved end seal for a sheeting apparatus. A sealing material is formed into a more effective sealing element which locks out doughy material out of associated side sealing parts near the sheeting nip. Such an improved end seal provides improved wiping and sealing functions. Such a seal also reduces wear thus reducing the frequency of seal replacement. Such a seal reduces the amount of installation time and amount of error associated with manual adjustment ordinarily required to replace end seals. | 0 |
This application is a divisional application of U.S. patent application Ser. No. 10/988,693, filed Nov. 16, 2004, which claims the benefit of U.S. Provisional Application No. 60/523,142, filed Nov. 19, 2003. The disclosure of each of the aforementioned applications is hereby incorporated herein by reference in their entirety.
FIELD OF THE INVENTION
This invention relates to colonic purgative formulations in solid dosage form and their use. In certain embodiments of this invention, the formulation contains at least one purgative and at least one soluble binder, which significantly improves the visualization of the colon and patient tolerance. In other embodiments of the invention, the formulation is free of insoluble binder or only contains levels of insoluble binder that do not impede the visualization of the colon. The binder may be nonfermentable in certain embodiments of the invention.
BACKGROUND OF THE INVENTION
It is desirable to identify compounds that sufficiently cleanse the colon, but do not cause adverse side effects. It is also desirable to identify compounds that are used to treat constipation and promote fecal elimination, for instance, but that do not produce uncomfortable or embarrassing side effects such as gas. Additionally, completely clearing the bowel of fecal debris is a necessary prerequisite before a variety of diagnostic and surgical procedures. Cleansing is important, for instance, in order to sufficiently view the gross or microscopic appearance of the colon during colonoscopy. However, the cleansing procedure must also be tolerable to patients so that they are fully compliant with the cleansing process. Poor bowel preparation, due to lack of patient compliance or insufficient cleansing, impacts the efficiency and cost of these procedures, especially if they must be repeated (Rex et al. (2002) Am. J. Gastroenterol. 97:1696-1700). Further, patients may not elect to undergo uncomfortable diagnostic procedures, which would significantly reduce early detection of disorders and increase medical costs. (Harewood et al. (2002) Am. J. Gastroenterol. 97:3186-3194).
Colonic cleansing is commonly accomplished using lavage with polyethylene glycol-electrolyte solutions. A major disadvantage of this method is that patients are required to ingest a significant amount of liquid volume within a short period of time for purgation. For instance, patients may have to ingest four liters of solution within a period of two to three hours (Afridi et al. (1995) Gastrointest. Endosc. 41:485-489). A large number of patients experience significant volume-related discomfort and adverse side effects such as nausea, cramping, and vomiting (Dipalma et al. (2003) Am. J. Gastroenterol. 98:2187-2191). Another drawback of these preparations is their salty taste, which may also lead to patient noncompliance and adverse effects. Attempts have been made to make the taste more palatable, for instance by flavoring or reducing salt content. However, these changes did not make the regimen more acceptable to the patient, nor was there an improvement in the quality of colon cleansing (Church (1998) Dis. Colon Rectum 41:1223-1225). Such preparations deter patients from colon cancer screening (Harewood et al. (2002) Am. J. Gastroenterol. 97:3186-3194).
In an attempt to avoid the problems associated with the high-volume type preparations, smaller-volume aqueous preparations consisting of phosphate salts have been marketed. The phosphate salt solution produces an osmotic effect, causing large amounts of water to be drawn into the bowel, thereby promoting bowel evacuation. Although the lower volume marginally favors these sodium phosphate preparations, adverse side effects such as nausea, vomiting (principally a result of unpalatable taste), abdominal bloating, pain and dizziness were of similar frequency compared to polyethylene glycol-electrolyte lavage (Kolts et al. (1993) Am. J. Gastroenterol. 88:1218-1223).
Oral tablets containing phosphate salts have been formulated (see U.S. Pat. Nos. 5,616,346 and 6,162,464) to increase preparatory compliance, reduce volume discomfort, and increase patient tolerance. The oral tablet formulation significantly reduced the incidence of gastrointestinal adverse events such as nausea, vomiting, and bloating (Rex et al. (2002) Aliment Pharmacol. Ther. 16:937-944). Further, these tablet formulations were significantly better accepted and preferred by patients. Applicants discovered, however, that these formulations were limited in their acceptance by physicians by the presence of visible microcrystalline cellulose (MCC) in the colon, especially in the cecum and ascending colon ( FIG. 1 ). MCC, a purified form of cellulose, is used as a binder in the tablet formulation and is not soluble in the alimentary fluid. Retained MCC can be removed by suctioning or irrigation, so that the colon can be adequately visualized. However, these processes may prolong colonoscopy procedure time (Rex et al. (2002) Aliment Pharmacol. Ther. 16:937-944; Balaban et al. (2003) Am. J. Gastroenterol. 98:827-832), thereby prolonging the time that the patient is under anesthesia and reducing productivity of physicians (Rex et al. (2002) Am. J. Gastroenterol. 97:1696-1700). These tablets, however, were also large and difficult for some to swallow.
Thus, there is need for colonic purgative compositions that can be tolerated by the patient, while also providing quality preparation of the bowel. Further, it is desirable that the composition provides adequate visualization of the colon and structures, without the need for additional removal steps.
It is also desirable to identify a preparation that could be produced easily and used either as a complete purgative or as a laxative for mild catharsis, depending on the dosage administered. Such a dual function composition would be very beneficial.
SUMMARY OF THE INVENTION
The present invention relates to solid dosage form colonic purgative formulations and methods of their use. In one embodiment of the invention, the solid dosage form colonic purgative formulation comprises at least one soluble binder and at least one purgative. In one embodiment of the invention, the binder is nonfermentable. In other embodiments of the invention, the formulation is free of insoluble binder or only contains levels of insoluble binder that do not impede the visualization of the colon.
The at least one purgative may be an osmotic, non-osmotic, or bulk-forming purgative. In one embodiment of the invention, the at least one purgative is an osmotic purgative chosen from sodium phosphate, magnesium phosphate, or a salt thereof. The sodium phosphate salt may be, for example, monobasic sodium phosphate, dibasic sodium phosphate, or tribasic sodium phosphate. In an additional embodiment of the invention, the at least one purgative is a non-osmotic purgative chosen from bisacodyl or picosulfate, for example.
In an additional embodiment of the invention, the colonic purgative formulation comprises at least one non-osmotic purgative and at least one osmotic purgative.
In one embodiment of the invention, the solid dosage form comprises polyethylene glycol as a soluble, nonfermentable binder.
The formulation of the invention may also comprise optional components to improve dosage form characteristics. In one embodiment of the invention, the formulation comprises a lubricant, such as magnesium stearate, to improve the manufacturing process.
The formulation of the invention is a dual function composition. Thus, the present invention encompasses methods of treating gastrointestinal disorders, such as constipation, by providing lower doses of the colonic purgative compositions of the invention as a laxative. The present invention also encompasses methods of complete purgation in order to prepare the colon for a colonoscopy or surgical procedure, by providing higher doses of the compositions of the invention as a complete purgative. Further, the present invention encompasses methods of maintaining the elimination or promoting the elimination of feces from the bowel by providing a colonic purgative composition of the invention.
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 of the invention. The objects and advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.
The accompanying drawings, which are incorporated in and constitute part of this specification, together with the description, serve to explain the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows that a prior art composition containing an insoluble binder, microcrystalline cellulose (MCC), leaves a white powdery substance after use for bowel preparation, which significantly impairs visualization of the colon.
FIG. 2 shows that the composition of the invention, which contains a soluble, nonfermentable binder, leaves little or no residue after use for bowel preparation, thereby increasing visualization of the colon.
DETAILED DESCRIPTION OF THE INVENTION
A. Definitions
In order that the present invention may be more readily understood, certain terms are first defined. Additional definitions are set forth throughout the detailed description.
The term “purgative” refers to any substance that promotes defecation. Thus, the term purgative encompasses a range of cathartic effects. For instance, the term purgative encompasses mild catharsis, producing laxation (“partial purgation”), as well as stronger catharsis, providing complete or near-complete emptying of the large bowel (“complete purgation”). In one embodiment of the invention, the term refers to diarrhea. In another embodiment of the invention, the term refers to a softening or loosening of the feces or laxation. Unless modified by “partial” or “complete,” purgative or purgation encompasses the full range of purgative processes, including both complete purgation and laxation (“partial purgation”).
The term “osmotic” refers to any substance that promotes the passage of a solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane that selectively prevents the passage of solute molecules, but is permeable to the solvent. In the present invention, the term “osmotic” may refer to the ability of a substance to draw water into the intestines.
The term “fermentable” refers to any substance that can be anaerobically catabolized to simpler compounds, usually by bacteria and/or yeast. There are many types of fermentation, differing in the waste products formed and the fermentable substance. Fermentable substances include, but are not limited to, sugars, sugar-alcohols, polysaccharides, lactose, sorbitol, and mannitol. A fermentable substance releases explosive gases upon fermentation. The compound mannitol, for instance, can be fermented by bacteria that are typically resident in the colon of most humans and other mammals, during which hydrogen gas is released. The term “nonfermentable” refers to a substance that is not fermentable.
The term “soluble” or “water soluble” refers to an aqueous solubility that is higher than 1/10,000 (mg/ml). The solubility of a substance, or solute, is the maximum mass of that substance that can be dissolved completely in a specified mass of the solvent, such as water. “Practically insoluble” or “insoluble,” on the other hand, refers to an aqueous solubility that is 1/10,000 (mg/ml) or less. Water soluble or soluble substances include, for example, polyethylene glycol.
The term “binder” refers to any substance that exerts a physicochemical attractive force between molecules, and hence may be used in formulation of a dosage form. In one embodiment of the invention, the binder may be mixed with other components of the composition, so that it is distributed uniformly throughout the dosage form. The binder may also provide a matrix upon which any additional components can associate. In one embodiment of the invention, the binder is soluble and nonfermentable. Soluble and nonfermentable binders suitable for use in the invention include, but are not limited to, polyethylene glycol (PEG).
As used herein, the term “salt” or “pharmaceutically acceptable salt” refers to acidic salts formed with inorganic and/or organic acids, as well as basic salts formed with inorganic and/or organic bases. Examples of these acids and bases are well known to those of ordinary skill in the art. Salts according to the present invention may be used in a variety of forms, for example anhydrous or a hydrated crystalline form. The salts may also be those that are physiologically tolerated by a patient.
B. Description of the Invention
Many binders used in solid dosage formulations are insoluble. Applicants discovered that insoluble binders, such as microcrystalline cellulose (MCC), are retained in the colon, hamper visualization of the colon, and prolong colonoscopy procedure time ( FIG. 1 ). Commonly used soluble binders, however, including sugars, sugar-alcohols, and polysaccharides, can be fermented by the intestinal flora. The formation of explosive gases during the fermentation process is an undesirable property during certain surgical and diagnostic procedures involving the colon, such as during a colonoscopy using equipment that may produce a spark. In some documented cases, the presence of these gases during colon electrosurgery has led to explosion (DeWilt et al. (1996) J. R. Coll. Surg. Edinb. 41:419). Gases produced during the use of a laxative can also be unpleasant and embarrassing. In one embodiment of the invention, such as to prepare the colon for a colonoscopy, the solid dosage form colonic purgative formulation comprises at least one soluble, nonfermentable binder and at least one purgative. In another embodiment, such as, to prepare the colon for a diagnostic procedure that cannot produce a spark in the colon, such as x-ray imaging, virtual colonoscopy (helical CT), and capsule endoscopy, any soluble binder may be used in the composition. In these instances, it is not necessary that the binder or other ingredients be nonfermentable. Soluble, nonfermentable binders may, however, be used in compositions to prepare the colon for procedures that cannot produce a spark.
1. Binders and Purgatives
Any binder that is soluble, or soluble and nonfermentable, may be used in the present invention. However, binders that are fermentable, like any other fermentable ingredient, should only be used in embodiments where a spark would not be produced in the colon. A soluble, nonfermentable binder that may be used in the formulations of the invention includes, but is not limited to, polyethylene glycol (PEG). Applicants discovered that a purgative composition containing the soluble, nonfermentable binder PEG, leaves little or no residue after use for bowel preparation, thereby increasing visualization of the colon ( FIG. 2 ). PEG is represented by the structural formula: HOCH 2 (CH 2 OCH 2 ) m CH 2 OH, wherein m represents the average number of oxyethylene groups.
Any PEG polymer may be employed in the compositions contemplated herein. In one embodiment, the PEG polymers are solid at room temperature (i.e., 25° C.) and/or soluble in (or miscible with) water at room temperature. In one embodiment of the invention, the average molecular weight of the PEG polymer is at least 200, at least 400, at least 600, at least 1,000, at least 1540, at least 3000, at least 4,000, or at least 8,000. In one embodiment of the invention, the average molecular weight of the PEG polymer is from 7,000 to 9,000.
The amount of soluble and/or non-fermentable binder may vary depending on the desired characteristics of the solid dosage form and can be determined by one of ordinary skill in the art. In one embodiment of the invention, a PEG binder comprises 5-20%, in another embodiment 7.5-15%, and in an additional embodiment 10% by weight.
In one embodiment of the invention, the composition of the invention is free of insoluble binder or only contains levels of insoluble binder that do not impede the visualization of the colon.
Various purgatives are available commercially, and any available form of the material can be used in the practice of this invention. Purgatives that may be used in the invention include, but are not limited to, non-osmotic, osmotic, and bulk-forming purgatives. The invention may contain one purgative, more than one purgative from the same category, or more than one purgative from different categories may be used. Many purgatives may have more than one role or function, or may be classified in more than one group. Such classifications are descriptive only, and not intended to limit any use of a particular purgative.
In one embodiment of the invention, at least one osmotic purgative is used in the formulation of the invention. Osmotic purgatives act by increasing intestinal osmotic pressure thereby promoting retention of fluid within the bowel. Osmotic purgatives that may be included in the composition include salts, for example, magnesium citrate, magnesium chloride, magnesium hydroxide, magnesium phosphate, magnesium sulfate, magnesium tartrate, sodium phosphate, sodium tartrate, sodium sulfate, potassium tartrate, magnesium oxide, sodium sulfate, or salts thereof. Other examples of osmotic purgatives include glycerin, sorbitol, mannitol, lactitol, alcohol sugars, L-sugars, polyethylene glycol, and lactulose. However, purgatives that are fermentable should only be used in embodiments where a spark would not be produced in the colon.
In one embodiment of the invention, the at least one purgative is sodium phosphate or a salt thereof. In an additional embodiment of the invention, the at least one purgative is monobasic sodium phosphate, dibasic sodium phosphate, or tribasic sodium phosphate.
Salts according to the present invention may be used in a variety of forms, for example anhydrous or a hydrated form. It is also contemplated that a change in the form of a salt may increase or decrease its molecular weight. To account for any change in molecular weight, components of the purgative formulation and/or amounts of the purgative salts may be adjusted according to the knowledge of the person of ordinary skill in the art. In one embodiment of the invention, monobasic sodium phosphate is used in a monohydrate form. In another embodiment of the invention, dibasic sodium phosphate is used in an anhydrous form.
In one embodiment of the invention, the formulation of the invention comprises at least one non-osmotic purgative. Non-osmotic purgatives include prokinetic laxatives that stimulate the motility of the gastrointestinal tract, as well as stimulant laxatives that act by directly stimulating nerve endings in the colonic mucosa. Emollient laxatives and mucosal protectants may also be used in the invention. Examples of non-osmotic purgatives that may be used in the invention include, but are not limited to, mineral oil, aloe, bisacodyl, sodium picosulfate, casanthranol, cascara, castor oil, danthron, dehydrocholic acid, phenolphthalein, sennosides, docusate, bethanachol, colchicines, misoprostol, cisapride, norcisapride, paraffin, rhein, and tegaserod.
In one embodiment of the invention, the colonic purgative composition contains at least one osmotic purgative and at least one non-osmotic purgative.
In addition to at least one osmotic purgative and/or at least one non-osmotic purgative, the colonic purgative formulations of the invention may also comprise at least one bulk-forming purgative. Bulk-forming purgatives cause retention of fluid and an increase in fecal mass, resulting in stimulation of peristalsis. Bulk-forming laxatives may include various natural and semisynthetic polysaccharides, cellulose derivatives, or other substances that dissolve or swell in water to form an emollient gel or viscous solution that serves to maintain the feces soft and hydrated. Examples of bulk-forming purgatives that can be used in the invention include, but are not limited to, methylcellulose, sodium carboxymethyl cellulose, bran, psyllium, sterculia, and testa ispaghula.
2. Additional Optional Ingredients
Additional optional components may be included in the formulations of this invention to, for example, enhance the characteristics of the solid dosage form, maintain the integrity of particles of the active ingredient during the formulation process, and/or enhance the safety of the formulation. Any additional components may be compatible with the other ingredients in the formulations of the invention, in particular the active ingredients, and may not adversely affect the osmolarity of the formulations. Additional optional ingredients that may be used in the formulations of the invention include, for example, coatings, diluents, binders, glidants, lubricants, colors, disintegrants, flavors, sweeteners, polymers or waxes.
Lubricants, for example, may be included in the formulations of the invention. Such lubricants include, but are not limited to, magnesium stearate, potassium stearate, talc, stearic acid, sodium lauryl sulphate, and paraffin. In one embodiment of the invention, the colonic purgative formulation further comprises magnesium stearate. Lubricants serve to facilitate the manufacturing of a solid dosage form.
Additional suitable ingredients also include, but are not limited to, carriers, such as sodium citrate and dicalcium phosphate; fillers or extenders, such as stearates, silicas, gypsum, starches, lactose, sucrose, glucose, mannitol, talc, and silicic acid; binders, such as hydroxypropyl methylcellulose, hydroxymethyl-cellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose, and acacia; humectants, such as glycerol; disintegrating agents, such as agar, calcium carbonate, potato and tapioca starch, alginic acid, certain silicates, colloidal silicon dioxide, sodium starch glycolate, crospovidone, and sodium carbonate; solution retarding agents, such as paraffin; absorption accelerators, such as quaternary ammonium compounds; wetting agents, such as cetyl alcohol and glycerol monostearate; absorbents, such as kaolin and bentonite clay; stabilizers, such as fumaric acid; coloring agents; buffering agents; dispersing agents; preservatives; organic acids; and organic bases.
In one embodiment of the invention, an additional component in the formulations of the invention may function to maintain the electrolyte balance in a patient. For example, formulations of the invention may further comprise calcium, phosphate, potassium, magnesium, other anions, or salts thereof, which may normally be lost in diarrhea fluid.
Acidic or basic compounds may also be optionally added to the composition to adjust the pH of the compound or to alter the disintegration characteristics. Acidic or basic compounds that may be included in the formulations of the invention include, but are not limited to, sodium carbonate, sodium bicarbonate, sodium phosphate, calcium carbonate, magnesium hydroxide, potassium hydroxide, magnesium carbonate, and aluminum hydroxide.
The aforementioned ingredients are given as examples only and are not meant to include all possible choices. Additionally, many may have more than one role or function, or be classified in more than one group. Such classifications are descriptive only, and not intended to limit any use of a particular component.
To optimize the solid dosage formulations, components and amounts of the colonic purgative formulations of the invention may be adjusted according to the knowledge of the person of ordinary skill in the art. Sample ingredient ranges for a colonic purgative formulation example are provided in Table 1. Not all of the components are necessary, but are provided for illustration only. For example, it may not be necessary to have two distinct purgatives and it may also not be necessary to have a lubricant, such as magnesium stearate.
TABLE 1
Example Ingredient Ranges for a Colonic Purgative Composition
Ingredient
Function
Qty % (w/w)
Sodium Phosphate, Monobasic Active
Active
45.00-75.00
Sodium Phosphate, Dibasic Active
Active
15.00-30.00
PEG-8000
Binder
5.00-20.00
Magnesium Stearate
Lubricant
0.10-1.50
3. Administration and Dosing
The present invention also encompasses methods of using the colonic purgative formulations. The colonic purgative formulations of the invention produce a broad range of activities, depending on the dosage administered. The present invention encompasses methods of purging the colon comprising administering to at least one patient a colonic purgative formulation and allowing said formulation to purge the colon. The formulations of the invention may also be used at lower doses in order to regulate, soften or loosen the stool.
Thus, the present invention also encompasses methods of maintaining the elimination or increasing the elimination of feces in the bowel, comprising administering to at least one patient a colonic purgative formulation and promoting the elimination of feces in the bowel. The colonic purgative formulations of the invention may also be used to treat a patient with constipation. The constipation may be caused by a variety of factors including, but not limited to at least one of travel; change in daily routine; lack of exercise; immobility caused by injury, illness, or aging; dehydration; irritable bowel syndrome; pregnancy; diabetes; hypothyroidism; hypercalcemia; cancer of the colon or rectum; uterine prolapse; vaginal vault prolapse; rectal prolapse; scarring from surgery; injury of the colon or rectum; Parkinson's disease; multiple sclerosis; stroke; hemorrhoid or anal fissures; delaying bowel movements; anxiety; depression; eating disorders; and obsessive-compulsive disorder. The constipation may also be idiopathic, i.e. of unknown causation.
In another embodiment of the invention the composition of the invention is used to treat a patient suffering from, or susceptible to, constipation due to administration of a medication that causes constipation. A medication that may cause constipation includes, but is not limited to antacids that contain aluminum; antidepressants; blood pressure medications; calcium channel blockers; calcium supplements; chemotherapy medications; cold medicines; antihistamines; diuretics; iron supplements; medications for Parkinson's disease; lipid-lowering agents; pain medications; opiates; codeine; and tranquilizers.
One of skill in the art will recognize that the appropriate dosage of the colonic purgative compositions may vary depending on the individual being treated and the purpose. For example, the age, body weight, and medical history of the individual patient may affect the therapeutic efficacy of the therapy. Further, a lower dosage of the composition may be needed to produce a mild catharsis, while complete purgation may require a higher dose. A competent physician can consider these factors and adjust the dosing regimen to ensure the dose is achieving the desired therapeutic outcome without undue experimentation. It is also noted that the clinician and/or treating physician will know how and when to interrupt, adjust, and/or terminate therapy in conjunction with individual patient response. Dosages also depend on the strength of the particular purgative(s) chosen for the formulation.
In one embodiment of the invention, the total dosage is administered in at least one application period. In an additional embodiment of the invention, the total dosage is administered in two or more separate application periods, or separate doses.
The dose of the colonic purgative formulations may vary. For example, a lower dose of a colonic purgative formulation of the invention may be needed to produce a mild catharsis, while complete purgation may require a higher dose. A total daily dosage used for mild catharsis, for example, can range from 1 g to 30 g of a purgative. For example, in general, a total daily dosage of a purgative, such as sodium phosphate, in formulations of the present invention ranges from 1 to 30 g, 2 to 25 g, 3 to 20 g, 4 to 18 g, 5 to 16 g, 6 to 14 g, or 8 to 12 g. A total daily dosage may be formulated to contain 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30 g of a purgative, such as sodium phosphate. Additional doses of the colonic purgative formulation may be necessary to produce the desired therapeutic effect. In one embodiment of the invention, the total daily dosage is administered every 24 hours until the desired therapeutic effects are reached.
A higher dose of a colonic purgative formulation of the invention may be needed to produce a complete purgation of the colon. A total dosage used for complete purgation, for example, can range from 20 g to 100 g of a purgative, optionally provided over a period of time of up to 24 hours. For example, in general, a total daily dosage of a purgative, such as sodium phosphate, in formulations of the present invention may range from 20 to 100 g, 30 to 90 g, 40 to 80 g, or 50 to 70 g. A dose may be formulated to contain 20, 30, 40, 50, 60, 70, 80, 90, or 100 g of a purgative, such as sodium phosphate.
Optionally, in both the laxative and complete purgative embodiments, the total daily dosage may be separated into divided doses. In one embodiment of the invention, the total daily dosage is divided into two doses, separated by a period of up to 24 hours. For instance, a total daily dosage of 60 g of a purgative, such as sodium phosphate, may be divided into two doses of 30 g each. One dose of 30 g may be administered in the evening before a colon procedure, while the second dose of 30 g may be administered in the morning, 3 to 5 hours before the colon procedure. In another embodiment of the invention, the total daily dose is divided into three, four, or more doses.
In one embodiment of the invention, the addition of one or more purgatives to the composition, for example a colonic purgative composition comprising sodium phosphate and bisacodyl, may lower the amount of active ingredient in each dose, the number of doses, the administration time, and/or the number of tablets administered in a dose.
In one embodiment of the invention, the colonic purgative formulation is in an easily administered, solid dosage form. Solid dosage forms include, for example, a tablet, capsule, or caplet. The dosage form may be coated or encapsulated. In one embodiment of the invention, the colonic purgative formulation is in the form of a tablet. The number of tablets administered in a dose may vary depending on the desired effect and on the amount of active ingredient in each solid dosage form. Clear liquids may be taken with each dose.
A colonic purgative composition of the invention may be part of a kit. In one embodiment of the invention, the kit further comprises materials to assist in the administration of the composition, for instance a cup. In another embodiment of the invention, the kit further comprises compositions that assist in laxation or complete purgation. Additional compositions that may be included in a kit with the colonic purgative compositions of the invention include, but are not limited to, at least one non-osmotic purgative, osmotic purgative, and/or bulk-forming laxative. In one embodiment of the invention, the kit comprises a colonic purgative composition of the invention and a composition containing bisacodyl.
A colonic purgative composition of the invention may be administered by various routes. In one embodiment of the invention, the purgative composition is administered orally. In an additional embodiment of the invention, the purgative composition is administered through a tube, for instance a feeding tube or nasogastric tube.
The colonic purgative formulations of the invention may be manufactured in a variety of ways. In one embodiment of the invention, the formulations may be produced using a direct-compression or hot-melt process. In an additional embodiment of the invention, a process of producing a colonic purgative formulation comprises mixing the components, warming the mixture to the melting point of the polyethylene glycol, and compressing the mixture into tablets. In the hot melt process, for instance, the ingredients may be mixed in a high-shear mixer equipped with a jacketed mixing bowl. The blend may be warmed up to the melting point of PEG during mixing and cooling down when the end-point is reached. The blend may be cooled down overnight, milled, lubricated, and compressed into tablets. One of ordinary skill in the art will recognize methods of varying the manufacturing process to optimize the dosage form or increase the product amount for large scale manufacturing.
C. Examples
The following examples are offered for illustrative purposes only.
Example 1
Preparation and Use of Colonic Purgative Formulations Containing an Insoluble Binder
Two colonic purgative formulations; comprising the components set forth in Table 2, were produced by milling and blending, followed by direct compression.
TABLE 2
Prior Art Colonic Purgative Compositions
Containing an Insoluble Binder
Diacol ®
Visicol ®
Ingredient
Function
Qty % (w/w)
Qty % (w/w)
Sodium Phosphate,
Active
55.10
62.44
Monobasic Active
Sodium Phosphate,
Active
19.90
22.55
Dibasic Active
Microcrystalline Cellulose
Binder
23.00
13.00
Colloidal Silicone Dioxide
Diluent
0.50
0.50
Magnesium Stearate
Lubricant
1.50
1.50
Total
100
100
The target weight of each Diacol® tablet (InKine Pharmaceutical Company, Blue Bell, Pa.) was 2000.0 mg, which was consistently achieved by the manufacturing process. The target weight of each Visicol® tablet (InKine Pharmaceutical Company, Blue Bell, Pa.) was 1764.8.0 mg, which was consistently achieved by the manufacturing process. Physical testing of both formulations revealed that the tablets exhibited an appropriate strength, hardness, and disintegration time.
Visicol® tablets were administered to humans in two, twenty tablet doses. One dose was administered the night before the colonoscopy procedure and the second dose was administered in the morning, 3 to 5 hours before the procedure. Colonoscopy revealed the presence of the binder, MCC, in the colon of patients. As shown in FIG. 1 , MCC leaves a white powdery substance in the colon after use for bowel preparation, which significantly impairs visualization of the colon.
Example 2
Preparation of a Colonic Purgative Formulation Containing a Soluble, Nonfermentable Binder
A colonic purgative formulation comprising the components set forth in Table 3, was produced using a hot melt process via high-shear granulation followed by milling, lubrication, and compression.
TABLE 3
Colonic Purgative Composition Containing
a Soluble, Nonfermentable Binder
Qty %
Qty/Dosage
Qty/Batch
Ingredient
Function
(w/w)
Form (mg)
(kg)
Sodium Phosphate,
Active
65.75
1102.0
295.9
Monobasic Active
Sodium Phosphate,
Active
23.75
398.0
106.9
Dibasic Active
PEG-8000
Binder
10.00
167.6
45.0
Magnesium Stearate
Lubricant
0.50
8.4
2.26
Total
100
1676.0
450.06
Specifically, sodium phosphate monobasic monohydrate (295.9 kg) was passed through a sieve equipped with a 10 mesh stainless steel screen. Sodium phosphate dibasic anhydrous (106.9 kg) and polyethylene glycol 8000 (45.0 kg) were each passed through a sieve equipped with a 20 mesh stainless steel screen. The sieved sodium phosphate monobasic monohydrate, sodium phosphate dibasic anhydrous, and polyethylene glycol 8000 were loaded into a 250 L bin and blended for 23 minutes±60 seconds at 12 rpm in a bin blender. The blended mixture was then transferred into suitable double poly-lined containers and milled through a cone mill, equipped with a stainless steel screen, at an impeller speed of 1400-1500 rpm. The milled mixture was then transferred back to the bin blender and further blended for 45 minutes±60 seconds at 12 rpm.
After the blending was complete, the materials were discharged into double poly-lined containers and divided into three sections. The lower jacket temperature on a mixer was set to 59° C., the upper jacket was turned on, and the heating water began circulating through the jacketed mixing bowl. When the lower jacket temperature reached 59° C.-60° C., the first section of blended materials was loaded into the mixing bowl of the mixer and the impeller speed was set at 30 rpm (with the granulator not running). The lower jacket temperature was then set to 66° C. and the impeller speed at 50 rpm. When the product temperature reached 40° C.-41° C., the impeller speed was increased to 100 rpm. When the product temperature reached 52° C., the granulator was set to speed 1 (slow) and the lower jacket temperature was set to 58° C. When the product temperature reached 54° C.-55° C., the granulation process was stopped. The lower jacket temperature was reduced to 20° C., the upper jacket was turned off, and the impeller speed was decreased to 10 rpm. The mixture was cooled until the product temperature reached 52° C. The granulation was then discharged into double poly-lined containers and stored in a closed container at room temperature overnight. The process detailed above was repeated for divided sections two and three of the blended materials.
The next day, the temperature of the granulation was checked to ensure that it was less than 30° C. The granulation was then milled through the cone mill, equipped with a stainless steel screen, at an impeller speed of 1400-1500 rpm. The milled granulation was loaded into a 1200 L bin and blended for 23 minutes±30 seconds at 12 rpm in a bin blender. Magnesium stearate (2.26 kg) was passed through a 30 mesh stainless steel hand screen and then added to the milled granulation in the 1200 L bin. The magnesium stearate was blended with the milled granulation for 10 minutes±30 seconds at 12 rpm in the bin blender. The blended mixture was then compressed into tablets using a tablet press and dedusted using a tablet deduster.
The target weight of each tablet was 1676.0 mg, which was consistently achieved by the manufacturing process. Physical testing of the tablet revealed that the tablet formulation exhibited an appropriate strength, hardness, and disintegration time. Surprisingly, the INKP-102 tablet could be formulated successfully as a smaller tablet than the prior art compositions, Diacol® and Visicol®, even though the same amount of active ingredient (1102 mg sodium phosphate monobasic monohydrate and 398 mg sodium phosphate dibasic anhydrous) was used in each of the three compositions (Table 4). This surprising result is very beneficial as the improved formulation is more tolerable to patients, allowing them to more easily administer the active ingredients. Further, the disintegration time of the INKP-102 tablet is decreased, resulting in a more rapid response to the colonic purgative composition. Additionally, this decrease in disintegration time cannot be accounted for merely by the reduced size of the tablet, as there is a steeper decline in disintegration time compared to tablet size. This more rapid response would be especially beneficial whether a patient administered the composition of the invention to treat constipation or to completely purge the colon.
TABLE 4
Colonic Purgative Composition Containing a Soluble, Nonfermentable Binder
Diacol ®
Visicol ®
INKP-102
Amount of
23%
13%
10%
Binder
Binder
MCC
MCC
PEG
Tablet
0.950 × 0.406 in.
0.850 × 0.352 in.
0.750 × 0.40 in.
Dimensions
thickness: 6.72 mm
thickness: 7.12 mm
thickness: 6.86 mm
Tablet
large, dry ,
large, dry ,
smaller, waxy, and
Properties
and difficult to
and difficult to
easy to swallow
swallow
swallow
Weight (mg)
2000.0
1764.8
1676.0
Disintegration
approx. 31 minutes
approx. 25 minutes
approx. 11 minutes
Time
Example 3
Preparation of a Colonic Purgative Formulation Containing a Soluble, Nonfermentable Binder
A colonic purgative formulation, comprising the components set forth in Table 5, is produced using a hot melt process via high-shear granulation followed by milling, lubrication, and compression.
TABLE 5
Colonic Purgative Composition Containing
a Soluble, Nonfermentable Binder
Ingredient
Function
Qty % (w/w)
Sodium Phosphate, Monobasic Active
Active
65.73%
Sodium Phosphate, Dibasic Active
Active
23.74%
Bisacodyl
Active
0.03%
PEG-8000
Binder
10.00
Magnesium Stearate
Lubricant
0.50
Total
100
Physical testing of the tablet formulation includes weight variation, strength, hardness, and disintegration time. It is expected that a tablet formulated according to the above parameters will have appropriate physical properties.
Example 4
A Colonic Purgative Composition to Purge the Colon
A patient undergoing a surgical or diagnostic procedure involving the colon is administered 40 tablets of a colonic purgative composition, such as the composition described in Example 2 or 3. The evening before the surgical or diagnostic procedure, 3 tablets are taken with at least 8 ounces of clear liquids every 15 minutes (the last dose will be 2 tablets) for a total of 20 tablets. Optionally, the day of the colonoscopy procedure, (starting 3 to 5 hours before the procedure) 3 tablets are taken with at least 8 ounces of clear liquids every 15 minutes (the last dose will be 2 tablets) for a total of 20 tablets. It is expected that the results of such treatment will provide an adequately cleansed bowel, demonstrate little or no residue that impairs visual inspection of the colon, and is tolerable to the patient both in its palatability and side effect profile.
Example 5
A Colonic Purgative Composition Containing an Osmotic and Non-Osmotic Purgative to Purge the Colon
A colonic purgative formulation of the invention may also be administered in a single application or dose. A patient undergoing a surgical or diagnostic procedure involving the colon is administered 20 tablets of a colonic purgative composition, such as the composition described in Example 3. The evening before the surgical or diagnostic procedure, 3 tablets are taken with at least 8 ounces of clear liquids every 15 minutes (the last dose will be 2 tablets) for a total of 20 tablets. It is expected that the results of such treatment will provide an adequately cleansed bowel, demonstrate little or no residue that impairs visual inspection of the colon, and is tolerable to the patient both in its palatability and side effect profile. Further, it is expected that no morning dose will be required to obtain quality cleansing of the bowel.
Example 6
A Colonic Purgative Composition to Treat Constipation
A patient with constipation is treated with a colonic purgative composition, such as the composition described in Example 2 or 3. The composition is administered in a total daily dose of 3 to 18 g, which is given over a period of up to 30 minutes. The dose may be repeated daily. It is expected that the results of such treatment will facilitate the passage of feces and promote elimination, by loosening or softening of the stool and/or the promotion of peristalsis due to increased amounts of water in the colon. It is beneficial to be able to use the same dual function composition for complete purgation and laxation.
Example 7
Colon Cleansing Efficacy of INKP-102
The primary objective of this study was to compare, by direct visualization, the colon cleansing efficacy of a composition of one embodiment of the invention (See Table 3; hereinafter “INKP-102”) versus the marketed Visicol® tablets (See Table 2; InKine Pharmaceutical Company, Blue Bell, Pa.) in patients undergoing colonoscopy. In addition, the safety of the INKP-102 composition was evaluated. The components of INKP-102 (1676 mg tablet) were as set forth in Table 3 above. Visicol® tablets were comprised of the same amount of active ingredient as INKP-102 (1102 mg sodium phosphate monobasic monohydrate and 398 mg sodium phosphate dibasic anhydrous). However, the inert ingredients of Visicol® tablets included MCC, colloidal silicon dioxide, and magnesium stearate, as set forth in Table 2 above.
Treatments
Patients were randomly assigned (approximately 30 patients per group) to one of the seven treatment arms (Arms A-G). Each arm had a unique dosing regimen, as described in Table 6. Patients received either Visicol® Tablets (Arm A; 60 g sodium phosphate dose, as label recommends) or one of 6 dosing regimens of INKP-102 (Arms B-G; 42-60 g of sodium phosphate). There were two scheduled visits: a screening visit (Visit 0) and the colonoscopy visit (Visit 1). The screening visit took place up to 14 days prior to Visit 1. Patients self-administered the trial medication.
TABLE 6
Dosing Instructions for Treatment Arms A-G
Treatment
Arm
Dosing Instructions
A
40 Visicol ® Tablets (60 g sodium phosphate) by mouth as follows:
20 tablets over 1.5 hours beginning at 6 p.m. the evening before
colonoscopy and 20 tablets over 1.5 hours beginning 3 to 5 hours
before colonoscopy, with tablets taken 3 at a time every 15
minutes with at least 8 oz. of clear liquid. (As recommended in the
approved labeling)
B
40 INKP-102 tablets (60 g sodium phosphate) by mouth as
follows: 20 tablets over 1.5 hours beginning at 6 p.m. the evening
before colonoscopy and 20 tablets over 1.5 hours beginning 3 to 5
hours before colonoscopy, with tablets taken 3 at a time every 15
minutes with at least 8 oz. of clear liquid.
C
40 INKP-102 tablets (60 g sodium phosphate) by mouth as
follows: 20 tablets over 1 hour beginning at 6 p.m. the evening
before colonoscopy and 20 tablets over 1 hour beginning 3 to 5
hours before colonoscopy, with tablets taken 4 at a time every 15
minutes with at least 8 oz. of clear liquid.
D
32 INKP-102 tablets (48 g sodium phosphate) by mouth as
follows: 20 tablets over 1 hour beginning at 6 p.m. the evening
before colonoscopy and 12 tablets over a half-hour period
beginning at 10 p.m. the same evening, with tablets taken 4 at a
time every 15 minutes with at least 8 oz. of clear liquid. No tablets
are taken on the day of colonoscopy.
E
32 INKP-102 tablets (48 g sodium phosphate) by mouth as
follows: 20 tablets over 1 hour beginning at 6 p.m. the evening
before colonoscopy and 12 tablets over a half-hour period the next
day beginning 3 to 5 hours before colonoscopy, with tablets taken
4 at a time every 15 minutes with at least 8 oz. of clear liquid.
F
28 INKP-102 tablets (42 g sodium phosphate) by mouth as
follows: 20 tablets taken over 1 hour beginning at 6 p.m. the
evening before colonoscopy and 8 tablets taken over 15 minutes
beginning at 9 p.m. the same evening, with tablets taken 4 at a
time every 15 minutes with at least 8 oz. of clear liquid.
G
28 INKP-102 tablets (42 g sodium phosphate) by mouth as
follows: 20 tablets beginning at 6 p.m. the evening before
colonoscopy and 8 tablets the next day beginning 3 to 5 hours
before colonoscopy, with tablets taken 4 at a time every 15
minutes with at least 8 oz. of clear liquid.
Efficacy
Two hundred and fourteen patients took at least one dose of the study drug and completed their colonoscopy. Unless otherwise noted, this population (“All-Assessed” population) was evaluated for treatment efficacy. Patients that completed at least 90% of their designated study regimen, were not known to have dosed >2 hours outside of the recommended time frame, and had their colonoscopy, were designated as the “Per Protocol” population and numbered 192.
The primary objective of the study was to evaluate the colon cleansing efficacy of INKP-102 compared with Visicol® tablets in patients undergoing colonoscopy. The overall quality of the colonic cleansing was evaluated based on (1) the amount of stool (liquid, semisolid, or solid) observed during the procedure and (2) the amount of “colonic contents” (including all liquid, semisolid, and solid material in the lumen of the colon) observed during the procedure rather than only “stool.” Both the “stool” and “colonic contents” endpoints were based on endoscopist assessment using the following 4-point scale:
1=Excellent: >90% of mucosa seen, mostly liquid colonic contents (or stool), minimal suctioning needed for adequate visualization. 2=Good: >90% of mucosa seen, mostly liquid colonic contents (or stool), significant suctioning needed for adequate visualization. 3=Fair: >90% of mucosa seen, mixture of liquid and semisolid colonic contents (or stool), could be suctioned and/or washed. 4=Inadequate: <90% of mucosa seen, mixture of solid and semisolid colonic contents (or stool), which could not be suctioned or washed.
Using this 4-point scale, endoscopists assessed the patients' colons overall, and also specifically assessed patients' ascending colons, where MCC residue especially impairs visualization of the colon.
Tables 7a and 7b display the results of endoscopist assessment of “colonic contents” overall and in the ascending colon, respectively, in the “All-Assessed” population. Comparison of Visicol® versus INKP-102 treatments revealed that mean overall colonic contents scores were significantly better with INKP-102 dosages (Arms B, C, and E) than with Visicol® (P<0.05; Arm A). Similarly, assessment of colonic contents in the ascending colon revealed that INKP-102 treatment with Arms B, C, and E resulted in significantly better mean colonic contents scores than with Visicol® treatment (P<0.05; Arm A).
Surprisingly, treatment with Arm E resulted in these significantly better mean colonic contents scores, even though the amount of sodium phosphate (48 g) was lower than the sodium phosphate content of the marketed Visicol® (60 g). In addition, treatment Arms D, F, and G performed as well as the marketed Visicol® (no statistically significant difference), even though the amount of sodium phosphate (48 g, 42 g, and 42 g, respectively) was lower than the sodium phosphate content of the marketed Visicol® (60 g). This surprising result is very beneficial as the improved formulation allows patients to use a lower dose of active ingredients to achieve the same result. It is expected that the same will hold true for laxative uses of the composition. Because the dosing regimens of treatment Arms D and F only involve an evening dose, they may be more preferable to patients who do not want to get up early before a procedure to complete a dosing regimen and more preferable to anesthesiologists who require that the patient receive nothing by mouth on the morning of the procedure.
Analysis of the smaller “Per Protocol” population yielded similar results. Additionally, in the per protocol group, improvement in “colonic content” overall and in the ascending colon upon INKP-102 Arm G treatment versus Arm A Visicol® treatment reached statistical significance (P<0.0346). Surprisingly, treatment with Arm G resulted in these significantly better mean colonic contents scores, even though the amount of sodium phosphate (42 g) was lower than the sodium phosphate content of the marketed Visicol® (60 g).
TABLE 7a
Overall Colonic Contents in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 29)
(n = 32)
(n = 29)
(n = 30)
(n = 33)
(n = 32)
(n = 29)
(n = 214)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Excellent
14 (48)
24 (75)
22 (76)
18 (60)
26 (79)
15 (47)
22 (76)
141 (66)
Good
11 (38)
7 (22)
7 (24)
9 (30)
6 (18)
8 (25)
4 (14)
52 (24)
Fair
4 (14)
1 (3)
0 (0)
1 (3)
1 (3)
5 (16)
2 (7)
14 (7)
Inadequate
0 (0)
0 (0)
0 (0)
2 (7)
0 (0)
4 (13)
1 (3)
7 (3)
Mean
1.66
1.28
1.24
1.57
1.24
1.94
1.38
1.47
Std. Dev.
0.72
0.52
0.44
0.86
0.50
1.08
0.78
0.76
P-value*
N/A
0.0472 †
0.0322 †
0.6422
0.0275 †
0.1332
0.1519
N/A
*P-values were obtained using an ANOVA with factor treatment used to compare the means between INKP-102 and Visicol ® groups.
† Statistically significant (at the 0.05 level)
TABLE 7b
Ascending Colon Colonic Contents in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 28)
(n = 32)
(n = 28)
(n = 29)
(n = 33)
(n = 32)
(n = 29)
(n = 211)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Excellent
11 (38)
24 (75)
21 (72)
15 (50)
27 (82)
15 (47)
20 (69)
133 (62)
Good
12 (41)
7 (22)
7 (24)
5 (17)
6 (18)
7 (22)
6 (21)
50 (23)
Fair
5 (17)
1 (3)
0 (0)
8 (27)
0 (0)
6 (19)
2 (7)
22 (10)
Inadequate
0 (0)
0 (0)
0 (0)
1 (3)
0 (0)
4 (13)
1 (3)
6 (3)
Mean
1.79
1.28
1.25
1.83
1.18
1.97
1.45
1.53
Std. Dev.
0.74
0.52
0.44
0.97
0.39
1.09
0.78
0.79
P-value*
N/A
0.0097 †
0.0078 †
0.8325
0.0019 †
0.3444
0.0894
N/A
*P-values were obtained using an ANOVA with factor treatment used to compare the means between INKP-102 and Visicol ® qroups.
† Statistically significant (at the 0.05 level)
Tables 8a and 8b display the results of endoscopist assessment of “stool” overall and in the ascending colon, respectively, in the “All-Assessed” population. Mean “stool” endpoint scores overall and in the ascending colon generally favored INKP-102 dose groups over Visicol®. However, only INKP-102 Arm E showed statistically significant improvement over Visicol®, and only in the ascending colon. In contrast, treatment with Visicol® was statistically superior to INKP-102 Arm F in the ANOVA comparisons of means for both the overall “stool” score and ascending colon stool scores. These results were comparable in the analyses of the Per Protocol population.
Surprisingly, treatment with Arm E resulted in the significantly better mean stool score in the ascending colon (P<0.05) and a similar mean stool score in the overall colon (no statistically significant difference), even though the amount of sodium phosphate (48 g) was lower than the sodium phosphate content of the Arm A Visicol® (60 g). Further, treatment with Arms D and G performed as well as the marketed Visicol®, even though the amount of sodium phosphate (48 g and 42 g, respectively) was lower than the sodium phosphate content of Arm A Visicol® (60 g). This surprising result is very beneficial as the improved formulation allows patients to use a lower dose of active ingredients to achieve the same result. It is expected that the same will hold true for laxative uses of the composition. Because the dosing regimen of treatment Arm D only involves an evening dose, it may be more preferable to patients who do not want to get up early before a procedure to complete a dosing regimen and more preferable to anesthesiologists who require that the patient receive nothing by mouth on the morning of the procedure.
TABLE 8a
Overall Stool in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 29)
(n = 32)
(n = 29)
(n = 30)
(n = 33)
(n = 32)
(n = 29)
(n = 214)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Excellent
20 (69)
28 (88)
24 (83)
19 (63)
29 (88)
16 (50)
24 (83)
160 (75)
Good
6 (21)
3 (9)
5 (17)
7 (23)
4 (12)
8 (25)
2 (7)
35 (16)
Fair
3 (10)
1 (3)
0 (0)
2 (7)
0 (0)
5 (16)
2 (7)
13 (6)
Inadequate
0 (0)
0 (0)
0 (0)
2 (7)
0 (0)
3 (9)
1 (3)
6 (3)
Mean
1.41
1.16
1.17
1.57
1.12
1.84
1.31
1.37
Std. Dev.
0.68
0.45
0.38
0.90
0.33
1.02
0.76
0.72
P-value*
N/A
0.1473
0.1846
0.3962
0.0975
0.0160 †
0.5690
N/A
*P-values were obtained using an ANOVA with factor treatment used to compare the means between INKP-102 and Visicol ® groups.
† Statistically significant (at the 0.05 level)
TABLE 8b
Ascending Colon Stool in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 29)
(n = 32)
(n = 29)
(n = 30)
(n = 33)
(n = 32)
(n = 29)
(n = 214)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Excellent
16 (55)
27 (84)
23 (79)
17 (57)
30 (91)
15 (47)
22 (76)
150 (70)
Good
7 (24)
4 (13)
5 (17)
3 (10)
3 (9)
8 (25)
4 (14)
34 (16)
Fair
4 (14)
1 (3)
0 (0)
8 (27)
0 (0)
5 (16)
2 (7)
20 (9)
Inadequate
0 (0)
0 (0)
0 (0)
1 (3)
0 (0)
4 (13)
1 (3)
6 (3)
Mean
1.56
1.19
1.18
1.76
1.09
1.94
1.38
1.44
Std. Dev.
0.75
0.47
0.39
0.99
0.29
1.08
0.78
0.78
P-value*
N/A
0.0553
0.0572
0.3000
0.0151 †
0.0468 †
0.3682
N/A
*P-values were obtained using an ANOVA with factor treatment used to compare the means between INKP-102 and Visicol ® groups.
† Statistically significant (at the 0.05 level)
Analysis of the two efficacy endpoints together demonstrates that the INKP-102 treatment arms were generally rated higher than the Visicol® treatment arm in the “colonic contents” efficacy endpoint versus the “stool” efficacy endpoint. These results indicate that components of the colon other than stool, such as microcrystalline cellulose (MCC), do not hinder visualization of the colon after INKP-102 treatment to the extent that Visicol® treatment hinders visualization. At the same time, INKP-102 is able to effectively purge the colon of stool in liquid, semisolid, or solid form.
Both “colonic contents” and “stool” efficacy endpoints were also analyzed by dividing the 4-point assessment scale into “responder” and “non-responder” categories. For each assessment, a patient was considered to be a “responder” if colon cleansing was rated as “excellent” or “good” and a “non-responder” if colon cleansing was rated as “fair” or “inadequate. Table 9a and 9b display the number of “responders” and “non-responders” to the various treatment arms using a “colonic contents” and “stool” endpoint, respectively, in the “All-Assessed” population.
TABLE 9a
Colonic Cleansing (Colonic Contents) Responder Rates in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 29)
(n = 32)
(n = 29)
(n = 30)
(n = 33)
(n = 32)
(n = 29)
(n = 214)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Responder
25 (86)
31 (97)
29 (100)
27 (90)
32 (97)
23 (72)
26 (90)
193 (90)
Non-
4 (14)
1 (3)
0 (0)
3 (10)
1 (3)
9 (28)
3 (10)
21 (10)
responder
P-value
N/A
0.1816
0.1120
0.7065
0.1762
0.2192
>0.9999
N/A
*P-values were obtained using a Fisher's Exact test to compare the response rates between Treatment arm A and the other Treatment arms (B-G).
TABLE 9b
Colonic Cleansing (Stool) Responder Rates in the “All-Assessed” Population
Visicol ®
INKP-102 Treatment Groups
40 Tabs (60 g)
40 Tabs (60 g)
32 Tabs (48 g)
28 Tabs (42 g)
A
B
C
D
E
F
G
All
3 tabs split
3 tabs split
4 tabs split
4 tabs
4 tabs split
4 tabs
4 tabs split
patients
(n = 29)
(n = 32)
(n = 29)
(n = 30)
(n = 33)
(n = 32)
(n = 29)
(n = 214)
Parameter
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Responder
26 (90)
31 (97)
29 (100)
26 (87)
33 (100)
24 (75)
26 (90)
195 (91)
Non-
3 (10)
1 (3)
0 (0)
4 (13)
0 (0)
8 (25)
3 (10)
19 (9)
responder
P-value*
N/A
0.3385
0.2368
>0.9999
0.0966
0.1884
>0.9999
N/A
*P-values were obtained using a Fisher's Exact test to compare the response rates between Treatment arm A and the other Treatment arms (B-G).
The results indicate that treatment arms B, C, and E had higher responder rates among all treatment groups, and had lower or negligible nonresponder rates. These rates were higher than those of Visicol® Tablets (Arm A), although the differences were not statistically significant. Further, Arm E (INKP-102; 48 g split dose) demonstrated comparable or better colon-cleansing efficacy when compared with high-dose treatments (60 g dose; Arms A, B, and C). On the other hand, dosages given only on the evening prior to the patient's colonoscopy demonstrated poorer efficacy than those doses given as “split doses.” The lower-dose (42 g) evening-only regimen of Arm F, only had a 72% responder rate, which was significantly lower than Arms B, C, and E (P<0.05; Fisher's Exact test).
Safety
The safety of the various dosing regimens was also evaluated by adverse event monitoring, changes in clinical laboratory evaluations, physical examination, and vital signs assessment (heart rate, blood pressure, respiratory rate, temperature, and testing for postural hypertension). No patients experienced a serious adverse event during the course of the study. Nearly all patients experienced mild to moderate adverse events related to the system organ class of gastrointestinal disorders, regardless of dosage or treatment. Such adverse events included abdominal distention, nausea, and abdominal pain. However, because the purpose of the treatment is to rapidly eliminate bowel contents, such events were to be expected.
Significant changes in clinical laboratory parameters from Visit 0 (screening) to Visit 1 (colonoscopy) were observed in all patient groups. Specifically, there was a significant increase (P<0.0001) in mean levels of inorganic phosphorus in all patient groups. There was a significant increase in mean levels of sodium in 6 of the 7 patient groups (P<0.02) and a significant decrease of BUN, potassium, calcium, magnesium, and bicarbonate from baseline in one or more patient groups (P<0.05). Mean levels of chloride and creatine in all patients, on the other hand, did not significantly change from baseline after treatment.
Of all the clinical parameters examined, only levels of inorganic phosphorus exhibited a significant, after-treatment difference between the INKP-102 and Visicol® treatment arms. Increases from baseline in inorganic phosphorus were anticipated and occurred with a mean increase of 88% over baseline levels in all patients, regardless of treatment arm. These increases in inorganic phosphorus levels were significantly higher among Arm A (Visicol® Tablets) than in patients in treatment arms D, E, F, and G (INKP-102; P<0.0170). The inorganic form of phosphate in the circulating plasma is excreted almost entirely by the kidneys and therefore some patients, such as those with renal disease, may have difficulty excreting a large phosphate load. Thus, use of INKP-102 beneficially reduces the burden on the kidneys during sodium phosphate treatment. This effect may be attributable to the reduced sodium phosphate doses in Arms D, E, F, and G. As described in several efficacy analyses above, however, INKP-102 more effectively cleanses the colon than a larger sodium phosphate dose of Visicol®, while at the same time reducing the increase in inorganic phosphorous normally observed with Visicol® administration.
All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supercede and/or take precedence over any such contradictory material.
All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.
Many modifications and variations of this invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only and are not meant to be limiting in any way. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims. | This invention relates to novel colonic purgative compositions in a solid dosage form, comprising at least one purgative and at least one soluble, or soluble, nonfermentable binder, such as polyethylene glycol. Further, this invention relates to methods of using the colonic purgative compositions. The present compositions and methods are designed to improve patient tolerance and compliance, while at the same time improving the quality of bowel cleansing. The formulations and methods of this invention are particularly useful to cleanse the bowel prior to diagnostic and surgical procedures and can also be employed in lower dosages as a laxative to promote elimination and/or to relieve constipation. | 0 |
FIELD OF THE INVENTION
This invention relates to detectors for signaling head movement in training a user to maintain a steady head while participating in activities where maintaining a steady head is advantageous.
PRIOR ART
It has long been recognized that when performing certain physical activities, such as swinging a golf club at a golf ball or a bat at a baseball, the best results are obtained if the practitioner moves his or her head only within established limits. Many people playing the game of golf, for example, recognize that their heads should move only within established limits while they swing a golf club. These persons may even believe that they are actually correctly holding their heads from movement beyond the established limits, while, in fact, they often-times are actually moving their heads in directions and for distances that are far outside the established desirable range of movement.
In playing golf, head movement can be generally classified in three ways, i.e. (1) from side-to-side, (2) up and down, and (3) toward and away from the ball to target line. Naturally, combinations of these classified movements can, and most often, do occur. In making a good swing a golfer usually has a bit of (1) and some (2) movement and this is perfectly acceptable. Too much of either or both of the (1) or (2) movements will result in flubbed shots, however. Movement (3), whether forward or backward with respect to the ball to target line, means that the golfer's weight is being rocked forwardly or rearwardly on toes and heels. This affects the golfer's balance and can result in shots being struck off the toe or heel of the club being used.
In U.S. Pat. No. 2,252,831 there is shown a device that holds the head and feet of a golfer in a fixed position, while allowing other body parts to move as the user of the device swings a club at a golf ball. This patented structure does not recognize that some limited amount of head movement is not only acceptable, but desirable and does not provide any indication to a user that desired head movement has been exceeded.
U.S. Pat. No. 3,104,880 discloses a golf training device that allows a golfer's head to move to one side during a backstroke but that stops head movement once the head is moved over the point of impact of the club with a golf ball.
U.S. Pat. Nos. 3,243,186, 3,326,558 and 4,326,718 each disclose devices including head movement indicators. U.S. Pat. No. 3,243,186 discloses a support post for an arm having movable components and electrical circuitry that will sound an indicator in response to movement of a cap connected to the arm and placed on a golfer's head.
U.S. Pat. No. 3,326,558 discloses a golfer's head movement indicating device wherein depending members are placed at opposite sides of a user's head. The spacing between the depending members determines an allowable movement of the head, but contact with either depending member will activate a signaling device to indicate that excessive head movement has ocurred.
U.S. Pat. No. 4,326,718 discloses a golf swing training and exercise device that includes, as part of a large multi-function device, an optional head restraining device with an electrical switch that is adjustable for an allowable degree of head movement before it is closed to activate a signal indicating excessive head movement.
BRIEF DESCRIPTION OF THE INVENTION
Objects of the Invention
Principal objects of the present invention are to provide an easily transported and operated head movement detector that can be used in the training of golfers, baseball players and the like, to signal undesired head movement and to indicate to the user the nature of the detected excess movement.
Other objects are to provide a head movement detector that is easily transported, set up for use and used, even by persons having no previous training in the use of the detector.
Features of the Invention
Principle features of the invention include a vertically adustable support mast; a telescoping projecting arm cantilevered from the top of the mast and movable to pivot up and down with respect to the top of the mast and to swivel with respect to the longitudinal shaft of the mast; a headgear attachment pad pivotally mounted on the end of the projecting arm remote from the mast; and circuit means mounted on the projecting arm and including switches actuated by movement of the projecting arm and of the headgear attachment pad relative to the projecting arm to actuate audible and/or visual signaling devices that will be indicative of the type excess head movement detected.
Accomodation is made for allowable head movement and adjustments are provided to vary the allowable head movement in different directions according to the skill of the user and the nature of the game or other activity for which head movement training is being practiced.
Indicators signal excess head movement as such movement occurs and may provide a lasting record of the maximum movements occuring during the activity performed.
Additional objects and features of the invention will become apparent to those skilled in the art to which the invention pertains from the following detailed description and drawings.
THE DRAWINGS
In the drawings:
FIG. 1 is a pictorial view of the head movement detector of the invention being used by an individual practicing swinging a golf club;
FIG. 2 is a perspective view, taken from one side, slightly above and at the unsupported end of the projecting arm of the head movement detector of the invention;
FIG. 3, a vertical section, taken on the line 3--3 of FIG. 2;
FIG. 4, a vertical section, taken on the line 4--4 of FIG. 2;
FIG. 5, a circuit diagram of the basic electrical circuit of the head movement detector of the invention;
FIG. 6, a fragmentary perspective view of another embodiment of the head movement detector of the invention; and
FIG. 7 a block diagram showing an expanded electrical system for use with the head movement detector shown in FIG. 6.
DETAILED DESCRIPTION
Referring now to the drawings:
In the illustrated preferred embodiment shown in FIGS. 1-5 the head movement detector of the invention s shown generally at 10. As shown, the detector 10 includes a tripod base 12, with legs 14, 16, 18 projecting equiangularly from a center fitting 20. An outer tube 22 projects upwardly from the center fitting 20 and a calibrated tube 24 telescopes into the upper end of tube 22 to be locked in place by a set screw 26 threaded through the outer tube 28. The base 12, fitting 20, outer tube 22 and telescoping tube 24 form an adjustable upright mast, shown generally at 28.
A slotted ball 30 is formed at one end 32 of a support shaft 34, the other end 36 of which extends through a bearing 38 that is press fitted into the projecting end 40 of the telescoping tube 24. A shoulder 42 formed on end 32 rests on an upper end of bearing 38 and a shoulder 44 at the end 36 of the shaft 34 engages the other end of the bearing 38.
A slot 46 formed in the ball 30 extends from near one side of the ball at 48 fully through the ball to an opposite side 50.
A telescoping projecting arm 52 includes an inner sleeve 54 and an outer sleeve 56. A fitting 58 has a hook end 60 that hooks beneath and pivots around a pivot pin 62. Pivot pin 62 extends centrally through ball 30 and above the bottom 64 of the slot 46. Rotation of projecting arm 52 one-hundred eighty degrees about the pivot pin, from the use position of the projecting arm, allows the arm 52 to be lifted off pin 62 and the projecting arm 52 to be separated from the mast 28, for storage or the like. A reverse procedure is used to lock the projecting arm 52 to the mast 28.
An opposite end 66 of the fitting 58 is press fitted into the projecting end 70 of inner sleeve 54 of the projecting arm 52. A micro-switch 74 is mounted to extend through a slot 72 provided therefor in the hook end 60 of fitting 58. Switch 74 is actuated by engagement of the switch actuator with the end of a screw 76 threaded through the ball 30. The extend to which screw 76 is threaded into groove 46 of ball 34 determines the sensitivity of micro-switch 74. Wires 80 and 82 connect the micro-switch 74 through fitting 58, telescoping projecting arm 52 and a fitting 84, into a circuit housing 88. Fitting 84 is part of circuit housing 88 and is press fitted into the projecting end 90 of the outer sleeve 56 of the projecting arm 52 to thereby hold the circuit housing to the projecting arm.
The circuit housing has a battery 94, an array 96 of display lights 98 projecting through the wall of the housing and a sound emitter 100. A slide-in cover 102 for the circuit housing 88 is removable and replaceable to allow removal and installation of the battery 94. A headgear attachment assembly, shown generally at 110, is pivotally connected to the circuit housing 88. The headgear attachment assembly includes a plate 112 that extends angularly across the longitudinal axis of the projecting arm 52. A pad 114 of a conventional loop and hook connector is fixed to the face 116 of the plate 112, remote from the mast 24.
A pivot plate 118, having a flexible neck 120 is affixed to the opposite face 121 of plate 112 and extends into a slot 122 provided therefore in the housing 88. The pivot plate is held in place by a pivot pin 124 that extends down through a hole 126 in the circuit housing 88 and through the pivot plate 118 to be threaded into the housing 88 at 130. The flexible neck 120 allows for limited lifting and lowering head movement before detector indicators are activated. Likewise, the pivoting of the pivot plate allows for limited forward and back movement of the head of a user before detector indicators are activated.
Another pad 134 of co-operating hook and loop material is releasably connected to the pad 114. Pad 134 is attached to a cap 138 or other headgear worn by the user of the head movement detector 10.
A magnet 140 is fixed to the interior of end 70 of inner sleeve 72 of projecting arm 52. A magnet detector switch 142 is fixed to the outer surface of end 90 of the outer sleeve 56 of projecting arm. The magnet detector switch 142 is activated by movement of the sleeve 56 (and movement of the magnet detector switch 142) relative to the inner sleeve 72 (and the magnet 140). Thus, the magnet detector switch 142 is activated to operate the array 96 of lights 98 and the sound emitter 100 when the outer sleeve 56 is moved either longitudinally with respect to the inner sleeve 72, or turned with respect to the inner sleeve 72 about the longitudinal axis of projecting arm 56.
A typical electrical circuit that will activate the lights 98 and or buzzer 100 whenever the switch 74 or switch 142 are activated is shown generally at 148, FIG. 5.
FIGS. 6 and 7 show another embodiment of the head movement detector of the invention. In the embodiment disclosed, the head movement detector, shown generally at 150 includes an upright mast 152, corresponding to the mast 28, previously described. A circuit box 154 is mounted on the top of mast 152, has a socket 158 formed in a face thereof and a ball 160 mounted on one end of an inner sleeve 162 of a telescopic projecting arm 164.
The ball 160 is mounted and held in the socket such that the ball will fully swivel in and is spring centered in the socket. Such a ball and socket control structure is a conventional type "joy stick", is well known in the art and is therefore not discussed in detail herein. The free end 168 of the outer sleeve 170 has a pivot plate 172 (corresponding to the pivot plate 118 previously described) attached thereto, in the manner previously described.
A magnetic potentiometer 192, having a magnet 174 fixed to the exterior of the end 176 of the outer sleeve, moves with respect to magnetic fields 178 generated by coils 193 inside the inner sleeve 162 to provide signals to a micro-controller 180.
Potentiometers 192, 194, and 196 are operated by movement of ball 160 and movement of the inner sleeve 162. Movement in any horizontal, vertical or combination of both directions moves the slides of the potentiometers to generate signals that will be processed through the A/D convertor and micro-controller 180 to be displayed on display unit 182. The display unit 182 will indicate graduated displacement and leave displayed the maximum displacement of the outer sleeve 170 relative to the inner sleeve 162 (Z axis), horizontal movement (X axis) and vertical movement (Y axis). The sensitivity of the horizontal axis potentiometer and of the vertical axis potentiometer are adjusted by manual movement of slides 194 and 196, respectively, that extend through slots provided therefor in the face of circuit housing 154.
Display unit 182 is mounted in the face of circuit housing 154 and additionally includes push button switches 186 to turn the circuit on and off; 188 to select the program and sensitivity of the program to be activated; and 190 to select a function.
Although preferred embodiments of the invention have been herein disclosed, it is to be understood that such disclosure is by way of example and that other variations are possible without departing from the subject matter coming within the scope of the following claims, which subject matter I regard as my invention. | A head movement detector for detecting head movement exceeding the allowable movement(s) for an activity and including a portable base supporting an upright mast, an arm projecting from the top of said mast and having a head attachment apparatus on the free end thereof and electronic signalling means to indicate the extent and nature of undesired excessive head movement in multiple directions and to display such movement while permitting limited allowable movement in such multiple directions without actuation of such signaling means. | 0 |
The present invention relates generally to printing mechanisms and, more particularly, to a printing device for a distance counter apparatus. The distance counter of the type to which the present invention relates comprises at least two sets of type wheels which are juxtaposed for rotation about parallel axes with at least one of the type wheels being driven as a function of distance with means being provided for simultaneous transfer of the numerical and/or alphanumerical values contained in the sets of type wheels to a voucher.
In the process of imprinting information on a voucher, the printing process can be accomplished either by a striking or rolling motion which involves the interaction between a type carrier and a movable element which cooperates with the fixed type carrier. Both printing techniques involving either a striking or a rolling motion involve advantages and disadvantages. When a hammer-type printing device is utilized, it is possible to achieve relatively short printing pulses and good printing contrast on the one hand. However, there exists a danger of chatter so that the printing quality may be impaired and there may be formed effects such as a shadow formation.
In contrast to this technique, a printing device employing the rolling principle will usually provide a weaker printing contrast but it will avoid the problem of chatter. Since the forces active in such a printing device are generally weaker than in a hammer-type of printing device, the design tends to be less complicated, particularly with respect to wear problems which may arise. On the other hand, considerable sophistication is required for retention of printed matter, i.e., the voucher, during the printing process.
The present invention is considered particularly applicable in arrangements wherein at least two juxtaposed sets of type wheels having parallel axes are used in a counting mechanism for printing distance information wherein space accommodation and voucher size are important from a design viewpoint. In particular, the invention is applicable in devices where two distinguishable types of information are to be furnished by the apparatus. The present invention is particularly intended to avoid the drawbacks of printing devices and, more particularly, it is directed toward the provision of a printing device which is suited to the application involved wherein production and assembly costs may be, to a great extent, minimized.
SUMMARY OF THE INVENTION
Briefly, the present invention may be described as a printing mechanism comprising print wheel means, means for passing sheet means such as a voucher or the like past the print wheel means to effect printing of information thereon, platen means arranged to press the sheet means against the print wheel means during the printing process, platen carrier means having the platen means mounted thereon, and overcenter spring means engaging the platen carrier means to drive the platen means against the print wheel means during the printing operation, said platen carrier means being mounted to be rotated against the overcenter spring means to effect spring loading thereof and to enable the overcenter spring means to then drive the platen carrier means through the printing operation.
In particular, the platen carrier means may be manually rotated through a first angle whereby the overcenter spring means are engaged and spring loaded. After the platen carrier means has traversed the angular position represented by said first angle, the platen carrier means will be in a position whereby as a result of a spring force developed by the overcenter spring means, the platen carrier means will be driven through a second angle during the printing process.
In accordance with the present invention, the first angle is smaller than the second angle.
Thus, in accordance with the invention, a solution to problems encountered with the prior art is provided in that each set of the print wheel means or type wheels will be coordinated with a platen, each platen will be disposed in a rotatably mounted platen carrier eccentric to the latter's axis, the shafts of the type wheel sets and of the platen carriers will be disposed in planes parallel in pairs and perpendicular to each other, and the platen carriers will be interconnected by gear means so that the platens will rotate in opposite directions.
In one preferred embodiment of the invention, at least one of the platen carriers is designed to act in conjunction with a spring loaded lever representing the overcenter spring means. Furthermore, in the preferred example of the invention, a guide roll is disposed at least in the platen carrier interacting with the spring loaded lever. The guide roll axis lies in a plane determined by the axis of the platen and of the platen carrier. The dimension of the radius of the platen plus the center distance between the platen carrier and the platen is arranged to be greater than the dimension of the radius of the guide roll plus the center distance between the platen carrier and the guide roll.
In the preferred embodiment of the invention, there are provided on the platen carriers teeth which will, on the one hand, enable the platen carriers to be driven and flanges which serve, on the other hand, for the mounting of the platen and guide roll shafts.
A particular advantage offered by the present invention arises in that the voucher will be retained clamped between the type wheel sets at the moment of printing due to the rolling action of the platen in opposite directions so that with no additional means required, the printing operation may be successfully performed. At the same time, chatter will be prevented due to the combination of a rolling and striking printing action which is accomplished while at the same time achieving good contrast and print quality in the results obtained.
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 specific objects attained by its use, reference should be had to the accompanying drawings and descriptive matter in which there are illustrated and described preferred embodiments of the invention.
DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a sectional view showing the essential elements of a printing mechanism in accordance with the present invention;
FIG. 2 is a side view of the printing mechanism of the invention;
FIG. 3 is a schematic sectional view depicting the essential features of the operating mode of the invention;
and
FIG. 4 is a partial sectional view depicting parts of another embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings wherein like reference numerals are used to refer to similar parts throughout the various figures thereof, and referring particularly to FIG. 1, an embodiment of the invention is depicted wherein a pair of sets of type wheels 2 and 3 are operatively disposed in a U-shaped frame member 1 in such a manner that the individual type wheels of the type wheel sets 2, 3 are rotatably mounted and arranged independently of each other on shafts 4 and 5 fastened in the frame 1.
The type wheel set 2 is, for example, designed as a distance counting mechanism which is so provided that a set of decimal transfer mechanisms 6 rotatably mounted on another shaft 7 are in engagement with the type wheels in a manner known, per se, and so that a switching lever 8 driven as a function of the distance is actuated and serves, by means of a pawl 9 which is spring mounted thereto, to advance a first type wheel 11 by means of suitable teeth 10 provided thereon. The type wheel set 3 of the present embodiment serves merely to represent a fixed value which means that the individual type wheels freely rotatable are locked by a rod 12 which penetrates all the type wheels eccentrically relative to the shaft 5 after the fixed value has been set.
As may be further seen from FIG. 1, a second U-shaped frame 13 is connected with the frame 1 so that a slot 14 will be formed therebetween. The slot 14 serves as an insertion opening within which there may be provided a voucher, card or the like upon which information may be printed.
As may be further seen, there is coordinated with each type wheel set 2 and 3 a platen 17 and 18, respectively, with the platens being provided with a rubberelastic jacket 15 and 16. The platens are themselves rotatably mounted in platen carriers 19 and 20, each of which are rotatably mounted in the frame 13.
The platen carriers 19 and 20 are mounted upon shafts 21 and 22 which are arranged so that, together with the shafts 4 and 5 of the type wheel sets 2 and 3, they are disposed in planes parallel in pairs.
The platen carriers 19 and 20 are provided with suitable flanges of which one each 29 and 30, respectively, are shown in FIG. 1 and of which an additional flange 31 is shown in FIG. 2, with the flanges being provided to accommodate the shafts 23 and 24 upon which the platens 17 and 18 are mounted. The flanges are provided also for additional shafts 25 and 26 upon which guide rolls 27 and 28 are rotatably mounted.
In the structure and arrangement of the device of the present invention, the platen, the platen carrier, and the guide roll shafts each lie in one plane and the sum of the platen radius plus the center distance between the platen carrier and the platen is greater than the sum of the guide roll radius plus the center distance between the platen carrier and the guide roll.
The dimension between the shafts 21 and 22 of the platen carriers 19 and 20 and the type surface is selected so that jackets 15 and 16 of the platens 17 and 18 will be elastically deformed at the instant when a printing action occurs with no contact taking place between the guide rolls 27 and 28 and the type wheels sets.
The platen carriers 19 and 20 are driven by means of a manually operable knob 32, best seen in FIG. 2. The knob 32 operates to rotate a shaft 33 mounted in the frame 13. Drivers 34 and 35 are located on the opposite end of the shaft 33 and they are arranged in driving engagement with corresponding lugs 37 and 38 provided upon a gear 36 which is rotatably mounted on the shaft 33. The gear 36 meshes with teeth 41 formed on the platen carrier 20 through a first intermediate gear 39 mounted in an overhung position on a shaft 40 fastened in the frame 13. Another intermediate gear 42 also mounted in an overhung position on the shaft 43 fastened in the frame 13 meshes with the first intermediate gear 39 and with teeth 44 formed on the platen 19 whereby the two platen carriers 19 and 20 may be rotated in opposite directions. It should be mentioned for the sake of completeness that the platen carriers 19 and 20 represent parts which are preferably produced by injection molding or die casting techniques and wherein the flanges and teeth mentioned may be molded directly to the actual platen carrier body integrally therewith.
In the detained position of the printing mechanism which is depicted in FIG. 1, an arched lever 45, 46 acts upon the respective platen carriers 19 and 20 with the levers 45, 46 resting upon a respective platen 17, 18 and upon a respective guide roll 27, 28. Of course, the arched levers 45 and 46 may also act upon an appropriately designed portion of the body of the respective platen carriers 19, 20.
The levers 45 and 46 are, in turn, pivotally mounted on shafts 47, 48 disposed in the frame 13 and they are under the influence of torsion springs 49/50 and 51/52, respectively, which are disposed upon the same shafts. A single spring may be used instead of the spring pairs 49/50, 51/52, but this would entail higher production costs.
In addition to the foregoing, an aligning element 53 is also mounted pivotally on the shaft 48 with the aligning element 53 being automatically moved with the printing process when the printing process is triggered, that is, when the lever 46 is pivoted, so that it may be caused to engage the decimal transfer mechanisms 6 thereby aligning the type wheels of the type wheel set 2. FIG. 2 shows, furthermore, that the frames 1 and 13 are disposed in a cupped housing 54 within which a slot 55 is formed coordinated with the slot 14 and being provided with a chassis 56 which encloses the apparatus.
In another embodiment of the invention shown in FIG. 4, the body of a platen carrier is designed as a cam 57 with which a roll 58 mounted to an appropriately designed lever interacts. In this embodiment, however, more space is required than in the embodiment previously described and it offers a less exact detained position.
During the operation of the printing mechanism of the invention previously described, the knob 32 is turned clockwise whereby the drivers 34 and 35 formed on the shaft 33 are rotated into driving connection with the lugs 37 and 38 formed on the gear 36 in accordance with the position shown in FIG. 1. The gear 36 is thereby driven and, hence, by means of the intermediate gears 39 and 42, the platen carriers 19 and 20 are also driven and moved out of their detained position designated I in FIG. 3 in opposite directions.
In the process, the guide rolls 27 and 28 roll off the respective levers 45 and 46 and pivot them counter to the springs 49/50 and 51/52. Accordingly, the levers 45 and 46 will be placed in a spring loaded position by the springs acting thereon, respectively.
When the mechanism reaches the position II shown in FIG. 3, an unstable condition is developed between the lever 46 and the guide roll 28, for example, whereby the platen carrier 20 will automatically continue moving clockwise under the action of the spring 49/50 imparting a driving spring force through the lever 46 until the mechanism reaches the detained position opposite to the position I.
Thus, with reference to FIG. 3, when an overcenter position is reached by virtue of rotation of the platen carrier 20 by operation of the knob 32, the lever 46 will be spring loaded by the action of the springs 49/50 as the platen carrier 20 rotates through an angle α shown in FIG. 3 and when the overcenter position is reached, the lever 46 will tend to move clockwise about the pivot shaft 48, as seen in FIG. 3, thereby driving the platen carrier in continued clockwise rotation as a result of the spring force which is developed. The term "overcenter spring" as used herein is intended to refer to the action of the springs 49/50, 51/52 acting, respectively, upon the platen carriers 20 and 19 through the levers 46, 45 in the manner described above.
In this process, both of the platen carriers 19 and 20, which of course operate similarly, will pass through a printing position III at relatively high speed simultaneously and in opposite directions. Thus, an inserted voucher 59 will be clamped in this manner during the printing operation in opposite direction by the platens acting thereupon and it will thus be retained in position with respect to the type wheel sets 2 and 3. The free wheeling which is required for the automatic advancement of the platen carriers 19 and 20 and which must, in the solution of the problem, not be influenced by knob actuation in the opposite direction, is assured as will be evident from FIG. 1 by an appropriate design of the drivers 34 and 35 and of the lugs 37 and 38. When the knob 32 is again actuated in a clockwise direction, actuation in the opposite direction can be prevented by a suitable locking mechanism and the platen carriers 19, 20 can be returned into their starting positions in that the platens 17 and 18 then roll off the levers 45 and 46 without another reproduction occurring.
It will be apparent that the printing device described may also be designed so that only one platen carrier interacts with a spring loaded lever in which case the spring force must be accordingly higher or differently designed springs must be used.
The decisive factor is that, in the selected arrangement, the angle α through which the platen carriers 19 and 20 are rotated by operation of the knob 32 is selected to be considerably smaller than an angle β through which the platen carriers 19 and 20 are drivingly rotated by operation of the spring force previously described. As a result, the platen carriers 19 and 20 are therefore accelerated over an entire range of motion through the angle β, having already assumed a relatively high speed in the printing position of the platens 17, 18. It will further result that the printing energy will be transmitted by a striking action rather than a rolling action, so that a relatively good print contrast will be obtained. Moreover, due to the effective lever ratios, an exact, stable, detained position of the platen carriers 19 and 20 will be provided in the example of the preferred embodiment of the invention.
While specific embodiments of the invention have been shown and described in detail to illustrate the application of the inventive principles, it will be understood that the invention may be embodied otherwise without departing from such principles. | A printing mechanism, particularly for a counter device which records distances, is formed with a pair of sets of print wheels with a housing defining a slot through which a voucher may be passed to have imprinted thereon information contained on the print wheels. Platens are arranged to press the voucher against the print wheels and platen carriers which are rotatably mounted have the platens eccentrically mounted thereon. Overcenter springs engage the platen carriers, and after the carriers have been rotated through a predetermined angle, the overcenter springs drive the carriers through a further angle of rotation during which the platens are pressed against the print wheels during the printing process. The angle through which the platen carrier is initially rotated to load the overcenter spring is less than the angle through which the platen carrier is driven by the loaded overcenter spring. | 1 |
DESCRIPTION
A first object of the invention is a process for the formation of a cleaning implement, such as a mop implement made up of strips of absorbing material or other strips or bristles clenched or tightened between them.
According to the invention, a bunch of said strips (or other) is clenched at one end and said end is introduced into a mould for the injection of synthetic resin under pressure; with the mould being closed, a clenching and anchoring core of said strips (or other) is formed. Said core ensures the connection with the handle for usage.
The core is advantageously moulded with a plurality of injection directions from the periphery towards the inside of the core and balanced; thereby ensuring the centering and anchorage of the bunch of strips in the core.
A further object of the invention is an apparatus for carrying out the above process, which substantially comprises: a device for temporarily clenching the ends of a bunch of strips made of absorbing (or other) material; a mould that can be opened and is able to receive in its cavity the clenched ends of said bunch of strips and to close up so as to clench said bunch of strips by itself; and in said mould, a plurality of injection orifices so distributed so as to inject thermoplastic resin in a balanced manner, to ensure the centering of said clenched ends and their anchorage.
The mould cavity may be shaped to create, on the core, means for the engagement with a handle having a body for the covering and engagement of said core. Alternatively, the mould cavity may be shaped to directly create the core with a finishing shape and a seat for a stick or other handling member.
Another object of the invention is a cleaning implement--such as a mop implement with a plurality of strips made of absorbing material or bristles, formed by the process and an apparatus as above defined, that is, having a core of injection-moulded thermoplastic resin, which clenches and anchors the ends of the strips or bristles or other. Said core may be coupled to a fitting for the handle or, alternatively, said core may create a finishing shape with a coupling for a stick or other handling member.
Through the above defined process and apparatus, an implement can be realized having particularly simple construction and with substantial economy, and above all, it is possible to realize an improved mechanization and thus an advanced automation of the operations for the formation of said implement so as to realize a manufacturing line which is in practice completely automated.
The invention will be better understood by following the description and the attached drawing, which shows a practical, non-limitative exemplification of the same invention. In the drawing:
FIG. 1 shows schematically an open mould with a bunch of strips, bristles or other articles, clenched and positioned therein;
FIG. 2 is a partial section view taken on line II--II of FIG; 1; and
FIG. 3 shows a partially sectioned view of an implement with a core, as it can be obtained by the apparatus of FIG. 1.
According to what is roughly illustrated in the attached drawing, numeral 1 indicates an apparatus for clenching a bunch F of strips with ribbons of flexible absorbing material of the type utilized as absorbent cloths also in houseworks. The bunch F may be realized with strips all of the same type or even with a portion of strips of one type and another portion of strips of a different type in order to obtain a dual functionality of the implement. The clenching apparatus 1 comprises at least two fork-like or otherwise shaped clenching members 3 to embrace the bunch of strips F which is introduced between said two wide open, that is, divaricated members 3 in order to clench circularly in a more or less homogeneous and uniform manner, according to an arrangement like that shown in FIG. 1, wherein the ends E of strips result clenched by said two members 3 of the apparatus 1; the operation of members 3 may be carried out by fluid-driven means 5, mostly of hydraulic or other equivalent type. The apparatus 1 may be separated from or advantageously associated with the moulding apparatus.
The moulding apparatus comprises in practice two substantially symmetrical parts of mould 7, which can be closed so as to engage, through an edge 7A, the bunch of strips F just next to the clenching zone E obtained by members 3 of the apparatus 1; as to the rest of mould 7, this can remain completely closed for the injection, while in the zone of the edges 7A, the clenching ensures a sufficient seal in cooperation with the clenched strips. Numeral 9 indicates a means, shown in an illustrative and summary way, for opening and closing mould 7.
As can be seen in particular in FIG. 2, the two mould parts have injection orifices, that is nozzles, 10 which are distributed around the axis of the closed mould, in such a way that the material, being injected under strong pressure and plasticized, goes into the mould with a substantially balanced distribution and thereby acts on the clenched ends E of the bunch F in a substantially balanced manner, so that these ends E remain substantially centered within the cavity of the mould filled with injected thermoplastic material. A core N is thus formed--shown in detail through a view and a section in FIG. 3--which embodies the ends E of strips of bunch F and is also capable of penetrating under pressure in particular between said strip ends, and even inside the material of the strips in some particular conditions and with certain particular qualities of the material of the strips and of thermoplastic material used. In any case, the core N injected onto the ends E held inside the mould ensures a stable anchorage of the ends of bunch of absorbent and flexible strips or bristles.
The core N may be formed in the outside so as to be coupled firmly to a covering and finishing body having a seat for a stick handle or the like. Alternatively, the core N may be formed so as to be removably screwed or bayonet or otherwise jointed on a body even making part of the recoverable handle, whereby the core N with the bunch F represents a spare part for the unit whose utilization of the covering and finishing body, as well as of the stick is thus prolonged. Still alternatively, the core N may itself be structured as a covering body, aesthetically shaped and presenting a joint seat for the stick.
In the illustrated example, the realization of a brush-like cleaning implement is provided, having a longitudinal axis of symmetry. Implements of different configuration may be realized by the described system, for example broom cores with bristles disposed according to an elongate, fan-wise arrangement, the core being correspondingly elongate so as to be received into a correspondingly elongate mould to form the shoulder or other connection means of the bristles and that may be then coupled to a handle and a possible finishing body of the broom.
The described process and apparatus allow--as already stated--a simplification of the operations for the formation of the implement and even a more or less advanced automation of the manufacturing process.
It is understood that the drawing shows an exemplification given only as a practical demonstration of the invention, as this may vary in the forms and dispositions without nevertheless departing from the scope of the idea on which the invention is based. | A cleaning implement is disclosed, such as a mop, comprising a lengthwise arrangement of a bunch of strips made of absorbing material, wherein an end portion of said lengthwise bunch of strips is compressed together with the opposite end of said bunch of strips remaining free, said compressed portion having an injection molded core of thermoplastic resin penetrating said compressed portion and peripherally surrounding said compressed end of strips. | 1 |
BACKGROUND OF THE INVENTION
The invention relates to a camshaft assembly for valve-controlled internal combustion engines. The camshaft assembly has two shaft elements which are positioned one inside the other. The elements are supported one inside the other and are rotatable relative to one another to a limited angle or slidable relative to one another for a limited axial distance. In the case of SOHC engines, the elements allow the inlet cams to be adjusted relative to the outlet cams. The second type of adjustment requires axially variable cam contours at a shaft element the invention makes it possible to change the control times of the inlet valve when the engine is in operation, thereby achieving improved torque characteristics, a reduced fuel consumption and improved exhaust gas values. This is of particular interest as far as diesel engines (charged) are concerned. With such a camshaft, cams referred to below as inner cams are connected to the inner shaft and cams referred to below as outer cams are connected to the outer shaft. The outer shaft includes circumferentially distributed wall apertures associated with the fixing parts of the inner cams and the inner cams include axially open slots or recesses which cover a sector of a circle respectively and which are penetrated by axial finger portions of the outer shaft positioned between the wall apertures respectively.
DE 39 43 427 C1, proposes to produce both the inner cams and the outer cams such that they are integral with the inner shaft and outer shaft respectively and subsequently to join the parts or connect them in a force-locking way to the shaft by inserting them or expanding the respective shaft or to weld them thereto after having been inserted. The first case requires complicated components because simple tube or rod portions can no longer be used for the shaft. The second case requires relatively sophisticated technologies to produce a connection capable of bearing torque loads.
DE 39 43 426 C1, proposes camshaft assemblies of the type where the inner cams are secured to the inner shaft by radially plugged-in pins. The outer cams are connected to the outer shaft by force-locking or material-locking means only, with entirely cylindrical pairs of surfaces being connected by being expanded or shrunk or by welding or soldering.
Finally, in DE 40 08 906 C2, inner cams are secured to the inner shaft by means of radially opposed form-fitting means while temporarily subjecting the inner cams to elastic deformation. The outer cams are connected to the outer shaft by applying prior art force-locking methods involving shaft expansion.
The disadvantage of the shafts referred to above is that for producing the force-locking connection by plastically expanding the shaft parts or by shrinking the cams it is necessary to provide vary accurately machined surfaces and accurate fits in order to obtain a connection capable of bearing torque loads. Under very high torque loads, the connections may temporarily loosen, which leads to the cam being rotated on the shaft. This may result in considerable damage to the internal combustion engine. The methods used for producing a material-locking connection, i.e. soldering or welding, are time-consuming and not suitable for mass production purposes.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a camshaft assembly of the type which can be produced by simple means and which ensures a high-accuracy connection between the cam and shaft, capable of bearing high torque loads.
The objective is achieved by the inner cams connecting to the inner shaft by form-fitting means and connecting the outer cams to the outer shaft by form-fitting means and at least the outer shaft including individual longitudinal portions which are connected to one another.
As compared to assemblies incorporating force-locking connections, the assemblies in accordance with the invention are easier and cheaper to produce. The centricity and angular position of the attached cams are more accurate and only small tolerances are obtained in respect to the contour of the cam.
According to a first embodiment, it is proposed that longitudinal teeth, constituting the form-fitting means, are provided at the outer shaft and at the outer cams. The teeth are easy to produce in a cam by axial broaching, whereas they may be rolled into the associated outer shaft. The teeth may be produced in portions on individual short shaft pieces of the outer shaft where axial stops for the cams may be produced at the same time. After the cams have been slid on, they may be axially secured by securing rings. After the inner shaft has been mounted, the individual portions of the outer shaft are welded together in stages.
According to a second embodiment, it is proposed that at least one pin passes through the outer shaft and outer cam which constitutes the respective form-fitting means. The solution of providing a form-fitting connection of this type is particularly cost-effective. The connection is produced by a one-piece pin sliding through the entire shaft diameter and into the region of the raised cam portion. It is also advantageous for two individual radial pins to be inserted into a sleeve axially integrally adjoining the outer cams, thus producing the connection with the outer shaft.
According to a further embodiment, it is proposed that radially opposed, circumferentially limited splines constitute the form-fitting means and on the remaining circumference, a gap is provided between the outer cams and the outer shaft. In this way it is possible for the outer cams to be slid on to the outer shaft after elastic deformation which generates a radial play in the region of form-fitting engagement, and subsequently, when the load is removed, the cams spring back and are secured on the outer shaft. Again, this is a very simple and cost effective way of producing the connection.
In accordance with the invention, the outer shaft is assembled of individual axial portions which are welded together to form the outer shaft after they have been slid onto the inner shaft and after the axial finger regions have been slid through axially open slots or recesses, shaped like a sector of a circle respectively, in the inner cams.
A first embodiment to connect the inner cams on the inner shaft includes the inner cams connected to the inner shaft by two radially opposed partial regions only while circumferentially cooperating therewith in a form-fitting way and slots are provided between the inner faces of the cams and the outer face of the inner shaft.
According to a further variant, the inner cams may engage the inner shaft over their entire circumference by means of longitudinal teeth. The slots enabling passage of the outer shaft are provided in the solid material of the inner cams.
A third embodiment already referred to includes the inner cams each connected to the inner shaft by a radially passing pin. The slots which enable passage of the outer shaft are formed by a circumferential gap between the inner cams and the inner shaft, which is interrupted only by the respective pin.
The inner shaft, too, may include individual longitudinal portions which are welded to one another, or it may be produced in one piece.
The inner shaft may be produced from a continuous piece of shaft tube or it may be assembled of individual longitudinal portions, like the outer shaft.
A further object of the invention consists in simplifying and reducing the costs of the production of camshafts of this type. The objective is achieved by the individual longitudinal portions form-fittingly connecting to at least one associated cam. Prior to assembling the individual longitudinal portions, the cams are finish-machined, hardened and ground. Finally, the individual longitudinal portions, with the completed cams secured thereto, are connected to one another.
The sequence of the first two process stages referred to may be reversed. First, the cams are form-fittingly connected to the individual longitudinal portions. Next, the cams are finish-machined or vice versa. In any case, assembling the camshaft constitutes the final process stage, after which no further machining operations take place, especially, it is no longer necessary to grind the cams. This objective can be achieved by carefully aligning the individual longitudinal portions prior to connecting them. The connecting methods may be welding, gluing, soldering or even cold forming in the connecting regions. In a preferred embodiment, the abutting ends of the individual longitudinal portions are provided with centering means adapted to one another.
The production method is preferably carried out in that, in an axial view, at least the outer shaft, including longitudinal portions, is assembled from the center. Alternately, a further cam or a further longitudinal portion is attached to the inner shaft during the production. Subsequently, a further longitudinal portion is attached to the outer shaft during the production.
The longitudinal portions are preferably connected to one another by laser welding. The type Of connection between the cams and the individual longitudinal portions provided in accordance with the invention constitutes a form-fitting connection which is cheap and accurate and represents the simplest way of ensuring the circumferential position and the centric position of the cams on the individual longitudinal portions relative to one another. The circumferential portion of the individual portions to one another may be ensured by projections in the region of the centering means, e.g. a longitudinally extending tongue and groove connection.
From the following detailed description taken in conjunction with the accompanying drawings and subjoined claims, other objects and advantages of the present invention will become apparent to those skilled in the art.
BRIEF DESCRIPTION OF THE DRAWINGS
Preferred embodiments of the invention are illustrated in the drawings wherein:
FIG. 1 is a longitudinal view of a first embodiment of a shaft in accordance with the invention, with the inner cams secured on the inner shaft and the outer cams on the outer shaft, in each case by engaging teeth.
FIG. 1a is a cross sectional view along line 1A--1A through a shaft according to FIG. 1.
FIG. 2 is a longitudinal sectional view of a second embodiment of a shaft in accordance with the invention, with the inner cams secured to the inner shaft by means of a radial journal and with the outer cams secured on the outer shaft by shaft teeth.
FIG. 2a is a cross sectional view along line 2A--2A through a shaft according to FIG. 2.
FIG. 3a is a cross sectional view through a first embodiment of an outer cam and an outer shaft to be combined with a shaft according to FIGS. 3c to 3e.
FIG. 3b is a cross sectional view through a second embodiment of an outer cam and an outer shaft to be combined with a shaft according to FIGS. 3c to 3e.
FIG. 3c is a cross sectional view through a first embodiment of an inner shaft and an inner cam, to be combined with an outer shaft according to FIG. 3a or 3b.
FIG. 3d is cross sectional view through a second embodiment of an inner shaft and an inner cam, to be combined with an outer shaft according to FIG. 3a or 3b.
FIG. 3e is a cross sectional view through a third embodiment of an inner shaft and an inner cam, to be combined with an outer shaft according to FIGS. 3a or 3b.
FIG. 4 is a longitudinal sectional view through a third embodiment of a shaft in accordance with the invention, with inner cams secured by journals and the outer cams secured by engaging teeth.
FIG. 4a is a cross sectional view through a shaft according to FIG. 4, along 4A--4A.
FIG. 4b is a cross sectional view through a shaft according to FIG. 4, along 4B--4B.
FIG. 5 is a longitudinal sectional view through a fourth embodiment of a shaft in accordance with the invention, with the inner cams secured by single journals and the outer cams by double journals.
FIG. 5a is a cross sectional view through a shaft according to FIG. 5, along FIG. 5A--5A.
FIG. 5b a cross sectional view through a shaft according to FIG. 5, along line 5B--5B.
FIG. 6 is a longitudinal sectional view through a fifth embodiment of a shaft in accordance with the invention, with the inner cams secure by a form-fitting clamping connection and the outer cams by double journals.
FIG. 6a is a cross sectional view through a shaft according to FIG. 6, along line 6A--6A.
FIG. 6b is a cross sectional view through a shaft according to FIG. 6, along line 6B--6B.
FIG. 7 is a longitudinal sectional view through a sixth embodiment of a shaft in accordance with the invention, with the inner cams connected by a form fitting clamping connection and the outer cams by engaging teeth.
FIG. 7a is a cross sectional view through a shaft according to FIG. 7, along line 7A--7A.
FIG. 7b is a cross sectional view through a shaft according to FIG. 7, along line 7B--7B.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a camshaft assembly 1 having an outer shaft 2, carrying outer cams 3a-3d on its outer circumference, and an inner shaft 4 carrying inner cams 5a-5d on its outer circumference. The outer shaft includes identical first longitudinal portions 6a-6d and a central longitudinal portion 6 m . The inner shaft 4 is produced in one piece.
The longitudinal portions 6 each include a cylindrical portion 7 with outer shaft teeth 8 and adjoining, radially opposed finger portions 9 1 , 9 2 . Only the finger portions 9 b1 and 9 b2 and 9 d1 , 9 d2 of the longitudinal portions 6b and 6d are shown. The respective finger portions of the longitudinal portions 6a and 6c are positioned in front of and behind the drawing plane. The finger portions pass through circumferential slots 10 1 , 10 2 , shaped like a sector of a circle, in associated inner cams 5b and 5d. The respective circumferential slots in the inner cams 5a and 5c also are assumed to be positioned in front of and behind the drawing plane.
The outer cams 3 and bearing cups 11 a -11 d are axially slid on to the cylindrical portions 7 including the outer teeth 8. The bearing cups run in corresponding friction bearings 12 a , 12 d . The outer face of the central tube portion 6 m is cylindrical and runs directly in a bearing 12 m .
The tubular inner shaft 4, along its entire length, is provided with outer teeth 15 accommodating the inner cams 5 a -5 d . The processes of fitting the inner cams on the inner shaft and assembly the longitudinal portions on the outer shaft with the outer cams, take place axially from the center towards the outside. First, the inner cams 5b and 5c are slid on to the inner shaft 4 inserted into the central portion 6 m . The longitudinal portions 6b and 6c are welded to the central longitudinal portion 6 m , with the finger portions 9 of the longitudinal portions passing through the circumferential slots 10 in the inner cams 5 b and 5 c . The longitudinal portions 6 b and 6 d already carry the respective outer cams 3b and 3c and the respective bearing cups 11b and 11d. Subsequently, the inner cams 5a and 5d are mounted on the inner shaft 4. The longitudinal portions 6a and 6d are slid on, with the finger portions 9 slid through the circumferential slots 10 of the latter inner cams 5a and 5d and with the respective longitudinal portions 6 then being welded together. The longitudinal portions 6a and 6d may already carry the associated outer cams 3a, 3d and the bearing sleeves 11a, 11d.
The cross section according to FIG. 1a shows the outer teeth 15 at the inner shaft 4. The teeth hold cam 5a with inner teeth 14. Axially extending recesses in the inner cam, arranged in pairs opposite one another, form the circumferential slots 10. The finger portions 9a of the longitudinal portion 6a of the outer shaft axially pass through said slots 10. The outer cam 3a which, around the whole of its inside, is provided with inner teeth, is form-fittingly slid on to the outer teeth 8 of the longitudinal portion 6a (not illustrated). As a result of the relation between the circumferential angles of the fingers 9 and slots 10, the shaft elements 2, 3 are rotatable relative to one another by a limited amount. The fingers 3 include smaller circumferential angles than the slots 10.
FIG. 2 shows a camshaft assembly 101 with an outer shaft 102 carrying outer cams 103a-103d on its outer circumference, and an inner shaft 104 carrying inner cams 105a-105d at a radial distance from its outer circumference. The inner cams 105 each include sleeve attachments 122, with fixing pins 123 extending radially therethrough. The fixing pins 123 are firmly accommodated in bores in the sleeve attachments and in through-bores of the inner shaft 104. The pins pass through circumferential slots (not illustrated in detail) in the longitudinal portions 106 of the outer shaft.
The outer shaft 102 includes first longitudinal portions 106a, second longitudinal portions 106b and 106c and a central longitudinal portion 106 m . The inner shaft 104 is produced in one piece. With the exception of the central longitudinal portion, the longitudinal portions each include a cylindrical portion 107 with outer shaft teeth 108. The outer longitudinal portions 106a, 106d include an expanded region 120 which hold a bearing bush 121.
The outer cams 103 and the bearing units 106 m are axially slid on to the longitudinal portions 106 with their outer teeth 108. The outer surface of the longitudinal portion 106 m is provided in the form of a smooth cylinder and runs in a bearing 111 m . The assembly, in its entirety, is assembled axially from the center towards the outside. First, the central bearing 111 m and the cams 105b and 105c are slid on to the central portion 106 with the inserted inner shaft 104 and secured to the inner shaft 104 by inserting the pins 123b and 123d. Subsequently, the longitudinal portions 106b and 106c are welded to the central portion 106 m , with the longitudinal portions 106b and 106c already carrying the respective outer cams 103b and 103c. Subsequently, the respective bearings 111 and cams 105a and 105d are slid on, with the latter connected to the inner shaft 104 in the same way as described above. Longitudinal portions 106a, 106d are again slid on, with the longitudinal portions 106 welded to one another. The longitudinal portions 106a and 106c already carry the associated cams 103a, 103d and the bearings 111a, 111d. The bearings are axially secured by sleeves 124a, 124d. Between the bearings and cams spacer sleeves are provided on the outer shaft 102, which are not referred to in greater detail.
The cross section according to FIG. 2a shows the way in which the inner cams 105a are secured on the inner shaft 104 by a pin 123a extending radially in the direction of the raised cam portion through an attached sleeve. The pin is slid through radially opposed circumferential slots 125 in a portion 106 of the outer shaft. The outer teeth 108 (not illustrated) of said portion 106 hold the outer cam 103b.
According to FIGS. 3a-3e, the process of securing the inner cams 205 to the inner shaft 204 may be combined with the process of securing the outer cams 203 to the outer shaft 202. The sections 3a and 3b should be assumed to overlap with the sections 3c to 3e, with the outer tube, behind the drawing plane, having to be given the shape of a finger with two circumferential regions.
FIG. 3b shows a cross section of an outer cam 203" according to FIG. 1a. The respective tube segment of the outer shaft 202" is shown as an axial section through the region outside the region of the fingers, and is thus shown with its entire circumference.
FIG. 3c shows an inner cam 205' according to FIG. 1a. The cam is secured to the inner shaft 204' in the same way as illustrated in FIG. 1a. However, the inner shaft 204' is a solid shaft.
FIG. 3d shows a modification in that the circumferential slots 210" are produced in the solid material of the cam 205" so that a complete annular member 218" with inner teeth is positioned on the solid shaft 204" whose outer circumference is fully toothed.
In FIG. 3e, the inner cam 205'" is provided with a complete through-bore. The inner shaft 204'" is unprofiled and provided in the form of a solid shaft. A pin 219'" inserted radially from the outside in the direction of the raised cam portion secures the parts relative to one another and at the same time forms the circumferential slots 210'".
FIG. 3a shows the outer shaft 202' with a smooth outer surface accommodating an outer cam 203'. The parts are form-fittingly connected by pins 219a, 219b inserted in the direction of the raised cam portion, with the pins inserted from the opposite end of the raised cam portion. The pin 219b has a greater diameter than the pin 219a.
FIG. 4 shows a camshaft assembly 401 having an outer shaft 402 carrying outer cams 403a-d on its outer circumference and an inner shaft 404 carrying inner cams 405a-d at a radial distance from its outer circumference, which slide on the outer shaft. Fixing pins 423 are radially slid through the inner cams 405 in the direction of the raised cam portions. The fixing pins 423 are firmly positioned in coaxial bores in the inner cams and in associated through-bores in the inner shaft 404. The pins pass through the outer shaft 402 in circumferential slots 410 (not shown in detail).
The outer shaft 402 includes identical longitudinal portions 406a-406d and of a final shorter longitudinal portion 406e, whereas the inner shaft is produced in one piece. With the exception of the final portion (e), the longitudinal portions each include a sleeve 407 with outer shaft teeth 408 provided at its end. At the axial end located opposite the shaft teeth, the ends each include inner bearing portions 421 with a lubrication core 420. The outer cams 403a-d and with inner teeth 409a-d nd are axially slid on to the matching outer teeth 408 of the longitudinal portions 406 to be held firmly. The outer surfaces of the sleeves 407 of the longitudinal portions 406 are cylindrical and run in bearings 411 which do not form part of the invention.
The assembly, in its entirety, is preferably assembled from right to left. The longitudinal portion 406e is slid on to the inner shaft 404. Subsequently, the preassembled unit including the longitudinal portion 406d and the slide on end secured cam 403d is added and welded to the longitudinal portion 406e. The inner cam 405d is slid on to the longitudinal portion 406d and secured to the inner shaft 404 by the fixing pin 423d. Subsequently, in the same sequence, the further longitudinal portions 406, with the outer cams 403 already secured thereto, are added and welded on. This operation is followed by the inner cams 405 slid on the sleeves 407 of the longitudinal portions 406 and secured by the fixing pins 423 on the inner shaft 404. At their abutting ends, the longitudinal portions 406 are provided with centering means 431, 432 which engage one another and center the portions. The weld 433 is produced therebetween.
An adjusting device 434, by means of which the two shaft parts (the outer shaft 402 and the inner shaft 404), may be rotated relative to one another is shown in the outline at the end of the camshaft.
FIG. 4a shows a cross section of the inner cam 405a which is secured to the one-piece inner shaft 404 by a radial fixing pin 423. The outer shaft 402, in this section, includes the finger regions 409 1 , 409 2 between which the circumferential slots 410 1 , 410 2 are formed, with the fixing pin 423 extending through the slots. As the circumferential angle of the slots 410 is greater than the thickness of the pin 423, the inner shaft 404 is able to rotate relative to the outer shaft 402.
FIG. 4b shows a cross section through the outer cam 403a which, by means of inter-engaging teeth 408, is located on the longitudinal portion 406a of the outer shaft 402. The inner shaft 404 is positioned in the outer shaft 402 with radial play.
FIG. 5 shows a camshaft assembly 501 having an outer shaft 502 carrying outer cams 503a-d on its outer circumference and an inner shaft 504 carrying inner cams 505a-d at a radial distance from its outer circumference, which slide on the outer shaft. Fixing pins 523 radially extend through the inner cams 505 in the direction of the raised cam portions. The fixing pins 523 are firmly positioned in coaxial bores in the inner cams and in associated through-bores in the inner shaft 504 and extend through the outer shaft 502 in circumferential slots 510 (not shown in detail). The outer shaft 502 includes identical longitudinal portions 506a-506d and a final shorter longitudinal portion 506e. The inner shaft is produced in one piece. The longitudinal portions each include an externally smooth sleeve 507. At their one axial end, they each include an inner bearing portion 521 with a lubrication bore 520. At the ends of the longitudinal portions 506 positioned axially opposite the inner bearing portion, outer cams 503 are slid on to the sleeves 507 and secured by two fixing pins 519 1 , 519 2 which are firmly positioned in coaxial bores in the outer cams 503 and in the longitudinal portion 506. The outer faces of the sleeves 507 of the longitudinal portions 506 are cylindrical and run in bearings 511 which do not form part of the invention.
The assembly, in its entirety, is preferably assembled from right to left. The longitudinal portion 506e is slid on to the inner shaft 504. Subsequently, the preassembled unit including the longitudinal portion 506d, with the cam 503d already slid on and secured, is added and welded to the longitudinal portion 506e. The inner cam 505d is slid on to the longitudinal portion 506d and secured to the inner shaft 504 by means of the fixing pin 523d. Subsequently, in the same sequence, the further longitudinal portions 506, with the outer cams 503 already secured thereto, are added and welded on, whereupon the inner cams 505 are slid on the sleeves 507 of the longitudinal portions 506 and secured by the fixing pins 523 to the inner shaft 504. At their abutting ends, the longitudinal portions 506 are provided with centering means 531, 532 which engage one another and center the portions. A weld 533 is produced therebetween.
An adjusting device 534 by means of which the shaft parts (the outer shaft 502 and the inner shaft 504) may be rotated relative to one another is indicated in outline at the end of the camshaft.
FIG. 5a shows a cross section of the inner cam 505a which is secured to the one-piece inner shaft 504 by the radial fixing pin 523. The outer shaft 502, in this section, includes finger regions 509 1 , 509 2 between which the circumferential slots 510 1 , 510 2 are formed, with the pin 523 passing therethrough. Because the circumferential angle of the slots 510 is greater than the thickness of the pins, it is possible for the inner shaft 504 to rotate relative to the outer shaft 502.
FIG. 5b shows a cross section through the outer cam 503a which, by means of two individual radial fixing pins 519 1 , 519 2 , is form-fittingly secured to the longitudinal portion 506 of the outer shaft 502. The inner shaft 504 is positioned with play in the outer shaft 502.
FIG. 6 shows a camshaft assembly 601 having an outer shaft 602 carrying outer cams 603a-d on its outer circumference, and an inner shaft 604 carrying inner cams 605a--also directly on its outer circumference. The inner cams 605, by fixing portions 629, radially extend through the outer shaft 602. The fixing portions 629 are positioned in a force-locking and form-fitting way on the inner shaft 604. They extend through the outer shaft 602 in circumferential slots 610. The outer shaft 602 is composed of identical longitudinal portions 606a-606d and of a final shorter longitudinal portion 606e, whereas the inner shaft is produced in one piece and comprises form-fitting means (not illustrated) for the fixing portions 629 of the inner cams 605. The longitudinal portions each consist of an externally smooth sleeve 607. At their one axial end, they each comprise an inner bearing portion 621 with a lubrication bore 620. The outer cams 603 are axially slid on to the ends of the longitudinal portions 606 positioned axially opposite the inner bearing portions and form-fittingly secured thereto by means of two pressed-in fixing pins 619 1 , 619 2 . Run in bearings 611 are also shown. The outer surfaces of the longitudinal portions 606 are cylindrical. The outer surfaces each comprise finger regions 609 1 , 609 2 which extend as far as their lefthand ends and which are separated by circumferential slots 610 1 , 610 2 .
The assembly, in its entirety, is preferably assembled from right to left. The longitudinal portion 606e is slid on to the inner shaft 604. Subsequently, the preassembled unit consisting of the longitudinal portion 606d with the cam 603d already slid on and secured is added and welded to the longitudinal portion 606e. Now the inner cam 605d is slid on to the inner shaft 604 and secured in a form-fitting way through engagement of the fixing portions 629 1 , 629 2 . Thereafter, in the same sequence, the further longitudinal portions 606 with the outer cams 603 already secured thereto are added and welded on, whereupon the inner cams 605 are mounted on the inner shaft and secured by the fixing portions 629. The abutting ends of the longitudinal portions 606 are provided with centering means 631, 632 which engage one another and center the portions. The weld 633 is arranged between the longitudinal portions.
An adjusting device 634 by means of which the two shaft parts (the outer shaft 602 and the inner shaft 604) maybe rotated relative to one another is indicated in outline at the end of the camshaft.
FIG. 6a shows a cross section through the inner cam 605a which, by means of fixing portions 629 1 , 629 2 , with form-fitting means, is secured to the inner shaft 604 in a form-fitting and force-locking way. In this section, the outer shaft 602 consists of finger regions 609 1 , 609 2 only, with circumferential slots 610 1 , 610 2 thus being formed therebetween. The fixing portions 629 1 , 629 2 extend through said slots. As the circumferential angle of the slots 610 is greater than the circumferential angle of the fixing portions 629, it is possible for the inner shaft 604 to rotate relative to the outer shaft 602.
FIG. 6b shows a cross section through the outer cam 603a which, by means of two individual radial fixing pins 619 1 , 619 2 , is secured to the longitudinal portion 606 of the outer shaft 602 in a form-fitting way. The inner shaft 604 is positioned in the outer shaft 602 with play.
FIG. 7 shows a camshaft assembly 701 having an outer shaft 702 carrying outer cams 703a-d on its outer circumference, and an inner shaft 704 carrying inner cams 705a-d also directly on its outer circumference. The inner cams 705, by fixing portions 729, radially extend through the outer shaft 702. The fixing portions 729 are positioned on the inner shaft 704 in a force-locking and form-fitting way. They pass through the outer shaft 702 in circumferential slots 710. The outer shaft 702 consists of identical longitudinal portions 706a-d and of a final shorter longitudinal portion 706e. The inner shaft is produced in one piece and comprises form-fitting means (not illustrated) for the fixing portions 729 of the inner cams 705. With the exception of the final portion (e), the longitudinal portions each consist of a sleeve 707 with outer shaft teeth 708 positioned at the end thereof. At the axial end located opposite the shaft teeth, they each comprise inner bearing portions 721 with a lubrication bore 720. The outer cams 703 with inner teeth are axially slid on to the matching outer teeth 708 of the longitudinal portions 706 so as to be held firmly. Run in bearings 711 are also shown. The outer surfaces of the sleeves 707 of the longitudinal portions 706 are cylindrical. The outer surfaces each comprise finger regions 709 1 , 709 2 which extend as far as their lefthand ends and which are separated by circumferential slots 710 1 , 710 2 .
The assembly, in its entirety, is preferably assembled from right to left. The longitudinal portion 706e is slid on to the inner shaft 704. Subsequently, the preassembled unit consisting of the longitudinal portion 706d with the cam 703d already slid on and secured is added and welded to the longitudinal portion 706e. Now, the inner cam 705d is slid on to the inner shaft 704 and secured in a form-fitting way through engagement of the fixing portions 729 1 , 729 2 . Thereafter, in the same sequence, the further longitudinal portions 706 with the outer cams 703 already secured thereto are added and welded on, whereupon the inner cams 705 are mounted on the inner shaft and secured by the fixing portions 729. The abutting ends of the longitudinal portions 706 are provided with centering means 731, 732 which engage one another and center the portions. The weld 733 is produced between the abutting ends.
An adjusting device 734 by means of which the two shaft parts (the outer shaft 702 and the inner shaft 704) may be rotated relative to one another is indicated in outline at the end of the camshaft.
FIG. 7a shows a cross section of an inner cam 705a which, by means of fixing portions 729 1 , 729 2 with form-fitting means, is secured to the inner shaft 704 in a form-fitting and force-locking way. In this cross-section, the outer shaft 702 consists of finger regions 709 1 , 709 2 only, with circumferential slots 710 1 , 710 2 thus being formed therebetween. The fixing portions 729 1 , 729 2 extend through said slots. As the circumferential angle of the slots 710 is greater than the circumferential angle of the fixing portions 729, it is possible for the inner shaft 704 to rotate relative to the outer shaft 702.
FIG. 7b shows a cross section through the outer cam 703a which, by means of inter-engaging teeth 708a, is held on the longitudinal portion 706 of the outer shaft 702. The inner shaft 704 is positioned in the outer shaft 702 with play.
While the above detailed description describes the preferred embodiment of the present invention, the invention is susceptible to modification, variation, and alteration without deviating from the scope and fair meaning of the subjoined claims. | A camshaft assembly for valve-controlled internal combustion engines, having two shaft elements, an inner shaft and an outer shaft, which are positioned one inside the other, which are supported one inside the other and which are rotatable relative to one another by a limited axial distance, with first cams referred to as inner cams, especially for the inlet valves, being connected to the inner shaft and with second cams referred to as outer cams, especially for the outlet valves, being connected to the hollow outer shaft, the outer shaft comprising wall apertures associated with fixing elements or fixing portions of the inner cams, and the inner cams forming axially open slots or recesses which are shaped like a sector of a circle and which are engaged by axial finger regions of the outer shaft, with the inner cams being connected to the inner shaft by form-fitting mechanisms and with the outer cams being connected to the outer shaft by form-fitting mechanisms and with at least the outer shaft consisting of individual longitudinal portions. | 1 |
BACKGROUND OF THE INVENTION
[0001] The present invention relates to moving goods and people from the surface of the earth to outer space. Currently, all loads sent into space are transported via chemical rockets. Not only do chemical rockets present serious safety concerns with the vast amounts of fuel and oxidizer, but the cost of sending cargo into space via chemical rockets is very expensive. It can cost $5000/kg or more to put cargo into low earth orbit, and $20,000/kg to put cargo into geostationary orbit.
[0002] An alternative to chemical rockets was put forth in 1960 by Yuri Artsutanov with the idea of a space elevator. The mathematical fundamentals for a space elevator were documented in 1975 by Jerome Pearson. However, to date, the limiting factor that has kept a space elevator from being built has been the lack of suitable material with which to build the elevator cable. Yet, recent developments with nanotubes and other allotropes and compounds of carbon or boron indicate that the lack of suitable materials will no longer be a problem in the not-too-distant future.
[0003] Even if suitable cable materials had been available in the past, the prior art and previous designs may still have kept a space elevator from being built. Existing designs have had very high costs for construction, and would not be very practical or economical to operate. Prior art required massive accumulations of materials in space from multiple rocket launches, and the slow build-up of the space elevator by the means of climbers once a “seed” cable has reached the earth. In addition, the throughput of cargo, per year, into space using climbers on a finished space elevator would be low.
[0004] Cable climbers using laser beams as an energy source have become the accepted idea for building and operating a space elevator. In fact, NASA has so thoroughly accepted the idea of space elevator climbers that it has offered a two million dollar prize for a top performing climber with its Elevator 2010 Challenge.
[0005] However, laser powered climbers are, at best, only one or two percent efficient. Therefore 50 to 100 times the actual energy needed would be required each time a climber goes up a space elevator. Also the motors, wheels, and energy conversion equipment for a climber comprise a large portion of the mass of the climber, which limits the cargo capacity. Therefore, the energy requirements for a climber may be 200 times the actual energy needed to take the cargo alone into space. In addition, climbers are inherently slow due to the power requirements and wheel limitations, and so the initial building and the ultimate operation of the space elevator would be slowed by both the speed and the cargo capacity of the climbers.
[0006] Another problem of previous designs is that the incremental cables lifted by the climbers to build the space elevator would always be dragging or sliding against the existing cable. That friction and proximity create a high probability for a snag or tangled cables which would be very difficult to deal with.
[0007] Against this background of problematic designs, the inventor has devised novel solutions which will allow the quick and economical construction of a practical space elevator and will insure its widespread acceptance and use.
SUMMARY OF THE INVENTION
[0008] It is therefore the objective of the present invention to provide a novel method and apparatus to quickly transport materials and personnel from the surface of the earth into outer space using substantially less energy and money than has been required heretofore, by means of a practical space elevator. The present invention is a great improvement over prior art for the construction of a space elevator in that it only requires a single rocket launch, regardless of the specific strength of the space elevator cables. All subsequent work is done by feeding cables from the ground. No sliding of cables against cables is ever needed.
[0009] The construction of a space elevator according to the present invention will be faster, simpler and less costly than by using any prior art. Also, the operation of the present invention will allow a higher throughput of cargo to space, a lower energy use, and a faster time to orbit than with any previous space elevator designs. The cables of the present invention would move in a big loop from earth to geostationary orbit, and would provide an almost 100% efficient means of energy transfer. Huge motor/generators on the ground would power loads up the space elevator faster than any prior designs could ever do, and they would regeneratively recoup any energy from slowing down or descending loads.
[0010] The present invention only requires a single rocket launch for construction, and the build-up of the cable strength would be many times faster than could be achieved by climbers. Also, after a space elevator of the present invention was constructed, the throughput of cargo into space per year would be many times greater than a space elevator using climbers.
[0011] For passenger travel into space, the present invention would require almost zero net energy, as the energy expended when the passengers went up would be recouped when they came back down. In addition, the fast transit time through the Van Allen radiation belts would mean less shielding requirements for passenger travel. Cargo into space would generally not come back down, but the elevator car that delivered it would come down, meaning that the net energy expended would only be the actual energy needed to raise the cargo itself.
[0012] The present invention would provide a significant improvement over the prior art in many aspects.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a diagram showing one embodiment of the present invention of a space elevator, with a single moving cable extending from the earth to geostationary orbit; and
[0014] FIG. 2 illustrates a construction satellite used by the present invention in initiating the building of a space elevator; and
[0015] FIG. 3 is a diagram of the construction process for building a space elevator as taught by the present invention; and
[0016] FIG. 4 illustrates a method of lifting a space elevator pulley into space as taught by the present invention; and
[0017] FIG. 5 is a diagram of the present invention of a space elevator composed of multiple loops of moving cables between earth and geostationary orbit; and
[0018] FIG. 6 illustrates the support, connection, and drive mechanism between two pulleys of a space elevator of the present invention with multiple loops; and
[0019] FIG. 7 illustrates the transfer of a space elevator car of the present invention from one loop to another; and
[0020] FIG. 8 is a diagram showing the method of construction of a space elevator of multiple loops as taught by the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0021] The following description is provided to enable any person skilled in the art to make and use the present invention, and sets forth the best modes contemplated by the inventor for using his invention. Variations to this description however, will be readily apparent to those skilled in the art, since only the generic principles of the present invention have been defined herein.
[0022] Referring now to FIG. 1 , the space elevator of the present invention includes a pulley 10 , securely fixed to the surface of the earth 11 , at a location near the equator. A belt 12 , is wrapped around pulley 10 , and extends in a great loop from the surface 11 to a second pulley 13 , located in space station 14 , in geostationary orbit. Belt 12 rotates in the direction shown by arrow 15 , and belt 12 is generally kept continually rotating in order that the Coriolis force, from the rotation of the earth, keeps the two opposite sides of the belt apart so that they cannot become entangled. Also located in space station 14 is third pulley 16 , to which second long belt 17 is attached. Belt 17 extends many thousands of kilometers beyond geostationary orbit and ends at a fourth pulley 18 . The rotation of belt 17 is shown by arrow 19 , and is in the same direction as the rotation of belt 12 in order that the Coriolis force also keeps both sides of belt 17 apart. Attached to pulley 18 is a counterweight cable 20 , which extends many thousands of kilometers farther from the earth than pulley 18 and provides the centrifugal force, via the rotation of the earth, to counter the weight of belt 12 , as well as provide initial tension on belt 12 .
[0023] The operation of the present invention, as depicted in FIG. 1 , is as follows: Regenerative braking motor 21 on pulley 10 stops the rotation of belt 12 , and a load 22 is clamped to the rising side of belt 12 , load 22 having a weight less than the initial tension on one side of belt 12 . As belt 12 is many thousands of kilometers long, and has a significant amount of stretch in it, any acceleration of pulley 10 will not directly transfer motion to lift load 22 . However, as pulley 10 is forced to rotate by motor 21 , that movement takes the tension off of belt 12 in the area 23 between pulley 10 and load 22 , which then allows the tension in belt 12 above load 22 to start lifting load 22 . As pulley 10 accelerates, so will load 22 accelerate until the desired speed of load 22 is achieved. The fact that belt 12 quickly stops to allow load 22 to be attached will not allow the two sides of belt 12 to come together to risk entanglement, due to the fact that the oscillation period of the two sides of belt 12 is measured in hours, due to the extreme length. Therefore, stopping belt 12 long enough to attach or detach loads would only induce slight ripples in the overall path of belt 12 , but would not allow the two sides of belt 12 to get close enough to risk entanglement.
[0024] Continuing with the operation of the present invention, as depicted in FIG. 1 , load 22 would rise with the rotational movement 15 of belt 12 until it neared space station 14 , at which point braking motor 24 , on pulley 13 , would slow belt 12 to a stop, and load 22 would be unclamped from belt 12 . The cargo of load 22 would then be accessible for unloading at space station 14 . Alternatively, if a lower earth orbit was the final destination of load 22 , then load 22 would be unclamped from belt 12 at a lower altitude. If the final destination of load 22 was an interplanetary location, then load 22 would be transferred and clamped to belt 17 at space station 14 , in like manner as it had been clamped to belt 12 at the surface of the earth. As the distance of load 22 from the earth increased by the movement 19 of belt 17 , the rotation of the earth would cause the tangential velocity of load 22 to increase. When the tangential velocity of load 22 , coupled with the orbital velocity of the earth, was sufficient to reach the desired interplanetary location, load 22 would then be unclamped from belt 17 with the required trajectory.
[0025] The space elevator as depicted in FIG. 1 can be quickly and easily constructed using a construction satellite 25 , as illustrated in FIG. 2 . Satellite 25 has two reels of cable, reel 26 , and reel 27 . Each of these reels is rotationally connected to a motor/generator 28 that either drives or brakes the rotation of the respective reel, depending on whether it is operating as a motor or generator. Between reels 26 and 27 is an extendable satellite frame 29 , needed to provide distance between the two reels, so that the extreme tension from cables 30 and 31 will always be very nearly tangential to the reels, with only a very small axial force. In addition, extendable frame 29 is covered by photovoltaic cells to power satellite 25 . Attached to cable 30 is earth-bound load 32 , initially guided by thrusters 33 ; and attached to cable 31 , is counterweight 34 , guided by thrusters 35 . Control centers 36 provide both the electronic controls needed as well as high power resistive elements to dissipate the energy generated by generators 28 .
[0026] The operation of the present invention, as illustrated in FIG. 2 is a follows: Satellite 25 is placed in geostationary orbit above the desired location of the space elevator base station. Once in that orbit, satellite 25 opens its extendable frame 29 to change from a compact rocket load to the required lengthy satellite. After extending frame 29 , satellite 25 would then orient itself, with cable 30 pointing toward the earth, and cable 31 pointing away from earth. At that point, thrusters 33 on earth-bound load 32 would gently fire, and motor 28 would simultaneously begin to unwind reel 26 , sending load 32 on a trajectory towards earth. At the same time, thrusters 35 on counterweight 34 would fire, and cable 31 from reel 27 would begin to unwind, sending counterweight 34 on a trajectory away from the earth. Once thrusters 33 and 35 got their respective loads up to a modest speed of perhaps 50 m/s, they would no longer be needed. The inertia of load 32 and counterweight 34 would keep them going, and the tangential velocity imparted to cables 30 and 31 by the rotation of their respective reels 26 and 27 would keep load 32 and counterweight 34 moving in their respective directions, with cable following them.
[0027] After a few hundred kilometers of cable were reeled out from reels 26 and 27 the tidal forces would be sufficient to keep the cables aligned with the earth. After a few thousand kilometers were reeled out, motors 28 would have to become generators to hold back the tension created by the gravitational force pulling on load 32 and the centrifugal force pulling on counterweight 34 .
[0028] Incidentally, it would probably be advantageous from an engineering, manufacturing, and operational standpoint to have reels 26 and 27 , with their motor/generators 28 , identical. The mass of counterweight 34 could be easily adjusted so that the necessary length of cable on reel 27 was exactly the same as the length of cable on reel 26 .
[0029] As load 32 and counterweight 34 got farther and farther away from satellite 25 , the center of gravity of the whole system could easily shift away from geostationary orbit, causing satellite 25 to drift with respect to the location of the space elevator ground station on earth. In order to keep the center of gravity at the desired geostationary location, a ground-based station-keeping control center would monitor the position of satellite 25 as cables 30 and 31 were being extended. Signals from that control center would speed up or slow down reels 26 or 27 as needed in order to always maintain the center of gravity in the appropriate geostationary location.
[0030] With load 32 approaching earth, and counterweight 34 approaching its specified distance, the tension on cables 30 and 31 would increase to very high levels, requiring the dissipation of a large amount of energy generated by the generators 28 . In fact, the last few thousand kilometers may require a slowing of the cable speed so as to not exceed the capacity of the generator and the power dissipation resistors. When load 32 arrived at the surface of the earth, it would have expended its propellent, and would just be an empty shell, therefore it would not weigh much. However, it would be brightly colored and carry a transmitter to signal its presence as it got close to the ground.
[0031] After load 32 reached the surface of the earth it would be located and transported to the designated space elevator base station. At that time, the tension on cable 30 , at the surface, would essentially be the weight of the empty shell of load 32 . Load 32 would then be removed from cable 30 , and the reels 26 and 27 of satellite 25 would be locked in place, as the work of satellite 25 would be finished.
[0032] Referring now to FIG. 3 , cable 38 from reel 37 at the base station on earth 11 would be attached via splice 39 to cable 30 . The tension on cable 30 that was originally supporting load 32 would then start pulling on cable 38 . The cross sectional size of cable 38 would be the same as the size of cable 30 , because even though there would be a little initial tension on cable 30 , that tension would not be sufficient to lift a larger cable very high. As reel 37 began to unwind, the tension on cable 30 would pull up any amount of cable 38 that was unwound, thereby increasing the distance of counterweight 34 from the surface of the earth. That increased distance would increase the tension on cable 30 due to the increased centrifugal force on the counterweight. Also, the additional cable 38 would move disabled satellite 25 to a distance farther out than geostationary orbit 40 , causing satellite 25 to become a counterweight itself.
[0033] The increased tension caused by the increased length of cable 38 can be calculated by knowing the mass of counterweight 34 , the mass of disabled satellite 25 , and the mass per unit length of the cables 30 , 31 , and 38 . The centrifugal force minus the gravitational force of each segment can be added to determine the net tension in cable 38 . When cable 38 has been extended sufficiently to produce the desired tension level, cable 38 can then be increased in cross sectional area, and fed out towards space. When an appropriate tension level was reached, the more massive cable 38 could then be pulled all the way out to geostationary orbit without the space elevator losing tension, so that more cable 38 could always be pulled up. That same process could then be continued with progressively larger cables.
[0034] Eventually, with enough additional cable 38 fed up from earth, counterweight 34 would get far enough from the surface of the earth that its centrifugal force would exceed the strength of cables 30 , 31 and the smaller section of cable 38 that support it. However, before these cables were allowed to be overstressed, the mass of counterweight would need to be decreased in order to reduce that centrifugal force. The majority of the mass of counterweight 34 could be in liquid form so that the mass could be gradually released as its distance from the earth increased. However, the time would come when even the empty shell of counterweight 34 would have to be jettisoned. Also, disabled satellite 25 would eventually get far enough from earth that its centrifugal force would require it to be jettisoned also, in order to keep from over-stressing the cables 30 and 38 .
[0035] After counterweight 34 , and satellite 25 were jettisoned, there would only be cables pulling cables into space. There would be no space-based mechanisms, controls, reels, satellites or other devices needed to finish the construction of the space elevator. However, even sections of the cables themselves would have to be jettisoned when they got so far from earth that their centrifugal force began to exceed the allowable stress limit. Those sections of cables could be jettisoned by a designed weak point where the cable would purposely break at a certain point once the stress got to a certain level, or by radio-controlled pyrotechnic devices periodically attached to the rising cable.
[0036] With cables pulling cables, the space elevator could be gradually increased in size until the design requirements of strength and initial tension were met. However, the end result would simply be a single cable extending from earth to over 150,000 km above the earth, not the rotating elevator belts as shown in FIG. 1 . This would be resolved by pulling the appropriate pulleys into space.
[0037] Referring now to FIG. 4 , the finished space elevator cable 41 would be attached to the axle 47 of pulley 18 , allowing axle 47 to spin freely, with belt 43 wrapped around pulley 18 and firmly attached to the surface at point 44 . The other end of belt 43 would be fed from reel 45 as cable 41 pulled pulley 18 up into space in direction 46 . As pulley 18 moved upward towards space, belt 43 would be forced to unwind from reel 45 at twice the speed of pulley 18 . That upwards velocity, coupled with the rotation of the earth, would create a Coriolis force 48 on belt 43 that would keep the rising side of belt 43 separated from the stationary side. Pulley 18 would continue to be raised by cable 41 until the distance between the earth and pulley 18 was the same as the distance between pulley 16 and pulley 18 in FIG. 1 . At that point, the fixed end 44 , of belt 43 , would be spliced to the rising end of belt 43 around pulley 16 , forming belt 17 , as shown in FIG. 1 . The same process illustrated by FIG. 4 would then be repeated, with pulley 16 and space station 14 attached to pulley 13 , with the belt material that becomes belt 12 being fed by a large reel similar to reel 45 . When space station 14 , with pulley 13 , arrived at it final location, belt 12 would be spliced together around reel 10 , and the space elevator would be completed.
[0038] In FIG. 5 , the present invention is diagrammed for a space elevator composed of multiple loops of moving belts between earth and geostationary orbit. This embodiment of the present invention is needed if the specific strength of the belt material is not strong enough to support its own weight between earth and geostationary orbit. An example, with numbers, will be shown for a case where the specific strength of the material is less than 20×10 6 N-m/kg.
[0039] The load on a segment of space elevator cable can be calculated as follows: The gravitational force dF on a section dr of cable of mass λ/m is:
[0000]
dF
=
GM
e
λ
dr
r
2
[0040] Where G is the gravitation constant, M e is the mass of the earth, and r is the distance from the center of the earth.
[0041] If we had a cable stretched from point A to point B, in a radial line above the surface of the earth, there would be a total force from gravity on the cable:
[0000]
F
=
∫
A
B
G
M
e
λ
r
r
2
=
G
M
e
λ
A
-
G
M
e
λ
B
(
1
)
[0042] There is also centrifugal force on the cable that tends to counter the gravitational force:
[0000] F=mω 2 r (ω 2 =5.317×10 −9 for the earth's rotation.)
[0043] So, for a segment of cable of mass λdr, dF=ω 2 λrdr. Integrating this we get:
[0000]
F
=
∫
A
B
ω
2
λ
r
r
=
λ
ω
2
B
2
2
-
λω
2
A
2
2
(
2
)
[0044] Subtracting equation 2 from equation 1, we have the net force on a segment of cable that extends from point A to point B:
[0000]
F
=
G
M
e
λ
A
-
G
M
e
λ
B
-
λω
2
B
2
2
+
λω
2
A
2
2
(
3
)
[0045] Using equation 3 the load on any of the belts of a multiple loop space elevator can be calculated. The calculated loads for the example of a material with a specific strength of less than 20 MN-m/kg are shown in the following description of FIG. 5 .
[0046] Referring now to FIG. 5 , a pulley 50 , is attached to the surface of the earth 11 , located at a distance of 6.38 Mm from the center of the earth, around which is wrapped a belt 51 , extending upward to pulley 52 , located 8.7 Mm from the center. This length of belt puts a load of 16.6 MN-m/kg on belt 51 at pulley 52 . Attached to pulley 52 is another pulley, 53 , around which belt 54 is wrapped and extended upward to pulley 55 , at a distance of 11.1 Mm. Belt 54 has twice the cross section of belt 51 . The load on belt 54 is 18.1 Mn-m/kg with its own weight plus the weight of belt 51 . Connected to pulley 55 is another pulley, 56 , around which belt 57 is wrapped and extended up to pulley 58 , located at a distance of 18 Mm. Belt 57 has six times the cross section of belt 51 . The load on belt 57 is 19.3 Mn-m/kg with its own weight plus the weights of belts 54 and 51 . Connected to pulley 58 is another pulley, 59 , around which belt 60 is wrapped and extended up to pulley 61 , located in space station 62 , at a distance of 42.2 Mm, which is the height of geostationary orbit. Belt 60 has eleven times the cross section of belt 51 , The load on belt 60 is 18.7 Mn-m/kg with its own weight plus the weights of belts 57 , 54 and 51 . Additional belts (not shown) would extend upward from space station 62 to a counterweight cable in order to maintain the appropriate tension in the space elevator.
[0047] The support, connection, and drive mechanism between pulleys 52 and 53 of the present invention is illustrated in FIG. 6 : A pulley, 63 , is rigidly attached to, and concentric with, pulley 52 , as is pulley 64 attached to, and concentric with, pulley 53 . A similar set of pulleys, not shown, are attached to the back sides of pulleys 52 and 53 . A belt 65 is stretched between pulleys 63 and 64 , and a similar belt 66 is stretched between the pulleys on the back sides of pulleys 52 and 53 . Belts 65 and 66 would serve the multiple purposes of providing the load-carrying support, the bearing surfaces, and the drive system between pulleys 52 and 53 . As belt 51 rotated, the present invention would also cause belt 54 to rotate synchronously with belt 51 . With the other pairs of pulleys of the present invention all having similar configurations, the bottom belt 51 of the present invention would drive all of the other belts of the space elevator.
[0048] Referring now to FIG. 7 , an elevator car of the present invention is shown crossing over a pair of pulleys of a multiple loop space elevator of the present invention. The elevator car 67 has three clamping mechanisms, shown as 68 , 69 , and 70 , the distance between adjacent clamps being greater than the distance between pulleys 52 and 53 , and clamping mechanisms 68 , 69 , and 70 each providing a firm grip to the elevator belts 51 or 54 . Each of the clamping mechanisms 68 , 69 , and 70 would have a clamp opening 71 , which would allow a pulley, such as pulley 52 , to pass through when in the unclamped state. As car 67 , rising via the movement of belt 51 , approached pulley 52 , belt 51 would slow down, allowing clamping mechanism 68 to unclamp itself from belt 51 . Clamp opening 71 would then allow clamp 68 to pass over pulleys 52 and 53 , where it would then be reclamped to belt 54 . Next, clamp 69 would unclamp from belt 51 and pass over the pulleys 52 and 53 until it could also reclamp on belt 54 . Finally, clamp 70 would follow the same process to transfer itself to belt 54 . With at least two clamps always attached to the belts, elevator car 67 would always be stable and secure as it rode the space elevator past the various pulley pairs.
[0049] The method of construction of a multiple loop space elevator of the present invention, as diagramed in FIG. 5 , will now be revealed. As the strength of the cable material of a multiple loop space elevator is insufficient for a space elevator to be constructed via the method shown in FIGS. 2 and 3 , a different construction method is required. An initial construction satellite, analogous to satellite 25 of FIG. 2 , would feed out multiple belts in the form shown in FIG. 5 , but with one exception. The exception is that although the ratio of belt sizes would be the same as taught by the present invention of FIG. 5 , the bottom belt 51 would be replaced by a single cable 72 , as shown in FIG. 8 , and the belt sizes would be very small compared to the desired finished size.
[0050] Continuing on with FIG. 8 , cable 72 would initially be lowered to the surface in like manner as was cable 30 in FIG. 3 , cable 72 also having a small initial tension due to a weight on the end. Cable 72 would then be attached to a new cable 73 , of the same size as cable 72 , via splice 74 , cable 73 being fed from reel 75 . Reel 75 would then feed out additional cable 73 , compelling the entire system to move further out into space, to increase the tension on cable 72 , at pulley 52 , to the maximum allowable tension. When the maximum tension was achieved, cable 72 would be wrapped around capstan 76 on pulley 52 , and clamp 77 would attach the end of cable 72 to belt 54 , which would begin to rise in direction 78 . The slight tension provided on cable 72 by belt 54 would engage the grip of capstan 76 , and cable 72 would begin to rise. The weight of cable 72 , from the earth to the pulleys, would be supported by the grip of capstan 76 , as the necessary additional cable 73 was being fed from reel 75 . Therefore, as cable 72 was lifted up by belt 54 , it would essentially only have to carry the weight of the cable above the capstan.
[0051] As clamp 77 , along with cable 72 , was lifted by belt 54 , it would eventually reach pulley 55 , as seen in FIG. 5 . At that point, a mechanism would transfer clamp 77 and cable 72 to be wrapped around a capstan on pulley 55 , and then clamp 77 would be reclamped onto belt 57 . Then cable 72 would rise with belt 57 , with the weight of cable 72 between pulleys 55 and 53 being supported by the capstan on pulley 55 . A similar transfer would occur when clamp 77 reached pulleys 58 and 59 , and clamp 77 would reclamp onto belt 60 , which would carry cable 72 all the way up to space station 62 at geostationary orbit.
[0052] As cable 72 initially began to be lifted above the height of pulley 52 , as diagrammed in FIG. 8 , one side of cable 54 would have more mass than before, and the weight of this mass would decrease the overall tension of the space elevator. With the example given above of a space elevator made of material with less than 20 MN-m/kg of specific strength, the end of cable 72 would only rise about 500 km above the height of pulley 52 until the overall tension had decreased sufficiently that a smaller diameter cable 73 would then be required in order to keep the tension from disappearing completely. In the example given, that reduction in cross section be about 36% of the original size of cable 73 , in order that the end of cable 72 could be lifted all the way to geostationary orbit without losing the overall tension in the space elevator.
[0053] Once cable 72 reached space station 62 , reel 75 would continue to feed out more cable 73 , and cable 72 , followed by cable 73 , would be collected on an empty reel in space station 62 , until a large mass of cable was accumulated on that reel. Because that mass would be in geostationary orbit, it would not affect the overall tension of the space elevator in any way, as all mass in geostationary orbit has its weight perfectly balanced by its centrifugal force. After a sufficient quantity of cable was accumulated in space station 62 , cable 73 would then be cut from the geostationary reel, and the cut end permanently attached to the downward-moving side of belt 60 . At about the same time, the other end produced by the cut in cable 73 would be permanently attached to the upward moving side of the belt extending upwards from space station 62 . Therefore, new cable from the earth, fed by reel 75 , would wrap around belt 60 at the same time that the accumulated cable in station 62 would wrap around the first belt extending above station 62 . Thus both belts would be strengthened at the same time, and in a way that would not adversely affect the overall tension of the space elevator. After belt 60 had been strengthened by multiple wraps of cable 73 , fed from reel 75 , then the end of cable 73 would again be wrapped around the reel in space station 62 , and the reel would again start being filled by more cable 73 from reel 75 . After that reel was sufficiently full again, then cable 73 would be cut again, and the end transferred down to belt 57 , where belt 57 would be strengthened by multiple wraps of cable 73 from reel 75 at the same time that an upper belt, above station 62 , was being wrapped by the cable from the space station reel. A similar process would then be used to strengthen belt 54 , Also, during this entire construction process, the cross section of cable 73 would be increased as often as the overall tension and the load carrying capacity of cable 73 would allow it.
[0054] Therefore, by continuing the above process of wrapping all of the space elevator belts, both above and below space station 62 , the entire space elevator could be strengthened as much as was desired. One of the final steps of the construction process would be changing single cable 73 to belt 51 , as shown in FIG. 5 , to finish the multiple loop space elevator.
[0055] Those skilled in the art will appreciate that various adaptations and modifications of the invention as described above can be configured without departing from the scope and spirit of the invention. Therefore, it is to be understood that, within the scope of the appended claims, the invention may be practiced other than as specifically described herein. | A space elevator and method of construction of the same that allows a space elevator to be constructed with a single rocket launch by simultaneously sending cables down to earth and away from earth via a construction satellite. When the earthbound cable reaches the surface, additional cable of gradually increasing cross section is fed from the surface of the earth to finish the construction. The finished space elevator uses moving cables to transport simplified elevator cars into space, thereby greatly increasing the throughput of cargo into space compared to prior art and previous designs. | 1 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Ser. No. 09/951,300 filed Sep. 13, 2001, now pending, which is a continuation-in-part of U.S. Ser. No. 09/949,344 filed Sep. 7, 2001, now abandoned, which is a continuation-in-part of U.S. Ser. No. 09/800,541 filed on Mar. 7, 2001, now pending, the contents of each of which are fully incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to methods for treatment and/or prevention of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and beta-cell apoptosis. More specifically, the methods and uses of the invention pertains to administration of a stable derivative of a GLP-1 analog in combination with administration of a non-thiazolidinedione peroxisome proliferating activated receptor (PPAR) ligand.
BACKGROUND OF THE INVENTION
[0003] Diabetes is a disorder of carbohydrate metabolism characterized by hyperglycemia and glucosuria resulting from insufficient production or utilization of insulin. Diabetes severely affects the quality of life of large parts of the populations in developed countries. Insufficient production of insulin is characterised as type 1 diabetes and insufficient utilization of insulin is type 2 diabetes.
[0004] Dyslipidemia, or abnormal levels of lipoproteins in blood plasma, is a frequent occurrence among diabetics. Dyslipidemia is typically characterized by elevated plasma triglycerides, low HDL (High Density Lipoprotein) cholesterol, normal to elevated levels of LDL (Low Density Lipoprotein) cholesterol and increased levels of small dense, LDL (Low Density Lipoprotein) particles in the blood. Dyslipidemia is one of the main contributors to the increased incidence of coronary events and deaths among diabetic subjects. Epidemiological studies have confirmed this by showing a several-fold increase in coronary deaths among diabetic subjects when compared with non-diabetic subjects. Several lipoprotein abnormalities have been described among diabetic subjects.
[0005] Insulin resistance is the diminished ability of insulin to exert its biologically action across a broad range of concentrations. In insulin resistance, the body secretes abnormally high amounts of insulin to compensate for this defect and a state of impaired glucose tolerance develops. Failing to compensate for the defective insulin action, the plasma glucose concentration inevitable rises, resulting in the clinical state of diabetes. It is being recognised that insulin resistance and relative hyperinsulinemia have a contributory role in obesity, hypertension, atherosclerosis and type 2 diabetes. The association of insulin resistance with obesity, hypertension and angina has been described as a syndrome, Syndrome X, having insulin resistance as the common pathogenic link.
[0006] Apoptosis is an active process of cellular self-destruction that is regulated by extrinsic and intrinsic signals occurring during normal development. It is well documented that apoptosis plays a key role in regulation of pancreatic endocrine beta cells. There is increasing evidence that in adult mammals the beta-cell mass is subject to dynamic changes to adapt insulin production for maintaining euglycemia in particular conditions, such as pregnancy and obesity. The control of beta cell mass depends on a subtle balance between cell proliferation, growth and programmed cell death (apoptosis). A disruption of this balance may lead to impairment of glucose homeostasis. For example, it is noteworthy that glucose intolerance develops with aging when beta cell replication rates are reduced and human autopsy studies repeatedly showed a 40-60% reduction of beta cell mass in patients with non-insulin-dependent-diabetes mellitus compared with nondiabetic subjects. It is generally agreed that insulin resistance is an invariable accompaniment of obesity but that normoglycemia is maintained by compensatory hyperinsulinemia until the beta cells become unable to meet the increased demand for insulin, at which point type 2 diabetes begins.
[0007] Attempts to treatment of the multiple abnormalities associated with diabetes have prompted for the administration of several anti-diabetic medicaments in order to address these abnormalities in the different patients. Examples of anti-diabetic medicaments are proteins such as insulin and GLP-1, and small molecules such as insulin sensitizers, insulin secretagogues and appetite regulating compounds.
[0008] Human GLP-1 is a 37 amino acid residue peptide originating from preproglucagon which is synthesized i.a. in the L-cells in the distal ileum, in the pancreas and in the brain. GLP-1 is an important gut hormone with regulatory function in glucose metabolism and gastrointestinal secretion and metabolism. Processing of preproglucagon to give GLP-1(7-36)amide, GLP-1(7-37) and GLP-2 occurs mainly in the L-cells. A simple system is used to describe fragments and analogues of this peptide. Thus, for example, Gly 8 -GLP-1(7-37) designates a fragment of GLP-1 formally derived from GLP-1 by deleting the amino acid residues Nos. 1 to 6 and substituting the naturally occurring amino acid residue in position 8 (Ala) by Gly. Similarly, Lys 34 (N ε -tetradecanoyl)-GLP-1(7-37) designates GLP-1(7-37) wherein the ε-amino group of the Lys residue in position 34 has been tetradecanoylated. PCT publications WO 98/08871 and WO 99/43706 disclose stable derivatives of GLP-1 analogs, which have a lipophilic substituent. These stable derivatives of GLP-1 analogs have a protracted profile of action compared to the corresponding GLP-1 analogs.
[0009] β-Aryl-α-oxosubstituted alkylcarboxylic acids (PCT publication WO 99/19313) and azolidinediones (PCT publication WO 97/41097) are insulin sensitizers useful as antidiabetic agents. Examples of these compounds are e.g. (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid (PCT publication WO 00/50414) and 5-[[4-[3-methyl-4-oxo-3,4-dihydro-2-quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione (PCT publication WO 97/41097). The compounds are useful for treatment and/or prophylaxis of e.g. type 2 diabetes, impaired glucose tolerance, dyslipidemia, and obesity.
[0010] PCT publication WO 00/78333 describes co-administration of GLP-1 and thiazolidinedione for treatment of NIDDM. A side effect of thiazolidinedione was stated to be reduced and a synergistic effect of combining GLP-1 with thiazolidinedione has been alleged.
[0011] Combined treatment with derivatives of GLP-1 analogs and non-thiazolidinedione PPAR ligands convey the benefits of both compounds while reducing side effects associated with each compound. Thus, there is a need for the therapeutic benefits of the individual compounds while simultaneously reducing the side effects.
SUMMARY OF THE INVENTION
[0012] One object of the present invention is to provide methods, which can effectively be used in the treatment or prophylaxis of type 1 diabetes, type 2 diabetes or dyslipidemia. Another object of the invention is to provide methods, which can effectively be used in the treatment or prophylaxis of impaired glucose tolerance, insulin resistance or obesity.
[0013] A further object of the present invention is to provide methods for treatment of beta-cell apoptosis.
[0014] The invention includes a method for the treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and beta-cell apoptosis, which method comprises administration of an effective amount of a stable derivative of a GLP-1 analog and an effective amount of a non-thiazolidinedione PPAR ligand to a patient in need thereof.
[0015] In one embodiment of the invention, the stable derivative of a GLP-1 analog is an analog with a lipophilic substituent, preferably Arg 34 , Lys 26 (N ε -(ε-Glu(N α -hexadecanoyl)))-GLP-1(7-37).
[0016] In another embodiment of the invention the non-thiazolidinedione PPAR ligand is an β-aryl-α-oxosubstituted alkylcarboxylic acid, preferably (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid or a salt thereof.
[0017] In yet another embodiment of the invention the non-thiazolidinedione PPAR ligand and the stable derivative of a GLP-1 analog are administered in suboptimal dosages.
[0018] In yet another embodiment of the invention the non-thiazolidinedione PPAR ligand and the stable derivative of a GLP-1 analog are administered in amounts and for a sufficient time to produce a synergistic effect.
DEFINITIONS
[0019] Co-Administration: In the context of the present application, co-administration of two compounds is defined as administration of the two compounds to the patient within 24 hours, including separate administration of two medicaments each containing one of the compounds as well as simultaneous administration whether or not the two compounds are combined in one formulation or whether they are in two separate formulations.
[0020] Effective Dosage: An effective dosage is a dosage which is sufficient in order for the treatment of the patient to be effective.
[0021] Medicament: Pharmaceutical composition suitable for administration of the pharmaceutically active compound to a patient.
[0022] Non-Thiazolidinedione PPAR Ligands: A class of compounds which through their binding to peroxisome proliferating activated receptors (PPARs), such as subtypes PPAR-alpha, PPAR-gamma and PPAR-delta, work as ‘lipid sensors’ providing the molecular link to glycaemic control and insulin sensitization in the treatment of type 2 diabetes and dyslipidemia. Normoglycaemic effect achieved upon ligand-PPAR interaction may be mediated through regulation of fatty acid homeostasis that apparently leads to enhanced insulin action with subsequent increase of glucose utilization in peripheral tissues such as muscle and fat, and suppression of hepatic gluconeogenesis, cf., The glucose fatty acid cycle (Randle P J, Garland P B, Hales C N, Newsholme E A. The glucose-fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; i:785-789.
[0023] Suboptimal Dosage: A suboptimal dosage of a pharmaceutically active compound is a dosage which is below the optimal dosage for that compound when used in single-compound therapy.
[0024] Synergistic Effect: A synergistic effect of two compounds is in terms of statistical analysis an effect which is greater than the additive effect which results from the sum of the effects of the two individual compounds.
[0025] Treatment: In this application treatment is defined as the management and care of a patient for the purpose of combating the disease, condition, or disorder and includes the administration of the active compounds to prevent the onset of the symptoms or complications, or alleviating the symptoms or complications, or eliminating the disease, condition, or disorder.
[0026] Stable Derivative of a GLP-1 Analog: A GLP-1 analog or a derivative thereof which exhibits an in vivo plasma elimination half-life of at least 10 hours in man, as determined by the method described below. Examples of stable derivatives of GLP-1 analogs can be found in WO 98/08871 and WO 99/43706. The method for determination of plasma elimination half-life of a compound in man is: The compound is dissolved in an isotonic buffer, pH 7.4, PBS or any other suitable buffer. The dose is injected peripherally, preferably in the abdominal or upper thigh. Blood samples for determination of active compound are taken at frequent intervals, and for a sufficient duration to cover the terminal elimination part (e.g. Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 (day 2), 36 (day 2), 48 (day 3), 60 (day 3), 72 (day 4) and 84 (day 4) hours post dose). Determination of the concentration of active compound is performed as described in Wilken et al., Diabetologia 43(51):A143, 2000. Derived pharmacokinetic parameteres are calculated from the concentration-time data for each individual subject by use of non-compartmental methods, using the commercially available software WinNonlin Version 2.1 (Pharsight, Cary, N.C., USA). The terminal elimination rate constant is estimated by log-linear regression on the terminal log-linear part of the concentration-time curve, and used for calculating the elimination half-life.
DETAILED DESCRIPTION OF THE INVENTION
[0027] It has been discovered that in the treatment of diabetes there is a synergistic effect of stable derivatives of GLP-1 analogs and non-thiazolidinedione PPAR ligands. Treatment of Zucker Diabetic Fatty (ZDF) rats with a combination of Arg 34 , Lys 26 (N ε (γ-Glu(N α -hexadecanoyl)))-GLP-1 (7-37) and a non-thiazolidinedione PPAR ligand was compared to the corresponding treatment of ZDF rats with Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) alone, and with non-thiazolidinedione PPAR ligand alone. Statistical analysis of the experimental results showed a significant interaction which demonstrate that combined treatment with non-thiazolidinedione PPAR ligands and Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) has profound synergistic effects on HbA 1c and the 24-hour plasma glucose profile.
[0028] A strong synergistic effect of two compounds permits the dosages of these compounds in the combined treatment to be below the optimal dosages of the individual compounds in single-compound treatment. Thus, these suboptimal dosages of the individual compounds reduce side effects since lower dosages are needed for the same therapeutic effect in the combined treatment.
[0029] Accordingly, the present invention relates to methods for treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and beta-cell apoptosis. The methods comprise administration of an effective amount of a stable derivative of a GLP-1 analog and administration of an effective amount of a non-thiazolidinedione PPAR ligand. The two compounds may be co-administered or they may be administered separately as two medicaments. Furthermore, the first compound may be administered in a regimen, which additionally comprises treatment with the second compound. Hence, according to the present invention the only provision is that there must be overlapping periods of treatment with the stable derivative of a GLP-1 analog and the non-thiazolidinedione PPAR ligand.
[0030] In one embodiment the stable derivative of a GLP-1 analog is Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1 (7-37). Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) is disclosed in WO 98/08871.
[0031] In another embodiment the non-thiazolidinedione PPAR ligand is (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid, or a salt thereof. (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid, or a salt thereof, is disclosed in WO 00/50414. A typically salt of this compound is the arginine salt disclosed in WO 00/63189.
[0032] In yet another embodiment the stable derivative of a GLP-1 analog and the non-thiazolidinedione PPAR ligand are co-administered to the patient. The two compounds may be administered as separately formulated compounds or they may be administered as one formulation comprising both compounds. In a further embodiment, the stable derivative of a GLP-1 analog is administered in a regimen, which additionally comprises administration of the non-thiazolidinedione PPAR ligand. In a preferred embodiment, the stable derivative of a GLP-1 analog is a parenteral medicament and the non-thiazolidinedione PPAR ligand is an oral medicament.
[0033] In yet another embodiment the method for treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and/or beta-cell apoptosis comprises administration of a stable derivative of a GLP-1 analog and (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid. In a still further embodiment the method for treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and/or beta-cell apoptosis comprises administration of Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1 (7-37) and a non-thiazolidinedione PPAR ligand.
[0034] In yet another embodiment, the stable derivative of a GLP-1 analog and the non-thiazolidinedione PPAR ligand are administered in suboptimal dosages, i.e. dosages lower than the optimal dosages for single compound therapy. In a further embodiment the stable derivative of a GLP-1 analog and the non-thiazolidinedione PPAR ligand are administered in sufficient amount and for a sufficient time to produce a synergistic effect, preferably for at least 4 weeks.
[0035] The subject or patient is preferably a mammal, more preferably a human.
[0036] Another aspect of the invention is a method for treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity or beta-cell apoptosis comprising administration of a stable derivative of a GLP-1 analog and 5-[[4-[3-Methyl-4-oxo-3,4-dihydro-2-quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione, or a salt thereof. 5-[[4-[3-Methyl-4-oxo-3,4-dihydro-2-quinazolinyl]methoxy]phenylmethyl]thiazolidine-2,4-dione is disclosed in WO 97/41097. In a preferred embodiment the 5-[[4-[3-Methyl-4-oxo-3,4-dihydro-2-quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione, or a salt thereof is administered in combination with Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37).
[0037] In another embodiment Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) is administered in combination with an insulin sensitizer selected from pioglitazone, rosiglitazone or a salt thereof. The insulin sensitizers pioglitazone and rosiglitazone are commercially available.
[0038] The route of administration may be any route, which effectively transports the active compound to the appropriate or desired site of action, such as oral, nasal, buccal, pulmonal, transdermal or parenteral.
[0039] Pharmaceutical compositions (or medicaments) containing a stable derivative of a GLP-1 analog, such as Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37), may be administered parenterally to patients in need of such a treatment. Parenteral administration may be performed by subcutaneous, intramuscular or intravenous injection by means of a syringe, optionally a pen-like syringe. Alternatively, parenteral administration can be performed by means of an infusion pump. A further option is a composition which may be a powder or a liquid for the administration of stable derivatives of GLP-1 analogs in the form of a nasal or pulmonal spray. As a still further option, the stable derivative of a GLP-1 analog can also be administered transdermally, e.g. from a patch, optionally a iontophoretic patch, or transmucosally, e.g. bucally. The above-mentioned possible ways to administer stable derivatives of GLP-1 analogs are not considered as limiting the scope of the invention.
[0040] Pharmaceutical compositions containing stable derivatives of GLP-1 analogs, such as Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37), may be prepared by conventional techniques, e.g. as described in Remington's Pharmaceutical Sciences, 1985 or in Remington: The Science and Practice of Pharmacy, 19 th edition, 1995.
[0041] Thus, the injectable compositions of stable derivatives of GLP-1 analogs can be prepared using the conventional techniques of the pharmaceutical industry which involves dissolving and mixing the ingredients as appropriate to give the desired end product.
[0042] According to one procedure, e.g. Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) is dissolved in an amount of water which is somewhat less than the final volume of the composition to be prepared. An isotonic agent, a preservative and a buffer are added as required and the pH value of the solution is adjusted—if necessary—using an acid, e.g. hydrochloric acid, or a base, e.g. aqueous sodium hydroxide as needed. Finally, the volume of the solution is adjusted with water to give the desired concentration of the ingredients.
[0043] Examples of isotonic agents are sodium chloride, mannitol and glycerol.
[0044] Examples of preservatives are phenol, m-cresol, methyl p-hydroxybenzoate and benzyl alcohol.
[0045] Examples of suitable buffers are sodium acetate and sodium phosphate.
[0046] Further to the above-mentioned components, solutions containing a stable derivative of a GLP-1 analog may also contain a surfactant in order to improve the solubility and/or the stability of the peptide.
[0047] According to one embodiment of the present invention, the stable derivative of a GLP-1 analog is provided in the form of a composition suitable for administration by injection. Such a composition can either be an injectable solution ready for use or it can be an amount of a solid composition, e.g. a lyophilised product, which has to be dissolved in a solvent before it can be injected. The injectable solution preferably contains not less than about 0.1 mg/ml, typically from 0.1 mg/ml to 5 mg/ml, such as from 1 mg/ml to 5 mg/ml of stable derivative of GLP-1 analog.
[0048] Derivatives of GLP-1 analogs such as Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) can be used in the treatment of various diseases. The optimal dose level for any patient (effective amount) will depend on the disease to be treated and on a variety of factors including the efficacy of the specific stable derivative of a GLP-1 analog employed, the age, body weight, physical activity, and diet of the patient, on a possible combination with other drugs, and on the severity of the case.
[0049] Pharmaceutical compositions (or medicaments) containing non-thiazolidinedione PPAR ligands, such as (−)-2-ethoxy-3-(4-(2-phenoxazin-1 0-yl-ethoxy)-phenyl)-propionic acid or a salt thereof, may be administered by suitable dosage forms such as oral, nasal, pulmonal, buccal or transdermal to patients in need of such a treatment. The preferred route of administration of non-thiazolidinedione PPAR ligands is orally. Pharmaceutical compositions containing non-thiazolidinedione PPAR ligands may be prepared by conventional techniques, e.g. as described in Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, Pa., 1995.
[0050] Typical compositions of e.g. (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid include a crystalline compound of the present invention associated with a pharmaceutically acceptable excipient, which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier, which can be in the form of a capsule, sachet, paper or other container. In making the compositions, conventional techniques for the preparation of pharmaceutical compositions may be used. For example, the active compound will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of a ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be solid, semi-solid, or liquid material, which acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container for example in a sachet. Some examples of suitable carriers are water, salt solutions, alcohol's, polyethylene glycol's, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, cyclodextrin, amylose, magnesium stearate, talc, gelatine, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents. The formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art.
[0051] The pharmaceutical compositions can be sterilized and mixed, if desired, with auxiliary agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or colouring substances and the like, which do not deleteriously react with the active compound.
[0052] If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.
[0053] For nasal administration, the preparation may contain the compound of the present invention dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application. The carrier may contain additives such as solubilizing agents, e.g. propylene glycol, surfactants, absorption enhancers such as lecithin (phosphatidyicholine) or cyclodextrin, or preservatives such as parabenes.
[0054] For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
[0055] Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, cornstarch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.
[0056] A typical tablet of a non-thiazolidinedione PPAR ligand, e.g. (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid, which may be prepared by conventional tabletting techniques, may contain:
Core: Active compound 5 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, microcryst. (Avicel) 70 mg Modified cellulose gum (Ac-Di-Sol) 7.5 mg Magnesium stearate Ad. Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx. 0.9 mg *Acylated monoglyceride used as plasticizer for film coating.
[0057] The non-thiazolidinedione PPAR ligands are effective over a wide dosage range. For example, in the treatment of adult humans, dosages from 0.01 mg/day to 10 mg/day, preferably from 0.1 mg/day to 3 mg/day may be used. A most preferable dosage is less than 2 mg/day. In choosing a regimen for patients it may frequently be necessary to begin with a dosage of from about 2 to about 10 mg per day and when the condition is under control to reduce the dosage as low as from about 0.01 to about 3 mg per day. The exact dosage will depend upon the mode of administration, on the therapy desired, the administration form, the subject to be treated and the body weight of the subject to be treated.
[0058] Generally, the non-thiazolidinedione PPAR ligands of the present invention are dispensed in unit dosage form comprising from about 0.01 to about 10 mg of active ingredient together with a pharmaceutically acceptable carrier per unit dosage.
[0059] Usually, dosage forms suitable for oral, nasal, pulmonary or transdermal administration comprise from about 0.01 mg to about 10 mg, preferably from about 0.1 mg to about 3 mg of the compound of the invention admixed with a pharmaceutically acceptable carrier or diluent.
[0060] Irrespective of the dosage forms for the stable derivative of a GLP-1 analog and for the non-thiazolidinedione PPAR ligand, they may advantageously be supplied as a kit for treatment of type 1 diabetes, type 2 diabetes, dyslipidemia, impaired glucose tolerance, insulin resistance, obesity and/or beta-cell apoptosis. The kit may contain a single dosage form or it may contain two dosage forms, i.e. one for each compound to be administered.
[0061] The combined treatment with a stable derivative of a GLP-1 analog and a non-thiazolidinedione PPAR ligand may also be combined with a third or more further pharmacologically active substances, e.g. selected from antidiabetic agents, antiobesity agents, appetite regulating agents, antihypertensive agents, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complications and disorders resulting from or associated with obesity. Examples of these pharmacologically active substances are: Insulin, GLP-1 agonists, sulphonylureas, biguanides, meglitinides, glucosidase inhibitors, glucagon antagonists, DPP-IV (dipeptidyl peptidase-IV) inhibitors, inhibitors of hepatic enzymes involved in stimulation of gluconeogenesis and/or glycogenolysis, glucose uptake modulators, compounds modifying the lipid metabolism such as antihyperlipidemic agents and antilipidemic agents as HMG CoA inhibitors (statins), compounds lowering food intake, RXR agonists and agents acting on the ATP-dependent potassium channel of the β-cells; Cholestyramine, colestipol, clofibrate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucol, dextrothyroxine; β-blockers such as alprenolol, atenolol, timolol, pindolol, propranolol and metoprolol, ACE (angiotensin converting enzyme) inhibitors such as benazepril, captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril, calcium channel blockers such as nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem and verapamil, and α-blockers such as doxazosin, urapidil, prazosin and terazosin; CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melanocortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releasing factor) agonists, CRF BP (corticotropin releasing factor binding protein) antagonists, urocortin agonists, β3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, mixed serotonin and noradrenergic compounds, 5HT (serotonin) agonists, bombesin agonists, galanin antagonists, growth hormone, growth hormone releasing compounds, TRH (thyreotropin releasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA agonists (bromocriptin, doprexin), lipase/amylase inhibitors, RXR (retinoid X receptor) modulators, TR β agonists; histamine H3 antagonists.
[0062] It should be understood that any suitable combination of the compounds according to the invention with one or more of the above-mentioned compounds and optionally one or more further pharmacologically active substances are considered to be within the scope of the present invention.
EXPERIMENTAL
[0063] Synergistic effect of combining (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid and Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) on glucose and HbA 1c (glycosylated hemoglobin) in the male ZDF rat.
[0000] Study Design:
[0064] Ninety male ZDF rats aged 15-16 weeks were used in the study. Before treatment start, measurements of glucose and HbA 1c were performed. All animals were overtly diabetic at the beginning of the study. Animals were allocated into the following 4 treatment groups:
[0000] Group 1: Vehicle-1+Vehicle-2 (n=10)
[0000] Group 2: (−)-2-ethoxy-3-(4-(2-phenoxazin-1 0-yl-ethoxy)-phenyl)-propionic acid, 1 mg/kg+Vehicle-2 (n=10)
[0000] Group 3: Vehicle-1+Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37), 50 μg/kg (n=10)
[0000] Group 4: (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid, 1 mg/kg+Arg 34 , Lys 26 (N ε (γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37), 50 μg/kg (n=10)
[0065] (−)-2-Ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid and Vehicle-1 were administered by oral gavage once daily at approx. 07:30. Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) and Vehicle-2 were administered subcutaneously twice daily at approx. 07:30 and 14:30.
[0066] After four weeks treatment, HbA 1c was measured and 24-hour glucose profiles were assessed.
[0000] Results:
[0067] The findings of group 1, 2, 3 and 4 are listed in the table below (mean±SEM). Delta HbA 1c refers to the numerical difference between the measurement after treatment and the measurement before treatment. Glucose 24hAUC refers to the total area under the glucose concentration curve during the 24-hour period. A two-way analysis of variance was performed for each parameter and the significance of the interaction term evaluated.
P value of interaction term in two- Group 1 Group 2 Group 3 Group 4 way ANOVA Delta HbA 1c 1.24 ± 0.17 −0.81 ± 0.36 0.28 ± 0.19 −3.78 ± 0.18 p < 0.0002 (% points) Glucose 24 hAUC 538 ± 6 456 ± 38 508 ± 4 256 ± 27 p < 0.001 (mM × h)
[0068] The highly significant interaction terms demonstrate that four weeks combination treatment with (−)-2-ethoxy-3-(4-(2-phenoxazin-10-yl-ethoxy)-phenyl)-propionic acid (1 mg/kg, once daily) and Arg 34 , Lys 26 (N ε -(γ-Glu(N α -hexadecanoyl)))-GLP-1(7-37) (50 μg/kg, twice daily) has synergistic (greater than additive) effects on HbA 1c and 24-hour glucose profiles in overtly diabetic ZDF rats.
[0069] All patents, patent applications, and literature references referred to herein are hereby incorporated by reference in their entirety.
[0070] Many variations of the present invention will suggest themselves to those skilled in the art in light of the above detailed description. Such variations are within the full intended scope of the appended claims. | The present invention provides methods and compositions for treatment and/or prevention of type 1 and type 2 diabetes, dyslipdemia, impaired glucose tolerance, insulin resistance, obesity, and beta-cell apoptosis, as well as methods for increasing the size and number of beta-cells in a subject and/or stimulating beta-cell proliferation, which comprise administering both a stable GLP-1 analogue and a non-thiazolidinedione PPAR ligand. | 0 |
BACKGROUND OF THE INVENTION
Description of the Related Art
Catalysts for olefin co-polymerization with functional monomers are rare compared to their olefin polymerization counterparts (See reference 1). PCT patent application WO01/92348 describes the co-polymerization of ethylene using zwitterionic nickel complexes requiring Lewis acids. Lewis Acids are deactivated by functionalities and they promote unwanted secondary reactions, e.g., chain transfer, which are detrimental to the polymer chain growth. Other types of neutral catalysts, capable of homo-and co-polymerizing olefins, have been reported by Younkin et al. (See reference 2). The catalysts are neutral species that do not require an activator, however, they are prone to an induction period and have lower activity compared to cationic systems which perform in the presence of methylaluminoxanes and Lewis acids.
Furthermore, co-polymerization catalysts displaying characteristics of living polymerizations, are even rarer (See reference 3). The ideal catalyst-system would produce a living or quasi-living polymer. There are seven accepted criteria for living polymerizations with living catalyst systems. These are: 1) The polymerization proceeds to a complete monomer conversion and restarts upon further addition of the monomer; 2) Linear dependence of Mn with time; 3) The number of active sites remains constant during polymerization; 4) The molecular weight can be precisely controlled by stoichiometry; 5) A narrow PDI; 6) Sequential monomer addition results in a block co-polymer; and 7) An end-functionalized co-polymer can be synthesized. Systems that partially fulfill this list of criteria are termed “quasi-living”. Jansen et. al., reported quasi-living catalysts for ethylene and norbornene co-polymerization (See reference 4). However, no functionalized norbornene derivatives were co-polymerized.
SUMMARY OF THE INVENTION
The present invention provides a method of using a novel quasi-living metal catalyst for homo-polymerization of olefins such as ethylene, α-olefins and functionalized olefins and for co-polymerization of olefins with functionalities such as acetates (e.g., 5-norbornen-2-yl acetate). Specifically, the catalyst comprises a combination of two neutral metal complexes, e.g., L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) [L=N-(2,6-diisopropylphenyl)-2-(2,6-diisopropylphenylimino)propanamide] (See reference 5) and Ni(COD) 2 (COD=cyclooctadiene) that produces high molecular weight polymers, found experimentally to be about (M n ) 2.20×10 4 to about 1.10×10 5 for ethylene homo-polymers and about (M n ) 3.90×10 4 to about 1.10×10 5 for acetate-functionalized co-polymers with narrow molecular weight distributions, in the range of about 1.3-1.6 for ethylene homo-polymers and about 1.2-1.6 for acetate-functionalized co-polymers, respectively.
In one embodiment, the present invention discloses a process comprising combining an amount of a first olefin monomer with an initiator metal compound so that a polymer chain is generated. The initiator metal compound comprises a Group VIII transition metal complex, the complex comprising a combination of any two neutral metal complexes of the general formulas (I-IV)
wherein:
M is a Group VIII transition metal such as Ni, Pt, or Pd;
A is a three electron donor such as π-allyl, substituted π-allyl, π-benzyl, or substituted π-benzyl;
X is N or P;
Y is O, CH 2 , or S;
L is N or P or a structure that is capable of forming a neutral two electron donor ligand;
L 2 is a neutral monodentate ligand;
L 1 is a neutral monodentate ligand which may be displaced by the olefin, and L 2 is an monoanionic monodentate ligand, or L 1 and L 2 taken together are a monoanionic bidentate ligand, provided that the monoanionic monodentate ligand or the monoanionic bidentate ligand may add to the olefin;
B is an atom or group of atoms connecting covalently the carbonyl group and L;
R 1 each independently is hydrogen, hydrocarbyl, substituted hydrocarbyl bearing functional group, or other hydrocarbyl group;
R 2 each independently is hydrogen, hydrocarbyl, substituted hydrocarbyl bearing functional group, or other hydrocarbyl group; and
R 3 each independently is hydrogen, hydrocarbyl, substituted hydrocarbyl bearing functional group, or other hydrocarbyl group; and combining an amount of a second olefin monomer with the polymer chain so that the second olefin monomer is added to the polymer chain. The process of the present invention includes continuous olefin monomer feeds to the metal compound.
In another embodiment of the present invention, the amount of the first and/or second olefin monomers is depleted, after the polymer chain is generated.
In yet another embodiment of the invention the transition metal of the metal catalyst is nickel.
In a further embodiment of the invention, the first and second olefin monomers are the same or different and are 5-norbornen-2-yl acetate or ethylene.
In a further embodiment of the present invention, R 1 =R 3 =(2,6-diisopropylphenyl); R 2 =methyl; X=L=Nitrogen; Y=Oxygen; B=carbon; L 1 =CH 2 Ph; and L 2 =PMe 3 .
In another embodiment, the present invention discloses a process for the quasi-living homo-polymerization and quasi-living co-polymerization of an olefin wherein the olefin is selected from one or more of R 4 CH═CH 2 , cyclopentene, a styrene, a norbornene, or a polar olefin of the general formula H 2 C═CR 5 (CH 2 ) S CO 2 R 6 , substituted cyclopentene, substituted styrene, norbornene derivative bearing functional group or other hydrocarbyl group, in the presence of a catalyst derived from a combination of two neutral transition metal complexes, at a temperature of about −100° C. to about 200° C. R 4 , R 5 and R 6 are each independently hydrogen, hydrocarbyl group, substituted hydrocarbyl bearing functional group, or other hydrocarbyl group and s is an integer from 0 to 100.
In yet a further embodiment of the invention, products prepared by the above-described processes are disclosed. These polymer products are characterized by having a narrow molecular weight distribution of about 1.2-1.6.
In still a further embodiment of the present invention, a polymer product prepared by the above-described processes is a block co-polymer, a star-shaped polymer, a graft polymer or an alternating polymer.
In still yet a further embodiment of the present invention, a polymer is made by the quasi-living co-polymerization of ethylene with 5-norbornen-2-yl acetate. The polymer has enhanced hydrophilic properties.
The quasi-living characteristics of the catalyst facilitates the generation of a novel polymeric product, such as functionalized block co-polymers that are of substantial industrial interest. The present invention displays quasi-living characteristics for ethylene homo-polymerization and also for co-polymerization with a functionalized polar monomer, thereby underscoring the versatility of the catalyst.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graphical representation of an embodiment of the present invention showing the number average molecular weight (M n ) versus time of the samples in Table 1 and described in Examples 2, 3, 4 and 5;
FIG. 2 is a Gel Permeation Chromatography (GPC) trace of the polyethylene obtained in Examples 4 and 5; and
FIG. 3 is a graphical representation of an embodiment of the present invention showing M n versus time for the co-polymerization of ethylene with 5-norbornen-2-yl acetate described in Examples 7, 8, 9 and 10 and shown in Table 3.
DETAILED DESCRIPTION OF THE INVENTION
The following examples were performed under an inert atmosphere using standard glove box and Schlenk techniques. Solvents like toluene, tetrahydrofuran (THF), hexane and pentane were distilled from benzophenone ketyl as required. All polymerization reactions were carried out in a glass reactor as described previously (see Reference 5). Toluene for polymerization runs was distilled from sodium/potassium alloy. Nickel was chosen as the transition metal for the metal complex. L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) [L=N-(2,6-diisopropylphenyl)-2-(2,6-diisopropylphenylimino)propanamide](see Reference 5) and Ni(COD) 2 (see Reference 6) were synthesized as reported and purified by re-crystallization prior to polymerization use. NMR spectra were obtained using Varian Unity 400 or 500 spectrometers. 1 H NMR spectra of the polymers were obtained in mixed solvent (C 6 D 6 /1,2,4-trichlorobenzene 1:4 ratio in volume) at about 115° C. GPC analyses were done at Mitsubishi Chemical Corporation., Japan, in o-dichlorobenzene at about 135° C.
The quasi-living nature of the nickel catalyst, L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) and Ni(COD) 2 , for ethylene homo-polymerization was established based on the following criteria that are characteristic of living polymerization.
EXAMPLE 1
Molecular Weight Information
Time dependence studies of ethylene homo-polymerization were carried out. A toluene solution containing [L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 0.34 mM) and Ni(COD) 2 (about 0.85 mM) was pressurized with about 100 psi of ethylene and stirred at about 20° C. The reactor was depressurized after varied amounts of time and the reaction mixture was quenched immediately with acetone. The polyethylene polymers were then isolated by filtratration and were then dried in vacuum.
As typical of living polymerizations, a linear increase of the number average molecular weight (M n ) with time was observed, as shown in Table 1 and FIG. 1 .
TABLE 1
Time
(min)
M w
M n
M w /M n
3
3.67 × 10 4
2.20 × 10 4
1.6
5
4.52 × 10 4
3.40 × 10 4
1.3
10
1.25 × 10 5
9.10 × 10 4
1.4
20
1.49 × 10 5
1.10 × 10 5
1.3
Table 1 shows the weight average molecular weight (M w ) and the number average molecular weight (M w ) as a function of time for ethylene homo-polymerization. L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 0.34 mM); Ni(COD) 2 (about 0.85 mM); about 100 psi ethylene pressure and about 20° C. temperature. Consistent with being a quasi-living polymerization system, narrow molecular weight distributions, M w /M n , in the range of about 1.3-1.6 were observed in all cases (see Table 1).
A living system has a number of active sites which equals the number of polymer chains. An estimate of the molecular weight of the polymer chains was obtained according to the calculations shown in Table 2 below.
For example, the 4 th sample entry of Table 2 shows the total amount of ethylene consumed was about 1222 standard cubic cm (sec) which equals about 1.527 g (0.055 moles) of ethylene (1 sec=1.25×10 −3 g of ethylene at STP. STP is standard temperature and pressure, i.e., 0 C. and 760 mm of mercury (1.01 kPa). The L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) loading was about 10×10 −6 moles. Therefore, considering a process whereby the rate of initiation is on the order of propagation, the number of ethylene units in a polymer chain per active-site corresponds to about 5500 (0.055 moles of ethylene/10×10 −6 moles of Ni catalyst). The molecular weight of the polymer under these conditions corresponds to about 1.54×10 5 {5500×MW ethylene (28 g/mole)}. For comparison, the experimental values were about 1.49×10 5 (M w ) and 1.10×10 5 (M n ). Similar estimates were made for other experiments shown by the 1 st , 2 nd , and 3 rd sample entries in Table 2.
Table 2 shows that the calculated molecular weights are in agreement with the experimental molecular weight values for the samples shown in Table 1 and described in Examples 2, 3, 4 and 5. Thus, the number of the active-sites corresponded to the number of initiator molecules used.
TABLE 2
C 2 H 4
Uptake
Polymer
MW
M w
M n
Mass flow
Estimated Value
Isolated
Time
Calc.
Exp.
Exp.
(scc)
(g)
(g)
(min)
(10 4 )
(10 4 )
(10 4 )
133
0.166
0.140
3
1.66
3.67
2.20
264
0.329
0.173
5
3.30
4.52
3.40
986
1.232
1.096
10
12.3
12.5
9.10
1222
1.527
1.322
20
15.4
14.9
11.0
The data in FIG. 1 and Tables 1-2 establish the quasi-living nature of the nickel catalyst with regards to ethylene homo-polymerization.
EXAMPLE 2
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 10 μmol; 1.00 g of 8.77 mM solution in toluene) and Ni(COD) 2 (about 25 μmol; 1.25 g of 17.6 mM solution in toluene) and toluene (about 23.7 g), such that the final volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 3 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. The reaction produced about 0.140 g of polyethylene polymer. The activity of the catalyst was about 499 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, 135° C.): M w =about 3.67×10 4 , M w /M n =about 1.6. DSC Analysis: T m =about 126.4° C. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 10.2 methyl branches per 1000 methylene carbons.
EXAMPLE 3
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 10 μmol; 1.00 g of 8.77 mM solution in toluene) and Ni(COD) 2 (about 25 μmol; 1.25 g of 17.6 mM solution in toluene and toluene (about 23.7 g) such that the final volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 5 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. The reaction produced about 0.173 g of polyethylene polymer. The activity of the catalyst was about 495 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): M w =about 4.52×10 4 , M w /M n =about 1.3. DSC Analysis: T m =about 127.9° C. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 12.1 methyl branches per 1000 methylene carbons.
EXAMPLE 4
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 10 μmol; 1.00 g of 8.77 mM solution in toluene) and Ni(COD) 2 (about 25 μmol; 1.25 g of 17.6 mM solution in toluene) and toluene (about 23.7 g), such that the final volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 10 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. The reaction produced about 1.10 g of polyethylene polymer. The activity of the catalyst was about 821 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): M w =about 1.25×10 5 , M w /M n =about 1.4. DSC Analysis: T m =about 123.6° C. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, 115° C.): 14.2 methyl branches per 1000 methylene carbons. The GPC trace of the polyethylene obtained shows a unimodal molecular weight distribution is shown in FIG. 2 .
EXAMPLE 5
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 10 μmol; 1.00 g of 8.77 mM solution in toluene) and Ni(COD) 2 (about 25 μmol, 1.25 g of 17.6 mM solution in toluene) and toluene (about 23.7 g) such that the final volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 20 minutes and acetone was added to quench to polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. The reaction produced about 1.322 g of polyethylene polymer. The activity of the catalyst was about 482 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): MW=about 1.49×10 5 , M w /M n =about 1.3. DSC Analysis: T m =about 125.6° C. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 7.8 methyl branches per 1000 methylene carbons. The GPC trace of the polyethylene obtained shows a unimodal molecular weight distribution is shown in FIG. 2 .
EXAMPLE 6
The quasi-living nature of the nickel catalyst, for co-polymerization of ethylene with 5-norbornen-2-yl acetate was then tested.
Molecular Weight Information
Time dependence studies of ethylene co-polymerization with 5-norbornen-2-yl acetate were carried out. Specifically, a toluene solution containing L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 0.68 mM), Ni(COD) 2 (about 1.70 mM) and 5-norbornen-2-yl acetate (about 0.15 M) was pressurized with about 100 psi of ethylene and stirred at about 20° C. The reactor was depressurized after varied amounts of time, as seen in Table 3, and the reaction mixture was quenched immediately with acetone. The functionalized co-polymers were then isolated by filtration and were dried in vacuum.
In case of the ethylene/5-norbornen-2-yl acetate co-polymerization a linear increase of the number average molecular weight (Mn) with time was observed as shown in Table 3 and FIG. 3 . Such a liner relationship is characteristics of a living polymerization.
TABLE 3
Time
(min)
M w
M n
M w /M n
15
4.68 × 10 4
3.90 × 10 4
1.2
30
6.71 × 10 4
4.20 × 10 4
1.6
60
1.08 × 10 5
8.00 × 10 4
1.4
90
1.56 × 10 5
1.10 × 10 5
1.4
Table 3 shows the weight average molecular weight (M w ) and number average molecular weight (M n ) as a function of time for ethylene co-polymerization with 5-norbornen-2-yl acetate. [L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 0.68 mM); Ni(COD) 2 (about 1.70 mM); 5-norbornen-2-yl acetate (about 0.15 M); about 100 psi ethylene pressure and about 20° C. temperature].
Consistent with being a quasi-living polymerizing system, narrow molecular weight distributions in the range of about 1.2-1.6 were observed in all cases (Table 3). The data in FIG. 3 and Table 3 are consistent with the quasi-living co-polymerization of ethylene with 5-norbornen-2-yl acetate initiated by a nickel catalyst formed by a combination of two neutral complexes, L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) and Ni(COD) 2 .
EXAMPLE 7
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 20 μmol 2.00 g of 8.77 mM solution in toluene), Ni(COD) 2 (about 50 μmol; 2.50 g of 17.6 mM solution in toluene), 5-norbornen-2-yl acetate (about 4.50 mmol; 3.00 g of 1.30 M solution in toluene) and toluene (about 18.45 g), such that the total volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 15 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. About 0.160 g of ethylene/5-norbornen-2-yl acetate co-polymer was obtained. The activity of the catalyst with respect to ethylene consumption was about 96 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, 135° C.): MW=about 4.68×10 4 , M w /M n =about 1.2. DSC Analysis: T m =broad glass transition. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 22.8 methyl branches per 1000 methylene carbons. 7.3% incorporation of norbornenyl group.
EXAMPLE 8
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 20 μmol; 2.00 g of 8.77 mM solution in toluene), Ni(COD) 2 (about 50 μmol; 2.50 g of 17.6 mM solution in toluene), 5-norbornen-2-yl acetate (about 4.50 mmol; 3.00 g of 1.30 M solution in toluene) and toluene (about 18.45 g) such that the total volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 30 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. About 0.526 g of ethylene/5-norbornen-2-yl acetate co-polymer was obtained. The activity of the catalyst with respect to ethylene consumption was about 63 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): M w =about 6.71×10 4 , M w /M n =about 1.6. DSC Analysis: T m =about 88° C. (broad). 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 30.7 methyl branches per 1000 methylene carbons. 14.5% incorporation of norbornenyl group.
EXAMPLE 9
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 20 μmol; 2.00 g of 8.77 mM solution in toluene), Ni(COD) 2 (about 50 μmol; 2.50 g of 17.6 mM solution in toluene), 5-norbornen-2-yl acetate (about 4.50 mmol; 3.00 g of 1.30 M solution in toluene) and toluene (about 18.45 g) such that the total volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 60 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. About 0.843 g of ethylene/5-norbornen-2-yl acetate co-polymer was obtained. The activity of the catalyst with respect to ethylene consumption was about 45 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): M w =about 1.08×10 5 , M w /M n =about 1.4. DSC Analysis: T m =broad glass transition. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 30.8 methyl branches per 1000 methylene carbons. 10.4% incorporation of norbornenyl group.
EXAMPLE 10
A glass reactor was loaded inside a glove box with L( i Pr 2 )Ni(CH 2 Ph)(PMe 3 ) (about 20 μmol; 2.00 g of 8.77 mM solution in toluene), Ni(COD) 2 (about 50 μmol; 2.50 g of 17.6 mM solution in toluene), 5-norbornen-2-yl acetate (about 4.50 mmol; 3.00 g of 1.30 M solution in toluene) and toluene (about 18.45 g) such that the total volume of the toluene solution was about 30 mL. The glass reactor was sealed inside the glove box and was attached to a vacuum/nitrogen line manifold. Ethylene was fed continuously into the reactor at about 100 psi and the pressurized reaction mixture was stirred at about 20° C. Ethylene was vented after about 90 minutes and acetone was added to quench the polymerization. The precipitated polymer was collected by filtration and dried under high vacuum overnight. About 1.031 g of ethylene/5norbornen-2-yl acetate co-polymer was obtained. The activity of the catalyst with respect to ethylene consumption was about 36 kg mol −1 h −1 .
Polymer Characterization: GPC Analysis (o-dichlorobenzene, about 135° C.): M w =about 1.56×10 5 , M w /M n =about 1.4. DSC Analysis: T m =broad glass transition. 1 H NMR (C 6 D 6 /1,2,4-trichlorobenzene, about 115° C.): 9.47 methyl branches per 1000 methylene carbons. 7.20% incorporation of norbornenyl group.
REFERENCES
The following references are hereby incorporated by reference: 1. Ittel, S. D.; Johnson, L. K.; Brookhart, M. Chem. Rev. 2000, 100, 1169 (and references therein); 2. Younkin, T.; Connor, E. F.; Henderson, J. L; Friedrich, S. K.; Grubbs, R. H.; Bansleben, D. A. Science, 2000, 287, 460; WO 9842664.; WO 9842665; 3. Coates, G. W.; Hustad, P. D.; Reinartz, S. Angew. Chem. Int. Ed. 2002, 41, 2236 (and references therein); 4. Jansen, J. C.; Mendichi, R.; Locatelli, P.; Tritto, I. Macromol. Rapid Commun. 2001, 22, 1394; 5. Lee, B. Y.; Bazan, G. C.; Vela, J.; Komon, Z. J. A.; Bu, X. J. Am. Chem . Soc. 2001, 123, 5352; and 6. Schunn, R. A.; Ittel, S. D.; Cushing, M. A. Inorg. Synth. 1990, 28, 94.
These and other changes and modifications are intended to be included within the scope of the invention. While for the sake of clarity and ease of description, several specific embodiments of the invention have been described; the scope of the invention is intended to be measured by the claims as set forth below. The description is not intended to be exhaustive or to limit the invention to the form disclosed. Other variations of the invention will be apparent in light of the disclosure and practice of the invention to one of ordinary skill in the art to which the invention applies. | Methods and compositions for the generation of quasi-living catalysts for homo-polymerization of olefins such as ethylene, α-olefins and functionalized olefins and for the co-polymerization of olefins with functionalized monomers is disclosed. A process for producing these homo- and co-polymers is also disclosed. A polymeric material with enhanced hydrophilic properties, generated by the co-polymerization of ethylene with 5-norbornen-2-yl acetate, is also disclosed. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a non-provisional application claiming priority based on provisional application Ser. No. 60/378,023, filed May 13, 2002.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
This invention was made with Government support under Subcontract No. 4000000723 funded by the Government. The Government has certain rights in the invention.
BACKGROUND OF THE INVENTION
1. Field of Invention
This invention relates to filters and filter systems which are operable at elevated temperatures and capable of extracting volatilizable particulates from a gas stream. In particular, this invention relates to ceramic fiber-paper based filters which may be regenerated in situ employing microwave energy.
2. Background of the Invention
Heretofore, it has been known in the art that ceramic fibers may be formed into a ceramic paper. It is also suggested in the prior art that this paper may be corrugated and wound into a cylindrical filter for the capture of volatilizable particulates from a gas stream, and that the filter may be regenerated employing microwaves.
However, these prior art filters and/or the systems within which they are employed suffer from problems of premature clogging of the entry ends of the tubular chambers defined by the corrugations, and from inadequate capacity to accommodate the anticipated or actual overall flow of gas streams through the filter, resulting in excessive pressure drop across the filter, at times creating undesirable or even disastrous results, and/or regeneration only during shut-down or diversion of the source of the gas stream, such diversion effectively taking the filtration system offline.
BRIEF SUMMARY OF THE INVENTION
In accordance with one aspect of the present invention, there is provided at least one filter module comprising a housing which defines an inlet and an outlet for the passage of a gas stream into and out of the housing. Within the housing there is disposed a pleated ceramic fiber-based filter medium which separates the interior of the housing into at least two filtration chambers, one of which is in fluid communication with the inlet to the housing and a second one of which is in fluid communication with the outlet of the housing. As desired, multiple further filtration chambers may be interposed in fluid flow communication between the “inlet” chamber and the “outlet” chamber. A gas stream entering the inlet chamber passes through the multiple pleats of the filter medium of each chamber wherein particulates are extracted from the gas stream and accumulate on the filter medium. The filtered air stream passes through the outlet chamber and any intervening chamber, and exits the housing through the outlet thereof. As desired, the inlet and/or the inlet to the housing may be in the form of a plenum extending along one side of the housing.
In accordance with a further aspect of the invention, there is provided an outlet plenum which extends along the outlet side of the housing (opposite the inlet side). In one embodiment, this plenum serves the dual function of a pathway for conveying away the exhaust gas stream from the filter and as a selectable pathway for the transmission of microwaves into the filter housing.
In one embodiment, the overall filter structure comprises at least one, and preferably a plurality of individual housing/pleated filter subassemblies, all aligned in a common plane or parallel planes so that their respective outlet sides are aligned such that they share a common elongated exhaust plenum. Within, and concentrically of, the interior of this exhaust plenum there is provided a rotatable, preferably tubular, member. This member includes a plurality (one for each filter subassembly or grouping of filter subassemblies) of ceramic microwave-permeable segments spaced apart from one another along the length of the wall of the tubular member. The remainder of the tube includes holes of a proper diameter to stop 2.45 GH microwaves while allowing the free passage of exhaust gas therethrough. Thus, each segment is sized and designed to cover a respective one or ones of the outlets of the aligned outlets of the multiple subassemblies to define a transparent window for the admission of microwaves (while preventing the flow of exhaust gas therepast), but stopping exhaust flow, passing along the length of the tubular member, into a respective one or ones of the filter subassemblies when the segment is in register with the outlet from a respective filter subassembly. In this embodiment, each segment also is positioned at a location which is progressively rotated about the outer circumferential wall of the tubular member. In one embodiment, no two filter subassemblies are open to microwaves at any given time. In other embodiments, only a limited number of filter subassemblies are open to microwaves at any given time Thus, through selective rotation of the tubular member about its longitudinal axis, admission of microwaves into a filter subassembly may be restricted to only a single filter subassembly or a selected group of filter subassemblies, at any given time, thereby providing for the regeneration of a single filter subassembly or selected group of filter subassemblies while the remaining filter subassemblies remain available for receiving and filtering of the inlet gas stream flowing through the inlet plenum and exhausting of the cleaned gas stream via the exhaust plenum. This selective regeneration of the filter subassemblies is conducted in situ and provides for sequential regeneration of the multiple subassemblies, thereby preventing any material interruption of the flow of the gas stream through the overall filter system, hence the ability of the overall filter system to accommodate a substantially larger volume of gas flow, and avoiding undesired pressure drop (back pressure) across any one of the multiple filter subassemblies, all without deleterious effects on the normal operation of the generator of the contaminated gas stream, e.g., a diesel engine.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
FIG. 1 is a representation of one embodiment of a filter system including various features of the present invention, including multiple stacked filter subassemblies;
FIG. 2 is a representation of the gas exhaust end of the filter depicted in FIG. 1 and partly cutaway to depict various internal features of the filter;
FIG. 3 is a representation, partly cutaway, depicting a filter system including various features of the present invention, including a single filter subassembly;
FIG. 4 is representation of an elongated tubular member for rotatable disposition within the exhaust plenum of the filter depicted in FIG. 1 ;
FIG. 5 is a representation of one embodiment of a housing/pleated ceramic fiber paper filter medium module suitable for use in the filter of the present invention; and,
FIG. 6 is a exploded view representing a top comb and a bottom comb employed in the disposition of a pleated ceramic-based filter paper within a module of the present system.
DETAILED DESCRIPTION OF THE INVENTION
Referring specifically to FIG. 1 , the depicted embodiment of a filter system 10 of the present invention includes a housing 12 , which in the depicted embodiment is of a generally rectangular cross-section having its opposite short sides 14 , 16 sealed by respective end plates 18 , 20 . Each of the opposite longer sides 22 , 24 of the housing preferably is rounded and partially defines an inlet plenum 26 and an outlet plenum 28 , respectively, for the flow of a gas stream (see arrows) through the filter system.
Internally of the housing there is provided at least one, and preferably a plurality of filter modules 25 (see FIG. 5 ), each of which, in the depicted embodiment includes a pleated ceramic filter paper 27 captured between first and second comb elements 29 , 31 (typical), respectively, (see FIGS. 6 and 7 ). As seen in FIGS. 2 and 5 , the top margins (ribs) 33 of each comb projects above the planar level of the pleated paper, thereby defining multiple gas flow channels 35 (typical, see arrow C)along the length of each module. The bottom of each module is of like construction as the top of the module and includes ribs 36 which define flow channels along the bottom of the module, the channels of both the top and bottom of the module being oriented in like directions from the inlet to the outlet end of the module (see FIG. 2 ).
The inlet end 37 of each module is closed by a gas impermeable wall 39 which extends from the bottom edge 41 of the inlet end of the module to a location short of the top portion 43 of each comb rib. The exhaust end 45 of each module includes an end wall 47 which extends from a height equal to the height of the ribs and extends from the rib height to terminate short of the bottom edge 49 of the module (See FIG. 2 ) thereby leaving an open space 51 at the inlet ends of the top flow channels and closure of the outlet ends of the top flow channels. The top and bottom of each module is overlaid by top and bottom panels 53 , 55 , respectively, of the housing, such panels being overlaid and sealed to the top surfaces of the ribs of the top and bottom of the module, respectively.
Referring to FIG. 6 , one embodiment of a filter module includes a first plurality of top combs 29 whose opposite ends are secured to end walls 39 and 47 and a second plurality of bottom combs 31 which are designed such that the teeth of the bottom combs mesh between the teeth of the top combs to capture therebetween a pleated sheet of ceramic fiber-based filter paper 27 .
In FIG. 2 , there are depicted two stacked modules 25 , 25 ′, the stack being formed by the placement of the bottom 57 of the upper module 25 in overlying relationship to bottom 57 ′ of the lower module 25 ′, with the bottom ribs of the top module abutting respective ones of the ribs of the bottom ribs of the bottom module of the stack, thereby defining a plurality of planar flow channels 41 between the two overlying bottoms of the modules.
At the exhaust end of the flow channels 41 of the stacked modules of FIG. 2 , there are provided first and second obliquely converging elongated panels 61 , 63 which extend along the full dimension of the exhaust ends of the stacked modules. One side 65 of the first panel 61 is secured to the end wall 47 of the top module 25 and one side 67 of the second panel 63 is secured to the end wall 47 ′ of the bottom module 25 ′. The opposite sides 69 , 71 of the converging panels are joined to one another by a porous ceramic microwave permeable wall 73 . This wall, in turn, is mounted within a slot in a tubular wall which extends along the length of the exhaust plenum of the housing.
In the depicted embodiment of FIG. 1 , the filter system further includes an inlet 77 at a first end 32 of the inlet plenum 26 , an outlet 34 at a first end of the outlet plenum 28 , and a hollow tubular microwave barrier 79 disposed internally of, concentric with, and extending along at least substantially the length dimension of the outlet plenum 28 and with a portion 81 thereof projecting beyond a second end 83 of the outlet plenum. This tubular barrier is rotatably mounted within the outlet plenum and is provided at its outboard portion 81 with a first ring gear 85 which encircles the tubular barrier. An indexing motor 87 is mounted to the housing and includes a driven shaft which carries a second ring gear 89 thereon, the teeth of the second ring gear 89 meshing with the teeth of the first ring gear whereby activation of the motor functions to rotate the tubular barrier about its longitudinal axis within the outlet plenum, as desired.
As seen in FIG. 4 , at least one, and most commonly a plurality of cutouts 90 through the wall 92 of the tubular barrier 79 are provided to define one or more outlet ports 95 , 95 ′ for the movement through such cutout(s) of microwaves from within the internal volume of the hollow tubular barrier.
Referring specifically to FIGS. 1 and 2 , microwaves are introduced from a source 99 thereof, into the end of the hollow tubular microwave barrier 79 , and move along the length of the tubular barrier toward the exhaust port. As required, a microwave barrier 101 may be provided adjacent the exhaust port to preclude the passage of microwaves out through the exhaust port. Thus the microwaves are contained within the exhaust plenum except in the instance where a port 95 , 95 ′ through the wall of the tubular barrier is in register with the ceramic wall 71 adjacent the exhaust ends of the stacked modules. In this latter situation, microwaves move from the exhaust plenum, through the ceramic wall and into the modules.
In the operation of filter system of the present invention, a gas stream bearing volatilizable particulates is directed into the filter system via the inlet and into the inlet plenum. This gas stream is distributed by the plenum into the inlet ends of the flow channels of both the top and bottom modules, hence along the exposed surfaces of the multiplicity of pleats of the ceramic-based filter paper. (see arrows in FIG. 2 indicating gas flow). The gas passes through the filter paper with the particulates in the gas stream being captured on the exposed surfaces of the pleats. The cleaned gas thereupon flows along the exhaust flow channels defined between the overlying bottoms of the modules, through the ceramic wall, thence out through the exhaust port of the exhaust plenum.
In a preferred embodiment, as indicated by the dashed lines 103 , 103 ′ of FIG. 1 , a plurality of stacked modules are ganged together are served by a common inlet plenum and a common exhaust plenum. In this embodiment, the length of the tubular microwave barrier is sufficient to include a cutout through its wall at multiple locations along the length of the barrier, a given cutout being spaced circumferentially apart from adjacent one or ones of others of the cutouts so that only one or a selected number of the cutouts are in register with their respective modules at any given time. (see FIG. 4 ). The registration of the cutouts with their respective modules is accomplished by means of the indexing motor operating through the first and second ring gears. In this manner, as desired, one or more than one of the modules are accessed by microwaves and closed to full exhaust flow at any given time, while during this given time, others of the modules are closed off from the microwaves and open to full exhaust flow.
Within those modules which are accessed by the microwaves, the microwaves react with the ceramic-based filter paper to heat the filter paper to the volatilization temperature of the particulate matter captured on the filter paper. The gaseous products from the volatilization of the particulates are swept out the exhaust plenum, thereby regenerating the filter paper in situ. During the time in which one (or more) module is being regenerated, there is no material change in the flow of gas through the others of the ganged modules, hence there is little or no deleterious effect with respect to back pressure, flow capacity, or interruption of the device which is generating the particulate-bearing gas stream. | A filtration system ( 10 ) operable at elevated temperatures and regenerateable in situ employing microwave energy ( 99 ). In one embodiment, the system includes multiple channels ( 35 ) with means for selectively placing individual ones of the channels on-line for filtration and off-line for regeneration. | 1 |
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 10/431,705, filed May 8, 2003, which is continuation of International Patent Application PCT/EP01/12660 filed on Oct. 31, 2001, designating the US, and published in German, which claims priority of German patent application DE 100 56 059.8 filed on Nov. 11, 2000, all which are incorporated herein by reference in their entireties.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a method for identifying substances causing differentiation in eukaryotic cells, to DNA constructs, plasmids, viruses and cell lines used in said method, and to a method of preparing a pharmaceutical composition.
[0004] 2. Description of the Related Art
[0005] Differentiation of cells from stem cells is a general biological phenomenon during embryonic development, but also plays a very large part in regeneration processes in the adult organism (e.g., skin regeneration, formation of blood, regeneration of intestinal epithelia, liver regeneration after poisoning or alcohol abuse, etc.). As in all important biological processes, disruptions may cause chronic diseases or may be lethal.
[0006] During tumorigenesis, there is very frequently, if not always, a “back”-differentiation of cells, i.e. cells revert to an undifferentiated, embryonic state. Despite great improvements in the methods for early diagnosis and therapy of tumor diseases, mortality is still very high and affected patients suffer immensely. Therefore, finding and developing novel and more effective cancer medicaments (cytostatics) is of extraordinary importance for health policy and have, from the perspective of the pharmaceutical industry, a very large growth potential on the drugs market.
[0007] Since many genetic modifications occur on the path from a normal healthy cell to a tumor cell, there are in principle also many possibilities of interfering with the metabolism of tumor cells and thus preventing growth and dissemination. Thus, the largest class of cytostatics leads to damage of cellular DNA. After cell division, this causes lethal mutations, or the cell dies as a direct result of the triggering of the so-called programmed cell death (apoptosis). This affects all rapidly growing cells, i.e. not only tumor cells but also healthy growing cells.
[0008] Another class of cytostatics is that of the antimetabolites which halt the metabolism of rapidly growing cells. A third class of cytostatics damages the so-called spindle fiber apparatus of dividing cells, thereby inhibiting cell division or killing the cells directly. A fourth and relatively new class is that of anti-angiogenetic substances which interfere with the ability of tumor cells to induce new blood vessels for their own supply.
[0009] A relatively new class of cytostatics, which is relevant in context with the present invention, interferes with the expression pattern of genes which have been partly switched off during tumorigenesis. These are frequently so-called tumor suppressor genes and differentiation genes. The renewed induction and expression of said genes usually leads to a loss of growth advantages of a cancer cell and may also make it easier for the immune system to attack said cell.
[0010] The fact that such differentiation-causing substances interfere with the state of methylation of so-called “CpG is-lands” has been known for a long time. CpG islands are found particularly frequently in the 5′-regulatory sequences of genes and play an important part in genomic imprinting, i.e. in regulating paternal versus maternal gene expression. It is possible to switch off genes by methylating the CpG islands present in promoters. If the DNA methylase mainly responsible for methylation is inactive, lethal disruptions in development occur, as can be shown in a knockout model in mice.
[0011] It is therefore assumed nowadays that there is a genetically controlled equilibrium of methylation and demethylation in embryogenesis. A disruption of this equilibrium is often present in tumor cells. Thus, it has been found that it is possible to switch off promoters of tumor suppressor genes by methylation of the CpG islands, which is why, for example, the hypomethylation-inducing substance 5′-azacytidine (Aza) acts as a potent cytostatic agent in many types of tumor.
[0012] Another mechanism important for differentiation is the influence of histone acetylation. Histones are DNA-binding proteins which can regulate chromatin structure and also influence gene expression. This takes place preferably via biochemical modifications of said histones, for example by acetylation or phosphorylation. Thus, the substance trichostatin A (TSA) is known as a specific inhibitor of histone deacetylase. Recently, it was shown that deacylation of histone H4 leads to chromatin condensation and thereby can suppress gene expression. Accordingly, inhibition of histone deacetylase by TSA leads to chromatin decondensation and can thereby remove suppression of gene expression.
[0013] It must be assumed that there are still many other, as yet unknown mechanisms which can be used by tumor cells to switch off expression of differentiation genes and tumor suppressor genes dangerous to them.
[0014] While for some classes of cytostatics there are already very good assay systems which also can be used to identify novel compounds, there is, however, a lack of methods for identifying, as mentioned above, such substances capable of causing differentiation. However, this novel class of cytostatics is particularly interesting, because it has great potential for controlling tumors and is associated with substantially fewer side effects than the traditional cytostatics.
[0015] The following widespread in vitro test systems are available for identifying substances which cause DNA damage and could therefore potentially be used as cytostatics: the Ames test, or else Salmonella typhimurium test (STY), is based on the mutagenicity of substances in bacteria, while the SOS-Chromotest is based on inducing the bacterial SOS system by genotoxic agents. Both tests have comparable sensitivities, but have the fundamental disadvantage that genotoxic action of substances can vary in bacteria and higher organisms.
[0016] For this reason, the Micronucleus test, the single cell gel test (SCG test), also known as comet assay, and the test for sister chromosome exchange (SCE test), which are based on eukaryotic cell systems, have been developed. In the literature, a cell line, A4/4, which contains a lacZ gene under the control of the heavy metal-inducible metallothionein promoter has been described. The authors report that the promoter is switched off during cultivation but can be induced again by the demethylating substance 5′-azacytidine (Biard et al. 1992 Cancer Res 52:5213-5218).
[0017] The previously known assay systems for identifying DNA-damaging agents, however, are not suited to identify substances causing differentiation, since the mechanism is completely different.
[0018] The reporter cell line described by Biard et al. has the decisive disadvantage of being an inducible system. The demethylating action of substances can be visualized only if the inducer for the promoter is used at the same time. The authors have chosen the metallothionein promoter which is induced by heavy metals such as cadmium and zinc. There are hundreds of indications in the literature for heavy metals themselves inducing gene expression. As a result, the gene expression-causing action of the heavy metals required for the system superimposes the demethylating action of some substances, i.e. unspecific, false negative or false positive results are very easily possible. The cell line was prepared for the purpose of being able to find demethylating substances. These substances may cause differentiation but are, as explained above, not the only substances capable thereof. Since there are, after 1992, no further publications regarding this cell line, it is neither known whether this cell line is stable nor whether it is suitable for detecting other differentiation processes as well.
SUMMARY OF THE INVENTION
[0019] In view of the above, it is an object of the present invention to provide a method of the type mentioned at the beginning, which can be used to identify in a rapid, simple and reliable manner substances causing differentiation, and auxiliary substances which can be used in said method.
[0020] This object is achieved by a DNA construct which comprises a fusion gene under the control of a promoter, wherein said fusion gene comprises at least one resistance gene and at least one reporter gene and is slightly toxic to a host cell transfected with said DNA construct so that said promoter is switched off when expression of the resistance gene is not required for growth of the transfected host cells, since, for example, the nutrient medium lacks the appropriate antibiotic.
[0021] Further objects of the invention are a plasmid having such a DNA construct, a virus having an expression cassette containing said DNA construct or coding therefor, i.e. a DNA virus or a retrovirus, and a eukaryotic cell, in particular human cell, which is stably transfected with said plasmid or infected with said virus, in particular the cell line U87-HGFP which was deposited in accordance with the Budapest Treaty at the DSMZ in Braunschweig, Germany, under deposition number DSMZ ACC 2473 on Nov. 9, 2000, and a method of using said DNA construct and/or said plasmid and/or said virus and/or said cell for identifying substances which cause differentiation in eukaryotic cells.
[0022] A further object is a method for identifying substances which are capable of causing differentiation in eukaryotic cells, comprising the steps:
[0023] a) incubating the novel cells in a culture medium containing a selection substance corresponding to the resistance gene,
[0024] b) inoculating a culture medium lacking said selection sub-stance with the incubated cells from step a) and incubating the inoculated cells for approx. 5 to approx. 100, preferably approx. 24, hours,
[0025] c) adding a substance to be identified to said culture medium of the cells from step b) and incubating further for approx. 1 to approx. 5, preferably approx. 2, days, and
[0026] d) checking the incubated cells from step c) for increased reporter gene expression compared to cells from step b).
[0027] The present invention completely solves the problem of identifying substances causing differentiation.
[0028] In this connection, preference is given to selecting the promoter from CMV promoter, RSV promoter, cellular promoters of tumor suppressor genes and promoters of differentiation genes, to selecting the reporter gene from GFP, LacZ, luciferase, to selecting the resistance gene from hygromycin gene, neomycin gene, puromycin gene, and/or to the fusion gene containing at least one gene coding for a polypeptide capable of developing an action toxic to the host cell, such as, for example, GFP, which itself is slightly toxic or cytosine deaminase or thymidine kinase which convert the prodrugs 5′-fluorocytosine and ganciclovir, respectively, into toxic substances.
[0029] The cell line also includes a fusion gene under the control of the human cytomegalovirus promoter (CMV promoter). This promoter is usually extremely strong in cells and therefore need not be induced, in contrast to the metallothionein promoter of the prior art. Moreover, it is known that the promoter can be switched off under certain conditions, in particular in vivo.
[0030] The fusion gene here consists of the resistance gene for the antibiotic hygromycin (hygro) and green fluorescent protein (GFP). Transfection of the glioblastoma cell line U87 with this construct generated the cell line U87-HGFP, after selection using the antibiotic hygromycin. This cell line expresses the fusion gene in the presence of the antibiotic, this being very clearly visible in fluorescence microscopy on the basis of GFP fluorescence. If the antibiotic is removed for just a few days, the cell downregulates the CMV promoter, since the fusion protein is slightly toxic to the cells. As the inventors observed, the said fusion protein accumulates in particular cell compartments (probably the ER). Treating said cells with the differentiation-causing substances 5′-azacytidine and/or trichostatin A at very low concentrations results in very strong upregulation of the CMV promoter, visible due to increased GFP fluorescence, within just two days.
[0031] Up until now, no cell line has been described or known in which substances causing differentiation can be detected using an expression unit consisting of CMV promoter and hygromycin-GFP fusion. The system is very reliable, with the presence of hygromycin during routine cultivation of the cell line preventing the loss of said expression unit. The cell line has the intrinsic capability of virtually completely downregulating the CMV promoter only a few days after removing hygromycin. The promoter is upregulated again when adding substances causing differentiation.
[0032] The advantage compared to the known system is, inter alia, the use of a fusion gene which combines a plurality of proper-ties: (I) positive selectability by the hygromycin gene, i.e. the expression unit is retained in a stable manner when adding the antibiotic; (II) negative selectability, i.e. in the absence of hygromycin B the toxic effect of the GFP gene selects for cells in which the promoter is switched off; (III) identifiability due to intrinsic fluorescence of GFP. These properties render the system very stable and reliable.
[0033] The system needs no inducer except the differentiation substance to be tested and is therefore unaffected by disruptions or superpositions by an inducer.
[0034] The system has proved to be capable of finding not only demethylation but also histone acetylation.
[0035] Using the GFP as reporter, it is possible to observe the promoter activity, and thus the action of substances causing differentiation, both in living cells and in fixed cells (fluorescence microscopy) and to quantify it exactly and reproducibly by means of flow cytometry.
[0036] According to another object, it is also possible in the novel method to use other reporter expression units consisting of a promoter (CMV promoter, RSV promoter, cellular promoters of tumor suppressor genes or differentiation genes), a selection marker (hygromycin gene, neomycin gene, puromycin gene, etc.) fused to a reporter (GFP, LacZ, luciferase), and a “toxic” gene (e.g. GFP, cytosine deaminase, HSV thymidine kinase).
[0037] Cytosine deaminase or thymidine kinase would then additionally need toxic but not lethal concentrations of the pro-drugs 5′-fluorocytosine and ganciclovir, respectively. This would select for cells which down-regulate the promoter.
[0038] These constructs may also be transfected in cell lines other than U87, or the studies may also be carried out in vivo, i.e. on transgenic animals.
[0039] The cell line U87-HGFP, which is still a further object of the invention, has a particular advantage in that the promoter can be switched off within a short time and reliably. Furthermore, the method can be automated, making it possible to screen many substances in a short time.
[0040] The cell line has the further advantage of being a tumor cell line so that the substances are searched for in a cancer cell which is thus not only a model system but also, at the same time, a test system. Another advantage is the fact that these cells differentiate with addition of the appropriate substances, and this can be seen due to the change in morphology.
[0041] A substance identified in this way is thus not only capable of reactivating a downregulated promoter but can also force a cancer cell to differentiate and is thus a potential cytostatic.
[0042] Against this background as another object, the invention also relates to a method of using a substance identified by the novel method for preparing a pharmaceutical composition for treating malignant and benign tumor diseases, and to a method for preparing a pharmaceutical composition, which comprises the novel method and mixing the identified substance with a pharmaceutically acceptable carrier.
[0043] Further advantages arise from the description and the attached drawings.
[0044] It is obvious that the features mentioned above and still to be illustrated below can be used not only in the combinations indicated in each case but also in other combinations or on their own, without leaving the scope of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] FIG. 1 shows detection of H-GFP gene amplification by 5′-azacytidine and trichostatin A by means of fluorescence microscopy: U87H-GFP cells, growing on coverslips, were treated with 5-azacytidine (0.5-2.5-20 μM) and trichostatin A (0.1-1 μM) for 48 h. Owing to amplification of the H-GFP gene, an increasing green fluorescence signal was observed when comparing untreated with treated cells. The parent cells had no signal sufficiently strong for observation by fluorescence microscopy (data not shown). All images correspond to a magnification of 400×.
[0046] FIG. 2 shows FACS fluorescence profiles, with U87H-GFP and parent cells obtained after treatment for 48 h using different concentrations of 5-azacytidine and trichostatin A: 1-2×10 5 cells of U87H-GFP and the parent line were seeded in 6-well plates, treated with 5-azacytidine and trichostatin A for 48 h and then analyzed by flow cytometry as described below. In all histograms, the abscissae correspond to an arbitrary and logarithmic scale which refers to fluorescence intensity, whereas the ordinates refer to the cell number. Each of the curves corresponds to 2×10 4 cells counted, and in the overlays, the darker profile corresponds to the untreated cells and the lighter one to the treated cells. Profiles (a) to (e): U87H-GFP. A shift toward higher fluorescence intensity is clearly visible at 2.5, 20 μM Aza and 1 μM TSA, whereas 0.5 μM Aza and 100 nM TSA curves completely superpose those of the untreated cells. Profiles (f) to (1): U87. Particularly when using 20 μM Aza and 1 μM TSA, a small shift is observed which, however, can be considered as a background increase not caused by the plasmid and cannot be observed by fluorescence microscopy.
[0047] FIG. 3 (A) shows U87 parent line and H-GFP, treated with different final concentrations of 5-azacytidine for 48 h. U87H-GFP shows a two-fold increase in the fluorescence intensity mean value already at 2.5 μM Aza (compared to untreated cells). This reporter cell line attains a three-fold increase when 20 μM Aza are used. We obtain an approximately two-fold increase in the fluorescence intensity mean value of U87 parents only at the highest concentration used.
[0048] FIG. 3 (B) shows the increase in H-GFP gene expression due to trichostatin A. Approximately 10 5 cells of each cell line were cultured with different final concentrations of trichostatin A for 48 h. As the histogram shows, we obtained a three-fold and four-fold increase in the fluorescence intensity mean value when using a final concentration of 1 μM and 3 μM TSA in U87H-GFP (compared to untreated cells). In both histograms, all mean values, standard deviations and P values are derived from at least five different values (n=5) obtained from two different independent experiments. All P values refer to untreated cells.
[0049] FIG. 3 (C) shows treatment with two different combinations of 5-azacytidine and trichostatin A. The two cell lines (10 5 cells/well) were cultured in the presence of two different combinations of Aza and TSA for 48 h. In both cases, a three-fold increase in the fluorescence intensity mean value is observed in U87H-GFP (compared to untreated cells). However, the difference is not significant (p=0.09) when we compare the increase for U87H-GFP which has been treated with the two different medicament combinations.
[0050] FIG. 3 (D) shows trichostatin A and 5-azacytidine, in each case individually and in combination. 10 5 cells of the U87H-GFP cell line were treated with 200 nM TSA, 1 μM Aza and with the combination of both for 48 h. When using the two medicaments in each case individually, we obtained an approximately two-fold increase in the fluorescence intensity mean value (P˜10 −9 and <10 −4 , compared to untreated cells). When using the combination of the two medicaments, we obtained a small and significant increase in the fluorescence intensity compared with each medicament alone (P˜0.02). The mean values, standard deviations and P-values are based on ten values (n=10) which were obtained in two independent experiments.
[0051] FIG. 4 shows dot plots obtained by FACS analysis of U87H-GFP and the parent line which were either treated or not treated with 5 μM 5-azacytidine for 48 h. Both cell lines were kept in culture in the presence of 5 μM Aza. Two days later, the cell cycles were determined as described. 10,000 cells were analyzed. The procedure for studying the cell cycle by FACS analysis is illustrated below.
[0052] [I and IV] show dot plots referred to DNA staining of treated and untreated cells. In order to exactly define a population of (2N+4N) nuclei, a region (R1) was utilized. [II and V] show dot plots referred to BrdU incorporation into DNA. The values 200 and 400 on the linear scale of FL3-A fluorescence correspond to the amount of 2N and 4N DNA in the nuclei. All events shown correspond to the R1 region. [III and VI] show an isotype control for establishing the quadrants for the dot plots of BrdU incorporation. The anti-isotype antibody represents nonspecific binding and was used as a negative control for the anti-BrdU antibody. The percentages of cells in different phases of the cell cycle were determined using the dot plots of BrdU incorporation (in quadrant: bottom left region=G1−G0; bottom right region=G2; top left region=S; top right region=M).
[0053] FIG. 5 shows plasmid pCMV-HygroEGFP which was used in the experiments.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0000] 1) Cloning of pCMV-HygroEGFP
[0000] Intermediate Plasmid 1 Called pScriptpolyA (3595 bp).
[0054] Starting plasmid pCRScript SK(+) AmpR+ cut with EcoRV and HindIII, and subsequent ligation with SmaI/HindIII fragment which contains a 625 bp HSV thymidine kinase polyadenylation signal from pTKneo (blunt end ligation).
[0000] Intermediate 2: pCMVA (4260 bp).
[0055] Insertion of a 670 bp hCMV promoter fragment from pL15Tk [cut with PstI, blunt-ended using T4 DNA polymerase] into intermediate 1, pScriptpolyA, cut with SrfI (blunt end ligation).
[0000] Intermediate 3: pCMV-EGFP (4975 bp).
[0056] Ligating of the EGFP reading frame from plasmid pEGFP (Clontech) cut with BamHI/NotI (end filled in using Klenow polymerase) into vector pCMVA opened with PstI (intermediate 2, blunt-ended using T4 DNA polymerase) (blunt end ligation).
[0000] Final pCMV-HygroEGFP (6052 bp).
[0057] Ligation of a 1026 bp PCR fragment containing the open reading frame of the hygromycin resistance gene from pTkHygro (Stopcodon removed by said PCR) into AgeI-opened vector pCMV-EGFP (blunt-ended by filling in ends using Klenow polymerase) (blunt end ligation).
[0058] The plasmid is depicted in FIG. 5 .
[0000] 2) Materials and Methods
[0000] Cell Lines
[0059] U87H-GFP is a cell line derived from the human glioblastoma cell line U87 after stable transfection with plasmid pCMV-hygroEGFP. This plasmid which is integrated into the genomic DNA is derived from PCR-Script™ (Stratagene) and carries a fusion gene downstream of the human CMV promoter. This fusion gene contains the gene for resistance to hygromycin, which is linked to the gene coding for the enhanced green fluorescent protein (EGFP). The resulting gene (called H-GFP) codes for a protein which imparts resistance to hygromycin B and which can be readily detected by fluorescence microscopy and flow cytometry analysis. In contrast, the parent cell line U87 does not contain any plasmid and can be used as a negative control.
[0060] U87H-GFP and the parent line U87 were cultured in Dulbecco's Modified Eagle's Medium, (D-MEM, low glucose, Gibco, BRL) supplemented with 10% fetal calf serum (Seromed), 100 units/ml penicillin, 100 μg/ml streptomycin and 1 μg/ml amphotericine B (Gibco, BRL) at 37° C. in a humidified atmosphere containing 5% CO 2 . For the U87H-GFP cell line, the culture medium was supplemented with 600 units/ml hygromycin B (Calbiochem).
[0061] U87H-GFP and the parent cells were seeded at 1-2×10 5 cells/well on 6-well plates (Nuclon, NUNC), using D-MEM without hygromycin B, and incubated for adhesion for 24 h. This was followed by adding 5-azacytidine and trichostatin A (Sigma Chemicals, Co.) at different final concentrations (2.5-5-10-20-40 μM for Aza; from 10 nM to 3 μM for TSA) to the culture medium. After two days of treatment, fluorescence microscopy and flow cytometry analyses were carried out.
[0000] Fluorescence Microscopy
[0062] Approximately 10 5 cells of each cell line were seeded on polylysine-coated coverslips, treated with different concentrations of Aza and TSA for 48 h and then fixed in 5% formaldehyde at room temperature for 30 min. This was followed by analyzing all samples under a fluorescence microscope (Axiophot, Zeiss, Germany) and recording various images which correspond to the different final concentrations of each medicament ( FIG. 1 ).
[0000] Flow Cytometry Analyses of Cells Expressing the Hygromycin-EGFP Fusion Gene.
[0063] In order to prepare samples for FACS analysis, cells were incubated in the 6-well plates in 0.05% trypsin containing 0.5 mM EDTA (Gibco, BRL) at 37° C. for 5 min, followed by stopping the trypsin action by adding two volumes of culture medium. The cells were harvested, centrifuged at 500×g for 5 min and resuspended in 1 ml complete D-MEM. In order to stain dead cells, propidium iodide (final concentration 10 μg/ml) was added to each sample. The cells were then again centrifuged and resuspended in phosphate-buffered saline (PBS 1 x, pH 7.4), before analyzing them by means of FACS.
[0064] The cells were analyzed using FACScalibur (Becton Dickinson) with the flow rate corresponding to approximately 500 events/s.
[0065] In order to exactly define a cell population and to exclude cell debris and aggregates, a region of interest was established on the dot plot (FSC compared to SSC). In the two-parameter histogram of propidium iodide, dead cells were distinguished by comparison to forward angle light scatter (FSC). The fluorescence intensity of individual cells was measured on a logarithmic scale, each logarithmic histogram representing 2×10 4 counted events. The fluorescence intensity mean value (MFI) was the parameter used for defining the increase in the fluorescence intensity in each cell population.
[0000] Cell Cycle Analysis
[0066] U87H-GFP and the parent cells were seeded at 5×10 3 /cm 2 in T25 flasks (Nuclon, NUNC), using D-MEM without hygromycin B for both cell lines. Half of the flasks were treated with 5 μM Aza and the other, as a negative control, without any medicaments. After 42 h, BrdU was added to the medium (final concentration of 10 μM), and 6 h later the cells were prepared for cell cycle analysis.
[0067] The cells were harvested, centrifuged at 500×g for 5 min and fixed in chilled 70% strength ethanol for 20 min. BrdU incorporation into the DNA was detected by using 3×10 5 cells of each Aza-treated or untreated cell line.
[0068] PBS 1 x/0.5% BSA (washing buffer) was added, and the cells were centrifuged at 500×g for 5 min. The pellet was then resuspended in a denaturing solution (HCl 1M, PBS 0.5×BSA 0.5%) and washed again after 20 min. This was followed by re-suspending the pellet in 0.1M sodium borate (Na 2 B 4 O 7 ), pH 8.5, for 2 min and then adding the washing buffer. After this passage, the total volume of each sample was divided into two halves (one half being used for the isotype antibody, the other one for the BrdU antibody), centrifuged at 500×g for 5 min, resuspended in the buffer containing the anti-isotype or anti-BrdU monoclonal antibodies (Becton Dickinson) and, after 30 min, washed with PBS 1 x/0.5% BSA. The supernatant was discarded and the pellet resuspended in RNAse A (final concentration 100 μg/ml); the DNA was stained by also adding to the solution 7-AAD (Via-PROBE, Becton Dickinson). After 1 h (in the dark), the samples were washed and then resuspended in PBS 1 x/0.5% BSA. DNA fluorescence of the nuclei (approximately 10 4 nuclei were analyzed for each cell population) was measured by means of the abovementioned FACScan flow cytometer (Becton Dickinson) and the percentages of cells in the G0 and G1, S, G2 and M phases of the cell cycle were analyzed on the basis of the FACScan software programs.
[0000] 3) Results
[0069] The cell line U87H-GFP contains the plasmid pCMV-hygroEGFP in which activation of the hCMV promoter is usually regulated at a low level. Said plasmid imparts to the cell line resistance to hygromycin B and a basic green fluorescence compared to the parent cell line. The hCMV promoter was shown as being completely repressed by methylation of the 5′-CpG site of cytosine (Prosh S. et al. 1996 Biol Chem Hoppe Seyler 377(3):195-201). In order to estimate the property of the promoter of being able to be activated by medicaments interfering with the DNA methylation state and chromatin condensation, U87H-GFP and the parent line U87 were kept in the presence of Aza and TSA for several days. Prior to the experiment, hygromycin B was removed from the medium in order to obtain a decrease in basic activation of the hCMV promoter and furthermore to detect promoter activation by Aza and TSA.
[0070] FIG. 1 shows fluorescence microscopy images of U87H-GFP cells treated with different final concentrations of Aza (0.5-2.5-20 μM) and TSA (100 nM, 1 μM) for 48 h. Comparison of basic expression of the reporter cell line (untreated cells) with those samples treated with different final concentrations of Aza and TSA makes it possible to detect an increase in H-GFP gene expression in the images. At 20 μM Aza and 1 μM TSA, the increase in the green fluorescent signal is clearly defined. Parent cells show a weak increase in basic green fluorescence, which was detectable only by FACS analysis and not by fluorescence microscopy.
[0071] Furthermore, a change in the morphology of the cells was observed at high concentrations of TSA and Aza, indicating that these substances may force the tumor cells U87 back into differentiation.
[0072] FIG. 2 depicts FACS profiles (logarithmic histograms) of samples which were treated with the same concentrations of Aza and TSA as in fluorescence microscopy.
[0073] The abscissae correspond to an arbitrary scale which refers to the logarithm of fluorescence intensity, and the ordinates represent the relative cell number. When comparing the control, which had not been treated with the reporter cell line, with the reporter cell line, which had been treated with the abovementioned final concentration, we obtained a shift in the fluorescence profile in the direction of higher intensity. The shift is already clearly-visible with additions of 2.5 μM Aza ( FIG. 2 , profile b) and is well defined at higher concentrations (profile c).
[0074] At a final concentration of 100 nM, TSA does not induce in any way an increase in H-GFP gene expression (profile d), but attains a saturation threshold at a final concentration of 1 μM (profile 1 ). It was not possible to use final TSA concentrations of more than 3 μM, since these proved highly toxic and drastically reduced the number of living cells, as was observed by means of FACS (data not shown).
[0075] The parent cell line is likewise sensitive to Aza ( FIG. 2 , profiles f to h) and TSA (profile i and l), but the shift in fluorescence intensity is not comparable to those obtained with the reporter cell line and can therefore be explained as a background increase rather than being caused by the plasmid.
[0076] The histogram in FIG. 3A corresponds to the experiment in which the reporter cell line (black bars) and the parent cell line (white bars) were treated with different Aza concentrations for only 48 h. The histogram depicts a two-fold increase in the fluorescence intensity mean value for a comparison of the control (untreated U87H-GFP) with cells treated with 2.5 μM Aza (P<10 −6 , compared to control). When using 20 μM Aza, H-GFP gene expression can achieve a three-fold increase in fluorescence intensity (P<10 −5 , compared to control). A slow increase in basic fluorescence (only by means of FACs analysis and not in fluorescence microscopy) is also visible in the parent cell line (white bars in the histogram), corresponding to less than twice that when using the highest concentration (40 μM Aza). This experiment was also repeated while retaining Aza for 144 h (five days) and with identical final concentrations. We obtained the same shift in the fluorescence intensity average (data not shown).
[0077] TSA can also cause amplification of the H-GFP gene, as FIG. 3B reveals. Both cell lines were kept in cultures which different final TSA concentrations for 48 h. The histogram reveals a slight but significant increase in the fluorescence intensity of U87H-GFP for TSA only at 500 nM and not at the lower concentrations used. However, when we used 1 μM and 3 μM TSA, we observed a three-fold and four-fold increase in fluorescence (P=0.001 and P<10 −5 , compared to untreated cells). In the parent cell line, a two-fold increase is visible only for 3 μM TSA.
[0078] In order to further investigate whether TSA can act synergistically with Aza, as has been shown for other tumor cell lines (Cameron E. E. et al. 1999 Nat Genet 21:103-107), we used TSA in combination with Aza for 48 h ( FIG. 3C ) In this experiment, we kept TSA at a fixed final concentration of 1 μM, while changing Aza from 2.5 to 5 μM. In both cases, a three-fold fluorescence increase is observed in U87H-GFP compared to untreated cells, but the difference is not significant when comparing the two combinations of the medicaments (p=0.09). In the next experiment ( FIG. 3D ) we used TSA and Aza in each case alone and in combination for 48 h. The increase due to the medicaments alone was significant and corresponded to about a two-fold increase, both for 200 nM TSA (P˜10 −9 , compared to untreated cells) and for 1 μM Aza (P<10 −4 compared to untreated cells). When we used the combination of the two (200 nM TSA+1 μM Aza), the small increase with respect to the medicaments alone was significant (P˜0.02, compared to the medicaments alone), but the medicaments appeared to act neither in a synergistic nor in an additive way, the reason for this being probably that the increase in fluorescence intensity corresponded to maximum activation of the CMV promoter at these medicament concentrations.
[0000] Effects of 5-Azacytidine on the Cell Cycle.
[0079] U87H-GFP and the parent cells were treated with 5 μM Aza for two days in order to study the effect of cytosine analog on the cell cycle. As FIG. 4 illustrates, the DNA was stained with 7-AAD and in the first two dot plots (I, IV) a single window was utilized (R1) in order to exactly define only one 2N and one 4N nuclei population (corresponds to values 200 and 400 on FL3-A scale). The enclosed population of nuclei was then tested for BrdU incorporation (II, V) by using a PE-conjugated antibody against BrdU. Isotype staining (dot plots III, VI) was used in order to define nonspecific binding of the BrdU antibody and in order to set the quadrant in the BrdU incorporation dot plots. The percentages of the cells in different cell cycle phases were obtained from the dot plots of BrdU incorporation. Table 1 shows the percentages of cells in different cell cycle phases. Azacytidine (at a concentration of 5 μM) has no significant effect on different phases of cells, with the exception of a small increase in the percentage of cells in G2. In contrast, the parent line (U87) appeared to be more sensitive to 5-azacytidine. In this cell line, 5-azacytidine caused a reduced number of cells in the M phase (˜15.7% in the control, compared to ˜10.6% for 5 μM Aza) and the G1-G0 phase (˜72.2% in the control, compared to ˜62.6% for 5 μM Aza), associated with an increased number in the S phase (˜6.9% in the control, compared to ˜13.5% for 5 μM Aza) and the G2 phase (˜5.2% in the control, compared to ˜13.1% for 5 μM Aza).
TABLE 1 Percentages of cells in different cell cycle phases G1-G0 G2 S M n U87 72.17 ± 1.49 5.21 ± 1.12 6.92 ± 1.3 15.7 ± 1.47 15 U87 + Aza 62.61 ± 0.47 13.1 ± 2.36 13.54 ± 1.25 10.58 ± 2.85 15 U87 H-GFP 65.28 ± 5.98 6.26 ± 1.71 12.33 ± 5.77 15.95 ± 2 11 U87 H-GFP + Aza 61.53 ± 4.06* 8.77 ± 1.44 13.3 ± 3.26* 16.26 ± 2.83* 11
4) Statistical Analysis
[0080] The P values were calculated using the program “Anova, 1-faktorielle-Varianz-Analyse” with MS Excel. The P values <0.05 were regarded as statistically significant.
[0081] Table 1 shows the cell cycle analysis: 5-azacytidine influences the cell cycle only in the parent cell line U87 but not in U87H-GFP. The percentages of the cells in the G1-G0, S, G2 and M phases of the cell cycle were obtained as described in FIG. 4 .
[0082] Apart from an increased number of cells in the G2 phase, U87H-GFP exhibited no significant differences in the cell cycle when treated with 5 μM Aza. In contrast, there were significant changes in the cell cycle phases of U87 when kept in a culture containing 5 μM Aza for 2 days. A reduced number of cells in the G1-G0 and M phases was associated with an increased number in the G2 and S phases. | A DNA construct is described which contains a fusion gene under the control of a promoter. The fusion gene comprises at least one resistance gene and at least one reporter gene and is slightly toxic to a host cell transfected with that DNA construct. That DNA construct can be encoded on a plasmid or a virus. Further, a method is described for using the DNA construct to identify substances that may cause a differentiation in eukaryotic cells. | 2 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to an injection molding machine, and more particularly, to an injection unit of an injection molding machine provided with a load detection unit for detecting resin pressure on the injection screw.
[0003] 2. Description of the Related Art
[0004] In an injection unit of an injection molding machine, a screw-type injection unit (that is, a screw-in-line-type injection unit) melts and kneads resin inside a heating cylinder by rotating an injection screw, and further, retracts the injection screw while applying pressure on the resin with the injection screw and measures the melted resin at that retracted position. Thereafter, the injection unit injects melted resin into a mold by advancing the screw.
[0005] As a result, it is necessary that the injection unit be provide with a mechanism that rotates the injection screw and a mechanism for driving the injection screw in an axial direction and injecting the resin.
[0006] An injection mechanism is known that comprises an injection unit by providing a pusher plate to which is fitted an injection screw so as to be freely rotatable but axially unmovable, providing on such pusher plate a pulley that rotates the injection screw and a screw rotation motor that drives the pulley by a belt, and further, providing thrust force drive means for injecting the resin with the injection screw by driving such pusher plate in the injection screw axial direction, and further, has a load detection unit such as a load cell for detecting the pressure on the injection screw (for example, JP 2-16023A and JP 9-174628A).
[0007] A load detection unit such as a load cell detects the resin pressure inside the heating cylinder, and the resin pressure detected by the load detection unit is used in back pressure control during a measuring step. In addition, in injection and pressure holding steps, the detected resin pressure is used in injection pressure feedback control, pressure holding feedback control and the like. Hence, it is desirable that the resin pressure be detected with greater accuracy.
[0008] As the means for rotating the screw, in that which uses a pulley-and-belt transmission mechanism, the belt is run between a drive pulley provided on the motor and a driven pulley provided on the injection screw side. This belt exerts a force in a radial direction on the pulley provided on the injection screw side, creating moment on the shaft on which the pulley is mounted, causing the force of friction of the injection mechanism unit to fluctuate and affecting the resin pressure detected by the load cell. Inventions that prevent these things from happening are also known (for example, JP 2000-117789A and JP 2000-334789A).
[0009] In an injection unit in which, as the means for rotating the injection screw mounted so as to be freely rotatable and axially unmovable on the pusher plate, the screw rotation motor is mounted on the pusher plate and a belt such as a timing belt is run between the drive pulley mounted on the output shaft of the motor and the driven pulley mounted on the injection screw side for driving the injection screw, and such belt transmission mechanism is used to rotate the injection screw, the force exerted by the belt on the drive pulley in the radial direction of the drive pulley also acts on the pusher plate through the motor that is mounted on the pusher plate, adversely affecting resin pressure detection of the load cell or other such load detection unit provided on that pusher plate.
SUMMARY OF THE INVENTION
[0010] The present invention is configured so that the effect of the force generated by the belt from the motor side does not reach the load detection unit.
[0011] An injection unit of the present invention rotates and axially moves an injection screw of an injection molding machine. The injection unit comprises: a first member arranged linearly movable and having a front face closer to the injection screw and a rear face remote from the injection screw; a pulley shaft rotatably supported by the first member and having a pulley fixed thereon on a rear side of the first member; a rotation-transmitting member connected with the pulley shaft such that a relative axial displacement in between is allowed, and connected with a rear end of the injection screw, for transmitting rotation of the pulley shaft to the injection screw; a load detection member mounted on the front face of the first member and having an inner annular portion supporting the rotation-transmitting member rotatably such that a relative axial displacement in between is inhibited, for measuring a resin pressure acting on the injection screw; a second member not integrally formed with the first member and attached to the rear face of the first member; a screw-rotation motor mounted on the second member for rotating the pulley fixed on the pulley shaft through a belt; and thrust force applying means for applying a thrust force to the second member so that the injection screw is axially moved.
[0012] The second member may have a main body and a mounting portion for mounting the screw-rotation motor to extend from the main body, and be fixed to the first member at positions remote from a proximal part of the mounting portion.
[0013] The screw rotation motor is drawn toward the second member by the tension of the belt run between the pulley shaft mounted on the first member and the screw rotation motor, causing the second member to deform. However, because the first member on which the load detection unit is mounted and the second member are configured as separate units, the first member is not affected by the tension of the belt, thus enabling high-accuracy resin pressure detection.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a diagram illustrating an injection unit of a first embodiment of the present invention;
[0015] FIG. 2 is a diagram showing a sectional view in a direction vertical to the plane of the paper in FIG. 1 , at an interface between pusher plate and housing in the first embodiment;
[0016] FIG. 3 is a diagram illustrating an injection unit of a second embodiment of the present invention; and
[0017] FIG. 4 is a diagram showing a sectional view in a direction vertical to the plane of the paper in FIG. 3 , at an interface between pusher plate and housing in the second embodiment.
DETAILED DESCRIPTION
[0018] FIG. 1 is a diagram illustrating an injection unit of a first embodiment of the present invention, showing a sectional view cut along a center line thereof.
[0019] An injection screw 17 is inserted into a heating cylinder 18 mounted on a front plate 16 , with a rear end shaft fixedly mounted on a rotation-transmitting member 4 . The rotation-transmitting member 4 is mounted through bearings 5 , 6 so as to rotate freely but is unable to move in an axial direction within an inner annular part 3 b of a load cell 3 operating as a load detection unit. An outer annular part 3 a of the load cell 3 is fixedly mounted on a pusher plate (first member) 1 . A pulley shaft 7 , on which is mounted a driven pulley 9 , is mounted so as to be freely rotatable but axially unmovable on the pusher plate 1 through bearings 8 . The pulley shaft 7 and the rotation-transmitting member 4 are connected by connecting means that limit only relative movement in a direction of rotation. In the present embodiment, the pulley shaft 7 and the rotation-transmitting member 4 are joined together by a spline coupling. Alternatively, instead of a spline coupling the pulley shaft 7 and the rotation-transmitting member 4 may be coupled by a key and key groove arrangement.
[0020] Further, a housing (second member) 2 is fixedly mounted on the pusher plate (the first member) 1 , and to the housing 2 is connected thrust force drive means for driving the injection screw 17 and the pusher plate 1 axially (left and right in FIG. 1 ) and injecting melted resin inside the heating cylinder 18 into a mold, not shown. In this first embodiment, the thrust force drive means is composed of a ball screw/nut mechanism 13 and a motor, in which the ball nut 13 b of the ball screw/nut mechanism 13 is fixed. In addition, a pair of motor mounts 2 a that mount a screw rotation motor 12 that drives the rotation of the injection screw 17 projects from both lateral sides of the housing 2 (that is, both lateral sides as seen from the axial direction of the injection screw; see FIG. 2 ). The screw rotation motor 12 is mounted between the pair of motor mounts 2 a , and a timing belt 10 is run between a drive pulley 11 provided on the output shaft of the motor 12 and the driven pulley 9 .
[0021] A ball screw shaft 13 a of the ball screw/nut mechanism 13 is mounted by bearings 14 on an end plate 15 so as to rotate freely, and mounts on its front end a driven pulley 19 for rotating the ball screw shaft 13 a . A timing belt is run between the driven pulley 19 and a drive pulley provided on the output shaft of an injection motor, not shown, for driving the injection screw 17 in the axial direction. The injection motor drives the injection screw 17 , the pusher plate 1 and the like axially. It should be noted that the ball nut 13 b screws onto a threaded part of the ball screw shaft 13 a . In addition, guide bars, not shown, that guide the pusher plate 1 are provided between the front plate 16 and the end plate 15 . The pusher plate 1 is guided by the guide bars so as to be movable in the direction of the axis of the injection screw 17 (to the left and right in FIG. 1 ). Alternatively, the means for guiding the pusher plate 1 may be a linear guide.
[0022] Next, a description is given of the operation of the injection unit. During measuring/kneading, the screw rotation motor 12 drives, the driven pulley 9 is driven by the drive pulley 11 and the timing belt 10 and rotates, and the pulley shaft 7 on which the driven pulley 9 is fixedly mounted, the rotation-transmitting member coupled to the pulley shaft 7 by splines and the injection screw 17 mounted on the rotation-transmitting member 4 all rotate. The rotation of the injection screw 17 melts the resin supplied to the interior of the heating cylinder 18 , and the pressure of the melted resin causes the injection screw 17 to retreat (that is, to move to the right in FIG. 1 ). The force of retraction of the retreating screw is transmitted to the rotation-transmitting member 4 , to the load cell 3 by the bearings 5 , and to the pusher plate 1 by the load cell 3 , causing the pusher plate 1 and the housing 2 to retreat.
[0023] At the same time, the driving of the injection motor creates back pressure. In other words, the injection motor is driven, creating a force corresponding to a set back pressure that causes the driven pulley 19 and the ball screw shaft 13 a to rotate, causing the ball nut 13 b to advance and the housing 2 and the pusher plate 1 to advance (that is, to move to the left in FIG. 1 ). However, when the resin pressure exceeds this set back pressure, the injection screw 17 , the rotation-transmitting member 4 , the load cell 3 , the pusher plate 1 and the housing 2 all retreat. During this time, the force of retraction of the injection screw 17 acts on the inner annular part 3 b of the load cell 3 through the rotation-transmitting member 4 , a distortion arises between the inner annular part 3 b and the outer annular part 3 a fixedly mounted on the pusher plate 1 , and the resin pressure is detected.
[0024] In addition, in the injection and the pressure holding steps, the driving of the screw rotation motor 12 is stopped, the injection motor is driven and the ball screw shaft 13 a is driven by the driven pulley 19 . As a result, because the ball nut 13 b engaged with threads of the ball screw shaft 13 a is fixedly mounted on the housing 2 it advances without rotating along the shaft of the ball screw shaft 13 a , the housing 2 , which is fixedly mounted on the ball nut 13 b , advances the pusher plate 1 on which the housing 2 is fixedly mounted, advancing the load cell 3 , which is fixedly mounted on the pusher plate 1 , the rotation-transmitting member 4 through the bearings 5 and the injection screw 17 fixedly mounted on the rotation-transmitting member 4 so as to inject resin into the mold. In addition, in the pressure holding step as well, the injection motor is driven so as to apply pressure on the resin at a set holding pressure by the injection screw 17 through the pusher plate 1 .
[0025] In these injection and pressure holding steps as well, a force generated by the driving of the injection motor that attempts to advance the pusher plate 1 is exerted on the outer annular part 3 a of the load cell 3 , the resin pressure exerted on the injection screw 17 acts on the inner annular part 3 b of the load cell 3 , a distortion between the load cell outer annular part 3 a and the inner annular part 3 b arises and the resin pressure is detected.
[0026] The foregoing describes the operation of the injection unit of the present embodiment. However, as can be appreciated by those skilled in the art, the timing belt 10 is run between the drive pulley 11 provided on the output shaft of the screw rotation motor 12 and the driven pulley 9 , and this timing belt 10 exerts on the screw rotation motor 12 a force that pulls the screw rotation motor 12 toward the housing side, and exerts a force on the driven pulley 9 that pulls the driven pulley 9 toward the screw rotation motor 12 . Consequently, a moment acts on the pulley shaft 7 supported on the pusher plate 1 by the bearings 8 . However, the pulley shaft 7 and the rotation-transmitting member 4 are coupled by splines, and since the play in the bearings is smaller than the play in this spline coupling, the moment force acting on the pulley shaft 7 is received and supported by the bearings 8 .
[0027] At the same time, the tension of the timing belt 10 exerts on the housing 2 through the screw rotation motor 12 and the motor mounts 2 a a force that pulls the drive pulley 11 mounted on the motor shaft toward the housing 2 . The distinctive feature of the present invention is that the pusher plate 1 and the housing 2 on which the screw rotation motor 12 is mounted are not integrally formed and connected with each other, so that this force that is exerted on the housing 2 does not affect the load cell 3 through the pusher plate 1 .
[0028] FIG. 2 is a diagram showing the interface between the pusher plate 1 and the housing 2 , as a sectional view cut along a direction vertical to the plane of the paper in FIG. 1 (that is, as seen from the front side of the injection screw 17 ).
[0029] The pusher plate 1 and the housing 2 are tightly connected and fixed in place by bolts or the like at an abutting portion 2 b indicated by cross-hatching in FIG. 2 . However, the housing 2 and the pusher plate 1 are not tightly connected and are not fixed at proximal portions 2 a′ of the pair of motor mounts 2 a each of which extends from both lateral sides of the housing 2 so as to mount the screw rotation motor 12 . The force exerted on the housing 2 by the tension of the timing belt 10 through the drive pulley 11 , the screw rotation motor 12 and the motor mounts 2 a concentrates at the proximal portions 2 a′ and the housing 2 distorts around the proximal portions 2 a′ of the motor mounts 2 a . However, the areas around the proximal portions 2 a′ of the motor mounts 2 a are not connected to the pusher plate 1 , and consequently, since the housing 2 and the pusher plate 1 are coupled at a distance from the proximal portions 2 a′ , the distortions that concentrate at the proximal portions 2 a′ of the motor mounts 2 a are dispersed without being transmitted to the pusher plate 1 , and thus do not adversely affect the load cell 3 .
[0030] FIG. 3 is a diagram illustrating an injection unit according to a second embodiment of the present invention, showing a sectional view cut along the central part thereof. In addition, FIG. 4 , like FIG. 2 , is a diagram showing the interface between the pusher plate 1 and the housing 2 , as a sectional view cut along a direction vertical to the plane of the paper in FIG. 3 (that is, as seen from the front side of the injection screw 17 ).
[0031] In the second embodiment of the present invention, only the structure of the thrust force drive means that drives the injection screw 17 axially and the interface between the pusher plate 1 and the housing 2 are different from their counterparts in the first embodiment.
[0032] In the second embodiment, the ball nut 13 b of the ball screw/nut mechanism 13 that forms the thrust force drive means is fixedly mounted on the end plate 15 , and the threaded part of the ball screw shaft 13 a screws into the ball nut 13 b . Then, the other end of the ball screw shaft 13 a is mounted on the housing 2 by bearings 14 so as to be rotatable but axially unmovable. In addition, the driven pulley 19 is mounted on the housing 2 side of the ball screw shaft 13 a , and a timing belt is run between the driven pulley 19 and a drive pulley mounted on the output shaft of an injection motor, not shown.
[0033] In addition, with respect to the housing 2 and the pusher plate 1 , 2 c and 2 d indicated by cross-hatching in FIG. 4 form abutting portions, with the housing 2 and the pusher plate 1 joined at these abutting portions 2 c , 2 d and fixed in place by bolts or the like. The remaining structures are the same as those in the first embodiment. In addition, in the operation of this injection unit, the driven pulley 19 is driven by the injection motor and the ball screw shaft 13 a rotates. The ball screw shaft 13 a engages the ball nut 13 b mounted on the end plate 15 , and therefore the ball screw shaft 13 a rotates as well as moves axially, causing the housing 2 , on which is mounted the ball screw shaft 13 a fixedly so as to be axially unmovable, and the pusher plate 1 , which is fixedly mounted on the housing 2 , to move axially, and moving the injection screw 17 axially to inject and the like. The operation of the thrust forcing drive means differs only slightly from that of the first embodiment, with the other operations identical to those of the first embodiment shown in FIG. 1 .
[0034] At the same time, as shown in FIG. 4 , the abutting portions 2 c , 2 d of the housing 2 and the pusher plate 1 are disposed at locations removed from the proximal portions 2 a′ of the projecting motor mounts 2 a . As with the first embodiment, a force generated by the tension of the timing belt 10 is exerted on the drive pulley 11 , the screw rotation motor 12 , and, through the motor mounts 2 a , on the housing 2 , and concentrates at the proximal portions 2 a′ of the mounts 2 a , causing the housing 2 to distort around the proximal portions 2 a′ . The proximal portions 2 a′ of the motor mounts 2 a and the abutting portions 2 c , 2 d are disposed at different locations, and therefore the distortion is diffused without being transmitted to the pusher plate 1 and without adversely affecting the load cell 3 mounted on the pusher plate 1 .
[0035] In each of the embodiments described above, the ball screw shaft rotates while the ball nut remains fixed. However, as can be understood by those skilled in the art, conversely, the ball screw shaft may be fixed while the ball nut rotates.
[0036] In addition, although a ball screw/nut mechanism 13 is used as the thrust force drive means, alternatively, a linear motor may be used instead. | The invention provides an injection molding machine injection unit that eliminates adverse effects on the load cell of belt tension due to belt drive. A load cell that detects resin pressure is mounted on a pusher plate and a rotation-transmitting member, on which an injection screw is fixedly mounted, is axially supported by an inner annular part of the load cell. The shaft of a pulley is axially supported on the pusher plate and coupled by splines to the rotation-transmitting member. A screw rotation motor is mounted on motor mounts of a housing mounted on the rear surface of the pusher plate. Tension on a belt run between the pulley and a pulley mounted on the motor output shaft concentrates a force at the base of the motor mounts. However, the housing is separate from the pusher plate and fixedly mounted on the pusher plate at a location other than that occupied by the base of the motor mounts. Therefore, the belt tension does not adversely affect the load cell, thus enabling high-accuracy resin pressure detection. | 1 |
This application claims the benefit of Provisional Application No. 60/984,274, filed Oct. 31, 2007.
TECHNICAL FIELD
The present disclosure relates generally to child resistant blister packaging for the packaging and dispensing of articles. More specifically, the present disclosure is directed to a package including a child resistant blister package housing with removable tab strips for encapsulating one or more blister packages and allowing controlled and child-resistant packaging and dispensing of articles.
BACKGROUND
It is known that blister packaging can be used to store and deliver a wide range of items. Among the many types of items that can be stored and delivered in blister packs are pharmaceutical products, such as tablets, pills, capsules, and other related items. Conventional blister packages include a blister tray that is typically a thermoformed plastic sheet with a plurality of blister cells or depressions formed therein. Typically, after items are placed in the cells, the items are retained and protected in the respective cells by securing a backing sheet to the blister tray. The backing sheet is often a thin layer of metal foil, plastic, paperboard, or other material secured to the back of the blister tray, thereby sealing the cells. In other types of blister packages, the contents are placed in substantially puncture-proof foil containers that can be covered with foil or paperboard backing.
In many blister packages, the foil backing is thin enough to be punctured mechanically, or ruptured by pressing the blister so that the encapsulated item penetrates the foil backing. If the backing sheet is made from, for example, paperboard, or similar material, then the backing often includes gates in the backing sheet that covers the openings of respective blister cells. In practice, each gate is deformed or manipulated so that it ruptures or partially separates from the surrounding paperboard to allow the item contained within the blister cell to be pushed out of the blister cell for use.
While the conventional blister packaging is viewed by many to be suitable for most applications, there are several design deficiencies. The conventional packages provide removal of the items from the blister cells, but offer little in the way of resisting child tampering. Child resistance is a feature that is desired, particularly for dose pharmaceutical packaging.
To address the desirability of child resistance, many blister packaging designs employ materials of increased rigidity, compared to conventional non-child-resistant packages. For example, in increased-rigidity packages, the backing sheet and/or the blister cells can be made thicker and/or more resistant to pressure. As such, a young child is unlikely to be able to generate the pressure required to force the package contents through the increased-strength materials. In addition to the benefits in terms of child-resistance, increased rigidity can provide additional protection for the enclosed materials, which may be, as is the case with pharmaceuticals, fragile and susceptible to breakage.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a plan view of an exemplary packaging blank and tab strip insert, according to an exemplary embodiment of the present disclosure.
FIG. 2 is a plan view of an exemplary package, made from the packaging blank and tab strip insert of FIG. 1 .
FIG. 3 illustrates a method for accessing products packaged in the exemplary package of FIG. 2 .
FIG. 4 illustrates an additional child resistance feature of the exemplary package of FIG. 2 .
FIG. 5 is a plan view of an exemplary packaging blank and tab strip insert, according to an alternative embodiment of the present disclosure.
FIG. 6 is a plan view of an exemplary package, made from the packaging blank and tab strip insert of FIG. 5 .
DESCRIPTION
As required, detailed embodiments of the present disclosure are disclosed herein. It must be understood that the disclosed embodiments are merely exemplary of the disclosure that may be embodied in various and alternative forms, and combinations thereof. As used herein, the word “exemplary” is used expansively to refer to embodiments that serve as an illustration, specimen, model or pattern. As used herein, the terms “foldable score line” and “severance line” refer to all manner of lines indicating optimal fold or cut locations, frangible or otherwise weakened lines, perforations, a line of perforations, a line of short slits, a line of half-cuts, a single half-cut, a cut line, scored lines, slits, any combination thereof, and the like.
The figures are not necessarily to scale and some features may be exaggerated or minimized to show details of particular components. In other instances, well-known components, systems, materials or methods have not been described in detail in order to avoid obscuring the present disclosure. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure.
It is contemplated that the present disclosure is not limited to the pharmaceutical and personal healthcare related articles referenced with the illustrated embodiment. Instead, embodiments of packaging made in accordance with the present disclosure can have application in packaging for any small, delicate, sensitive, or portable article. Furthermore, the packaging can be used for larger items as a method of decreasing the incidence of product theft. Examples of articles for which such packaging can be employed include all manner of consumable products such as candy, food, vitamins, tobacco, and the like; all manner of personal care products such as contact lens, birth control devices, smoking cessation patches, hearing aid batteries, and the like; as well as any item that can fit within a portable container.
Referring now to the drawings, wherein like elements are represented by like numerals, and wherein like articles and respective elements are, at times, represented by primed numerals, FIG. 1 is a plan view of an exemplary packaging blank 10 and a tab strip insert 12 made according to the present disclosure.
The packaging blank 10 includes a face panel 14 a and a back panel 14 b . The face panel 14 a and the back panel 14 b are hingedly connected along a foldable score line 16 . Although, in this exemplary embodiment, the panels 14 a , 14 b are illustrated as integrally formed as one piece, it should be understood that the respective panels 14 a , 14 b can be formed as two separate and distinct pieces.
The packaging blank 10 and the tab strip insert 12 can be constructed from any suitable substrate material. Suitable substrate materials include, but are not limited to, plastics, conventional paperboard, including solid bleached sulfate (SBS) paperboard of suitable weight, size and shape, and combinations thereof. Commercial examples of suitable substrate include EASY SEAL® and EASY SEAL PLUS® self-sealing boards, both of which are currently available from MeadWestvaco Corporation. Additionally, it is contemplated that embodiments of the present disclosure may be used in conjunction with NATRALOCK® packaging material. Additionally, a tear-resistant layer may or may not be adhered to the packaging blank 10 and/or the tab strip insert 12 . Tear-resistant layers, if included, are often laminated to the blank before cutting. Even if no tear-resistant layers are included as part of the packaging blank 10 and/or the tab strip insert 12 , the packaging blank and/or a package made from the packaging blank 10 and/or tab strip insert 12 may be augmented by tear resistant materials such as, but not limited to, tear resistant tapes, labels, glues, coating, combinations thereof, or the like. Furthermore, it is possible, and in fact contemplated, that an adhesive layer or material may be added to the packaging blank 10 and/or the tab strip insert 12 prior to assembling the packaging blank 10 and the tab strip insert 12 into a package, as will be explained below. The packaging blank 10 and/or the tab strip insert 12 may also be an unbleached board, depending on the desired appearance of the final package.
The face panel 14 a can further include one or more blister apertures 18 . The blister apertures 18 are shaped and dimensioned to receive the blisters 20 of a blister pack 22 . As illustrated, one or more blisters 20 can contain a product 24 , illustrated in FIG. 1 as a capsule of medication. The face panel 14 a can further include bending lines 26 and 28 . The bending lines 26 and 28 can be interrupted by one or more tab strip access pads 30 . The tab strip access pads 30 can be defined by severance lines 32 and 34 , and cut lines 36 and 38 .
The back panel 14 b includes one or more product access apertures 40 . The product access apertures 40 are defined by severance lines 42 . The severance lines 42 can be shaped and dimensioned to allow the packaged product to pass therethrough, after or during removal of the material defined by the severance lines 42 , by interfacing with and/or receiving a tool or a force from the product itself in a method that will be described below with reference to FIG. 3 . The back panel 14 b further includes one or more tab strip grasping pads 44 . The tab strip grasping pads 44 can be defined by severance lines 46 and 48 , and cut lines 50 and 52 . The tab strip grasping pads 44 can align with and cooperate with the tab strip access pads 30 of the face panel 14 a . It should be understood that the tab strip access pads 30 and the tab strip grasping pads 44 can have any desired shape and dimensions.
The tab strip insert 12 can include one or more tab strips 54 . The tab strips 54 can be defined by severance lines 56 , 58 , and 60 . As illustrated, the tab strips 54 can include various features. In FIG. 1 , these features are illustrated by assigning regions to the tab strips 54 in accordance with the general purpose of that region. A tab strip 54 can include a grasping region 62 , a tamper safety region 64 , and a product access prevention region 66 .
The grasping region 62 of a tab strip 54 can be shaped and dimensioned substantially similar to the tab strip access pads 30 of the face panel 14 a , and the tab strip grasping pads 44 of the back panel 14 b . When the tab strip insert 12 is assembled with the packaging blank 10 , the grasping region 62 of the tab strips 54 can align with and cooperate with the tab strip access pads 30 of the face panel 14 a , and the tab stress grasping pads 44 of the back panel 14 b.
The tamper safety region 64 of a tab strip 54 is included to increase the tamper-resistance of the tab strips 54 , as will be explained below with respect to FIG. 2 . In the illustrated embodiment, the tamper safety region 64 is formed by narrowing the tab strip 54 in the area adjacent the grasping region 62 . The purpose of the tamper safety region 64 is illustrated and described below with respect to FIGS. 3 and 4 .
The product access prevention region 66 is designed to further impede unauthorized access to the product 24 in a blister pack 22 . The product access region 66 aligns with and cooperates with the product access apertures 40 of the back panel 14 b and the blisters 20 . This function of the tab strips 54 is illustrated and described below with respect to FIGS. 3 and 4 .
With additional reference now to FIGS. 2-3 , a package 70 , made from the packaging blank 10 and the tab strip insert 12 , is shown. A package 70 is formed by inserting the blisters 24 of a blister pack 22 into respective blister apertures 18 , such that the blisters 24 protrude from the face panel 14 a . After the blister pack 22 is in position, the tab strip insert 12 can be placed into position. To place the tab strip insert 12 into position, the grasping portions 62 of the tab strips 54 can be aligned with the tab strip access pads 30 of the face panel 14 a . Similarly, the product access prevention regions 66 of the tab strips 54 can be aligned with the blister apertures 18 of the face panel 14 a . After the tab strip insert 12 is in position, the face panel 14 a and the back panel 14 b of the blank 10 can be folded into a face contacting arrangement, and secured. To fold the blank 10 , the facing surfaces of the face panel 14 a and the back panel 14 b are brought toward each other by folding along foldable score line 16 . In completing the folding step, the tab strips 54 are aligned with respective blister apertures 18 , and thereby with blisters 20 of blister pack 22 . Likewise, as mentioned above, the tab strip access pads 30 of the face panel 14 a and the tab strip grasping pads 44 of the back panel 14 b can be aligned with each other, and with the tab strip grasping regions 62 . The face panel 14 b and the back panel 14 a can be secured to one another and to the tab strip insert 12 . Additionally, one or more blister packs 22 can be held in place, using any desired means or methods.
In practice, to access an item 24 from a package 70 , a user bends the package 70 along one of the bending lines 26 , 28 . If the user is looking at the face panel 14 a , then the package portion between the bending line 26 , 28 and the edge of the package 70 is bent away from the user, as shown in FIG. 3 . After the package is bent, the tab strip access pads 30 will generally be accessible. As illustrated, the tab strip access pads 30 can be joined to respective grasping regions 62 of the tab strips 54 , and tab strip grasping pads 44 of the back panel 14 b . The user can grasp the tab strip access pads 30 , and any other material joined thereto, and lift the material, i.e., apply a force to the material that pulls a tab strip access pad 30 toward the user if the user is looking at the face panel 14 a . By applying this force to a tab strip access pad 30 , and any material joined thereto, the user can sever the perforations of severance lines 32 and 34 that partially define the tab strip access pads 30 . As illustrated, this force can also sever the perforations of severance lines 46 and 48 , which partially define the tab strip grasping pads 44 , if the tab strip grasping pads 44 are aligned with the tab strip access pads 30 , as illustrated.
Once the perforations of the severance lines 32 , 34 , 46 , and 48 are severed, the tab strip 54 can be pulled out of the package 70 . The tab strip 54 may be pulled out of the package 70 by withdrawing laterally the tab strip 54 and sliding the tab strip 54 out from between the face panel 14 a and back panel 14 b , approximately through the area formed by removing the tab strip access panel 30 .
After the tab strip 54 is removed, the product 24 is more easily removable by applying a force to the top of the blister 20 behind which the tab strip 54 has been removed. As a force is applied to the blister 20 , the product 24 can be pushed through the backsheeting of the blister pack 22 , and into the product access aperture 40 , defined by a severance line 42 . The applied force must be sufficient to sever the perforations of severance line 42 , after which the product 24 can exit the package 70 through the product access aperture 40 .
Turning now to FIG. 4 , an additional safety feature of the package 70 is illustrated. As explained above, the tamper safety region 64 can increase the tamper resistance of the package 70 . As illustrated in FIG. 4 , if a skewed force is applied to a tab strip access panel 30 , then the grasping region 62 of the tab strip 54 that is joined to the tab strip access panel 30 may be severed from the product access prevention region 66 of that tab strip 54 , making removal of the tab strip 54 from the package 70 difficult, if not impossible. If the product access prevention region 66 of the tab strip 54 remains in the package 70 , then it may be difficult, if not impossible, to push the product 24 out of the package in the intended manner. This feature can add an additional layer of tamper prevention and/or child resistance to the package 70 .
Referring now to FIG. 5 , an alternative design for a packaging blank 10 ′ and a tab strip insert 12 ′ is illustrated. In FIG. 5 , primed numerals are used to denote features that can have similar structure, design, and/or purpose as the features denoted by unprimed numerals in FIGS. 1-4 .
The packaging blank 10 ′ includes a face panel 14 a ′, and a back panel 14 b ′. The panels 14 a ′, 14 b ′ are hingedly connected along a foldable score line 16 ′. Although in this exemplary embodiment, the panels 14 a ′, 14 b ′ are illustrated as integrally formed as one piece, it should be understood that the respective panels 14 a ′, 14 b ′ can be formed as two separate and distinct pieces.
The face panel 14 a ′ can include one or more blister apertures 18 ′. The blister apertures 18 ′ can be shaped and dimensioned to receive the blisters 20 of a blister pack 22 . As illustrated, one or more blisters 20 can contain a product 24 , illustrated in FIG. 5 as a capsule of medication. The face panel 14 a ′ can also include one more tab strip access pads 30 ′. The tab strip access pads 30 ′ can be defined by severance lines 72 , 74 , and 76 .
As illustrated in FIG. 5 , the back panel 14 b ′ can be substantially identical to the face panel 14 a ′. Hence, though the features of the back panel 14 b ′ are given different names and different reference numerals, relative to the face panel 14 a ′, it should be understood that the determination as to which panel is the face panel 14 a ′ and which panel is the back panel 14 b ′ can be determined solely by orientation of the packaging blank 10 ′.
The back panel 14 b ′ can include one or more product access apertures 40 ′. The product access apertures 40 ′ be shaped and dimensioned to allow the packaged product to pass therethrough. As explained above, the product access apertures 40 ′ can have the same shape and dimensions as the blister apertures 18 ′ of the face panel 14 a ′. The back panel 14 b can further include one or more tab strip grasping pads 44 ′. The tab strip grasping pads 44 ′ can be defined by severance lines 80 , 82 , and 84 . The tab strip grasping pads 44 ′ can align with and cooperate with the tab strip access pads 30 ′ of the face panel 14 a ′. It should be understood that the tab strip access pads 30 ′ and the tab strip grasping pads 44 ′ can have any desired shape and dimensions.
The tab strip insert 12 ′ can include one or more tab strips 54 ′. The tab strips 54 ′ can be defined by severance lines 86 . As illustrated in FIG. 5 , the severance lines 86 can have any desired features. For example, some or all of a severance line 86 can be replaced with a cut line. Additionally, or in the alternative, the number of perforations along a severance line 86 can be increased or decreased to make severance of a tab strip 54 ′ from the tab strip insert 12 ′ more or less difficult. This may be useful when tailoring the tab strip insert 12 ′ for a desired purpose. Although not illustrated in FIG. 5 , it should be understood that the tab strips 54 ′ can include a tamper safety region that is substantially similar in function to the tamper safety region 64 of the tab strips 54 illustrated in FIGS. 1-4 .
With additional reference now to FIG. 6 , a package 70 ′, made from packaging blank 10 ′ and tab strip insert 12 ′, is shown. A package 70 ′ can be formed by inserting the blisters 20 of a blister pack 22 into respective blister apertures 18 ′, such that the blisters 20 protrude from the face panel 14 a ′. After the blister pack 22 is in position, the tab strip insert 12 ′ can be aligned with the blisters 20 of the blister pack 22 . It should be understood that the dimensions of the tab strip insert 12 ′, as illustrated, are substantially identical to the dimensions of the face panel 14 a ′ and the back panel 14 b ′. Therefore, the tab strips 54 ′ of the tab strip insert 12 ′ line up with the tap strip access pads access pads 30 ′, the tab strip grasping pads 44 ′, and the blister apertures 18 ′. After the tab strip insert 12 ′ is in position, the blank 10 ′ can be folded into a face contacting arrangement, and secured. To fold the blank 10 ′, the facing surfaces of the face panel 14 a ′ and the back panel 14 b ′ are brought toward each other by folding along foldable score line 16 ′. After completing the folding step, the tab strips 54 ′ are aligned with respective blister apertures 18 ′, and thereby with blisters 20 of blister pack 22 . The face panel 14 a ′ and the back panel 14 b ′ can be secured to one another and/or to the tab strip insert 12 ′, and the blister pack 22 can thereby be held in place, using any desired means or methods.
In practice, to access an item 54 from a package 70 ′, upward pressure, i.e., a pressure that pulls away from the face panel 14 a ′ and the back panel 14 b ′, is applied to a tab strip access pad 30 ′. When such a force is applied to the tab strip access pad 30 ′, the perforations of the severance lines 72 , 74 and 76 are severed, thereby severing the tab strip access pad 30 ′ from the surrounding material of the face panel 14 a ′. Additionally, this force can sever the perforations of the severance line 86 of the tab strip insert 12 ′, and the severance lines 80 , 82 , and 84 of the back panel 14 b ′. After the perforations of severance lines 72 , 74 , 76 , 86 , 82 , and 84 are severed, the tab strip 54 ′ can be pulled out of the package 70 ′, similar to the tab strip 54 of FIGS. 1-4 . After the tab strip 54 ′ is pulled out of the package 70 ′, the product access apertures 40 ′ are unobstructed by additional material. Once an adequate force is applied to a blister 20 , the product 24 ruptures or tears through the backsheeting of the blister pack 22 , and the product 24 can pass out of the package 70 ′ through the product access aperture 40 ′
It should be understood that while the product access apertures 40 ′ of FIG. 5 are illustrated as substantially similar to blister apertures 18 ′, the product access apertures 40 ′ can be defined by a severance line, thereby requiring the removal of material before a product 24 can pass therethrough.
While only one blister pack 22 is illustrated in the figures, it should be understood that any number of blister packs 22 can be included in any of the illustrated embodiments. Furthermore, the blister apertures 18 , 18 ′ need not have identical shape or dimensions. Similarly, product access apertures 40 , 40 ′ of all embodiments can have an irregular shape to provide gates (not illustrated) and or can include additional layers of material to increase the amount of force required to gain access to the product 24 housed in a blister 20 of a blister pack 22 . It should also be understood that the inclusion of an adhesive layer may be required for some or all of the described embodiments.
Additionally, while the illustrated embodiments have generally shown the face panels, back panels, and the tab strip inserts to be of substantially identical shape, dimensions, and/or material, it should be understood that the face panels and back panels of all embodiments made according to the present disclosure need not be symmetrical or substantially identical, and need not be made from material having substantially identical properties. Substantial variations in the shape and dimensions of, as well as the materials used to form the face panels, the back panels, and/or the tab strip inserts are possible and are, in fact, contemplated.
While the illustrated embodiments have included packaging blanks made from self-sealing material, it should be understood that glue or other fastening means can be used when assembling the packaging blanks 10 , 10 ′ and tab strip inserts 12 , 12 ′ into packages 70 , 70 ′.
The law does not require and it is economically prohibitive to illustrate and teach every possible embodiment of the present claims. Hence, the above-described embodiments are merely exemplary illustrations of implementations set forth for a clear understanding of the principles of the disclosure. Variations, modifications, and combinations may be made to the above-described embodiments without departing from the scope of the claims. All such variations, modifications, and combinations are included herein by the scope of this disclosure and the following claims. | A child resistant product package includes a first panel, a second panel, a tab strip insert, and a blister package. The first panel incorporates at least one blister aperture and at least one tab strip access pad. The second panel includes at least one product access aperture and at least one tab strip grasping pad. The tab strip insert has at least one tab strip. The first panel and the second panel are fastened together. Once fastened together, the first panel and the second panel collectively form a housing for the tab strip insert and the blister package. | 1 |
This is a Divisional Application of application U.S. Ser. No. 09/165,409 filed Oct. 2, 1998 now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to office furniture. More particularly, the invention concerns an improved, multifunction office furniture system having a novel interlocking connecting mechanism which permits the easy assembly of a variety of different structural components in a variety of different configurations to form highly efficient work areas.
2. Discussion of the Prior Art
Office furniture systems that exhibit superior structural characteristics and which exhibit flexibility and interchangeability among the parts to create multi-purpose and multi-function work stations are in wide demand for many institutional applications. Entities having great need for such office systems include schools, hotels, business offices, and various governmental entities. Particularly in demand are flexible office systems that are easily altered to fit the work environment and meet the work requirements.
While many types of office systems have been suggested in the past, a typical drawback of such office systems is lack of flexibility to fit the space allowed for the work environment requiring the work environment to fit the office system. As a general rule, when the prior art furniture designers have attempted to overcome this limitation in prior art designs, such designs lack the structural strength and flexibilty to meet the work requirements.
The prior art systems typically use a variety of different arrangements to interconnect together desk tops, cabinets, files and other structural components to form variously configured work stations. Exemplary of a typical prior art adjustable desk system is that described in U.S. Pat. No. 5,544,593 issued Canfield et. al. The Canfield patent discloses a basic superstructure that permits various cantilever supports to be connected thereto for supporting desk tops, pedestals and the like so that the various components can be adjusted relative to one another. The basic Canfield superstructure also permits back to back mounting of cabinets, desk tops and like components to provide separated work spaces.
Another prior art desk system is disclosed in U.S. Pat. No. 5,038,539 issued to Kelly et. al. This later patent describes a work space management system for dividing an open work space into separate, discrete work areas. The Kelly et al system includes a wall system having a framework formed of rigid rectangular frames joined together at their edges to form the defined work areas. The Kelly et al patent also discloses various wire management components which are secured to the frames for routing communication and power wiring.
A drawback of many of the prior art adjustable desk systems resides in the fact that the systems are generally quite complex, are often ergonomically unsound and, while often providing for adjustability of some components, fail to provide the overall convenience and flexibility required by modem computer intensive offices. In this connection, the constantly changing technology and the rapid emergence of computer networking systems have created an ever increasing demand for easily adaptable office furniture. Additionally, because of increases in repetitive stress injuries, there is a great demand for systems of the aforementioned character which offer ergonomic features that effectively guard against stress injury.
As will be discussed in detail in the paragraphs which follow, the desk system of the present invention overcomes many of the drawbacks of prior art systems by providing a system which is of a simple, ergonomically sound design and yet has great versatility. The system of the present invention is not only practical in use but provides an extremely attractive, structurally sound, free-standing work-area defining unit which is ideally suited for modem office complexes. The system is easy to assemble and disassemble by relatively unskilled workers and is uniquely designed to provide a safe and productive work environment.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a novel office system construction that is ideally suited for use in schools, hotels, business offices, and governmental offices, and similar commercial establishments.
Another object of the present invention is to provide a flexible construction for an office system that will permit the user to fit the office system to the work environment rather than fitting the work environment to the office system.
Another object of the invention is to provide a highly versatile work station system which is very attractive, is easy to assemble, disassemble and adjust, and yet, is structurally sound and durable in use.
Another object of the invention is to provide a system of the character described which is capable of readily accommodating changing work conditions in the users facilities.
Another object of the invention is to provide a fully adjustable, highly versatile work station system which includes a number of ergonomic features which provide a safe and productive work environment.
Another object of the invention is to provide a desk system which includes uniquely configured, vertical support columns to which a number of different types of structural components can be quickly and easily connected.
Another object of the invention is to provide a system of the character described in the preceding paragraph which is specially designed to eliminate under work surface obstacles.
Another object of the invention is to provide an adjustable desk system that includes a novel cable management systems which enables effective cable management within the structural components of the apparatus so that the cables are well protected from damage and yet are easily accessible so as to provide a wide range of electrical and communication capabilities.
Another object of the invention is to provide a desk system of the class described that is designed for ease and speed of installation and is readily adjustable into various configurations using a number of different types of readily interchangeable components.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a generally perspective view of one form of the desk system of the present invention.
FIG. 2 is a generally perspective, exploded view illustrating the manner by which certain of the components, such as the divider panels of the system, are releasably interconnected with one of the novel vertical support columns of the apparatus.
FIG. 3 is a generally perspective, exploded view similar to FIG. 2 illustrating the manner by which the outwardly extending side members of the leg assembly of the desk system are releasably interconnected with one of the novel vertical support columns of the apparatus.
FIG. 4 is a generally perspective, exploded view similar to FIGS. 2 and 3 illustrating the manner of interconnection of the structural panels of the system with one of the novel vertical support columns of the apparatus.
FIG. 5 is a cross-sectional view of one of the novel vertical support columns of the apparatus and a portion of one of the angularly extending attachment brackets that can be engaged into incremental notches formed in the corners of the support columns.
FIG. 6 is a generally perspective view of a closure shroud element which is receivable within radially outwardly extending grooves formed in each of the vertical support columns.
FIG. 7 is a cross-sectional view of a stiffener element of the character used to interconnect together two or more lengths of the support columns of the invention.
FIG. 8 is a generally perspective, exploded view illustrating the manner of interconnection of several of the different component parts of the desk system with longitudinally spaced apart vertical support columns of the character shown in FIGS. 2 through 5.
FIG. 9 is a generally perspective, exploded view illustrating the manner of interconnection of the wing-like side members of the leg assemblies and the floor engaging, stabilizing members of the leg assembly with an elongated connector element that permits interconnection of the leg assemblies with a selected one of the vertical support columns of the invention.
FIG. 10 is a generally perspective, exploded view of one form of the structural panel of the desk system.
FIG. 11 is a generally perspective, exploded view of one form of the connector means of the invention which is used to interconnect first and second lengths or segments of the vertical support columns.
FIG. 12 is an enlarged, cross-sectional view showing the wing-like sides of the leg assembly interconnected with one of the vertical support columns and also illustrating the column segment connector means of the invention including the stiffener element shown in FIG. 7 which is disposed internally of the vertical support column.
DESCRIPTION OF THE INVENTION
Referring to the drawings and particularly to FIGS. 1 through 8, one form of the desk system of the present invention is there illustrated. As best seen in FIG. 1, one embodiment of the desk system comprises four identical, individual work stations 12 which are interconnected in a back-to-back relationship to provide a free standing array. Each of the four work stations 12 includes a generally horizontally extending first work surface 14 and a second elevated work surface 16 . The back edges 14 a and 14 b and 16 a and 16 b of each of the work surfaces 14 and 16 extend at right angles to one another and the front edges of each of the work surfaces are curved in the manner shown in FIG. 1 to permit ergonomically desirable access to the work surfaces by one or two persons using the work station.
One end of work surface 14 is supported by a storage unit 18 which includes a plurality of slidably mounted, stacked drawers 20 . The other, or right edge of work surface 14 as viewed in FIG. 1 is supported by one of the novel leg assembly of the invention generally designated in FIG. 1 the numeral 22 . This novel leg support assembly 22 includes a pair of outwardly extending, floor engaging stabilizer members 24 and a pair of wing-like side members 30 which are connected to central support 27 in a manner presently to be discussed.
A key aspect of the desk system of the present invention is the previously mentioned support member or column 27 which has the unique cross-sectional configuration shown in FIGS. 2 through 5 of the drawings. This novel support is used in several key locations in the system configuration shown in FIG. 1 . For example, the central support column is used in the previously identified leg assembly 22 , in a somewhat similar leg assembly 22 a disposed at the left end of the work station as viewed in FIG. 1, and in an intermediate location where the leg assembly is designated as 22 b . This highly novel support column not only functions to support the work surfaces of the system, but also functions to support plurality of laterally extending and longitudinally extending structural panels 32 which are disposed below the work surface 14 . Additionally, the novel support columns support a plurality of longitudinally and laterally extending divider panels 34 which are disposed above the work surface. Divider panels 34 function to separate the four back-to-back work stations in the manner illustrated in FIG. 1 .
The lower structural panels 32 , which are of a unique construction presently to be described, provide structural integrity to the array and extend generally perpendicularly outwardly from the walls of support columns 27 in the manner illustrated in FIGS. 1 and 4. For example, several lateral structural panels extend from column 27 of leg assembly 22 , while several longitudinal structural panels extend from column 27 of leg assembly 22 a (FIG. 1 ). Similarly, a lateral divider panel extends from an upper column segment 27 a of leg assembly 22 while a longitudinal divider panel extends from an upper column segment 27 a of leg assembly 22 a . At least one of the longitudinally extending structural support panels, (designated in FIG. 8 by the numeral 33 ), comprises a wire management control panel. This novel wire support panel 33 includes a tray-like member 33 a which functions to support and separate electrical cables and the like which can be connected to conventional floor outlet 35 and then introduced into the interior of a selected one or more of the support columns 27 and the structural panels 32 a . The cables can also be connected to a ceiling outlet and run downwardly through stacked column segments.
Another novel feature of the desk system of the present invention comprises the column segment connector means which functions to connect together first and second lengths or segments of support columns 27 . For example, as shown in FIG. 8, the previously identified lower support columns 27 can be interconnected with upper support columns designated in FIG. 8 as 27 a to conveniently extend the overall height of the support column. For example, the novel segment connector means, the details of which will presently be described, can be used to securely interconnect lower segments 27 with upper segments 27 a so that the upper segments 27 a can rigidly support the longitudinally extending divider panels 34 in the manner indicated in FIGS. 1 and 8.
As also indicated in FIG. 8, certain of the wing-like, side members 30 can be provided with vertically spaced-apart slots 39 which are adapted to receive outwardly extending cantilever type support members 40 which can, where desired, function to support outward extending, auxiliary work surfaces such as the work surface identified in FIG. 8 by the numeral 42 .
Turning next to FIGS. 2 through 5, the details of construction of the important central support members or columns 27 and 27 a of the invention are there illustrated. As best seen in FIG. 5, the columns are generally octagonal shaped in cross section with each of the support members 27 having a central axis 46 , first and second opposing side walls 48 and 50 respectively. Front and back walls 52 and 54 are integrally formed with or otherwise connected to side walls 48 and 50 by wall connecting portions in the manner best seen in FIG. 3 . Each of the front, back and side walls includes a central portion 56 and first and second spaced-apart marginal portions 58 . Disposed between the central portions and the marginal portions of each of the walls are first and second generally coplanar grooves generally designated in the drawings by the numeral 60 . Each of the marginal portions 58 of each of the side walls 48 and 50 includes a first edge 62 . Similarly, each of the marginal portions 58 of each of the front and back walls 54 and 52 includes a second edge 64 (FIG. 3 ). Disposed between-each of the edges 62 and 64 is a corner groove 67 which extends generally radially outwardly from central axis 46 of the support column. These radially outwardly extending grooves 67 are closed by back walls which are provided with spaced-apart slots 67 a (FIG. 2 ). Slots 67 a are adapted to receive engagement fingers 150 a of cantilevered supports 150 which are of the same general character as those shown in FIG. 8 and can be used to support auxiliary work surfaces such as shelves.
A unique feature of the desk system of the present invention resides in the fact that each of the components which is interconnected with the columns 27 includes a specially configured connector strip which is provided with a pair of spaced-apart tongues that are slidably receivable within grooves 60 provided in each of the support column segments 27 and 27 a . Grooves 60 are substantially coplanar and reside within a plane generally parallel to the plane of central portions 56 . This novel feature permits the various components of the desk system to be quickly and easily interconnected with and removed from the various spaced-apart support columns 27 which provide vertical support to the components of the assembled array. More particularly, as can best be seen by referring to FIG. 2, each of the divider panels 34 includes a uniquely configured connector member 70 which is provided with spaced-apart tongues 70 a . As indicated in FIG. 2, tongues 70 a are slidably receivable within selected grooves 60 provided in the support column 27 a . As indicated in FIG. 2, connector member 70 is, in turn, adapted to be interconnected along its length with a selected divider panel 34 by any suitable means such as threaded connector or the like. It is apparent that with this construction, selected panels 34 can be quickly and easily removably interconnected with any one of the support columns 27 a to construct the arrays shown in FIGS. 1 and 8.
Referring particularly to FIGS. 3 and 12, it is to be noted that each of the wing-like side members 30 which form the previously identified leg assemblies 22 , 22 a and 22 b include a specially configured connector member 74 which includes spaced-apart, substantially coplanar tongues 74 a and 74 b which are slidably receivable within substantially coplanar grooves 60 provided in the support column 27 shown in FIG. 3 . In this latter case, connector member 74 is also provided with a pair of grooves 74 c which slidably accept spaced-apart tongues 76 formed proximate the in-board ends of wing-like members 30 . Connector member 74 further includes a pair of substantially coplanar grooves 74 d which are disposed proximate tongues 74 a and 74 b and are constructed and arranged to receive marginal portions 58 of the side walls.
Turning to FIGS. 4 and 10, it can be seen that, in similar fashion, each of the structural panels 32 and 33 of the invention include novel end plates 80 , each of which is provided with a pair of spaced-apart tongues 80 a which are slidably receivable within grooves 60 formed in the side walls 48 and 50 of the various spaced-apart support columns which are spanned by the structural support panels 32 in the manner shown in FIG. 8 . Once again, it is apparent that with the novel construction of the structural panels as is shown in FIGS. 4, 6 , and 10 , the panels can be readily interconnected with spaced-apart support columns 27 in the manner shown in FIG. 8 to provide a high degree of structural integrity to the desk system arrays shown in FIGS. 1 and 8. It is also to be understood that the wire management panels such as panel 33 also includes connector members 80 provided at each end thereof which connector members are also slidably receivable within grooves 60 provided in the spaced-apart support columns which function to support the wire management panels.
Referring particularly to FIGS. 4 and 10, each of the structural panels 32 can be seen to comprise, in addition to end connector assemblies 80 , first and second uniquely configured structural beams 84 and 86 which are connected to and span spaced-apart end connectors 80 . Structural beams 84 and 86 are generally mushroom shaped in cross-section so as to resist bending forces exerted on the members and each includes laterally spaced-apart, tab-receiving openings 87 a and 87 b (FIG. 10 ). Openings 87 a and 87 b are adapted to closely telescopically receive tab-like protuberances 80 a and 80 b formed proximate the upper and lower ends of each connector member 80 .
Connected proximate to each end of beams 84 are 86 are connector blocks 88 , each of which has spaced-apart screw receiving openings 88 a which are sized to receive connector means shown here as a plurality of thread forming metal screws 89 (FIG. 10 ). Thread forming metal screws 89 extend through openings 91 formed in each of the end plates 80 and are threadably received within the screw receiving channels 88 a formed in connector blocks 88 . With the construction thus described, when tabs 80 a and 80 b of end connectors 80 are inserted into openings 87 a , and 87 b , provided in each of the structural beams 84 , the assemblage thus formed can be securely drawn together and locked in position relative to the end plates by threading the thread forming screws 89 into the screw receiving channels 88 a provided in each of the connector blocks 88 . It is to be understood that rivets can also be used as connectors to connect blocks 88 to end plates 80 . After the end connectors 80 have been securely interconnected with the structural beams and the connector blocks, the assemblage thus formed is covered by first and second side closure panels 96 and 98 so as to enclose therebetween the spanner members and the connector blocks.
Also forming a part of each of the structural panels 32 are locking means for locking the end connectors 80 in a fixed position relative to the structural supports 27 from which they extend in the manner shown in FIG. 8 . These locking means are here provided in the form of a spring loaded locking mechanism 100 which comprises a supporting bracket 102 which is connected to connectors 80 , and a spring biased locking finger 104 which is carried by a bracket. Locking finger 104 is continuously biased outwardly through a slot 105 formed in the connector body by biasing means, shown here as coil spring 106 (see also FIG. 4 ). With this construction, when the end plates 80 are assembled with a selected support column 27 , locking finger will snap into engagement with one of a plurality of slit like openings 109 formed in all four walls of the vertical support column segments 27 and 27 a (FIGS. 2 and 8 ).
It is to be understood that the locking means of the invention can also be disposed internally of leg assembly side members 30 and can function to position the side members relative to the support columns 27 with which they are associated (see for example FIG. 9 ).
Turning to FIG. 9, it can be seen that side members 30 are interconnected with the previously identified elongated connector member 74 with the locking means of the invention, or mechanisms 100 being interconnected to the interface of connector 74 . Receivable within the lower open end of side member 30 is a connector block 112 which enables interconnection of the stabilizer members 24 with side members 30 by means of threaded connectors 114 which are threadably received within block 112 . More particularly, connector block 112 is telescopically received within the lower open end of the side members 30 and is held in position by fasteners 112 a which extend through connector member 74 and function to connect connector block 112 with connector member 74 and member 30 . The assemblage thus formed is then connected with the stabilizer member 24 in the manner previously described. Cavity 116 includes a bottom wall which receives threaded connectors 114 so that when the connectors are threadably interconnected with connector block 112 , the assemblage made up of side member 30 and connector 74 will be securely locked in position relative to stabilizer member 24 to form a stable, securely interconnected subassembly. In the leg assemblage illustrated in FIG. 9, the side member 30 is provided with a cable receiving opening 117 which permits convenient cable routing into the wire management structural panels. Openings 117 can be closed by removable closure panels 117 a . Similarly, the outboard ends of members 30 and 30 a can be closed by elongated closure strips 119 .
In the desk system construction illustrated in FIG. 1, upper side members 30 a are connected to lower side members 30 in the manner there shown and function to provide structural stability to the upper portions of the array. Providing further structural stability are the divider panels 34 which are disposed proximate the right and left ends of the array as viewed in FIG. 1 . As shown in FIG. 9, side members 30 a are interconnected with vertical support column 27 a by means of an elongated connector member 74 a which is of a construction similar to that of connector 74 . The upper open end of side members 30 a are preferably closed by a plastic closure cap 120 of the general configuration shown in FIG. 9 .
When desired, floor engaging castors 122 can be connected to stabilizer 24 in the manner indicated in FIG. 9 (see also FIG. 1 ). When desired, similar castors 122 can be connected directly to side members 30 in the manner shown in FIG. 1 . In this latter instance, a connector bracket 125 , to which the castor is threadably connected is connected to side members 30 .
Turning next to FIGS. 11 and 12, the details of the construction of the previously identified segment connector means of the invention can there be seen. In the present form of the invention, the segment connector means comprise a plurality of spaced-apart connector assemblies 126 . Each of the side connector assemblies comprise a bearing plate 128 having corner portions which are cammingly received within internal grooves 131 formed in supports 27 (FIG. 2 ). Each assembly also includes a washer 130 , a self-clinching nut 132 , and a plate lock 134 . A first connector assemblage 126 a is secured internally of support columns 27 proximate the lower extremities thereof. And a second threaded connector element assembly 126 b is disposed within support columns 27 proximate their upper extremities (FIG. 11 ). The assemblies are held securely in position within the support columns by the bearing plates 128 which, when rotated within columns 27 will cam into grooves 131 . The resiliently deformable, outwardly extending wing-like tabs 134 a formed on the plate locks 134 bite into the interior walls of the support columns 27 and prevent the bearing plates 128 from counter-rotating out of grooves 131 once the connector assembly is in position. In similar fashion, a connector assembly 126 c is disposed within the upper portion of the column segment 27 a . Connector assembly 126 c is similar in construction to assemblies 126 a and 126 b . However, the self-clinching nut 132 has been replaced with an internally threaded coupling nut 132 a which allows for further extension of the support columns as may be necessary.
Also forming a part of the connector means of the invention is a uniquely configured stiffener member 138 which is telescopically received within the upper portion of support column 27 and within the lower portion of support column 27 a . The configuration of this stiffener member, which is of the character shown in FIG. 7, provides a substantial reinforcement against and tendency column segment 27 a may have to bend relative to column segment 27 . As best seen in right-hand portion of FIG. 11, connector assemblies 126 b and 126 c are interconnected by an elongated, externally threaded tie rod 140 which extends interiorly of stiffener member 138 . Where desired, a castor 139 can be connected to connector assembly 126 a in the manner shown in the lower right-hand portion of FIG. 11 . If desired, a tie rod 140 can be used to interconnect connector assemblies 126 a and 126 b (see FIG. 12 ). To close the open upper ends of support columns, plastic closure caps 142 such as are shown in FIGS. 1 and 9 are used.
Turning once again to FIG. 5, it is to be noted radially outwardly extending grooves 67 formed in each of the vertical support columns 27 and 27 a is closed by a closure shroud 144 which is of the unique configuration shown in FIG. 6 . Each of the shrouds 144 is provided with a longitudinally extending, generally arrow-shaped protuberance 144 a which is receivable within a similarly shaped cavity 146 formed at each corner of the support columns 27 and 27 a (FIG. 5 ). Each shroud 144 also has a yieldably deformable curved wall portion 144 b which functions to close each of the radially extending grooves 67 in the manner best seen in FIG. 5 . With this novel construction, cantilever supports, such as supports 150 (FIGS. 7 and 8 ), can be inserted into a selected radially extending groove 67 by deforming the shroud member 144 in the manner shown in the lower right-hand portion of FIG. 7 .
Having now described the invention in detail in accordance with the requirements of the patent statutes, those skilled in this art will have no difficulty in making changes and modifications in the individual parts of their relative assembly in order to meet specific requirements or conditions. Such changes and modifications may be made without departing from the scope and spirit of the invention, as set forth in the following claims. | An improved, multifunction office furniture system having a novel interlocking connecting mechanism which permits the easy assembly of a variety of different structural components in a variety of different configurations to form highly efficient work areas. The system includes uniquely configured, vertical support columns to which a number of different types of structural components can be quickly and easily connected and provides a highly versatile work station system which is very attractive, is easy to assembly, disassemble and adjust, and yet, is structurally sound and durable in use. Because of its novel construction, the system is capable of readily accommodating changing work conditions in the users' facilities. | 0 |
RELATED PATENT APPLICATIONS
This is a continuation patent application of International Application No. PCT/SE99/00020 filed Jan. 12, 1999 also entitled CHILD SEAT FOR VEHICLES that designates the United States. The full disclosure of said application, in its entirety, is hereby expressly incorporated by reference into the present application.
TECHNICAL FIELD
The present invention relates to a child seat for vehicles according to the preamble of the accompanying claim 1 . The invention is particularly intended for use in connection with that type of child seats, which is provided with safety belts.
BACKGROUND OF THE INVENTION
In connection with vehicles, e.g. passenger cars, safety belts are used in a known manner to protect those traveling in the vehicle. In the case of a collision or of hard braking, the passenger can be retained in his seat by means of the safety belt, which provides enhanced safety.
Normal vehicle seats and safety belts are not adapted and dimensioned for achieving optimum protective action where the passenger is a small child. For this reason it is previously known to use special child seats, more particularly in the form of separate child seats that can be detachably fitted in one of the existing vehicle seats. Child seats, particularly those for infants, are commonly adapted to be fitted in a reverse position in the passenger seat of the vehicle, i.e., so that the passenger in the child seat will be traveling with his back turned towards the front of the vehicle. Hereby, a high safety is achieved for the passenger in the child seat in case of a collision or of hard braking.
It is known in the art to provide detachable child seats with a safety belt with the intention of providing a particularly high safety level. In this way, the child traveling in the child seat can be fastened and prevented from being thrown out of the child seat, for example, in a collision. Regarding the function of the safety belt, there is a general requirement to arrange it so as to run from a point behind the passenger and to be redirected at a point close to the shoulders of the passenger, i.e., at a position adapted to the length of the passenger.
Against this background, it is previously known to provide a child seat with a safety belt that has an adjustable height thereby being able to adapt to children having different body sizes. For example, within a family there may be a need for letting different children with different body sizes use the same child seat on different occasions. A requirement for adjusting the safety belt may also occur depending upon the clothing worn by the child seated in the child seat. For example, children may often change from thick winter clothing to thinner clothes. This will also contribute to the requirement of being able to adjust the height of the safety belt. In summary, it can be stated that a height-adjustable safety belt in a child seat provides an opportunity of achieving an optimum protective action for the child, in general independently of the child's body size or of the thickness of the clothing worn by the child.
A previously known child seat comprising a vertically adjustable safety belt is shown in U.S. Pat. No. 5,098,161. The child seat according to this document is detachably arranged on an existing seat of a vehicle and is provided with a safety belt by which a child can be fastened. The safety belt is designed with two belt bands running from two points above each shoulder of the child and onto a fastening element, which in turn is adapted to be fastened into a lock in the seat of the child seat between the child's legs.
The child seat of U.S. Pat. No. 5,098,161 adapts to children of varying size by providing the backrest of the seat with a number of vertically spaced openings. The two belt bands may then be arranged to run through appropriately selected openings in the backrest. Depending on the size of the child, the belt band can be detached from a previously selected opening and moved to another opening, giving the optimum fit for the passenger of the child seat.
Although the known child seat discussed above generally functions to satisfaction, it has one substantial drawback in that it is cumbersome and time-consuming to rearrange the belts traps vertically. As small children grow quickly, the child seat will have to be adjusted frequently, and, this being a cumbersome operation, it may easily be neglected, which might in turn entail that the child seat will not provide the desired protective action in case of a collision.
In view of the above described deficiencies associated with conventionally designed child seats, the present invention has been developed. These enhancements and benefits are described in greater detail hereinbelow with respect to several alternative embodiments of the present invention.
SUMMARY OF THE INVENTION
The present invention in its several disclosed embodiments alleviates the drawbacks described above with respect to conventionally designed child seats for vehicles and incorporates several additional beneficial features.
The object of the present invention is to provide an improved child seat for vehicles, which solves the above problem and which provides an automatic vertical adjustment according to the body size of the child. This object is achieved by a device, the characteristics of which are stated in the accompanying claim 1 .
The child seat according to the invention comprises a seat, a backrest and a vertically adjustable seat belt consisting of at least one belt band, equipped with a locking device arranged for lockable co-operation with a belt lock that is fixedly anchored in said child seat. The backrest of the present invention is designed with at least one vertically extending slot, with the belt band arranged to run through said slot and up to said belt lock. When a child is placed and fastened into the child seat according to the invention, each individual belt band will automatically adapt to the body size of the child so as to run over the shoulder portion of the child. Accordingly, the belt band in question can thus be adapted to the passenger of the child seat, in general, independently of the body size, or of the clothes worn by the child.
According to a preferred embodiment of the invention, it is utilized as a separate child seat, for detachable attachment into an existing seat of a vehicle. Preferred embodiments of the invention are further defined in the accompanying dependent claims.
The term “child seat” in this context refers to a particularly designed location in a vehicle that is intended primarily for children of an age of up to about 4 years. This term comprises detachable child seats as well as parts of existing, fixedly mounted vehicle seats. The term “child seat” shall further be regarded as comprising seats turned either forwards or backwards in relation to the traveling direction of the vehicle.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be described in greater detail in the following way, by example only, and with reference to the attached drawings, in which:
FIG. 1 shows a front view of a child seat according to an embodiment of the present invention;
FIG. 2 shows a rear view of a child seat according to an embodiment of the present invention;
FIG. 3 shows a rear view of a child seat according to an embodiment of the present invention; and
FIG. 4 shows a rear view of a child seat according to an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
As required, detailed embodiments of the present invention are disclosed herein. However, it is to be understood that the disclosed embodiments are merely exemplary of the invention that may be embodied in various and alternative forms. The figures are not necessarily to scale, some features may be exaggerated or minimized to show details of particular components or processes. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention.
FIG. 1 illustrates a somewhat simplified front view of a child seat according to the present invention. According to a preferred embodiment, the invention is shaped as a separate child seat 1 intended for detachable mounting inside a vehicle , e.g., a passenger car. The child seat 1 is constructed with a seat 2 and a backrest 3 , and is preferably manufactured from a hard plastic shell with soft padding in appropriate places. The hard plastic shell is then conveniently covered by upholstery made, for example, of a textile material. The seat 2 is bound sideways by two seat sides 4 , 5 . Preferably, the backrest 3 is somewhat bowl-shaped, i.e., has an extension in depth. In this way a child, preferably with an age of from newborn up to about 4 years, can travel in the child seat 1 and thereby be retained in a safe way.
In one manner of use, the child seat 1 is mounted in a reverse direction in the vehicle in question, i.e., with the backrest 3 turned towards the front of the vehicle. To this end, the child seat 1 comprises fastening elements (not shown) for attachment preferably in the front passenger seat of the vehicle, i.e., the seat beside the driver's seat. Such fastening elements may preferably be comprised of one or more loops or hooks, thereby providing attachments for an existing safety belt for retaining the child seat 1 in the passenger seat.
According to the invention, the backrest 3 is designed with a first through slot 6 and a second through slot 7 , both of which extend through the backrest 3 . The slots 6 , 7 are preferably straight, elongated and generally oriented vertically, but other configurations are also conceivable. Furthermore, the child seat 1 is provided with a safety belt comprising a first belt band 8 and a second belt band 9 running through the slots 6 and 7 , respectively. The two belt bands 8 , 9 are, in a conventional manner, made of a woven band of textile or a corresponding material. Each belt band 8 , 9 is arranged to run freely through a locking unit 10 , 11 . The locking unit 10 , 11 is in the form of a handle carrying a locking plate 12 , 13 . Further, the belt bands 8 , 9 run from the slots 6 , 7 to a fixation point in the seat 2 , preferably adjacent to each seat side 4 , 5 , respectively. The two locking plates 12 , 13 may, in a known manner, be locked into a further locking device in the form of a belt lock 14 . This belt lock is in turn fixedly anchored in the seat 2 via a short band 15 , preferably of the same type of material as the belt bands 8 , 9 .
According to a conceivable variant of the invention (not shown in the figures), each belt band 8 , 9 may be fixedly attached to each locking unit 10 , 11 , respectively, i.e., without running on further to a fastening point in the seat 2 .
FIG. 1 shows the child seat 1 according to the invention in a state where the locking units 10 , 11 are not locked into the belt lock 14 . For locking of the locking units 10 , 11 , the locking plates 12 , 13 may be inserted into receiving openings (not shown) of the belt lock 14 . Each locking plate 12 , 13 may be locked inside the belt lock 14 according to any manner known in the art based on a locking element with a catch arranged inside the belt lock 14 and cooperating with each locking plate 12 , 13 and is therefore not described in detail here. The locking plates 12 , 13 may further be released from the belt lock 14 by means of a separate release button 16 .
FIG. 2 shows a rear view of the child seat 1 illustrating one method of how the belt bands 8 , 9 may be attached to the rear side of the backrest 3 . As previously explained, the slots 6 , 7 extend through the backrest 3 so that each belt band 8 , 9 comes out on the rear side of the child seat 1 . Furthermore, those portions of the belt bands 8 , 9 running along the rear side of the backrest 3 are arranged so as to cross each other. The first belt band 8 runs through a re-directing device in the form of a first guide plate 1 7 pivotally attached to the rear side of the backrest 3 by means of a fastening screw 19 . In a corresponding manner, the other belt band 9 is arranged to run through a redirecting device in the form of a second guide plate 18 . This plate 18 is pivotally attached to the rear side of the backrest 3 by means of another fastening screw 20 . Both guide plates 17 , 18 can pivot freely in relation to the remainder of the child seat 1 .
The end portions of the belt bands 8 , 9 are attached to a fastening plate 21 . This fastening plate 21 is a loose member, i.e., it is free from or not attached to the child seat 1 . Also attached to the fastening plate 21 is the end portion of another band 22 . This band 22 is of the same type as the above-mentioned belt bands 8 , 9 , 15 , and arranged to run through a guiding device 23 in the shape of a mounting or plate on the rear side of the backrest 3 . The band 22 runs from the guiding device 23 along the bottom side of the child seat 1 to the front side of the seat 1 (see FIG. 1) where the band 22 protrudes.
The child seat 1 further comprises an attachment device (not shown) arranged to allow alternate loosening and tightening of the band 22 . In this way, a person can simply place a child in the child seat 1 , then fasten it by locking the locking units 10 , 11 and subsequently lock the band 22 that protrudes on the front side of the child seat 1 in a suitable position.
Preferably, the rear side of the backrest 3 is designed so as not to prevent any movement of the various bands 8 , 9 , 22 . For example, if the child seat 1 is placed in such a way that the backrest 3 is turned towards a vehicle instrument panel, it is important that the bands 8 , 9 , 22 not be pinched between the instrument panel and the child seat 1 , thereby preventing any movement of the bands 8 , 9 , 22 , and, in turn, possibly impairing the function of the safety belt. In order to prevent this, the invention may be arranged so as to shape the rear side of the backrest 3 with a countersunk portion (not illustrated), housing the bands 8 , 9 , 22 . Such a countersunk portion may then preferably be covered by a thin sheet or plate.
The slots 6 , 7 are shaped with a width adapted for allowing the belt bands 8 , 9 to run freely in a direction through the slots 6 , 7 , respectively, as well as vertically along the length of slots 6 , 7 , respectively. Preferably, the width of the slots 6 , 7 is in the range of 0.5-2.0 cm. Furthermore, the slots 6 , 7 have a vertical extension corresponding to that height, within which the shoulder portion of a child seated in the child seat 1 can be expected to be located. The vertical mobility of the belt bands 8 , 9 is achieved by the vertical length of the slots 6 , 7 being substantially larger than the width of the belt bands 8 , 9 , respectively. Suitably, the child seat 1 according to the invention is used for children of ages up to about 4 years, whereby the length of the slots 6 , 7 is of the order 10-20 cm.
After having placed a child in the child seat 1 according to the invention, the child can be fastened by initially placing the belt bands 8 , 9 over each shoulder portion of the child and then locking them into the belt lock 14 (comp. FIG. 1 ). For this purpose, the belt lock 14 is located at a point in front of the child's abdomen, the band 15 running between the legs of the child to a fastening point in the seat 2 . Due to the vertical mobility of the belt bands 8 , 9 in the slots 6 , 7 , the extension of each belt band 8 , 9 will, according to the invention, automatically be adapted to the body size of the child, and can always be made to run over the shoulder portion of the child.
On the rear side of the backrest 3 (comp. FIG. 2) each guide plate 17 , 18 will pivot to a position dependent on the vertical position of each belt band 8 , 9 in the slots 6 , 7 , respectively. With the belt bands 8 , 9 locked in place, the band 22 should be tightened and fixed in the manner described above. In this way, the child seat 1 can be used for children of various body size with the belt bands 8 , 9 providing optimum protection, in general, independently of the body size of the child. For adaptation of the safety belt to the body size of the child, the band 15 may furthermore be provided with a length adjustment mechanism (not shown) for correct positioning of the belt lock 14 .
FIG. 3 shows a rear view of a child seat illustrating one method of how the belt bands 8 , 9 may be attached to the rear side of the backrest 3 using rollers 24 , 25 . Such rollers 24 , 25 are known in the art and are designed to be spring loaded, rolling up its adherent belt band automatically when not in use. When the safety belt is not in use, the belt bands 8 , 9 will thus be rolled up and each locking unit 10 , 11 will be positioned right in front of their respective slots 6 , 7 . Such a roller would be fitted to the backrest in an articulated manner similar to that of the guide plates 17 , 18 described above. According to this embodiment, two belt rollers 24 , 25 can thus be used to replace the guide plates 17 , 18 , the fastening plate 21 and the band 22 described above.
FIG. 4 shows a variation of this alternative embodiment, the belt rollers 24 , 25 may be arranged inside the backrest 3 instead of on its rear side. In this case, the two slots 6 , 7 will not extend all the way through the backrest 3 , but only through the front side of the backrest 3 , i.e., that side facing the passenger in the child seat 1 . The belt rollers 24 , 25 will then be arranged in a cavity 26 defined inside the backrest 3 , i.e., between its front and rear sides.
The invention is not limited to the embodiment examples described above and depicted in the drawings, but may be varied within the scope of the appended patent claims. For example, the invention can also be used in those cases where the child seat 1 is placed facing forwards, i.e., where the passenger in the child seat 1 is facing towards the front of the vehicle.
Furthermore, the invention can in principle also be used in those cases where the safety belt only consists of a belt band running diagonally across the upper part of the body of the passenger. In this case, only one through slot in the backrest of the child seat is used. Likewise, the invention may be used in connection with safety belts of the three, four or five point types.
The invention can be completed with various mechanisms for tightening the belt bands 8 , 9 . For example, each belt band 8 , 9 can be provided with a device for adjusting the length of the respective belt band 8 , 9 . Such devices would preferably be arranged at shoulder height for the passenger of the child seat 1 .
The child seat according to the invention may further comprise part of an existing vehicle seat, e.g., an integrated part of the rear seat of a vehicle or an integrated part of the backrest of the front passenger seat.
It should be understood that the child seat according to the invention is not limited for use by passengers of a certain age or body size. The invention, however, is mainly suitable for children up to about 4 years of age.
The slots 6 , 7 may be made rectilinear or, alternatively, somewhat curved in shape in order to be adapted in an optimal way to the body shape of a passenger in the child seat 1 . Moreover, the slots 6 , 7 may be oriented completely vertically or alternatively somewhat obliquely relative to the vertical line.
Finally, the two guide plates 17 , 18 (see FIG. 2) may be arranged such that they are adjustable vertically or transversally. This can be achieved by displaceably arranging the guide plates 17 , 18 along a groove or the like and providing them with a locking mechanism, e.g., in the form of a spring-biased cotter pin, by which each guide plate 17 , 18 can be adjusted to a suitable position. | A child seat for vehicles having a seat, a backrest and a vertically adjustable seat belt. The vertically adjustable seat belt includes at least one belt band, equipped with a locking device arranged for lockable co-operation with a belt lock that is fixedly anchored in the child seat. The backrest is designed with at least one vertically extending slot, with the belt band arranged to run through the slot and up to the belt lock. The improved child seat provides an automatic adjustment of a safety belt in relation to the body size of the passenger is obtained. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. 119 of Danish application 1426/95 filed Dec. 15, 1995, which is specifically incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to the use of compounds of the general formula I for reducing blood glucose and/or inhibit the secretion, circulation or effect of insulin antagonizing peptides like CGRP or amylin. Hence the compound can be used in the treatment of patients suffering from NIDDM (non-insulin-dependent diabetes mellitus) in order to improve the glucose tolerance. The present invention also embraces pharmaceutical compositions comprising those compounds and methods of using the compounds and their pharmaceutical compositions.
BACKGROUND OF THE INVENTION
The potent effects of CGRP on skeletal muscle glycogen synthase activity and muscle glucose metabolism, together with the notion that this peptide is released from the neuromuscular junction by nerve excitation, suggest that CGRP may play a physiological role in skeletal muscle glucose metabolism by directing the phosphorylated glucose away from glycogen storage and into the glycolytic and oxidative pathways (Rosetti et al. Am. J. Physiol. 264, E1-E10, 1993). This peptide may represent an important physiological modulator of intracellular glucose trafficking in physiological conditions, such as exercise, and may also contribute to the decreased insulin action and skeletal muscle glycogen synthase in pathophysiological conditions like NIDDM or aging-associated obesity (Melnyk et al. Obesity Res. 3, 337-344, 1995) where circulating plasma levels of CGRP are markedly increased. Hence inhibition of release and/or activity of the neuropeptide CGRP may be useful in the treatment of insulin resistance related to type 2 diabetes or aging.
In U.S. Pat. Nos. 4,383,999 and 4,514,414 and in EP 236342 as well as in EP 231996 some derivatives of N-(4,4-disubstituted-3-butenyl)azaheterocyclic carboxylic acids are claimed as inhibitors of GABA uptake. In EP 342635 and EP 374801, N-substituted azaheterocyclic carboxylic acids in which an oxime ether group and vinyl ether group forms part of the N-substituent respectively are claimed as inhibitors of GABA uptake. Further, in WO 9107389 and WO 9220658, N-substituted azacyclic carboxylic acids are claimed as GABA uptake inhibitors. EP 221572 claims that 1-aryloxyalkylpyridine-3-carboxylic acids are inhibitors of GABA uptake.
In addition to the above cited references, U.S. Pat. No. 3,074,953 discloses 1-(3-(10,11 -dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-4-phenyl-4-piperidinecarboxylic acid ethyl ester as a psychotropic drug. Analogous 1-substituted 4-phenyl-4-piperidinecarboxylic acid ester derivatives to the above cited compound are described (J. Med. Chem. 1967, 10, 627-635 and J. Org. Chem. 1962, 27, 230-240) as analgesics, antispasmodics and psychotropics. In JP 49032544, JP 48040357, FR 2121423, GB 1294550 and DE 2101066, 1-substituted 4-dialkylamino-4-piperidinecarboxamides are disclosed as psychotropic agents, for the treatment of schizophrenia and as inhibitors of inflammation.
WO 9518793 discloses N-substituted azaheterocyclic carboxylic acids and esters thereof, methods for their preparation, compositions containing them and their use in treatment of hyperalgesic and/or inflammatory conditions.
One object of the invention is to provide compounds which can effectively be used in the treatment of insulin resistance in NIDDM or aging.
DESCRIPTION OF THE INVENTION
It has surprisingly been found that compounds of the general formula I below can be used in the treatment of insulin resistance related to NIDDM or aging.
Accordingly, the present invention relates to the use of compounds of the general formula I ##STR2## wherein R 1 and R 2 independently are hydrogen, halogen, trifluoromethyl, C 1-6 -alkyl or C 1-6 -alkoxy; Y is >N--CH 2 --, >CH--CH 2 -- or >C═CH--wherein only the underscored atom participates in the ring system; X is --O--, --S--, --CR 7 R 8 --, --CH 2 CH 2 --, --CH═CH--CH 2 --, --CH 2 --CH═CH--, --CH 2 CH 2 CH 2 --, --CH═CH--, --NR 9 --(C═O)--, --O--CH 2 --, --(C═O)-- or --(S═O)-- wherein R 7 , R 8 and R 9 independently are hydrogen or C 1-6 -alkyl; r is 1, 2, or 3; m is 1 or 2 and n is 1 when m is 1 and n is 0 when m is 2; R 4 and R 5 each represents hydrogen or may--when m is 2--together represent a bond; and R 6 is OH or C 1-8 -alkoxy; or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for reducing blood glucose and/or inhibit the release and/or activity of CGRP, e.g. in the treatment of insulin resistance related to NIDDM or aging.
The compounds of formula I may exist as geometric and optical isomers and all isomers and mixtures thereof are included herein. Isomers may be separated by means of standard methods such as chromatographic techniques or fractional crystallization of suitable salts.
Preferably, the compounds of formula I exist as the individual geometric or optical isomers.
The compounds according to the invention may optionally exist as pharmaceutically acceptable acid addition salts or--when the carboxylic acid group is not esterified--as pharmaceutically acceptable metal salts or--optionally alkylated--ammonium salts.
Examples of such salts include inorganic and organic acid addition salts such as hydrochloride, hydrobromide, sulphate, phosphate, acetate, fumarate, maleate, citrate, lactate, tartrate, oxalate or similar pharmaceutically acceptable inorganic or organic acid addition salts, and include the pharmaceutically acceptable salts listed in Journal of Pharmaceutical Science, 66, 2 (1977) which are hereby incorporated by reference.
The term "C 1-6 -alkyl" as used herein, alone or in combination, refers to a straight or branched, saturated hydrocarbon chain having 1-6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert.butyl, n-pentyl, neopentyl, n-hexyl and 2,2-dimethylpropyl.
The term "C 1-6 -alkoxy" as used herein, alone or in combination, refers to a monovalent substituent comprising a C 1-6 -alkyl group linked through an ether oxygen having its free valence bond from the ether oxygen, e.g. methoxy, ethoxy, propoxy, butoxy, pentoxy.
The term "halogen" means fluorine, chlorine, bromine and iodine.
As used herein, the term "patient" includes any mammal which could benefit from treatment of insulin resistance related to NIDDM or aging. The term particularly refers to a human patient, but is not intended to be so limited.
Illustrative examples of compounds encompassed by the present invention include:
(R)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
(S)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid;
(R)-1-(3-(Fluoren-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
1-(3-(5H-Dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
1-(3-(Thioxanthen-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10,11-Dihydro-5H-dibenz b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(4-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-butyl)-3-piperidinecarboxylic acid;
(R)-1-(2-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)ethyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(3-Chloro-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10H-Phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10H-Phenoxazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(S)-1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid;
(R)-1-(3-(3-Methyl-10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(2-Trifluoromethyl-10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(5-Oxo-10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(11H-10-Oxa-5-aza-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid;
(R)-1-(3-(6,7-Dihydro-5H-dibenzo b,g!azocin-12-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-Methoxy-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10-Methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(9(H)-Oxo-10H-acridin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(2-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-ethyl)-3-piperidinecarboxylic acid;
(R)-1-(2-(6,11-Dihydrodibenz b,e!oxepin-11-ylidene)-1-ethyl)-3-piperidinecarboxylic acid.
A particularly preferred compound for use within the present invention is
(R)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid;
It has been demonstrated that the compounds of general formula I improves the glucose tolerance in diabetic ob/ob mice and that this may result from the reduced release of CGRP from peripheral nervous endings. Experimentally this has been demonstrated by the subcutaneous administration of glucose into ob/ob mice with or without previous oral treatment with a compound of general formula I. Not only did the test substance reduce plasma CGRP to near normal levels, but also was the glucose metabolism improved in terms of capacity to normalized plasma glucose after a subcutaneous glucose load to the animals. Hence the compounds of general formula I may be used in the treatment of NIDDM as well as aging-associated obesity.
The compounds of general formula I may be prepared by using the methods taught in WO 9518793 which are hereby incorporated by reference.
The compounds of general formula I may be prepared by the following method: ##STR3## A compound of formula II wherein R 1 , R 2 , X, Y, and r are as defined above and W is a suitable leaving group such as halogen, p-toluene sulphonate or mesylate may be reacted with an azaheterocyclic compound of formula III wherein R 4 , R 5 , R 6 , m and n are as defined above. This alkylation reaction may be carried out in a solvent such as acetone, dibutylether, 2-butanone, methyl ethyl ketone, ethyl acetate, tetrahydrofuran (THF) or toluene in the presence of a base e.g. potassium carbonate and a catalyst, e.g. an alkali metal iodide at a temperature up to reflux temperature for the solvent used for e.g. 1 to 120 h. If esters have been prepared in which R 6 is alkoxy, compounds of formula I wherein R 6 is OH may be prepared by hydrolysis of the ester group, preferably at room temperature in a mixture of an aqueous alkali metal hydroxide solution and an alcohol such as methanol or ethanol, for example, for about 0.5 to 6 h.
Compounds of formula II and Ill may readily be prepared by methods familiar to those skilled in the art.
Under certain circumstances it may be necessary to protect the intermediates used in the above methods e.g. a compound of formula III with suitable protecting groups.
The carboxylic acid group can, for example, be esterified. Introduction and removal of such groups is described in "Protective Groups in Organic Chemistry" J. F. W. McOrnie ed. (New York, 1973).
Pharmacological Methods
The reduction of plasma levels of CGRP in diabetic mice treated with a compound of the general formula I is described in the following.
ob/ob female mice, 16 weeks of age, where injected glucose (2 g/kg) subcutaneously. At times hereafter blood glucose was determined in tail venous blood by the glucose oxidase method. At the end of the study the animals were decapitated and trunck blood collected. Immunoreactive CGRP was determined in plasma by radio-immunoassay. Two groups of animals were used. The one group was vehicle treated, whereas the other group received the compound of example 1a via drinking water (100 mg/l) for five days before the test. The group treated with the compound of example 1a had significantly improved glucose metabolism as compared with controls.
Hence, whereas blood glucose increased (peaked) with 300% in the control group, it only increased by 200% in the group treated with the compound of example 1a. At the same time, the treatment with the compound of example 1a had reduced plasma CGRP levels from 260 pg/ml to 152 pg/ml.
For the above indications the dosage will vary depending on the compound of general formula I employed, on the mode of administration and on the therapy desired. However, in general, satisfactory results are obtained with a dosage of from about 0.5 mg to about 1000 mg, preferably from about 1 mg to about 500 mg of compounds of formula I, conveniently given from 1 to 5 times daily, optionally in sustained release form. Usually, dosage forms suitable for oral administration comprise from about 0.5 mg to about 1000 mg, preferably from about 1 mg to about 500 mg of the compounds of formula I admixed with a pharmaceutical carrier or diluent.
The compounds of formula I may be administered in pharmaceutically acceptable acid addition salt form or where possible as a metal or a lower alkylammonium salt. Such salt forms exhibit approximately the same order of activity as the free base forms.
This invention also relates to pharmaceutical compositions comprising a compound of formula I or a pharmaceutically acceptable salt thereof and, usually, such compositions also contain a pharmaceutical carrier or diluent. The compositions containing the compounds of this invention may be prepared by conventional techniques and appear in conventional forms, for example capsules, tablets, solutions or suspensions.
The pharmaceutical carrier employed may be a conventional solid or liquid carrier. Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate and stearic acid. Examples of liquid carriers are syrup, peanut oil, olive oil and water.
Similarly, the carrier or diluent may include any time delay material known to the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax.
If a solid carrier for oral administration is used, the preparation can be tabletted, placed in a hard gelatin capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.
Generally, the compounds of this invention are dispensed in unit dosage form comprising 50-200 mg of active ingredient in or together with a pharmaceutically acceptable carrier per unit dosage.
The dosage of the compounds according to this invention is 1-500 mg/day, e.g. about 100 mg per dose, when administered to patients, e.g. humans, as a drug.
A typical tablet which may be prepared by conventional tabletting techniques contains
______________________________________Core:Active compound (as free compound 100 mgor salt thereof)Collioidal silicon dioxide (Areosil ®) 1.5 mgCellulose, microcryst. (Avicel ®) 70 mgModified cellulose gum (Ac-Di-Sol ®) 7.5 mgMagnesium stearateCoating:HPMC approx. 9 mg*Mywacett ® 9-40 T approx. 0.9 mg______________________________________ *Acylated monoglyceride used as plasticizer for film coating.
The route of administration may be any route which effectively transports the active compound to the appropriate or desired site of action, such as oral or parenteral e.g. rectal, transdermal, subcutaneous, intranasal, intramuscular, topical, intravenous, intraurethral, ophthalmic solution or an ointment, the oral route being preferred.
EXAMPLES
The process for preparing compounds of formula I is further illustrated in the following examples, which, however, are not to be construed as limiting.
Hereinafter, TLC is thin layer chromatography and THF is tetrahydrofuran, CDCl 3 is deuterio chloroform and DMSO-d 6 is hexadeuterio dimethylsulfoxide. The structures of the compounds are confirmed by either elemental analysis or NMR, where peaks assigned to characteristic protons in the title compounds are presented where appropriate. NMR shifts (δ) are given in parts per million (ppm). M.p. is melting point and is given in °C. Column chromatography was carried out using the technique describe by W. C. Still et al, J. Org. Chem. 1978, 43, 2923-2925 on Merck silica gel 60 (Art. 9385). HPLC analysis was performed using a 5 μm C18 4×250 mm column, eluting with a 20-80% gradient of 0.1% trifluoroacetic acid/acetonitrile and 0.1% trifluoroacetic acid/water over 30 minutes at 35° C. Compounds used as starting materials are either known compounds or compounds which can readily be prepared by methods known per se.
Example 1a
(R)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
A solution of cyclopropylmagnesium bromide in dry THF (prepared from cyclopropylbromide (12.1 g, 0.10 mol), magnesium turnings (2:45 g, 0.10 mol) and dry THF (65 ml)) was placed under an atmosphere of nitrogen. A solution of 10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-one (10.4 g, 0.05 mol) in dry THF (25 ml) was added dropwise and when addition was complete the mixture was heated at reflux for 30 minutes. The reaction mixture was cooled on an ice-bath and saturated ammonium chloride (50 ml) was carefully added. The mixture was neutralized with 2N hydrochloric acid and extracted with diethyl ether (2×200 ml). The combined organic extracts were dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give 13.1 g of crude 5-cyclopropyl-10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-ol.
The above crude alcohol (13.1 g) was dissolved in dichloromethane (150 ml) and a solution of trimethylsilyl bromide (9.2 g, 0.06 mol) in dichloromethane (50 ml) was added dropwise. When addition was complete the mixture was stirred at room temperature for 15 minutes and water (50 ml) was added. The phases were separated and the organic phase was washed with saturated sodium bicarbonate (2×50 ml). The organic phase was dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give 16.5 g of crude 5-(3-bromo-1-propylidene)-10,11-dihydro-5H-dibenzo a,d!cycloheptene as a solid.
A mixture of the above crude bromide (6.3 g, 20 mmol), ethyl (R)-3-piperidinecarboxylate (4.7 g, 30 mmol), potassium carbonate (5.5 g, 40 mmol) and acetone (50 ml) was stirred at room temperature for 124 h. The mixture was filtered and the solvent was evaporated in vacuo. The oily residue was purified on silica gel (200 g, ethyl acetate/n-heptane=1/1) to give 4.4 g of (R)-1-(3-(10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f =0.38 (SiO 2 ;ethyl acetate/n-heptane=1:1).
The above ester (4.4 g, 11 mmol) was dissolved in ethanol (40 ml) and 4N sodium hydroxide (8.3 ml) was added. The mixture was stirred vigorously at ambient temperature for 7 h. Dichloromethane (700 ml) was added followed by 2.5N hydrochloric acid until pH 1. The phases were separated, the organic phase dried (MgSO 4 ) and the solvent was evaporated in vacuo. The residue was re-evaporated twice with acetone and then triturated with a mixture of acetone and diethyl ether. The solid was isolated by filtration and dried in air to give 2.2 g of the title compound as a solid.
M.p. 206°-208° C. Calculated for C 24 H 27 NO 2 ,HCl: C, 72.4%; H, 7.1%; N, 3.5%; Found: C, 72.1%; H, 7.3%; N, 3.3%.
By a similar procedure as described in Example 1a the following compounds have been prepared:
Example 1b
(S)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid dihydrochloride
M.p. 216°-218° C. 1 H-NMR (200 MHz, DMSO-d 6 ) δ H 1.43 (bs, 1H), 1.78 (bs, 2H), 1.96 (bs, 1H), 2.5 (bd, 1H, CH--COOH), 2.84 (bm, 2H), 3.16 (bs, 2H), 3.26 (bs, 4H), 3.34 (s, 4H), 5.78 (t, 1H), 7.07 (dd, 1H, C═CH--CH 2 ), 7.12-7.29 (m, 7H).
Example 1c
1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride
M.p. 140°-145° C. Calculated for C 25 H 2 NO 2 ,HCl,C 3 H 6 O: C, 71.4%; H, 7.1%; N, 3.1%; Found: C, 71.5%; H, 6.9%; N, 3.1%.
Example 1d
(R)-1-(3-(Fluoren-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
M.p. 217°-219° C. Calculated for C 22 H 23 NO 2 ,HCl,1/4H 2 O: C, 70.6%; H, 6.5%; N, 3.7%; Cl, 9.5%; Found: C, 70.8%; H, 6.6%; N, 3.5%; Cl, 9.4%.
Example 1e
(R)-1-(3-(3-Methyl-10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
M.p. 218°-221° C. Calculated for C 24 H 29 NO 2 , HCl: C, 72.87%; H, 7.35%; N, 3.40%; Found: C, 72.60%; H, 7.58%; N, 3.24%.
Example 2
1-(3-(5H-Dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid sodium salt
A solution of cyclopropylmagnesium bromide in dry THF (prepared from cyclopropylbromide (8.0 g, 0.067 mol), magnesium turnings (1.3 g, 0.053 mol) and dry THF (35 ml)) was placed under an atmosphere of nitrogen. A solution of 5H-dibenzo a,d!cyclohepten-5-one (6.0 g, 0.028 mol) in dry THF (15 ml) was added dropwise and when addition was complete the mixture was heated at reflux for 30 minutes. The reaction mixture was cooled on an ice-bath and saturated ammonium chloride (35 ml) was carefully added. The mixture was diluted with water (50 ml) and extracted with diethyl ether (2×50 ml). The combined organic extracts were washed with water, dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give 8.6 g of crude 5-cyclopropyl-5H-dibenzo a,d!cyclohepten-5-ol.
To the above crude alcohol (8.6 g) was added glacial acetic acid (60 ml). The mixture was cooled on an ice-bath and a mixture of glacial acetic acid (30 ml) and 47% hydrobromic acid (15 ml) was added. The mixture was stirred for 30 minutes, poured into water (300 ml) and extracted with diethyl ether (2×100 ml). The combined organic phases were washed with water, dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give a residue which was recrystallized from diethyl ether.
This afforded 6.8 g of 5-(3-bromo-1-propylidene)-5H-dibenzo a,d!cycloheptene as a solid. M.p. 88°-89° C.
A mixture of the above bromide (5.0 g, 16 mmol), ethyl 3-piperidinecarboxylate (3.2 g, 20 mmol), potassium carbonate (7.3 g, 53 mmol) and acetone (150 ml) was heated at reflux for 15 h. The mixture was filtered and the solvent was evaporated in vacuo. The oily residue was dissolved in ethyl acetate (60 ml) and washed with 2N hydrochloric acid (2×30 ml). The organic phase was dried and the solvent evaporated in vacuo. The residue was dissolved in acetone (25 ml), treated with hydrogenchloride gas and the mixture was diluted with diethyl ether (120 ml). The solvent was decanted and the oily residue was dried in vacuo to give 5.6 g of 1-(3-(5H-dibenzo a,d!cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarboxylic acid ethyl ester hydrochloride as an amorphous solid.
The above ester (4.5 g, 11 mmol) was dissolved in ethanol (80 ml), 32% sodium hydroxide (180 ml) was added and the mixture was heated at reflux for 1 h. To the cooled reaction mixture a mixture of dichloromethane and ethyl acetate was added. The phases were separated and the aqueous phase was treated with activated charcoal and filtered through millipore (0.22 μm). The solvent was evaporated from the filtrate in vacuo and the residue was dissolved in a mixture of water and dichloromethane (1:3). The phases were separated, the organic phase dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue was dissolved in water and freezedried to give 3.0 g of the title compound as an amorphous solid.
1 H-NMR (DMSO-d 6 ) δ5.47 (t, 1H); 6.94 (s, 2H).
Example 3
1-(3-(Thioxanthen-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
A solution of cyclopropylmagnesium bromide in dry THF (prepared from cyclopropylbromide (18.2 g, 0.15 mol), magnesium turnings (2.9 g, 0.12 mol) and dry THF (80 ml)) was placed under an atmosphere of nitrogen. A solution of thioxanthen-9-one (12.7 g, 0.06 mol) in dry THF (70 ml) was added dropwise and when addition was complete the mixture was heated at reflux for 20 minutes. The reaction mixture was cooled on an ice-bath and saturated ammonium chloride (70 ml) was carefully added. The mixture was diluted with water (100 ml) and extracted with diethyl ether (2×100 ml). The combined organic extracts were washed with water, dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give 25.2 g of crude 9-cyclopropyl-9H-thioxanthen-9-ol.
To the above crude alcohol (25.2 g) was added glacial acetic acid (120 ml). The mixture was cooled on an ice-bath and a mixture of glacial acetic acid (60 ml) and 47% hydrobromic acid (30 ml) was added. The mixture was stirred for 30 minutes, poured into water (600 ml) and extracted with diethyl ether (3×200 ml). The combined organic phases were washed with water, dried (Na 2 SO 4 ) and the solvent was evaporated in vacuo to give 19.5 g of crude 9-(3-bromo-1-propylidene)-9H-thioxanthene. R f =0.35 (SiO 2 ; THF/heptane=1:9).
A mixture of the above crude bromide (2.0 g, 6.3 mmol), ethyl 3-piperidinecarboxylate (1.2 g, 7.5 mmol), potassium carbonate (2.9 g, 21 mmol) and acetone (60 ml) was stirred at ambient temperature for 3 h and then heated at reflux for 16 h. The mixture was filtered and the solvent was evaporated in vacuo. The oily residue was purified on silica gel (dichloromethane/methanol=98:2) to give 1.3 g of 1-(3-(thioxanthen-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f =0.21 (SiO 2 ; dichloromethane/methanol=98:2).
The above ester (0.74 g, 1.8 mmol) was dissolved in ethanol (25 ml) and 40% sodium hydroxide (6 ml) was added. The mixture was heated at reflux for 1 h. 10% Hydrochloric acid (25 ml) was added followed by dichloromethane (150 ml). The phases were separated and the organic phase was washed with water, dried (NaSO 4 ) and the solvent was evaporated in vacuo to give 0.6 g of the title Compound as a solid. M.p. 150°-160° C. A sample was dissolved in acetone and precipitated with diethyl ether. The solid formed was isolated by filtration and dried in vacuo.
Calculated for C 22 H 23 NO 2 S,HCl,1/2H 2 O: C, 64.3%; H, 6.1%; N, 3.4%; Found: C, 64.0%; H, 6.2%; N, 3.5%.
1 H-NMR (CDCl 3 ) δ5.74 (t, 1H).
Example 4
(R)-1-(3-(10,11-Dihydro-5H-dibenz b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of 10,11-dihydro-5H-dibenz b,f!azepine (8.1 g, 0.040 mol) in dry dibutyl ether (60 ml) kept under an atmosphere of nitrogen, sodium hydride (1.6 g, 0.040 mol, 60% oil dispersion) was carefully added. The reaction mixture was heated at reflux temperature for 4 h and then allowed to cool to 80° C. 3-Bromo-1-propyl tetrahydro-2-pyranyl ether (10.7 g, 0.048 mol) was added and the mixture was heated at reflux temperature for 16 h. To the cooled reaction mixture was added water (20 ml) and the phases were separated. From the organic phase the solvent was evaporated and the residue was dissolved in a mixture of methanol (150 ml) and a 4N HCl solution (50 ml). The mixture was heated at reflux temperature for 15 minutes and then stirred for 1 h at ambient temperature. Water (250 ml) was added and the mixture was extracted with ethyl acetate (2×200 ml). The combined organic extracts were dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo.
This afforded a residue which was purified further by chromatography on silica gel (200 g) using a mixture of n-heptane and ethyl acetate (3:2) as eluent to give 5.5 g of 3-(10,11-dihydro-5H-dibenz b,f!azepin-5-yl)-1-propanol as an oil. R f : 0.30 (SiO 2 ; n-heptane/ethyl acetate=1:1 ).
The above alcohol (3.0 g, 12 mmol) was dissolved in toluene (100 ml) and triethylamine (4.0 ml) was added. Methanesulfonyl chloride (1.5 g, 19 mmol) was added dropwise and when addition was complete the reaction mixture was stirred for 2 h. Water was added and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent was evaporated in vacuo to give a residue which was dissolved in acetone (50 ml). To this solution (R)-3-piperidinecarboxylic acid ethyl ester tartrate (5.4 g, 18 mmol) and potassium carbonate (4.1 g, 30 mmol) were added and the mixture was heated at reflux for three days. The mixture was allowed to cool, then filtered and the solvent evaporated in vacuo to give a residue which was dissolved in diethyl ether. The resulting mixture was extracted with a 5% tartaric acid solution (2×100 ml). The combined aqueous extracts were washed with diethyl ether and pH was adjusted to 7-8 with potassium carbonate solution. The neutralised aqueous mixture was extracted with ethyl acetate (2×200 ml). The combined ethyl acetate extracts were washed with water, brine and dried (MgSO 4 ). The solvent was evaporated in vacuo to give a residue which was dissolved in diethyl ether (50 ml) and filtered through silica gel. This afforded 2.8 g of (R)-1-(3-(10,11-dihydro-5H-dibenz b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil.
The above ester (2.8 g, 7.1 mmol) was dissolved in ethanol (10 ml) and 4N sodium hydroxide (5.3 ml) was added. The mixture was stirred at ambient temperature for 10 h and concentrated hydrochloric acid was added until acidic reaction (pH 1). The resulting mixture was extracted with dichloromethane (300 ml) and the organic extract was dried
(MgSO 4 ). The solvent was evaporated in vacuo to give a foamy residue which was re-evaporated with acetone. This afforded 2.3 g of the title compound as an amorphous solid.
Calculated for C 23 H 28 N 2 O 2 ,HCl,H 2 O: C, 65.9%; H, 7.5%; N, 6.7%; Found: C, 66.1%; H, 7.6%; N, 6.2%.
Example 5
(R)-1-(4-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-butyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of 10,11-dihydro-5H-dibenzo b,f!azepine (16.2 g, 0.083 mol) in dry dibutyl ether (120 ml) kept under an atmosphere of nitrogen, sodium hydride (3.2 g, 0.08 mol, 60% dispersion in oil) was carefully added. The reaction mixture was heated at reflux temperature for 4 h and then allowed to cool to 80° C. 4-Chloro-1-butyl tetrahydro-2-pyranyl ether (18.5 g, 0.096 mol) was added and the mixture heated at reflux temperature for 16 h. After cooling to room temperature, water (40 ml) was added, and the phases were separated. The organic phase was evaporated until dryness. The residue was dissolved in a mixture of methanol (300 ml) and 4N HCl (100 ml). The mixture was heated at reflux temperature for 15 minutes and then stirred for 1 h at room temperature. Water (500 ml) was added and the mixture was extracted with ethyl acetate (6×200 ml). The combined organic extracts were dried (Na 2 SO 4 ), filtered and the solvent evaporated. This afforded a residue which was purified by column chromatography on silica gel (400 g) using a mixture of n-heptane and ethyl acetate (3:2) as eluent. 13.1 g (59%) of 4-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-butanol was obtained as an oil, that solidified upon cooling in a refrigerator overnight. R f : 0.34 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above alcohol (5.4 g, 0.02 mol) was dissolved in toluene (160 ml) and triethylamine (7 ml) was added. Methanesulfonyl chloride (2.5 ml, 0.032 mol) was added dropwise and when addition was complete the reaction mixture was stirred for 2 h. Water was added and the phases were separated.
The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo affording a residue which was dissolved in acetone (85 ml). To this solution (R)-3-piperidinecarboxylic acid ethyl ester tartrate (9.0 g, 0.03 mol) and potassium carbonate (7.0 g, 0.051 mol) were added and the mixture was heated at reflux temperature for 16 h. After cooling to room temperature and filtration on filter aid (celite) the solvent was removed by evaporation. The residue was dissolved in diethyl ether (100 ml) and extracted with a 5% tartaric acid solution (3×125 ml). The combined aqueous extracts were washed with diethyl ether and pH was adjusted to 7-8 with a potassium carbonate solution. The neutralised aqueous mixture was extracted with ethyl acetate (4×200 ml). The combined ethyl acetate extracts were washed with water, brine and dried (MgSO 4 ). The solvent was evaporated in vacuo affording 2.6 g (32%) of 1-(4-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-butyl!-3-piperidinecarboxylic acid ethyl ester, obtained as an oil. The residue was purified further by column chromatography on silica gel (65 g) using a mixture of dichloromethane and methanol (99.2:0.8) as eluent. R f : 0.20 (SiO 2 ; n-heptane/ethyl acetate=1:1 ).
The above ester (1.5 g, 0.0037 mol) was dissolved in ethanol (10 ml) and a solution of NaOH (0.52 g) in water (2 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (2 ml). Dichloromethane (75 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. Acetone (15 ml) was added to the residue which was re-evaporated. Acetone (30 ml) was added to the dry white product, affording, after filtration and drying, 1.3 g (84%) of the title compound as a white solid.
M.p. 222°-224° C. Calculated for C 24 H 30 N 2 O 2 , HCl: C, 69.47%; H, 7.53%; N, 6.75%; Found: C, 69.26%; H, 7.88%; N, 6.50%.
Example 6
(R)-1-(2-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)ethyl)-3-piperidinecarboxylic acid hydrochloride
In a 500 ml roundbottom flask equipped with magnetical stirring, thermometer, addition funnel and scrubber 10,11-dihydro-5H-dibenzo b,f!azepine (19.5 g, 0.10 mol) was dissolved in dry toluene (100 ml). Chloroacetyl chloride (13.6 g, 0.12 mol) was slowly added. The reaction mixture was heated to 95° C. for 30 minutes and then allowed to cool to room temperature. Under stirring, 0.2N NaOH (50 ml) was added. More toluene was added (100 ml) and the phases were separated. The organic phase was washed with 0.2N NaOH (3×50 ml) until pH>10, and then with water (3×50 ml) and brine (50 ml). After drying (MgSO 4 ) the organic phase was evaporated in vacuo affording an oily residue that crystallised upon standing overnight. The product was obtained in quantitative yield and used for further reactions without purification.
The above crude amide (20.0 g, 0.074 mol) was dissolved in dry THF (150 ml) under a nitrogen atmosphere and cooled to 5° C. Sodium borohydride (2.3 g, 0.06 mol) was added followed by slow dropwise addition of BF 3 Et 2 O (9.4 ml, 0.076 mol). The reaction mixture was left stirring overnight. Further amounts of NaBH 4 (2.0 g. 0.053 mol) and BF 3 Et 2 O (6 ml, 0.049 mol) were added, and stirring was continued overnight. Methanol (20 ml) was added dropwise and stirring was continued for 1 h. Water (80 ml) was added to dissolve precipitated salt, followed by ethyl acetate (100 ml). The phases were separated, and the aqueous phase was extracted with ethyl acetate (2×100 ml). The combined organic extracts were washed with water (4×100 ml) and brine (100 ml). The solvent was evaporated in vacuo and the residue was stripped twice with toluene. The crude product was purified by column chromatography on silica gel (400 g) using dichloromethane as eluent. This afforded 15.0 g (79%) of 5-(2-chloroethyl)-10,11-dihydro-5H-dibenzo b,f!azepine. R f : 0.70 (SiO 2 ; dichloromethane).
The above chloride (10.0 g, 0.039 mol) was dissolved in acetone (175 ml) and potassium iodide (3.3 g) was added. To this solution (R)-3-piperidinecarboxylic acid ethyl ester tartrate (18.0 g, 0.06 mol) and potassium carbonate (14.0 g, 0.12 mol) were added and the mixture was heated at reflux temperature for 72 h. After cooling to room temperature and filtration on filter aid (celite) the solvent was removed by evaporation. The residue was purified by column chromatography on silica gel (300 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 1.6 g (11%) of (R)-1-(2-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.34 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (1.28 g, 0.0034 mol) was dissolved in ethanol (10 ml) and a solution of NaOH (0.52 g) in water (2 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (2 ml). Dichloromethane (75 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. Acetone (15 ml) was added to the residue which was re-evaporated. Acetone (30 ml) was added to the dry white product, affording, after filtration and drying, 1.1 g (80%) of the title compound as a white solid.
M.p. 246°-248° C. Calculated for C 22 H 26 N 2 O 2 , HCl, 1/4 H 2 O: C, 67.44%; H, 7.02%; N, 7.15%; Found: C, 67.72%; H, 7.23%; N, 7.01%.
Example 7
(R)-1-(3-(3-Chloro-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
In a 100 ml roundbottom flask equipped with magnetical stirring, thermometer, nitrogen-inlet and addition funnel, 3-chloro-10,11-dihydro-5H-dibenzo b,f!azepine (1.3 g, 0.0056 mol) was dissolved in dry toluene (30 ml). Under nitrogen, ethyl malonyl chloride (1.01 g, 0.0067 mol) was slowly added. The reaction mixture was heated at reflux temperature for 2 h and then allowed to cool to room temperature. Under stirring, 0.2N NaOH (2.5 ml) and water (30 ml) was added. More toluene was added (100 ml) and the phases were separated. The organic phase was washed with water (3×50 ml) and brine (50 ml). After drying (MgSO 4 ) the organic phase was evaporated in vacuo affording an oily residue. The product was obtained in quantitative yield and used for further reactions without purification.
LiAlH 4 (920 mg, 0.024 mol) was placed in a dry 250 ml three-necked roundbottom flask, equipped with thermometer, magnetical stirring and addition funnel. Under nitrogen dry toluene (40 ml) was added followed by slow addition of THF (4 ml). A temperature at 15°-25° C. was assured by the use of a water/ice-bath. The above amide (2.1 g, 0.0061 mol) was dissolved in dry THF (12 ml) and slowly added to the LiAlH 4 -slurry. The temperature was kept at 20°-25° C. The reaction mixture was left stirring overnight at room temperature. Water (1 ml) was added dropwise, followed by 4N NaOH (1 ml) and finally water (3 ml). The resulting precipitate was filtered off on filter aid (celite) and the toluene solution was dried (MgSO 4 ). The crude product was purified by column Chromatography on silica gel (75 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.9 g (50%) of 3-(3-chloro-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propanol as an oil. R f : 0.36 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above alcohol (870 mg, 0.003 mol) was dissolved in toluene (25 ml) and triethylamine (1 ml) was added. Methanesulfonyl chloride (0.5 ml, 0.006 mol) was added dropwise and the reaction mixture was stirred for 2 h. Water (100 ml) was added, followed by further amounts of toluene (100 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo affording a residue which was dissolved in methyl ethyl ketone (50 ml).
To this solution (R)-3-piperidinecarboxylic acid ethyl ester tartrate (1.4 g, 0.0047 mol) and potassium carbonate (1.0 g, 0.0072 mol) were added and the mixture was heated at reflux for 24 h, and left stirring at room temperature for 24 h. After filtration on filter aid (celite) the solvent was removed by evaporation. The residue was purified by column chromatography on silica gel (100 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 1.0 g (79%) of (R)-1-(3-(3-chloro-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.34 (SiO 2 ; n-heptane/ethyl acetate=1:1)
The above ester (500 mg, 0.0012 mol) was dissolved in ethanol (4 ml) and a solution of NaOH (0.2 g) in water (1 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (0.75 ml). Dichloromethane (75 ml) was added followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue crystallized upon addition of ethyl acetate, affording, after filtration and drying, 0.4 g (68%) of the title compound as a white solid.
M.p. 135°-138° C. Calculated for C 23 H 27 N 2 O 2 , HCl, 3/4 H 2 O: C, 61.48%; H, 6.57%; N, 6.23%; Found: C, 61.35%; H, 6.67%; N, 5.70%.
Example 8a
(R)-1-(3-(10H-Phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of phenothiazine (4.0 g, 0.02 mol) in dry dimethylformamide (100 ml) kept under an atmosphere of nitrogen, sodium hydride (1.0 g, 0.025 mol, 60% dispersion in oil) was carefully added. The reaction mixture was left stirring for 15 minutes. 1-Bromo-3-chloropropane (8.0 g, 0.05 mol) was added and the mixture was left stirring overnight. Ammonium chloride (2.0 g, 0.04 mol) was added, and after continued stirring for 30 minutes the solution was poured onto water (300 ml).
The mixture was extracted with dichloromethane (2×200 ml). The combined organic extracts were dried (MgSO 4 ), filtered and the solvent evaporated. This afforded a residue which was purified by column chromatography on silica gel (250 g) using a mixture of n-heptane and ethyl acetate (9:1) as eluent. 4.4 g (80%) of 10-(3-chloropropyl)-10H-phenothiazine was obtained as an oil. R f : 0.55 (SiO 2 ; n-heptane/ethyl acetate=1:1).
Potassium iodide (10.0 g, 0.06 mol) was dissolved in methyl ethyl ketone (100 ml) and heated at reflux temperature for 1 h. The above chloride (2.64 g, 0.09 mol) was dissolved in methyl ethyl ketone (10 ml) and added. The mixture was heated at reflux temperature for 3 h. After cooling to about 60° C., (R)-3-piperidinecarboxylic acid ethyl ester tartrate (2.64 g, 0.009 mol) and potassium carbonate (2.0 g, 0.014 mol) were added. The mixture was heated at reflux temperature for 24 h and left stirring at room temperature for 24 h. After filtration on filter aid (celite) the solvent was removed by evaporation. The residue was purified by column chromatography on silica gel (150 g) using a mixture of heptane and ethyl acetate (6:4) as eluent. This afforded 2.5 g (87%) of (R)-1-(3-(10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.20 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (1.7 g, 0.0043 mol) was dissolved in ethanol (15 ml) and a solution of NaOH (0.63 g) in water (2.5 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (2.5 ml); Dichloromethane (100 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue crystallized upon addition of diethyl ether, followed by a small amount of dichloromethane. This afforded, after filtration and drying, 0.3 g (18%) of the title compound as a white solid. Subsequent re-evaporation of the filtrate afforded 1.08 g (62%) of the product.
M.p. 123°-128° C. Calculated for C 21 H 25 N 2 O 2 S, HCl, 5/4 H 2 O: C, 58.95%; H, 6.43%; N, 6.55%; Found: C, 59.19%; H, 6.52%; N, 6.17%.
By a similar procedure as described in Example 8a the following compounds have been prepared:
Example 8b
(R)-1-(3-(2-Trifluoromethyl-10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
M.p. 198°-200° C. 1 H-NMR (200 MHz, DMSO-d 6 ) δ H 1.45 (bs, 1H), 1.79-2.13 (bm, 4H), 2.76-3.44 (bm, 8H), 4.06 (t, 2H), 7.02 (t, 1H), 7.12-7.42 (m, 6H).
Example 8C
(R)-1-(3-(5-Oxo-10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
10-(3-Chloropropyl)-10H-phenothiazine (2 g, 0.007 mol) was dissolved in glacial acetic acid (40 ml), 30% aqueous hydrogen peroxide (2.25 ml, 0.022 mol) was added and the mixture stirred for 48 h under an atmosphere of nitrogen. The reaction mixture was left overnight. Precipitated crystals were filtered off and washed with water (2×20 ml), diethyl ether (2×50 ml) and dried in vacuo. Yield 1.38 g (64%) of 10-(3-chloropropyl)-10H-phenothiazine 5-oxide as light brown crystals. M.p. 171°-173° C.
1 H-NMR (200 MHz, CDCl 3 ) δ H 2.35 (m, 2H), 3.63 (t, 2H), 4.43 (t, 2H), 7.25 (t, 2H), 7.40 (d, 2H), 7.61 (dt, 2H), 8.09 (dd, 2H).
The title compound was prepared using 10-(3-chloropropyl)-10H-phenothiazine 5-oxide instead of 10-(3-chloropropyl)-10H-phenothiazine by a method similar to that described in Example 8a.
M.p.>280° C. 1 H-NMR (400 MHz, DMSO-d 6 ) δ H 1.46 (bd, 1H), 1.84 (bs, 2H), 2.01 (bd, 1H), 2.28 (bs, 2H), 2.89 (bd, 2H), 3.39 (bm, 2H), 3.54 (bd, 1H), 4.39 (t, 2H, N--CH 2 --CH 2 --), 7.41 (m, 2H), 7.79 (d, 4H), 8.03 (d, 2H), 10.95 (bs, 1H), 12.85 (bs, 1H),
Example 9
(R)-1-(3-(10H-Phenoxazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of phenoxazine (3.7 g, 0.02 mol) in dry dimethylformamide (100 ml) kept under an atmosphere of nitrogen, sodium hydride (1.2 g, 0.03 mol, 60% dispersion in oil) was carefully added. The reaction mixture was left stirring for 15 minutes. 1-Bromo-3-chloro-propane (8.0 g, 0.05 mol) was added and the mixture was left stirring overnight. Ammonium chloride (2.0 g, 0.04 mol) was added, and after continued stirring for 30 minutes, the solution was poured onto water (300 ml). The mixture was extracted with dichloromethane (2×200 ml). The combined organic extracts were dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. 10-(3-Chloropropyl)-10H-phenoxazine was obtained in quantitative yield as an oil and used without further purification. R f : 0.68 (SiO 2 ; n-heptane/ethyl acetate=1:1).
Potassium iodide (10.0 g, 0.06 mol) was dissolved in methyl ethyl ketone (100 ml) and heated at reflux temperature for 1 h. The above chloride (5.2 g, 0.02 mol) was dissolved in methyl ethyl ketone (10 ml) and added. The mixture was heated at reflux temperature for 3 h. After cooling to about 60° C., (R)-3-piperidinecarboxylic acid ethyl ester tartrate (5.3 g, 0.0018 mol) and potassium carbonate (4.0 g, 0.028 mol) were added. The mixture was heated at reflux temperature for 24 h, and left stirring at room temperature for 24 h.
After filtration on filter aid (celite) the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (250 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 5.2 g (67%) of (R)-1-(3-(10H-phenoxazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.25 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (2.34 g, 0.006 mol) was dissolved in ethanol (25 ml) and and a solution of NaOH (0.9 g) in water (3.5 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (3.5 ml). Dichloromethane (150 ml) was added, followed by water (70 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo, affording 1.8 g (77%) of product. To further purify the product, it was washed with diethyl ether, ethyl acetate and subsequently acetone, affording 1.2 g (50%) of the title compound.
M.p. 217°-220° C. Calculated for C 21 H 24 N 2 O 3 , HCl: C, 64.86%; H, 6.48%; N, 7.20%; Found: C, 64.56%; H, 6.70%; N, 6.89%.
Example 10
(S)-1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of 10,11-dihydro-5H-dibenzo b,f!azepine (8.1 g, 0.040 mol) in dry dibutyl ether (60 ml) kept under an atmosphere of nitrogen, sodium hydride (1.6 g, 0.04 mol, 60% dispersion in oil) was carefully added. The reaction mixture was heated at reflux temperature for 4 h and then allowed to cool to 80° C. 3-Bromo-1-propyl tetrahydro-2-pyranyl ether (10.7 g, 0.048 mol) was added and the mixture was heated at reflux temperature for 16 h. After cooling to room temperature, water (20 ml) was added, and the phases were separated.
The organic phase was evaporated until dryness. The residue was dissolved in a mixture of methanol (150 ml) and 4N HCl (50 ml). The mixture was heated at reflux temperature for 15 minutes and then stirred for 1 h at room temperature. Water (250 ml) was added and the mixture was extracted with ethyl acetate (2×200 ml). The combined organic extracts were dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. This afforded a residue which was purified by column chromatography on silica gel (200 g) using a mixture of n-heptane and ethyl acetate (3:2) as eluent. This afforded 5.5 g (54%) of 3-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propanol as an oil, that solidified upon cooling in a refrigerator overnight. R f : 0.30 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above alcohol (2.5 g, 0.0099 mol) was dissolved in dry THF (20 ml) and triethylamine (2.0 ml) was added under a nitrogen atmosphere. Methanesulfonyl chloride (0.77 ml, 0.0099 mol) was added dropwise and when addition was complete the reaction mixture was stirred for 45 minutes and then filtered. Triethylamine (3.4 ml) was added to the filtrate, followed by (S)-3-piperidinecarboxylic acid ethyl ester tartrate (4.55 g, 0.015 mol). The mixture was heated at reflux temperature for 48 h, and left at room temperature for 7 days. After filtration on filter aid (celite) the solvent was removed by evaporation in vacuo. The residue was purified further by column chromatography on silica get (200 g) using a mixture of dichloromethane and methanol (9:1 ) as eluent, affording 0.4 g (9%) of (S)-1-(3-(10,11-dihydro-5H-dibenzo b,f!-azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.30 (SiO 2 ; dichloromethane/methanol=9:1).
The above ester (0.35 g, 0.89 mmol) was dissolved in ethanol (3 ml) and 12N NaOH (0.26 ml) was added. The mixture was stirred at room temperature for 1.5 h and 4N HCl was added until pH<1 (1 ml). Dichloromethane (50 ml) was added and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue was re-evaporated twice with acetone, affording after drying 0.2 g (62%) of the title compound as a white amorphous product.
HPLC retention time=21.36 minutes.
Calculated for C 23 H 28 N 2 O 2 , HCl, 3/4 H 2 O: C, 66.65%; H, 7.42%; N, 6.76%; Found: C, 66.99%; H, 7.48%; N, 6.36%.
Example 11
1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid hydrochloride
3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propanol (2.0 g, 0.0079 mol, prepared as described in example 10) was dissolved in dry THF (25 ml) under an atmosphere of nitrogen, and triethylamine (2.75 ml) was added. Methanesulfonyl chloride (0.61 ml, 0.0079 mol) was added dropwise and when addition was complete the reaction mixture was stirred for 45 minutes. The mixture was filtered and 3-pyrrolidinacetic acid methyl ester (2.4 g, 0.012 mol) was added to the filtrate. The mixture was heated at reflux temperature for 4 h and then stirred at room temperature for 48 h. Triethylamine (2.2 ml) was added and the mixture was heated at reflux temperature for 24 h. After cooling to room temperature the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (125 g) using a mixture of dichloromethane and methanol (9:1) as eluent, affording 0.9 g (27%) of 1-(3-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid methyl ester as an oil. R f : 0.15 (SiO 2 ; dichloromethane/methanol/acetic acid=20:2:1).
The above ester (0.85 g, 0.0022 mol) was dissolved in ethanol (6 ml) and 0.5N NaOH was added. By continued addition of 0.25N NaOH pH was kept at approximately 12 for 3 days. Dilute HCl (approx. 1N) was added until pH=7, and the solvent was evaporated in vacuo.
The residue was purified by column chromatography on silica gel (50 g) using a mixture of dichloromethane, methanol and acetic acid (20:2:1) as eluent. The product fractions were stripped with dichloromethane, affording 0.04 g (3.8%) of 1-(3-(10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid as an amorphous product.
HPLC retention time=21.66 minutes.
1 H-NMR (400 MHz, CDCl 3 ) δ H 1.68 (1H, m), 2.01 (2H, m), 2.15 (2H, m), 2.38 (2H, m), 2.63 (1H, m), 2.81 (1H, m), 2.95 (2H, m), 3.13 (6H, m), 3.80 (2H, t), 6.92 (2H, t), 7.01 (2H, m), 7.06-7.18 (4H, m).
Example 12
(R)-1-(3-(11H -10-Oxa-5-aza-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
In a 500 ml roundbottom flask equipped with magnetical stirring, thermometer and addition funnel 5,11-dihydro-10-oxa-5-azadibenzo a,d!cycloheptene (4.0 g, 0.02 mol, prepared in a similar way as described in J. Med. Chem., 7, (1964), 609) was dissolved in dry toluene (50 ml) and 3-bromopropionyl chloride (4.2 g, 0.024 mol) was slowly added. The reaction mixture was heated to 95° C. for 30 minutes and then allowed to cool to room temperature. Under stirring 0.2N NaOH (10 ml) was added. More toluene was added (50 ml) and the phases were separated. The organic phase was washed with 0.2N NaOH (3×20 mi) until pH >10, and then with water (3×20 ml) and brine (20 ml). After drying (MgSO 4 ), the organic phase was evaporated in vacuo affording an oil. The product was obtained in quantitative yield and used for further reactions without purification.
The above amide (3.5 g, 0.01 mol) was dissolved in dry THF (20 ml) under a nitrogen atmosphere and cooled to 5° C.
Sodium borohydride (0.31 g, 0.008 mol) was added followed by slow dropwise addition of boron trifluoride etherate (2.0 ml, 0.016 mol). The reaction mixture was left stirring overnight. Further amounts of sodium borohydride (1.2 g. 0.032 mol) and boron trifluoride etherate (5 ml, 0.040 mol) were supplied, and stirring was continued overnight. Water was added to dissolve precipitated salt, followed by ethyl acetate (100 ml). The phases were separated, and the aqueous phase was extracted with ethyl acetate (2×100 ml). The combined organic extracts were washed with water (4×100 ml) and brine (100 ml). After drying (MgSO 4 ) the solvent was removed by evaporation in vacuo and the crude product was purified by column chromatography on silica gel (200 g) with dichloromethane as eluent. This afforded 0.8 g (13%) of the product, 3-bromo-1-(11H-10-oxa-5-aza-5H-dibenzo a,d!cyclohepten-5-yl)propane. R f : 0.62 (SiO 2 ; dichloromethane).
Potassium iodide (3.0 g, 0.018 mol) was dissolved in methyl ethyl ketone (50 ml) and heated at reflux temperature for 30 minutes. The above bromide (0.8 g, 0.0025 mol) was dissolved in methyl ethyl ketone (20 ml), and added. The mixture was heated at reflux temperature for 90 minutes. After cooling to about 60° C., (R)-3-piperidinecarboxylic acid ethyl ester tartrate (0.8 g, 0.0027 mol) and potassium carbonate (0.62 g, 0.0053 mol) were added. The mixture was heated at reflux temperature for 24 h, and left stirring at room temperature for 48 h. After filtration on filter aid (celite) the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (100 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.4 g (37%) of (R)-1-(3-(11H-10-oxa-5-aza-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.17 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (0.37 g, 0.00094 mol) was dissolved in ethanol (5 ml) and a solution of NaOH (0.13 g) in water (0.5 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (0.5 ml). Dichloromethane (50 ml) was added, followed by water (10 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo.
The residue was re-evaporated twice with acetone and once with ethyl acetate, affording, after drying, 0.3 g (77%) of the title compound as an amorphous compound. HPLC retention time=22.57 minutes
Calculated for C 22 H 26 N 2 O 3 , HCl, 1/2 C 4 H 8 O 2 : C, 64.49%; H, 6.99%; N, 6.27%; Found: C, 64.32%; H, 7.05%; N, 5.99%.
Example 13
1-(3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride
3-(10,11-Dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propanol (1.75 g, 0.0069 mol, prepared as described in Example 4) was dissolved in THF (20 ml) and kept under an atmosphere of nitrogen. Triethylamine (1.44 ml) was added, followed by dropwise addition of methanesulfonyl chloride (0.54 ml, 0.0069 mol). When addition was complete the reaction mixture was stirred for 45 minutes. The reaction mixture was filtered and 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid ethyl ester hydrochloride (1.99 g, 0.01 mol) and triethylamine (2.4 ml) were added. The mixture was stirred at room temperature for 9 days. More THF was added, the reaction mixture was filtered and the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (100 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 2.1 g (78%) of 1-(3-(10,11-dihydro-5H-dibenzo- b,f!azepin-5-yl)-1-propyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid ethyl ester as an oil. R f : 0.25 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (1.7 g, 0.0044 mol) was dissolved in ethanol (10 ml) and 4N NaOH (2.7 ml) was added. The mixture was stirred at room temperature for 3 h. 4N HCl (3.8 ml) was added followed by dichloromethane (100 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo, affording 1.3 g (76%) of the title compound as a white amorphous product.
HPLC retention time=21.16 minutes
Calculated for C 23 H 26 N 2 O 2 , HCl, H 2 O: C, 66.26%; H, 7.01%; N, 6.72%; Found: C, 66.57%; H, 7.21%; N, 6.33%.
Example 14
(R)-1-(3-(6,7-Dihydro-5H-dibenzo b,g!azocin-12-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
In a 100 ml roundbottom flask equipped with magnetical stirring, thermometer and addition funnel, 5,6,7,12-tetrahydrodibenzo b,g!azocine (2.1 g, 0.01 mol, prepared in a similar way as described in Chem. Pharm. Bull., 26, (1978), 942) was dissolved in dry toluene (60 ml) and ethyl malonyl chloride (2.0 g, 0.013 mol) was slowly added. The reaction mixture was heated at reflux temperature for 2 h and then allowed to cool to room temperature. Under stirring, 0.2N NaOH (5 ml) and water (60 ml) were added. More toluene was added (100 ml) and the phases were separated. The organic phase was washed with water (3×75 ml) and brine (75 ml). After drying (MgSO 4 ), the organic phase was evaporated in vacuo affording 3.1 g (95%) of 3-(6,7-dihydro-5H-dibenzo b,g!azocin-12-yl)-3-oxopropionic acid ethyl ester as an oil.
LiAIH 4 (1.4 g, 0.037 mol) was placed in a dry, 250 ml, three-necked, roundbottom flask, equipped with thermometer, magnetical stirring and addition funnel. Under nitrogen, dry toluene (60 ml) was added followed by slow addition of THF (6 ml). A temperature at 15°-25° C. was assured by the use of a water/ice-bath. After stirring for 30 minutes, the above amide (3.0 g, 0.0093 mol) was dissolved in dry toluene (18 ml) and slowly added to the LiAlH 4 -slurry at 20°-25° C. The reaction mixture was left stirring overnight at room temperature.
Water (1.5 ml) was slowly added dropwise, followed by 4N NaOH (1.5 ml) and finally water (4.5 ml). The resulting precipitate was filtered off on filter aid (celite). The toluene solution was dried (MgSO 4 ) and evaporated in vacuo. The crude residue was purified by column chromatography on silica gel (75 g), using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.4 g (48%) of 3-(6,7-dihydro-5H-dibenzo b,g!azocin-12-yl)-1-propanol, as an oil. R f : 0.37 (SiO 2 ; n-heptane/ethyl acetate=1:1)
The above alcohol (1.2 g, 0.0045 mol) was dissolved in toluene (25 ml) and triethylamine (1.5 ml) was added. Methanesulfonyl chloride (0.75 ml, 0.009 mol) was added dropwise and the reaction mixture was stirred for 2 h. Water (100 ml) was added, followed by further amounts of toluene (100 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo affording a residue which was dissolved in methyl ethyl ketone (75 ml). To this solution, (R)-3-piperidinecarboxylic acid ethyl ester tartrate (2.1 g, 0.007 mol) and potassium carbonate (1.5 g, 0.011 mol) were added and the mixture was heated at reflux temperature for 24 h, and left stirring at room temperature for 8 days. After filtration on filter aid (celite) the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (75 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 1.1 g (61%) of (R)-1-(3-(6,7-dihydro-5H-dibenzo b,g!azocin-12-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.29 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above ester (500 mg, 0.0012 mol) was dissolved in ethanol (7 ml) and a solution of NaOH (0.2 g) in water (1.5 ml) was added. The mixture was stirred at room temperature for 2 h, and concentrated HCl was added until pH<1 (0.75 ml). Dichloromethane (100 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue was re-evaporated with acetone, ethyl acetate was added and the product was filtered and washed with diethyl ether. This afforded, after drying, 0.4 g (71%) of the title compound as an amorphous compound.
HPLC retention time=22.70 minutes.
Calculated for C 24 H 30 N 2 O 2 , HCl, 1/4 C 4 H 8 O 2 : C, 68.72%; H, 7.56%; N, 6.41%; Found: C, 69.12%; H, 7.94%; N, 6.12%.
Example 15
(R)-1-(3-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
In a 50 ml roundbottom flask equipped with magnetical stirring, thermometer and addition funnel, sodium hydride (0.8 g, 0.02 mol, 60% dispersion in oil) was suspended in dry toluene under an atmosphere of nitrogen. A solution of 10,11-dihydro-5H-dibenzo a,d!cycloheptene-5-carbonitrile (3.0 g, 0.014 mol, prepared in a similar way as described in J. Med. Chem., 6, (1963), 251) in dry toluene (15 ml) was added. The reaction mixture was heated to reflux temperature in 30 minutes and then heated at reflux temperature for 150 minutes. After cooling to about 50° C., a solution of 3-bromopropyl tetrahydropyranyl ether (4.5 g, 0.02 mol) in dry toluene (6 ml) was added dropwise. The reaction mixture was heated at reflux temperature for 5 h and then left stirring at room temperature overnight. After filtration of precipitated salts, the solution was washed with 1N HCl (100 ml), diluted with more toluene (100 ml) and finally washed with water. After drying (MgSO 4 ), the organic phase was evaporated in vacuo affording 7.2 g (99%) of 5-(3-(tetrahydropyran-2-yloxy)-1-propyl)-10,11-dihydro-5 H-dibenzo a, d!cycloheptene-5-carbonitrile.
Under nitrogen, sodium amide (3.5 g, 0.045 mol, 50% suspension in toluene) was added to a 100 ml three-necked roundbottom flask. The above nitrile (4.0 g, 0.011 mol) was dissolved in dry toluene (50 ml) and added. The reaction mixture was heated at reflux temperature for 16 h. After cooling to room temperature, water was added with caution (100 ml).
More toluene was added and the organic phase was washed with dilute HCl. After drying (MgSO 4 ), the organic phase was evaporated in vacuo affording 3.0 g (81%) of crude 2-(3-(10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyloxy)tetrahydropyran as an oil.
The above tetrahydropyran (3.0 g, 0.009 mol) was dissolved in methanol (30 ml) and 4N HCl (10 ml) was added. The reaction mixture was heated at reflux temperature for 15 minutes and left stirring at room temperature for 1 h. Water (50 ml) was added and the aqueous phase was extracted with ethyl acetate (3×75 ml). The combined organic extracts were dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. This afforded a residue which was purified by column chromatography on silica gel (100 g) using a mixture of n-heptane and ethyl acetate (2:1) as eluent. This afforded 0.6 g (24%) of 3-(10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-yl)-1-propanol as an oil. R f : 0.37 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above alcohol (0.55 g, 0.002 mol) was dissolved in toluene (25 ml) and triethylamine (1 ml) was added. Methanesulfonyl chloride (0.5 ml, 0.006 mol) was added dropwise and the reaction mixture was stirred for 2 h. Water (75 ml) was added, followed by a further amount of toluene (100 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo affording a residue which was dissolved in methyl ethyl ketone (50 ml). To this solution, (R)-3-piperidinecarboxylic acid ethyl ester tartrate (1.0 g, 0.0033 mol) and potassium carbonate (0.75 g, 0.0055 mol) were added and the mixture was heated at reflux for 24 h, and then left stirring at room temperature for 72 h. After filtration on filter aid (hyflo) the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (50 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.25 g (29%) of (R)-1-(3-(10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.21 (SiO 2 ; n-heptane/ethyl acetate=1:1)
The above ester (240 mg, 0.00061 mol) was dissolved in ethanol (4 ml) and a solution of NaOH (0.1 g) in water (1 ml) was added. The mixture was stirred at room temperature for 2 h and concentrated HCl was added until pH<1 (0.4 ml). Dichloromethane (100 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue was re-evaporated with acetone, ethyl acetate was added and the product was filtered and washed with diethyl ether. This afforded, after drying, 0.2 g (73%) of the title compound as an amorphous product.
MS(El) 363.2 (M + --HCl, 15%).
Calculated for C 24 H 29 NO 2 , HCl, 3/2 H 2 O: C, 67.52%; H, 7.74%; N, 3.28%; Found: C, 67.70%; H, 7.77%; N, 3.44%.
Example 16
(R)-1-(3-Methoxy-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
In a 100 ml roundbottom flask equipped with magnetical stirring, thermometer, N 2 -inlet and addition funnel, 3-methoxy-10,11-dihydro-5H-dibenzo b,f!azepine (1.2 g, 0.0053 mol) was dissolved in dry toluene (30 ml). Under nitrogen, ethyl malonyl chloride (1.01 g, 0.0067 mol) was slowly added. The reaction mixture was heated at reflux temperature for 2 h and then allowed to cool to room temperature. Under stirring a solution of 0.2N NaOH (2.5 ml) in water (30 ml) was added. More toluene was added (100 ml) and the phases were separated. The organic phase was washed with water (3×50 ml), and brine (50 ml). After drying (MgSO 4 ), the organic phase was evaporated in vacuo affording an oily residue. The product was obtained in quantitative yield and used for further reactions without purification.
LiAlH 4 (800 mg, 0.021 mol) was placed in a dry, 250 ml, three-necked, roundbottom flask, equipped with thermometer, mechanical stirring and addition funnel. Under nitrogen, dry toluene (40 ml) was added followed by slow addition of THF (4 ml). A temperature at 15°-25° C. was assured by the use of a water/ice-bath. After stirring for 30 minutes, the above amide (1.96 g, 0.0053 mol) was dissolved in dry toluene (10 ml) and slowly added to the LiAlH 4 -slurry, keeping the temperature at 20°-25° C. The reaction mixture was left stirring overnight at room temperature. Water (1 ml) was added dropwise, followed by 4N NaOH (1 ml) and finally water (3 ml). The resulting precipitate was filtered off on filter aid (celite). The toluene solution was dried (MgSO 4 ) and the solvent was removed by evaporation in vacuo. The crude residue was purified by column chromatography on silica gel (75 g), using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.9 g (61%) of the product, 3-(3-methoxy-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propanol, as an oil. R f : 0.25 (SiO 2 ; n-heptane/ethyl acetate=1:1).
The above alcohol (900 mg, 0.0032 mol) was dissolved in toluene (25 ml) and triethylamine (1.1 ml) was added. Methanesulfonyl chloride (1.0 ml, 0.013 mol) was added dropwise and the reaction mixture was stirred for 2 h. Water (100 ml) was added, followed by a further amount of toluene (100 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo affording a residue which was dissolved in methyl ethyl ketone (50 ml). To this solution, (R)-3-piperidinecarboxylic acid ethyl ester tartrate (1.44 g, 0.0048 mol) and potassium carbonate (1.1 g, 0.008 mol) were added and the mixture was heated at reflux for 24 h, and left stirring at room temperature for 72 h. After filtration on filter aid (hyflo) the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (50 g) using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.2 g (14%) of 1-(3-(3-methoxy-10,11-dihydro-5H-dibenzo b,f!azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. R f : 0.15 (SiO 2 ; n-heptane/ethyl acetate=1:1)
The above ester (190 mg, 0.00045 mol) was dissolved in ethanol (4 ml) and a solution of NaOH (0.1 g) in water (1 ml) was added. The mixture was stirred at room temperature for 2 h. Concentrated HCl was added until pH<1 (0.4 ml). Dichloromethane (100 ml) was added, followed by water (50 ml) and the phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo. The residue was re-evaporated with acetone, ethyl acetate was added and the product was filtered and washed with diethyl ether. This afforded, after drying, 0.13 g (67%) of the title compound as an amorphous product.
HPLC retention time=22.25 minutes.
Calculated for C 24 H 30 N 2 O 3 , HCl, 2H 2 O: C, 61.74%; H, 7.50%; N, 6.00%; Found: C, 61.83%; H, 7.51%; N, 5.98%.
Example 17
(R)-1-(3-(10-Methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of 11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepine (10 g, 0.048 mol, Synthesis. (1985), 550) in dry dimethylformamide (100 ml) kept under an atmosphere of nitrogen, sodium hydride (2.1 g, 0.052 mol, 60% dispersion in oil) was added, and the reaction mixture was stirred for 1.5 h. Iodomethane (3.27 ml, 0.052 mol) was slowly added keeping the temperature below 30° C. and the mixture was stirred overnight. The reaction mixture was quenched with saturated ammonium chloride (20 ml) and poured onto ice water (300 ml). The solid was filtered off and washed with plenty of water and dried. This yielded 10.4 g of crude 10-methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepine which was recrystallised from methanol (200 ml), to give 6.7 g (63%) of 10-methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepine. M.p. 210°-211° C.
1 H-NMR (200 MHz, DMSO-d 6 ) δ H 3.37 (s, 3H, N--CH 3 ), 6.90 (t, 1H) 6.97-7.14 (m, 4H), 7.24-7.36 (m, 2H), 7.66 (dd, 1H), 7.91 (bs, 1H, NH).
10-Methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepine (5 g, 0.022 mol) was dissolved in dry THF (50 ml) under an atmosphere of nitrogen. n-Butyl lithium (9.1 ml, 0.025 mol, 23% solution in hexane) was slowly added with cooling on an ice bath and stirred for 30 minutes. A solution of 2-(3-bromo-1-propyloxy)tetrahydro-2H-pyran (6.28 g, 0.027 mol) in dry THF (10 ml) was slowly added at room temperature. The reaction mixture was heated to 60° C. for 1 h and stirred at room temperature overnight. The reaction mixture was quenched with saturated ammonium chloride (20 ml) and poured onto ice water (200 ml). The mixture was extracted with dichloromethane (3×150 ml). The combined organic extracts were washed with water (2×80 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. This afforded a residue (9.8 g) which was purified by column chromatography on silica gel (900 ml) using a mixture of dichloromethane and ethyl acetate (6:1) as eluent. This yielded 5.7 g (69%) 10-methyl-5-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propyl)-5,10-dihydro-5H-dibenzo b,e! 1,4!diazepin-11-one as an oil. R f : 0.57 (SiO 2 ; Dichloromethane/ethyl acetate=8:2).
10-Methyl-5-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propyl)-5,10-dihydro-5H-dibenzo b,e! 1,4!diazepin-11-one (5.6 g, 0.015 mol) was dissolved in a mixture of glacial acetic acid (40 ml), THF (20 ml) and water (10 ml), and the mixture was heated at 45° C. for 6 h. Water (200 ml) was added and the mixture extracted with ethyl acetate (4×100 ml). The combined organic extracts were washed with water (4×100 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. This afforded a residue (5.3 g) which was purified by column chromatography on silica gel (500 ml) using a mixture of ethyl acetate and n-heptane (3:1) as eluent. This afforded 2.3 g (53%) of 10-methyl-5-(3-hydroxy-1-propyl)-5,10-dihydro-5H-dibenzo b,e! 1,4!diazepin-11-one as white crystals. R f : 0.34 (SiO 2 ; ethyl acetate/n-heptane=3:1). M.p. 177°-178° C.
10-Methyl-5-(3-hydroxy-1-propyl)-5, 10-dihydro-5H-dibenzo b,e! 1,4!diazepin-11-one (2 g, 0.007 mol) was dissolved in a mixture of dry THF (50 ml) and triethylamine (3 ml) under an atmosphere of nitrogen. Methanesulfonyl chloride (0.69 ml, 0.009 mol) in THF (10 ml) was added dropwise and the reaction mixture was stirred for 1 h. The solvent was removed by evaporation in vacuo and the residue was dissolved in dichloromethane (200 ml). The organic solution was washed with water (3×50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. This afforded 3,0 g 3-(11-oxo-10-methyl-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepin-5-yl)-1-propyl methanesulfonate as a syrup.
A mixture of the above methanesulfonate (2.5 g, 0.007 mmol), (R)-3-piperidinecarboxylic acid ethyl ester tartrate (2.56 g, 0.0083 mol) and dry potassium carbonate (5.81 g, 0.042 mol) in methyl ethyl ketone (50 ml) was heated at reflux temperature for 60 h under an atmosphere of nitrogen. The reaction mixture was filtered and the filter cake washed with plenty of ethyl acetate. The combined organic phases were washed with saturated ammonium chloride (1×100 ml), water (2×100 ml), brine (1×50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The crude product 3.13 g of (R)-1-(3-(10-methyl-11-oxo-10,11-dihydro-5H-dibenzo b,e! 1,4!diazepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester was used without further purification.
The above ester (2.5 g, 0.006 mol) was dissolved in a mixture of ethanol (20 ml) and water (10 ml). Sodium hydroxide (0.3 g, 0.007 mol) was added and the reaction mixture stirred overnight at room temperature. Water (300 ml) was added and the mixture was washed with diethyl ether (2×100 ml) and ethyl acetate (1×100 ml). The aqueous phase was acidified with concentrated HCl (2.2 ml) and washed with dichloromethane (3×100 ml). Evaporation of the water gave a foam which was trituated with a mixture of acetone and 2-propanol (1:1) (3×50 ml) and evaporated in vacuo. The residue was dissolved in a mixture of acetone (100 ml) and 2-propanol (30 ml). Diethyl ether (100 ml) was added and the mixture was stirred overnight.
The precipitate was filtered off and washed with diethyl ether and dried in vacuo to give 1.14 g (45%) of the title compound as white crystals.
M.p. 204°-206° C. Calculated for C 23 H 27 N 3 O 3 , HCl, 7/4 H 2 O: C, 59.86%; H, 6.88%; N, 9.11%; Found C, 59.93%; H, 6.97%; N, 8.97%;
Example 18
(R)-1-(3-(9(H)-Oxo-10H-acridin-10-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of acridone (15 g, 0.077 mol) in dry dimethylformamide (200 ml), sodium hydride (3.7 g, 0.092 mol, 60% dispersion in mineral oil) was added in 4 portions under an atmosphere of nitrogen. The reaction mixture was stirred until gas evolution had ceased. A solution of 2-(3-bromo-1-propyloxy)tetrahydro-2H-pyran (21.7 g, 0.092 mol) in dry dimethylformamide (100 ml) was added dropwise. The reaction mixture was heated to 80° C. for 4 h and stirred overnight at room temperature. The reaction mixture was poured onto ice water (800 ml) and extracted with ethyl acetate (4×200 ml). The combined ethyl acetate extracts were washed with water (3×300 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was dissolved in diethyl ether (150 ml) and unchanged starting material was filtered off. The solvent was evaporated in vacuo and the residue was crystallised from 96% ethanol (150 ml), filtered and washed with ethanol (96%, 30 ml) and diethyl ether (50 ml). This procedure was repeated twice, yielding 8.5 g (33%) of 10-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propyl)acridin-9-one as yellowish crystals. M.p. 140.5°-141.5° C.
1 H-NMR (200 MHz, CDCl 3 ) δ H 1.50-2.00 (m, 6H), 2.22 (m, 2H), 3.61 (m, 2H), 3.97 (m, 2H), 4.53 (dt, 2H), 4.63 (t, 1H), 7.24-7.32 (dd, 2H), 7.61-7.76 (m, 4H), 8.58 (dd, 2H).
10-(3-(Tetrahydro-2H-pyran-2-yloxy)-1-propyl)acridin-9-one was transformed into the title compound using the same procedure as described in Example 17.
M.p.>280° C. 1 H-NMR (400 MHz, DMSO-d 6 ) δ H 1.48 (bs, 1H), 1.89 (bm, 2H), 2.02 (bd, 1H), 2.30 (bs, 2H), 2.98 (bd, 2H), 3.42 (bm, 4H), 3.62 (bs, 1H), 4.57 (t, 2H, N--CH 2 --CH 2 --), 7.37 (t, 2H), 7.86 (dt, 2H), 7.97 (d, 2H), 8.38 (dd, 2H), 11.00 (bs, 1H), 12.85 (bs, 1H).
Example 19
(R)-1-(2-(10,11-Dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-ethyl)-3-piperidinecarboxylic acid hydrochloride
To a solution of 5-(2-bromoethylidene)-10,11-dihydro-5H-dibenzo a,d!cycloheptene (5 g, 0.0167 mol)in acetone (100 ml), (R)-3-piperidinecarboxylic acid ethyl ester hydrogen tartrate (7.89 g, 0.0256 mol), potassium carbonate (6 g, 0.0433 mol) and potassium iodide (1.4 g) were added. The reaction mixture was heated at reflux temperature for 15 h. After filtration on celite, the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (300 g) using a mixture of hexane and ethyl acetate (1:1) as eluent. This afforded 1.78 g (28%) of (R)-1-(2-(10,11-dihydro-5H-dibenzo a,d!cyclohepten-5-ylidene)-1-ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil.
TLC: R f =0.3 (SiO 2 , hexane/ethyl acetate 1:1).
The above ester (1.69 g, 0.0045 mol) was dissolved in ethanol (13 ml) and a solution of sodium hydroxide (0.685 g) in water (2.6 ml) was added. The mixture was stirred at room temperature for 1 h and left overnight. Concentrated hydrochloric acid (2.62 ml) was added followed by dichloromethane (65 ml). The phases were separated. The organic phase was dried (MgSO 4 ) and the solvent evaporated in vacuo.
The residue was re-evaporated with acetone (15 ml), and acetone (30 ml) was added. The precipitated product was filtered off and washed with diethyl ether. After drying, this afforded 1.1 g (64%) of the title compound as a crystalline product.
M.p. 196°-203° C.
Calculated for C 23 H 25 NO 2 , HCl: C, 71.95%; H, 6.83%; N, 3.65%; Cl, 9.23%; Found: C, 71.42%: H, 6.91%; N, 3.39%; Cl, 8.97%.
Example 20
(R)-1-(2-(6,11-Dihydrodibenz b,e!oxepin-11-ylidene)-1-ethyl)-3-piperidinecarboxylic acid hydrochloride
Magnesium (4.94 g, 0.203 mol) kept under tetrahydrofuran (25 ml) was activated using a grain of iodine and 1,2-dibromoethane (0.4 ml). When the reaction was finished, a 10% of solution of vinylbromide (21.4 g, 0.2 mol) in 60 ml tetrahydrofuran was added (dry ice-ethanol condenser, nitrogen atmosphere). The reaction started immediately and the remaining part of the vinylbromide solution was added dropwise under stirring, at such a rate (over 45 minutes) as to maintain the temperature at 58°-62° C. When addition was finished, the mixture was heated at reflux temperature for 30 minutes and then cooled to 10° C. Over 30 minutes, a solution of 6,11-dihydrodibenz b,e!oxepine (21.0 g, 0.1 mol) in tetrahydrofuran (60 ml) was added dropwise under stirring (8°-11° C.). The mixture was allowed to stand overnight at room temperature, and then quenched under cooling (0°-5° C.) with a solution of ammonium chloride (20 g) in water (100 ml). Benzene (100 ml) was added, and the mixture was filtered. The aqueous layer was extracted with benzene (200 ml) and the benzene solutions were combined, dried over MgSO 4 and evaporated. The oily residue was purified by column chromatography on silica gel (120 g) using benzene as eluent. This afforded 20.2 g (85%) of 11-vinyl-6,11-dihydrodibenz b,e!oxepin-11-ol.
The above alcohol (9.7 g, 0.041 mol) was dissolved in dichloromethane (100 ml) and a solution of trimethylsilyl bromide (7.0 g, 0.0457 mol) in dichloromethane (50 was added dropwise over 30 minutes at 0° C. When addition was complete, the mixture was stirred at room temperature for 45 minutes. Ice water (50 ml) was added, the phases were separated and the organic phase was washed with saturated sodium bicarbonate (200 ml). The organic phase was dried (MgSO 4 ) and the solvent was evaporated in vacuo to give 9.0 g (93%) of crude 11-(2-bromoethylidene)-6,11-dihydrodibenz b,e!oxepine.
To a solution of above bromide (4.55 g, 0.015 mol) in dimethylsulfoxide (90 ml), potassium carbonate (7.25 g, 0.053 mol), (R)-3-piperidinecarboxylic acid ethyl ester tartrate (5.07 g, 0.015 mol) and sodium iodide (50 mg) were added, and the mixture was stirred at 70°-80° C. for 5 h. The reaction mixture was diluted with benzene (250 ml), the precipitated solid was filtered off and the filtrate was washed with water (5×100 ml). The benzene solution was dried (MgSO 4 ) and the solvent removed in vacuo. The oily residue (5.6 g) was dissolved in acetone and neutralised using an ethanolic solution of oxalic acid. Crude 1-(2-(6,11-dihydrodibenz b,e!oxepin-11-ylidene)-1-ethyl)-3-piperidinecarboxylic acid ethyl ester hydrogen oxalate was filtered off and washed with hot acetone. Yield 3.15 g (56%).
The above ester (2.18 g base liberated from the hydrogen oxalate, 0.0058 mol) was dissolved in ethanol (17 ml) and 4N sodium hydroxide (5 ml) was added. The reaction mixture was stirred at room temperature for 18 h, then poured into dichloromethane (350 ml) and acidified with concentrated hydrochloric acid. The dichloromethane layer was separated, dried over MgSO 4 and evaporated in vacuo. The residue (2.18 g) was re-evaporated twice with acetone and crude product was crystallised from acetone, affording 1.7 g (76%) of the title compound as crystals.
M.p. 230°-237° C. (decomp.).
Calculated for C 22 H 23 NO 3 , HCl: C, 68.47%; H, 6.27%; Cl, 9.19%; N, 3.63%; Found: C, 68.04%, H, 6.32%; Cl, 8.92%, N, 3.49%. | The present invention relates to the use of compounds of the general formula ##STR1## for reducing blood glucose and/or inhibit the secretion, circulation or effect of insulin antagonizing peptides like CGRP or amylin. Hence the compound can be used in the treatment of insulin resistance related to NIDDM (non-insulin-dependent diabetes mellitus) or aging. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 13/316,801, filed Dec. 12, 2011, which was a continuation of Patent Cooperation Treaty Application Ser. No. PCT/US11/37260, filed May 19, 2011; which claimed the benefit of U.S. Provisional Patent Application Ser. No. 61/346,143, filed May 19, 2010, entitled “TRAILER DOCKING REPOSITIONABLE SUPPORT” and U.S. Provisional Patent Application Ser. No. 61/438,232, filed Jan. 31, 2011, entitled “TRAILER STABILIZER,” the disclosure of each is incorporated herein by reference.
RELATED ART
[0002] 1. Field of the Invention
[0003] The present disclosure is directed to supports utilized to secure freight trailers at a loading dock while dock personnel load and/or unload cargo from the freight trailers.
[0004] 2. Related Art of Interest
[0005] Distribution warehouses are a necessary component of commerce in the twenty-first century. These warehouses may act as a clearinghouse for shipments from various product suppliers and centralize the distribution of goods. Large chain retailers utilize warehouses to generate shipments to particular points of sale that are specific to the needs of consumers in that area, without requiring the original manufacturer of the goods to identify consumer demand at each point of sale and correspondingly deliver the particular goods to each point of sale.
[0006] An exemplary distribution warehouse generally includes fifteen or more loading docks, with each loading dock adapted to receive a single freight trailer of a semi truck. A loading dock typically includes an opening elevated above ground level to match the height of the floor of the freight trailer. The relatively equal height between the floor of the loading dock and the floor of the trailer enables lift trucks (i.e., forklifts) and other material handling devices to move freely back and forth between the warehouse and interior of the freight trailer.
[0007] In an exemplary sequence, a loading dock opening of a warehouse is initially unoccupied by a freight trailer. Thereafter, a semi trailer driver or yard truck driver backs the rear opening of a freight trailer into alignment with the opening of the dock. After the rear of the freight trailer is properly aligned and positioned adjacent to the dock opening, the driver will either continue the engagement between the truck and trailer, or discontinue the engagement and relocate the truck to a remote location. In the context of yard trucks, the yard truck is only connected to the freight trailers long enough to position it adjacent to the loading dock opening. In an exemplary day, the yard truck may connect to and disconnect from one hundred or more freight trailers.
[0008] In summary fashion, a yard truck is a dedicated tractor that stays at the warehouse location and is only used to reposition freight trailers (not to tow the trailers on the open highways). By way of example, a warehouse may have ten dock openings, but have fifty trailers waiting to be unloaded. In order to expedite freight unloading and loading, as well as the convenience of the semi truck drivers that deliver to or pick up the freight trailers from the warehouse, the freight trailers need to be shuffled. This means that freight trailers do not include dedicated semi tractors continuously connected to them. Instead, because no semi truck is connected to many, if not all, of the freight trailers at a warehouse location, a yard truck is necessary to reposition the freight trailers while at the warehouse location.
[0009] An exemplary process for discontinuing engagement between the yard truck and the freight trailer includes initially raising a hydraulic fifth wheel on the yard truck to raise the front end of the trailer above its normal ride height. While the front end is raised, the yard truck driver lowers landing gear of the freight trailer, which comprises a pair of equal length jacks permanently mounted to the trailer, so that lowering of the fifth wheel is operative to set down the freight trailer on its landing gear. When the freight trailer is set down on its landing gear, the freight trailer is freestanding (i.e., without a mechanical connection between the king pin of the freight trailer and the fifth wheel of the yard truck). After the freight trailer is freestanding, associated pneumatic and electrical connections between the yard truck and trailer are disconnected so that the brakes of the freight trailer are locked. Thereafter, the yard truck pulls out from under the freight trailer, thereby leaving the trailer adjacent to the dock opening and being supported at the front end using only the trailer's landing gear.
[0010] When loading and unloading cargo from a freestanding freight trailer, the movement of the lift truck along the floor of the freight trailer causes the freight trailer to move as well. While some movement of the freight trailer is inevitable, considerable movement can result in the trailer becoming separated from the dock or possibly tipping over. More importantly, the landing gear of the freight trailer is not designed to accommodate the weight of a fully loaded trailer, let alone the dynamic forces generated by a lift truck moving through a partially loaded freight trailer. Even further, the high center of gravity associated with most trailers makes the likelihood of tipping over a real possibility. The obvious implications of a freight trailer tipping over include damage to the goods within the trailer, the trailer itself, and the lift truck, not to mention the possible serious injury to or death of the lift truck operator.
[0011] There is a need in the industry for a reliable support that maintains the relative position of the freight trailer with respect to the dock and inhibits the trailer from tipping over, possibly causing serious bodily injury or death, which does not rely solely on the landing gear of the freight trailer.
INTRODUCTION TO THE INVENTION
[0012] The present disclosure is directed to supports associated with a loading/unloading dock and, more specifically, to repositionable supports that secure freight trailers in position at a loading dock while dock personnel load and/or unload cargo from the trailers. The present disclosure includes a repositionable structure having a fifth wheel to capture the king pin of a freight trailer, thereby securing the repositionable structure to the trailer. The repositionable support may also include one or more of an electrical, a hydraulic, and a pneumatic interface for coupling directly to the yard truck or other truck using conventional connections, such as glad hands and electrical disconnects. Unlike conventional stabilizing products, the exemplary embodiments of the instant disclosure may provide support for the front end of a parked freight trailer without the need for deployment of the landing gear (i.e., the landing gear touching the ground). After the repositionable structure has been mounted to the trailer by way of the king pin and fifth wheel interface, wheel chocks may be deployed and brakes associated with the repositionable device may be locked to inhibit horizontal movement of the trailer away from the loading dock. In exemplary form, the repositionable structure may include a winch that is adapted to engage a pavement cleat, thereby forming a compression fit between the king pin and fifth wheel of the repositionable support using the tension from the winch cable. The repositionable support may also include a communicator operative to relay a communication to an internal display within the warehouse that indicates whether the repositionable support is properly mounted to the freight trailer.
[0013] An exemplary repositionable structure includes a frame and an axle mounted to the frame. By way of example, the axle includes a pair of tandem wheels, with brakes, mounted proximate opposite ends of the axle. However, the wheels may be single wheels and not include brakes. A vertically repositionable fifth wheel is also mounted to the frame and is adapted to receive the king pin of a freight trailer. A pair of repositionable wheel chocks may also be mounted to the frame. Also on board the frame may be a freight trailer positioning communicator adapted to signal a warehouse display indicating whether the trailer has been secured while at the loading dock. Pneumatic, hydraulic, and electrical lines may also be associated with the frame that are in communication with any wheel brakes, the repositionable fifth wheel, and any positioning communicator. The foregoing lines may be powered directly from the yard truck, or the frame may include individual power sources for one or more of the foregoing lines.
[0014] After the yard truck has positioned the repositionable support into engagement with the king pin of the freight trailer, the brakes (if included) are applied and the winch (if included) is deployed to lock the support in position below a frontal portion of the trailer. Thereafter, the support remains under the frontal portion of the trailer as the trailer is loaded or unloaded. Similarly, after the support is secured in position beneath the frontal portion of the freight trailer, the yard truck disconnects from the repositionable structure and continues jockeying the remaining freight trailers at the warehouse location.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is an elevated perspective view of an exemplary trailer stabilizer in accordance with the instant disclosure.
[0016] FIG. 2 is a bottom perspective view of the exemplary trailer stabilizer of FIG. 1 .
[0017] FIG. 3 is a left side profile view of the exemplary trailer stabilizer of FIG. 1 .
[0018] FIG. 4 is a top view of the exemplary trailer stabilizer of FIG. 1 .
[0019] FIG. 5 is a front view of the exemplary trailer stabilizer of FIG. 1 .
[0020] FIG. 6 is a rear view of the exemplary trailer stabilizer of FIG. 1 .
[0021] FIG. 7 is an elevated perspective view, from the left rear, of an exemplary gooseneck frame and cart frame in accordance with the instant disclosure.
[0022] FIG. 8 is a bottom perspective view of the exemplary gooseneck frame and cart frame of FIG. 7 .
[0023] FIG. 9 is an elevated perspective view, from the front right, of the exemplary gooseneck frame and cart frame of FIG. 7 .
[0024] FIG. 10 is a right side profile view of the exemplary gooseneck frame and cart frame of FIG. 7 .
[0025] FIG. 11 is an overhead view of the exemplary gooseneck frame and cart frame of FIG. 7 .
[0026] FIG. 12 is an elevated perspective view, from the left side, of the exemplary repositionable hook assembly and lock box in accordance with the instant disclosure.
[0027] FIG. 13 is a top view of the exemplary repositionable hook assembly and lock box of FIG. 12 .
[0028] FIG. 14 is an elevated perspective view of the exemplary repositionable hook assembly and internal components of the lock box of FIG. 12 .
[0029] FIG. 15 is a left side profile view of the exemplary repositionable hook assembly and lock box of FIG. 12 .
[0030] FIG. 16 is a right side profile view of the exemplary repositionable hook assembly and internal components of the lock box of FIG. 12 .
[0031] FIG. 17 is a top view of an exemplary tilt subassembly of an exemplary fifth wheel assembly in accordance with the instant disclosure.
[0032] FIG. 18 is a bottom perspective view, from the front, of the exemplary tilt subassembly of the exemplary fifth wheel assembly of FIG. 17 .
[0033] FIG. 19 is a bottom view of the exemplary tilt subassembly of the exemplary fifth wheel assembly of FIG. 17 .
[0034] FIG. 20 is a profile view, from the front, of the exemplary tilt subassembly of the exemplary fifth wheel assembly of FIG. 17 .
[0035] FIG. 21 is an elevated perspective view, from the left rear, of an exemplary pivoting subassembly of an exemplary fifth wheel assembly in accordance with the instant disclosure.
[0036] FIG. 22 is a bottom perspective view, from the left front, of the exemplary pivoting subassembly of the exemplary fifth wheel assembly in accordance with the instant disclosure.
[0037] FIG. 23 is an elevated perspective view, from the right front, of a portion of the exemplary pivoting subassembly of the exemplary fifth wheel assembly in the context of the cart frame.
[0038] FIG. 24 is an elevated perspective view, from the right rear, of an exemplary repositionable jack assembly in the context of the cart frame in accordance with the instant disclosure.
[0039] FIG. 25 is an elevated perspective view, from the left side, of the exemplary repositionable jack assembly in the context of the cart frame shown in FIG. 24 .
[0040] FIG. 26 is an overhead view of the exemplary repositionable jack assembly in the context of the cart frame shown in FIG. 24 .
[0041] FIG. 27 is a magnified view of a left half of the exemplary repositionable jack assembly of FIG. 24 , shown without the cross-plate.
[0042] FIG. 28 is a forward view of the left half of the exemplary repositionable jack assembly of FIG. 24 , shown without the cross-plate.
[0043] FIG. 29 an elevated perspective view of the right half of the exemplary repositionable jack assembly of FIG. 24 , shown without the cross-plate.
[0044] FIG. 30 is an exemplary schematic diagram showing the fluid network, using a liquid, incorporated in the alternate exemplary embodiment.
[0045] FIG. 31 is an elevated perspective view, from the right rear, of yet another alternate exemplary trailer stabilizer that includes integrated wheel stops.
[0046] FIG. 32 is an overhead view of the alternate exemplary trailer stabilizer of FIG. 31 .
[0047] FIG. 33 is an elevated perspective view from the front left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing certain features.
[0048] FIG. 34 is an elevated perspective view from the front left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing other features.
[0049] FIG. 35 is an elevated perspective view from the rear left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing certain features.
[0050] FIG. 36 is a magnified, elevated perspective view from the rear left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing certain features.
[0051] FIG. 37 is a rear view from the rear left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing certain features.
[0052] FIG. 38 is a frontal view from the rear left of a second exemplary trailer stabilizer in accordance with the instant disclosure showing certain features.
[0053] FIG. 39 is a frontal view from a stabilizer housing for transmitters and receivers in accordance with the instant disclosure.
[0054] FIG. 40 is a frontal view from a dock cabinet for transmitters, receivers, and displays in accordance with the instant disclosure.
[0055] FIG. 41 is a frontal view from an interior warehouse cabinet in accordance with the instant disclosure.
[0056] FIG. 42 is an exemplary wiring diagram showing at least a portion of the control structure of the control circuitry of the second exemplary embodiment relating to the stabilizer and the dock cabinet.
[0057] FIG. 43 is an exemplary wiring diagram showing at least a portion of the control structure of the control circuitry of the second exemplary embodiment as it relates to the interior warehouse cabinet.
[0058] FIG. 44 is an overhead view of the second exemplary embodiment positioned underneath a parked trailer at a loading dock facility, along with an exemplary position of the dock cabinet and interior warehouse cabinet.
[0059] FIG. 45 is an overhead view of an exemplary trailer stabilizer in accordance with the instant disclosure.
[0060] FIG. 46 is a perspective, cut away view of an exemplary brake assembly for use with the exemplary trailer stabilizer of FIG. 45 .
[0061] FIG. 47 is a schematic diagram of an exemplary braking system for use with the exemplary trailer stabilizer of FIG. 45 .
[0062] FIG. 48 is an underneath, perspective view of an exemplary repositioning assembly for use in repositioning the wheel chocks of the exemplary trailer stabilizer of FIG. 45 .
[0063] FIG. 49 is an elevated perspective view of a repositionable wheel chock, in the storage position, for use with the exemplary trailer stabilizer of FIG. 45 .
[0064] FIG. 50 is an elevated perspective view of the repositionable wheel chock of FIG. 49 , shown just prior to complete deployment.
[0065] FIG. 51 is an elevated perspective view of the exemplary trailer stabilizer of FIG. 45 .
[0066] FIG. 52 is a profile view of an exemplary yard truck coupled to the trailer stabilizer of FIG. 45 , shown being backed under a commercial freight trailer.
[0067] FIG. 53 is a profile view of the trailer stabilizer of FIG. 45 mounted and secured to the commercial freight trailer of FIG. 52 .
[0068] FIG. 54 is an overhead view of an exemplary layout at a warehouse or loading dock facility showing placement of the trailer stabilizer of FIG. 45 and the visual display components.
[0069] FIG. 55 is a profile view of another exemplary trailer stabilizer in a disengaged position.
[0070] FIG. 56 is a profile view of the exemplary trailer stabilizer of FIG. 55 in an engaged position.
[0071] FIG. 57 is a profile view of the exemplary draw bar and associated hook in FIG. 55 .
[0072] FIG. 58 is a top view of the exemplary draw bar and associated hook in FIG. 55 .
[0073] FIG. 59 is a top view of the exemplary pavement cleat in FIG. 55 .
[0074] FIG. 60 is a cross-sectional view of the exemplary pavement cleat in FIG. 55 taken along lines 16 - 16 in FIG. 59 .
[0075] FIG. 61 is a cross-sectional view of the exemplary pavement cleat in FIG. 55 taken along lines 17 - 17 in FIG. 59 .
DETAILED DESCRIPTION
[0076] The exemplary embodiments of the present disclosure are described and illustrated below to encompass apparatuses and associated methods to secure a freight trailer in position at a loading dock while the trailer is loaded or unloaded. Of course, it will be apparent to those of ordinary skill in the art that the embodiments discussed below are exemplary in nature and may be reconfigured without departing from the scope and spirit of the present disclosure. However, for clarity and precision, the exemplary embodiments as discussed below may include optional steps and features that one of ordinary skill should recognize as not being a requisite to fall within the scope and spirit of the present disclosure.
[0077] Referencing FIGS. 1-6 , a first exemplary freight trailer stabilizer 100 includes an elevated king pin 102 operatively coupled to a gooseneck frame 104 . This gooseneck frame 104 is concurrently operatively coupled to cart frame 106 and a stiff leg assembly 108 . Operatively coupled to the cart frame 106 are repositionable jack assembly 110 , an axle 112 and wheels 114 , as well as a repositionable hook assembly 116 . As will be discussed in more detail hereafter, the repositionable hook assembly 116 is adapted to interact with a lock box 118 in order to secure the stabilizer 100 to the ground. In addition, the trailer stabilizer 100 includes a fifth wheel assembly 120 that is adapted to engage a king pin of a parked freight trailer to mount the stabilizer 100 to the trailer. Once mounted to the trailer, the hook assembly 116 may be utilized, as well as the repositionable jack assembly 110 , to provide support for the parked trailer.
[0078] Referring to FIGS. 7-11 , the gooseneck frame 104 comprises lower right and left tubular supports 130 , 132 fabricated from rectangular tubular steel. The supports 130 , 132 are welded at one end to a block C-shaped mount plate 134 that is mounted to the cart frame 106 using nut and bolt fasteners. At the opposing end, the supports 130 , 132 are beveled at approximately forty-five degrees and welded to corresponding right and left side diagonal tubular supports 136 , 138 . In order to reinforce the welded joints between the supports 130 , 132 , 136 , 138 , cap plates 140 are mounted over and on the outside of the diagonal weld seams. Similar to the other supports, the diagonal supports 136 , 138 are fabricated from rectangular tubular steel and include generally flat end surfaces (as opposed to being beveled). The diagonal supports operate to, raise the height of the frame 104 and are coupled to corresponding right and left upper tubes 142 , 144 . In particular, one end of the upper tubes 142 , 144 has been beveled at approximately forty-five degrees and welded to corresponding ends of the right and left side diagonal tubular supports 136 , 138 . As with the prior weld joints, cap plates 140 are mounted over and on the outside of the diagonal weld seams to reinforce the coupling between the supports 136 , 138 and the upper tubes 142 , 144 . An opposite end of each tube is generally flat (as opposed to being beveled) and is seated within a cavity 146 of the king pin plate 148 .
[0079] The king pin plate 148 is fabricated from a rectangular plate having been formed to have a block C-shaped end 160 . Two holes 162 , which are generally centered as a group, extend through the front of the block C-shaped end 160 . Though not shown, these holes may accommodate one or more fluid lines (e.g., pneumatic, hydraulic, etc.) for coupling to jacks and motors associated with the stabilizer 100 . It is this C-shaped end 160 , which faces toward the cart frame 106 , that delineates the cavity 146 receiving the corresponding ends of the upper tubes 142 , 144 . Each end of the upper tubes 142 , 144 received within the cavity 146 may be machined so that the angle of the tubes (which taper inward) does not inhibit the entire end surface from contacting a vertical portion 164 of the block C-shaped end 160 . The block C-shaped end 148 cooperates with a generally rectangular portion 166 to comprise the king pin plate 148 . This rectangular portion 166 is positioned underneath and extends between the right and left upper tubes 142 , 144 . Each of the right and left upper tubes 142 , 144 is welded to the rectangular portion 166 in order to secure the king pin plate 148 to the tubes. Centered from side to side, the rectangular portion 166 includes a hole that receives the king pin 102 . In exemplary form, the king pin 102 is welded to the rectangular portion 166 . The king pin 102 extends through the rectangular portion 166 and faces toward the ground in order for the king pin to be available for coupling to a fifth wheel of a tractor (not shown).
[0080] While not coupled to a tractor, the stabilizer 100 may be parked in a storage position. When parked in a storage position, the cart frame 106 of the stabilizer 100 does not bottom out to contact the ground. Rather, the stiff leg assembly 108 is operative to maintain the gooseneck frame 104 and king pin 102 at a height readily accessible by a tractor.
[0081] In exemplary form, the stiff leg assembly 108 is a fixed position device that includes a stiff leg 180 operatively coupled to the gooseneck frame 104 . Specifically, the stiff leg 180 is mounted at one end to a stiff leg brace 182 that is mounted to and extends between the lower right and left tubular supports 130 , 132 . In this exemplary embodiment, the stiff leg brace 182 is fabricated from angle iron and has a first horizontal aspect 184 and an upstanding vertical aspect 186 . The vertical aspect 186 includes at least one hole that is aligned with at least one corresponding hole extending through the stiff leg 180 so that nut a bolt fasteners mount the stiff leg to the stiff leg brace. In exemplary form, the stiff leg 180 is fabricated from block C-shaped metal stock and includes two upstanding, parallel flanges 188 that extend away from a base 190 . The stiff leg 180 is positioned to extend vertically so that the flanges 188 extend toward the cart frame 106 . In this manner, it is the base 190 that is adjacent and mounted to the upstanding vertical aspect 186 of the stiff leg brace 182 , while the opposite end (i.e., lower end) is adapted to be proximate the ground.
[0082] The opposite, lower end of the stiff leg 180 is machined to remove a portion of the base 190 . In so doing, the lower end of the stiff leg 180 includes medial and lateral rectangular flaps 192 . These rectangular flaps 192 are really extensions of the two upstanding flanges 188 that remain at the lower end once a portion of the base 190 is removed. Each flap 192 includes a through hole in order to accommodate a nut and bolt fastener to secure a rubber block 194 to the stiff leg 180 . In exemplary form, the rubber block 194 includes a widthwise dimension to fit between the flaps 192 and a vertical, lengthwise dimension great enough to extend outward beyond the flaps when the block is mounted to the stiff leg 180 . It should be noted that materials other than rubber may be used for the block. Likewise, one may omit the block altogether and have the stiff leg itself contact the ground.
[0083] Diagonal braces 200 , 202 are concurrently mounted to the stiff leg 180 and the block C-shaped mount plate 134 in order to provide additional stability to the stiff leg. In exemplary form, the diagonal braces 200 , 202 each comprise angle iron and are mounted to corresponding parallel flanges 188 . More specifically, one end of each diagonal brace 200 , 202 is mounted to the outside of a corresponding flange 188 , while the opposite end of each diagonal brace 200 , 202 is mounted to a bracket 204 inset within the block C-shaped mount plate 134 . In this exemplary embodiment, the flanges 188 , diagonal braces 200 , 202 , and the brackets 204 include corresponding through holes that are aligned and receive bolts secured in place by nuts. In lieu of nut and bolt fasteners, the diagonal braces 200 , 202 may be welded to the flanges 188 and the block C-shaped mount plate 134 . It should be noted that the block C-shaped plate includes a plurality of through orifices 204 that may accommodate one or more fluid lines (e.g., pneumatic, hydraulic, etc.) for coupling to jacks and motors associated with the stabilizer 100 .
[0084] The block C-shaped plate 134 signifies the transition between the gooseneck frame 104 and the cart frame 106 . As will be described in more detail hereafter, the cart frame 106 has mounted to it the repositionable jack assemblies 110 , the axle 112 , and the repositionable hook assembly 116 . In order to accommodate these assemblies 110 , 116 and axle 112 , the cart frame 106 includes right and left frame rails 210 , 212 that are mounted to forward and rear cross-members 214 , 216 . The frame rails 210 , 212 are straight, block C-shaped and extend in parallel to one another so that the side flanges are directed toward the ground and the base faces upward. Specifically, the side flanges are oriented perpendicular to the base of the frame rails 210 , 212 . These side flanges (on the inside that face one another) are welded to the front cross-member 214 in order to provide lateral support to the cart frame 106 .
[0085] In this exemplary embodiment, the front cross-member includes a longitudinal pan 218 with integral front and rear flanges 220 . It is the top of the longitudinal pan and the front and rear flanges 220 that are welded to the inside flanges of the frame rails 210 , 212 . The longitudinal pan 218 includes opposed vertical longitudinal walls 222 interposed by a bottom wall 224 . The bottom wall 224 includes a plurality of orifices 226 , where two of the orifices are surrounded by an upstanding ring 228 mounted to the bottom wall. As will be discussed in greater detail hereafter, the upstanding ring 228 is sized to be circumscribed by a coil spring that biases the fifth wheel assembly 120 . In this manner, the upstanding ring 228 inhibits lateral movement at the base of the spring. In exemplary form, the vertical longitudinal walls 222 are perpendicular to the bottom wall 224 and the entire bottom wall, as well as a portion of the longitudinal walls, is positioned vertically below the height of the frame rails 210 , 212 .
[0086] Also positioned vertically below the height of the frame rails 210 , 212 are the axle 112 and the wheels 114 . In this exemplary embodiment, the axle 112 is mounted to the frame rails 210 , 212 using corresponding pairs of U-bolts and nuts 240 . More specifically, the U-bolts 240 extend around the axle and are received through corresponding holes in the base of the frame rails 210 , 212 and mounted thereto using the nuts. In order to increase the forward-to-rearward stability of the axle 112 , each frame rail 210 , 212 includes a semi-circular cutout 242 formed at the bottom of each flange. These semi-circular cut-outs 242 are linearly aligned in the medial-lateral direction and operate to seat the axle 112 within the frame rails 210 , 212 . As would be expected, the axle 112 is generally centered in the medial-lateral direction underneath the cart frame 106 . And the axle 112 interposes the forward and rear cross-members 214 , 216 .
[0087] In this exemplary embodiment, the rear cross-member 216 comprises a block C-shaped plate. The cross-member 216 includes a pair of vertical walls 246 perpendicular to a base wall 248 , where the vertical walls are parallel to one another. In exemplary form, the vertical walls 246 are closer to the ground than is the base wall 248 , where the height of the vertical walls 246 is substantially the same as the flanges for the frame rails 210 , 212 . Specifically, the rear cross-member 216 is positioned in between the frame rails 210 , 212 at the rear of each of each frame rail to be substantially flush with the rear of the frame rails. More specifically, the exposed ends of the flanges of the frame rails 210 , 212 lie along the same plane as the exposed ends of the vertical walls 246 . When the frame rails 210 , 212 are welded to the rear cross-member 216 , the flanges of the frame rails cap the longitudinal ends of the cross-member 216 .
[0088] In order to complete the cart frame 106 , a number of vertical walls and elevated walls are mounted to the frame rails 210 , 212 . In exemplary form, the cart frame 106 also includes right and left rear frame walls 250 , 252 and right and left front frame walls 254 , 256 . The right and left rear frame walls 250 , 252 comprise a rectangular plate 260 having a perpendicular vertical flange 262 at one end and an associated rectangular wall 263 with its own perpendicular flange 265 at the opposite end. The plate 260 , flanges 262 , 265 , and wall 263 all have the same vertical dimension and vertical ends that lie along the same corresponding planes (top and bottom). The plate 260 embodies the greatest width of the frame walls and includes a semicircular cut-out 264 and various through holes 266 . These cutouts 264 and holes 266 may be included to provide openings for various electrical wirings and/or fluid conduits. At the same time, these cutouts 264 and holes 266 may reduce the operating weight of the stabilizer 100 without sacrificing load bearing potential.
[0089] The right and left rear frame walls 250 , 252 are mounted to the top of the base of the frame rails 210 , 212 and the base wall 248 of the rear cross-member 216 . Specifically, the frame walls 250 , 252 are oriented so that the right angle corner formed by the intersection of the plate 260 and the wall 263 overlies a rear corner of a corresponding frame rail. In this manner, the plate 260 extends toward the front of the cart frame 106 so that its edge sits upon the outer edge of the base of a respective frame rail 210 , 212 . Concurrent with this positioning, the wall 263 is positioned to overlay the rear edge of the cart frame 106 . This rear edge is cooperatively formed by the rear edge of the base of a corresponding frame rail 210 , 212 in combination with outside edge of the base wall 248 of the rear cross-member 216 . When in this position, the right and left rear frame walls 250 , 252 are welded to the frame rails 210 , 212 and rear cross-member 216 . On the interior of each right and left rear frame walls 250 , 252 , proximate the top upper corner where the plate 260 and wall 263 intersect, are tubular brackets 270 . As will be discussed in more detail hereafter, the tubular brackets 270 receive a hitch plate pivot shaft as part of the fifth wheel assembly 120 .
[0090] At the rear of the cart frame 106 , a rear brace 280 extends between and is mounted to the wall 263 of both frame walls 250 , 252 . The rear brace 280 comprises a vertical wall 282 that is perpendicularly oriented with respect to a horizontal extension 284 that extends from the vertical wall. The vertical wall 282 has a cut-out 286 in order to ensure the brace 280 does not contact a king pin from a parked trailer. In this exemplary embodiment, nut and bolt fasteners 288 are utilized to mount the rear brace 280 to the frame walls 250 , 252 . It should also be noted that, as with the foregoing use of nut and bolt fasteners, the exemplary embodiment may utilize other means of fastening such as, without limitation, welding.
[0091] Extending from the rear to the front of the cart frame 106 , are a pair of frame links 300 , 302 that are positioned above and run in parallel with the frame rails 210 , 212 . The right link 300 is concurrently mounted to the right rear frame wall 250 and right front frame wall 254 . Similarly, the left link 302 is concurrently mounted to the left rear frame wall 252 and left front frame wall 256 . Each link 300 , 302 comprises angle iron that is mounted to a respective side's frame walls using nut and bolt fasteners 304 . In exemplary form, the right link 300 cooperates with the right frame rail 210 and the right front and rear frame walls 250 , 254 to delineate a generally rectangular right side opening 306 . Likewise, the left link 302 cooperates with the left frame rail 212 and the left front and rear frame walls 252 , 256 to delineate a generally rectangular left side opening 308 . As will be discussed in more detail below, these openings 306 , 308 are utilized to link components of the repositionable jack assemblies 110 .
[0092] The right and left front frame walls 254 , 256 are mounted to the base of respective frame rails 210 , 212 . More specifically, each frame wall 254 , 256 comprises a block C-shape with a base wall 320 and two corresponding side walls 322 that expend parallel to one another. In this exemplary embodiment, the side walls 322 are perpendicular to the base wall 320 and are substantially shorter in width that the base wall. In order to mount the right and left front frame walls 254 , 256 are mounted to the base of respective frame rails 210 , 212 , the frame walls are oriented so that the base wall 320 is aligned with the outside edge of the frame walls. At the same time, the side walls 322 are positioned to sit on top of the base wall of the frame rails 210 , 212 . More specifically, the forward most corner (where the side wall 322 and the base wall 320 intersect) of each frame wall 254 , 256 is oriented to overly the outermost corner of a respective frame rail 210 , 212 . In this orientation, the bottom edge of the side wall 322 sits upon the front top edge of a respective frame rail 210 , 212 , while the base wall 320 sits upon the outer top edge of the same frame rail, and the frame walls 254 , 256 are welded to the frame rails 210 , 212 .
[0093] In order to couple the remainder of the cart frame 106 to the gooseneck frame 104 , the cart frame also includes gussets 326 concurrently mounted to respective right and left front frame walls 254 , 256 and the block C-shaped mount plate 134 . Specifically, the block C-shaped mount plate 134 includes two, spaced apart horizontal walls 330 , 332 linked together by a vertical wall 334 . In exemplary form, the vertical wall is positioned adjacent to the forward most side wall 322 of each right and left front frame wall 254 , 256 so that the ends of the block C-shaped mount plate 134 do not extend laterally beyond the base walls 320 . Likewise, the block C-shaped mount plate 134 is positioned so that the top edge of the right and left front frame walls 254 , 256 is at the same vertical height as the upper horizontal wall 330 . When in this position, respective gussets 326 lie flush on top of the respective right and left front frame walls 254 , 256 and the upper horizontal surface 330 of the block C-shaped mount plate 134 . In particular, the gussets 326 interpose the links 300 , 302 and the right and left front frame walls 254 , 256 . The gussets 326 are then mounted to the block C-shaped mount plate 134 using a first set of fasteners 340 and also mounted to the links 300 , 302 using a second set of fasteners 342 . Complementary brackets 350 are also mounted to the forward most side wall 322 of each right and left front frame wall 254 , 256 to wedge the block C-shaped mount plate 134 in between the gussets 326 and the brackets. By way of example, the brackets may be welded to the forward most side wall 322 of each right and left front frame wall 254 , 256 or coupled thereto using any conventional fastener or fastener technique. Likewise, the brackets 350 are mounted to the block C-shaped mount plate 134 and may be mounted thereto by welding or using any conventional fastener (e.g., nut and bolts fasteners) or fastener technique.
[0094] Referring to FIGS. 12-16 , the repositionable hook assembly 116 is mounted to the cart frame 106 and adapted to interact with the lock box 118 in order to fasten the stabilizer to the ground. The lock box 118 is adapted to be mounted securely to the ground using ground spikes, nails, or other similar fasteners (not shown) so that the lock box is not readily repositionable.
[0095] In exemplary form, the lock box 118 includes corresponding right and left side ramps 400 , 402 that cooperate with corresponding front and rear ramps 404 , 406 to provide a frustopyramidal structure. More specifically, the ramps 400 , 402 are comprised of generally flat metal plates having an upper lip 408 opposite a substantially wider base 410 . The front and rear ramps 404 , 406 comprise generally flat metal plates but for angled flanges 411 at opposing lateral ends. The angle of the flanges 411 is adapted to match the angle of incline of the right and left side ramps 400 , 402 . Moreover, the flanges 411 include orifices 412 that overlap countersunk orifices 414 formed through the lateral sides of the right and left side ramps 400 , 402 . More specifically, the medial and lateral sides of the right and left side ramps 400 , 402 overly the flanges 411 of the front and rear ramps 404 , 406 so that the orifices 412 , 414 overlap in order to receive nut and bolt fasteners to mount the ramps to one another. When assembled, the ramps 400 , 402 , 404 , 406 provide an incline on all four sides without appreciable seams for large objects (such as snow plows) to catch the seams and rip apart the ramps. In addition, the lips 408 are oriented in parallel with the ground when the ramps 400 , 402 , 404 , 406 are assembled in order to provide overhead protection for components on the interior of the lock box that are not intended to be contacted by the hook assembly 116 .
[0096] The interior of the lock box 118 includes an anchor 420 having one or more holes (not shown) to receive ground spikes, nails, or other similar fasteners (not shown) in order to secure the lock box to the ground. In exemplary form, the anchor 420 comprises an elongated rectangular plate 422 having upstanding medial and lateral walls 424 , 426 . Each wall 424 , 426 is oriented generally perpendicular to the plate 422 and is beveled at its ends to match the intended incline of the front and rear ramps 404 , 406 . The medial and lateral walls 424 , 426 include four identical cutouts 430 having rounded, cupped shape (and may be semicircular) to act as a seat in order to receive a cylindrical anchor bar 432 . The cutouts 430 are generally evenly spaced apart and cooperate with anchor bar orifices 438 extending through the right and left side ramps 400 , 402 in order to secure the cylindrical anchor bars 432 in position, but also allow the anchor bars to axially rotate. Each anchor bar 432 includes an outer cylinder 434 having a length at least long enough to laterally span corresponding cutouts 430 . The outer cylinder 434 may be machined to include cylindrical extensions 436 from each end that are of a smaller diameter. Alternatively, the outer cylinder 434 may have an internal cylindrical cavity that is occupied by a cylindrical insert 436 having an overall length long enough to extend axially outward from the outer cylinder. In either circumstance, the cylinders 434 , 436 are mounted to one another so that rotation of one results in rotation of the other. A trap door 440 is mounted to three of the four outer cylinders 434 .
[0097] Interposing the four cutouts 430 are three identical cutouts 444 having a generally arcuate path with a flat end. The three cutouts 444 receive corresponding ends of each trap door 440 . In this manner, as the outer cylinder 434 is rotated, so too is the trap door rotated, thus the arcuate path of the cutout 444 . In exemplary form, the lengthwise dimension of each trap door 440 approximates the horizontal distance between adjacent outer cylinders 434 . Likewise, the widthwise dimension of each trap door 440 approximates the lateral distance between the medial and lateral walls 424 , 426 . In this way, the trap door 440 attempts to prohibit foreign debris of problematic size from entering the lock box 118 and inhibiting its operation.
[0098] For the three outer cylinders 434 that includes a trap door 440 , a spring 446 (e.g., a torsion spring) is mounted to the smaller cylinder 436 and is operative to bias the trap door in the horizontal, blocking position (see FIG. 13 ). Thought not necessary, at least one of the medial and lateral walls 424 , 426 includes a stop 450 mounted to the anchor 420 that is adapted to engage a spring, such as a torsion spring, in order cooperate with the spring to bias the trap door 440 to the blocking position. But, when contacted by the hook as will be described hereafter, the hook is operative to overcome the bias and force the trap door downward so the hook can couple to a corresponding outer cylinder 434 .
[0099] The repositionable hook assembly 116 includes an airbag 460 operatively coupled to a linear rod 462 . The linear rod 462 includes a fitting 464 having a ball joint that receives a clevis pin 466 in order to transfer motion from the airbag 460 to a pivot shaft 468 . The pivot shaft 468 includes a pivot arm 470 having a hole 472 therethrough. This hole 472 receives the clevis pin 466 , where motion of the clevis pin is transferred to the pivot shaft 468 by way of the pivot arm 470 . Specifically, the airbag 460 is operative to expand (i.e., inflate) and turn the pivot arm 470 and pivot shaft 468 in the clockwise direction that is operative to lower a hook 480 . Alternatively, the airbag 460 may be omitted and the hook 480 may be lowered using gravity. But the hook assembly 116 also includes a second airbag 482 having a linear rod 484 and a fitting 486 with a ball joint to receive the clevis pin 466 . This second airbag 482 is operative to expand (i.e., inflate) and turn the pivot arm 470 and pivot shaft 468 in the counterclockwise direction to raise the hook 480 or retain the hook in a raised position. Both of the airbags 460 , 482 are mounted to a bracket 490 that is mounted to the top of the rear cross-members 216 . Specifically, the bracket 490 includes a pair of holes 492 that receive nut and bolt fasteners to mount the bracket to the rear cross-member. In exemplary form, the bracket 490 includes a pair of opposed flanges 494 , 496 having corresponding holes that receive nut and bolt fasteners to couple the airbags 460 , 482 to the respective flanges 494 , 496 . Interposing the flanges 494 , 496 is a section of angle iron 498 that includes the pair of holes 492 used to mount the bracket 490 to the rear cross-member 216 . A pair of shaft brackets 500 is utilized to mount the pivot shaft 468 to the rear cross-member 216 and the rectangular wall 263 of the right and left rear frame walls 250 , 252 .
[0100] The hook 480 is mounted to the pivot shaft 468 so that rotation of the pivot shaft results in arcuate movement of the hook, generally in an upward and downward direction. In this exemplary embodiment, the hook 480 comprises mirror image hook halves 510 , 512 . Each hook half 510 , 512 comprises a first bar stock section 514 having a rounded proximal end 516 and a through orifice allowing throughput of the pivot shaft 468 . Specifically, the bar stock section 514 is welded to the pivot shaft 468 and gussets 518 are concurrently welded to the bar stock section and the pivot shaft. A distal end of the bar stock section 514 includes a bend that transitions into a second bar stock section 520 . Alternatively, the bar stock sections 514 , 520 may be separate pieces that are welded together. This second bar stock section 520 includes a distal bend and comprises a hook section 524 . In exemplary form, the hook sections 524 from each hook half 510 , 512 are welded together to create a two-ply end hook 530 .
[0101] Referring to FIGS. 17-20 , the fifth wheel assembly 120 comprises two primary subassemblies, the tilt subassembly 550 and the pivot subassembly 560 . The tilt subassembly 550 includes a tilt plate 570 having a generally rectangular shape, but for a tapered cutout 572 that leads into a king pin cavity 574 . The king pin cavity 574 is adapted to be occupied by the king pin of a parked freight trailer. In this exemplary embodiment, the king pin cavity 574 is partially defined by the tilt plate 570 and partially defined by a king pin block 576 mounted to the underside of the tilt plate. The lateral sides 578 of the tilt plate 570 are formed by lateral extensions of the plate having been rounded over to form perpendicular flanges. A frame 580 is mounted to the underside of the tilt plate 570 and includes lateral and vertical cross members 582 , 584 . The frame also includes a front plate 586 that spans a proximal portion of the tilt plate 570 , as well as distal plates 588 that span between angled frame members 590 and the lateral sides 578 . The angled frame members 590 lie along the cutout 572 in order to reduce wear upon the tilt plate where the king pin from the freight trailer would otherwise contact.
[0102] As will be described in more detail hereafter, the tilt plate 570 is repositionable with respect to the pivot subassembly 560 . In particular, parallel, vertical cross members 584 each include extensions 594 through which holes are bored to receive a tilt shaft 596 . The sides 578 of the tilt plate 570 also include extensions 598 through which holes are bored to receive the tilt shaft 596 . In this exemplary embodiment, the tilt shaft 596 is welded to the extensions 594 , 598 so that rotation of the shaft results in corresponding movement of the tilt plate 570 . Interposing the extensions 594 , 598 are a pair of brackets 600 that are mounted to the pivot subassembly 560 . These brackets 600 allow the tilt shaft 596 to rotate so that tilting of the tilt plate 570 is possible with respect to the pivot subassembly 560 is possible, but to a limit. The brackets 600 each have corresponding holes adapted to overlap with holes in the pivot subassembly and receive nut and bolt fasteners to repositionably mount the tilt subassembly 550 and the pivot subassembly 560 .
[0103] Referring to FIGS. 21-23 , the pivot subassembly 560 includes a right and left side pivot tubes 610 , 612 fabricated from rectangular metal tubing. Each tube 610 , 612 includes corresponding holes 614 that overlap with the holes 602 in the brackets to receive nut and bolt fasteners to repositionably mount the tilt subassembly 550 and the pivot subassembly 560 . At the rear of each tube 610 , 612 are a pair of circular openings that allow throughput of a pivot shaft 616 . In exemplary form, the pivot shaft 616 extends through each tube 610 , 612 a predetermined distance and is welded to each tube. At the front of each tube 610 , 612 is a cross-tube 620 that is positioned between the tubes and is welded thereto. By way of example, the tubes 610 , 612 , 620 , and the shaft 616 form a rectangle. It should be noted that the extension of the pivot shaft 616 extending beyond the tubes 610 , 612 is at least partially received within the tubular brackets 270 of the cart frame 106 to allow the pivot subassembly 560 to pivot with respect to the cart frame. Finally, each tube 610 , 612 includes a rocker 626 mounted to the front of each tube on the opposite side as the brackets 600 . The rocker 626 comprises arcuate projection 628 that is received within a corresponding bracket of the repositionable jack assemblies 110 to that the rocker can move in a rocking motion when the pivot subassembly 560 pivots with respect to the cart frame 106 .
[0104] Referring to FIGS. 24-29 , the repositionable jack assembly 110 is operative to deploy a pair of jacks 650 mount on the medial and lateral sides of the cart frame 106 to at least partially support some of the weight at the front of the freight trailer and provide greater lateral stability than is possible using the freight trailer's landing gear. In this exemplary embodiment, the jacks 650 are screw jacks. Those skilled in the art are familiar with the operation of screw jacks and therefore the internal structure and operation of screw jacks will not be discussed for purposes of brevity.
[0105] Each screw jack 650 includes a telescopic screw jack leg 652 mounted to front and rear brackets 654 , 656 . Each bracket 654 , 656 comprises an I-beam construction with a first section 658 that is welded to the jack leg and extends laterally outward therefrom. A second I-beam section 660 is welded to the first section 658 and is oriented perpendicularly with respect to the first section and extends through a corresponding side opening 306 , 308 in the cart frame 106 . The end of the second section 660 not mounted to the first section 658 includes a vertical end plate 662 that spans between the top and bottom of the I-beam on one side of the vertical wall of the I-beam. The vertical end plate is welded in position and includes a plurality of orifices 664 for mounting to a side plate 666 .
[0106] The side plate 666 extends parallel with the plane of the opening 306 , 308 and includes a vertical wall 680 that is rounded over to provide a pair of vertical flanges 682 , 684 that are oriented generally perpendicular to the vertical wall. Each flange 682 , 684 is mounted to at least one follower 686 that follows a respective section of vertical track 688 mounted to a vertical flange 690 of one of four frame walls (right rear frame wall 250 , left rear frame wall 252 , right front frame wall 254 , left front frame wall 256 ). In this fashion, as the screw jack leg 652 is extended and eventually contacts the ground, the screw jack leg 652 will operate to push upward on the jack, which will push upward on the brackets 654 , 656 , thereby pushing upward on the side plate 666 so the side plate travels vertically in a straight path as dictated by the followers 686 following the track 688 .
[0107] The side plate 666 also includes a third flange 687 , also rounded over from the vertical wall 680 , that extends horizontally toward the center of the cart frame 106 . This flange 687 has mounted to it a guide track 700 that receives the arcuate projection of the rocker 626 so the pivot subassembly 560 can rock with respect to the side plate 666 .
[0108] Underneath the third flange 687 is a welded gusset 701 that contacts a cross-plate 702 . The cross-plate 702 includes a horizontal plate 704 that extends laterally (i.e., medial to lateral direction) in between opposing side plates 666 and is spaced apart from the third flange 687 by the gusset 701 . The cross-plate 702 also includes a vertical plate 706 that extends perpendicularly from the horizontal plate 704 at a front edge of the horizontal plate. In exemplary form, the gusset 701 is welded to the horizontal plate 704 , while the end of the vertical plate 706 is welded to the underside of the third flange 687 .
[0109] The side plate 666 also includes a lateral orifice 710 to allow throughput of a rotating shaft. In this exemplary embodiment, the rotating shaft comprises a drive shaft 712 coupled to a first jaw coupling 714 . This first jaw coupling 714 is coupled to a second jaw coupling 716 , which is itself coupled to a screw jack shaft 718 that extends through the jack leg 652 . An opposite end of the drive shaft 712 is coupled to a clutch 720 . The clutch 720 receives an output shaft 722 from a gearbox 724 coupled to an air motor 726 . In exemplary form, the gearbox 724 is mounted to the horizontal plate 704 , while the air motor 726 is mounted to the gearbox. The other components such as the drive shaft 712 , the jaw couplings 716 , 718 , the clutch 720 , and the output shaft are 722 suspended in the air.
[0110] Underneath the cross-plate 702 are two upstanding rings 730 that are vertically aligned with the two upstanding rings 228 mounted to the forward cross-member 214 . Circumscribing these upstanding rings 228 , 730 are two coil springs 732 . In this manner, the repositionable jack assembly 110 floats on top of the two coil springs when the screw jack legs 652 are raised. This means that the amount of force required to position the fifth wheel assembly 120 underneath a parked trailer is only as great as the bias exerted by the springs. But after the stabilizer 100 is coupled to the parked trailer and the jack assembly is operative to extend the jack legs 652 , it is the jack legs that are bearing the weight of the fifth wheel assembly 120 and at least a portion of the weight of the parked freight trailer.
[0111] In order to power the repositionable jack assembly 110 and the repositionable hook assembly 116 , the exemplary stabilizer 100 uses pneumatic power. Those skilled in the art are familiar with pneumatic power. Accordingly, for purposes of clarity, the pneumatic lines running to the air motor 726 and airbags 460 , 482 have been omitted. Nevertheless, the stabilizer 100 includes an on-board fluid tank 740 that may be used to store compressed air to power the repositionable jack assembly 110 and the repositionable hook assembly 116 . In this exemplary embodiment, the fluid tank 740 is mounted to the front ends of the right and left frame rails 210 , 212 using brackets 742 and nut and bolt fasteners. It should also be noted that the fluid tank 740 may be supplemented by an air supply from a tractor or hustler. While glad-hands have not been shown in the drawings, it is understood that the instant stabilizer 100 may include pneumatic lines linking the fluid tank 740 to a glad-hand connection. Alternatively, the stabilizer may include pneumatic lines that by-pass the fluid tank and connect optionally to a glad-hand. In such a circumstance, when a by-pass approach is utilized, the stabilizer need not be supplied with a fluid tank 740 .
[0112] The exemplar stabilizer 100 is adapted to be coupled to a tractor or a hustler via the king pin 102 . While not required, the stabilizer may also couple to one or more power supplies on the tractor or hustler to power one or more of the foregoing assemblies. In exemplary form, the parked freight trailer would already be parked over the lock box 118 . After the stabilizer 100 is coupled to the tractor or hustler, the stabilizer is backed under a parked trailer at a loading dock so that the repositionable hook assembly 116 first goes under the trailer, followed by the rear of the cart frame 106 in order for the fifth wheel assembly 120 to capture the king pin of the parked trailer. In exemplary form, the fifth wheel assembly 120 include an automatic lock that capture the king pin of the parked trailer and does not allow the stabilizer to be disengaged without affirmatively disengaging the lock.
[0113] After the stabilizer 100 captures the king pin, the repositionable hook assembly 116 is engaged to lower the hook 480 by supplying air to inflate the airbag 460 . Depending upon the dimensions of the freight trailer and the position of the lock box 118 , the hook 480 may contact a trap door 440 and fall in between anchor bar 432 . Thereafter, the stabilizer may be repositioned forward to lock the hook 480 within the lock box 118 . Alternatively, the hook 480 may contact one of the anchor bars 432 , at which time the stabilizer is move slightly rearward so the hook rides upon the anchor bar and then drops down onto the next trap door 440 . Thereafter, the stabilizer is pulled slightly forward to lock the hook 480 within the lock box 118 .
[0114] After the repositionable hook assembly 116 has been positioned to lock the hook 480 within the lock box 118 , the repositionable jack assembly 110 is engaged to deploy the jacks. In exemplary form, air is supplied to the air motor 726 , which in turn turns gears within the gearbox 724 to correspondingly rotate the output shaft 722 . The drive shaft 712 is driven by the output shaft, interposed by the clutch 720 , and operates to drive the screw jack legs 652 downward. If an impediment is sensed, such as a wood block under one of the screw jack legs, but not under the other screw jack leg, the clutch will engage to disallow further rotation of the screw jack until the resistance of both jack legs is approximately the same. It should be noted that the stabilizer, while able to accommodate the entire weight of a fully loaded trailer at the front of the trailer, is more often utilized to share the load of the loaded trailer with the trailer's landing gear. As soon as the repositionable jack assembly 110 has been positioned to transfer some of the trailer's load onto the stabilizer 100 , dock personnel are notified that it is appropriate to load or unload the parked trailer. This may be done with manually operated signals or may be accomplished via automated signals associated with the stabilizer that send a signal to dock personnel as soon as the repositionable hook assembly 116 and the repositionable jack assembly 110 have been successfully deployed.
[0115] To remove the stabilizer, a similar process is followed in the opposite sequence. First, the repositionable jack assembly 110 is disengaged, followed by disengaging the repositionable hook assembly 116 . Thereafter, the stabilizer 100 is removed from the parked trailer and put in a storage position or moved underneath another parked trailer.
[0116] Referring to FIG. 30 , while the foregoing exemplary embodiment has been explained using pneumatic power, an alternate exemplary embodiment for a trailer stabilizer is identical to the foregoing exemplary embodiment, except that the power supply, associated motors, and airbags are exchanged for hydraulic power and hydraulic cylinders. In exemplary form, the on-board fluid tank 740 of the stabilizer is at least partially filled by a glycol liquid (e.g., propylene glycol). The fluid tank 740 includes at least one outlet to a liquid supply line in order to supply glycol from inside the tank to the supply lines and to convey glycol back into the fluid tank when appropriate (such as when the hook is raised and/or when the jacks are raised. In this alternate exemplary embodiment, the jacks of the repositionable jack assembly 110 include hydraulic cylinders having a piston that extends by supplying glycol to the cylinder. Moreover, the cylinders are also operative to retract the piston when glycol is added to the other side of the seal within the cylinder. Moreover, the airbags 460 , 482 of the repositionable hook assembly 116 are replaced by a single hydraulic cylinder having a piston that extends and retracts based upon the glycol supplied to the cylinder. While it is the glycol supplying the fluid to reposition the piston with respect to the cylinder, this alternate exemplary embodiment used compressed air to force the glycol through the supply lines.
[0117] Referencing FIGS. 31 and 32 , a further alternate exemplary embodiment 800 of a trailer stabilizer is identical to the first exemplary trailer stabilizer 100 , but for wheel brakes 802 . In exemplary form, the pivot shaft 468 of the repositionable hook assembly 116 is lengthened in the medial and lateral directions to extend outward to behind the wheels 114 , thus forming a lengthened shaft 468 ′. Corresponding brackets 804 are mounted to the pivot shaft 468 ′ right behind each wheel 114 and each include a pair of plates 806 that sandwich a rubber block 808 therebetween. The plates 804 , 806 may be mounted to the rubber block 808 using any acceptable technique to retain the rubber block. In this exemplary embodiment, the plates 804 , 806 include a through hole that is aligned with a through hole of the rubber block so that nut and bolt fasteners are utilized to secure the block to the plates.
[0118] In exemplary form, when the hook is in the retracted position (hook is up and disengaged from the lock box), the rubber block does not contact the wheels 114 . But when the hook is in the extended position (hook is down and engaging the lock box) the rubber block comes in contact with the rear of the wheel 114 . In this manner the rubber block acts as a stop to inhibit the wheels 114 from rotating when the hook is in the extended position. Those skilled in the art will realize that the brakes 802 may be employed by repositioning the hook even in the case where the hook has no lock box to interface with.
[0119] Referring to FIGS. 33-44 , a second exemplary freight trailer stabilizer 900 is essentially the same as the first exemplary freight trailer stabilizer 100 . However, the second exemplary trailer stabilizer 900 includes a different repositionable hook assembly 902 (as opposed to the repositionable hook assembly 116 ), the wheel brakes 802 discussed previously, a control system, and a dock notification and communication system. Because the trailer stabilizer includes almost all of the same structure and features as discussed with respect to the first exemplary freight trailer stabilizer 100 , a detailed recitation of the features in common has been omitted for purposes of brevity. Accordingly, unless noted otherwise, the second exemplary freight trailer stabilizer 900 makes use of the same structure and features as the first exemplary freight trailer stabilizer 100 .
[0120] Referring to FIGS. 33-37 , the second exemplary freight trailer stabilizer 900 includes a different repositionable hook assembly 902 . In exemplary form, this different repositionable hook assembly 902 is mounted to the cart frame 106 and adapted to interact with a lock box 920 in order to fasten the stabilizer 900 to the ground. The lock box 920 is adapted to be mounted securely to the ground using ground spikes, nails, or other similar fasteners (not shown) so that the lock box is not readily repositionable.
[0121] In exemplary form, the lock box 920 includes a corresponding right side ramp (not shown) and a left side ramp 932 cooperating with corresponding front and rear ramps 934 , 936 to provide a frustopyramidal structure. The sides and top of the frustopyramidal structure are partially open and include a series of slots 940 that are sized to receive a drop bar of the repositionable hook assembly 902 in order to secure the repositionable hook assembly (and thus the stabilizer 900 ) to the ground. In particular, the slots 940 are incrementally spaced apart and inclined away from the stabilizer 900 so that once the drop bar is received initially within one of the slots 940 , the trailer stabilizer may be slightly moved forward (away from the lock box 920 ) so that the drop bar falls down completely within a particular slot and thereafter sits upon the left and/or right side ramps. When the drop bar is captured within one of the slots 940 , only minimal movement (forward or backward) of the stabilizer 900 is possible.
[0122] In exemplary form, the lock box 920 is fabricated from metal plate. However, in view of the aforementioned and following disclosure, those skilled in the art will readily understand that the described materials and techniques for forming the lock box comprises only a small subset of the materials and techniques that may be available to form a lock box 920 . By way of example, the front and rear ramps 934 , 936 are comprised of generally flat metal plates having a trapezoidal configuration. These plates 934 , 936 are welded to a single, formed metal piece that comprises the right and left side ramps 932 . In order to form the right and left side ramps 932 from a single piece of metal plate, a flat metal plate is stamped to create a series of cut-outs that will ultimately form the slots 940 , as well as the general outline of the finished piece. After the plate has been stamped, the plate is bent to have a three-dimensional shape embodying the respective right and left sides interconnected by the top side. The bending of the plate is operative to convert the cut-outs into the slots 940 .
[0123] Alternatively, the lock box 920 may be fabricated so the front and rear ramps 934 , 936 are integrally formed with a portion of the right and left side ramps. In such a circumstance, a forwardmost and rearwardmost portion of the right and left side ramps 932 are integrally formed with the front and rear ramps 934 , 936 , thereby resulting in a three dimensional cap that may be welded to or otherwise fastened to the remaining portion(s) that defines the remainder of the left and right side ramps 932 and slots 940 .
[0124] In order to secure the lock box 920 to the ground, a pair of pavement ties 942 are secured to opposite sides of the lock box. These pavement ties 942 may be comprised of any permanent fastener that is securely mounted to the ground and can withstand a predetermined amount of force. By way of example, the pavement ties are metal bands that are bolted to the ground using an embedded anchor (not shown). The pavement ties 942 may be welded, bolted, or otherwise fastened to the lock box 920 . In exemplary form, the pavement ties 942 are removably mounted to the lock box 920 in order to allow the lock boxes to be removed for clearing operations including, without limitation, snow plowing.
[0125] The repositionable hook assembly 902 also includes a repositionable hook 948 that uses many of the same components as the first exemplary embodiment. In this case, the hook 948 is mounted to the pivot shaft 468 so that rotation of the pivot shaft results in arcuate movement of the hook, generally in an upward and downward direction. In this exemplary embodiment, the hook 948 comprises mirror image hook halves 950 , 952 . Each hook half 950 , 952 comprises a bar stock section having a rounded proximal end 956 and a through orifice allowing throughput of the pivot shaft 468 . Specifically, the bar stock sections 954 are welded to the pivot shaft 468 and gussets 958 are concurrently welded to the bar stock section and the pivot shaft. A distal end of the bar stock section includes an enlarged head 959 having a triangular opening 960 . This triangular opening 960 accommodates a floating cylinder 961 that has a pair of washers 962 to inhibit substantial lateral movement of the cylinder. In other words, the washers operate to retain the cylinder 961 ends within the triangular openings 960 and thus have the cylinder spanning between the hook halves 950 , 952 . In this context, the term “floating” refers to the triangular openings 960 being considerably larger than the cross-section of the cylinder 961 , which provides play of the cylinder within the openings as defined by the bounds of the openings. Finally, the hook halves 950 , 952 are also coupled to one another using a cross-member 966 to reduce torsion between the hook halves.
[0126] Because the operation of the repositionable hook assembly 902 in terms of raising and lowering the hook 948 , and the structure utilized to raise and lower the hook, is substantially the same as the structure utilized in the first exemplary embodiment, a duplication discussion has been omitted for purposes of brevity.
[0127] Referring to FIGS. 33 and 39 - 43 , the second exemplary freight trailer stabilizer 900 includes a control system and a dock notification and communication system that work in tandem to impact the operation of the trailer stabilizer. The control system includes a control circuitry 970 housed within a control panel 972 , which itself includes a visual display 974 and operator controls 976 . In exemplary form, the visual display comprises a light that can be selectively illuminated, as well as illuminated in different colors. By way of example, the visual display 974 of the control panel 972 comprises a bulb housing containing a green light emitting diode (LED) and a red LED. As will be discussed in more detail hereafter, this structure provides for three options: (1) no light is illuminated; (2) the green LED is illuminated; and, (3) the red LED is illuminated.
[0128] The control panel 972 receives inputs from a plurality of different sensors. In exemplary form, the control system includes seven different sensors that provide indications about the position of various components of the second exemplary freight trailer stabilizer 900 . A first of these sensors 980 is a king pin sensor. This sensor 980 comprises a proximity sensor that is positioned adjacent to a biased plunger (not shown) that extends into the portion of the king pin cavity 574 defined by the king pin block 576 (see FIG. 18 ). In this manner, whenever a king pin of a parked trailer is within the king pin block 576 , the king pin will contact the biased plunger and displace the plunger in order that the proximity sensor 980 senses the displaced plunger and sends a signal to the control circuitry 970 indicative of the king pin being within the king pin block. Conversely, when no king pin of a parked trailer is within the king pin block 576 , the plunger is biased away from the proximity switch 980 and the switch does not send a signal to the control circuitry 970 indicative of the king pin being within the king pin block. In addition to monitoring the position of a king pin, the control system also monitors the position of the jacks 650 of the repositionable jack assembly 110 .
[0129] In exemplary form, the right side jack 650 includes a proximity sensor 984 mounted to the stationary portion of the screw jack leg 652 that detects when the boot (the portion of the jack contacting the ground) is fully raised. Likewise, the left side jack 650 includes a proximity sensor 986 mounted to the stationary portion of the screw jack leg 652 that detects when the boot (the portion of the jack contacting the ground) is fully raised. In this manner, both sensors 984 , 986 are operative to communicate with the control circuitry 970 and indicate when each of the jacks 650 is fully raised. As will be discussed in greater detail hereafter, when the control circuitry receives signals from both sensors 984 , 986 that the jacks 650 are fully raised, the control circuitry 970 turns off an electric motor 726 operatively coupled to the jacks. And the control system 970 also tracks when the jacks 650 are lowered to contact the ground.
[0130] In exemplary form, the drive shaft 712 engaging the right side jack 650 includes a magnet (not shown) being mounted thereto. The magnetic proximity sensor 985 is operative to detect the magnet as it rotates past the sensor. As discussed previously, a clutch 720 is coupled to the drive shaft 712 (see FIG. 25 ) so that when the jacks 650 are deployed, presuming one jack hits the ground before the other, the drive shaft to the jack hitting first will discontinue rotation, while the drive shaft to the other jack will continue to rotate until that jack reaches the ground. The sensor 985 sends a signal to the control circuitry 970 when the magnet is detected, as occurs once for each rotation of the drive shaft 712 . But when the right side jack 650 reaches the ground, the drive shaft 712 no longer rotates. Based upon preprogrammed logic, the absence of a signal from the sensor 985 for a predetermined period of time is identified as the right side jack having reached the ground. Similarly, the drive shaft 712 driving the left side jack 650 also includes a magnet permanently mounted thereto and detectable by the left side magnetic proximity sensor 987 . The sensor 987 sends a signal to the control circuitry 970 when the magnet is detected, as occurs once for each rotation of the drive shaft 712 . But when the left side jack 650 reaches the ground, the drive shaft 712 no longer rotates. Based upon preprogrammed logic, the absence of a signal from the sensor 987 for a predetermined period of time is identified as the left side jack having reached the ground. After the control circuitry 970 determines that both jacks have reached the ground, a power source is disconnected from the motor 726 , in this case an electric motor.
[0131] The control circuitry 970 is also communicatively coupled to a pair of sensors 988 , 990 that indicate the position of the repositionable hook assembly 902 . In exemplary form, a pair of proximity sensors 988 , 990 are mounted to the bracket 490 (see FIG. 14 ) of the repositionable hook assembly 902 in order to track the relative position of the pivot arm 470 . When the pivot arm 470 is rotated toward the airbag 460 the hook 948 is raised, while rotation of the pivot arm toward the second airbag 482 is operative to lower the hook. In this manner, a signal from the first hook sensor 988 to the control circuitry 970 indicates the hook 948 is raised, while a signal from the second hook sensor 990 to the control circuitry 970 indicates the hook is lowered (or engaged with the lock box 920 ). As will be discussed in more detail hereafter, the control circuitry uses the output from these sensors 988 , 990 to control outputs to various output devices.
[0132] Referring to FIGS. 39-44 , the dock notification and communication system interacts with the control system and vice versa to provide visual indications including, without limitation, that the stabilizer 900 is properly aligned, the jacks are or are not deployed, the hook is or is not deployed, the trailer is safe or not yet safe to load, and the parked trailer has or has not been loaded/unloaded.
[0133] Referring to FIGS. 33-44 , the dock notification and communication system includes a repositionable arm 1000 that is mounted to the cart frame 106 . The repositionable arm 1000 includes a sensor and transmitter housing 1002 that houses a pair of infrared (IR) transmitters 1004 , 1006 , and an infrared receiver 1008 . In this exemplary embodiment, the IR transmitters 1004 , 1006 use different frequencies to avoid information or signal crossing. An elongated, rectangular tubular pole 1012 is mounted to the housing 1002 at one end and pivotally mounted to the cart frame 106 at an opposite end. Specifically, the cart frame 106 includes a left rear frame wall 252 to which a pair of brackets 1016 , 1018 are mounted. The first bracket is mounted closer to the jacks 650 and has mounted to it a damper 1020 , in this case a coiled spring. The coiled spring 1020 is also mounted to the tubular pole 1012 and operates to bias the pole to the extended position (extending laterally from the stabilizer 900 ). As will be discussed in more detail hereafter, the pole 1012 floats with respect to the frame 106 when the stabilizer 900 is parked under the trailer and not coupled to a hustler. The second bracket 1018 is mounted closer to the hook 948 and extends laterally outward from the left side of the frame 106 . The bracket includes opposing top and bottom parts that operate to sandwich an end of the pole therebetween. In exemplary form, the pole 1012 and bracket parts 1018 are fabricated from metal and a plastic bushing 1024 interposes the bracket parts and the pole to reduce friction. Each of the pole 1012 , the bracket parts 1018 , and the plastic bushings 1024 include an aligned through hole that receives a through pin 1028 . In this manner, the pole 1012 and housing 1002 are able to pivot, about the pin, with respect to the stabilizer frame 106 .
[0134] A pneumatic cylinder 1030 is concurrently mounted to the pole 1012 and the stabilizer frame 106 . Specifically, a bracket 1032 is mounted to the left rear corner of the frame 106 and includes a coupling 1034 mounted to the cylinder 1030 that allows the cylinder to pivot about the coupling. The cylinder includes a piston 1033 that is coupled to the pole 1012 by way of a bracket 1038 . The cylinder 1030 includes fittings 1040 operative the provide fluid delivery to the cylinder to move the piston inward and outward with respect to the cylinder. As will be discussed in more detail hereafter, the cylinder 1030 is operative to move the pole 1012 and housing 1002 between a lateral position (extending laterally out from the left side of the frame) and a storage position where the pole pivots approximately ninety degrees toward the rear of the stabilizer 900 to fold into the side and position the housing rearward.
[0135] The dock notification and communication system includes an exterior dock cabinet 1050 that houses a pair of IR receivers 1052 , 1054 that are adapted to receive the IR signals sent from the IR transmitters 1004 , 1006 housed within the transmitter housing 1002 of the repositionable arm 1000 . As discussed previously, the first IR transmitter 1004 is transmitting at a first frequency and is oriented to align with the first IR receiver 1052 . Similarly, the second IR transmitter 1006 is transmitting at a second frequency and is oriented to align with the second IR receiver 1054 . In order to increase the likelihood of alignment, the IR transmitters 1004 , 1006 have a predetermined spacing, while this predetermined spacing is maintained by the dock cabinet 1050 when mounting the IR receivers 1052 , 1054 . Moreover, the configuration of a triangular pattern is also maintained by the dock cabinet 1050 . In the case of the transmitter housing 1002 associated with the stabilizer 900 , the apex comprises an IR receiver 1008 , while the two lower parts comprise the IR transmitters 1004 , 1006 . This same orientation is mirrored by the dock cabinet 1050 by orienting an IR transmitter 1056 at the apex to communicate to the IR receiver 1008 , while the two lower parts comprise the IR receivers 1052 , 1054 adapted to receive communication from the IR transmitters 1004 , 1006 .
[0136] In exemplary form, the dock cabinet 1050 is mounted to the exterior of a loading dock facility or similar building in a fixed orientation. In other words, the dock cabinet 1050 is adapted to maintain its position with respect to the loading dock facility, regardless of the position of the parked trailers or the position of the stabilizer 900 . In this manner, it is the job of the hustler operator to ensure that the stabilizer is properly aligned so that the transmitters 1004 , 1006 , 1056 can send signals and be received by the receivers 1052 , 1054 , 1008 . In this manner, the circuitry of the stabilizer is able to communicate with loading dock circuitry and vice versa. It should be noted that each loading dock bay would have its own dock cabinet 1050 .
[0137] The dock cabinet 1050 may also include, or have remotely positioned from the cabinet, a visual display 1058 for the hustler operator. In exemplary form, the visual display includes a plurality of lights that are able to be selectively illuminated. By way of example, the visual display 1058 may include, without limitation, (1) a green pattern of LEDs; (2) a yellow pattern of LEDs; and, (3) a red pattern of LEDs. The pattern may take on any form such as, without limitation, geometric forms including a circle, a square, a triangle, and written text including “caution,” “stop,” and “go.” In exemplary form, the visual display 1058 includes the ability to flash the lights or maintain the illumination. In this exemplary embodiment, the visual display includes three concentric circles 1060 of yellow, green, and red LEDs. As will be discussed in more detail hereafter, the LEDs are selectively illuminated to provide various information to the hustler operator.
[0138] The dock cabinet 1050 is also in communication with an internal cabinet 1066 on the inside of the loading dock facility or similar building. This internal cabinet 1066 includes a visual display 1068 and a lock/unlock switch 1070 to be manipulated by a dock worker inside of the loading dock facility or similar building. In this exemplary embodiment, the visual display 1068 comprises an illuminated tower having a red light and a green light. When the red light is illuminated, dock workers inside the loading dock facility or similar building know what it is not safe to load or unload the parked trailer at the loading dock opening. Conversely, when the light is green, workers know that it is safe to load or unload the parked trailer. It should be noted that each loading dock bay would have its own internal cabinet 1066 .
[0139] An exemplary sequence for using the second exemplary freight trailer stabilizer 900 in conjunction with the operation of the control system and the dock notification and communication system will now be explained. Initially, the parked trailer is spotted at a loading dock facility or similar building so that the rear of the trailer is aligned with and against a loading dock bay. At this time, the landing gear of the trailer are down and the trailer king pin is exposed.
[0140] An exemplary sequence begins by a hustler operator coupling to the stabilizer 900 and coupling an air supply and an electrical supply to the stabilizer and putting the stabilizer in transport mode. It should be noted that in this exemplary sequence, the stabilizer 900 is not under a trailer but is simply sitting out in the yard. Mounting the stabilizer 900 to the hustler includes coupling the fifth wheel of the hustler with the king pin 102 of the stabilizer. After coupling to the king pin 102 of the stabilizer, the hustler operator couples air and electric supplies to the stabilizer 900 using electric and pneumatic adapters (glad-hands). Supplying electricity to the control circuitry and air via the glad-hands is operative to raise the hook 948 , release the wheel brakes 802 , and ensure the repositionable arm 1000 is folded against the frame 106 . Thereafter, the hustler operator is dispatched to position the stabilizer underneath a trailer so it can be unloaded. And the hustler operator visually confirms that he is at the right bay by confirming that the visual display 1058 of the dock cabinet 1050 is displaying a green light.
[0141] In exemplary form, the hustler operator backs the stabilizer 900 underneath the trailer so that the king pin of the trailer is aligned with the tapered cutout 572 and ultimately the king pin enters the king pin cavity 574 . In particular, the stabilizer 900 is adapted to be backed under the trailer in a straight line with the hook pointing toward the rear of the parked trailer. In this orientation, the stabilizer 900 should be longitudinally aligned with the trailer. As the hustler operator back the stabilizer 900 underneath the parked trailer, ultimately, the kingpin of the trailer will reach the stop at the proximal end of the cavity 574 , thereby limiting the distance underneath the trailer that the stabilizer 900 may be positioned. After reaching this point, the hustler operator will realize that the stabilizer cannot be backed any farther underneath the parked trailer and begin to disengage from the stabilizer. At the same time, presuming the king pin remains within the cavity 574 , the king pin sensor 980 sends a signal to the control circuitry 970 that the kingpin is within a predetermined tolerances for disengaging the stabilizer 900 from the hustler. At the same time, the visual display 1058 of the dock cabinet 1050 continues to display a green light, while the visual display 1068 of the internal cabinet 1066 displays a red light.
[0142] The hustler operator then disengages or disconnects the air supply from the hustler to the stabilizer 900 . This action causes a series of events. One such event is that the absence of positive pressure on the hook 948 is operative to lower the hook so that that hook engages the lock box 920 . Unless the hook 948 falls to the bottom of one of the slots 940 , the proximity sensor 990 will not detect that the hook has been correctly deployed. As will be discussed, if the hook 948 is not properly deployed, the hustler operator may have to slightly move the stabilizer forward or rearward to seat the hook within the lock box 920 . At the same time the hook 948 is being repositioned to engage the lock box 920 , the repositionable arm 1000 swings out laterally from the side of the stabilizer 900 to a generally perpendicular position. In this position, the housing 1002 of the arm 1000 should be aligned with the dock cabinet 1050 so that the transmitters 1004 , 1006 , 1056 can communicate to the receivers 1008 , 1052 , 1054 . The swing arm 1000 is principally repositioned to a deployed position by the damper 1020 . But it should be noted that because the damper 1020 is responsible for repositioning the arm 1000 in the absence of pneumatic pressure, objects contacting the arm may be able to overcome the bias of the damper. But in such a case, presuming the contact is temporary, the arm 1000 will return to the deployment position (extending laterally outward from the stabilizer frame). But during this time, a number of problem conditions may occur.
[0143] The problem conditions that may occur include not properly positioning the stabilizer 900 under the parked trailer. This condition can be remedied simply by the hustler operator repositioning the stabilizer. The hustler operator will know the stabilizer needs to be repositioned because of a number of conditions. First, if the stabilizer 900 is not positioned properly, the transmitters 1004 , 1006 , 1056 cannot communicate to the receivers 1008 , 1052 , 1054 . At the same time, if the hook 948 is not fully down into one of the slots 940 , the proximity sensor will not send feedback to the control circuitry 970 . Before the operator can deploy the repositionable jack assembly 110 , because the control circuitry will not provide power to the motor 726 , the control circuitry requires two conditions to be satisfied. The first condition is that the hook 948 is properly engaged, which is evidenced by a signal from the proximity sensor 990 . The second condition is that the IR receiver 1008 of the repositionable arm 1000 receives a signal from the IR transmitter 1056 of the dock cabinet 1050 indicating that the stabilizer 900 is properly aligned. Unless both conditions are met, the control circuitry 970 will not power the electric motor to reposition the repositionable jack assembly 110 . But both conditions can be met by having the hustler operator properly align the stabilizer 900 under the parked trailer.
[0144] Presuming the trailer stabilizer 900 is properly positioned so that the transmitters 1004 , 1006 , 1056 can communicate to the receivers 1008 , 1052 , 1054 , and the hook 948 has properly engaged the lock box 920 , the visual display 1058 of the dock cabinet 1050 illuminates a yellow light or set of lights. In other words, after the stabilizer 900 is properly positioned so the king pin is received, the transmitters and receivers are aligned, and the hook 948 is properly deployed, the visual display 1058 of the dock cabinet 1050 illuminates both a green and a yellow light (because the green light has not been extinguished. In order for this to occur, the control circuitry 970 has received a signal from the tail hook proximity sensor 990 indicative of the tail hook being properly positioned, and then sends a signal via the first IR transmitter 1004 to the first IR receiver 1052 indicating that the tail hook 948 is secure. After these conditions have been met, the control circuitry 970 allows power to go to the motor 726 .
[0145] After the hook 948 engaged and the dock cabinet illuminates the yellow and green lights, the control circuitry 970 allows the hustler operator to deploy (i.e., lower) the repositionable jack assemblies 110 . As discussed previously, the control panel 972 includes a visual display 974 and operator controls 976 . Among the operator controls are separate buttons for raising and lowering the jacks 650 . Accordingly, when the operator wants to lower the jacks 650 , the operator simply presses the down jack button on the control panel 972 . Thereafter, the deployment of the jacks 650 is automated. The control circuitry 970 receives the input from the control panel 972 button to lower the jacks 650 and causes the motor 726 to be turned to lower the jacks 650 . In exemplary form, the jacks 650 comprise screw jacks and the motor is coupled to a transmission 724 shaft having individual clutches 720 that are mounted to the transmission shaft and respective drive shafts 712 . The control circuitry continues to power the motor 726 until both proximity switches 984 , 986 provide an indication that the jacks are fully down. As mentioned previously, each drive shaft 712 includes a magnet that is detected by a respective proximity switch 984 , 986 as the shafts rotate to lower the jacks 650 . The control circuitry 970 is programmed to shut off the motor after both proximity switches indicate the further rotation of the drive shafts is not occurring. This may occur, for example, because the magnet is not being sensed by the proximity sensor 984 , 986 for a predetermined period of time (e.g., 0.5 seconds) or the proximity sensor continues to sense the magnet for more than a predetermined, constant period of time (e.g., 0.5 seconds). Because the surface that the stabilizer is sitting on may be uneven or may have debris underneath one or both jacks, it is not always the case that the jacks will be lowered to the same extent. Accordingly, to accommodate for varying heights of deployment, the clutches allow the transmission shaft to rotate, but not rotate the corresponding drive shaft when the bottom of the jack 650 is touching the ground (including any ground debris, etc.).
[0146] It should be noted that in lieu of the magnetic proximity switches, one may use limit switches mounted to the bottom of each jack 650 .
[0147] After the jacks have been deployed, the visual display 974 of the control panel 972 illuminates a red light. When the red light illuminates on the control panel 972 , a signal is sent via the control circuitry 970 to the second IR transmitter 1006 to transmit a signal indicative of the jacks 650 being deployed. This IR signal is received by the second IR receiver 1054 , which causes the visual display 1058 of the dock cabinet 1050 to change to a red light and extinguish the yellow and green lights. After the hustler driver sees the red light of the dock cabinet 1050 , the operator knows that both the jacks 650 and the hook 948 have been properly deployed and he can disconnect the electric power supply to the stabilizer 900 , disconnect from the stabilizer king pin, and go on to his next task. By disconnecting the power supply to the stabilizer, the control circuitry and all electrical circuitry of the stabilizer is unpowered. In other words, the IR transmitters 1004 , 1006 are no longer transmitting to the IR receivers 1052 , 1054 of the dock cabinet 1050 .
[0148] The red light of the visual display 1058 of the dock cabinet 1050 also has an impact on the internal cabinet 1066 . Specifically, prior to the visual display turning on the red light, a loading dock person on the inside of the facility could turn the lock/unlock switch, but the visual display 1068 would remain red. But after the outside dock cabinet 1050 light turns red, the loading dock person on the inside of the facility has the ability to turn the switch to the lock position and the visual display 1068 will illuminate the green light. In other words, until the stabilizer 900 is deployed properly and completely, as documented by the outside dock cabinet 1050 , loading dock personnel cannot change the visual display 1068 on the inside to green, thereby signaling that it was safe to load or unload the parked trailer. It should also be noted that as long as the visual display 1068 displays a green light, the hustler operator will be unable to remove the stabilizer 900 . Simply put, the warehouse personnel control when the stabilizer is removed and must do so by first turning the switch 1070 to the unlock position, thereby changing the visual display 1068 back to a red light and then having the internal cabinet 1066 communicate with the dock cabinet 1050 . While the visual display 1068 on the inside of the warehouse is green, a hustler operator cannot remove the stabilizer 900 . The following is a description of the structure and process that would inhibit removal of the stabilizer 900 while the visual display 1068 of the internal cabinet 1066 is illuminated green (indicative of a safe condition to load or unload the trailer).
[0149] First, presuming one of the warehouse personnel does not turn the switch 1070 to the unlock position on the internal cabinet 1066 , the visual display 1058 of the dock cabinet 1050 will remain a red light. When the visual display of the dock cabinet 1050 is red, the trailer stabilizer 900 cannot be removed. The first indication to the hustler operator is a visual one in that the light of the display 1058 is red instead of green.
[0150] Second, when the display 1058 is red instead of green, the transmitter of the 1056 of the dock cabinet 1050 is dead. Yet the IR transmitter 1056 of the dock cabinet 1050 needs to be operative to send a signal to the IR receiver 1008 so that the control circuitry 970 will provide power to raise the jacks 650 and air to raise the hook 948 . And if the hustler operator has not hooked up the electric connection, the entire system on the stabilizer is dead. More specifically, the control circuitry 970 controls a center return solenoid 1074 that is operative to vent any air pressure imparted to the system when the electrical system of the stabilizer 900 is dead or if the IR transmitter 1056 of the dock cabinet 1050 has not sent a signal to the IR receiver 1008 of the aim 1000 . In other words, when the control circuitry 970 is powered, the circuitry is looking for a signal from the IR transmitter 1056 of the dock cabinet 1050 that it is appropriate to remove the stabilizer 900 . And this signal will never occur when the indicator light is red or if power is not provided to the system. So if the red light of the display 1058 is on, and the hustler operator attempts to remove the stabilizer 900 by hooking up the air supply glad-hand, the air in the stabilizer system will vent. As an additional safety feature, if the hustler operator hooks up the electric power supply and the air supply, and then attempts to raise the jacks 650 , the operation of attempting to raise the jacks by pushing one of the operator controls 976 , the control circuitry shifts the solenoid valve 1074 to vent the air through an on-board air horn 1076 the creates loud horn sound telling the operator and surround people that the operator is erroneously attempting to remove the stabilizer. But presuming the warehouse personnel turns the switch 1070 to the unlock position on the internal cabinet 1066 , the visual display 1058 of the dock cabinet 1050 will discontinue illuminating the red light and now illuminate the green light.
[0151] The green light of the dock cabinet visual display 1058 is the first signal to a hustler operator that it is appropriate to remove the stabilizer 900 because the trailer is ready to leave the warehouse. This also presumes that the IR transmitter 1056 of the dock cabinet 1050 has been operative to send a signal to the IR receiver 1008 so that the control circuitry 970 will allow removal of the stabilizer 900 .
[0152] In order to remove the stabilizer 900 , the hustler operator couples the fifth wheel of the hustler to the king pin 102 of the stabilizer. In addition, the operator couples the electric power connection to the stabilizer 900 . The operator first raises the jacks 650 by pushing the jack up button 977 on the control panel. The control circuitry then sends a signal to the motor 726 to rotate the motor in an opposite direction to raise the jacks 650 . Each of the jacks includes a proximity sensor 984 , 985 that signals the control circuitry when the jacks are fully raised. This fully raised condition may not be met by turning the drive shafts 712 equally, so the control circuitry waits until both proximity sensor 984 , 985 signal that each jack is fully raised. After receive signals from both sensors 984 , 986 that the jacks have been raised, the control circuitry 970 discontinues power to the motor 726 and the green light illuminates on the visual display 974 indicating the jacks are up. Thereafter, the control circuitry 970 , presuming the air lines are coupled to the stabilizer, automatically raises the hook 948 and folds in the arm 100 to lay along side the stabilizer side. At this point, the stabilizer may be removed from underneath the trailer and repositioned under another trailer or stored by discontinuing engagement with the hustler and allowing the stiff leg assembly 108 and the wheels 114 to hold up the stabilizer. At the point in time the stabilizer 900 is disconnected from the hustler, the absence of air pressure results in application of the brakes and dropping of the hook 948 .
[0153] Referencing FIGS. 45-51 , another exemplary trailer support 101 includes a frame 121 and an axle 141 mounted to the frame 121 . The axle 141 includes one or more wheels 161 mounted proximate the ends of the axle 141 . In this exemplary embodiment, the axle 141 includes tandem wheels 161 mounted at each end, with the tandem wheels including an associated braking assembly 181 . However, it should be noted that the wheels 161 are not required to include a braking assembly 181 .
[0154] Referring specifically to FIGS. 45-47 , the braking assembly 181 includes a brake pad 201 which applies a force necessary to either a drum or disc 221 to retard rotation of the brake drum and wheel 161 with respect to the axle 141 . A pneumatic brake cylinder 241 is coupled to the brake pads 201 by way of a push rod and cam shaft 251 in order to force the pads 201 against the drum 221 after a predetermined positive pressure is reached within the pneumatic lines 261 feeding the brake chamber. However, the brake cylinder 241 is also operative to force the pads 201 against the drums 221 when insufficient air pressure occurs within the pneumatic lines 261 feeding the cylinder 241 . By way of example, if an air leak occurs within the pneumatic line or a yard truck 2001 (see FIG. 52 ) is not pneumatically coupled to the trailer support 101 , the brake pads 201 will engage the drums 221 to inhibit rotation of the wheels 161 . In other words, it takes a positive air pressure within the pneumatic brake lines 261 in order to discontinue engagement between the brake pads 201 and the drums 221 . In this exemplary embodiment, the pneumatic lines 261 are in series with a compressed air storage vessel/tank 281 that is mounted to the frame 121 . Thus, the compressed air storage vessel 281 provides an on-frame reservoir of compressed air. As will be discussed in more detail hereafter, the pneumatic lines 261 also includes quick connects 301 (e.g, a glad hand) adapted to be coupled to quick connects 321 of the yard truck 2001 in order for the yard truck to supply compressed air to the braking assembly 181 .
[0155] Referring back to FIG. 45 , the frame 121 includes a pair of C-shaped cross-section frame rails 341 , 361 that are equally spaced apart from one another and oriented in parallel toward the rear of the trailer support 101 . Toward the front of the trailer support 101 , the frame rails 341 , 361 are angled toward one another and eventually converge proximate the front of the trailer support. For the sections of the frame rails 341 , 361 oriented in parallel, one or more cross-members 381 are joined to the frame rails, such as by welding or bolted fasteners. The cross members 381 may optionally include a block C-shape cross-section.
[0156] The frame 121 also has mounted to it a fifth wheel 401 . Exemplary fifth wheels 401 include class 6, 7, and 8 fifth wheels such as the Fontaine No-Slack 6000 and 7000 Series, available from Fontaine International (www.fifthwheel.com). In this exemplary embodiment, the fifth wheel 401 is mounted in an elevated fashion above the frame rails 341 , 361 using conventional nut and bolt fasteners. Those skilled in the art will understand that other fifth wheels 401 besides a Fontaine No-Slack may be utilized so long as the fifth wheel is operative to selectively engage and disengage a king pin of a freight trailer. It should also be noted that the king pin lock/receiver may be pneumatically, electrically, or hydraulically operated, or may simply be manually operated. Those skilled in the art are familiar with the various types of fifth wheels and the various types of locks/receivers that hold the king pin of a freight trailer in place until it is intentionally released.
[0157] Referencing FIGS. 45 and 48 - 50 , the trailer support 101 may also include a pair of repositionable wheel chocks 501 that operate to retard rolling motion of the wheels 161 when deployed. In exemplary form, each wheel chock 501 is mounted to a repositioning device 521 that utilizes fluid power (pneumatic, hydraulic, etc.) to switch between deployment and storage of the wheel chocks 501 . It should also be noted that the wheel chocks 501 may alternatively be deployed using a manual crank (not shown) that is mounted to the through rod 641 . In either circumstance, when the wheel chocks 501 are deployed, the chocks are wedged between the wheels 161 and the ground. Consequently, as the wheels 16 attempt to rotate forward, the deployed chocks 501 provide a resistive force sufficient to retard forward rotation of the wheels. Conversely, when the chocks 501 are stored, the wheels 161 are able to rotate (forward or rearward), presuming some other device is not operative to retard rotational motion such as the braking assembly 181 .
[0158] Referring to FIGS. 45 and 48 , the repositioning device 521 includes a pneumatic cylinder 541 , which is supplied with air from pneumatic supply lines 551 . One end of the pneumatic cylinder 541 is mounted to the underside of the cross-member 381 . The opposite end of the pneumatic cylinder 541 includes an actuating piston 561 with a clevis 581 mounted to the far end of the piston. The clevis 581 is pivotally mounted to an L-shaped bracket 601 by way of a pin 621 that extends through both the clevis and bracket. A through rod 641 , having a circular cross-section, is received within a cylindrical cavity formed by a cylindrical housing 681 mounted to the opposite end of the L-shaped bracket 601 . A through hole extending into the cylindrical cavity is threaded to receive a fastener, such as a bolt 661 , that extends into contact with an exterior of the through rod 641 to secure the cylindrical housing 681 to the through rod 641 . Accordingly, rotational motion of the cylindrical housing 681 , when the bolt 661 is tightened within the through hole, is transferred to the through rod 641 , thereby causing the through rod to correspondingly rotate when the cylindrical housing is rotated. The rotational motion of the through rod 641 is transferred to the chocks 501 and is operative to reposition the chocks 501 between deployment and storage positions.
[0159] In this exemplary embodiment, the through rod 641 is located beneath and mounted to a cross-member 381 of the frame 121 using several brackets 701 with circular bushings 721 . The bushings 721 operate to allow the through rod 641 to axially rotate with respect to the brackets 701 , while retaining the horizontal and vertical position of the through rod. In exemplary form, a single through rod 641 is utilized to extend across the entire width of the frame 121 and outward beyond the frame in front of the wheels 161 .
[0160] Referencing FIGS. 45 , 49 and 50 , each repositionable wheel chock 501 includes a telescopic pole 801 mounted to the through rod 641 that extends laterally beyond the frame 121 . In exemplary form, the telescopic pole 801 comprises a first hollow tube 821 and a second, larger hollow tube 841 , where the first tube has an exterior that is small enough to be received within the interior of the second tube. Because of the size differential between the tubes 821 , 841 , the tubes are operative to slide against one another to increase or decrease the length of the pole 801 as necessary. In this regard, the second tube 841 has a closed opposite end that optionally houses a spring (not shown), which is operative to bias the first hollow tube 821 with respect to the second tube. However, it should be noted that the tubes need not be telescopic or operative to slide with respect to one another in order to deploy the wheel chock 501 . For example, tubes 821 , 841 may be replaced by a single tube or multiple tubes that are rigidly mounted to one another to avoid longitudinal length changes.
[0161] Opposite the closed end of the second tube 841 , the first tube 821 includes a transverse hollow cylinder 861 . A cavity on the interior of the cylinder 861 allows for throughput of the through rod 641 . Additionally, the through rod 641 includes a longitudinal keyway 871 formed on its exterior that is aligned with a longitudinal keyway 891 formed on the interior of the cylinder 861 . In this fashion, after the keyways 871 , 891 have been aligned (i.e., overlap) with one another, a key 911 is inserted into both keyways 871 , 891 so that rotation of the through rod 641 results in corresponding rotation of the cylinder 861 . In this exemplary embodiment, the keyways 871 , 891 exhibit a rectangular, axial cross-section that accommodates the key 911 , which also exhibits a rectangular, axial cross-section. A hole (not shown), which extends through the cylinder 861 and into the keyway 891 , is adapted to receive a threaded fastener 881 . By inserting the threaded fastener 881 into the hole, where the hole overlaps the keyway 891 , the threaded fastener is operative to contact the key 911 and lock the key within the keyways 871 , 891 .
[0162] Opposite the closed end of the second tube 841 , an arm 901 is mounted to the lateral exterior of the second tube. The arm 901 extends away from the closed end of the second tube 841 and extends beyond the open end of the second tube 841 in parallel with the first tube 821 . In this exemplary embodiment, the arm 901 by way of a through bolt is mounted to a spring 921 , where the spring is coupled to a cable 941 , which is itself mounted to a chock block 961 . As will be discussed in more detail below, the spring 921 provides a tension force that retains the chock block 961 in a predetermined position, thereby retarding the chock block 961 from digging into the ground as the repositionable wheel chock 501 is moved from its storage position to its deployment position. In order to maintain the proper tension on the chock block 961 , a guide pulley 981 is mounted to the second tube 841 , where the guide pulley 981 receives the cable 941 .
[0163] Proximate the closed end of the second tube 841 , a bracket 1001 is mounted to the second tube. This bracket 1001 , in exemplary form, includes a block C-shaped segment 1021 that is spaced apart from the second tube by way of an extension 1041 . The blockC-shaped segment 1021 includes extension plates 1031 pivotally mounted by way of a pivot pin 1051 to allow articulation of the chock block 961 and provide an allowance for coaxial discrepancy between the through rod 641 and the stabilizer's wheels 161 . A guide arm 1061 is mounted to the rear exterior of the C-shaped segment 1021 . In this exemplary embodiment, the guide arm 1061 includes a through hole that receives a fastener to pivotally mount a roller assembly 1081 to the guide arm.
[0164] The roller assembly 1081 includes a first roller 1101 mounted opposite a second roller 1121 , where both rollers are mounted to opposing rails 1141 that are tied together by a cross-brace 1161 . The first roller 1101 is rotationally repositionable with respect to the rails 1141 and is adapted to contact the ground when the wheel chock 501 is deployed in its barrier or deployment position. Similarly, the second roller 1121 is rotationally repositionable with respect to the rails 1141 and is adapted to contact the rear of the chock block 961 and overcome the bias of the spring 921 to rotate the chock block when the first roller 1101 reaches the ground.
[0165] The chock block 961 is accommodated within the C-shaped segment 1021 . The chock block 961 is pivotally mounted to the extension plates 1031 by way of a pivot shaft 1181 that concurrently extends through the chock block and the extension plates. A rear portion of the chock block 961 includes a connector 1201 that couples the chock block to the cable 941 .
[0166] Referring to FIGS. 45 and 51 , the trailer support 101 may also includes a winch 1301 mounted to a rear cross member 381 . The winch 1301 may be pneumatically, hydraulically, or electrically driven using a power connection line 1321 that includes a quick connect 1341 in order to receive power from a power source, such as from a yard truck 2001 (see FIG. 52 ). Alternatively, the winch 1301 could be manually actuated using a hand crank (not shown). In this exemplary embodiment, the winch 1301 includes a motor and a cable 1361 mounted to a rotating spool. A free end of the cable 1361 includes a hook 1381 that is adapted to interface with a ground cleat 1501 (see FIG. 53 ) in order to pull the rear of the trailer support 101 toward the ground cleat. For use with the instant embodiment, exemplary electric winches 1301 include, without limitation, the RN30W Rufnek worm gear winch available from Tulsa Winch (www.team-twg.com).
[0167] Referencing FIGS. 45 and 54 , the trailer support 101 may further include a signaling system 1601 . This signaling system 1601 provides a visual display 1621 that alerts personnel within a warehouse or loading dock facility 1641 when the trailer 2201 is stabilized using the trailer support 101 . In exemplary form, the visual display 1621 is mounted on the interior of the warehouse or loading dock facility 1641 proximate the loading dock. As will be appreciated by those skilled in the art, when the rear of the trailer 2201 is backed up adjacent and aligned with respect to the loading dock opening, personnel within the warehouse or loading dock facility 1641 often cannot see through the loading dock opening because the rear of the trailer 2201 is occupying the entire loading dock opening. Therefore, the visual display 1601 takes the place of a manual visual inspection and indicates whether the trailer 2201 is stabilized or not to accommodate for the absence of a direct line of sight. In order for the visual display 1601 to know when to display an indicia that it is safe to load/unload the trailer 2201 , the trailer stabilizer 101 includes an on-board infrared light source 1661 .
[0168] In this exemplary embodiment, the infrared light source 1661 is powered by an electrical source associated with the yard truck 2001 (see FIG. 52 ). However, it should be noted that the infrared light source could also be powered by an on-board power source (such as a battery or generator) associated with the trailer stabilizer 101 . The infrared light source 1661 is selectively powered, however, only after the trailer support 101 has been secured. The infrared light source 1661 , when powered, is operative to generate infrared light that is detected by an infrared detector 1681 located on the exterior of the warehouse or loading dock facility 1641 . When infrared light is detected by the detector 1681 , the detector communicates this detection to the visual display 1621 so that personnel within the warehouse or loading dock facility 1641 know it is safe to load or unload the trailer 2201 . However, the visual display 1601 may provide more than a simple visual indication that the trailer stabilizer is secured.
[0169] The signaling system 1601 also includes a king pin sensor 1701 and a wheel chock sensor 1721 . The king pin sensor 1701 is operative to determine whether or not a trailer king pin 2221 (see FIG. 52 ) is secured to the fifth wheel 401 . When the king pin 2221 is secured to the fifth wheel 401 , the sensor 1701 senses the position of the king pin within the opening of the fifth wheel. The sensor 1701 may also include an ancillary sensor (not shown) that confirms the king pin 2221 is locked within the fifth wheel 401 . Likewise, the wheel chock sensor 1721 is operative to detect the position of the wheel chocks 501 , such as when the wheel chocks are deployed on the ground in a blocking position directly in front of the wheels 161 . Both the king pin sensor 1701 and the wheel chock sensor 1721 are in communication with a controller 1741 that uses a wireless transmitter to communicate information concerning the position of the king pin 2221 and the position of the wheel chocks 501 to the visual display 1601 , which itself includes a wireless receiver.
[0170] Referring to FIGS. 52 and 53 , a yard truck 2001 includes a cab 2021 , a chassis 2041 , an engine 2061 , electrical connections 2081 , pneumatic connections 2101 , and a repositionable fifth wheel 2121 . In addition, the yard truck 2001 includes a tow hook 2141 that receives the tow eye 2161 of the trailer support 101 in order to couple the yard truck 2001 to the trailer support 101 .
[0171] In practice, the yard truck 2001 attaches itself to the trailer support 101 by way of the yard truck's tow hook 2141 being coupled to the tow eye 2161 of the trailer support 101 . In addition to attaching the yard truck 2001 to the trailer support 101 using the hook 2141 and eye 2161 , the yard truck operator also connects quick connects 1341 , 301 of the trailer stabilizer 101 to quick connects 2171 , 2181 associated with the yard truck to supply electrical and pneumatic power. It should also be noted that the yard truck 2001 may include hydraulic pump(s), lines, and connections (not shown) that connect to connections, lines, and devices of the trailer support 101 , such as when the winch 1301 and/or repositioning device 521 is hydraulically driven. After completing connections between the yard truck 2001 and the trailer support 101 , the yard truck operator then drives the yard truck into position with respect to a trailer 2201 having already been parked at a loading dock so that the doors of the trailer are open and the associated opening at the rear of the trailer is adjacent a loading dock opening.
[0172] At such a point in time, the trailer 2201 is initially supported by its landing gear (not shown). But, as discussed previously, the landing gear is not made to accommodate the high forces associated with a forklift repetitively entering and exiting the trailer to load or unload goods. As is evident to those skilled in the art, when loading a trailer, the initial weight of the loaded goods is positioned at the front of the trailer and is disproportionally born by the landing gear. Similarly, when a trailer is unloaded, the last weight to be taken off the trailer comes from the goods located at the front of the trailer, where this weight is disproportionally born by the landing gear. In order to ensure that the trailer does not nosedive in case of landing gear failure, or that the trailer tips over on either lateral side, the instant disclosure provides a stabilizing device to retard nose dive or lateral tip over.
[0173] Referring again to FIGS. 52 and 53 , after the yard truck 2001 has attached itself to the trailer stabilizer 101 and located a trailer that has yet to be stabilized, the yard truck thereafter backs the trailer stabilizer 101 underneath the trailer 2201 . When backing the trailer stabilizer 101 , the rear of the stabilizer (where the winch 1301 is located) moves underneath the trailer first and is aligned so that the fifth wheel 401 receives the trailer king pin 2221 . While the trailer stabilizer 101 is being backed underneath the trailer 2201 and before the king pin 2221 is secured within the fifth wheel 401 , the repositionable wheel chocks 501 are in a storage position and the brake assemblies 181 are free (i.e., not locked). It should also be noted that while the yard truck 2001 is backing the stabilizer 101 underneath the trailer 2201 , the winch 1301 is preferably retracted. Continued backing of the yard truck 2001 causes the trailer stabilizer 101 to be further repositioned underneath the trailer 2201 , eventually so much so that the king pin 2221 engages the fifth wheel 401 and becomes locked within the fifth wheel, thereby coupling the trailer stabilizer to the trailer. At this time, the king pin sensor 1701 detects the position of the king pin 2221 with respect to the fifth wheel 401 and communicates a signal indicative of the king pin position to the controller 1741 (see FIG. 45 ). Thereafter, the controller 1741 wirelessly communicates a signal to the visual display 1681 (see FIG. 54 ), which in turn displays visual indicia representing to dock workers that the king pin 2221 is secured to the trailer stabilizer 101 .
[0174] After the trailer stabilizer 101 is coupled to the trailer 2201 , a number of events occur to lock the position of the trailer stabilizer with respect to the trailer. One of these events may include the yard truck operator locking the braking assembly 181 of the trailer stabilizer by depressurizing the pneumatic lines 261 (see FIG. 45 ). This depressurization causes the brake pads 201 (see FIG. 46 ) to be forced against the brake drum/disc 221 , thereby retarding rotational motion of the wheels 161 . Another possible event is the deployment of the repositionable wheel chocks 501 using the repositioning device 521 .
[0175] The yard truck operator controls, using standard internal controls within the yard truck 2001 to control the air pressure though line 2101 , the pneumatic pressure applied to the pneumatic cylinder 541 to extend or retract the piston 561 , thereby rotating the through rod 641 in either a clockwise or a counterclockwise direction. As discussed previously, rotation of the through rod 641 is operative to reposition the wheel chocks 501 between the storage position and the blocking position. In this manner, the yard truck operator is able to lower or raise the wheel chocks 501 without ever leaving the cab of the yard truck 2001 . When the wheel chocks 501 are deployed so that the chocks are in front and adjacent at least one of the wheels 161 , the wheel chock sensor 1721 senses this position and communicates a signal to the controller 1741 (see FIG. 45 ). Thereafter, the controller 1741 wirelessly communicates a signal to the visual display 1681 (see FIG. 54 ), which in turn displays visual indicia representing to dock workers that one or all of the wheel chocks 501 is deployed in a blocking position with respect to the wheels 161 of the trailer stabilizer 101 . But the yard truck operator may need to exit the cab to couple the cable 1361 and hook 1381 to the ground, as well as to disconnect pneumatic and electrical connections extending from the yard truck 2001 to the trailer stabilizer 101 .
[0176] In exemplary form, after the brake assembly 181 has been locked and the wheel chocks 501 have been deployed, the yard truck operator may exit the cab to secure the trailer support 101 to the ground using the winch 1301 . The winch may be powered from an electrical power source on board the trailer stabilizer 101 or on board the yard truck 2001 . In either circumstance, the winch 1301 is unwound a predetermined amount so that there is enough cable 1361 for the hook 1381 to reach the ground cleat 1501 . The hook 1381 is thereafter mounted to the cleat 1501 , and the winch 1301 is driven to wind the cable 1361 in order to remove the slack from the line. The winch 1301 associated controls (not shown) that are operative to discontinue winding of the cable 1361 after the cable reaches a predetermined tension. When taught, the cable 1361 and winch 1301 are operative to pull the trailer stabilizer 101 toward the rear of the trailer 2201 , which acts to pull the fifth wheel 401 toward the rear of the trailer. Because the fifth wheel 401 at this point has received the king pin 2221 , the fifth wheel 401 pushes against the front of the king pin to effectively wedge the trailer 2201 between the loading dock (not shown) and the fifth wheel 401 and wedge the king pin between the fifth wheel 401 and the ground cleat 1501 .
[0177] As soon as the winching operation is complete, a switch 1691 associated with the infrared light source 1661 is tripped, thereby powering the light source and generating infrared light. The placement of the infrared light source 1661 is at the rear of the trailer support 101 and is designed to provide a direct line of sight between the light source and the light detector 1681 (see FIG. 54 ) mounted to the warehouse or loading dock facility 1641 . It should be noted that the light source may be powered by the yard truck 2001 or may be powered by an on-board energy source (not shown) such as a generator or a battery. In exemplary form, the light source includes a timing circuit that only allows the infrared light source to be powered for a predetermined time. Regardless of the power source used, the light source 1661 is operative to generate infrared light that will be detected by the detector 1681 .
[0178] The detector 1681 , which is mounted to the warehouse or loading dock facility 1641 , is operative to detect infrared light generated by the light source 1661 . When infrared light is detected by the detector 1681 , a signal is sent to the visual display 1621 indicating that the trailer stabilizer 101 is in a secured position with respect to the trailer 2201 . In exemplary form, the visual display 1621 includes a red and green light. When illuminated, the red light indicates that the trailer 2201 parked at the loading dock is not ready to be loaded or unloaded because the trailer support 101 has not yet been secured to the trailer. In contrast, when illuminated, the green light indicates that the trailer 2201 parked at the loading dock is ready to be loaded or unloaded because the trailer support 101 is secured to the trailer.
[0179] When a trailer 2201 is fully loaded or unloaded, the yard truck 2001 reattaches itself to the trailer support 101 , which includes reattaching the quick connects 301 , 1341 . Thereafter, to the extent the support 101 is coupled to the ground cleat 1501 , the winch 1301 is unwound and the hook 1381 is disengaged from the cleat, followed by winding of the cable 1361 . As soon as the winch cable 1361 is unwound, thereby allowing decoupling of the hook 1381 from the cleat 1501 , the infrared light source 1661 is powered and generates infrared light. This light is in turn detected by the detector 1681 , which is operative to send a signal to the visual display 1621 indicating that the trailer support 101 is not longer secured to the trailer 2201 . As discussed previously, a red light is illuminated on the display 1621 indicating to dock personnel that it is not safe to load or unload goods from the trailer. It should be noted that in case the visual display 1621 gets out of sequence, it may be manually reset to display the red light or some other indicia reflecting that the trailer 2201 is not mounted to the trailer support 101 .
[0180] Presuming the winch 1301 has been disengaged from the cleat 1501 or not even used, the yard truck operator the supplies power to the repositioning device 521 in order to retract the repositionable wheel chocks 501 . Presuming the wheel chocks 501 were not used or have already been retracted, the yard truck operator supplies power to the brake assemblies 181 in order to free the brakes and allow the wheels to turn with respect to the frame 121 . At this point, the king pin 2221 is released from the fifth wheel 401 and the trailer support may be removed from under the trailer 2201 . At the point in time where the trailer stabilizer 101 is removed from under the front of the trailer 2201 , it is up to the landing gear to support the frontal load of the trailer.
[0181] Referring to FIGS. 55 and 56 , a second exemplary trailer support 3101 includes a frame 3121 and an axle 3141 mounted to the frame 3121 . The axle 3141 includes one or more wheels 3161 mounted proximate the ends of the axle 3141 . In this exemplary embodiment, the axle 3141 includes tandem wheels 3161 mounted at each end, with the tandem wheels including an associated braking assembly (not shown), which is identical to that of the first exemplary embodiment 101 (see FIGS. 45-47 ). The braking assembly includes brake pads, brake drum/discs, and a pneumatic brake cylinder to apply a brake force to the trailer support 3101 when insufficient air pressure occurs within the pneumatic line feeding the cylinder. For purposes of brevity, reference is had to FIGS. 46 and 47 and the corresponding written description for a braking assembly that may be used as the instant braking assembly 3101 .
[0182] The frame 3121 includes a pair of C-shaped cross-section frame rails 3341 that are equally spaced apart from one another and oriented in parallel toward the rear of the trailer support 3101 . Toward the front of the trailer support 3101 , the frame rails 3341 are angled toward one another and eventually converge at a hitch 3361 proximate the front of the trailer support. When oriented in parallel, the frame rails 3341 are jointed together by mounting one or more cross-members (not shown) to the frame rails (via welding, nuts and bolts, etc.), where the cross-members may optionally include a block C-shape cross-section.
[0183] At least one of the cross-members of the frame 3121 has mounted to it a fifth wheel 3401 in an elevated fashion above the frame rails 3341 (using conventional nut and bolt fasteners and/or welds). Again, the fifth wheel 3401 is analogous to the fifth wheel 401 discussed with respect to the first exemplary embodiment 101 .
[0184] The trailer support 3101 also includes an actuatable draw bar and associated hook 3801 that is pivotally mounted to the frame 3121 between an elevated position and an engaged position (compare FIGS. 55 and 56 ). When in the draw bar and associated hook 3801 is in the engaged position (see FIG. 56 ), the hook is at or approximate ground level to engage a cleat 4201 mounted to the ground. When the draw bar and associated hook 3801 engage the cleat, appreciable forward movement of trailer support 3101 away from the cleat 4201 is not possible. Conversely, when the draw bar and associated hook 3801 is in the disengaged position (see FIG. 55 ), the hook is above ground level and inoperative to engage the cleat 4201 . Thus, when the draw bar and associated hook 3801 are disengaged from the cleat 4201 , appreciable forward movement of trailer support 3101 may be possible, presuming wheel chocks are not deployed in a barrier position.
[0185] Referring to FIGS. 55-58 , in this exemplary embodiment, the draw bar and associated hook 3801 comprises quarter inch steel rectangular tubing 3821 extending longitudinally and having opposing ends 3841 , 3861 . At one end 3841 , a cylindrical coupling 3881 is fastened to the tubing, such as by welding, and oriented so that a through opening 4001 is generally perpendicular to the longitudinal length of the tubing 3821 . This opening 4001 receives an axle 4021 that is mounted to the trailer support 3101 so that the coupling 3881 pivots around the axle 4021 . In exemplary form, the axle 4021 is sized to concurrently extend through the opening 4001 and corresponding openings that are aligned through spaced apart brackets 4041 mounted to the trailer support 3101 so that the longitudinal ends of the axle extend through the brackets. Each end of the axle 4021 includes a radial through hole that is sized to receive a respective cotter pin (not shown) and thereby inhibit the axle from being displaced laterally (i.e., from side to side). One or both of the cotter pins may be removed to allow the axle 4021 to be laterally repositioned with respect to the brackets 4041 and the cylindrical coupling 3881 . When the draw bar and associated hook 3801 is mounted to the trailer support 3101 , the cylindrical coupling 3881 interposes the brackets 4041 so that the through opening 4001 is longitudinally aligned with the corresponding openings of the brackets. At the same time, the axle 4021 is inserted through the openings in the coupling 3881 and brackets 4041 so that the ends of the axle extend just beyond the bracket openings. Thereafter, the cotter pins are installed, and the draw bar and associated hook 3801 is pivotally mounted to the trailer support 3101 .
[0186] A heavy duty hook 4061 is mounted to the end 3861 of the rectangular tubing 3821 opposite the cylindrical coupling 3881 . This heavy duty hook 4061 is fabricated from high strength steel and includes a linear segment 4081 that extends substantially coaxial with the tubing 3821 . The far end of the segment 4081 is rounded over 4101 . The hook 4061 defines a cavity 4121 on its interior that is adapted to retain at least one of a plurality of dowel pins 4501 associated with the cleat 4201 when the draw bar and associated hook 3801 is in the engaged position.
[0187] Referring to FIGS. 59-61 , the exemplary cleat 4201 comprises an open top with a longitudinal block U-shaped tunnel 4221 having opposed vertical sidewalls 4241 , 4261 and a bottom wall 4281 . Trapezoidal plates 4301 , 4321 , 4341 , 4361 are mounted to tapered ends and to the top of the vertical sidewalls 4241 , 4261 . In addition, the trapezoidal plates 4301 , 4321 , 4341 , 4361 are mounted to each other at their angled ends. In this manner, the trapezoidal plates 4301 , 4321 , 4341 , 4361 operate to provide an angled incline so that unintended objects contacting the cleat 4201 can pass thereover.
[0188] On the interior of the cleat 4201 are a series of spaced apart dowel pins 4501 that span laterally across the vertical sidewalls 4241 , 4261 . Each dowel pin 4501 includes a flange 4521 that extends perpendicularly from the circumference and extends substantially the entire distance between the vertical sidewalls 4221 , 4261 of the tunnel 4221 . The vertical sidewalls 4221 , 4261 , 4221 include corresponding openings in order to receive the dowel pins 4501 . But it should be noted that in this exemplary cleat 4201 , the dowel pins 4501 are not rotationally repositionable with respect to the vertical sidewalls 4221 , 4261 . However, it is within the scope of the disclosure to provide dowel pins 4501 and flanges 4521 that are rotationally repositionable. Specifically, the flanges 4521 may be spring biased and operative to close the gap between adjacent pins 4501 in order to prohibit unintended objects from entering the interior of the cleat 4201 .
[0189] In exemplary form, the forward most dowel pin 4501 is mounted to the vertical sidewalls 4241 , 4261 so that its flange 4521 extends to meet the top edge of the forward trapezoidal plate 4301 . As will be discussed in more detail below, this orientation ensures that the hook 4061 does not inadvertently snag the top edge of the forward trapezoidal plate 4301 . The remaining dowel pins 4501 are oriented so that the flanges 4521 are upwardly sloped from front to back.
[0190] The orientation for the flanges 4521 of the second and successive dowel pins 4501 provides a series of ramps that allow the hook 4061 to move from front to back across the dowel pins without becoming snagged. Simply put, the hook 4061 , when moving from front to back, slides up the flange and over one of the dowel pins, to only drop down and contact a successive flange of a successive dowel pin. The same process may be repeated until the hook reaches the top of last dowel pin or the hook is moved forward. At this point, the hook 4061 slides over the last dowel pin and begins to slide down the face of the rear trapezoidal plate 4341 . In contrast, when the hook 4061 is repositioned from rear to front, the cavity 4121 of the hook receives whichever dowel pin 4501 is nearest in order to retain the hook within the cleat 4201 . This retention occurs because the angled surfaces provided by the flanges 4521 operate to direct the hook 4061 into contact with the nearest dowel pin 4501 so that the dowel pin is received within the cavity. In this received position, the draw bar and associated hook 3801 cannot be moved forward to the next nearest dowel pin, nor can the hook 4061 be vertically repositioned out of engagement with the dowel pin. In order to discontinue engagement of the hook 4061 with the instant dowel pin 4501 , the draw bar and associated hook 3801 is repositioned rearward (from front to back) until the tip of the hook 4061 clears the instant dowel pin. Thereafter, the draw bar and associated hook 3801 may be vertically raised to remove the hook 4061 from within the cleat 4201 .
[0191] Referring back to FIGS. 55 and 56 , in order to vertically reposition the draw bar and associated hook 3801 , a pneumatic cylinder 4601 is concurrently coupled to the rectangular tubing 3821 and corresponding brackets 4621 mounted at the rear of the frame 3121 . In this exemplary embodiment, air supply lines (not shown) are coupled to the pneumatic cylinder 4601 and are adapted to receive air from a yard truck or other tractor (see e.g., FIGS. 52 and 53 ). The pneumatic cylinder 4601 is pivotally mounted to the rear of the frame 3121 by way of the corresponding brackets 4621 , while the pneumatic cylinder piston 4661 is repositionably mounted to a clevis 4681 on the rectangular tubing 3821 using a through pin (not shown). The clevis 4681 is formed by two parallel metal plates that are welded to the rectangular tubing, where each plate has an aligned hole that receives the through pin. In this manner, when the piston 4661 is extended from the cylinder 4601 , the draw bar and associated hook 3801 are pivoted about the axle 4021 in order to lower the hook 4061 . Conversely, when the piston 4661 is retracted into the cylinder 4601 , the draw bar and associated hook 3801 are pivoted about the axle 4021 in order to raise the hook 4061 .
[0192] In addition, the exemplary trailer support 3101 may include a pair of repositionable wheel chocks 4801 having generally the same structure and mode of operation as the wheel chocks 501 discussed with respect to the foregoing embodiment. Accordingly, for purposes of brevity, a detailed discussion of the components and mode of operation has been omitted.
[0193] In operation, a yard truck (not shown) attaches itself to the trailer support 3101 by way of the yard truck's tow hook being coupled to the hitch 3361 of the trailer support. In addition to attaching the yard truck to the trailer support 3101 using the hitch 3361 , the yard truck operator also connects quick connects of the trailer stabilizer 3101 to quick connects associated with the yard truck to supply electrical and pneumatic power to the trailer stabilizer. It should also be noted that the yard truck may include hydraulic pump(s), lines, and connections (not shown) that connect to connections, lines, and devices of the trailer support 3101 , such as when the draw bar and associated hook 3801 is hydraulically repositioned by way of a hydraulic cylinder instead of a pneumatic cylinder 4601 .
[0194] After completing connections between the yard truck and the trailer support 3101 , the yard truck operator then drives the yard truck into position with respect to a trailer having already been parked at a loading dock so that the doors of the trailer are open and the associated opening at the rear of the trailer is adjacent a loading dock opening. The yard truck operator then begins to back the trailer stabilizer 3101 underneath the trailer, with the rear of the stabilizer where the draw bar and associated hook 3801 is located moving underneath the trailer first so that the fifth wheel 3401 is aligned with the king pin of the trailer. While the trailer stabilizer 3101 is backed underneath the trailer, the repositionable wheel chocks 4801 are in a storage position, the brake assemblies of the trailer stabilizer are free (i.e., not locked), and the draw bar and associated hook 3801 are in a raised position. Continued backing of the yard truck causes the trailer stabilizer 3101 to be further repositioned underneath the trailer, eventually so much so that the king pin engages the fifth wheel 3401 and becomes locked within the fifth wheel, thereby coupling the trailer stabilizer to the trailer. At this time, a king pin sensor detects the position of the king pin with respect to the fifth wheel 3401 and communicates a signal indicative of the king pin position to a controller associated with the yard truck. Thereafter, the controller wirelessly communicates a signal to a visual display (not shown), which displays visual indicia within a warehouse to dock workers telling them that the king pin is secured to the trailer stabilizer 3101 .
[0195] After the trailer stabilizer 3101 is coupled to the trailer, a number of events occur to lock the position of the trailer stabilizer with respect to the trailer. First, the yard truck operator lowers the draw bar and associated hook 3801 so that the hook 4061 contacts the top of the cleat 4201 , which is already securely mounted to the pavement/concrete underneath the trailer, in order for the hook to float on top of the cleat. The yard truck operator then pulls slightly forward so that the hook 4061 captures one of the dowel pins 4501 within the cavity 4221 and retards further forward movement of the stabilizer 3101 . A sensor associated with the stabilizer 3101 detects the deployed position of the draw bar and associated hook 3801 and communicates this to the controller. The controller then wirelessly communicates a signal to a visual display (not shown) or powers an infrared light source to communicate with an infrared light detector operatively coupled to the visual display letting dock workers know that the draw bar and associated hook 3801 is deployed.
[0196] In addition to securing the hook 4061 to the cleat 4201 , the yard truck operator also locks the braking assembly of the trailer stabilizer by depressurizing the pneumatic lines feeding the drum assemblies. This depressurization causes the brake pads to be forced against the brake drum/disc, thereby retarding rotational motion of the wheels 3161 . Another event is the deployment of the repositionable wheel chocks 4801 using a pneumatic cylinder 4821 . Deployment of the wheel chocks 4801 is essentially the same as that discussed for the first exemplary embodiment and has been omitted only to further brevity. Thereafter, the yard truck unhooks any pneumatic and electrical connections with the trailer stabilizer and continues on to the next spotted trailer.
[0197] After the trailer is fully loaded or unloaded, the yard truck reattaches itself to the trailer support 3101 , which includes reattaching any pneumatic and electrical connections. After these connections have been reestablished, the repositionable wheel chocks 4801 are raised to a storage position and the brake assemblies are freed (i.e., not locked). This allows the yard truck operator to slightly reposition the trailer support 3101 toward the rear of the trailer to unseat the hook 4061 from the nearest dowel pin 4501 of the cleat 4201 . After the hook 4061 is unseated, the yard truck operator manipulates valves to supply air to the air supply lines coupled to the pneumatic cylinder 4601 . This, in turn, causes the piston 466 to retract within the cylinder 4601 , thereby pivoting the draw bar and associated hook 3801 about the axle 4021 , thus raising the hook 4061 . After the hook 4061 has been raised to no longer potentially come in contact with the cleat 4201 , and the landing gear of the trailer has been lowered, the yard truck pulls the trailer support 3101 out from under the trailer so that the king pin of the trailer no longer engages the fifth wheel 3401 .
[0198] The exemplary trailer stabilizer 3101 is operative to inhibit trailer nosedives, tip-overs, and trailer creep. Moreover, the exemplary trailer stabilizer 3101 includes a means for informing dock personnel when the trailer stabilizer 3101 is mounted to the trailer, thereby informing the dock personnel that it is safe or unsafe to load/unload the trailer, similar to that discussed for the first exemplary embodiment.
[0199] Following from the above description and invention summaries, it should be apparent to those of ordinary skill in the art that, while the methods and apparatuses herein described constitute exemplary embodiments of the present invention, the invention contained herein is not limited to this precise embodiment and that changes may be made to such embodiments without departing from the scope of the invention as defined by the claims. Additionally, it is to be understood that the invention is defined by the claims and it is not intended that any limitations or elements describing the exemplary embodiments set forth herein are to be incorporated into the interpretation of any claim element unless such limitation or element is explicitly stated. Likewise, it is to be understood that it is not necessary to meet any or all of the identified advantages or objects of the invention disclosed herein in order to fall within the scope of any claims, since the invention is defined by the claims and since inherent and/or unforeseen advantages of the present invention may exist even though they may not have been explicitly discussed herein. | A trailer stabilizer and signaling system comprising: (a) a repositionable freight trailer stabilizer comprising a frame having mounted thereto a wheel, the repositionable freight trailer stabilizer including a repositionable jack; and, (b) a stabilizer signaler operatively coupled to the trailer stabilizer, the stabilizer signaler including a deployable signal configured to confirm the trailer stabilizer is secured under a parked freight trailer. | 1 |
FIELD OF THE INVENTION
[0001] This invention relates to a method of producing a running board for a motor vehicle. In particular, the invention relates to a method of creating a running board which includes a step plate and optionally one or more trim inserts.
BACKGROUND OF THE INVENTION
[0002] Many motor vehicles which are mounted on large wheels and tires or have raised suspension systems, have a vehicle floor which is well above the road surface on which the vehicle travels. Many such vehicles are provided with a step to facilitate entry into the vehicle. These are often referred to as a running board. Typically, running boards are used on trucks or sport utility vehicles or the like. The running board provides a structural step which projects outwardly from the rocker panel area of the vehicle and gives enough supporting surface area to support the foot of a person desiring entry or exit from a vehicle. The running board may be a separate structure from the rocker panel and requires structural support to support the load of the person standing on the running board when entering or leaving the vehicle. The running board, when installed, will have an upper supporting surface on which the person using the running board, steps. The surface extends along the length of the running board but may be relatively narrow. Accordingly, it is desirable that the surface on which the user steps, includes a step pad. The step pad may include raised portions to provide a traction aid to help resist slipping of the user's foot off the surface as the user applies weight to their foot. The step pad may also include patterns of raised and lowered areas, ribs and the like which provide a pleasing visual appearance to the installed running board.
[0003] A running board has an outer surface which is highly visible, extending between the front and rear wheels of the vehicle. It is often desirable to include one or more trim strips which may extend along portions of the running board to enhance the appearance of the running board and the vehicle on which the running board may be installed.
[0004] The blow molding procedure is a very cost efficient way of producing items which have a hollow structure and may be used to produce items requiring structural strength such as running boards. Accordingly, it is desirable to use the blow molding process to create such running boards.
[0005] In order to meet all of the desired criteria of appearance, structural strength and anti-slip characteristics, running board assemblies may include a pluralities of parts. These may include the running board itself, a step pad and one or more trim pieces.
[0006] It would be desirable to create a subassembly including all of these components for manufacture by an automotive equipment supplier for shipment to automotive assembly plants where the running board subassembly may then be assembled to the vehicle.
[0007] Accordingly, there exists a need to produce the components for such a subassembly and to create the subassembly in a commercially economic fashion.
SUMMARY OF THE INVENTION
[0008] In accordance with this invention, a process for making, a running board assembly of a running board and an insert comprises providing complimentary mold components having respective molding cavities. At least one of the mold components has at least one insert subcavity within the cavity of that mold component. The process includes providing an insert. The process further includes inserting the insert into the subcavity and applying vacuum pressure into the subcavity to hold the insert in place. A parison is then extruded between the mold components. The mold components are closed and the parison is expanded within the closed cavity of the mold components to simultaneously mold the running board and to integrate the insert and the running board to produce the running board assembly.
[0009] In accordance with one aspect of the invention, the insert is a step plate.
[0010] In accordance with another aspect of the invention, the insert is a trim piece.
[0011] In accordance with a particularly preferred embodiment of the invention, the step plate is formed of a moldable, anti-slip material which is compatible for thermal bonding with the parison. In a further preferred aspect of the invention, the process includes the step of expanding the parison so that the parison contacts the moldable step plate to raise its temperature to a temperature suitable for molding. The process further includes expanding the parison to force the moldable step plate against a molding pattern within the subcavity to mold a surface of the step plate and at the same time incorporate the step plate into the running board formed from the parison.
[0012] In accordance with a further aspect of the invention, the step plate may be formed from a metallic material and the step plate includes at least one key shaped rib. In accordance with a preferred embodiment of this aspect of the invention the process includes the step of blow molding the parison against the metallic step plate so that the key shaped rib is encapsulated within the molded parison.
[0013] In accordance with another aspect of the invention, the insert is a trim strip which is not thermally bondable with the parison. In a preferred embodiment of this aspect of the invention, the subcavity includes an undercut around at least a portion of the perimeter of the subcavity so that upon expansion of the parison, a portion of the parison may flow into the undercut.
[0014] Various other aspects and objects of the invention may be understood from reference to the following description of preferred embodiments of the invention and the following drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a top perspective view of a running board assembly in accordance with a first embodiment of the invention;
[0016] FIG. 2 is a cross section through the running board assembly of FIG. 1 taken along the lines 2 - 2 shown in FIG. 1 ;
[0017] FIG. 3 is an expanded view of a portion of the cross-section illustrated in FIG. 2 ;
[0018] FIGS. 4 through 11 illustrate various steps of the process in accordance with the preferred embodiment of the invention;
[0019] FIG. 12 illustrates an alternative component which may be used in accordance with the invention;
[0020] FIG. 13 is a cross-sectional view of a running board assembly which makes use of the component of FIG. 12 which may be manufactured in accordance with the invention;
[0021] FIG. 14 is a cross-sectional view similar to FIG. 4 showing an alternate embodiment, and
[0022] FIG. 15 is a cross section of a molding subcavity in accordance with another aspect of the invention for use in making the component illustrated in FIGS. 1, 2 and 3 .
DETAILED DESCRIPTION OF THE INVENTION
[0023] FIG. 1 illustrates a running board assembly generally at 20 .
[0024] The running board assembly comprises a running board 22 , a step pad 24 and a trim strip 26 .
[0025] The running board 22 has an upper support surface 30 . The step pad 24 is adhered to the supporting surface 30 in accordance with the process of this invention which is explained more fully below. The running board 20 may be formed in a blow molding procedure. From review of FIG. 2 , it will be noted that the running board includes a plurality of recesses 32 which may be formed by moving components within a blow mold in a known fashion. The recesses 32 bring the internal surface of the parison in contact with an opposite portion to form a plurality of ribs. These ribs provide the structural strength to the blow molded running board so that it meets the necessary structural requirements. Any pattern of ribs may be formed so as to provide sufficient strength to the running board 22 .
[0026] The process will now be explained in greater detail with reference to FIGS. 4 through 11 . FIG. 4 illustrates diagrammatically the blow molding mold 40 . The blow molding mold comprises a first mold half or component 42 and a complimentary mold half or component 44 . Diagrammatically, the mold halves 42 and 44 are shown as being movable toward and away from each other by rams 46 and 48 respectively. The mold halves 42 and 44 each have supply conduits 50 and 52 respectively. The supply conduits 50 and 52 supply cooling fluids as need be. In addition, the supply conduit 52 also includes a source of vacuum pressure as will be explained more fully below.
[0027] The mold halves 42 and 44 each include a mold cavity. In the view illustrated in FIG. 4 , only the cavity 60 within mold half 44 is visible. The mold cavity 60 determines the shape of a portion of the running board and includes the necessary configuration to mold a substantial portion if not all of the support surface 30 . The mold cavity 60 within the mold half 42 also includes a subcavity 62 . The subcavity 62 includes a configuration for molding a desired pattern on what will become the upper surface of a step pad.
[0028] In accordance with this aspect of the invention, a process includes providing a moldable step pad 70 and the extrusion of a parison 72 . The parison 72 may be extruded from a well known extrusion head.:
[0029] FIG. 5 illustrates the movement of the step pad 70 to a position between the mold halves 42 and 44 . FIG. 6 illustrates the movement of the moldable step pad 70 into the cavity 60 of the mold half 44 . FIG. 7 illustrates the final position of the step plate 70 entirely within the subcavity 62 . The movement of the step pad 70 as shown diagrammatically in FIGS. 4, 5 , 6 and 7 can most easily be accomplished using a programmable robotic arm. A supply of step pads 70 may be located where they be grasped and extracted by one or more robot arms. The robot arm moves the moldable step pad 70 until it is placed within the subcavity 62 . Once the robot arm has placed the movable step pad 70 within the subcavity 62 , then vacuum pressure, available from supply conduit 52 is applied to the subcavity 62 , so that the moldable step plate 70 is retained and accurately positioned within the subcavity 62 . The robot arm then retracts so that it is no longer located between the mold halves 42 and 44 . When that has been completed, the parison 72 is extruded to extend between the mold halves as shown in FIGS. 7 and 8 , FIG. 8 illustrates the completion of the extrusion of the parison and the mold halves are now ready to be closed about the parison.
[0030] FIG. 9 illustrates the closure of the mold halves 42 and 4 . 4 to form a closed blow mold ready for application of a blow molding gas under appropriate pressure.
[0031] In this embodiment of the invention, the moldable step plate 70 is made from a material which may be thermal formed within the mold 42 and which is compatible with the material of the parison 72 so that the materials may fuse together to form an integral structure under suitable pressure and temperature.
[0032] The vacuum pressure applied to the submold 62 is intended primarily to hold the moldable step plate 70 in place. If the moldable step plate has not been raised to a temperature close to its molding temperature, no substantial molding of the step plate 70 will occur under the vacuum force alone. However, when the blow molding gas is supplied to the interior of the parison 72 , the parison is at a moldable temperature and the parison will then expand within the mold 40 . As the parison expands, a portion of the parison will then come into contact with the moldable step plate 70 . This will result in the transfer of heat from the wall of the parison to the moldable step plate 70 . In addition, as the parison 72 continues to expand, it will deliver substantial pressure to the moldable step plate 70 and forcing it against the pattern included within the subcavity 62 .
[0033] Preferably the blow molding pressure is substantial. Most preferably the blow molding pressure may be at or above 90 psi.
[0034] The moldable step plate 70 as illustrated in FIG. 4 , is a relatively thin strip of moldable plastic. The strip of plastic may be of the order of one to one and a half millimeters thick. The subcavity 62 is preferably less deep than the thickness of the strip. Preferably for a strip having a thickness of one to one and a half millimeters, the cavity may be of about one half millimeter depth. This means that upon completion of the molding, the step will project upwardly from the formed surface 30 by approximately one half millimeter or more, while the remainder of the step plate will be below and integrated into the wall of the parison. This is illustrated in FIG. 2 .
[0035] After the blow molding pressure is released, in typical blow molding fashion, the mold 40 is cooled and opened. The opened mold is shown diagrammatically in FIG. 10 with the running board assembly 20 being shown having been ejected from the mold halves ready for trimming.
[0036] 5 After ejection of the molded running board assembly 20 , the running board assembly is trimmed as desired and removed from the mold. This is shown in FIG. 11 .
[0037] The running board assembly 20 shown in FIG. 1 includes a step pad 24 . The step pad 24 is incorporated into the running board assembly 10 by means of thermal fusion between the step pad 24 and the running board 22 which occurs during the blow molding process. In accordance with an alternate aspect of the invention, the step pad need not be comprised of a moldable material nor a material that will thermally fuse with the material of the running board.
[0038] FIG. 12 illustrates a step pad 124 . The step pad 124 is a metal strip. The metal strip includes a raised pattern 125 on one surface and at least one and preferably a plurality of longitudinally extending key shaped ribs 128 on the other surface.
[0039] FIG. 13 illustrates in cross-section, a running board assembly 120 . The running board assembly 120 includes the step pad 124 which has been incorporated during blow molding into a running board 122 .
[0040] The process for manufacturing the running board assembly 120 illustrated in FIGS. 12 and 13 is similar to the process illustrated in FIGS. 4 through 11 . In accordance with this aspect of the invention, the metal step pad 124 is placed within a subcavity 162 within one mold half 144 of a mold 140 .
[0041] The step pad 124 may be obtained from a storage location and placed into the subcavity 162 by a computer controlled robot arm. Once the step pad 124 is placed within the subcavity 162 , then vacuum pressure is applied to the subcavity 162 holding the step pad in place.
[0042] Once the step pad is held in place by the vacuum pressure, then a parison 72 is extruded between the mold halves 42 and 144 , the mold is closed and a blowing pressure is applied to the interior of the parison. As the parison expands under the blowing pressure, a portion of the wall of the parison will encounter the surface of the step pad 124 which includes the plurality of key shaped ribs 128 . The raised portions 125 of the step pad 124 will bear against the surface of the subcavity 162 .
[0043] With reference to FIG. 13 , it will be observed, that as the wall of the parison is forced under blowing pressure against the ribs 128 , a portion of the wall will flow around the ribs. Each rib is substantially key-shaped. By this, it is meant that the portion of the rib which becomes embedded in the wall of the parison has an undercut or smaller width. In a preferred embodiment of the invention as shown in FIG. 13 , the ribs are T-shaped. When the wall of the parison solidifies as the mold is cooled, then the cooled plastic of the parison wall extends into the undercut or thinner region of the rib thereby permanently incorporating the step pad 124 into the running board 120 as the running board is formed. Thus, when the mold opens, the part which is ejected is the running board assembly 120 with an integrated step pad 124 .
[0044] Reference is now made to FIGS. 1, 2 , 3 and 15 . As shown, the running board assembly 20 includes a trim strip 26 . The trim strip may be a moldable plastic which can thermally fuse with the parison 70 as the running board 22 is formed. Alternatively, the trim strip 26 may be manufactured from a material which does not thermally fuse with the running board 20 . In this regard, the trim strip 26 may be a metallic strip similar to the step pad 124 .
[0045] The trim strip 26 is in the form of an insert which may be positioned within a mold half 43 in a manner analogous to the step pad 70 or the step plate 124 . In order to accomplish this, there may be a separate subcavity 263 . The subcavity 263 may either be in the same mold half as the subcavity 62 or in the other mold half. While the trim strip 26 may use a similar retention means as the ribs 128 of step pad 124 , an alternate retention system is shown in the enlarged view of FIGS. 3 and 15 .
[0046] The subcavity 263 into which the trim strip 26 may be placed and retained by vacuum pressure advantageously includes an undercut 264 extending around the perimeter of the subcavity 263 . The running board assembly including both the step pad 24 or a step pad 124 and one or more trim strips 26 , may be formed using the process discussed in connection with FIGS. 4 through 11 . As the wall of the parison is expanded toward the trim strip 26 , material from the parison will be forced against the surface of the trim strip 26 . Under the blowing pressure, a small portion 80 of the parison material will be forced into the undercut. That portion of the parison then is adjacent the other surface of the trim strip 26 . Sufficient length of undercut along the perimeter of the subcavity containing trim strip 26 is provided so that upon completion of the molding process, the trim strip 26 is permanently retained in the running board assembly 20 . Most preferably, the undercut extends substantially around the perimeter of the subcavity so that in effect, the portion 80 of the parison material flows around substantially all of the perimeter edge of the trim strip 26 . This in effect provides a permanent picture frame type retention of the trim strip 26 .
[0047] The trim strip 26 is retained by the cooled material of the parison. Thus, the trim strip 26 may be manufactured from any desirable material which would include metals or plastics which are not compatible with the material of the running board 22 or materials which are compatible with the material of the running board 22 .
[0048] As has been explained above, there are various aspects of preferred embodiments of the invention. The above description is to be taken as illustrative only with the full scope of the invention to be determined from reference to the following claims. | A process for making a molded running board assembly for installation on a vehicle includes blow molding the body of the running board and incorporating one or more additional components such as a step plate or a trim strip. The process involves placing the insert into the blow mold cavity in a subcavity, holding the insert by vacuum pressure and then extruding and blow molding a parison to simultaneously mold the running board and integrate the insert. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This patent application claims the benefit of U.S. Provisional Patent Application 61/814,583 filed on Apr. 22, 2013 entitled “Methods and Devices for Brain Activity Monitoring Supporting Mental State Development and Training.”
FIELD OF THE INVENTION
The present invention relates to EEG-based brain activity monitoring devices, and more particularly to portable systems for brain activity recording, storage, analysis, and neurofeedback that operate in conjunction with an application and web-based framework for more extensive storage and analysis.
BACKGROUND OF THE INVENTION
Brain Computer Interfaces (BCIs) are devices that allow the human brain to directly interact with technology via signals emitted from the skull. As with many such new technologies relating to the human brain and body, BCIs were first developed and used in laboratory, clinical, medical, and research settings. However, in recent years electroencephalography (EEG)-based BCI headsets have reached consumer-accessible prices, and are now being deployed in mobile applications, especially those focused on gaming and mental development. Medical applications of BCIs are beginning to include helping people with locked-in syndrome communicate; providing more autonomy to people with neuromuscular disorders; and helping with the rehabilitation of stroke survivors. Additionally, BCIs may aid in diagnosis and lead to preventative protocols for brain disorders, which are particularly important, in part due to increasing average life-expectancy, population growth, and number of people over the age of 65, i.e. Alzheimer's disease and other forms of age-related dementia are becoming an increasingly large problem. Furthermore, surveys consistently show that a large (and increasing) portion of the population suffers from some sort of mental illness: e.g. in 2010 approximately 1 in 3 Europeans met DSM-IV criteria for a mental or neurological disorder, see for example Wittchen et al. in “The Size and Burden of Mental Disorders and other Disorders of the Brain in Europe 2010” (European Neuropsychopharmacology, Vol. 21(9), pp. 655-679), in 2004 the rate was 1 in 4 in the United States, see for example Wittchen et al. in “Size and Burden of Mental Disorders in Europe—A Critical Review and Appraisal of 27 Studies” (European Neuropsychopharmacology, Vol. 15(4), pp 0.357-376).
Beyond medical applications, BCIs can provide members of the general public with insight into various aspects of their mental health, and act as tools for controlling/interacting with electronic systems. Additionally, EEG-based BCI devices can be used for neurofeedback, a series of techniques that give users the opportunity to train their brain by (among other things) increasing their ability to focus, reducing stress and anxiety levels, elevating mood, improving sleep, and enhancing cognitive processing and mental clarity. Also, neurofeedback can also be used as a treatment for a number of brain disorders, e.g. attention deficit hyperactivity disorder (ADHD), see for example Gevensleben et al. in “Is Neurofeedback an Efficacious Treatment for ADHD? A Randomised Controlled Clinical Trial.” (J. Child Psychology and Psychiatry, Vol. 50(7), pp. 780-789), and epilepsy, see for example Kotchoubey et al. in “Negative Potential Shifts and the Prediction of the Outcome of Neurofeedback Therapy in Epilepsy (Clinical Neurophysiology, Vol. 110(4), pp. 683-6).
Current BCIs range in complexity from medical/research-grade EEG devices with hundreds of sensors, to small headphone-like plastic headsets with only one or two. EEG headsets are designed for numerous purposes, but they typically fall into 2 categories: 1) medical/research headsets with a large number of sensors; and 2) simple devices with a small number of electrodes geared towards consumer devices and applications: e.g. games and general health and wellness software. Typically, medical/research headsets are bulky, stationary, uncomfortable, complex, user-unfriendly (and can thus only be operated by technicians and medical professionals), unattractive, and often require electrolyte solutions, glues, or gels for connectivity. Accordingly, it is beneficial to design sensors/electrodes/user interfaces with these issues in mind, i.e. a BCI that supports use for durations considerably longer than those of discrete medical visits and laboratory studies, but that still exhibits many of the most useful features of currently existing consumer and especially medical/research BCI headsets.
Electroencephalography (EEG) is a well-established technology that gathers information about what's going on inside a person's brain by recording signals produced by the firing of their neurons. When a neuron receives enough excitatory signals from sensory cells and other neurons, it produces a response called an action potential, which causes the neuron to release chemicals that excite all cells connected to a part of the firing neuron called the axon. During this process, there is a rapid exchange of ions (electrically-charged particles) that changes the voltage of the fluid surrounding the firing neuron in a predictable fashion. This voltage change then travels spherically outward from the firing neuron until it reaches the skull. EEG takes advantage of this to record brain activity by detecting voltages at one or more scalp locations over time (which alter in response to the firing of many neurons simultaneously), using electrodes attached to the surface of the head. Voltages are sampled from the electrodes at high frequencies—typically 1 kHz to 2 kHz—to provide an effectively continuous stream of data known as an EEG waveform. Spectral information is then extracted from this continuous stream, which results in discrete frequency-band ratios (wave types) generated from the raw data at frequencies in the ballpark of 100 Hz; for example, see Tatum et al in “Handbook of EEG Interpretation” (Demos Medical Publishing, 2008). These are generally divided into delta, theta, alpha, beta, mu, and gamma waves, with each type representing a specific range of frequencies. Some systems further subdivide these waveforms into subcategories, such as alpha1, alpha2, etc.—which essentially subdivide the frequency range of the entire waveform into smaller frequency ranges.
Past research has shown that different EEG waveforms correlate with activity in different regions of the brain, and thus with various internal mental states, for example particular emotions and thoughts, phases of sleep such as REM, and medically relevant neurological activity (e.g. seizures). Specific mental states can be identified by mathematically pre-processing the raw EEG data (e.g. using Fourier transforms; with various filters such as high-pass filters, low-pass filters, and bandpass filters; etc.), then applying algorithms that recognize EEG waveform features associated with a particular state—known as classification algorithms; see for example Shaker in “EEG Waves Classifier using Wavelet Transform and Fourier Transform” (Int. J. Biol. Life. Sci., Vol. 1, Iss. 2, p85-90). Algorithms exist for the quantification and tracking of mood, energy levels, epileptic seizures and seizure-like states, stages and quality of sleep, desire or craving for a particular object (e.g. a specific food), blinks, concentration/focus, relaxation/stress, and anxiety; see for example Rebolledo-Mendez et al in “Assessing Neurosky's Usability to Detect Attention Levels in an Assessment Exercise: (Human and Computer Interaction, pp 149-158, Springer-Verlag, 2009); and Crowley et al in “Evaluating a Brain-Computer Interface to Categorise Human Emotional Response” (IEEE 10 th Int. Conf. Adv. Learning Technologies, pp 276-278). Accordingly, within the prior art EEG waveforms have been used to document a range of a user's neural processes and mental states.
This ability to externally read and record specific mental states led to neurofeedback: EEG-based treatments for neurological and/or mental disorders that use exercises developed to allow a person to alter these mental states directly (by manipulating its constituent waveforms). For example, knowledge of the EEG patterns correlated with attention—mainly beta waves—led to effective neurofeedback exercises for improving concentration, in which the feedback a user receives from the EEG analysis informs them of the extent to which they are focused. This allows users to purposefully induce these states by repeating the thought patterns they were engaged in when high levels of focus were reported by the EEG device. Increasing concentration in this manner actually strengthens the involved areas of the brain, such that the user sees improved focus in their day-to-day life, beyond the context of the exercise itself. This was demonstrated by research showing that 1) these areas of the brain observably grow, see for example Beauregard et al in “Functional Magnetic Resonance Imaging Investigation of the Effects of Neurofeedback Training on the Neural Bases of Selective Attention and Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder” (Appl. Psychophysiology and Biofeedback, Vol. 31, pp 3-20; and 2) it significantly improves symptoms of attention-deficit hyperactivity disorder (ADHD), a condition marked by a pathologically low attention span; see for example Arms et al in “Efficacy of Neurofeedback Treatment in ADHD: The Effects on Inattention, Impulsivity, and Hyperactivity: A Meta-Analysis” (Clinical EEG Neurosciences et al, Vol. 40(3), pp 180-189). This, however, is merely an example, as other research has demonstrated the efficacy of neurofeedback-related therapies for the treatment of conditions involving other mental states, such as depression using mood-elevating exercises and anxiety with neurofeedback-informed relaxation techniques, see for example Baehr et al in “Clinical Use of an Alpha Asymmetry Neurofeedback Protocol in the Treatment of Mood Disorders: Follow-Up Study One to Five Years Post Therapy” (J Neurotherapy, Vol. 4(4), pp 11-18) and Hammond in “Neurofeedback Treatment of Depression and Anxiety” (J Adult Dev., Vol. 12(2-3), pp 131-137).
Neurofeedback can also benefit people without mental or neurological disorders. Recent research has shown improvements in attention, semantic memory, and musical performance in healthy people after using neurofeedback exercises specifically designed to target each of those attributes. These performance enhancements were shown to translate into real-world settings; see for example Egner et al in “Ecological Validity of Neurofeedback: Modulation of Slow Wave EEG Enhances Musical Performance” (Neuroreport, Vol. 14, pp 1221-1224). Thus, neurofeedback can be used to cultivate desirable personal traits and improve quality of life, rather than simply to treat disorders. It is therefore a valuable tool for self-improvement that can allow healthy people to strengthen areas of cognitive and emotional weakness, and to improve their existing strengths.
Until recently, EEG measurement devices were expensive, bulky, stationary, and extremely difficult to use, and thus confined to a laboratory, clinic, or hospital setting. They were therefore only useful for research, diagnosis of various brain diseases, and for treatment of certain disorders in a clinical practice setting—which is very expensive. Accordingly, numerous potential treatments targeting neurological and mental disorders that require frequent, long-term, and self-administered EEG (IE a neurofeedback regiment that requires an extremely large number of sessions, which continue to be done intermittently near-indefinitely) were essentially impossible, as were all non-medical uses of EEG such as self-improvement or controlling video games. However, this has changed in recent years with the advent of small, inexpensive, and easy-to-use EEG headsets designed to be used by members of the general public rather than medical professionals and researchers. Typically, these consumer orientated EEG headsets exploit a small number of electrodes (e.g. 2-12), in contrast to the hundreds employed in medical and research systems. Such headsets are worn by the user throughout a neurofeedback activity, which typically last between a few minutes and an hour.
Early consumer EEG headsets were still relatively stationary, and coupled to fixed electronic devices (FEDs)—primarily desktop and laptop computers. However, due to the recent explosive market penetration of portable electronic devices (PEDs) such as personal digital assistants, smartphones, and tablet computers, this has begun to change. Certain consumer EEG devices have now been released that can interface with PEDs. Consumer EEG devices linked to PEDs have numerous advantages over consumer EEG devices that interface with FEDs. Such benefits include localized wireless interfacing, e.g. Bluetooth; portability. as EEG headsets interfaced to PEDs can be used essentially anywhere, and—since PEDs now outnumber FEDs—access to a larger market
Despite the great potential consumer EEG—especially PED-linked consumer EEG—has for medical, self-monitoring, and self-improvement applications, it is usually still treated as a novelty or toy, and used almost solely for entertainment purposes. Much of this has to do with limitations in development tools and supporting programs, which are geared primarily towards stationary use and games, which makes it difficult to create other types of software for consumer EEG. Also, these tools are geared toward developing applications intended for short-term use, and as such do not support numerous uses of consumer EEG applicable only when the devices are used for longer periods and/or continuously throughout the day, such as uses applicable to embedding EEG-based BCI into everyday activities or for the tracking of user medical information recorded throughout the day by EEG. Furthermore, existing development tools for consumer EEG are not conducive to web integration, which makes it nearly impossible to create consumer EEG applications that do such things as link EEG data to existing global databases, integrate EEG data with social media, send user EEG data to a dedicated server for deeper analysis than is practical on a smartphone, etc.
Another limitation in the prior art relating to neurofeedback and consumer EEG devices is the number of detectable and alterable mental states, which have mostly been confined to level of attention, relaxation, stress, and quality of sleep. Outside of academic research, the detection and alteration of states of mental clarity—which could otherwise be called level of mental fogginess, cognitive tempo, acute intelligence, mental “sharpness,” cognitive performance, or level of mental confusion—have been ignored. This state is associated with numerous forms of mental/cognitive processing and abstract thought, such as ability to reason and current level of creativity. Mental clarity is a detectable metric, as is strongly suggested by research on a phenomenon called “feature binding,” which is a person's ability to link information from different sources together to solve problems or be creative. On a simpler level, this can simply be the combination of 2 different types of sensory information coming in from different modalities to solve a small puzzle—for example figuring out what a particular object is when presented with a colour and a shape separately (e.g. the colour red is shown at one point, and a semi-circular shape later on, and the person is able to connect the separate pieces of information to determine that the object is an apple); see Keizer et al, 2010 in “Enhancing Cognitive Control Through Neurofeedback: A Role of Gamma-band Activity in Managing Episodic Retrieval” (Neuroimage, 49(4): p3404-3413)
Furthermore, the detection and alteration (through neurofeedback) of meditative states has primarily been treated as synonymous with relaxation, despite the numerous differences in the brain activity observed between relaxation and meditation. Meditative states also relate strongly to other detectable mental states—most notably level of attention. This fact has been largely ignored in algorithms used in previous embodiments of the invention.
According to embodiments of the invention the inventors have established new technologies and solutions that address these limitations within the prior art and provide benefits including, but not limited to, global acquisition and storage of acquired EEG data and processed EEG data, development interfaces for expansion and re-analysis of acquired EEG data, long-term/continuous user wearability, detection of states of mental clarity, and improved detection of states of meditation.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
SUMMARY OF THE INVENTION
It is an objective of the present invention to mitigate drawbacks within the prior art relating to EEG-based brain activity monitoring devices, and more particularly to portable systems for brain activity recording, storage, analysis, and neurofeedback that operate in conjunction with an application and web-based framework for more extensive storage and analysis.
In accordance with an embodiment of the invention there is provided a method comprising: receiving electroencephalography (EEG) data relating to a user; generating processed EEG data by applying a first processing algorithm to the obtained EEG data; transferring the processed EEG data to a remote storage device together with at least a unique identity of the user.
In accordance with an embodiment of the invention there is provided a system comprising:
a first interface operating according to a predetermined standard for receiving electroencephalography (EEG) data relating to a user from a portable electronic device associated with the user; a storage device for storing the received EEG data; a microprocessor for executing a software application applying at least a first processing algorithm to a predetermined portion of the stored EEG data to generate processed EEG data and establishing an outcome in dependence upon at least the processed EEG data; a second interface for communicating the outcome to the portable electronic device for presentation to the user.
In accordance with an embodiment invention there is provided a device comprising:
a headband to fit around the back of a user's head; a pair of arms connected to the headband projecting forward to fit along the sides of the user's head and for supporting the front of the device by the user's ears; a pair of support guides, each coupled to an arm; a pair of first electroencephalography (EEG) sensors, each first EEG sensor disposed upon a support guide; a pair of second EEG sensors disposed within the headband.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the present invention will now be described, by way of example only, with reference to the attached Figures, wherein:
FIGS. 1A through 1C depict EEG sensor electrode configurations for obtaining EEG signals from a user with non-amplified “passive electrodes”;
FIG. 1D depicts a drive circuit for amplifying an EEG signal obtained with an EEG sensor to convert “passive electrodes” to “active electrodes” with increased resistance to movement;
FIG. 1E depicts an exploded view of a novel sensor electrode configuration according to an embodiment of the invention;
FIG. 2A depicts an exemplary EEG system configuration according to an embodiment of the invention;
FIGS. 2B and 2C depict exemplary configurations of EEG detection and EEG Control Systems as depicted within FIG. 2A ;
FIGS. 3A and 3B depict an EEG headset configuration according to an embodiment of the invention providing extended user wearability according to embodiments of the invention;
FIG. 3C depicts an EEG headset configuration according to an embodiment of the invention providing extended user wearability according to embodiments of the invention;
FIG. 4 depicts an exemplary process flow for processing EEG signal(s);
FIG. 5 depicts an exemplary EEG system configuration according to an embodiment of the invention comprising EEG embedded headset, local EEG processing module, and remote EEG processing module;
FIG. 6 depicts an exemplary EEG signal amplification/filter block for use within an EEG embedded headset according to an embodiment of the invention;
FIG. 7 depicts a mapping of EEG sensor locations from prior art research for minimal electrodes;
FIG. 8 depicts the EEG sensor locations of an EEG headset according to an embodiment of the invention for minimal electrodes and high user acceptability;
FIG. 9 depicts typical EEG bands for an adult in each stage of sleep;
FIGS. 10A and 10B depict a typical EEG spectrum for an adult together with the typical EEG bands for an adult;
FIG. 11 depicts a communications network supporting communications with EEG embedded headsets, local EEG processing module, and remote EEG processing modules according to an embodiment of the invention;
FIG. 12 depicts schematically the electronic elements of an EEG embedded headset, local EEG processing module upon a user's portable electronic device and ancillary network access point according to an embodiment of the invention;
FIG. 13 depicts exemplary screenshots for Transcend™ implemented using a software development kit exploiting techniques and devices according to an embodiment of the invention; and
FIG. 14 depicts an exemplary layout for a software development kit exploiting techniques and devices according to an embodiment of the invention.
DETAILED DESCRIPTION
The present invention is directed to EEG-based brain activity monitoring devices, and more particularly to portable systems for brain activity recording, storage, analysis, and neurofeedback that operate in conjunction with an application and web-based framework for more extensive storage and analysis.
The following description provides exemplary embodiment(s) only, and is not intended to limit the scope, applicability or configuration of the disclosure. Rather, the following description of the exemplary embodiment(s) will enable those skilled in the art to implement an exemplary embodiment. It being understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope as set forth in the appended claims.
A “portable electronic device” (PED) as used herein and throughout this disclosure, refers to devices used for wireless communications and other applications that requires an energy storage unit such as a battery for power. These include (but are not limited to) cellular telephones, smartphones, personal digital assistants (PDAs), portable computers, pagers, portable multimedia players, portable gaming consoles, laptop computers, tablet computers, and electronic readers.
A “fixed electronic devices” (FED) as used herein and throughout this disclosure refer to wireless and/or wired devices used for communications (and other applications) that require a connection to a fixed interface to obtain power. These include (but are not limited to) laptop computers, personal computers, computer servers, electronic kiosks, stationary gaming consoles, digital set-top boxes, Internet-enabled appliances, Internet-enabled televisions, and stationary multimedia players.
An “EEG Assembly” as used herein and throughout this disclosure, refers to an assembly worn by a user that includes one or more EEG sensors for recording changes in scalp voltage resulting from brain activity (EEG data). Certain embodiments of the invention include one or more reference sensors—generally placed on one or both of the ears, the nose, or potentially the mid-neck to upper-neck—for recording reference signals. These signals are intended to be subtracted from the voltages recorded from the EEG sensor. Other embodiments may instead use an “average reference,” where no specific reference electrode is used, with the average signals from all electrodes used as a reference instead. Various embodiments of the invention may include assemblies which are interfaced wirelessly and/or via a wired interface to an associated electronics device (either PED or FED) providing at least one of: pre-processing, processing, and/or analysis of the EEG data discretely or in conjunction with the reference signal(s). Said EEG Assembly may be wirelessly connected and/or wired to an ancillary electronic device, such as a PED or FED, to provide recording, pre-processing, processing, and analysis of the EEG data discretely and/or in conjunction with reference signal(s); as well as supporting other functions including, but not limited to, Internet access, data storage, sensor integration with other biometric data, user calibration data, and user personal data. Such an EEG Assembly may be employed with or without additional elements such as a headset and/or support.
Referring to FIG. 1A there are presented perspective 100 A and sectional views 100 B of an EEG electrode which is an example of an EEG electrode, and does not account for all variations allowing exploitation of a metal contact to record skin/scalp voltage. The EEG electrode may be one or more different shapes including, but not limited to, circular, elliptical, square, rectangular, triangular, regular N-sided polygon, and irregular N-sided polygon. Alternatively, it may take the take the form of clips/snaps that fasten to the skin, or a small needle inserted through a small electrode base or EEG cap. As depicted, the EEG electrode comprises a base 103 formed, for example, of foam, a fabric, a nonwoven fabric, or a tape including synthetic polymer and natural polymer, and is optionally provided with an acryl-grouped biocompatible adhesion paste deposited on one surface thereof; a stiffener 102 made of polymer and attached to the other surface of the base 103 for preventing evaporation of moisture; a snap 101 made of metal, for example brass and installed at the central portion of the stiffener 102 , and an electrode element 104 , for example made of plastic reinforced with glass fiber and deposited with silver/silver chloride, the snap 101 and the electrode element 104 being fixed to each other; a conductive hydro gel adhesive agent 105 coating the exposed surface of the electrode element 104 ; and a release film 106 attached to the hydro gel adhesive agent 105 and the remaining adhesion paste on the base 103 for protecting the hydro gel adhesive agent 105 and the remaining adhesion paste on the base 103 . The EEG electrode may optionally use a conductive adhesion gel, glue, or adhesive tape for attaching the assembly to the skin, for example on the forehead, temple, and/or one earlobe or both earlobes.
Although FIG. 1A does not depict this, an EEG electrode may also optionally use a pad for soaking in a conductive liquid solution for improving conductivity between the scalp and electrode, or optionally require soaking in a liquid solution for improving conductivity without the presence of a pad. Other EEG electrodes may also optionally use a thin needle to produce connectivity between the electrode and the skull surface—rather than the scalp. The skin below the location where an EEG electrode is placed may optionally be lightly scraped to remove detritus such as dead skin cells that may lower conductivity between the scalp and the EEG. In cases where an EEG electrode uses a conductive adhesion gel or glue, and/or a conductive liquid solution or needle, and/or requires scraping of the skin below the electrode, a period of time for preparation may be required. These techniques for increasing conductivity and all aforementioned methods of preparation can also be used with active electrodes, such as that depicted in FIG. 1B 100 C.
Referring to FIG. 1B there is depicted a cross-sectional view 100 C of an example of an active dry sensor electrode for the measurement of scalp voltage in accordance with an embodiment of the invention comprising an active electrode 154 , a resilient member 155 , such as a spring, an amplification circuit 157 , a main body 153 , and a holder 152 and a cap 151 necessary for fixing the sensor module 100 C when the sensor module 100 C is installed in a headset 160 . The active electrode 154 is interlocked with the cap 151 , and vertically slides relative to the cap 151 . The upper part of the active electrode 154 is exposed to the outside to contact skin of a user, such as via optional disposable pad 150 . The main body protrusion which restricts the movement of holder 152 which latches to the cap 151 when inserted so that the lower portion of the active electrode 154 projects from the surface of the cap 151 when attached to retain the active dry sensor electrode within the headset 160 . The active electrode 154 is the element either directly contacting the scalp wherein the active electrode 154 measures a biomedical signal, for example, EEG, or via optional disposable pad 150 . The resilient member 155 is retained laterally within the active dry sensor electrode by retainer 158 whilst the amplification circuit 157 is mounted upon spacer 156 within the main body 153 . Main body 153 may be sectioned such that it assembles laterally around the active electrode 154 , amplification circuit 157 , resilient member 155 etc. or section for assembly vertically, e.g. by attaching a second part of the body to the first when the resilient member 155 is inserted through the amplification circuit 157 and retainer 158 assembled.
Accordingly, since the reliability of the measured value of the EEG signal depends on the active electrode 154 having good contact with the scalp, then the active electrode 154 may be plated with another material such as gold, silver, or indium tin oxide (ITO) to improve the conductivity of the active electrode 154 and allow electrical current to easily flow through the active electrode 154 . Similarly, optional disposable pad 150 would be electrically conductive, such as for example through the use the use of an electrically conductive polymer and / or the use of a coating with an electrical conductor such as a metallic thin film, ITO thin film, or electrically conductive polymer. As depicted, amplification circuit 157 receives the electrical voltage from the user's scalp and electrically amplifies the signal using an amplification circuit such as that depicted in respect of FIG. 1D or in FIG. 4 . Active electrode 154 may similarly be formed from a conductive plastic or be a plastic with a conductive coating. Optionally, the surface of the active electrode 154 and / or optional disposable pad 150 may be concave or toothed so that the contact surface has stable, long-lasting contact with the scalp of the user. A concave active electrode 154 may for example be used to directly contact a bare portion of the scalp whilst a toothed active electrode 154 may provide contact to a portion of the user having hair on the scalp.
Referring to FIG. 1C there is depicted an active electrode 100 D according to an embodiment of the invention. As depicted, active electrode 100 D comprises a carrier 175 onto which a flexible circuit 174 is mounted. On the first and second contact pads 176 and 178 are embedded the first and second contacts 177 and 179 , respectively, which are coupled via carrier 175 and flexible circuit 174 to integrated circuit (IC) 172 . Also mounted to flexible circuit 174 are discrete components 171 representing inductors, resistors, and capacitors required for the IC 172 . Within active electrode 100 D IC 172 is coupled to a remote device via cabling 173 which may for example include power, signaling to IC 172 , and signaling from 172 . Optionally, IC 172 may be locally powered through a thin film battery source rechargeable wirelessly and/or include a wireless interface such that signaling is provided wirelessly. Optionally, cabling 173 may provide low voltage DC power only. First contact 177 in conjunction with first contact pad 176 may provide an EEG sensor, with second contact 179 and second contact pad 178 providing a second EEG sensor for detecting scalp voltage/receiving EEG data at a location extremely near to the location where first contact 177 and first contact pad 176 are detecting scalp voltage/receiving EEG data. Optionally, second contact 179 and/or second contact pad 178 can be omitted, or alternatively, first contact 177 and/or first contact pad 176 can be omitted. Also, first contact 177 , first contact pad 176 , second contact 179 , and second contact pad 178 can be used in tandem to act as one single electrode. An average voltage can be taken between first contact 177 and first contact pad 176 , and second contact 179 and second contact pad 178 to produce a single voltage reading of greater accuracy than that which could be taken from a single contact electrode.
Referring to FIG. 1D there is depicted an exemplary amplifier circuit for an EEG sensor such as depicted in respect of FIGS. 1A through 1C wherein an EEG electrode 185 has its output coupled to a second differential amplifier 180 B wherein the second input of the second differential amplifier 180 B is the output of a first differential amplifier 180 A which is coupled to a reference signal, denoted as V REF , such that the output of the second differential amplifier 180 B is a reference corrected signal, V OUT . As depicted both the first and second differential amplifiers 180 A and 180 B respectively are coupled to positive and negative power rails V DD and V SS respectively. The reference signal, V REF , may be derived for example from a precision voltage reference, a voltage derived from an IC such as IC 172 , and/or from a reference sensor/electrode.
The electrical signal emitted from the scalp that EEG data is comprised of is very weak: in the order of microvolts. Accordingly, it is not easy to detect such signals with the typical amount of noise which may arise from multiple sources, including but not limited to the circuit itself, external sources such as wireless transmitters, background skin voltage, and non-relevant sources of change in voltage in the detected signal, for example those arising from the sensors such as dry contact sensor(s), wet contact sensor(s), or non-contact EEG sensor(s). Accordingly, some embodiments of the invention reduce the noise using a reference electrode otherwise known as a “common reference” meaning an electrode placed at a location unaffected by the electrical activity of the brain, but still affected by all of these sources of noise. The voltage detected by the reference electrode is subtracted from the voltage detected by the EEG electrode, which results in a waveform that only contains sources of variance in voltage that are unique to the EEG electrode, which means only brain activity-related changes in voltage should be present. Other embodiments of the invention reduce the noise using an “average reference” method instead, in which the average voltage detected by all electrodes is subtracted from each individual electrode's voltage. Since brain activity varies more across different locations on the skull than other sources of variance in the voltage, subtracting the average voltage across all electrodes should only result in subtracting waveforms that don't occur as a result of brain activity (since the brain-activity related waveforms should be relatively unique at different places on the head).
Now referring to FIG. 1E there is depicted a unique electrode design created by the inventors that makes it easier to read scalp voltages / receive EEG signals through the user's hair. As depicted, multiple small conductive metal cylinders / wide-topped flat pins 187 are soldered onto a small conductive metal plate 188 . Although 13 wide-topped flat pins 187 are depicted in FIGS. 1E , the number of pins 187 soldered onto the conductive mental plate 188 can vary, as long as there are at least 3 pins to prevent piercing the skin of the scalp. The bottom of small conductive metal plate 188 (the side opposite to the conductive pins 187 ) is attached to an electrically insulating plate 189 . A metal “lid” 186 with holes 190 punched in it that directly fit the configuration of pins 187 is attached to the other side of conductive metal plate 188 , with pins 187 slid through the holes 190 . The inner rim of metal “lid” 186 is soldered to the inner rim of electrical insulator plate 189 . A wire 191 may pass through a hole 191 (depicted in Figure lE) in electrical insulator plate 189 to connect to electrical conductor plate 188 .
The pins 187 and conductive metal plate 188 in FIG. 1E can be made out of any solid conductive material or combination of materials, including (but not limited to) metals such as copper, silver, silver chloride, aluminum, tin, gold, iron; metal chlorides such as silver chloride; conductive polymers such as polyaniline, poly(3,4-ethylenedioxythiophene)/PEDOT, or polyphenylene vinylene; plated metals such as tin-plated copper, gold-plated copper, or silver-plated copper; conductive metal alloys such as copper-magnesium alloy, lead-tin alloy, tin-lead-silver alloy, copper-silver-alloy, or copper-silver-zinc alloy; or carbon-based conductive materials such as graphite, graphene, colossal carbon tubes, conducting carbon nanotubes, conducting metallic nanotubes, or IsoNanotubes™. Electrical insulator plate 189 can be made out of any non-conductive/insulating material or combination of materials, including (but not limited to) glass; electrical insulation paper; ceramics such as porcelain, aluminium oxide, or sintered beryllium oxide; non-conductive polymers/plastic such as polyvinyl chloride (PVC), Kapton, ethylene tetrafluoroethylene (ETFE), or Teflon; or nonconductive composite materials. Metal lid 186 can be made of any material that can be strongly bonded to electrical insulator plate 189 .
FIG. 2A depicts a block diagram illustrating an EEG system in accordance with some embodiments of the invention which comprises an EEG Detection System 230 for picking up EEG signals from a user, an EEG Control System 210 for doing initial processing on the data and preparing it for digital transmission, and a System under Control (SUC) 250 , which is any hardware or software that can be communicated with by (and can alter its behavior in response to) EEG data outputted from EEG Control System 210 . Some embodiments of the invention can have each of these components built into a separate device, rather than having all 3 components built into the same system. In one exemplary embodiment, EEG Detection System 230 is contained in an EEG headset that is attached in a wired or wireless configuration to a separate device containing EEG control system 210 , which sends EEG data via another wired or wireless interface to a PED for example. Other embodiments may integrate the EEG Control System 210 , EEG Detection System 230 and SUC 250 into one device. Other embodiments have the EEG Control System 210 and EEG Detection System 230 integrated into a single device generally a one-piece headset, for example, that detects EEG signals from the skull and transmits them to SUC 250 either through a wired or wireless interface. Still other embodiments have the EEG Detection System 230 in its own standalone device which transmits completely unprocessed EEG data to a PED or FED containing an implementation of EEG Control System 210 and SUC 250 which may be implemented in hardware and/or software.
In some embodiments of the invention, the EEG Control System 210 sends corresponding control signal(s) to the SUC 250 , whilst in other embodiments the EEG Detection System 230 sends raw EEG signal data, or in some embodiments processed EEG signal data (e.g. to filter out noise) to the EEG Control System 210 . FIG. 2B depicts a functional diagram illustrating EEG Control System 210 in accordance with some embodiments of the invention wherein the EEG Control System 210 includes an EEG Detection Communications 211 module for communicating with the EEG Detection System 230 , a Processor 212 for applying analysis algorithms to EEG signals detected by EEG Detection System 230 in order to, for example, generate spectral power values for wavebands (delta, theta, etc.) based on specific frequency ranges, an Output Control 213 for communicating with the SUC 250 , a Local Communications 214 for communicating with one or more local devices and/or interfaces, and a Data Storage 216 which may for example provide functionality for storing received EEG signal samples and associated timing data such as for the audible, visual and tactile cue patterns/frequencies etc. These are linked via an internal Communication Link 2151 n certain embodiments of the invention, EEG Control System 210 contains a component for sending detected EEG signal samples to a computer, which in some embodiments includes a processor configured to run algorithms—such as spectral decompositions—on the EEG signals it receives from EEG Detection System 230 . Following the analysis, the microprocessor can then provide the resulting metrics, such as for example spectral power values for specific wavebands, to other components of the system, which can include the EEG Control System 210 and/or the SUC 250 based on the results of the analysis of the EEG signal samples. In some embodiments, all or just a portion of the analyses of the EEG signal samples are performed by the programmed computer, while in other embodiments, all or just a portion of the analyses of the EEG signal samples are performed in EEG Detection System 230 , EEG Control System 210 , or both; e.g., using an Application Specific Integrated Circuit (ASIC) or Field Programmable Gate Array (FPGA) integrated with or in communication with EEG sensors. Following the analyses, the EEG data can be put to functional use, such as to e.g. directly control the device or to communicate the user's mental state.
FIG. 2C depicts a functional diagram illustrating an EEG Detection System 230 in accordance with some embodiments of the invention wherein the EEG Detection System 230 includes a Processor 232 , e.g., an FPGA, ASIC, or microprocessor, an EEG Sensor 231 , an EEG Reference Sensor 234 , an Output Control 233 for communicating with EEG Control System 210 , and an internal Communication Link 235 . Measured EEG signals are provided to the EEG Control System 210 by Output Control 233 following local processing by Processor 232 and appropriate voltage correction based upon the associated EEG Reference Sensor 234 . Calibration data, user data, information about processes currently in execution by Processor 232 , and other data associated with the EEG Detection System 230 are stored within local Storage 236 . In some embodiments, a continuous stream of EEG signal samples are detected and provided to the EEG Control System 210 , whilst in other embodiments these are periodically transmitted, averaged and filtered prior to transmission, and only transmitted when/if certain predetermined criteria are met.
Prior to analysis and all other forms of data cleaning and pre-processing, the voltage of the reference electrode is subtracted from that of the EEG electrode(s). As discussed earlier, this immediately removes a great deal of noise from the data. The data is then run through a variant of the Discrete Fourier Transform, e.g. a Fast Fourier Transform (FFT) within some embodiments of the invention, to decompose the EEG data into constituent EEG waveforms/neural oscillations. The result of the FFT is then spectrally analyzed using high- and low-pass filters that are applied to restrict the EEG data to a frequency range where brainwave activity is relatively easy to identify. For example, typically 1-50 Hz is wide enough to include all of the classic EEG wavebands (e.g. theta, delta), but not so wide as to include frequencies that are excessively prone to contamination by artifacts. Artifacts are voltage spikes and/or troughs caused by phenomena other than brain electrical activity—such as small muscle movements or heartbeat. Although the data will still be affected by artifacts regardless of what frequency range is chosen, restricting the range as such reduces the degree of contamination. Optionally, the EEG data may be filtered prior to the FFT process.
Accordingly, it would be evident that the inventors primarily exploit an EEG analysis system based on neural oscillations/“non-phase-locked induced rhythms” to determine the user's background mental state, rather than using a system based on examining evoked potentials/evoked activity, such as those that focus on the analysis of event-related potentials (ERPs), steady-state evoked potentials (SSEPs), visual evoked potentials (VEPs), or steady-state visual-evoked potentials. Although other embodiments can include functionality relating to some of these other frameworks for EEG data analysis, they are not necessary, and do not play a primary role in any core aspect or feature of this invention.
Consider “Introspect” a multi-purpose software bundle by the inventors that as part of its features provides users with a series of EEG-derived numerical metrics,—e.g. a numeric rating of how positive or negative their current mood is, so that they can track aspects of their brain health. Scores on the main functions/metrics of interest discussed in greater detail below, are established entirely through EEG waveform analysis. “Introspect” uses these scores to recommend specific built-in neurofeedback-based exercises intended to improve areas of weakness for the user. These EEG waveform-dependent results will be reported to users in the form of visual elements such as graphs that show progress in specific areas over time, which will be displayed on a dashboard-type User Interface (UI). Areas of interest can be selected by users for inclusion on the dashboard, to avoid displaying unnecessary information (e.g. only epileptics would be interested in seizure data). The portability of the headset and software will allow users to take readings throughout the day, including if users activate the option reminders to perform scans. This will help prevent all readings from being taken in the same states of mind (e.g. states in which users are self-motivated enough to use the software), and/or at the same general times of day (e.g. before and after work). Avoiding these issues will allow “Introspect” to collect data that is much more representative of the user's day-to-day mental life, i.e. the data is more meaningful and thus useful. “Introspect” may trigger self-report measures, for example based upon questionnaires presented randomly throughout the day, at requested intervals, and/or when users choose to fill them out. For example, a clinical neurophysiologist monitoring a user exploiting more extensive software analysis algorithms than those on the user's PED may trigger such questionnaires on their own or in combination with the “Introspect” software. It would be evident that this information may be used in tandem with the EEG readings to generate more comprehensive data and more accurate results. This more comprehensive data would result in neurofeedback exercise suggestions that are better-targeted to the user's mental weaknesses, resulting in greater improvements.
Mental states which the EEG waveform analysis roughly quantifies and displays to users in the form of a metric may include, but are not limited to, stress, relaxation, concentration, meditation, emotion and/or mood, valence (positiveness/negativeness of mood), arousal (intensity of mood), dominance (feeling of “control”), anxiety, drowsiness, state mental clarity/acute cognitive functioning (i.e. “mental fogginess” vs. “mental clarity”, creativity, reasoning, memory), sleep, sleep quality (for example based on time spent in each stage of sleep as easily detected with EEG), amount of time asleep, presence of a seizure, presence of a seizure “prodromal stage” (indicative of an upcoming seizure), presence of stroke or impending stroke, presence of migraine or impending migraine, severity of migraine, heart rate, panic attack or impending panic attack.
Biomarkers for numerous mental and neurological disorders, to aid in screening and diagnosis, may also be established through biosignal detection and analysis, e.g. using EEG signals. In addition, multiple disorders are expected to have detectable EEG footprints with increased EEG sample acquisition for a single user and increased user statistics/data. Such disorders may include, but are not limited to, depression, bipolar disorder, generalized anxiety disorder, Alzheimer's disease, schizophrenia, various forms of epilepsy, sleep disorders, panic disorder, ADHD, and autism.
Accordingly, after EEG data obtained from a user is pre-processed as discussed previously, the spectral power of each selected frequency EEG band is extracted on a block-by-block-basis, with blocks defined as stretches of raw EEG voltage value samples. Blocks 1 second long with approximately 512 voltage samples are employed according to an exemplary embodiment of the invention although different block lengths and voltage samples/block can be used. The specific frequency ranges of each EEG band in an exemplary embodiment of the invention are delta at 1-3Hz, theta at 4-7Hz, low alpha at 8-9Hz, high alpha at 10-12Hz, low beta at 13-17Hz, high beta at 18-30Hz, low gamma at 31-40Hz, and high gamma at 41-50Hz. Other embodiments of the invention can use other frequency bands, such as those depicted in FIGS. 9 and 10B . Optionally, this determination may be weighted, for example through a cluster analysis process, with additional information derived from other biosensors, location information, and other information derived by the overall EEG system associated with the user such as described below for example in respect of FIG. 12 wherein the user's PED may for example associate heart rate and pulse biosensor information together with location in determining a user's mental state. Optionally, the EEG data may be pre-processed, or left raw, before being processed in preparation for feature classification, i.e. mental state classification using an FFT process described for the exemplary embodiment of the invention although other feature classification processed may be employed. See FIG. 10A for an example of weightings of spectral content determined based upon FFT bin data for use in e.g. finding spectral power values for each selected EEG frequency band (as described above).
The amount of variance in the EEG wave that can be accounted for by each brainwave type may be calculated, producing numeric values for each selected EEG frequency band, generally based upon relative weightings of the spectral power in each band as listed in Table 3 and discussed supra. Based upon analysis of the resulting data generated for each frequency band and their weightings against one another, one or more features may then be extracted. An example of a feature extraction rule, which is simpler than those which will be implemented with the commercial products of the inventors, is given by Equations (1A) and (1B) for roughly quantifying a user's level of concentration.
(( N THETA −1)<(2 ·N BETA )) then Conc=(2 ·N BETA −N THETA ) (1A)
(( N THETA −1)≧(2 ·N BETA )) then Conc=(1 /N BETA ) (1B)
where Conc is the weighting given to concentration and N BETA and N THETA are the numeric values for beta and theta brainwaves respectively.
It would be evident that other algorithms may be exploited. Examples of two novel two novel feature extraction rules established by the inventors are described below for mental clarity and meditation values.
Mental Clarity Extraction Algorithm: This exploits the low beta (13-17 Hz), low gamma (31-40 Hz), and mid gamma (41-50 Hz) ranges of EEG activity. Power in each waveband is fitted to a curve that removes artifacts related to the hardware of the EEG device and converts the raw EEG voltage data into a normalized 1 to 100 scale. These modified EEG values are then scaled against one another to form a conglomerate score for mental clarity. Equations (2)-(5) provide an exemplary embodiment of this metric developed by the inventors using 1s epochs of data to generate waveband values.
Adj β L = ( ( - ( 1.06 β L + 75 ) = 80 ) - ( β L - 30 ) ( β L - 70 ) 210 + 10 ) + 15 ⅇ - 4.1 ⅇ - 0.25 ( β L - 70 ) ) ( 2 ) Adj γ L = ( ( - ( 1.06 γ L + 75 ) = 80 ) - ( γ L - 30 ) ( γ L - 70 ) 210 + 10 ) + 15 ⅇ - 4.1 ⅇ - 0.25 ( γ L - 70 ) ) ( 3 ) Adj γ M = ( ( - ( 1.06 γ M + 75 ) = 80 ) - ( γ M - 30 ) ( γ M - 70 ) 210 + 10 ) + 15 ⅇ - 4.1 ⅇ - 0.25 ( γ M - 70 ) ) ( 4 ) Score CLARITY = 3 Adj γ M + 2 Adj γ L + Adj β L 6 ( 5 )
where Adjγ L is the current adjusted power in the low-beta EEG band; Adjβ L is the current adjusted power in the low-gamma EEG band; Adjγ M , is the current adjusted power in the high-gamma EEG band; β L is the current (unadjusted) power in the low-beta EEG band; γ L is the current unadjusted power in the low-gamma band, γ M is the current unadjusted power in the high-gamma band; and Score CLARITY is the clarity score for the current 1 second epoch.
Meditation Value Algorithm: This involves the use of a metric for relaxation, generally on a scale of 1 to 100, and a metric for attention. The meditation value is generated by taking whichever of these two values is the lowest, and then in some cases adding a portion of the distance between the lower value and higher value. Meditation is a state of relaxed attention, and it is thus especially important that both be present for a state to be considered meditative. We considered meditation quality primarily in terms of which value is the weakest to account for the essential requirement that both be present. The metrics for relaxation and attention may be generated using algorithms known within the prior art.
In addition to the algorithms discussed supra Personal Neuro Devices algorithms are primarily centered on spectral density analysis of raw EEG data (scalp voltage). Such analyses involve estimating the strength/spectral power of specific selected wavebands/EEG frequency ranges (with ranges measured in Hz e.g. 3-8 Hz), then sometimes comparing them against each other, e.g. calculating the ratio of the 0-4 Hz waveband's spectral power to that of the 10-12 Hz band. Because so many different waveband ranges can be selected, and so many comparisons made between selected wavebands' power values, spectral analysis on its own is able to extract a huge number of discrete features from the raw EEG data.
PND's algorithms may, for example, exploit a predetermined set of standard wavebands ranges such as those commonly used in EEG research or alternatively specific waveband ranges may be established for specific algorithms to enhance their accuracy based upon extended analysis. Standard wavebands may include, for example, the mu rhythm (˜8-14 Hz), the sensorimotor rhythm (˜12-15 Hz), and wavebands classified as the delta (˜0-4 Hz), theta (˜4-8 Hz), alpha (˜8-12 Hz), low alpha (˜8-10 Hz), high alpha (˜10-12 Hz), beta (˜12-30 Hz), low beta (˜12-20 Hz), high beta (˜20-30 Hz), and gamma (˜30-50 Hz) bands. These common bands can be particularly useful as in many instances the ranges are defined in the research literature based on mental phenomena they are closely coupled to. For example, high spectral power levels in the “high beta” waveband is associated with anxiety because higher spectral power is seen in this range in anxious subjects and because neurofeedback techniques that reduce spectral power in this frequency range can reduce anxiety.
In addition to spectral power based determinations asymmetry-based methods may be employed in isolation or in conjunction with spectral power analysis to compare activity occurring in electrodes in one part of the brain with activity in electrodes in another. This comparison may, for example, be left and right hemispheres of the brain, due to the importance of left-right asymmetry for detection of mood valence (positiveness versus negativeness of mood. Since this has major implications for the detection and possible treatment of mood disorders, i.e. one of the world's biggest medical causes of mortality and lost productivity this is an important expansion in the analysis technique.
Entropy & fractal dimension analysis may also be applied to provide analysis of the complexity and irregularity of an EEG signal. In other words, they measure how “chaotic” the signal is. More random-seeming signals have a higher number of fractal dimensions, and higher entropy scores in general. These methods can be particularly useful for us because of the ease with which they can be implemented using pseudocode methods of calculating a data set's fractal dimension value. Such analysis may also be particularly effective when there are a restricted number of electrodes and when used in combination with other analytical methods, this type of analysis is able to generate a fair number of neurometrics with a reasonable degree of accuracy. These can include 2 dimensions of emotional state, namely arousal and valence together with attention levels.
Alternatively, linear time domain-based features, typically simple features, can be extracted from EEG data which have predictive value for some Neurometrics as well as disorders, stages of sleep, etc. particularly when used with other more complex feature analysis. Accordingly, through a combination of local algorithmic features, i.e. on the user's PED, and remote algorithmic features, i.e. those processing statistically or algorithmically extracted EEG data with machine learning classifiers running on remote servers, e.g. a cloud sourced backend, then these simpler features will essentially augment the more complex ones, to produce an overall greater classification accuracy. Examples of linear time-domain-based features that may be implemented/provided include, but are not limited to, the following:
Zero-crossing rate. This refers to how many times the voltage passes from a negative-to-positive or positive-to-negative value per second. Inclusion of this measure has been shown to increase the accuracy of ensemble classifier-type algorithms that detect stages of sleep.
Further this feature is reasonably effective on its own at detecting certain discrete features in sleep that relate to sleep quality, such as sleep spindles.
Mean (average) voltage. Variance. Skewness. Kurtosis. Useful in e.g. artifact removal. Average Peak Amplitude. Relating to average distance between consecutive peaks, with peaks being either extreme minimum or maximum voltages where its temporally neighbouring voltages on both sides, i.e. voltages recorded within a few milliseconds before and after the “peak” point are all higher (for minimum) or all lower (for maximum). This feature is useful for increasing accuracy of sleep stage detection when used with other features in classifier algorithms or for helping classify what task someone is performing (albeit in artificially restricted settings).
Amongst the neurometric-detection algorithms in use by PND are
Clarity: wherein the “clarity” neurometric is based directly on the power values in the upper alpha range of EEG brainwaves (10-12 Hz) wherein power values produce higher scores. Individuals with post-concussion syndrome show reduced power in this range which may be related to impaired top-down processing, or an impaired ability to direct attention internally. Attention: wherein analysis of alpha and beta waves extracted from the raw EEG voltages provides a method of calculating users' attention levels. Relaxation: where frontal alpha and theta bands provide data for the analysis of relaxation and mindfulness. Different weights may be given to each band in the calculation of the index as the appearance of activity in each of the bands also depends on the expertise of the meditator. For example, if the user is able to produce alpha consistently for a period of time (which often dominates the brain activity of a novice meditator), additional weighting may be added to the theta band (seen in intermediate meditators) to encourage further relaxation. Mindfulness: wherein “mindfulness” values are calculated through a combination of their relaxation and attention levels. For example, an algorithm according to the inventors begins by subtracting the value of the lower metric (between attention and relaxation) from that of the higher metric and dividing the result by 3. This result is then added to the value of the lowest metric. Accordingly, a lower weighting is given to the higher of the two metrics simply because both relaxation and attention must be present for the user to be in a state of mindfulness; the score rewards users that concurrently increase both more than if a simple average of attention and relaxation was employed. Emotions: Certain emotions can be detected using restricted-electrode EEG through the combining of information from multiple EEG features that are indicative of emotional state to produce a strong prediction through ensemble classification techniques, especially those involving “boosting”, such as bagging and AdaBoost. Examples of weak but significant predictors include differences in the symmetry of brain activity in relation to mood, with negative moods somewhat tending to produce greater activity in the right hemisphere, and positive ones in the left, although it is reversed in some people. Calibration methods exploited by PND include experience sampling, where the software periodically asks the user to rate how they feel a few times during the day, then compares the surrounding EEG activity to the self-rated mood to determine which direction the asymmetry goes in the user. Other predictors include the coupling between EEG delta and beta oscillations is enhanced in anxious states and the alpha peak frequency reducing during sadness and fear, but increasing during happiness and anger. Visuospatial Ability: the algorithm is based upon the power in the upper alpha band. Memory: wherein the algorithm for measuring memory activity is based on increasing power in the theta and decreasing power in the alpha bands. Processing Speed: where the calculation of an index for mental processing speed is based on the beta wave given the relation between beta wave activity and reaction times.
Other neurometric detection algorithms in use by PND relate to sleep quality, sleep quantity detection, stress, depression:
Sleep Quantity: wherein sleep has characteristic patterns of EEG activity wherein each pattern of the multiple patterns is associated with a different stage and hence can be calculated simply by adding up the cumulative quantity of time any one of these patterns is present. Sleep Latency: also referred to as quantity of time it takes to fall asleep. Ultra-low sleep latency (0-5 minutes) is closely linked to fatigue and daytime feelings of sleepiness and is also a biomarker of narcolepsy. In contrast very high sleep latency indicates the presence of primary insomnia. Sleep Quality: Determined by the amount of time spent in each stage of sleep, and sleep continuity. Although, a very simple indicator can be based upon the time spent in stage 4 (slow wave) sleep and fewer nighttime awakenings Daytime Stress. Sleep EEG data cannot on its own detect daytime stress, but it can provide extra information that increases our ability to detect it when analyzed in tandem with daytime EEG data as stress within the preceding day is indicated by a reduction in REM, slow wave sleep, and overall sleep efficiency/sleep quality, as well as an increase in the number of middle-of-the-night awakenings. Depression: Where a user self-reports stressful events during the day but does not show the characteristic sleep pattern indicative of preceding-day stress, it's predictive of depression and may be a factor in screening for symptoms of depression wherein the degree of change in sleep pattern following a (self-reported) stressful day will be included in a multifactorial analysis as a single predictive factor. Further, biomarkers for depression have been identified in sleep EEG data separate this stress-related effect.
Introspect™ the multi-purpose software bundle by the inventors performs complex multifactorial analyses to provide users with a series of EEG-derived numerical metrics exploiting local and remote processing with backend algorithms and historical data. Accordingly, through the local and remote determinations of patterns in their data, such as potential underlying disorders (for screening, not diagnosis), Introspect™ will suggest a user see a doctor for a particular disorder if there are enough factors in place to suggest it may be present. In many instances the more accurate neurometrics for a user cannot be calculated on a PED and accordingly embodiments of the invention exploit neurofeedback based on quantitative EEG (qEEG) which is utilized in conjunction with cloud based backend processing via learning algorithms.
Quantitative EEG is an approach to EEG analysis, particularly neurofeedback, which requires the storage of large quantities of normative EEG data. qEEG involves taking and storing scans from a large pool of a certain type of research subject doing a particular task. Most commonly, the subject group is “healthy people” with no brain disorders, and the task simply a “resting state” wherein no task is explicitly defined except whether eyes should be open or closed. Features, such as power values in different wavebands, basic statistical components (e.g. mean voltage), and entropy scores etc. are then extracted from each subject's data. Average values of each feature over the whole scan are determined for each user. Whole-scan averages are then averaged between all users in the database, which generates normative values for each EEG feature in that population for that task. The more subjects and sessions there are stored in the database, the more accurate the normative scores will be. Accordingly, Introspect by virtue of pushing user data to cloud based and/or remote storage allows analyses to be performed upon a very large population base and further allows the population data to be divided by factors such as sex, race, and age.
Accordingly, databases established through Introspect™ can be used to automatically identify biomarkers of brain disorders, and as a result, aid diagnosis for users. Where a database of normative scores for a particular metric (on a particular task) exists for healthy subjects, a comparison can be made with average scores in a clinical population suffering from a specific disorder. Any differences found can then potentially act as biomarkers for the disorder, with their presence acting as diagnostic indicators, wherein the task plus scan can be used as a medical test to help diagnose said disorder.
Treatment-oriented neurofeedback in clinical populations can be guided by qEEG once biomarkers are identified. This involves taking the patient's EEG activity during the associated task (virtually always resting state for qEEG neurofeedback), then training them to produce EEG activity on the feature(s) similar to that generated by healthy controls. In other words, it “normalizes” disorder-associated brain activity. This has already proven effective for a number of brain disorders such as ADHD. As the Introspect™ backend database through all users contains an unprecedentedly large quantity of EEG data to be available over a diverse population of users both with and without various brain disorders. Accordingly, Introspect can average scores on a wide variety of metrics for a wide variety of sub-populations, such as specific disorders and accordingly Introspect™ provides a very beneficial tool for the application of qEEG as in many instances the resting state data can be automatically extracted from the acquired EEG data. Classifier ensemble machine learning algorithms may constantly sort incoming data to use for each new metric to create more accurate normative values for healthy controls, such that qEEG data generated through Introspect will be of higher accuracy. Introspect™ may also run ongoing clustering analyses that will automatically sub-classify users based both on psychological and demographic variables, and their EEG metrics.
Additionally, Introspect™ may for certain types of groups, e.g. a population with a particular disorder, it will instead alert when it thinks it's found a sub-population. Introspect™ through its cloud based backend processing will allow conglomeration data of different types from multiple users in order to learn how to better calculate the neurometrics of interests, screen for disorders, provide lifestyle suggestions, and provide exercise suggestions. Numerous algorithms exist for this purpose, but of these support vector machines (SVMs) are potentially of most interest as these are learning methods intended for binary classification, that is, dividing data up to determine if it does or doesn't fit into a particular group or set of groups. The initial groups are defined based on “training data”, that is, pre-classified existing data. The larger this training data set, the more accurate the SVM (as a rule of thumb). Further, SVMs can calculate the odds that their result is correct, and newer forms can perform regression classification, i.e. not just yes/no but that these return a decimal value similar to a Pearson's r value that is representative of the data point's correlation with a given group of interest. The basic idea of an SVM is to find a hyperplane (basically an n-dimensional plane—so a 3D, 4D, 5D or so on plane) that separates d-dimensional data into 2 classes. This isn't always possible in the number of dimensions of data there is, but we can get around this by increasing the number of dimensions until there is a hyperplane that can divide the data into 2 classes.
Prior art consumer EEG devices have been focused to either analysis of sleep quality, training specific patterns of activity, and/or on calculating levels of attention and relaxation/stress, which are typically exemplified by alpha, theta, beta, and delta brainwaves below approximately 30 Hz. However, real-time analysis of brainwaves with systems according to embodiments of the invention may also operate directly upon brainwaves characterized as gamma, at 31 Hz and above (although the exact frequency range of gamma may be defined as beginning at a slightly different frequency in certain cases). Neural network style learning, e.g. systems using multilayer perceptrons, may also be applied to the processed EEG brainwave data to determine particular patterns that occur with user actions/physical state such as determined through other biosensors or data acquired through the user's PED. For example, user brainwaves from playing a first person shooter game versus a motor racing game (or portions of a single game) may be associated with e.g. different FFT profiles or ratios of delta/theta/alpha/beta/alpha/gamma.
Referring to FIG. 3A there is depicted an example of a consumer orientated EEG detection system according to an embodiment of the invention established by the inventors. As depicted in first to fourth images 300 A to 300 D the user is wearing an EEG headset 330 in conjunction with a head mounted display (HMD) 350 , e.g. Google Glass™. The HMD 360 is attached to a frame 360 similar to glasses such that it is supported on the user's ears and the bridge of their nose. It also comprises a controller 370 for communicating with an electronic device, e.g. a PED, via a wireless short-range and/or personal area network protocol. The EEG headset 330 in contrast mounts to the back of the user's head and comprises arms 340 that project forward to support guides 320 that end in EEG sensors 310 . Through appropriate design of the arms 340 , support guides 320 , and EEG sensors 310 then the EEG headset 330 can measure at the temples of the user. Now referring to FIG. 3B the EEG headset 330 is depicted in isolation in first and third images 300 E to 300 G and in use in fourth image 300 H. In second image 300 F rear EEG contacts 380 are visible on either side of the rear of the EEG headset 330 such that these act in conjunction with the EEG sensors 310 . Optionally, one of more additional pairs of electrodes may be disposed within EEG headset 330 including the arms 340 , the support guides 320 , and the body of the portion of the EEG headset 330 against the rear of the user's head. The support guides 320 and/or arms 340 may be shaped and formed from a material or materials allowing a flexibility in them such that when the EEG headset 330 is placed over the user's head slight pressure of the EEG sensors 310 against the user's head results.
As depicted as an isolated EEG headset 330 allows for reduced conspicuousness when worn by the user and it may in fact be offered with rear portion in a range of colours or with clip-on covers to support a wide range of colours allowing increased blending/reduced visibility of the EEG headset 330 against the user's hair and/or skin. However, it would be evident that the EEG headset 330 may also be incorporated into, for example, other types of headwear, such as a hat, motorcycle helmet, safety helmet, and flight helmet. Alternatively, EEG Detection System 230 or a variant of EEG Detection System 230 may be integrated into/incorporated with the EEG headset 330 . Optionally, the EEG headset 330 may be incorporated with other wearable designs including, but not limited to, headphones, an application specific headset, ear-pieces, headbands, and headsets. As discussed earlier, In in many some instances the EEG sensors and all/part of the EEG Detection System 230 , EEG Control System 210 , and SUC 250 may be associated within the EEG headset 330 whilst in other embodiments of the invention the EEG Detection System 230 may be entirely/partially associated with the EEG headset 330 whilst the EEG Control System 210 and/or SUC 250 are interfaced by at least one of one or more wired interfaces, wireless interfaces and/or networks and housed within an electronic device, e.g. PED.
Accordingly, since EEG headset 330 or parts of EEG headset can be incorporated into / linked to / associated with wearable items of normal use and can thus be used during a day's regular activities, additional contextual association of the EEG determinations may be required such that the correct SUC 250 is communicated to, and that information specific to the function of the wearable item is included. For example, EEG data and metrics associated with mental states recorded whilst a user is wearing safety helmet in conjunction with EEG headset 330 or within which EEG headset 330 is integrated may include data relating specifically to user's activities whilst wearing the safety helmet such that a machine, e.g. PED, FED, or assembly line robot, when receiving the EEG data may act only when the data relating to safety helmet matches that within a database and / or a control system and / or memory location associated with the machine. Furthermore, certain item-specific information may be gathered by an item-specific peripheral attached to the user assembly. For example, a bicycle helmet may have a movement detecting device built into it to determine what speed a user is moving at, which could be set up such that the user assembly could receive information from it, which could also be transmitted to the machine, e.g. PED, FED, or electronic bicycle brakes. Alternatively, the user assembly may be set up such that certain forms of information are transmitted and / or certain algorithms are run on the EEG data only when the user assembly is incorporated into or associated with a specific device. For example, if incorporated into a safety helmet for use in a factory, the assembly may start running algorithms and / or transmitting data specific to detecting pain or head impacts, which if detected, could shut off the factory robot with which the user is working if pain and head impacts could be a result of injury generated by the machine as an added form of safety.
Accordingly, such a User Assembly could provide a user with mobile, continuous (or quasi-continuous), consumer-friendly, unobtrusive (EEG-based) mental state monitoring. It could also gather EEG data during events and tasks within which this was not previously practical—such as while riding a bus or working on a construction site. EEG measurements, EEG-based decisions, EEG-based BCIs, and EEG-based neural training and self-improvement techniques (primarily neurofeedback) could thus be integrated into the day-to-day life of a general consumer. The User Assembly's (or variants of the User Assembly's) comfort, ease-of-use, modularity, and—with certain iterations—ability to be easily incorporated into numerous forms of socially appropriate headwear will help promote consumer/market acceptance, i.e. widespread general-purpose use.
From the point of view of a programmer or clinician, all implementations/variants of the User Assembly should provide a good signal quality and two or more sensors (a minimum of one reference electrode, and one EEG electrode). Accordingly, amongst the factors affecting a User Assembly from the user's perspective are those listed in Table 1 below which have been grouped into broader categories for simplicity. As evident some criteria appear in in more than one category.
TABLE 1
Design Factors for EEG User Assembly
Practicality
Sensors
Aesthetics
Cost
Number of sensors
Size
Size
Location of sensors
Location of sensors
Stability/wearability
Contact or non-contact sensors
Visibility of headset
Battery life
Active or passive electrodes
Conspicuousness of
Durability
Weight
headset/sensors
Weight
Cost
Modularity
Water resistance
Water resistance
Colour/Fashion
Modularity
Comfort
Customizability
Comfort
Modularity
Material(s) used
Communications (wired or
Size
wireless)
Material(s) used
Which specific devices it can be
associated with
Material(s) used
Uses/functions/applications
Referring to FIG. 3C there are depicted first to fourth images 3000 A through 3000 D of a wireless user assembly according to an exemplary embodiment of the invention, displaying a design not present in the prior art that is itself an aspect of the invention. As depicted in first image 3000 A the wireless user assembly comprises an EEG sensor 3030 , earpiece 3035 , and body 3040 . Referring to second image 3000 B the earpiece 3035 is coupled to the body 3040 via first arm 3020 which provides in conjunction with the body 3040 the structure that rests upon the user's upper portion of the ear thereby supporting the wireless user assembly when worn by the user. The EEG sensor 3030 is coupled to the body 3040 via flexible arm 3010 allowing the EEG sensor 3030 to be positioned against the user's head. Second arm 3050 provides additional engagement against the user's ear close to the joint of the ear to the head whilst the thicker body 3040 sits away from their ear providing improved comfort. It would be evident that with a wireless interface within the body 3040 , the user assembly can communicate EEG data with a user's PED/FED, as well as receive wireless audio signals given to the user via earpiece 3035 .
Optionally, a microphone may be included in the wireless assembly, allowing it to concurrently act as both portable EEG device and wireless hands free headset for use with a PED or FED. The microphone could be positioned in numerous locations, such as behind the ear attached to body 3040 at position 3062 or inside the body 3040 sitting below the user's ear, with the microphone facing forward and receiving sound through a slit (or series of slits) at position 3061 . Optionally (and ideally), the body 3040 may be small enough to fit behind the user's ear, providing a more discrete user assembly. Similarly, an EEG sensor embedded within the body of the user assembly would provide further footprint reduction, i.e. cover less of a user's head) and discrete provisioning of an EEG sensor within a wireless user assembly.
Now referring to FIG. 4 there is depicted an exemplary flow chart for signal processing of EEG data according to an embodiment of the invention. As depicted in first step 410 raw EEG data is received from an EEG sensor via intermediate circuitry, e.g. a low leakage ESD proof structure and analog-to-digital converter (ADC), wherein the EEG data is then structured into a series of 1-second long data sequences clumped into a discrete “packet” of data in an exemplary embodiment of the invention, with each packet containing up to 1000 raw EEG voltage value samples. The length of and number of samples within each sequence may vary in other embodiments. Each packet is coupled to a plurality of Wavelet Filters 420 A through 420 N for processing, whereby each of the different Wavelet Filters 420 A through 420 N applies a different process to the packet (each extracts a different wavelet). The processed outputs from the plurality of Wavelet Filters 430 A through 430 N are then coupled to a plurality of Variance Computation blocks 430 A through 430 N (respectively, where 420 A couples to 430 A, 420 B couples to 430 B, and so on) which generate statistical data relating to each processed 1-second long sequence of EEG data (packet) in order to calculate, for example, the variance of each packet. The variance results for the current 1-second sequence and the raw EEG data within the packet are simultaneously forwarded from all Variance Computation blocks 430 A through 430 N, to High Thresholding 440 , wherein spikes and/or events are identified. The processed EEG data is then processed by Low Thresholding block 450 in order to remove offsets within the data and then this is coupled to Parameter Extraction block 460 wherein parameters for the user are derived from modeling analysis according to one or different time periods including any determined critical time thresholds.
It would be evident that removal of artifacts, e.g. muscle movement, from EEG data can be accomplished via other methodologies besides the aforementioned wavelet transform-based analysis paradigms. Artifacts can also be removed using, for example, empirical mode decomposition, canonical correlation analysis, independent component analysis, or some combination of methodologies. Furthermore, learning algorithms such as support vector machines and multilayer perceptrons can be employed for greater accuracy albeit slower and with more complex processing. As such, aspects of FIG. 4 relating to artifact removal merely represent (parts of) an exemplary process of artifact removal and furthermore, since many variants of wavelet transform filtering exist and can be employed to this end, it is also merely an example of one exemplary method of using wavelet transforms to remove artifacts.
Now referring to FIG. 5 there is depicted a functional schematic for a distributed neurological data acquisition system (DNAS) 500 according to an embodiment of the invention. DNAS 500 in this example is another exemplary system for processing EEG data. DNAS 500 is comprised of a Data Acquisition Unit (DAU) 510 , a Local Data Processing Module (LDPM) 520 , which may be for example a user's PED, and a Remote Data Processing Module (RDPM) 530 , e.g. a server accessible through the internet. Electrodes 511 detect analog signals (voltage readings) generated by electrical-neurological activity in the brain of the user, i.e. EEG signals. The electrodes 511 are coupled to Differential Amplifiers/Filters 512 which are part of DAU 510 and increase the magnitude of the electrical signal detected by the electrodes 511 whilst filtering out/discarding voltage readings that are too high or low to have been produced by brain activity. These pre-processed EEG signals are then coupled via a Multiplexer 513 to a first Wireless Transmitter 514 , wherein they are transmitted via Network 5000 to the LDPM 520 and first Wireless Receiver 521 . The output from the first Wireless Receiver 521 is coupled to Signal Processing 522 which also receives input from Local Storage 524 and Local User Specific Settings 525 . The processed output from the Signal Processing 522 is then coupled to Local Data Analysis & Decision Processing 523 which also receives data from the Local User Specific Settings 525 . The processed output from the Local Data Analysis & Decision Processing 523 is then coupled to second Wireless Transmitter 526 , which transmits the processed data through network 5000 to RDPM 530 , where it is received by second Wireless Receiver 531 . The processed output from LDPM 520 is then further processed by the series of algorithms present in the Remote Data Analysis & Decision Processing 532 module in conjunction with a module storing information about the user and their selected settings (Remote User Specific Settings 534 ), as well as data retrieved from Remote Storage 533 . Once these analyses are complete, the processed data is fed to a directed input of a software application/software system/machine interface (SASSMI)—often associated with LDPM 520 (and often involving transmitting the data back to LDPM 520 and sometimes to a separate SASSMI)—wherein the processed EEG data is employed in an action such as (but not limited to) controlling a system, controlling a machine, establishing a decision, triggering a medical event (e.g. a warning for an impending seizure), triggering a response, directly displaying information in real-time about the user's mental activity (especially if the user is performing a neurofeedback exercise), and modifying at least one of the user-specific data stored within the local or remote setting databases, e.g. Local User Specific Settings 525 and/or Remote User Specific Settings 534 . This data can also be stored in the SASSMI and/or LDPM 520 for later use—e.g. to display the data to the user on a “history screen” through which the user can track their changes in mental activity over time—especially in relation to metrics generated from mental activity such anxiety level.
According to an embodiment of the invention a user may have multiple User Assemblies, e.g. DAU 510 , such as for example an earpiece, Bluetooth headset, motor bicycle crash helmet, a safety headset at work, etc. Each may have at least an EEG sensor and an EEG reference sensor and accordingly, each may associate with the user's PED (or PEDs, if the user has associated the device with more than one) during their use of each, with a calibration routine switching which user assembly is currently connected to the PED each time the user switches which user assembly they are wearing (e.g. when the user removes their motorcycle helmet and puts on their Bluetooth headset). Accordingly, the User Assembly currently in use provides EEG data to the PED for processing and/or classification plus coupling to the remote systems and/or applications. Hence, applications of embodiments of the invention allow for multiple User Assemblies to be used and the retrieved EEG data to be processed and pushed to the remote storage. Optionally, multiple PEDs and FEDs may be associated to the user such that their EEG data acquisition continues as they e.g. walk around their work or home, drive their car, etc. wearing different User Assemblies. Additionally, each User Assembly, e.g. DAU 510 , may contain memory for storing a predetermined duration of data to allow for handovers, failures, communication outages etc. If the User Assembly is out of communication for more than the predetermined duration of time for which EEG data can be stored then the User Assembly may exploit a first-in first-out methodology and simply keep the latest data. In other instances where some pre-processing is performed within the User Assembly then data relating to initially assessed events may be preferentially stored. In other embodiments of the invention, the need for procedures that switch which User Assembly is connected to the PED (or PEDS and/or FEDs) may not be present, such as through the use of a more versatile form of the User Assembly that can be worn/used in a larger variety of contexts (IE fits under a wide variety of different forms of headwear and/or can be continuously worn inconspicuously without the presence of headwear, thus eliminating the need for multiple user assemblies).
Accordingly, biomedical data, in this instance EEG data received from the EEG sensors, e.g. electrodes 511 , may be processed locally (i.e. in close proximity to the DAU 510 ) by the LDPM 520 , remotely by the RDPM 530 , or in both the LDPM 520 and RDPM 530 , with different analyses occurring in each. Accordingly, the DAU 510 with DNAS 500 is assumed to simple provide EEG signal conditioning and hence LDPM 520 and RDPM 530 may apply one or more processes relating to analyzing and/or determining EEG signals including but not limited to K-nearest neighbour algorithms, K-means algorithms, support vector machines, support vector networks, relevance vector machines, relevance vector networks, multilayer perceptron neural networks, neural networks, single layer perceptron models, logistic regression, logistic classifiers, decision trees, Bayesian linear classifiers, naïve Bayes, fuzzy entropy, fuzzy logic, linear discriminant analysis, linear regression, signal space projections, hidden Markov models, and ensemble classifiers including but not limited to bagging, random forests, random subspaces, bootstrapping aggregating, and AdaBoost.M1. More complex analyses would generally be conducted by the RDPM 530 , with less processor intensive analyses/classification methods conducted by the LDPM 520 .
Now referring to FIG. 6 there is depicted a functional layout of an exemplary sensor interface circuit, e.g. Differential Amplifier and Filter (DAF) stage 512 within DAU 510 of FIG. 5 . As depicted multiple signals from sensors, e.g. electrodes 611 , are received by a plurality of Operational Amplifiers (OpAmps) 612 A wherein the output of the plurality of OpAmps are then passed through High Pass Filters 612 B and Low Pass Filters 612 C, followed by more amplifiers in Gain Stage 612 D. The amplifiers in Gain Stage 612 D may for example be low ESD leakage structures such as described in respect of FIG. 4 with unitary gain, the amplification circuit depicted in FIG. 1D , or another amplification circuit supporting low noise, low frequency amplification of electrical signals.
Within the description supra in respect of FIGS. 3A and 3B for the EEG headset 330 according to an embodiment of the invention a design using four EEG sensors, these being a pair of EEG sensors 310 and a pair of EEG contacts 380 . Historically, as discussed supra EEG headsets fall into 2 categories, namely those for medical/research applications with a large number of sensors; and simple devices with a small number of electrodes geared towards consumer devices and applications e.g. games and general health and wellness software. However, the inventors wished to establish with their EEG headset 330 a device capable of supporting a wide range of EEG based analysis, metric determination, etc. to support a wider range of applications.
Within the prior art work on what may be termed, minimal electrode placements, includes Bos et al. in “EEG-based Emotion Recognition—The Influence of Visual and Auditory Stimuli” (Technical Report, pp. 1-17, 2006); Johnstone et al. in “EEG From a Single-Channel Dry-Sensor Recording Device” (Clin EEG Neurosci, Vol. 43(2), pp. 112-120); Kostyunina et al. in “Frequency Characteristics of EEG Spectra in the Emotions” (Neurosci. & Behav. Physio., Vol. 26(4), pp. 340-3); Mikhail et al in “Using Minimal Number of Electrodes for Emotion Detection using Brain Signals Produced from a New Elicitation Technique” (Int. J. Autonomous and Adaptive Communications Systems, Vol. 6(1), pp. 80-97); and Takahashi in “Remarks on Emotion Recognition from Bio-Potential Signals” (Interface, pp. 186-191). The placement of the electrodes within these prior art experiments are depicted in FIG. 7 with respect to a view from above a user's head showing the conventional labelling of nodes together with the node configurations employed by Mikhail, Takahashi, Bos, Kostyunina, and Johnstone together with a essentially a research configuration of Mikhail. Within these prior art trials then primarily research has focused to frontal lobe measurements, e.g. Takahashi exploits FP1, FP2, and FPz; Mikhail exploits F3, F4, FP1, and FP2; and Box exploits F3, F4, FPz, and A2. Some research has addressed occipital lobe measurements, e.g. Mikhail exploited O3, O4, P3, and P4 in a second setup whereas Kostyunina exploited O1, F3, C4, and T4. Generally reference electrode positions have been at one or both ears, i.e. A1 and/or A2.
However, based upon analysis and experimentation the inventors have been able to establish that exploiting O1, O2, F3 and F4 as depicted in FIG. 8 provides sufficiently accurate data for analysis with their processing algorithms. Beneficially this allows the design and implementation of the EEG headset 330 with a rear headband design removing many of the issues for users of EEG wearable devices in respect of their visibility to others and their impacting the user's ability to exploit a HMD such as Google Glass™ as well as wear/place/remove hats etc. Optionally, additional sensors within the EEG headset 330 may include T5, T3, T4, and T6. Optionally, a further sensor or sensors in addition to O1, O2, F3 and F4 may be attained by adding an EEG sensor to the HMD 360 just above the bridge of the nose thereby adding FPz and/or Nz node measurements. As the HMB 360 and EEG headset 330 both exploit WPAN/short range wireless communications their data may be merged upon the user's PED for example or communicated from HMD 360 to EEG headset 330 for initial processing and communication with a PED and/or FED associated with the EEG headset 330 .
Now referring to FIG. 9 there are depicted first to sixth EEG traces 910 to 960 taken over an approximately 10 second period, generally in relation to sleep. These being:
Awake 910 which is characterized by low voltage, random, and fast EEG variations. This doesn't represent a person's only awake state, merely an example of one, which is primarily comprised of beta and alpha waves, with a small influence from gamma. It could also be described as an “alert” state; Drowsy 920 , dominated by periodic 8-12 Hz alpha waves—generally seen in states in which a person is tired, though it can also appear in states of relaxation where the subject does not report drowsiness; Stage 1 Sleep 930 —dominated by 3-7 Hz theta waves; Stage 2 Sleep 940 —dominated by 12-14 Hz waves, with sleep spindles 941 and K-complexes 942 occurring at seemingly random (though not truly random) intervals; Delta Sleep 950 , also known as stage 4 sleep or “deep sleep”. This is difficult to differentiate from stage 3 sleep, which is frequently described as merely a transitional phase between “light sleep” (stage 2 sleep 940 ) and deep sleep 950 rather than a discrete stage of sleep in and of itself. As such, the more readily distinguishable stage 4 sleep 950 is displayed here. 0.5-2.0 Hz delta waves predominate during delta sleep 950 , but as with all stages, do not account for all variation in the EEG wave; REM Sleep 960 which is primarily composed of low voltage, seemingly (but not truly) random waves of comparatively high frequency in comparison to other stages of sleep. EEG waves present in REM sleep 960 have a greater resemblance to waves seen in awake states (e.g. Awake 910 ), but contain unique and distinctive saw tooth waveform segments 961 not generally seen a person's waking EEG.
EEG can be broken down into its frequency spectra via Discrete Fourier transforms (e.g. FFTs), which are used to categorize the waves into frequency bands. Though there is variance in which frequency bands are selected and which ranges chosen for each, there are typical spectral regions within which each band is placed. An exemplary and fairly typical set of selected wave bands and the frequencies chosen for each band are depicted in FIG. 10B , wherein the raw EEG band 1060 is broken down into delta waves 1061 from 0-4Hz, theta waves 1062 from 4-8Hz, alpha waves 1063 from 8-12Hz, beta waves 1064 from 12-31Hz, and gamma waves 1065 from 30-60Hz. Other embodiments choose other wave bands, and ranges for wave bands. Some embodiments break certain wave bands down into sub-bands, such as alpha1 from e.g. 8-10Hz and alpha2 from e.g. 10-12Hz. A more in-depth
Now referring to FIG. 10 there is depicted an exemplary EEG spectrum 1000 , depicting an example of how the power within a user's EEG can vary. The spectra depicted in 1000 are fairly typical, but vary considerably between users/subjects dependent on numerous factors including (but not limited to) age, the presence of neurological disorders, and the activity the user is engaged in. The exemplary band definitions for EEG spectra are presented below together with mental/neurological/psychology states roughly connected to changes in each band, along with pathologies roughly associated with abnormalities in each band.
Delta—0 Hz to 4 Hz: Normally associated with deep sleep (NREM stages 3 and 4 and certain continuous attention tasks (less well-accepted). Pathologies associated with abnormalities in this band include increased frequency in waking states in brain injury and brain tumour patients, increased in waking states in schizophrenia patients, and reduced levels during sleep are associated with low-quality sleep and disorders that cause low-quality sleep (such as major depression).
Theta—4 Hz to 8 Hz: Normally associated with sleep (NREM stages 1 and 2), drowsy states when awake, active suppression of thoughts and behaviours previously elicited by stimuli, and meditation. Pathologies associated with abnormalities in this band include hydrocephalus, focal brain lesions, and increased in ADHD.
Mu—8 Hz to 13 Hz (directly over the sensori-motor cortex): Normally associated with observation of behaviour in other people, suppressed when performing or visualizing motor activities, and increased before and after motor activities. Pathologies associated with abnormalities in this band include autism.
Alpha—8 Hz to 14 Hz: Normally associated with relaxation, behaviour inhibition, closed-eye resting state, rumination and self-reflection, and meditation. Pathologies associated with abnormalities in this band include coma.
Beta—14 Hz to ˜40 Hz: Normally associated with normal waking consciousness with eyes-open, visual attention, active concentration, anxiety/nervousness, voluntary suppression of movement, and alertness together with maintenance of current behaviour. Pathologies associated with abnormalities in this band include reduction in ADHD and increased in generalized anxiety disorder.
Gamma—˜40 Hz to ˜100 Hz: Normally associated with combining sensory information from multiple senses, reasoning, creative and abstract thinking, and short-term memory tasks involving matching stimuli with existing memories together with switching between behaviours. Pathologies associated with abnormalities in this band include increased frequency associated with cognitive decline.
Insert 1050 in FIG. 10A zooms in on a segment of EEG spectrum 1000 to depict a common power spike observed in EEG spectra known as the peak alpha frequency which describes an often-occurring sudden increase and immediately subsequent rapid drop in spectral power appearing approximately one-third of the way through a user's alpha frequency band. Peak alpha frequency 1050 is a particularly important phenomenon because it can be used to calibrate the frequency ranges of each band to be specific to each user peak. This is possible because the peak alpha frequency 1050 almost always occurs ⅓ of the way through the alpha band, most bands including the alpha band have approximately the same width in most users, and bands are always positioned in a specific order. Certain embodiments of the invention take advantage of peak alpha frequency 1050 to calculate frequency band ranges for individual users to better determine their mental states—as opposed to the use of predefined frequency band ranges as utilized in other embodiments. Note that in other embodiments other features of a user's EEG can be used instead of peak alpha frequency 1050 to calibrate a user's frequency band ranges. Furthermore, other embodiments may use other features in tandem with peak alpha frequency 1050 to more accurately and/or precisely define a user's frequency band ranges. Such methods are a major aspect of a now commonly-used set of EEG methodologies known as “quantitative EEG” (qEEG) that use quantitatively determined rather than semi-arbitrarily pre-defined frequency band ranges. qEEG, variants of various qEEG methods, or certain aspects of qEEG may be utilized by certain embodiments of the invention.
Now referring to FIG. 11 there is depicted a network 1100 supporting communications to and from electronic devices according to an embodiment of the invention wherein EEG waveform data for an individual may be transferred online remote processing elements, e.g. remote servers, server farms, data centers, etc., further deeper analysis using increased online computing resources, i.e. cloud computing, storage, and optionally sharing user EEG data/EEG analysis results/user mental states via one or more formats including, but not limited to, social media, social network(s), email, short message services (SMS), blogs, posts, etc. As shown, first and second user groups 1100 A and 1100 B interface to a telecommunications network 1100 . Within the representative telecommunication architecture a remote central exchange 1180 communicates with the remainder of a telecommunication service providers network via the network 1100 which may include for example long-haul OC-48/OC-192 backbone elements, an OC-48 wide area network (WAN), a Passive Optical Network, and/or a Wireless Link. The central exchange 1180 is connected via the network 1100 to local, regional, and international exchanges (not shown for clarity) and therein through network 1100 to first and second wireless access points (AP) 1195 A and 1195 B which provide Wi-Fi cells for first and second user groups 1100 A and 1100 B respectively. Also connected to the network 1100 are first and second Wi-Fi nodes 1110 A and 1110 B, the latter of which is coupled to network 1100 via router 1105 . Second Wi-Fi node 1110 B is associated with Enterprise 1160 A, in this instance Personal Neuro Devices Inc. (a provider of User Assemblies and software applications exploiting EEG biosignals), and environment 1160 within which are first and second user groups 1100 A and 1100 B. Second user group 1100 B may also be connected to the network 1100 via wired interfaces including, but not limited to, DSL, Dial-Up, DOCSIS, Ethernet, G.hn, ISDN, MoCA, PON, and Power line communication (PLC) which may or may not be routed through a router such as router 1105 .
Within the cell associated with first AP 1110 A in FIG. 11 the first group of users 1100 A may employ a variety of portable electronic devices (PEDs) including for example, laptop computers 1155 , portable gaming consoles 1135 , tablet computers 1140 , smartphones/superphones 1150 , cellular telephones/cellphones 1145 , and portable multimedia players 1130 . Within the cell associated with second AP 1110 B are the second group of users 1100 B who may employ a variety of fixed electronic devices (FEDs) including for example gaming consoles 1125 , personal computers 1115 , wireless/Internet-enabled televisions 1120 , and cable modems 1105 . Also connected to the network 1100 are first and second APs which provide, for example, cellular GSM (Global System for Mobile Communications) telephony services as well as 3G and 4G evolved services with enhanced data transport support. Second AP 1195 B provides coverage in the exemplary embodiment to first and second user groups 1100 A and 1100 B. Alternatively the first and second user groups 1100 A and 1100 B may be geographically disparate and access the network 1100 through multiple APs, not shown for clarity, distributed geographically by the network operator or operators. First AP 1195 A as show provides coverage to first user group 1100 A and environment 1160 , which comprises second user group 1100 B as well as first user group 1100 A. Accordingly, the first and second user groups 1100 A and 1100 B may according to their particular communications interfaces communicate to the network 1100 through one or more wireless communications standards such as, for example, IEEE 802.11, IEEE 802.15, IEEE 802.16, IEEE 802.20, UMTS, GSM 850, GSM 900, GSM 1800, GSM 1900, GPRS, ITU-R 5.28, ITU-R 5.150, ITU-R 5.280, and IMT-2000. It would be evident to one skilled in the art that many portable and fixed electronic devices (PEDs and FEDs, respectively) may support multiple wireless protocols simultaneously, such that for example a user may employ GSM services such as telephony and SMS, Wi-Fi/WiMAX data transmission, VoIP, Internet access etc. Accordingly portable electronic devices within first user group 1100 A may form associations either through standards such as IEEE 802.15 and Bluetooth, and/or in an ad-hoc manner.
Accordingly, any of the PEDs and/or FEDs may provide and/or support the functionality of a local biosensor processing unit (LBPU), such as LDPM 620 in FIG. 6 for example, to process and/or store biosignals acquired from a User Assembly (mainly EEG signals, but in some embodiments not exclusively EEG signals) such as depicted supra in respect of User Assembly 310 in FIG. 3A or first to third User Assemblies 3000 A to 3000 C respectively in FIG. 3B for example as processed and transmitted by a Data Acquisition Unit (DAU) e.g. DAU 610 in FIG. 6 . Accordingly, such LDPUs may receive biosignals—mainly EEG signals (i.e. scalp voltage recordings) but in some embodiments not exclusively EEG signals—and perform localized storage, processing, etc. on these signals. In some embodiments of the invention the PEDs/FEDs may also provide the required functionality of the DAU in addition to that of a LBPU. Further, as depicted first and second servers 1190 A and 1190 B respectively which are connected to network 1100 and accordingly can receive communications from any PED/FED within first and second user groups 1100 A and 1100 B respectively as well as other PED/FED devices connected to the network 1100 . Accordingly, the first and second network servers 1190 A and 1190 B may support the functionality discussed supra in respect of a remote biosignal processing unit (RBPU) such as a RDPM 530 presented supra in respect of FIG. 5 such that additional processing and/or storage may be supported. Within another embodiment of the invention the User Assembly, depicted as User Assembly 1165 in FIG. 11 , may be remotely connected to the LBPU and/or LDPM through a wireless interface other than a local area network interface such as Bluetooth for example such that data communications may be undertaken over a larger area and in the event of a lost or misplaced PED for example. Optionally the User Assembly may include local and network wireless interfaces and select which to employ based upon the automatic association or lack of association with the user's PED and/or FED.
External servers connected to network 1100 include servers belonging to research institutes 1170 C for analyzing our data for scientific purposes. Such purposes can include, but are not limited to, finding information for treating mental disorders, discovering new ways to filter EEG data to get a less noisy signal, and developing algorithms that detect new mental states. Outside servers also include medical services 1175 , which can use the data for such purposes as tracking neurological events like seizures or notifying doctors and emergency services in the event of serious events like heart attacks and strokes that have an impact on brain activity. Third party servers 1170 B also connect to our network for purposes like e.g. determining ads that are more likely to be of interest to a particular user based on their EEG activity, or associating emotions derived from EEG data with specific locations such as restaurants and theme parks.
Also connected to network 1100 are social networks 1170 D such as Facebook™, Twitter™, LinkedIn™, Instagram™, Pinterest™, Yelp™ and Reddit™ for example. These may also be connected to first and second servers 1190 A and 1190 B respectively for example to acquire abstractions derived from EEG data of a registered user of one or more of the social networks 1170 or it may obtain data from User Assembly 1165 as well as the RBPU and/or RDPM for example. Accordingly, a registered user of an associated social network or social networks 1170 D may post information relating to their emotional state derived from the EEG waveform data, self-ratings provided by users, scores on “cognitive” tasks relating to emotions, and/or ERP reactions to presented stimuli (mainly emotional imagery such as affectively negative and positive images). Such information may be posted directly e.g. as an emoticon, or through a color coding or style tagging method, including those that are directly applied to the displayed webpage(s)/profile(s) of the user of a social network or social networks within 1170 D for example. Optionally, the user may elect to include such colour coding, style tagging, and/or emoticons as part of communications made by the user such as posts, tweets, and alike, as well as in electronic communications outside the scope of social networking, such as email and SMS. In other embodiments the social networks 1170 D provider may combine derived data for a plurality of users in association with a single topic, thread, re-tweet etc. to provide an averaged or weighted sentiment of the plurality of users such as anger, sadness, etc. in response to the topic in question.
It would be evident that first and second servers 1190 A and 1190 B respectively may securely store information relating to a user's biosignals, including but not limited to raw EEG data, processed EEG data, and EEG event determinations for at least one of a predetermined period of time, for all sampled data, and within predetermined periods prior to and after any determined event. In some instances the EEG data may be strictly time-locked to an event as is necessary for certain EEG paradigms such as those based on ERPs or it may be more loosely linked to the event e.g. by applying tags to individual segments of EEG data. Such tags indicating what “state” a user is or was in, such as walking, or indicating that a specific notable event had just passed, such as the elicitation of a startle response from the user). In other embodiments of the invention the data stored upon a remote server—such as first and second servers 1190 A and 1190 B respectively—may include, but not be limited to, data acquired from activities relating to gaming, mental training such as meditation, neurofeedback training, self-monitoring of mental states (e.g. mood, anxiety, attention, stress), and/or self-monitoring of neurological states (e.g. seizures, strokes).
According to other embodiments of the invention exploiting the user assemblies, PEDs, FEDs, DAUs, LPDMs, RDPMs, LBPUs, and RBPUS in various combinations, games, software upgrades, firmware upgrades, analysis algorithms etc. may be associated with enterprises and/or organizations associated with financial transactions in order for the user to access/acquire these. Accordingly, financial service providers who may be associated with financial transactions of registrants with enterprises may similarly access the network and user-associated devices to acquire credentials, verify credentials, and associate firmware versions, hardware identities, etc. These together with first and second servers 1190 A and 1190 B, which together with others not shown for clarity, may host according to embodiments of the inventions multiple services associated with a provider of the software operating system(s) and/or software application(s) associated with the electronic device(s), a provider of the electronic device, provider of one or more aspects of wired and/or wireless communications, event databases, registration databases, credential identification databases, license databases, customer databases, websites, and software applications for download to or access by PEDs and/or FEDs. First and second primary content sources 1190 A and 1190 B may also host, for example, other Internet services such as search engine(s), financial services, third party internet-based or internet-requiring applications.
Now referring to FIG. 12 there is depicted a PED 1204 supporting interfacing to a User Assembly (USAS) 1270 according to an embodiment of the invention such as described supra in respect of embodiments of the invention as well as the functions for a LBPU or LDPM, similarly described supra. Also depicted within the PED 1204 is the protocol architecture as part of a simplified functional diagram of a system 1200 that includes a portable electronic device (PED) 1204 , such as a smartphone, an access point (AP) 1206 , such as first Wi-Fi Access Point 1110 , and one or more network devices 1207 , such as communication servers, streaming media servers, and routers. Network devices 1207 may be coupled to AP 1206 via any combination of networks, wired, wireless and/or optical communication. The PED 1204 includes one or more processors 1210 and a memory 1212 coupled to processor(s) 1210 . AP 1206 also includes one or more processors 1211 and a memory 1213 coupled to processor(s) 1211 . A non-exhaustive list of examples for any of processors 1210 and 1211 includes a central processing unit (CPU), a digital signal processor (DSP), a reduced instruction set computer (RISC), a complex instruction set computer (CISC) and the like. Furthermore, any of processors 1210 and 1211 may be part of application specific integrated circuits (ASICs), Field Programmable Gate Arrays (FPGAs) or may be a part of application specific standard products (ASSPs). A non-exhaustive list of examples for memories 1212 and 1213 includes any combination of the following semiconductor devices such as registers, latches, ROM, EEPROM, flash memory devices, non-volatile random access memory devices (NVRAM), SDRAM, DRAM, double data rate (DDR) memory devices, SRAM, universal serial bus (USB) removable memory, and the like.
PED 1204 may include an audio input element 1214 , for example a microphone, and an audio output element 1216 , for example, a speaker, coupled to any of processors 1210 . PED 1204 may include a video/visual input element 1218 , for example, a digital camera, video camera, infrared sensor, or motion sensor; and a visual output element 1220 , for example an LCD display, coupled to any of processors 1210 . The visual output element 1220 is also coupled to display interface 1220 B and display status 1220 C. PED 1204 includes one or more applications 1222 that are typically stored in memory 1212 and are executable by any combination of processors 1210 . PED 1204 includes a protocol stack 1224 and AP 1206 includes a communication stack 1225 . Within system 1200 protocol stack 1224 is shown as IEEE 802.11/15 protocol stack but alternatively may exploit other protocol stacks such as an Internet Engineering Task Force (IETF) multimedia protocol stack for example. Likewise AP stack 1225 exploits a protocol stack but is not expanded for clarity. Elements of protocol stack 1224 and AP stack 1225 may be implemented in any combination of software, firmware and/or hardware. Protocol stack 1224 includes an IEEE 802.11/15-compatible PHY module 1226 that is coupled to one or more Front-End Tx/Rx & Antenna 1228 , an IEEE 802.11/15-compatible MAC module 1230 coupled to an IEEE 802.2-compatible LLC module 1232 . Protocol stack 1224 includes a network layer IP module 1234 , a transport layer User Datagram Protocol (UDP) module 1236 and a transport layer Transmission Control Protocol (TCP) module 1238 . Also shown is a wireless personal area network (WPAN) Tx/Rx & Antenna 1260 , for example supporting IEEE 802.15.
Protocol stack 1224 also includes a session layer Real Time Transport Protocol (RTP) module 1240 , a Session Announcement Protocol (SAP) module 1242 , a Session Initiation Protocol (SIP) module 1244 and a Real Time Streaming Protocol (RTSP) module 1246 . Protocol stack 1224 includes a presentation layer media negotiation module 1248 , a call control module 1250 , one or more audio codecs 1252 and one or more video codecs 1254 . Applications 1222 may be able to create maintain and/or terminate communication sessions with any of devices 1207 by way of AP 1206 . Typically, applications 1222 may activate any of the SAP, SIP, RTSP, media negotiation and call control modules for that purpose. Typically, information may propagate from the SAP, SIP, RTSP, media negotiation and call control modules to PHY (physical layer) module 1226 through TCP module 1238 , IP module 1234 , LLC module 1232 and MAC module 1230 .
It would be apparent to one skilled in the art that elements of the PED 1204 may also be implemented within the AP 1206 , including—but not limited to—one or more elements of the protocol stack 1224 , including for example an IEEE 802.11-compatible PHY module, an IEEE 802.11-compatible MAC module, and an IEEE 802.2-compatible LLC module 1232 . The AP 1206 may additionally include a network layer IP module, a transport layer User Datagram Protocol (UDP) module and a transport layer Transmission Control Protocol (TCP) module as well as a session layer Real Time Transport Protocol (RTP) module, a Session Announcement Protocol (SAP) module, a Session Initiation Protocol (SIP) module and a Real Time Streaming Protocol (RTSP) module, media negotiation module, and a call control module.
Also depicted is USAS 1270 which is coupled to the PED 1204 through a WPAN interface between Antenna 1271 and WPAN Tx/Rx & Antenna 1260 . Antenna 1271 is connected to USAS Stack 1272 and therein to USAS Processor 1273 . USAS Processor 1273 is coupled to Biosignal Sensor A 1274 , Reference Biosignal Sensor 1275 , and Biosignal Sensor B 1276 which can include, for example, electrodes for detecting data relating to one or more of EEG, EMG, EOG, etc. Furthermore, there can be further biosignal sensors besides those depicted. USAS 1270 being for example DAU 610 described above in respect of FIG. 6 with the addition of the USAS Processor 1273 and USAS Stack 1272 . USAS 1270 may, for example, split processing with Processor 1210 within PED 1204 for processing functionality such that a lower power USAS Processor 1273 is deployed within USAS 1270 , controlling acquisition of biosignal data from Biosignal Sensor A 1274 , Reference Biosignal Sensor 1275 , Biosignal Sensor B 1276 , and any other biosignal sensors with instruction sets and some algorithms for example stored within the device's memory, not shown for the sake of clarity. It would be evident that data relating to the particular individual and/or biosignal characteristics for analysis defects may be stored within memory 1212 of PED 1204 and/or the memory of USAS 1270 . Such data being stored within USAS 1270 when processing and/or pre-processing is performed by USAS 1270 rather than within PED 1204 and/or remote systems provided the data via AP 1206 . This information may be remotely transferred to the PED 1204 and/or USAS 1270 from a remote system such as described above in respect of FIG. 11 via Network Device 1207 and AP 1206 . Additionally, in software implemented filters or electronically controlled filters within a DAU, such as DAU 610 of FIG. 6 for example, such data may include the filter characteristics such as passband edge frequency, passband centre frequency, etc.
Accordingly it would be evident to one skilled the art that the USAS with associated PED may accordingly download original software and/or revisions (e.g. updates) for a variety of functions including diagnostics, EEG signal acquisition, EEG signal processing algorithms, etc. as well as revised user characteristic data relating to the individual's brain and/or other body regions for which biosignals are obtained. Accordingly, in certain embodiments a single generic USAS is manufactured then configured to the individual through software and user data, such that e.g. acquisition cycles, acquisition rates, processing, low pass filter characteristics, high pass filter characteristics, low pass filter characteristics, amplifier gain, etc. are calibrated to/customized for a specific user. Optionally, the elements of the PED required for network interfacing via a wireless network (where implemented), USAS interfacing through a WPAN protocol, processor, etc. may be implemented in certain embodiments in a discrete standalone PED as opposed to exploiting a consumer PED. A PED such as described in respect of FIG. 12 allows the user to adapt the algorithms employed through selection from internal memory, to define variants and in some instances control the operation of the USAS through for example a touchscreen, touchpad, keypad interface, externally connected keyboard, externally connected mouse, etc.
Accordingly, within the embodiments of the invention described supra various techniques, assemblies, algorithms, interfaces, and sensors have been described as examples of techniques for the detection, analysis, and response triggering of various physical, biological, physiological, and psychological/mental states of a human user (i.e. biosignals). Accordingly, techniques for providing various biosignal-based PED applications with capabilities that are more conducive to/allow long term monitoring and/or acquisition of biosignals, including but not limited to those detectable via ElectroCardioGraphy (ECG), ElectroEncephalography (EEG), ElectroMyoGraphy (EMG), ElectrOculoGraphy (EOG), Galvanic Skin Response (GSR), Body Temperature, Heart/Pulse Rate, fNIRS (functional near-infrared spectroscopy), non-EMG-based movement tracking, eye tracking/gaze detection, and other biosignals.
Various new and innovative applications can be provided that use enhanced interfaces for PEDs based on the detection and monitoring of various biosignals. For example, by integrating biosensors into the feature-rich environment of the PED, the addition of the user's physiological data gathered by the biosensor, in combination with the audio, multi-media, location, and/or movement data already collected by the PED provides a new platform for advanced user-aware interfaces and innovative applications. For example, a simulation environment intended to aid mental agility and/or skill development may adjust characteristics based upon the user's mental state. Similarly, a gaming environment might adapt to biosignals indicating fear, exhaustion, excitement, boredom, etc. by making the game easier if biosignals indicating frustration are detected, for example, or harder if excitement and concentration are detected. In some embodiments, a PED can include or be directed equipped with various biosensors or interfaces to various biosensors, e.g. biosignal sensors (capable of detecting biosignals) such as for detection/monitoring of one or more of for example the following: ECG, EEG, EMG, EOG, GSR, body temperature, heart/pulse rate, etc. For example, the user can either actively choose to interact with the biosignal sensors for a specific function or have the sensors passively detect/monitor certain biosignal information. This information may be stored on a user assembly with sensors, on a device associated with the user communicating with the user assembly, shared with other devices through a wired connection, shared with other devices through a wireless connection, or communicated to remote devices or services/applications over a network. Applications can then use this information for performing certain functions.
Certain embodiments of the invention as discussed supra are intended for use in establishing neurological events as well as the mental state of the user. By establishment of the appropriate algorithms and analysis routines mental states detected and classified for a user may include, but not be limited to, stress, relaxation, concentration, meditation, emotion and/or mood, valence (positiveness/negativeness of mood), arousal (intensity of mood), dominance (feeling of control present with the mood), anxiety, drowsiness, acute cognitive functioning (i.e. “mental fogginess” vs. “mental clarity”), sleep, sleep quality (for example based on time spent in each stage of sleep as easily detected with EEG), amount of time asleep, presence of a seizure, presence of seizure “prodromal stage” (indicative of an upcoming seizure), stroke detection, migraine presence, severity of migraine if migraine is present and prediction of impending migraine, heart rate, impending panic attack, and the presence of a panic attack. Biomarkers for numerous mental and neurological disorders—to e.g. aid in screening for said disorders—may also be established through biosignal detection and analysis. In addition, multiple disorders are expected to have detectable EEG biomarkers—or already have detectable EEG biomarkers—with increased EEG sample acquisition for a single user and increased user statistics/data. Such disorders may include, but are not limited to, depression, bipolar disorder (both type 1, type 2, and NOS), cyclothymia, generalized anxiety disorder, Alzheimer's disease, schizophrenia, sleep disorders, eating disorders, borderline personality disorder (and to a lesser extent other personality disorders), panic disorder, ADHD, epilepsy, Autism/Asperger's, sleep disorders, and potentially various substance abuse and dependence disorders. It would be evident to one skilled in the art that the determination in respect of EEG biomarkers may be performed in conjunction with statistics/data of a demographic associated with the user, along with self-report information, scores on various cognitive/emotional tasks, and biomarkers of types other than EEG (e.g. EMG, EOG, ECG, etc.).
As discussed supra multiple classification methods and algorithms may be applied to biosignals obtained for a user including, but not limited to, K-nearest neighbour algorithms, K-means algorithms, support vector machines, support vector networks, relevance vector machines, relevance vector networks, multilayer perceptron neural networks, neural networks, single layer perceptron models, logistic regression, logistic classifiers, decision trees, Bayesian linear classifiers, naïve Bayes, fuzzy entropy, fuzzy logic, linear discriminant analysis, linear regression, signal space projections, hidden Markov models, and ensemble classifiers including but not limited to bagging, random forests, random subspaces, bootstrapping aggregating, and AdaBoost.M1. Such classification algorithms may be applied to raw EEG data, filtered EEG data, and pre-processed EEG waveform data, including but not limited to EEG data that has been split into spectral components/Discrete Fourier transformed (FFT), split by waveform complexity (“fractal dimension”), and/or synchronization/synchronicity/synchrony of EEG activity between disparate brain regions.
As discussed within embodiments of the invention biosensor data, e.g. EEG data, may be stored within remote storage. This concept entitled by the inventors as MyBrain™ provides for the online storage and analysis of brainwave data using online cloud storage, deeper remote analysis, and optionally social media based sharing of user EEG data/analysis. Applications using this technology can upload EEG data temporarily stored on a user's PED to MyBrain™ whenever the PED is connected to a network with sufficient battery life or is on charge. MyBrain™ allows this temporarily stored EEG data to be stored for a longer period of time or indefinitely as well as allowing deeper and more processor-intensive analyses on the data to be performed rather than the more limited analyses on their PED. Further, such analyses may be performed over extended time periods, data sets, algorithms, etc. as well as correlated with databases of analyses of other users or those with known medical and/or neurological conditions. Once generated, these deeper and intensive analyses may be transmitted back to the user's PED and/or another device for use by an application and/or machine. MyBrain™ also allows users to share certain aspects of their information over social media with friends or for a group to collaborate such as within a group meditation for example even when the users cannot be present as may be the norm.
Additionally, the inventors have established generalized development tools for therapeutic applications of portable EEG, a software development kit (SDK) called Amygdala™ geared towards these purposes. Amygdala™ provides functionality that eases the creation of EEG-based applications for a User Assembly, and includes tools that specifically aid development of software intended for medical purposes, and self-improvement in the initial configuration. Amygdala provides developers and potentially users to exploit MyBrain™ for the remote storage of EEG data, the inclusion of third-party algorithms for EEG analysis, and the automated integration of audiovisual and various graphical elements within EEG applications. The inventors have exploited Amygdala™ and MyBrain™ in establishing EEG applications for a User Assembly, e.g. Neurosky™ Mindwave™ headset, of which three use the Amygdala™ SDK, three use MyBrain™, and two use both. These applications include two neurofeedback-based video games and two self-improvement applications, one based upon mindfulness meditation practice which is a well-established therapy for ADHD of all three subtypes, namely inattentive subtype, hyperactive subtype, and combined subtype, depression, anxiety, post-traumatic stress disorder, etc., and the other is based on an inventor established unique research-backed personality profiling method. These applications include “Upcake”, “Upcake 2”, “Psych Showdown” and “Transcend.”
Transcend™ is a mobile application intended improve a user's ability to meditate, mindfulness meditation which is a core component of numerous neurofeedback exercises. The program works via the unique aforementioned meditation calculation method to detect a user's current meditation quality using their EEG data. Users meditate in “sessions” of a length they select, during which their meditation quality is recorded. During a session, a visual indicator is displayed onscreen that varies in accordance with their progress providing immediate feedback (neurofeedback). Following each session, users are shown what their average meditation quality was during the session. A session can either be done silently, or with voice guidance and advice, such that it essentially helps users through a variety of techniques for focusing attention on a single stimulus or action while tuning all others out—for example, focusing on one's breathing or repeating a single phrase over and over in one's head. Users are also able to view their average meditation quality over time, by viewing their previous session scores on a graph—thus allowing them to keep track of their progress.
Transcend™ interfaces with smartphones allowing users to practice EEG-guided meditation anytime and anywhere, which is a useful tool for improving one's meditation skill/meditation quality that can be applied in the practice of numerous subtypes of meditation (e.g. mindfulness meditation, transcendental meditation, etc.). It is also important for research purposes, as a meditation application tied solely to a stationary device, e.g. a FED, gives a sample of brain activity from only a single time of day and location under essentially controlled conditions. Further circadian rhythms and settings have a large impact on brain activity, such that since most people work from mid-morning to later afternoon, most readings would thus come from early evening and early morning, whilst a PED allows for use at any time with varying environments.
Transcend™ also adds an online component, allowing users to share their meditation information with other mindfulness practitioners. Furthermore, having a dedicated server (cloud) perform analyses on the data allows for the generation of more complex metrics using algorithms too processor-intensive (and thus battery-unfriendly) for use on a smartphone (or PED in general). It also allows for the storage of a virtually unlimited quantity of their EEG data safely and indefinitely. Additionally, Transcend™ takes information from users beyond the simple meditation readings, such as the date and time of each meditation session. Information about a user's context is essential for accurate interpretation of EEG data and accordingly, future embodiments of Transcend™ will merge the forms of data currently recorded (such as EEG data) with additional automatically acquired information through the PED such as ambient noise (by turning on and sampling the microphone during the meditation when the user would typically be silent), location using Global Positioning System (GPS), date/time information, and user information. Furthermore, a research-specific embodiment of Transcend exists that is solely designed for gathering data on users' meditation quality and associated metrics as mentioned supra (e.g. date and time of meditation session). Also, Transcend™ encourages its continued use by offering achievements/awards to users who improve their meditation abilities in ways detectable by the software.
Referring to FIG. 13 there are depicted first to sixth exemplary screenshots of Transcend™ wherein:
first screenshot 1310 depicts a user menu screen allowing them to begin meditating, view their progress via historical data, view their achievements, and obtain information about Transcend™; second screenshot 1320 represents a user screen depicting connection of the user's EEG headset to their electronic device; third screenshot 1330 represents a meditation screen for a user wherein the user can establish the duration of the meditation session as well as selecting whether they wish to have audio guidance, and if so whether it is a male or female voice; fourth screenshot 1340 depicts a meditation screen for a user during a meditation session wherein the time remaining and their mental state progress are depicted; fifth screenshot 1350 depicts a meditation screen for a user showing their meditation history indicating time meditating, total time, progress in last meditation session, and their maximum sustained meditation period; and sixth screen shot 1360 depicts a progress screen for a user.
With respect to the software development kit (SDK) then this represents a collection of libraries (with accompanying documentation and examples) that are designed to simplify the development of neuro-based applications. Originally implemented for the Android platform the SDK may be ported to other platforms including, but not limited to, iOS, Windows, Blackberry, etc. Also, initially supporting the Neurosky Mindwave Mobile and Personal Neuro Devices headsets library extensions will allow the SDK to support a wide variety of different portable EEG headsets for use with a common application or development of platform specific applications. Referring to FIG. 14 the high level design of the Personal Neuro Devices (PND) SDK is depicted as comprising API, Documentation, and Examples/Tutorials. The rectangular shaped elements in the API indicate parts that are required whilst the oval shaped elements indicate parts that are optional or which might be implemented at a later date. The dashed rectangle around the BCI, Callback, Custom Storage, and Send EEG modules highlights the separation between the algorithms and the rest of the API. Accordingly, the SDK comprises essentially two independent libraries, one which is purely algorithms, and one that provides a standard interface to an EEG headset. Developers will therefore be able to include either library, or both, depending on their needs.
Algorithms (Amygdala™) is the module that contains all neuro based algorithms. Accordingly, these can contain any algorithm from mood (happy, sad, etc.) detection, to seizure detection, for example. Algorithms may be further grouped into subcategories. A requirement for the algorithms module is that it should work independently of other modules so that a developer can use PND algorithms without having to import the rest of our API
BCI (Headset) Management handles connecting to and disconnecting from the headset, state recognition (i.e. in which state is the headset currently in? is it connecting, connected, disconnecting, disconnected, not found, etc.), and feature availability. In addition to handling state change related events, the headset module will also manage EEG related events, for example any new attention value being detected or a possible oncoming seizure.
Some exported applications from the PND SDK may through functionality to pick and choose which events need to be detected offer variable configurations for a headset supporting for example, multiple subscriber levels, upgrades, etc. In some embodiments of the invention the SDK may enable one of a plurality of applications within a PED for example such that a reduced functionality application may be exploited to lighten the load on the processor and prolong battery life when the battery within a PED reaches a predetermined threshold. The BCI Management offers a simple, standard way for the developer to connect to a headset which includes required preliminary steps (e.g. the connect method could include a check for Bluetooth connectivity)
Callback Management module allows the developer to attach various callback handlers to specified events. Handlers can be easily registered or unregistered from a specified event. When the specified event happens, all handlers registered to that event are executed (i.e. the system supports multiple handlers for each event).
Custom Storage for EEG data supports data structures for EEG data which are compatible with all or subsets of EEG headsets. Where possible a single data structure would allow the developer to save or retrieve EEG data without having to know the specifics of the current headset being used.
EEG Data Transmission/Reception Protocols provides for simplified upload/download of EEG to a server or servers. For example, this may be the PND server for data archiving, analysis etc. or the developer's server of choice.
Documentation (API Reference) describes the use and purpose of every publicly accessible class, method, parameter, and field.
Examples and Tutorials will help and encourage developers to use the PND API/SDK.
Considering the custom storage for EEG data wherein different storage structure versus a unified structure may be addressed within the API allowing a data structure to work seamlessly across different headsets. This may be achieved through the lowest common denominator/data conversion. In some cases, some sort of data conversion might simply mean reorganizing data in a certain way, while in others cases it might mean a loss of data (e.g. one headset returns raw data at 512 Hz while another returns data at 1024 Hz, then potentially the API may simply ignore each other data point from the second headset so that regardless of the headset used, the effective sample rate is always 512 Hz). Alternatively the 512 Hz data may be interpolated/replicated to simulate a 1024 Hz stream. Whether the loss or addition of data is significant will mostly depend on the algorithm(s) employed and the information to be extracted from the data. Whilst a unified data structure would also ease third party analysis and characterization plus integration with medical databases etc. this may provide a limitation depending on how the various headsets differ.
In some instances, some algorithms may not be supported on certain headsets either because they require proprietary data (e.g. Neurosky Attention/Relaxation), or the sampling rate is too low or the number of electrodes is insufficient, or the location of the electrode might not allow the headset to gather the required data. These are just some of the different ways that a headset's design might affect whether a certain algorithm can be used with a specific headset or not. As such, the SDK will include mechanisms to identify the requirements for each algorithm, e.g. this algorithm requires raw data sampled at a minimum of 200 Hz, with a minimum 8 bit resolution), or alternatively, each headset could be “aware” of which algorithms it is capable of using. In the case of proprietary data it may also be possible to develop functionally compatible custom implementations based on raw data.
Extending the MyBrain™ and Amygdala™ SDK the inventors are establishing “Introspect” a portable electronic device based consumer EEG software application which monitors and improves mental health. “Introspect” is intended to provide users with a multipurpose software bundle that provides users with a series of EEG-derived numerical metrics, e.g. mood rating, which allows the user to track multiple aspects of their brain health. The application then uses scores on these metrics to recommend specific built-in neurofeedback-based exercises intended to improve areas of weakness. Optionally, “Introspect” may also acquire non-built-in neurofeedback based exercises as the user progresses or particular characteristics of their advancement are identified. The derived results may be reported to users in the form of visual elements such as graphs that show progress in specific areas over time, which will be displayed on a dashboard-type Graphical User Interface (GUI). Areas of interest can be selected by users for inclusion on the dashboard, to avoid displaying unnecessary information, e.g. only epileptics would be interested in seizure data, although the epilepsy algorithm may still be executed to detect events which may indicate an onset or minor occurrences
Certain iterations of Introspect will also include cognitive “brain training” tasks intended to help users improve on a variety of mental skills/characteristics traits such as working memory and attention. These tasks will augment the built-in neurofeedback exercises that are also intended to improve these features—thus providing another avenue through which users can improve themselves on their mental characteristics of choice. Furthermore, cognitive tasks augmented by neurofeedback in a variety of ways—and neurofeedback augmented by cognitive tasks—are also aspects of “Introspect.” This includes but is not limited to: 1) the recommendation of a cognitive task/mental activity or cognitive tasks/mental activities as methods for users to increase or decrease the amplitude of certain EEG wavebands; 2) sessions in which users concurrently perform a neurofeedback exercise and a cognitive task, and are scored on both—i.e. a conglomerate measure of the quality of the session is generated; 3) testing the efficacy of a neurofeedback session by the performance of a cognitive task directly prior and following a neurofeedback exercise; and/or 4) testing the efficacy of a cognitive task in changing user EEG band activity by having users perform a neurofeedback exercise directly prior and following a cognitive task—thus allowing the software to alter which exercises are recommended to the user in response to the prior impact various exercises have had on user mental state/EEG activity.
The portability of the User Assembly, e.g. headset and software will allow users to take readings 24/7/365 (i.e. continuously). In certain embodiments the headset will be wearable continuously, thus allowing continuous scanning, whilst other embodiments will use experience sampling methods wherein users are reminded (if they activate the option), to perform scans at various intervals throughout the day. This will help prevent all readings from being taken in the same states of mind (e.g. states in which users are self-motivated enough to use the software), and/or at the same general times of day, e.g. before and after work. Avoiding these issues will allow Introspect to collect data that is much more representative of the user's day-to-day mental life—IE data that is much more meaningful and thus useful—to users and potentially various clinicians and medical professionals that may also refer to the recorded EEG data. “Introspect” includes self-report measures, for example 1-to-4 item (or perhaps more if allowed by the user) questionnaires presented randomly throughout the day, at requested intervals, and/or when users choose to fill them out. This information is then used in tandem with the EEG readings to generate more comprehensive data and more accurate results. Further, “Introspect” can be paired with other devices and/or systems such as the Nintendo™ Wii™ to compliment in the treatment for certain illnesses or overall physiological and psychological condition of the user. In the case of associating “Transcend” or other applications exploiting embodiments of the invention together with MyBrain™ and Amygdala™ SDK Wii then these can help with diseases related to poor physical fitness like heart disease and obesity as well as providing extra therapies for neurological and psychological conditions to associate with the physical remedies.
“Introspect” establishes algorithm-derived metrics for several neurological and psychological conditions including for example mood, concentration, stress, anxiety, cognitive functioning, stroke, and seizure detection.
Mood: for example an algorithm may calculate a simple numeric representation of the user's mood on an emotional valence (pleasant vs. unpleasant) scale going from 1 to 7 for example, where 1 is an extremely negative mood, and 7 extremely positive, see for example Schupp et al in “Affective Picture Processing as a Function of Preceding Picture Valence: An ERP Analysis” (Biol. Psychol., Vol. 91, pp 81-87).
Concentration: Algorithms for detecting this already exist in EEG based APIs for some headsets, e.g. Neurosky™ MindWave™. However, enhanced concentration metrics will include tracking other user activities such as one or more of speech, movement, blinking etc. via their PED and the EEG data. The rate of blinking has been shown to correlate strongly with attention level and is easily detectable with EEG, see for example Smilek et al in “Out of Mind, Out of Sight: Eye Blinking as Indicator and Embodiment of Mind Wandering” (Psychol. Sci., Vol. 21, pp 786-789).
Stress: This may be established upon a modification to a meditation metric of the inventors included in the Amygdala™ SDK. Furthermore, stress readings are roughly analogous to the inverse of relaxation, with several other factors taken into account. Including information of the “sweat potential”, a large waveform generated when any moisture appears on the skin under the EEG electrode, will provide a second EEG feature that can be used to calculate stress levels given that sweating and stress are so closely linked.
Anxiety: A combination of self-report and EEG data on emotional valence, sweat potentials, and stress may be employed to provide an estimate of anxiety levels. However, the inventors are establishing sophisticated algorithms based upon identification of active regions. Specific sub-regions of the brain at the front of the head called the prefrontal cortex have descending inhibitory pathways into regions of the limbic system, the brain's emotion structures, involved in anxiety. Accordingly, waveforms indicative of activity in these regions can be established and inversely correlated with levels of anxiety.
Mental Clarity: This can be conceptualized as the speed and clarity of thought, ability to cognitively process, mental “sharpness,” cognitive tempo, “acute intelligence,” or inversely, level of confusion or mental “fogginess.” Synchronized waveforms in separate areas of the brain can be analysed to provide a metric relating to cognitive functioning, especially in the gamma and beta bands. Research into this field includes Koenig et al in “Decreased EEG Synchronization in Alzheimer's Disease and Mild Cognitive Impairment” (Neurobiol. Aging, Vol. 26, pp 165-171).
Seizure Detection and Prediction: Whilst not necessarily useful for most users, epilepsy sufferers can use this metric to track the frequency and length of seizures, identify triggers, and provide early warnings for impending seizures. In the broader population rather than identifying the EEG activity which is significantly and distinctly changed by seizures, algorithms may be established that indicate early events not recognizable to the user necessarily or associated by the user to some other neurological, psychological, environmental, physical event. For epileptic customers many seizure-related features in EEG data can be mathematically extracted, of which some appear prior to the seizure. For well-established epileptic sufferers algorithms exist that can use these early features to predict upcoming seizures, with a very high degree of success, see for example Chisci et al in “Real-Time Epileptic Seizure Prediction Using AR Models and Support Vector Machines” (IEEE Trans. Biomed. Eng., Vol. 57, pp 1124-1132). The inventors note that such predictions can be used to alert medical personnel, family, friends, etc. as well as helping co-workers support an epileptic co-worker wherein the alert is communicated from the user's PED when the algorithm(s) detect the condition(s).
In a similar manner to Transcend™ and other applications developed exploiting embodiments of the invention the inventors have established MindMender™, a software suite for Android devices consisting of 3 EEG neurofeedback exercises intended to help treat certain symptoms resulting from traumatic brain injuries (TBI) and/or concussions, notably post-concussion syndrome. EEG data is recorded from the user via their EEG headset, which transmits the user's raw EEG data and some pre-calculated neurometrics (the user's attention and relaxation levels) to an Android PED. Other wavebands are extracted from the EEG data within our software via discrete Fourier transforms to calculate clarity. Whilst MindMender™ is not intended to directly repair physical damage produced by the initial injury, or cure the illness, it provides symptomatic treatment. Furthermore, it does not replace other treatments/more traditional forms of rehabilitation but rather it augments these therapies to potentially produce additional improvement, and provides patients with a therapy that can be continued once the medical system is no longer able to help.
To begin, users select a specific exercise based on improving one of three mental traits that tend to be deficient in TBI and concussion patients: attention, stress control, and “mental clarity”. While performing each exercise, users are provided with a direct score from 1 to 100 in real-time for the metric said specific exercise is intended to improve. By altering their thinking or performing specific mental exercises, users are able to alter their mental state into that which the specific exercise aims for (e.g. an attentive state); with the numeric feedback informing the user of how successfully they're achieving that mental state. The techniques learned and used during the exercise allow the user to call up the desired state when needed (e.g. high attention) when not performing the exercise, by strengthening neural connections associated with said state. Included with each neurofeedback exercise is a series of methods for calling up the desired state: mental strategies, which are based on those used to increase the associated metrics. Also, feedback is given following each session on ways the user can improve their performance. Scores are tracked over time, so patients can monitor their progress on each of the 3 metrics.
Following a neurofeedback session (of any exercise), a total score is shown to the user, along with a chart showing how their brain activity went up and down throughout the session. Advice for improvement is also provided. Users are therefore able to see their progress over time on each exercise on a series of charts. Scores for all previous exercise sessions are included, so users can see their improvement. This will provide users with motivation to continue, i.e. a gamification element, and help them understand the kinds of functional improvements they should be seeing in day-to-day life. It also introduces a placebo element as while the exercises are effective on their own, any intervention is more effective if users know they're receiving it.
Within embodiments of the invention described supra in respect of FIGS. 1 through 12 the signal processing and analysis of raw EEG data acquired from an EEG sensor or sensors has been described and presented as being performed on a PED/FED associated with the user with further analysis being performed on a remote server system. It would be evident to one skilled in the art that the analysis of EEG data relating to a user may be performed in some embodiments solely on the user's PED/FED, in other embodiments of the invention this processing may be solely on the remote server system, and in others distributed between the user's PED/FED and the remote server system. In other embodiments of the invention initial processing or pre-processing of the EEG data may be performed at the user's PED/FED and then more detailed analysis and post-processing applied at the remote server. In other embodiments of the invention initial processing may be performed upon the current EEG data and/or an EEG data stored relating to a recent predetermined period of time whilst processing over a longer historical period of time is performed on the remote server that stores user EEG data historically. This historical backup of EEG data being performed for example by MyBrain™ as described supra.
Specific details are given in the above description to provide a thorough understanding of the embodiments. However, it is understood that the embodiments may be practiced without these specific details. For example, circuits may be shown in block diagrams in order not to obscure the embodiments in unnecessary detail. In other instances, well-known circuits, processes, algorithms, structures, and techniques may be shown without unnecessary detail in order to avoid obscuring the embodiments.
Implementation of the techniques, blocks, steps and means described above may be done in various ways. For example, these techniques, blocks, steps and means may be implemented in hardware, software, or a combination thereof. For a hardware implementation, the processing units may be implemented within one or more application specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), Programmable Logic Devices (PLDs), field programmable gate arrays (FPGAs), processors, controllers, micro-controllers, microprocessors, other electronic units designed to perform the functions described above and/or a combination thereof.
Also, it is noted that the embodiments may be described as a process which is depicted as a flowchart, a flow diagram, a data flow diagram, a structure diagram, or a block diagram. Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be rearranged. A process is terminated when its operations are completed, but could have additional steps not included in the figure. A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc. When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function.
Furthermore, embodiments may be implemented by hardware, software, scripting languages, firmware, middleware, microcode, hardware description languages and/or any combination thereof. When implemented in software, firmware, middleware, scripting language and/or microcode, the program code or code segments to perform the necessary tasks may be stored in a machine readable medium, such as a storage medium. A code segment or machine-executable instruction may represent a procedure, a function, a subprogram, a program, a routine, a subroutine, a module, a software package, a script, a class, or any combination of instructions, data structures and/or program statements. A code segment may be coupled to another code segment or a hardware circuit by passing and/or receiving information, data, arguments, parameters and/or memory contents. Information, arguments, parameters, data, etc. may be passed, forwarded, or transmitted via any suitable means including memory sharing, message passing, token passing, network transmission, etc.
For a firmware and/or software implementation, the methodologies may be implemented with modules (e.g., procedures, functions, and so on) that perform the functions described herein. Any machine-readable medium tangibly embodying instructions may be used in implementing the methodologies described herein. For example, software codes may be stored in a memory. Memory may be implemented within the processor or external to the processor and may vary in implementation where the memory is employed in storing software codes for subsequent execution to that when the memory is employed in executing the software codes. As used herein the term “memory” refers to any type of long term, short term, volatile, nonvolatile, or other storage medium and is not to be limited to any particular type of memory or number of memories, or type of media upon which memory is stored.
Moreover, as disclosed herein, the term “storage medium” may represent one or more devices for storing data, including read only memory (ROM), random access memory (RAM), magnetic RAM, core memory, magnetic disk storage mediums, optical storage mediums, flash memory devices and/or other machine readable mediums for storing information. The term “machine-readable medium” includes, but is not limited to portable or fixed storage devices, optical storage devices, wireless channels and/or various other mediums capable of storing, containing or carrying instruction(s) and/or data.
The methodologies described herein are, in one or more embodiments, performable by a machine which includes one or more processors that accept code segments containing instructions. For any of the methods described herein, when the instructions are executed by the machine, the machine performs the method. Any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine are included. Thus, a typical machine may be exemplified by a typical processing system that includes one or more processors. Each processor may include one or more of a CPU, a graphics-processing unit, and a programmable DSP unit. The processing system further may include a memory subsystem including main RAM and/or a static RAM, and/or ROM. A bus subsystem may be included for communicating between the components. If the processing system requires a display, such a display may be included, e.g., a liquid crystal display (LCD). If manual data entry is required, the processing system also includes an input device such as one or more of an alphanumeric input unit such as a keyboard, a pointing control device such as a mouse, and so forth.
The memory includes machine-readable code segments (e.g. software or software code) including instructions for performing, when executed by the processing system, one of more of the methods described herein. The software may reside entirely in the memory, or may also reside, completely or at least partially, within the RAM and/or within the processor during execution thereof by the computer system. Thus, the memory and the processor also constitute a system comprising machine-readable code.
In alternative embodiments, the machine operates as a standalone device or may be connected, e.g., networked to other machines, in a networked deployment, the machine may operate in the capacity of a server or a client machine in server-client network environment, or as a peer machine in a peer-to-peer or distributed network environment. The machine may be, for example, a computer, a server, a cluster of servers, a cluster of computers, a web appliance, a distributed computing environment, a cloud computing environment, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine. The term “machine” may also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.
The foregoing disclosure of the exemplary embodiments of the present invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many variations and modifications of the embodiments described herein will be apparent to one of ordinary skill in the art in light of the above disclosure. The scope of the invention is to be defined only by the claims appended hereto, and by their equivalents.
Further, in describing representative embodiments of the present invention, the specification may have presented the method and/or process of the present invention as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process of the present invention should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the present invention. | With explosive penetration of portable electronic devices (PEDs) recent focus into consumer EEG devices has been to bring advantages including localized wireless interfacing, portability, and a low-cost high-performance electronics platform to host the processing algorithms to bear. However, most development continues to focus on brain-controlled video games which are nearly identical to those created for earlier, more stationary consumer EEG devices and personal EEG is treated as of a novelty or toy. According to embodiments of the invention the inventors have established new technologies and solutions that address these limitations within the prior art and provide benefits including, but not limited to, global acquisition and storage of acquired EEG data and processed EEG data, development interfaces for expansion and re-analysis of acquired EEG data, integration to other non-EEG derived user data, and long-term user wearability. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
The present invention is a continuation of U.S. patent application Ser. No. 13/411,348 entitled VENTILATION MASK WITH INTEGRATED PILOTED EXHALATION VALVE filed Mar. 12, 2012, which claims priority to U.S. Provisional Patent Application Ser. No. 61/499,950 entitled VENTILATION MASK WITH INTEGRATED PILOTED EXHALATION VALVE filed Jun. 22, 2011 and U.S. Provisional Patent Application Ser. No. 61/512,750 entitled VENTILATION MASK WITH INTEGRATED PILOTED EXHALATION VALVE AND METHOD OF VENTILATING A PATIENT USING THE SAME filed Jul. 28, 2011, the disclosures of which are incorporated herein by reference.
STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT
Not Applicable
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to systems and methods for controlling delivery of a pressurized flow of breathable gas to a patient and, more particularly, to a ventilation mask such as a full face mask, nasal mask, nasal prongs mask or nasal pillows mask for use in critical care ventilation, respiratory insufficiency or OSA (obstructive sleep apnea) with CPAP (Continuous Positive Airway Pressure) therapy and incorporating a piloted exhalation valve inside the mask.
2. Description of the Related Art
As is known in the medical arts, mechanical ventilators comprise medical devices that either perform or supplement breathing for patients. Early ventilators, such as the “iron lung”, created negative pressure around the patient's chest to cause a flow of ambient air through the patient's nose and/or mouth into their lungs. However, the vast majority of contemporary ventilators instead use positive pressure to deliver gas to the patient's lungs via a patient circuit between the ventilator and the patient. The patient circuit typically consists of one or two large bore tubes (e.g., from 22 mm ID for adults to 8 mm ID for pediatric) that interface to the ventilator on one end, and a patient mask on the other end. Most often, the patient mask is not provided as part of the ventilator system, and a wide variety of patient masks can be used with any ventilator. The interfaces between the ventilator, patient circuit and patient masks are standardized as generic conical connectors, the size and shape of which are specified by regulatory bodies (e.g., ISO 5356-1 or similar standards).
Current ventilators are designed to support either “vented” or “leak” circuits, or “non-vented” or “non-leak” circuits. In vented circuits, the mask or patient interface is provided with an intentional leak, usually in the form of a plurality of vent openings. Ventilators using this configuration are most typically used for less acute clinical requirements, such as the treatment of obstructive sleep apnea or respiratory insufficiency. In non-vented circuits, the patient interface is usually not provided with vent openings. Non-vented circuits can have single limb or dual limb patient circuits, and an exhalation valve. Ventilators using non-vented patient circuits are most typically used for critical care applications.
Vented patient circuits are used only to carry gas flow from the ventilator to the patient and patient mask, and require a patient mask with vent openings. When utilizing vented circuits, the patient inspires fresh gas from the patient circuit, and expires CO2-enriched gas, which is purged from the system through the vent openings in the mask. This constant purging of flow through vent openings in the mask when using single-limb circuits provides several disadvantages: 1) it requires the ventilator to provide significantly more flow than the patient requires, adding cost/complexity to the ventilator and requiring larger tubing; 2) the constant flow through the vent openings creates and conducts noise, which has proven to be a significant detriment to patients with sleep apnea that are trying to sleep while wearing the mask; 3) the additional flow coming into proximity of the patient's nose and then exiting the system often causes dryness in the patient, which often drives the need for adding humidification to the system; and 4) patient-expired CO2 flows partially out of the vent holes in the mask and partially into the patient circuit tubing, requiring a minimum flow through the tubing at all times in order to flush the CO2 and minimize the re-breathing of exhaled CO2. To address the problem of undesirable flow of patient-expired CO2 back into the patient circuit tubing, currently known CPAP systems typically have a minimum-required pressure of 4 cm H2O whenever the patient is wearing the mask, which often produces significant discomfort, claustrophobia and/or feeling of suffocation to early CPAP users and leads to a high (approximately 50%) non-compliance rate with CPAP therapy.
When utilizing non-vented dual limb circuits, the patient inspires fresh gas from one limb (the “inspiratory limb”) of the patient circuit and expires CO2-enriched gas from the second limb (the “expiratory limb”) of the patient circuit. Both limbs of the dual limb patient circuit are connected together in a “Y” proximal to the patient to allow a single conical connection to the patient mask. When utilizing non-vented single limb circuits, an expiratory valve is placed along the circuit, usually proximal to the patient. During the inhalation phase, the exhalation valve is closed to the ambient and the patient inspires fresh gas from the single limb of the patient circuit. During the exhalation phase, the patient expires CO2-enriched gas from the exhalation valve that is open to ambient. The single limb and exhalation valve are usually connected to each other and to the patient mask with conical connections.
In the patient circuits described above, the ventilator pressurizes the gas to be delivered to the patient inside the ventilator to the intended patient pressure, and then delivers that pressure to the patient through the patient circuit. Very small pressure drops develop through the patient circuit, typically around 1 cm H2O, due to gas flow though the small amount of resistance created by the tubing. Some ventilators compensate for this small pressure drop either by mathematical algorithms, or by sensing the tubing pressure more proximal to the patient.
Ventilators that utilize a dual limb patient circuit typically include an exhalation valve at the end of the expiratory limb proximal to the ventilator, while ventilators that utilize a single limb, non-vented patient circuit typically include an exhalation valve at the end of the single limb proximal to the patient as indicated above. Exhalation valves can have fixed or adjustable PEEP (positive expiratory end pressure), typically in single limb configurations, or can be controlled by the ventilator. The ventilator controls the exhalation valve, closes it during inspiration, and opens it during exhalation. Less sophisticated ventilators have binary control of the exhalation valve, in that they can control it to be either open or closed. More sophisticated ventilators are able to control the exhalation valve in an analog fashion, allowing them to control the pressure within the patient circuit by incrementally opening or closing the valve. Valves that support this incremental control are referred to as active exhalation valves. In existing ventilation systems, active exhalation valves are most typically implemented physically within the ventilator, and the remaining few ventilation systems with active exhalation valves locate the active exhalation valve within the patient circuit proximal to the patient. Active exhalation valves inside ventilators are typically actuated via an electromagnetic coil in the valve, whereas active exhalation valves in the patient circuit are typically pneumatically piloted from the ventilator through a separate pressure source such a secondary blower, or through a proportional valve modulating the pressure delivered by the main pressure source.
BRIEF SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided a mask (e.g., a nasal pillows mask) for achieving positive pressure mechanical ventilation (inclusive of CPAP, ventilatory support, critical care ventilation, emergency applications), and a method for a operating a ventilation system including such mask. The mask preferably includes a pressure sensing modality proximal to the patient connection. Such pressure sensing modality may be a pneumatic port with tubing that allows transmission of the patient pressure back to the ventilator for measurement, or may include a transducer within the mask. The pressure sensing port is used in the system to allow pressure sensing for achieving and/or monitoring the therapeutic pressures. Alternately or additionally, the mask may include a flow sensing modality located therewithin for achieving and/or monitoring the therapeutic flows.
The mask of the present invention also includes a piloted exhalation valve that is used to achieve the target pressures/flows to the patient. In the preferred embodiment, the pilot for the valve is pneumatic and driven from the gas supply tubing from the ventilator. The pilot can also be a preset pressure derived in the mask, a separate pneumatic line from the ventilator, or an electro-mechanical control. In accordance with the present invention, the valve is preferably implemented with a diaphragm.
One of the primary benefits attendant to including the valve inside the mask is that it provides a path for patient-expired CO2 to exit the system without the need for a dual-limb patient circuit, and without the disadvantages associated with a single-limb patient circuit, such as high functional dead space. For instance, in applications treating patients with sleep apnea, having the valve inside the mask allows patients to wear the mask while the treatment pressure is turned off without risk of re-breathing excessive CO2.
Another benefit for having the valve inside the mask is that it allows for a significant reduction in the required flow generated by the ventilator for ventilating the patient since a continuous vented flow for CO2 washout is not required. Lower flow in turn allows for the tubing size to be significantly smaller (e.g., 2-9 mm ID) compared to conventional ventilators (22 mm ID for adults; 8 mm ID for pediatric). However, this configuration requires higher pressures than the patient's therapeutic pressure to be delivered by the ventilator. In this regard, pressure from the ventilator is significantly higher than the patient's therapeutic pressure, though the total pneumatic power delivered is still smaller than that delivered by a low pressure, high flow ventilator used in conjunction with a vented patient circuit and interface. One obvious benefit of smaller tubing is that it provides less bulk for patient and/or caregivers to manage. For today's smallest ventilators, the bulk of the tubing is as significant as the bulk of the ventilator. Another benefit of the smaller tubing is that is allows for more convenient ways of affixing the mask to the patient. For instance, the tubing can go around the patient's ears to hold the mask to the face, instead of requiring straps (typically called “headgear”) to affix the mask to the face. Along these lines, the discomfort, complication, and non-discrete look of the headgear is another significant factor leading to the high non-compliance rate for CPAP therapy. Another benefit to the smaller tubing is that the mask can become smaller because it does not need to interface with the large tubing. Indeed, large masks are another significant factor leading to the high non-compliance rate for CPAP therapy since, in addition to being non-discrete, they often cause claustrophobia. Yet another benefit is that smaller tubing more conveniently routed substantially reduces what is typically referred to as “tube drag” which is the force that the tube applies to the mask, displacing it from the patient's face. This force has to be counterbalanced by headgear tension, and the mask movements must be mitigated with cushion designs that have great compliance. The reduction in tube drag in accordance with the present invention allows for minimal headgear design (virtually none), reduced headgear tension for better patient comfort, and reduced cushion compliance that results in a smaller, more discrete cushion.
The mask of the present invention may further include a heat and moisture exchanger (HME) which is integrated therein. The HME can fully or at least partially replace a humidifier (cold or heated pass-over; active or passive) which may otherwise be included in the ventilation system employing the use of the mask. The HME is positioned within the mask so as to be able to intercept the flow delivered from a flow generator to the patient in order to humidify it, and further to intercept the exhaled flow of the patient in order to capture humidity and heat for the next breath. The HME can also be used as a structural member of the mask, adding q cushioning effect and simplifying the design of the cushion thereof.
The present invention is best understood by reference to the following detailed description when read in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
These, as well as other features of the present invention, will become more apparent upon reference to the drawings wherein:
FIG. 1 is top perspective view of a nasal pillows mask constructed in accordance with the present invention and including an integrated diaphragm-based piloted exhalation valve;
FIG. 2 is an exploded view of the nasal pillows mask shown in FIG. 1 ;
FIG. 3 is a partial cross-sectional view of the nasal pillows mask shown in FIG. 1 taken along lines 3 - 3 thereof, and depicting the valve pilot lumen extending through the cushion of the mask;
FIG. 4 is a partial cross-sectional view of the nasal pillows mask shown in FIG. 1 taken along lines 4 - 4 thereof, and depicting the pressure sensing lumen extending through the cushion of the mask;
FIG. 5 is a cross-sectional view of the nasal pillows mask shown in FIG. 1 taken along lines 5 - 5 thereof;
FIG. 6 is a top perspective view of cushion of the nasal pillows mask shown in FIG. 1 ;
FIG. 7 is a top perspective view of exhalation valve of the nasal pillows mask shown in FIG. 1 ;
FIG. 8 is a bottom perspective view of exhalation valve shown in FIG. 7 ;
FIG. 9 is a cross-sectional view of exhalation valve shown in FIGS. 7 and 8 ;
FIG. 10 is a cross-sectional view similar to FIG. 5 , but depicting a variant of the nasal pillows mask wherein an HME is integrated into the cushion thereof;
FIGS. 11A , 11 B and 11 C are a series of graphs which provide visual representations corresponding to exemplary performance characteristics of the exhalation valve subassembly of the nasal pillows mask of the present invention;
FIG. 12 is a schematic representation of an exemplary ventilation system wherein a tri-lumen tube is used to facilitate the operative interface between the nasal pillows mask and a flow generating device;
FIG. 13 is a schematic representation of an exemplary ventilation system wherein a bi-lumen tube is used to facilitate the operative interface between the nasal pillows mask and a flow generating device; and
FIG. 14 is a side-elevational view of the nasal pillows mask of the present invention depicting an exemplary manner of facilitating the cooperative engagement thereof to a patient through the use of a headgear assembly.
Common reference numerals are used throughout the drawings and detailed description to indicate like elements.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the drawings wherein the showings are for purposes of illustrating various embodiments of the present invention only, and not for purposes of limiting the same, FIGS. 1-4 depict a ventilation mask 10 (e.g., a nasal pillows mask) constructed in accordance with the present invention. Though the mask 10 is depicted as a nasal pillows mask, those skilled in the art will recognize that other ventilation masks are contemplated herein, such as nasal prongs masks, nasal masks, fill face masks and oronasal masks. As such, for purposes of this application, the term mask and/or ventilation mask is intended to encompass all such mask structures. The mask 10 includes an integrated, diaphragm-implemented, piloted exhalation valve 12 , the structural and functional attributes of which will be described in more detail below.
As shown in FIGS. 1-5 , the mask 10 comprises a housing or cushion 14 . The cushion 14 , which is preferably fabricated from a silicone elastomer having a Shore A hardness in the range of from about 20 to 60 and preferably about 40, is formed as a single, unitary component, and is shown individually in FIG. 6 . The cushion 14 includes a main body portion 16 which defines a first outer end surface 18 and an opposed second outer end surface 20 . The main body portion 16 further defines an interior fluid chamber 22 which is of a prescribed volume. In addition to the main body portion 16 , the cushion 14 includes an identically configured pair of hollow pillow portions 24 which protrude from the main body portion 16 in a common direction and in a prescribed spatial relationship relative to each other. More particularly, in the cushion 14 , the spacing between the pillow portions 24 is selected to facilitate the general alignment thereof with the nostrils of an adult patient when the mask 10 is worn by such patient. As seen in FIGS. 3 and 4 , each of the pillow portions 24 fluidly communicates with the fluid chamber 22 .
As shown in FIG. 2 , the main body portion 16 of the cushion 14 includes an enlarged, circularly configured valve opening 26 which is in direct fluid communication with the fluid chamber 22 . The valve opening 26 is positioned in generally opposed relation to the pillow portions 24 of the cushion 14 , and is circumscribed by an annular valve seat 27 also defined by the main body portion 16 . As also shown in FIG. 2 , the main body portion 16 further defines opposed first and second inner end surfaces 28 , 30 which protrude outwardly from the periphery of the valve opening 26 , and are diametrically opposed relative thereto so as to be spaced by an interval of approximately 180°. The valve opening 26 , valve seat 27 , and first and second inner end surfaces 28 , 30 are adapted to accommodate the exhalation valve 12 of the mask 10 in a manner which will be described in more detail below.
As shown FIGS. 3-6 , the main body portion 16 of the cushion 14 further defines first and second gas delivery lumens 32 , 34 which extend from respective ones of the first and second outer end surfaces 18 , 20 into fluid communication with the fluid chamber 22 . Additionally, a pressure sensing lumen 36 defined by the main body portion extends from the first outer end surface 18 into fluid communication with the fluid chamber 22 . The main body portion 16 further defines a valve pilot lumen 38 which extends between the second outer end surface 20 and the second inner end surface 30 . The use of the first and second gas delivery lumens 32 , 34 , the pressure sensing lumen 36 , and the valve pilot lumen 38 will also be discussed in more detail below. Those of ordinary skill in the art will recognize that the gas delivery lumens 32 , 34 , may be substituted with a single gas delivery lumen and/or positioned within the cushion 14 in orientations other than those depicted in FIG. 6 . For example, the gas delivery lumen(s) of the cushion 14 may be positioned frontally, pointing upwardly, pointing downwardly, etc. rather than extending laterally as shown in FIG. 6 .
Referring now to FIGS. 2-5 and 7 - 9 , the exhalation valve 12 of the mask 10 is made of three (3) parts or components, and more particularly a seat member 40 , a cap member 42 , and a diaphragm 44 which is operatively captured between the seat and cap members 40 , 42 . The seat and cap members 40 , 42 are each preferably fabricated from a plastic material, with the diaphragm 44 preferably being fabricated from an elastomer having a Shore A hardness in the range of from about 20-40.
As is most easily seen in FIGS. 2 , 7 and 9 , the seat member 40 includes a tubular, generally cylindrical wall portion 46 which defines a distal, annular outer rim 48 and an opposed annular inner seating surface 49 . As shown in FIG. 9 , the diameter of the outer rim 48 exceeds that of the seating surface 49 . Along these lines, the inner surface of the wall portion 46 is not of a uniform inner diameter, but rather is segregated into first and second inner surface sections which are of differing inner diameters, and separated by an annular shoulder 51 . In addition to the wall portion 46 , the seat member 40 includes an annular flange portion 50 which protrudes radially from that end of the wall portion 46 opposite the outer rim 48 . As shown in FIGS. 2 and 7 , the flange portion 50 includes a plurality of exhaust vents 52 which are located about the periphery thereof in a prescribed arrangement and spacing relative to each other. Additionally, as is apparent from FIG. 9 , the seat member 40 is formed such that each of the exhaust vents 52 normally fluidly communicates with the bore or fluid conduit defined by the wall portion 46 .
The cap member 42 of the exhaust valve 12 comprises a circularly configured base portion 54 which defines an inner surface 56 and an opposed outer surface 58 . In addition to the base portion 54 , the cap member 42 includes an annular flange portion 60 which circumvents and protrudes generally perpendicularly relative to the inner surface 56 of the base portion 60 . The flange portion 60 defines a distal annular shoulder 62 . As shown in FIG. 9 , the shoulder 62 and inner surface 56 extend along respective ones of a spaced, generally parallel pair of planes. Further, as shown in FIG. 8 , formed in the outer surface 58 of the base portion 54 is an elongate groove 64 which extends diametrically across the outer surface 58 . The use of the groove 64 will be described in more detail below. The seat and cap members 40 , 42 , when attached to each other in the fully assembled exhalation valve 12 , collectively define an interior valve chamber 59 of the exhalation valve 12 . More particularly, such valve chamber 59 is generally located between the inner surface 56 defined by the base portion 54 of the cap member 42 and the seating surface 49 defined by the wall portion 46 of the seat member 40 .
The diaphragm 44 of the exhalation valve 12 , which resides within the valve chamber 59 , has a circularly configured, central body portion 66 , and a peripheral flange portion 68 which is integrally connected to and circumvents the body portion 66 . The body portion 66 includes an annular lip 72 which circumvents and protrudes upwardly from one side or face thereof. The flange portion 68 includes an arcuately contoured primary region and a distal region which protrudes radially from the primary region. As such, the primary region of the flange portion 68 extends between the distal region thereof and the body portion 66 , and defines a continuous, generally concave channel 70 .
In the exhalation valve 12 , the flange portion 68 of the diaphragm 44 is operatively captured between the flange portions 50 , 60 of the seat and cap members 40 , 42 . More particularly, the annular distal region of the flange portion 68 is compressed (and thus captured) between the shoulder 62 defined by the flange portion 60 of the cap member 42 , and a complimentary annular shoulder 53 which is defined by the flange portion 50 of the seat member 40 proximate the exhaust vents 52 . The orientation of the diaphragm 44 within the valve chamber 59 when captured between the seat and cap members 40 , 42 is such that the channel 70 defined by the arcuately contoured primary region of the flange portion 68 is directed toward or faces the seating surface 49 defined by the wall portion 46 of the seat member 40 .
The diaphragm 44 (and hence the exhalation valve 12 ) is selectively moveable between an open position (shown in FIGS. 3-5 and 9 ) and a closed position. When in its normal, open position, the diaphragm 44 is in a relaxed, unbiased state. Importantly, in either of its open or closed positions, the diaphragm 44 is not normally seated directly against the inner surface 56 defined by the base portion 54 of the cap member 42 . Rather, a gap is normally maintained between the body portion 66 of the diaphragm 44 and the inner surface 56 of the base portion 54 . The width of such gap when the diaphragm 44 is in its open position is generally equal to the fixed distance separating the inner surface 56 of the base portion 54 from the shoulder 62 of the flange portion 60 . Further, when the diaphragm 44 is in its open position, the body portion 66 , and in particular the lip 72 protruding therefrom, is itself disposed in spaced relation to the seating surface 49 defined by the wall portion 46 of the seat member 40 . As such, when the diaphragm 44 is in its open position, fluid is able to freely pass through the fluid conduit defined by the wall portion 46 , between the seating surface 49 and diaphragm 44 , and through the exhaust vents 52 to ambient air. As shown in FIGS. 3 , 8 and 9 , the flange portion 60 of the cap member 42 is further provided with a pilot port 74 which extends therethrough and, in the fully assembled exhalation valve 12 , fluidly communicates with that portion of the valve chamber 59 disposed between the body portion 66 of the diaphragm 44 and the inner surface 56 of the base portion 54 . The use of the pilot port 74 will also be described in more detail below.
As will be discussed in more detail below, in the exhalation valve 12 , the diaphragm 44 is resiliently deformable from its open position (to which it may be normally biased) to its closed position. An important feature of the present invention is that the diaphragm 44 is normally biased to its open position which provides a failsafe to allow a patient to inhale ambient air through the exhalation valve 12 and exhale ambient air therethrough (via the exhaust vents 52 ) during any ventilator malfunction or when the mask is worn without the therapy being delivered by the ventilator. When the diaphragm 44 is moved or actuated to its closed position, the lip 72 of the body portion 66 is firmly seated against the seating surface 49 defined by the wall portion 46 of the seat member 40 . The seating of the lip 72 against the seating surface 49 effectively blocks fluid communication between the fluid conduit defined by the wall portion 46 and the valve chamber 59 (and hence the exhaust vents 52 which fluidly communicate with the valve chamber 59 ).
In the mask 10 , the cooperative engagement between the exhalation valve 12 and the cushion 14 is facilitated by the advancement of the wall portion 46 of the seat member 40 into the valve opening 26 defined by the cushion 14 . As best seen in FIG. 5 , such advancement is limited by the ultimate abutment or engagement of a beveled seating surface 76 defined by the flange portion 50 of the seat member 40 against the complimentary valve seat 27 of the cushion 14 circumventing the valve opening 26 . Upon the engagement of the seating surface 76 to the valve seat 27 , the fluid chamber 22 of the cushion 14 fluidly communicates with the fluid conduit defined by the wall portion 46 of the seat member 40 . As will be recognized, if the diaphragm 44 resides in its normal, open position, the fluid chamber 22 is further placed into fluid communication with the valve chamber 59 via the fluid conduit defined by the wall portion 46 , neither end of which is blocked or obstructed by virtue of the gap defined between the lip 72 of the diaphragm 44 and the seating surface 49 of the wall portion 46 .
When the exhalation valve 12 is operatively coupled to the cushion 14 , in addition to the valve seat 27 being seated against the seating surface 76 , the first and second inner end surfaces 28 , 30 of the cushion 14 are seated against respective, diametrically opposed sections of the flange portion 68 defined by the cap member 42 . As best seen in FIGS. 3 and 4 , the orientation of the exhalation valve 12 relative to the cushion 14 is such that the end of the valve pilot lumen 38 extending to the second inner end surface 30 is aligned and fluidly communicates with the pilot port 74 within the flange portion 60 . As such, in the mask 10 , the valve pilot lumen 38 is in continuous, fluid communication with that portion of the valve chamber 59 defined between the inner surface 56 of the base portion 54 and the body portion 66 of the diaphragm 44 .
To assist in maintaining the cooperative engagement between the exhalation valve 12 and the cushion 14 , the mask 10 is further preferably provided with an elongate frame member 78 . The frame member 78 has a generally V-shaped configuration, with a central portion thereof being accommodated by and secured within the complimentary groove 64 formed in the outer surface 58 defined by the base portion 54 of the cap member 42 . As shown in FIGS. 3 and 4 , the opposed end portions of the frame members 78 are cooperatively engaged to respective ones of the first and second outer end surfaces 18 , 20 of the cushion 14 . More particularly, as shown in FIG. 2 , the frame member 78 includes an identically configured pair of first and second connectors 80 , 82 which extend from respective ones of the opposed end portions thereof. An inner portion of the first connector 80 is advanced into and frictionally retained within the first gas delivery lumen 32 of the cushion 14 . Similarly, an inner portion of the second connector 82 is advanced into and frictionally retained within the second gas delivery lumen 34 of the cushion 14 . In addition to the inner portions advanced into respective ones of the first and second gas delivery lumens 32 , 34 , the first and second connectors 80 , 82 of the frame member 78 each further include an outer portion which, as will be described in more detail below, is adapted to be advanced into and frictionally retained within a corresponding lumen of a respective one of a pair of bi-lumen tubes fluidly coupled to the mask 10 .
As shown in FIGS. 3 and 4 , the frame member 78 further includes a tubular, cylindrically configured pressure port 84 which is disposed adjacent the first connector 80 . The pressure port 84 is aligned and fluidly communicates with the pressure sensing lumen 36 of the cushion 14 . Similarly, the frame member 78 is also provided with a tubular, cylindrically configured pilot port 86 which is disposed adjacent the second connector 82 . The pilot port 86 is aligned and fluidly communicates with the valve pilot lumen 38 of the cushion 14 . As will also be discussed in more detail below, the pressure and pilot ports 84 , 86 of the frame member 78 are adapted to be advanced into and frictionally maintained within corresponding lumens of respective ones of the aforementioned pair of bi-lumen tubes which are fluidly connected to the mask 10 within a ventilation system incorporating the same. The receipt of the frame member 78 within the groove 64 of the cap member 42 ensures that the cushion 14 , the exhalation valve 12 and the frame member 78 are properly aligned, and prevents relative movement therebetween. Though not shown, it is contemplated that in one potential variation of the mask 10 , the cushion 14 may be formed so as not to include the valve pilot lumen 38 . Rather, a suitable valve pilot lumen would be formed directly within the frame member 78 so as to extend therein between the pilot port 86 thereof and the pilot port 74 of the exhalation valve 12 .
In the mask 10 , the exhalation valve 12 is piloted, with the movement of the diaphragm 44 to the closed position described above being facilitated by the introduction of positive fluid pressure into the valve chamber 59 . More particularly, it is contemplated that during the inspiratory phase of the breathing cycle of a patient wearing the mask 10 , the valve pilot lumen 38 will be pressurized by a pilot line fluidly coupled to the pilot port 86 , with pilot pressure being introduced into that portion of the valve chamber 59 normally defined between the body portion 66 of the diaphragm 44 and the inner surface 56 defined by the base portion 54 of the cap member 42 via the pilot port 74 extending through the flange portion 60 of the cap member 42 . The fluid pressure level introduced into the aforementioned region of the valve chamber 59 via the pilot port 74 will be sufficient to facilitate the movement of the diaphragm 44 to its closed position described above.
Conversely, during the expiratory phase of the breathing cycle of the patient wearing the mask 10 , it is contemplated that the discontinuation or modulation of the fluid pressure through the valve pilot lumen 38 and hence into the aforementioned region of the valve chamber 59 via the pilot port 74 , coupled with the resiliency of the diaphragm 44 and/or positive pressure applied to the body portion 66 thereof, will facilitate the movement of the diaphragm 44 back to the open position or to a partially open position. In this regard, positive pressure as may be used to facilitate the movement of the diaphragm 44 to its open position may be provided by air which is exhaled from the patient during the expiratory phase of the breathing circuit and is applied to the body portion 66 via the pillows portions 24 of the cushion 14 , the fluid chamber 22 , and the fluid conduit defined by the wall portion of the seat member 40 . As will be recognized, the movement of the diaphragm 44 to the open position allows the air exhaled from the patient to be vented to ambient air after entering the valve chamber 59 via the exhaust vents 52 within the flange portion 50 of the seat member 40 which, as indicated above, fluidly communicate with the valve chamber 59 .
As will be recognized, based on the application of pilot pressure thereto, the diaphragm 44 travels from a fully open position through a partially open position to a fully closed position. In this regard, the diaphragm 44 will be partially open or partially closed during exhalation to maintain desired ventilation therapy. Further, when pilot pressure is discontinued to the diaphragm 44 , it moves to an open position wherein the patient can inhale and exhale through the mask 10 with minimal restriction and with minimal carbon dioxide retention therein. This is an important feature of the present invention which allows a patient to wear the mask 10 without ventilation therapy being applied to the mask 10 , the aforementioned structural and functional features of the mask 10 making it more comfortable to wear, and further allowing it to be worn without carbon dioxide buildup. This feature is highly advantageous for the treatment of obstructive sleep apnea wherein patients complain of discomfort with ventilation therapy due to mask and pressure discomfort. When it is detected that a patient requires sleep apnea therapy, the ventilation therapy can be started (i.e., in an obstructive sleep apnea situation).
To succinctly summarize the foregoing description of the structural and functional features of the mask 10 , during patient inhalation, the valve pilot lumen 38 is pressurized, which causes the diaphragm 44 to close against the seating surface 49 , thus effectively isolating the fluid chamber 22 of the mask 10 from the outside ambient air. The entire flow delivered from a flow generator fluidly coupled to the mask 10 is inhaled by the patient, assuming that unintentional leaks at the interface between the cushion 14 and the patient are discarded. This functionality differs from what typically occurs in a conventional CPAP mask, where venting to ambient air is constantly open, and an intentional leak flow is continuously expelled to ambient air. During patient exhalation, the pilot pressure introduced into the valve pilot lumen 38 is controlled so that the exhaled flow from the patient can be exhausted to ambient air through the exhalation valve 12 in the aforementioned manner. In this regard, the pilot pressure is “servoed” so that the position of the diaphragm 44 relative to the seating surface 49 is modulated, hence modulating the resistance of the exhalation valve 12 to the exhaled flow and effectively ensuring that the pressure in the fluid chamber 22 of the mask 10 is maintained at a prescribed therapeutic level throughout the entire length of the exhalation phase. When the valve pilot lumen 38 is not pressurized, the exhalation valve 12 is in a normally open state, with the diaphragm 44 being spaced from the seating surface 49 in the aforementioned manner, thus allowing the patient to spontaneously breathe in and out with minimal pressure drop (also referred to as back-pressure) in the order of less than about 2 cm H2O at 601/min. As a result, the patient can comfortably breathe while wearing the mask 10 and while therapy is not being administered to the patient.
Referring now to FIGS. 11A , 11 B and 11 C, during use of the mask 10 by a patient, the functionality of the exhalation valve 12 can be characterized with three parameters. These are Pt which is the treatment pressure (i.e., the pressure in the mask 10 used to treat the patient; Pp which is the pilot pressure (i.e., the pressure used to pilot the diaphragm 44 in the exhalation valve 12 ); and Qv which is vented flow (i.e., flow that is exhausted from inside the exhalation valve 12 to ambient. These three particular parameters are labeled as Pt, Pp and Qv in FIG. 9 . When the patient is ventilated, Pt is greater than zero, with the functionality of the exhalation valve 12 being described by the family of curves in the first and second quadrants of FIG. 11A . In this regard, as apparent from FIG. 11A , for any given Pt, it is evident that by increasing the pilot pressure Pp, the exhalation valve 12 will close and the vented flow will decrease. A decrease in the pilot pressure Pp will facilitate the opening of the valve 12 , thereby increasing vented flow. The vented flow will increase until the diaphragm 44 touches or contacts the inner surface 56 of the base portion 54 of the cap member 42 , and is thus not able to open further. Conversely, when the patient is not ventilated, the inspiratory phase can be described by the third and fourth quadrants. More particularly, Qv is negative and air enters the mask 10 through the valve 12 , with the pressure Pt in the mask 10 being less than or equal to zero. Pilot pressure Pp less than zero is not a configuration normally used during ventilation of the patient, but is depicted for a complete description of the functionality of the valve 12 . The family of curves shown in FIG. 11A can be described by a parametric equation. Further, the slope and asymptotes of the curves shown in FIG. 11A can be modified by, for example and not by way of limitation, changing the material used to fabricate the diaphragm 44 , changing the thickness of the diaphragm 44 , changing the area ratio between the pilot side and patient side of the diaphragm 44 , changing the clearance between the diaphragm 44 and the seating surface 49 , and/or changing the geometry of the exhaust vents 52 .
An alternative representation of the functional characteristics of the valve 12 can be described by graphs in which ΔP=Pt−Pp is shown. For example, the graph of FIG. 11B shows that for any given Pt, the vented flow can be modulated by changing ΔP. In this regard, ΔP can be interpreted as the physical position of the diaphragm 44 . Since the diaphragm 44 acts like a spring, the equation describing the relative position d of the diaphragm 44 from the seating surface 49 of the seat member 40 is k·d+Pt·At =Pp·Ap, where At is the area of the diaphragm 44 exposed to treatment pressure Pt and Ap is the area of the diaphragm 44 exposed to the pilot pressure Pp. A similar, alternative representation is provided in the graph of FIG. 11C which shows Pt on the x-axis and ΔP as the parameter. In this regard, for any given ΔP, the position d of the diaphragm 44 is determined, with the valve 12 thus being considered as a fixed opening valve. In this scenario Pt can be considered the driving pressure pushing air out of the valve 12 , with FIG. 11C further illustrating the highly non-linear behavior of the valve 12 .
FIG. 12 provides a schematic representation of an exemplary ventilation system 88 wherein a tri-lumen tube 90 is used to facilitate the fluid communication between the mask 10 and a blower or flow generator 92 of the system 88 . As represented in FIG. 12 , one end of the tri-lumen tube 90 is fluidly connected to the flow generator 92 , with the opposite end thereof being fluidly connected to a Y-connector 94 . The three lumens defined by the tri-lumen tube 90 include a gas delivery lumen, a pressure sensing lumen, and a valve pilot lumen. The gas delivery lumen is provided with an inner diameter or ID in the range of from about 2 mm to 15 mm, and preferably about 4 mm to 10 mm. The pressure sensing and valve pilot lumens of the tri-lumen tube 90 are each preferably provided with an ID in the range of from about 0.5 mm to 2 mm. The outer diameter or OD of the tri-lumen tube 90 is preferably less than 17 mm, with the length thereof in the system 88 being about 2 m. The Y-connector 94 effectively bifurcates the tri-lumen tube 90 into the first and second bi-lumen tubes 96 , 98 , each of which has a length of about 6 inches. The first bi-lumen tube 96 includes a gas delivery lumen having an ID in the same ranges described above in relation to the gas delivery lumen of the tri-lumen tube 90 . The gas delivery lumen of the first bi-lumen tube 96 is fluidly coupled to the outer portion of the first connector 80 of the frame member 78 . The remaining lumen of the first bi-lumen tube 96 is a pressure sensing lumen which has an ID in the same range described above in relation to the pressure sensing lumen of the tri-lumen tube 90 , and is fluidly coupled to the pressure port 84 of the frame member 78 . Similarly, the second bi-lumen tube 98 includes a gas delivery lumen having an ID in the same ranges described above in relation to the gas delivery lumen of the tri-lumen tube 90 . The gas delivery lumen of the second bi-lumen tube 98 is fluidly coupled to the outer portion of the second connector 82 of the frame member 78 . The remaining lumen of the second bi-lumen tube 98 is a valve pilot lumen which has an ID in the same range described above in relation to the valve pilot lumen of the tri-lumen tube 90 , and is fluidly coupled to the pilot port 86 of the frame member 78 .
In the system 88 shown in FIG. 12 , the pilot pressure is generated at the flow generator 92 . In the prior art, a secondary blower or proportional valve that modulates the pressure from a main blower is used to generate a pressure to drive an expiratory valve. However, in the system 88 shown in FIG. 12 , the outlet pressure of the flow generator 92 is used, with the flow generator 92 further being controlled during patient exhalation in order to have the correct pilot pressure for the exhalation valve 12 . This allows the system 88 to be inexpensive, not needing additional expensive components such as proportional valves or secondary blowers.
FIG. 13 provides a schematic representation of another exemplary ventilation system 100 wherein a bi-lumen tube 102 is used to facilitate the fluid communication between the mask 10 and the blower or flow generator 92 of the system 100 . As represented in FIG. 13 , one end of the bi-lumen tube 102 is fluidly connected to the flow generator 92 , with the opposite end thereof being fluidly connected to the Y-connector 94 . The two lumens defined by the bi-lumen tube 102 include a gas delivery lumen and a pressure sensing lumen. The gas delivery lumen is provided with an inner diameter or ID in the range of from about 2 mm to 10 mm, and preferably about 4 mm to 7 mm. The pressure sensing lumen of the bi-lumen tube 102 is preferably provided with an ID in the range of from about 0.5 mm to 2 mm. The outer diameter or OD of the bi-lumen tube 90 is preferably less than 11 mm, with the length thereof being about 2 m. The Y-connector 94 effectively bifurcates the bi-lumen tube 102 into the first and second bi-lumen tubes 96 , 98 , each of which has a length of about 6 inches. The first bi-lumen tube 96 includes a gas delivery lumen having an ID in the same ranges described above in relation to the gas delivery lumen of the bi-lumen tube 102 . The gas delivery lumen of the first bi-lumen tube 96 is fluidly coupled to the outer portion of the first connector 80 of the frame member 78 . The remaining lumen of the first bi-lumen tube 96 is a pressure sensing lumen which has an ID in the same range described above in relation to the pressure sensing lumen of the bi-lumen tube 102 , and is fluidly coupled to the pressure port 84 of the frame member 78 . Similarly, the second bi-lumen tube 98 includes a gas delivery lumen having an ID in the same ranges described above in relation to the gas delivery lumen of the bi-lumen tube 102 . The gas delivery lumen of the second bi-lumen tube 98 is fluidly coupled to the outer portion of the second connector 82 of the frame member 78 . The remaining lumen of the second bi-lumen tube 98 is a valve pilot lumen which has an ID in the same range described above in relation to the pressure sensing lumen of the bi-lumen tube 102 , and is fluidly coupled to the pilot port 86 of the frame member 78 .
In the system 100 shown in FIG. 13 , the valve pilot lumen 38 is connected to the gas delivery air path at the Y-connector 94 . More particularly, the gas delivery lumen of the bi-lumen tube 102 is transitioned at the Y-connector 94 to the valve pilot lumen of the second bi-lumen tube 98 . As such, the pilot pressure will be proportional to the outlet pressure of the flow generator 92 minus the pressure drop along the bi-lumen tube 102 , which is proportional to delivered flow. This solution is useful when small diameter tubes are used in the system 100 , since such small diameter tubes require higher outlet pressure from the flow generator 92 for the same flow. In this regard, since the pressure at the outlet of the flow generator 92 would be excessive for piloting the exhalation valve 12 , a lower pressure along the circuit within the system 100 is used. In the system 100 , though it is easier to tap in at the Y-connector 94 , anywhere along the tube network is acceptable, depending on the pressure level of the flow generator 92 which is the pressure required by the patient circuit in order to deliver the therapeutic pressure and flow at the patient.
In each of the systems 88 , 100 , it is contemplated that the control of the flow generator 92 , and hence the control of therapeutic pressure delivered to the patient wearing the mask 10 , may be governed by the data gathered from dual pressure sensors which take measurements at the mask 10 and the output of the flow generator 92 . As will be recognized, pressure sensing at the mask 10 is facilitated by the pressure sensing lumen 36 which, as indicated above, is formed within the cushion 14 and fluidly communicates with the fluid chamber 22 thereof. As also previously explained, one of the lumens of the first bi-lumen tube 96 in each of the systems 88 , 100 is coupled to the pressure port 84 (and hence the pressure sensing lumen 36 ). As a result, the first bi-lumen tube 96 , Y-connector 94 and one of the tri-lumen or bi-lumen tubes 90 , 102 collectively define a continuous pressure sensing fluid path between the mask 10 and a suitable pressure sensing modality located remotely therefrom. A more detailed discussion regarding the use of the dual pressure sensors to govern the delivery of therapeutic pressure to the patient is found in Applicant's co-pending U.S. application Ser. No. 13/411,257 entitled Dual Pressure Sensor Continuous Positive Airway Pressure (CPAP) Therapy filed Mar. 2, 2012, the entire disclosure of which is incorporated herein by reference.
Referring now to FIG. 10 , there is shown a mask 10 a which comprises a variant of the mask 10 . The sole distinction between the masks 10 , 10 a lies in the mask 10 a including a heat and moisture exchanger or HME 104 which is positioned within the fluid chamber 22 of the cushion 14 . The HME 104 is operative to partially or completely replace a humidifier (cold or heated pass-over; active or passive) which would otherwise be fluidly coupled to the mask 10 a . This is possible because the average flow through the system envisioned to be used in conjunction with the mask 10 a is about half of a prior art CPAP mask, due to the absence of any intentional leak in such system.
The HME 104 as a result of its positioning within the fluid chamber 22 , is able to intercept the flow delivered from the flow generator to the patient in order to humidify it, and is further able to capture humidity and heat from exhaled flow for the next breath. The pressure drop created by the HME 104 during exhalation (back-pressure) must be limited, in the order of less than 5 cm H2O at 601/min, and preferably lower than 2 cm H2O at 601/min. These parameters allow for a low back-pressure when the patient is wearing the mask 10 a and no therapy is delivered to the patient.
It is contemplated that the HME 104 can be permanently assembled to the cushion 14 , or may alternatively be removable therefrom and thus washable and/or disposable. In this regard, the HME 104 , if removable from within the cushion 14 , could be replaced on a prescribed replacement cycle. Additionally, it is contemplated that the HME 104 can be used as an elastic member that adds elasticity to the cushion 14 . In this regard, part of the elasticity of the cushion 14 may be attributable to its silicone construction, and further be partly attributable to the compression and deflection of the HME 104 inside the cushion 14 .
The integration of the exhalation valve 12 into the cushion 14 and in accordance with the present invention allows lower average flow compared to prior art CPAP masks. As indicated above, normal masks have a set of apertures called “vents” that create a continuous intentional leak during therapy. This intentional leak or vented flow is used to flush out the exhaled carbon dioxide that in conventional CPAP machines, with a standard ISO taper tube connecting the mask to the flow generator or blower, fills the tubing up almost completely with carbon dioxide during exhalation. The carbon dioxide accumulated in the tubing, if not flushed out through the vent flow, would be inhaled by the patient in the next breath, progressively increasing the carbon dioxide content in the inhaled gas at every breath. The structural/functional features of the exhalation valve 12 , in conjunction with the use of small inner diameter, high pneumatic resistance tubes in the system in which the mask 10 , 10 a is used, ensures that all the exhaled gas goes to ambient. As a result, a vent flow is not needed for flushing any trapped carbon dioxide out of the system. Further, during inspiration the exhalation valve 12 can close, and the flow generator of the system needs to deliver only the patient flow, without the additional overhead of the intentional leak flow. In turn, the need for lower flow rates allows for the use of smaller tubes that have higher pneumatic resistance, without the need for the use of extremely powerful flow generators. The pneumatic power through the system can be kept comparable to those of traditional CPAP machines, though the pressure delivered by the flow generator will be higher and the flow lower.
The reduced average flow through the system in which the mask 10 , 10 a is used means that less humidity will be removed from the system, as well as the patient. Conventional CPAP systems have to reintegrate the humidity vented by the intentional leak using a humidifier, with heated humidifiers being the industry standard. Active humidification introduces additional problems such as rain-out in the system tubing, which in turn requires heated tubes, and thus introducing more complexity and cost into the system. The envisioned system of the prent invention, as not having any intentional leak flow, does not need to introduce additional humidity into the system. As indicated above, the HME 104 can be introduced into the cushion 14 of the mask 10 a so that exhaled humidity can be trapped and used to humidify the air for the following breath.
In addition, a big portion of the noise of conventional CPAP systems is noise conducted from the flow generator through the tubing up to the mask and then radiated in the ambient through the vent openings. As previously explained, the system described above is closed to the ambient during inhalation which is the noisiest part of the therapy. The exhaled flow is also lower than the prior art so it can be diffused more efficiently, thus effectively decreasing the average exit speed and minimizing impingement noise of the exhaled flow on bed sheets, pillows, etc.
As also explained above, a patient can breathe spontaneously when the mask is worn and not connected to the flow generator tubing, or when therapy is not administered. In this regard, there will be little back pressure and virtually no carbon dioxide re-breathing, due to the presence of the exhalation valve 12 that is normally open and the inner diameters of the tubes integrated into the system. This enables a zero pressure start wherein the patient falls asleep wearing the mask 10 , 10 a wherein the flow generator does not deliver any therapy. Prior art systems can only ramp from about 4 m H2O up to therapy pressure. A zero pressure start is more comfortable to patients that do not tolerate pressure.
As seen in FIG. 14 , due to the reduced diameter of the various tubes (i.e., the tri-lumen tube 90 and bi-lumen tubes 96 , 98 , 102 ) integrated into the system 88 , 100 , such tubes can be routed around the patient's ears similar to conventional O2 cannulas. More particularly, the tubing can go around the patient's ears to hold the mask 10 , 10 a to the patient's face. This removes the “tube drag” problem described above since the tubes will not pull the mask 10 , 10 a away from the face of the patient when he or she moves. As previously explained, “tube drag” typically decreases mask stability on the patient and increases unintentional leak that annoys the patient. In the prior art, head gear tension is used to counter balance the tube drag, which leads to comfort issues. The tube routing of the present invention allows for lower head gear tension and a more comfortable therapy, especially for compliant patients that wear the mask 10 approximately eight hours every night. The reduction in tube drag in accordance with the present invention also allows for minimal headgear design (virtually none), reduced headgear tension for better patient comfort as indicated above, and reduced cushion compliance that results in a smaller, more discrete cushion 14 . The tube dangling in front of the patient, also commonly referred to as the “elephant trunk” by patients, is a substantial psychological barrier to getting used to therapy. The tube routing shown in FIG. 14 , in addition to making the mask 10 , 10 a more stable upon the patient, avoids this barrier as well. Another benefit to the smaller tubing is that the mask 10 , 10 a can become smaller because it does not need to interface with large tubing. Indeed, large masks are another significant factor leading to the high non-compliance rate for CPAP therapy since, in addition to being non-discrete, they often cause claustrophobia.
This disclosure provides exemplary embodiments of the present invention. The scope of the present invention is not limited by these exemplary embodiments. Numerous variations, whether explicitly provided for by the specification or implied by the specification, such as variations in structure, dimension, type of material and manufacturing process may be implemented by one of skill in the art in view of this disclosure. | In accordance with the present disclosure, there is provided a mask for achieving positive pressure mechanical ventilation (inclusive of CPAP, ventilator support, critical care ventilation, emergency applications), and a method for a operating a ventilation system including such mask. The mask of the present disclosure includes a piloted exhalation valve that is used to achieve the target pressures/flows to the patient. The pilot for the valve may be pneumatic and driven from the gas supply tubing from the ventilator. The pilot may also be a preset pressure derived in the mask, a separate pneumatic line from the ventilator, or an electro-mechanical control. The mask of the present disclosure may further include a heat and moisture exchanger (HME) which is integrated therein. | 0 |
[0001] This application claims priority under 35 U.S.C. §119(e) (1) to provisional application No. 60/083,472, filed Apr. 29, 1998.
FIELD OF THE INVENTION
[0002] The present invention is directed towards methods and compositions for inhibiting neural sprouting in neurons that have been subjected to botulinum toxin. Also disclosed are methods and compositions for extending the period of time during which treatment of nerve cells with botulinum toxin is effective to prevent innervation of a cell or tissue, such as muscle cells or tissue. Such methods and compositions are effective in the treatment of spasms or muscular tetanus. Disclosed as well are methods and compositions for stimulating neural outgrowth.
BACKGROUND OF THE INVENTION
[0003] Neurotoxins, such as those obtained from Clostridium botulinum and Clostridium tetanus , are highly potent and specific poisons of neural cells. These Gram positive bacteria secrete two related but distinct toxins, each comprising two disulfide-linked amino acid chains: a light chain (L) of about 50 KDa and a heavy chain (H) of about 100 KDa, which are wholly responsible for the symptoms of these diseases.
[0004] The tetanus and botulinum toxins are among the most lethal substances known to man, having a lethal dose in humans of between 0.1 ng and 1 ng per kilogram of body weight. Tonello et al., Adv. Exp. Med . & Biol. 389:251-260 (1996). Both toxins function by inhibiting neurotransmitter release in affected neurons. The tetanus neurotoxin (TeNT) acts mainly in the central nervous system, while botulinum neurotoxin (BoNT) acts at the neuromuscular junction by inhibiting acetylcholine release from the axon of the affected neuron into the synapse, resulting in a localized flaccid paralysis. The effect of intoxication on the affected neuron is long-lasting and has been thought to be irreversible.
[0005] The tetanus neurotoxin (TeNT) is known to exist in one immunologically distinct type; the botulinum neurotoxins (BoNT) are known to occur in seven different immunogenic types, termed BoNT/A through BoNT/G. While all of these types are produced by isolates of C. botulinum , two other species, C. baratii and C. butyricum also produce toxins similar to /F and /E, respectively. See e.g., Coffield et al., The Site and Mechanism of Action of Botulinum Neurotoxin in Therapy with Botulinum Toxin 3-13 (Jankovic J. & Hallett M. eds. 1994), the disclosure of which is incorporated herein by reference.
[0006] Regardless of type, the molecular mechanism of intoxication appears to be similar. In the first step of the process, the toxin binds to the presynaptic membrane of the target neuron through a specific interaction between the heavy chain and a cell surface receptor; the receptor is thought to be different for each type of botulinum toxin and for TeNT. The carboxy terminus of the heavy chain appears to be important for targeting of the toxin to the cell surface.
[0007] In the second step, the toxin crosses the plasma membrane of the poisoned cell. The toxin is first engulfed by the cell through receptor-mediated endocytosis, and an endosome containing the toxin is formed. The toxin then escapes the endosome into the cytoplasm of the cell. This last step is thought to be mediated by the amino terminus of the heavy chain, which triggers a conformational change of the toxin in response to a pH of about 5.5 or lower. Endosomes are known to possess a proton pump which decreases intra-endosomal pH. The conformational shift exposes hydrophobic residues in the toxin, which permits the toxin to embed itself in the endosomal membrane. The toxin then translocates through the endosomal membrane into the cytosol.
[0008] The last step of the mechanism of botulinum toxin activity appears to involve reduction of the disulfide bond joining the heavy and light chain. The entire toxic activity of botulinum and tetanus toxins is contained in the light chain of the holotoxin; the light chain is a zinc (Zn++) endopeptidase which selectively cleaves proteins essential for recognition and docking of neurotransmitter-containing vesicles with the cytoplasmic surface of the plasma membrane, and fusion of the vesicles with the plasma membrane. TxNT, BoNT/B BoNT/D, BoNT/F, and BoNT/G cause degradation of synaptobrevin 2 (also called vesicle-associated membrane protein (VAMP)), a synaptosomal membrane protein. Most of the VAMP present at the cytosolic surface of the synaptic vesicle is removed as a result of any one of these cleavage events. Each toxin specifically cleaves a different bond.
[0009] BoNT/A and /E selectively cleave the plasma membrane-associated protein SNAP-25; this protein is bound to and present on the cytosolic surface of the plasma membrane. BoNT/C cleaves syntaxin, an integral protein having most of its mass exposed to the cytosol. Syntaxin interacts with the calcium channels at presynaptic terminal active zones. See Tonello et al., Tetanus and Botulism Neurotoxins in Intracellular Protein Catabolism 251-260 (Suzuki K & Bond J. eds. 1996), the disclosure of which is incorporated by reference as part of this specification. BoNT/C 1 also cleaves SNAP-25 at a peptide bond next to that cleaved by BoNT/A.
[0010] Both TeNT and BoNT are taken up at the neuromuscular junction. BoNT remains within peripheral neurons, and blocks release of the neurotransmitter acetylcholine from these cells. Through its receptor, TeNT enters vesicles that move in a retrograde manner along the axon to the soma, and is discharged into the intersynaptic space between motor neurons and the inhibitory neurons of the spinal cord. At this point, TeNT binds receptors of the inhibitory neurons, is again internalized, and the light chain enters the cytosol to block the release of the inhibitory neurotransmitters 4-aminobutyric acid (GABA) and glycine from these cells. Id.
[0011] Because of its specifically localized effects, dilute preparations of BoNT have been used since 1981 as therapeutic agents in the treatment of patients having various spastic conditions, including strabismus (misalignment of the eye), bephlarospasm (involuntary eyelid closure) and hemifacial spasm. See e.g., Borrodic et al., Pharmacology and Histology Botulinum Toxin in Therapy with Botulinum Toxin 3-13 (Jankovic J. & Hallett M. eds. 1994), incorporated by reference herein. Of the seven toxin types, BoNT/A is the most potent of the BoNTs, and the most well characterized. Intramuscular injection of spastic tissue with dilute preparations of BoNT/A has been also used effectively to treat spasticity due to brain injury, spinal cord injury, stroke, multiple sclerosis and cerebral palsy. The extent of paralysis depends on both the dose and dose volume delivered to the target site. Typically, the neurotoxin is administered in a preparation that also contains several non-toxic proteins as well, including hemagglutins and associated glycoproteins that assist in maximizing its stability and presentation to the target motor neuron.
[0012] Typically there is a 24 to 72 hour delay between the administration of the toxin and the onset of the clinical effect. Exposure to the toxin causes denervation atrophy. See e.g., Dutton J., Acute and Chronic Effects of Botulinum Toxin in the Management of Blepharospasm , in Therapy with Botulinum Toxin at 199, incorporated by reference herein. Although the therapeutic application of BoNT has been extraordinarily effective, what side effects have been observed are mainly immediate effects associated with the treatment event itself. Peripheral effects causing weakness in adjacent muscles may sometimes occur; these effects usually do not persist beyond 1 to two weeks. The specific manifestations of these effects upon adjacent muscle groups depend upon the particular indication being treated. For example, patients treated for blepharospasm sometimes experience ptosis, and swallowing problems may occur after injection of neck muscles for torticollis.
[0013] Other possible consequences of treatment include the potential for overdosage through miscalculation or differences in activity between different preparations of the toxin, generalized fatigue, and the potential for allergic reactions.
[0014] A feature of treatment with BoNT/A, and other clostridial neurotoxin types, is that the paralytic action is temporary with symptoms reappearing in patients within a few months after toxin injection. This characteristic has been thought to be associated with the observed sprouting of nascent, synaptically active processes at the neuromuscular junction (NMJ). The production of such sprouts following BoNT/A therapeutic treatment has appeared to contribute to the reinervation of the treated tissue and therefore the need for repeated serial injections of the toxin.
[0015] The duration of paralytic action caused by clostridial neurotoxin and the extent of sprouting, appears to depend on the neurotoxin subtype studied and therefore appears to be related to the specific SNARE target cleaved by each neurotoxin. Thus, BoNT/A and BoNT/C 1 , which cleave the t-SNARE protein SNAP-25 within one amino acid of each other, cause a long lasting paralysis with a long average sprout length observed. BoNT/F, which cleaves the v-SNARE protein VAMP, causes a paralysis of shorter duration and sprouts of shorter average length. BoNT/E, which cleaves SNAP-25 at a different position than that of BoNT/A and BoNT/C 1 (thereby liberating a SNAP fragment of different size from the plasma membrane), has a short duration period of about 5 days, and virtually no neural sprouting is observed. Without wishing to be bound by theory, these observations suggest that neural sprouting and duration of paralysis are normally related events, and that the cleavage products of BoNT proteolytic digestion (i.e., the liberated fragment or the membrane-bound fragment) can directly or indirectly regulate, or be coregulated with, neural sprouting.
[0016] It would therefore be advantageous to design a method whereby the sprouting phenomenon may be uncoupled from duration of therapeutic effect, and thus delayed, blocked or attenuated so as to prolong the effects of injection of tissue with toxin. Although the experiments described herein utilize a BoNT/A preparation, it will be recognized by those of skill in the art that the methods shown herein will be suitable for employment using other clostridial toxins, such as BoNT/B through /G, and TeNT, in which a sprouting pathway can be observed.
[0017] Additionally, it would be advantageous to provide herein compositions effective for the inhibition or prevention of the sprouting phenomenon. Such compositions and methods would lessen the need for patients to undergo repeated neurotoxin treatment.
SUMMARY OF THE INVENTION
[0018] The present invention concerns methods for increasing the period of time between therapeutic treatments of neural tissue with a clostridial neurotoxin; thus the method provides a method of increasing the effectiveness of such treatments. A direct advantage of such methods is an increased therapeutic “life”, and a concomitant lessening in the required frequency of treatment of the patient with neurotoxin. Reducing frequency of treatment would provide less opportunity for a patient to experience the side effects described above that are observed following treatment, but which tend to subside long before the effectiveness of the toxin in the target area has subsided. Additionally, reduced frequency of treatment provides less opportunity for miscalculation of dosage amount and other treatment-specific risks.
[0019] Accordingly, an aspect of the invention concerns a composition comprising a first agent comprising a clostridial neurotoxin for use as a therapeutic agent and a second agent able to extend the duration of therapeutic benefit of said first agent, wherein the second agent is effective to attenuate the production of nerve terminal sprouts following treatment of a neuromuscular junction with the clostridial neurotoxin.
[0020] In a particular embodiment of this aspect of the invention, the first and second agent may comprise a single entity which is provided the patient in a single treatment session. For example, the entity may comprise a single molecule, or a disulfide-linked multichain polypeptide. Additionally or alternatively, the entity may comprise one or more adsorbed or linked heterogroup, such as a small organic molecule or a nucleic acid linked thereto. The entity preferably comprises both the receptor binding and translocation activities of a clostridial heavy chain and an active portion of a clostridial toxin light chain. The light chain may also comprise an auxiliary enzymatic activity, such as a ribonuclease, which specifically cleaves a nucleic acid encoding an intraneuronal factor which is responsible for the expression, activation and/or secretion of neurotrophic factors or cell adhesion molecules. In a preferred embodiment, such an auxiliary activity is provided by a ribozyme. By ribozyme is meant a nucleic acid or nucleic acid analog having a sequence-specific nuclease activity; the construction and use of ribozymes are well known in the art; see e.g., Cech, T., Science 236:1532-1539(1987); Cech, T. R., Curr. Opin. Struct. Biol. 2:605-609 (1992); and Usman et al., Nucleic Acids & Mol. Biol. 10:243-264 (1996), the disclosures of which are hereby incorporated by reference herein. By nucleic acid analog is meant a polymeric molecule able to form a sequence-specific hybrid with a target single-stranded nucleic acid; such analogs may contain modified nucleotides (or ribonucleotides) such as 3′-O methyl nucleotides, phosphorothioate modified nucleotides, methylphosphonate nucleotides, or nucleotide bases separated by a peptide-like bond.
[0021] Alternatively, a nucleic acid or nucleic acid analog comprised in the single entity referred to above may be an antisense agent able to selectively bind to a nucleic acid encoding an intraneuronal factor which is responsible for the expression, activation and/or secretion of neurotrophic factors or cell adhesion molecules. This antisense agent may further provide a double-stranded substrate for the action of an intracellular RNAse H activity. Details concerning certain embodiments of these aspects of the invention are contained in e.g., Dolly et al., International Publication No. WO95/32738, entitled Modification of Clostridial Toxins for Use as Transport Proteins and Uherek et al., J. Biol. Chem. 273:8835-8841 (1998). These two references are incorporated by reference as part of the present application.
[0022] A nucleic acid moiety linked polypeptide portion of the entity may encode a protein or polypeptide having the ability to be expressed within a neuron and to directly or indirectly regulate the expression, activation and/or secretion of neurotrophic factors or cell adhesion molecules.
[0023] In preferred aspects of the invention, the second agent is selected from the group consisting of agents able to compete with, down-regulate, or neutralize the effects of: IGFI, IGF II, a neurotrophic factor, leukemia inhibitory factor, a nerve cell adhesion molecule and neural agrin. In a more preferred aspect of the invention, the neurotrophic factor is selected from the group consisting of: ciliary neurotrophic factor, NT-3, NT-4, and brain-derived neurotrophic factor and/or the nerve cell adhesion molecule is selected from the group consisting of tenascin-C, ninjurin, neural cell adhesion molecule.
[0024] Applicants have surprisingly discovered that recovery of neural function following poisoning of nerve terminals with clostridial neurotoxin involves two distinct and apparently coordinated events. First, the poisoned endplate becomes synaptically inactive. Shortly thereafter the endplate elaborates thin nascent axon neural processes. These processes or “sprouts” are synaptically competent after about 14 days following treatment with clostridial neurotoxin. The sprouts continue growing, reaching a maximal length and level of complexity after about 42 days following treatment with neurotoxin. During this time, the endplate remains synaptically inactive.
[0025] Secondly, after about 42 days, the sprouts begin to regress, shortening in length and decreasing in complexity. At the same time, the original endplate begins to become synaptically active, undergoing synaptic vesicle turnover. The increase in such turnover reaches that of the unpoisoned endplate after about 91 days post-treatment, at approximately the same time that the sprouting phenomenon has completely regressed, and no sprouts can be observed. These findings are reported in DePaiva et al., Proc. Nat'l. Acad. Sci. 96:3200-3205 (March 1999), which is hereby incorporated by reference herein.
[0026] These observations are diametrically opposed to the prevailing wisdom in the art, in which it has largely been assumed that the original endplate is permanently inactivated upon treatment with clostridial toxin, and that all return of synaptic activity is due to extension of sprouts to compensate for the lack of a neurologically functional endplate. However, as indicated, the old paradigm has been shown by the present Applicants to be in error, in that the poisoned endplate regains neurological function over time, while the axon sprouts regress so that after a given time period the nerve terminal appears essentially as it did prior to treatment. Therefore, Applicants have discovered that, far from being a permanent feature, the axonal sprouts assume a temporary role in the rehabilitation of the poisoned endplate.
[0027] Although not wishing to be limited by theory, Applicants believe that these results indicate that the two events outlined above are temporally coordinated, in that a blockage of the neural sprouting phenomenon would delay or block the recovery of the functional endplate. Such temporal coordination could be due to the secretion of one or more factor by the damaged neural endplate (or the inactive muscle fiber) that has neurotrophic effects resulting in the formation of neural sprouts; these sprouts may then elaborate a factor (either the same or different from the first factor) which promotes continued sprouting. This factor may be produced during neurite sprouting in amounts sufficient for the reinervation of the neurotoxin-damaged endplate even after treatment with clostridial toxin. Thus, treatment of cells with an agent able to block neural sprouting would also delay or otherwise attenuate the ability of the treated endplate to experience return of neurological function, and in fact may well block such return altogether.
[0028] As indicated, the signaling event indicating the initiation of the neural sprouting phenomenon appears to be mediated by a cytokine or other intercellular messenger. One such agent, agrin, appear to be an important player, if not the key molecule, in the formation of the neuromuscular junction in development, and in neuromuscular regeneration. See Ruegg M. A. and Bixby J. L., Trends in Neurol. Sci. 21:22-27 (1998), the disclosure of which is incorporated herein by reference. Agrin appears to be present in a number of isoforms, which result from alternative mRNA splicing. Soluble agrin isolated from synaptic basal lamina extracts (to which it binds following secretion) is able to induce the aggregation of acetylcholine receptors in the postsynaptic portions of muscle cells. Agrin present in motor neuron terminals (n-agrin) contains an insert, relative to other agrin species, in a region termed the B/z region; this insert is important in conferring the ability on n-agrin to aggregate acetylcholine receptors in postsynaptic tissue. Neural agrin is released by the motor-nerve terminal and is believed by Applicants to induce post-synaptic specialization and up-regulation of other factors, such as muscle-diffusable factors, involved in the neural sprouting response.
[0029] It is anticipated that methods which interfere with the sprouting phenomenon (such as by the preventing the action of agrin) would delay the return of innervation to cells which are controlled by neurons which have been therapeutically poisoned (i.e., by BoNT or TeNT) or otherwise damaged. This is because, as indicated above, the rate of return of neural function appears to be partly dependent upon the presence of synaptically active sprouts. Additionally, agents to be used in the inhibition of sprouting may very well also delay or prevent the recovery of neural activity of the endplate following poisoning.
[0030] Thus utilization of such methods would therefore be expected to extend the effective period of treatment of tissue with a clostridial toxin, by delaying the regeneration of active neuromuscular synapses, both through inhibition of sprouting and of recovery of the poisoned endplate.
DETAILED DESCRIPTION OF THE INVENTION
[0031] This invention is drawn to methods and compositions for increasing the therapeutic effectiveness of treatment of tissue with clostridial neurotoxin. This increase in effectiveness is made possible by the surprising discovery that regeneration of neural tissue damaged by treatment with clostridial neurotoxin is a complex occurrence in which two coordinated events take place.
[0032] In the first of these events, the poisoned neuromuscular endplate becomes synaptically inactive, demonstrating no exocytosis of synaptic vesicles and thus no transport of intracellular acetylcholine. In four days after treatment, the endplate begins to form neural sprouts that are shown to release and regenerate synaptic vesicles. These sprouts grow in length and complexity until approximately 42 days following treatment with the neurotoxin; at this point the neural sprouts begin to regress and shorten. At ninety-one days following treatment, the neural sprouts can no longer be seen.
[0033] In the second event, simultaneously with the beginning of regression of the neural sprouts, the synaptically inactive endplate begins to regain the ability to release acetylcholine and begin to recycle synaptic vesicles. This ability, which begins at relatively low levels, increases over the time period indicated above. At approximately 91 days following treatment with clostridial neurotoxin the endplate is histologically and synaptically indistinguishable from the condition of the endplate before treatment with clostridial neurotoxin.
[0034] These findings indicate that one may therapeutically intervene at one of the major steps of the sprouting phenomenon to prevent or attenuate the neural sprouting as a method of extending the effective period during which tissue treated with the toxin remains paralyzed. In an initial step, the muscle cells surrounding the neural endplate respond, either sensing the inactive muscle or in response to a signal from the poisoned nerve terminal, by producing muscle-derived diffusable factors. The expression of a number of muscle-derived signaling factors appears to be upregulated by muscle inactivation; such factors include insulin-like growth factors (IGF-1 and IGF-2). A factor such as neural agrin is believed to be the initial signal directing the muscle cell to produce the IGF molecules. Reports have demonstrated that IGF I and IGF II effect neurite outgrowth in cultured BoNT/A treated dorsal root ganglia, and also are able to stimulate the initial sprouting response in paralyzed mouse gluteus muscle. See Caroni, P. and Schneider, C. J. Neurosci. 14:3378-3388 (1994) and Caroni, P., et al. J. Cell Biol. 125:893-902 (1994).
[0035] Thus, blocking the effects of such muscle derived diffusable factors that positively affect neurite outgrowth and sprouting may attenuate not only clostridial neurotoxin-induced sprouting, but may also delay the eventual recovery of neurotransmission at the poisoned nerve terminals. Such blocking may occur through the use of antibodies specific for the muscle derived diffusable factor in question, or that are common to such muscle derived diffusable factors. Alternatively, there are naturally occurring binding proteins, such as the IGF binding proteins IGF-BP 4 and IGF-BP 5, which can bind to, and therefore block, the neurotrophic effect of such diffusable factors.
[0036] IGF-BP 4 has an amino acid sequence (from the amino terminus) of:
MLPLCLVAALLLAAGPGPSLGDEAIHCPPCSEEKLA (SEQ ID NO: 1) RCRPPVGCEELVREPGCGCCATCALGLGMPCGVYTP RCGSGLRCYPPRGVEKPLHTLMHGQGVCMELAEIEA IQESLQPSDKDEGDHPNNSFSPCSAHDRRCLQKHFA KIRDRSTSGGKMKVNGAPREDARPVPQGSCQSELHR ALERLAASQSRTHEDLYIIPIPNCDRNGNFHPKQCH PALDGQRGKCWCVDRKTGVKLPGGLEPKGELDCHQL ADSFRE
[0037] This is encoded within the nucleotide base sequence. (from 5′ to 3′) of:
GTGCCCTCCG CCGCTCGCCC GCGCGCCCGC GCTCCCCGCC TGCGCCCAGC (SEQ ID NO: 3) GCCCCGCGCC CGCGCCCCAG TCCTCGGGCG GTCATGCTGC CCCTCTGCCT CGTGGCCGCC CTGCTGCTGG CCGCCGGGCC CGGGCCGAGC CTGGGCGACG AAGCCATCCA CTGCCCGCCC TGCTCCGAGG AGAAGCTGGC GCGCTGCCGC CCCCCCGTGG GCTGCGAGGA GCTGGTGCGA GAGCCGGGCT GCGGCTGTTG CGCCACTTGC GCCCTGGGCT TGGGGATGCC CTGCGGGGTG TACACCCCCC GTTGCGGCTC GGGCCTGCGC TGCTACCCGC CCCGAGGGGT GGAGAAGCCC CTGCACACAC TGATGCACGG GCAAGGCGTG TGCATGGAGC TGGCGGAGAT CGAGGCCATC CAGGAAAGCC TGCAGCCCTC TGACAAGGAC GAGGGTGACC ACCCCAACAA CAGCTTCAGC CCCTGTAGCG CCCATGACCG CAGGTGCCTG CAGAAGCACT TCGCCAAAAT TCGAGACCGG AGCACCAGTG GGGGCAAGAT GAAGGTCAAT GGGGCGCCCC GGGAGGATGC CCGGCCTGTG CCCCAGGGCT CCTGCCAGAG CGAGCTGCAC CGGGCGCTGG AGCGGCTGGC CGCTTCACAG AGCCGCACCC ACGAGGACCT CTACATCATC CCCATCCCCA ACTGCGACCG CAACGGCAAC TTCCACCCCA AGCAGTGTCA CCCAGCTCTG GATGGGCAGC GTGGCAAGTG CTGGTGTGTG GACCGGAAGA CGGGGGTGAA GCTTCCGGGG GGCCTGGAGC CAAAGGGGGA GCTGGACTGC CACCAGCTGG CTGACAGCTT TCGAGAGTGA GGCCTGCCAG CAGGCCAGGG ACTCAGCGTC CCCTGCTACT CCTGTGCTCT GGAGGCTGCA GAGCTGACCC AGAGTGGAGT CTGAGTCTGA GTCCTGTCTC TGCCTGCGGC CCAGAAGTTT CCCTCAAATG CGCGTGTGCA CGTGTGCGTG TGCGTGCGTG TGTGTGTGTT TGTGAGCATG GGTGTGCCCT TGGGGTAAGC CAGAGCCTGG GGTGTTCTCT TTGGTGTTAC ACAGCCCAAG AGGACTGAGA CTGGCACTTA GCCCAAGAGG TCTGAGCCCT GGTGTGTTTC CAGATCGATC CTGGATTCAC TCACTCACTC ATTCCTTCAC TCATCCAGCC ACCTAAAAAC ATTTACTGAC CATGTACTAC GTGCCAGCTC TAGTTTTCAG CCTTGGGAGG TTTTATTCTG ACTTCCTCTG ATTTTGGCAT GTGGAGACAC TCCTATAAGG AGAGTTCAAG CCTGTGGGAG TAGAAAAATC TCATTCCCAG AGTCAGAGGA GAAGAGACAT GTACCTTGAC CATCGTCCTT CCTCTCAAGC TAGCCAGAGG GTGGGAGCCT AAGGAAGCGT GGGGTAGCAG ATGGAGTAAT GGTCACGAGG TCCAGACCCA CTCCCAAAGC TCAGACTTGC CAGGCTCCCT TTCTCTTCTT CCCCAGGTCC TTCCTTTAGG TCTGGTTGTT GCACCATCTG CTTGGTTGGC TGGCAGCTGA GAGCCCTGCT GTGGGAGAGC GAAGGGGGTC AAAGGAAGAC TTGAAGCACA GAGGGCTAGG GAGGTGGGGT ACATTTCTCT GAGCAGTCAG GGTGGGAAGA AAGAATGCAA GAGTGGACTG AATGTGCCTA ATGGAGAAGA CCCACGTGCT AGGGGATGAG GGGCTTCCTG GGTCCTGTTC CCTACCCCAT TTGTGGTCAC AGCCATGAAG TCACCGGGAT GAACCTATCC TTCCAGTGGC TCGCTCCCTG TAGCTCTGCC TCCCTCTCCA TATCTCCTTC CCCTACACCT CCCTCCCCAC ACCTCCCTAC TCCCCTGGGC ATCTTCTGGC TTGACTGGAT GGAAGGAGAC TTAGGAACCT ACCAGTTGGC CATGATGTCT TTTCT
[0038] IGFBP 5 has an amino acid sequence (from the amino terminus) of:
MVLLTAVLLLLAAYAGPAQSLGSFVHCEPCDEKALS (SEQ ID No. 2) MCPPSPLGCELVKEPGCGCCMTCALAEGQSCGVYTE RCAQGLRCLPRQDEEKPLHALLHGRGVCLNEKSYRE QVKIERDSREHEEPTTSEMAEETYSPKIFRPKHTRI SELKAEAVKKDRRKKLTQSKFVGGAENTAHPRIISA PEMRQESEQGPCRRHMEASLQELKASPRMVPRAVYL PNCDRKGFYKRKQCKPSRGRKRGICWCVDKYGMKLP GMEYVDGDFQCHTFDSSNVE
[0039] and is encoded within a nucleotide base sequence (from 5′ to 3′) of:
GGGGAAAAGA GCTAGGAAAG AGCTGCAAAG CAGTGTGGGC TTTTTCCCTT (SEQ ID NO: 4) TTTTTGCTCCT TTTCATTAC CCCTCCTCCG TTTTCACCCT TCTCCGGACT TCGCGTAGAA CCTGCGAATT TCGAAGAGGA GGTGGCAAAG TGGGAGAAAA GAGGTGTTAG GGTTTGGGGT TTTTTTGTTT TTGTTTTTGT TTTTTAATTT CTTGATTTCA ACATTTTCTC CCACCCTCTC GGCTGCAGCC AACGCCTCTT ACCTGTTCTG CGGCGCCGCG CACCGCTGGC AGCTGAGGGT TAGAAAGCGG GGTGTATTTT AGATTTTAAG CAAAAATTTT AAAGATAAAT CCATTTTTCT CTCCCACCCC CAACGCCATC TCCACTGCAT CCGATCTCAT TATTTCGGTG GTTGCTTGGG GGTGAACAAT TTTGTGGCTT TTTTTCCCCT ATAATTCTGA CCCGCTCAGG CTTGAGGGTT TCTCCGGCCT CCGCTCACTG CGTGCACCTG GCGCTGCCCT GCTTCCCCCA ACCTGTTGCA AGGCTTTAAT TCTTGCAACT GGGACCTGCT CGCAGGCACC CCAGCCCTCC ACCTCTCTCT ACATTTTTGC AAGTGTCTGG GGGAGGGCAC CTGCTCTACC TGCCAGAAAT TTTAAAACAA AAACAAAAAC AAAAAAATCT CCGGGGGCCC TCTTGGCCCC TTTATCCCTG CACTCTCGCT CTCCTGCCCC ACCCCGAGGT AAAGGGGGCG ACTAAGAGAA GATGGTGTTG CTCACCGCGG TCCTCCTGCT GCTGGCCGCC TATGCGGGGC CGGCCCAGAG CCTGGGCTCC TTCGTGCACT GCGAGCCCTG CGACGAGAAA GCCCTCTCCA TGTGCCCCCC CAGCCCCCTG GGCTGCGAGC TGGTCAAGGA GCCGGGCTGC GGCTGCTGCA TGACCTGCGC CCTGGCCGAG GGGCAGTCGT GCGGCGTCTA CACCGAGCGC TGCGCCCAGG GGCTGCGCTG CCTCCCCCGG CAGGACGAGG AGAAGCCGCT GCACGCCCTG CTGCACGGCC GCGGGGTTTG CCTCAACGAA AAGAGCTACC GCGAGCAAGT CAAGATCGAG AGAGACTCCC GTGAGCACGA GGAGCCCACC ACCTCTGAGA TGGCCGAGGA GACCTACTCC CCCAAGATCT TCCGGCCCAA ACACACCCGC ATCTCCGAGC TGAAGGCTGA AGCAGTGAAG AAGGACCGCA GAAAGAAGCT GACCCAGTCC AAGTTTGTCG GGGGAGCCGA GAACACTGCC CACCCCCGGA TCATCTCTGC ACCTGAGATG AGACAGGAGT CTGAGCAGGG CCCCTGCCGC AGACACATGG AGGCTTCCCT GCAGGAGCTC AAAGCCAGCC CACGCATGGT GCCCCGTGCT GTGTACCTGC CCAATTGTGA CCGCAAAGGA TTCTACAAGA GAAAGCAGTG CAAACCTTCC CGTGGCCGCA AGCGTGGCAT CTGCTGGTGC GTGGACAAGT ACGGGATGAA GCTGCCAGGC ATGGAGTACG TTGACGGGGA CTTTCAGTGC CACACCTTCG ACAGCAGCAA CGTTGAGTGA TGCGTCCCCC CCCAACCTTT CCCTCACCCC CTCCCACCCC CAGCCCCGAC TCCAGCCAGC GCCTCCCTCC ACCCCAGGAC GCCACTCATT TCATCTCATT TAAGGGAAAA ATATATATCT ATCTATTTGA GGAAAAAAAA AAAAAAAAAA AA
[0040] These binding proteins can be made synthetically or cloned and produced for therapeutic purposes, while a cell line producing a desired monoclonal antibody can be maintained for relatively large-scale antibody production. Cloning and general antibody methodologies are commonplace in the art; such methodologies are disclosed within Sambrook et al., Molecular Cloning: A Laboratory Manual (2nd ed. Cold Spring Harbor Laboratory Press 1989), the disclosure of which is hereby incorporated by reference as part of this disclosure.
[0041] Rather than using competitive methods, another aspect of the invention involves the use of a cholinergic special transporter to insert a gene which produces inactive receptors for one or more factor involved in promotion of neural sprouting. Such receptors would maintain high specific binding constants to their ligands, but the biological activity of the receptors would be abrogated; such receptors could be easily be generated and screened through the introduction of mutations in the nucleotide sequence encoding the protein, and assaying the mutants for binding strength and biological activity. Alternatively, the neurotrophic activities of factors produced by the neural endplate or nascent sprouts may be inhibited through intracellular targeting and delivery of a competitive inhibitor, ribozyme, transcriptional suppresser or other agent specifically able to block or attenuate such activities, as described above. Such intracellular targeting is disclosed in references such as, e.g., Dolly et al., International Patent Publication No. WO95/32738, previously incorporated by reference herein.
[0042] The second point at which intervention in the sprouting phenomenon may be made is during the stage of axonal outgrowth and arbor development. At this stage such outgrowth has already been initiated, but auxiliary factors appear to be necessary in order to maintain axonal growth. A number of factors are known to affect the rates of outgrowth, and may also effect the survivability of many types of neurons. Such factors include ciliary neurotrophic factor (CNTF); neurotrophins, including NT-3, NT-4, and brain-derived neurotrophic factor (BDNF); and leukemia inhibitory factor (LIF). Not only are these factors important in establishing an initial rate of axonal outgrowth, but they appear to either directly or indirectly stimulate their own production—therefore blocking the initial outgrowth of sprouts may be essential in preventing further propagation through the continued expression of such factors.
[0043] The same methods as disclosed above can be used to prevent one or more of the agents listed above to manifest its activity. As would be expected by those of skill in the art in light of the present disclosure, such agents, destroy or bind to, and therefore attenuate the activity of these factors or their block their ability to bind to their receptors, or inactive forms of their receptors, would be useful when used in conjunction with a clostridial neurotoxin to prevent or reduce the rate of sprouting of neurites from the poisoned or damaged endplate.
[0044] The third stage at which the sprouting phenomenon may be attenuated or inhibited concerns the binding of axons to the extracellular matrix. Axons are guided to cellular processes containing the appropriate neurotransmitter receptors by binding to components of the extracellular matrix. Such binding involves a variety of cell-borne or matrix associated adhesion molecules. Tenascin-C is an extracellular matrix component derived from Schwann cells that appears to bind neural processes. Ninjurin is a cell surface adhesion molecule that is up-regulated following peripheral nerve injury and thought to be involved in exonal guidance. See Araki, T., et al., J. Biol. Chem. 272:21373-21380 (1997), incorporated by reference herein. Similarly, neural-cell adhesion molecule (N-CAM), is an adhesion molecule which is thought to be involved in binding of neural sprouts to the extracellular matrix. The same techniques indicated above may be employed to prevent the expression or inhibit the activity of these molecules when used as part of a clostridial neurotoxin therapy.
[0045] Thus, in one aspect the present invention is drawn to a method for extending the effective period during which tissue treated with clostridial toxin is paralyzed, comprising: Contacting said tissue with a composition comprising an agent able to prevent the neuroregenitive activity of a polypeptide selected from the group consisting of IGF-1, IGF-2, cilary neurotrophic factor, NT-3, NT-4, brain-derived neurotrophic factor, leukemia inhibitory factor, tenascin-C, ninjurin, neural cell adhesion molecule, and neural agrin.
[0046] In one preferred embodiment, the agent comprises a polypeptide able to bind to IGF-1 and/or IGF-2 in a manner that prevents an IGF molecule from binding to or activating a cell surface receptor involved in the initiation of neural sprouting. In a most preferred embodiment the polypeptide comprises at least a portion of a amino acid sequence selected from the group consisting of: IGFBP-4 (SEQ ID NO: 1) or IGFBP5 (SEQ ID NO: 2). Preferably said portion comprises at least 10 contiguous amino acids of said sequence; more preferably said portion comprises at least 20 contiguous nucleotides of said sequence. Most preferably, the portion comprises an amino acid sequence selected from the group consisting of the entire amino acid sequence of IGFBP-4 or IGFBP-5.
[0047] Treatment of cells with such a composition may be accomplished either before or simultaneously with treatment with clostridial toxin. Preferably, the clostridial toxin is a botulinum toxin. Even more preferably, the botulinum toxin comprises BoNT/A. In other embodiments, the clostridial toxin is TeNT. Agent which are able to bind to any of these factors in a manner that inhibits their neurotrophic activity, or which bind to the receptors for such factors, would, in light of the present application, be expected to function as agents for extending the effective period between treatments of tissue with a neurotoxin.
[0048] Another embodiment comprises a cholinergic specific transporter joined to a gene encoding a gene which produces an inactive receptor for one or more factor involved in promotion of neural sprouting when delivered to a neural cell in vivo. Preferably the receptors maintain high specific binding constants to said factor(s) and the biological activity of the receptor is reduced or absent. In a particularly preferred embodiment the transporter comprises some or all of a clostridial neurotoxin heavy chain, although other transporters such as the diphtheria toxin transporter may be effective in this regard as well.
[0049] In another embodiment the invention comprises a cholonergic specific transporter that is covalently or non-covalently joined to a nucleic acid which comprises a ribozyme or antisense nucleic acid able to specifically destroy the nucleic acids encoding neurotrophic agents or their receptors. Said joining may be made through methods including, but not limited to, covalent bonding or electrostatic forces.
[0050] In another embodiment, the present invention is drawn to the methods for stimulating the outgrowth of neural sprouts from damaged neural tissue. Such methods could be effective ways of increasing the rate at which reinnervation occurs after a neural injury. These methods comprise: Contacting said tissue with a composition comprising a polypeptide which comprises a neurotrophically active domain derived from an agent selected from a group consisting of IGF-1, IGF-2, cilary neurotrophic factor, NT-3, NT-4, brain derived neurotrophic factor, leukemia inhibitory factor, tenascin-C, ninjurin, neural cell adhesion molecule, and neural agrin. Such damage may be a result of neurotoxin poisoning or due to a traumatic event, including but not limited to nerve or spinal cord crush injuries, traumatic brain injuries, glaucoma-induced damage to the retina and/or optic nerve, or surgical trauma or injury.
[0051] The following examples illustrate various embodiments of the present invention, and are not intended to limit the scope of the invention, which is solely defined by the claims which conclude this specification.
EXAMPLE 1
[0052] Blepharospasm is a medical condition characterized by uncontrolled eyelid movement. In its early stages, the condition is characterized by excessive blinking or fluttering of the eyelids. The condition is generally a progressive one, in which excessive blinking is replaced in the later stages with spasms of eye closure that interfere with visual function. The spasms become more frequent and severe, and involve the preseptal, pretarsal, and orbicularis oculi muscle. The condition often results in functional blindness relatively quickly (in a matter of two to three years) after the symptoms are first encountered.
[0053] A patient suffering from moderate idiopathic blepharospasm is treated with injections of BoNT/A toxin preparation containing non-toxic proteins and hemagglutins in sterile saline. Alternatively, the same toxin preparation without hemagglutins may be used. The injections are generally in the volume of 100 μl; and each injection contains 1.25 to 2.5 units of the toxin preparation. The injections are made into the pretarsal orbicularis oculi of the upper lid laterally and medially and in the lower lid laterally and medially. Additionally, 2.5 unit injections (100 μl each) are made lateral to the lateral canthus and into the brow medially. Total amount of BoNT/A toxin injected is roughly 6.25 to 12.5 units per eye. The BO/A toxin is provided in a sterile, preservative-free saline, and the same solution is used to dilute the BoNT/A toxin if the master preparation of it is too concentrated.
[0054] Following injection the treated muscles are sufficiently paralyzed due to this treatment to alleviate the major symptoms of blepharospasm. Some mild concomitant weakness in the surrounding muscle tissue is observed; these side effects are mild and tolerated well by the patient. The effect of this treatment lasts approximately 8 weeks, and must be repeated at the end of this time to maintain the beneficial effects.
EXAMPLE 2
[0055] A patient with blepharospasm is pre-treated with BoNT/A toxin as indicated in Example 1 with the following difference. Prior to injection with BoNT/A toxin preparation, the patient is given a ten-fold excess of IGFBP-4, having an amino acid sequence of SEQ ID NO: 1. The binding protein preparation is dissolved in sterile, preservative-free saline. Each injection is in the same area as the toxin injections that follow the pre-treatment; the volume of each injection is 100 μl. The BoNT/A toxin preparation is injected ten minutes after the injection of the IGFBT 4 injection.
[0056] The patient's therapeutic response to the BoNT/A toxin is similar to that seen in Example 1. The duration of the benefit provided by the BoNT/A toxin treatment is extended to 12 weeks or more, during which time no further injection need be made.
EXAMPLE 3
[0057] A patient with blepharospasm is pre-treated with BoNT/A toxin as indicated in Example 1 with the following difference. The BoNT/A toxin has been modified to have joined thereto a nucleic acid comprising a ribozyme specifically targeted to enzymatically destroy neural agrin mRNA. No supplemental injections are made.
[0058] The patient's therapeutic response to the BoNT/A toxin is similar to that seen in Example 1. The duration of the benefit provided by the BoNT/A toxin treatment is extended to 12 weeks or more, during which time no further injection need be made.
EXAMPLE 4
[0059] A patient with blepharospasm is pre-treated with BoNT/A toxin as indicated in Example 1 with the following difference. The BoNT/A toxin has been modified to have joined thereto a nucleic acid encoding an inactive neurotrophin receptor which retains the ability to bind its target neurotrophin. No supplemental injections are made.
[0060] The patient's therapeutic response to the BoNT/A toxin is similar to that seen in Example 1. The duration of the benefit provided by the BoNT/A toxin treatment is extended beyond that seen with BoNT/A alone, during which time no further injection need be made.
[0061] It will be understood that, while reference is made to BoNT/A in the Examples above, any other of the species of botulinum toxins (e.g., BoNT/B through G) could be substituted therefor, with appropriate adjustments possibly necessary due to differences in specific activity of the toxin. Additionally, the light chain segment could be derived from any clostridial neurotoxin (or other neurotoxin), with the heavy chain retaining the motor neuron receptor binding and exo-vescular transport activities retained from the BoNT heavy chain.
[0062] These Examples are not intended to exhaust the embodiments of the present invention, and the invention is not to be seen as limited thereby. Further embodiments will be disclosed within the claims that conclude this specification.
1
4
1
258
PRT
Homo sapiens
1
Met Leu Pro Leu Cys Leu Val Ala Ala Leu Leu Leu Ala Ala Gly Pro
1 5 10 15
Gly Pro Ser Leu Gly Asp Glu Ala Ile His Cys Pro Pro Cys Ser Glu
20 25 30
Glu Lys Leu Ala Arg Cys Arg Pro Pro Val Gly Cys Glu Glu Leu Val
35 40 45
Arg Glu Pro Gly Cys Gly Cys Cys Ala Thr Cys Ala Leu Gly Leu Gly
50 55 60
Met Pro Cys Gly Val Tyr Thr Pro Arg Cys Gly Ser Gly Leu Arg Cys
65 70 75 80
Tyr Pro Pro Arg Gly Val Glu Lys Pro Leu His Thr Leu Met His Gly
85 90 95
Gln Gly Val Cys Met Glu Leu Ala Glu Ile Glu Ala Ile Gln Glu Ser
100 105 110
Leu Gln Pro Ser Asp Lys Asp Glu Gly Asp His Pro Asn Asn Ser Phe
115 120 125
Ser Pro Cys Ser Ala His Asp Arg Arg Cys Leu Gln Lys His Phe Ala
130 135 140
Lys Ile Arg Asp Arg Ser Thr Ser Gly Gly Lys Met Lys Val Asn Gly
145 150 155 160
Ala Pro Arg Glu Asp Ala Arg Pro Val Pro Gln Gly Ser Cys Gln Ser
165 170 175
Glu Leu His Arg Ala Leu Glu Arg Leu Ala Ala Ser Gln Ser Arg Thr
180 185 190
His Glu Asp Leu Tyr Ile Ile Pro Ile Pro Asn Cys Asp Arg Asn Gly
195 200 205
Asn Phe His Pro Lys Gln Cys His Pro Ala Leu Asp Gly Gln Arg Gly
210 215 220
Lys Cys Trp Cys Val Asp Arg Lys Thr Gly Val Lys Leu Pro Gly Gly
225 230 235 240
Leu Glu Pro Lys Gly Glu Leu Asp Cys His Gln Leu Ala Asp Ser Phe
245 250 255
Arg Glu
2
272
PRT
Homo Sapiens
2
Met Val Leu Leu Thr Ala Val Leu Leu Leu Leu Ala Ala Tyr Ala Gly
1 5 10 15
Pro Ala Gln Ser Leu Gly Ser Phe Val His Cys Glu Pro Cys Asp Glu
20 25 30
Lys Ala Leu Ser Met Cys Pro Pro Ser Pro Leu Gly Cys Glu Leu Val
35 40 45
Lys Glu Pro Gly Cys Gly Cys Cys Met Thr Cys Ala Leu Ala Glu Gly
50 55 60
Gln Ser Cys Gly Val Tyr Thr Glu Arg Cys Ala Gln Gly Leu Arg Cys
65 70 75 80
Leu Pro Arg Gln Asp Glu Glu Lys Pro Leu His Ala Leu Leu His Gly
85 90 95
Arg Gly Val Cys Leu Asn Glu Lys Ser Tyr Arg Glu Gln Val Lys Ile
100 105 110
Glu Arg Asp Ser Arg Glu His Glu Glu Pro Thr Thr Ser Glu Met Ala
115 120 125
Glu Glu Thr Tyr Ser Pro Lys Ile Phe Arg Pro Lys His Thr Arg Ile
130 135 140
Ser Glu Leu Lys Ala Glu Ala Val Lys Lys Asp Arg Arg Lys Lys Leu
145 150 155 160
Thr Gln Ser Lys Phe Val Gly Gly Ala Glu Asn Thr Ala His Pro Arg
165 170 175
Ile Ile Ser Ala Pro Glu Met Arg Gln Glu Ser Glu Gln Gly Pro Cys
180 185 190
Arg Arg His Met Glu Ala Ser Leu Gln Glu Leu Lys Ala Ser Pro Arg
195 200 205
Met Val Pro Arg Ala Val Tyr Leu Pro Asn Cys Asp Arg Lys Gly Phe
210 215 220
Tyr Lys Arg Lys Gln Cys Lys Pro Ser Arg Gly Arg Lys Arg Gly Ile
225 230 235 240
Cys Trp Cys Val Asp Lys Tyr Gly Met Lys Leu Pro Gly Met Glu Tyr
245 250 255
Val Asp Gly Asp Phe Gln Cys His Thr Phe Asp Ser Ser Asn Val Glu
260 265 270
3
1955
DNA
Homo Sapiens
3
gtgccctccg ccgctcgccc gcgcgcccgc gctccccgcc tgcgcccagc gccccgcgcc 60
cgcgccccag tcctcgggcg gtcatgctgc ccctctgcct cgtggccgcc ctgctgctgg 120
ccgccgggcc cgggccgagc ctgggcgacg aagccatcca ctgcccgccc tgctccgagg 180
agaagctggc gcgctgccgc ccccccgtgg gctgcgagga gctggtgcga gagccgggct 240
gcggctgttg cgccacttgc gccctgggct tggggatgcc ctgcggggtg tacacccccc 300
gttgcggctc gggcctgcgc tgctacccgc cccgaggggt ggagaagccc ctgcacacac 360
tgatgcacgg gcaaggcgtg tgcatggagc tggcggagat cgaggccatc caggaaagcc 420
tgcagccctc tgacaaggac gagggtgacc accccaacaa cagcttcagc ccctgtagcg 480
cccatgaccg caggtgcctg cagaagcact tcgccaaaat tcgagaccgg agcaccagtg 540
ggggcaagat gaaggtcaat ggggcgcccc gggaggatgc ccggcctgtg ccccagggct 600
cctgccagag cgagctgcac cgggcgctgg agcggctggc cgcttcacag agccgcaccc 660
acgaggacct ctacatcatc cccatcccca actgcgaccg caacggcaac ttccacccca 720
agcagtgtca cccagctctg gatgggcagc gtggcaagtg ctggtgtgtg gaccggaaga 780
cgggggtgaa gcttccgggg ggcctggagc caaaggggga gctggactgc caccagctgg 840
ctgacagctt tcgagagtga ggcctgccag caggccaggg actcagcgtc ccctgctact 900
cctgtgctct ggaggctgca gagctgaccc agagtggagt ctgagtctga gtcctgtctc 960
tgcctgcggc ccagaagttt ccctcaaatg cgcgtgtgca cgtgtgcgtg tgcgtgcgtg 1020
tgtgtgtgtt tgtgagcatg ggtgtgccct tggggtaagc cagagcctgg ggtgttctct 1080
ttggtgttac acagcccaag aggactgaga ctggcactta gcccaagagg tctgagccct 1140
ggtgtgtttc cagatcgatc ctggattcac tcactcactc attccttcac tcatccagcc 1200
acctaaaaac atttactgac catgtactac gtgccagctc tagttttcag ccttgggagg 1260
ttttattctg acttcctctg attttggcat gtggagacac tcctataagg agagttcaag 1320
cctgtgggag tagaaaaatc tcattcccag agtcagagga gaagagacat gtaccttgac 1380
catcgtcctt cctctcaagc tagccagagg gtgggagcct aaggaagcgt ggggtagcag 1440
atggagtaat ggtcacgagg tccagaccca ctcccaaagc tcagacttgc caggctccct 1500
ttctcttctt ccccaggtcc ttcctttagg tctggttgtt gcaccatctg cttggttggc 1560
tggcagctga gagccctgct gtgggagagc gaagggggtc aaaggaagac ttgaagcaca 1620
gagggctagg gaggtggggt acatttctct gagcagtcag ggtgggaaga aagaatgcaa 1680
gagtggactg aatgtgccta atggagaaga cccacgtgct aggggatgag gggcttcctg 1740
ggtcctgttc cctaccccat ttgtggtcac agccatgaag tcaccgggat gaacctatcc 1800
ttccagtggc tcgctccctg tagctctgcc tccctctcca tatctccttc ccctacacct 1860
ccctccccac acctccctac tcccctgggc atcttctggc ttgactggat ggaaggagac 1920
ttaggaacct accagttggc catgatgtct tttct 1955
4
1722
DNA
Homo sapiens
4
ggggaaaaga gctaggaaag agctgcaaag cagtgtgggc tttttccctt tttttgctcc 60
ttttcattac ccctcctccg ttttcaccct tctccggact tcgcgtagaa cctgcgaatt 120
tcgaagagga ggtggcaaag tgggagaaaa gaggtgttag ggtttggggt ttttttgttt 180
ttgtttttgt tttttaattt cttgatttca acattttctc ccaccctctc ggctgcagcc 240
aacgcctctt acctgttctg cggcgccgcg caccgctggc agctgagggt tagaaagcgg 300
ggtgtatttt agattttaag caaaaatttt aaagataaat ccatttttct ctcccacccc 360
caacgccatc tccactgcat ccgatctcat tatttcggtg gttgcttggg ggtgaacaat 420
tttgtggctt tttttcccct ataattctga cccgctcagg cttgagggtt tctccggcct 480
ccgctcactg cgtgcacctg gcgctgccct gcttccccca acctgttgca aggctttaat 540
tcttgcaact gggacctgct cgcaggcacc ccagccctcc acctctctct acatttttgc 600
aagtgtctgg gggagggcac ctgctctacc tgccagaaat tttaaaacaa aaacaaaaac 660
aaaaaaatct ccgggggccc tcttggcccc tttatccctg cactctcgct ctcctgcccc 720
accccgaggt aaagggggcg actaagagaa gatggtgttg ctcaccgcgg tcctcctgct 780
gctggccgcc tatgcggggc cggcccagag cctgggctcc ttcgtgcact gcgagccctg 840
cgacgagaaa gccctctcca tgtgcccccc cagccccctg ggctgcgagc tggtcaagga 900
gccgggctgc ggctgctgca tgacctgcgc cctggccgag gggcagtcgt gcggcgtcta 960
caccgagcgc tgcgcccagg ggctgcgctg cctcccccgg caggacgagg agaagccgct 1020
gcacgccctg ctgcacggcc gcggggtttg cctcaacgaa aagagctacc gcgagcaagt 1080
caagatcgag agagactccc gtgagcacga ggagcccacc acctctgaga tggccgagga 1140
gacctactcc cccaagatct tccggcccaa acacacccgc atctccgagc tgaaggctga 1200
agcagtgaag aaggaccgca gaaagaagct gacccagtcc aagtttgtcg ggggagccga 1260
gaacactgcc cacccccgga tcatctctgc acctgagatg agacaggagt ctgagcaggg 1320
cccctgccgc agacacatgg aggcttccct gcaggagctc aaagccagcc cacgcatggt 1380
gccccgtgct gtgtacctgc ccaattgtga ccgcaaagga ttctacaaga gaaagcagtg 1440
caaaccttcc cgtggccgca agcgtggcat ctgctggtgc gtggacaagt acgggatgaa 1500
gctgccaggc atggagtacg ttgacgggga ctttcagtgc cacaccttcg acagcagcaa 1560
cgttgagtga tgcgtccccc cccaaccttt ccctcacccc ctcccacccc cagccccgac 1620
tccagccagc gcctccctcc accccaggac gccactcatt tcatctcatt taagggaaaa 1680
atatatatct atctatttga ggaaaaaaaa aaaaaaaaaa aa 1722 | Methods and compositions for modulating neurite outgrowth in damaged neural endplates. Also disclosed are methods for introducing drugs, ribozymes, antisense oligonucleotides and defective receptor genes within neurons. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application Ser. No. 60/968,593 filed 29 Aug. 2007. The disclosure of this application is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates generally to deuterium-enriched doxazosin, pharmaceutical compositions containing the same, and methods of using the same.
BACKGROUND OF THE INVENTION
[0003] Doxazosin, shown below, is a well known alpha blocker.
[0000]
[0000] Since doxazosin is a known and useful pharmaceutical, it is desirable to discover novel derivatives thereof. Doxazosin is described in U.S. Pat. No. 4,188,390; the contents of which are incorporated herein by reference.
SUMMARY OF THE INVENTION
[0004] Accordingly, one object of the present invention is to provide deuterium-enriched doxazosin or a pharmaceutically acceptable salt thereof.
[0005] It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the deuterium-enriched compounds of the present invention or a pharmaceutically acceptable salt thereof.
[0006] It is another object of the present invention to provide a method for treating a disease selected from high blood pressure and/or benign prostatic hyperplasia, comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the deuterium-enriched compounds of the present invention or a pharmaceutically acceptable salt thereof.
[0007] It is another object of the present invention to provide a novel deuterium-enriched doxazosin or a pharmaceutically acceptable salt thereof for use in therapy.
[0008] It is another object of the present invention to provide the use of a novel deuterium-enriched doxazosin or a pharmaceutically acceptable salt thereof for the manufacture of a medicament (e.g., for the treatment of high blood pressure and benign prostatic hyperplasia).
[0009] These and other objects, which will become apparent during the following detailed description, have been achieved by the inventor's discovery of the presently claimed deuterium-enriched doxazosin.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0010] Deuterium (D or 2 H) is a stable, non-radioactive isotope of hydrogen and has an atomic weight of 2.0144. Hydrogen naturally occurs as a mixture of the isotopes 1 H (hydrogen or protium), D ( 2 H or deuterium), and T ( 3 H or tritium). The natural abundance of deuterium is 0.015%. One of ordinary skill in the art recognizes that in all chemical compounds with a H atom, the H atom actually represents a mixture of H and D, with about 0.015% being D. Thus, compounds with a level of deuterium that has been enriched to be greater than its natural abundance of 0.015%, should be considered unnatural and, as a result, novel over their non-enriched counterparts.
[0011] All percentages given for the amount of deuterium present are mole percentages.
[0012] It can be quite difficult in the laboratory to achieve 100% deuteration at any one site of a lab scale amount of compound (e.g., milligram or greater). When 100% deuteration is recited or a deuterium atom is specifically shown in a structure, it is assumed that a small percentage of hydrogen may still be present. Deuterium-enriched can be achieved by either exchanging protons with deuterium or by synthesizing the molecule with enriched starting materials.
[0013] The present invention provides deuterium-enriched doxazosin or a pharmaceutically acceptable salt thereof. There are twenty-five hydrogen atoms in the doxazosin portion of doxazosin as show by variables R 1 -R 25 in formula I below.
[0000]
[0014] The hydrogens present on doxazosin have different capacities for exchange with deuterium. Hydrogen atoms R 1 and R 2 are easily exchangeable under physiological conditions and, if replaced by deuterium atoms, it is expected that they will readily exchange for protons after administration to a patient. Certain aromatic hydrogen atoms might be exchangeable with strong deuterated acid, but are relatively easy to incorporate these deuterium atoms by synthesis. The hydrogen atoms represented by R 3 -R 25 are not easily exchangeable and may be incorporated by the use of deuterated starting materials or intermediates during the construction of doxazosin.
[0015] The present invention is based on increasing the amount of deuterium present in doxazosin above its natural abundance. This increasing is called enrichment or deuterium-enrichment. If not specifically noted, the percentage of enrichment refers to the percentage of deuterium present in the compound, mixture of compounds, or composition. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %. Since there are 25 hydrogens in doxazosin, replacement of a single hydrogen atom with deuterium would result in a molecule with about 4% deuterium enrichment. In order to achieve enrichment less than about 4%, but above the natural abundance, only partial deuteration of one site is required. Thus, less than about 4% enrichment would still refer to deuterium-enriched doxazosin.
[0016] With the natural abundance of deuterium being 0.015%, one would expect that for approximately every 6,667 molecules of doxazosin (1/0.00015=6,667), there is one naturally occurring molecule with one deuterium present. Since doxazosin has 25 positions, one would roughly expect that for approximately every 233,345 molecules of doxazosin (25×6,667), all 25 different, naturally occurring, mono-deuterated doxazosins would be present. This approximation is a rough estimate as it doesn't take into account the different exchange rates of the hydrogen atoms on doxazosin. For naturally occurring molecules with more than one deuterium, the numbers become vastly larger. In view of this natural abundance, the present invention, in an embodiment, relates to an amount of an deuterium enriched compound, whereby the enrichment recited will be more than naturally occurring deuterated molecules.
[0017] In view of the natural abundance of deuterium-enriched doxazosin, the present invention also relates to isolated or purified deuterium-enriched doxazosin. The isolated or purified deuterium-enriched doxazosin is a group of molecules whose deuterium levels are above the naturally occurring levels (e.g., 4%). The isolated or purified deuterium-enriched doxazosin can be obtained by techniques known to those of skill in the art (e.g., see the syntheses described below).
[0018] The present invention also relates to compositions comprising deuterium-enriched doxazosin. The compositions require the presence of deuterium-enriched doxazosin which is greater than its natural abundance. For example, the compositions of the present invention can comprise (a) a μg of a deuterium-enriched doxazosin; (b) a mg of a deuterium-enriched doxazo sin; and, (c) a gram of a deuterium-enriched doxazosin.
[0019] In an embodiment, the present invention provides an amount of a novel deuterium-enriched doxazosin.
[0020] Examples of amounts include, but are not limited to (a) at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, to 1 mole, (b) at least 0.1 moles, and (c) at least 1 mole of the compound. The present amounts also cover lab-scale (e.g., gram scale), kilo-lab scale (e.g., kilogram scale), and industrial or commercial scale (e.g., multi-kilogram or above scale) quantities as these will be more useful in the actual manufacture of a pharmaceutical. Industrial/commercial scale refers to the amount of product that would be produced in a batch that was designed for clinical testing, formulation, sale/distribution to the public, etc.
[0021] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof.
[0000]
[0022] wherein R 1 -R 25 are independently selected from H and D; and the abundance of deuterium in R 1 -R 25 is at least 4%. The abundance can also be (a) at least 8%, (b) at least 12%, (c) at least 16%, (d) at least 20%, (e) at least 24%, (f) at least 28%, (g) at least 32%, (h) at least 36%, (i) at least 40%, (j) at least 44%, (k) at least 48%, (l) at least 52%, (m) at least 56%, (n) at least 60%, (o) at least 64%, (p) at least 68%, (q) at least 72%, (r) at least 76%, (s) at least 80%, (t) at least 84%, (u) at least 88%, (v) at least 92%, (w) at least 96%, and (y) 100%%.
[0023] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 1 -R 2 is at least 50%. The abundance can also be 100%.
[0024] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 25 is at least 5%. The abundance can also be (a) at least 9%, (b) at least 14%, (c) at least 18%, (d) at least 23%, (e) at least 27%, (f) at least 32%, (g) at least 36%, (h) at least 41%, (i) at least 45%, (j) at least 50%, (k) at least 55%, (l) at least 59%, (m) at least 64%, (n) at least 68%, (o) at least 73%, (p) at least 77%, (q) at least 82%, (r) at least 86%, (s) at least 91%, (t) at least 95%, (u) and 100%.
[0025] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 4 is at least 50%. The abundance can also be (a) at least 100%.
[0026] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 5 -R 10 is at least 17%. The abundance can also be (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 100%.
[0027] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 11 -R 18 is at least 13%. The abundance can also be (a) at least 25%, (b) at least 38%, (c) at least 50%, (d) at least 63%, (e) at least 75%, (f) at least 88%, and (g) 100%.
[0028] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 19 -R 21 is at least 33%. The abundance can also be (a) at least 67%, and (b) 100%.
[0029] In another embodiment, the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 22 -R 25 is at least 25%. The abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
[0030] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof.
[0000]
[0031] wherein R 1 -R 25 are independently selected from H and D; and the abundance of deuterium in R 1 -R 25 is at least 4%. The abundance can also be (a) at least 8%, (b) at least 12%, (c) at least 16%, (d) at least 20%, (e) at least 24%, (f) at least 28%, (g) at least 32%, (h) at least 36%, (i) at least 40%, (j) at least 44%, (k) at least 48%, (l) at least 52%, (m) at least 56%, (n) at least 60%, (o) at least 64%, (p) at least 68%, (q) at least 72%, (r) at least 76%, (s) at least 80%, (t) at least 84%, (u) at least 88%, (v) at least 92%, (w) at least 96%, and (y) 100%.
[0032] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 1 -R 2 is at least 50%. The abundance can also be 100%.
[0033] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 25 is at least 5%. The abundance can also be (a) at least 9%, (b) at least 14%, (c) at least 18%, (d) at least 23%, (e) at least 27%, (f) at least 32%, (g) at least 36%, (h) at least 41%, (i) at least 45%, (j) at least 50%, (k) at least 55%, (l) at least 59%, (m) at least 64%, (n) at least 68%, (o) at least 73%, (p) at least 77%, (q) at least 82%, (r) at least 86%, (s) at least 91%, (t) at least 95%, (u) and 100%.
[0034] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 4 is at least 50%. The abundance can also be (a) at least 100%.
[0035] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 5 -R 10 is at least 17%. The abundance can also be (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 100%.
[0036] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 11 -R 18 is at least 13%. The abundance can also be (a) at least 25%, (b) at least 38%, (c) at least 50%, (d) at least 63%, (e) at least 75%, (f) at least 88%, and (g) 100%.
[0037] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 19 -R 21 is at least 33%. The abundance can also be (a) at least 67%, and (b) 100%.
[0038] In another embodiment, the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 22 -R 25 is at least 25%. The abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
[0039] In another embodiment, the present invention provides novel mixture of deuterium enriched compounds of formula I or a pharmaceutically acceptable salt thereof.
[0000]
[0040] wherein R 1 -R 25 are independently selected from H and D; and the abundance of deuterium in R 1 -R 25 is at least 4%. The abundance can also be (a) at least 8%, (b) at least 12%, (c) at least 16%, (d) at least 20%, (e) at least 24%, (f) at least 28%, (g) at least 32%, (h) at least 36%, (i) at least 40%, (j) at least 44%, (k) at least 48%, (l) at least 52%, (m) at least 56%, (n) at least 60%, (o) at least 64%, (p) at least 68%, (q) at least 72%, (r) at least 76%, (s) at least 80%, (t) at least 84%, (u) at least 88%, (v) at least 92%, (w) at least 96%, and (y) 100%%.
[0041] In another embodiment, the present invention provides a novel mixture of deuterium enriched compounds of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 1 -R 2 is at least 50%. The abundance can also be 100%.
[0042] In another embodiment, the present invention provides a novel mixture of deuterium enriched compounds of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 25 is at least 5%. The abundance can also be (a) at least 9%, (b) at least 14%, (c) at least 18%, (d) at least 23%, (e) at least 27%, (f) at least 32%, (g) at least 36%, (h) at least 41%, (i) at least 45%, (j) at least 50%, (k) at least 55%, (l) at least 59%, (m) at least 64%, (n) at least 68%, (o) at least 73%, (p) at least 77%, (q) at least 82%, (r) at least 86%, (s) at least 91%, (t) at least 95%, (u) and 100%.
[0043] In another embodiment, the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 3 -R 4 is at least 50%. The abundance can also be (a) at least 100%.
[0044] In another embodiment, the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 5 -R 10 is at least 17%. The abundance can also be (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 100%.
[0045] In another embodiment, the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 11 -R 18 is at least 13%. The abundance can also be (a) at least 25%, (b) at least 38%, (c) at least 50%, (d) at least 63%, (e) at least 75%, (f) at least 88%, and (g) 100%.
[0046] In another embodiment, the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 19 -R 21 is at least 33%. The abundance can also be (a) at least 67%, and (b) 100%.
[0047] In another embodiment, the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 22 -R 25 is at least 25%. The abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
[0048] In another embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a deuterium-enriched compound of the present invention.
[0049] In another embodiment, the present invention provides a novel method for treating high blood pressure and benign prostatic hyperplasia comprising: administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of the present invention.
[0050] In another embodiment, the present invention provides an amount of a deuterium-enriched compound of the present invention as described above for use in therapy.
[0051] In another embodiment, the present invention provides the use of an amount of a deuterium-enriched compound of the present invention for the manufacture of a medicament (e.g., for the treatment of high blood pressure and benign prostatic hyperplasia).
[0052] The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. This invention encompasses all combinations of preferred aspects of the invention noted herein. It is understood that any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe additional more preferred embodiments. It is also to be understood that each individual element of the preferred embodiments is intended to be taken individually as its own independent preferred embodiment. Furthermore, any element of an embodiment is meant to be combined with any and all other elements from any embodiment to describe an additional embodiment.
DEFINITIONS
[0053] The examples provided in the definitions present in this application are non-inclusive unless otherwise stated. They include but are not limited to the recited examples.
[0054] The compounds of the present invention may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. All tautomers of shown or described compounds are also considered to be part of the present invention.
[0055] “Host” preferably refers to a human. It also includes other mammals including the equine, porcine, bovine, feline, and canine families.
[0056] “Treating” or “treatment” covers the treatment of a disease-state in a mammal, and includes: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, e.g., arresting it development; and/or (c) relieving the disease-state, e.g., causing regression of the disease state until a desired endpoint is reached. Treating also includes the amelioration of a symptom of a disease (e.g., lessen the pain or discomfort), wherein such amelioration may or may not be directly affecting the disease (e.g., cause, transmission, expression, etc.).
[0057] “Therapeutically effective amount” includes an amount of a compound of the present invention that is effective when administered alone or in combination to treat the desired condition or disorder. “Therapeutically effective amount” includes an amount of the combination of compounds claimed that is effective to treat the desired condition or disorder. The combination of compounds is preferably a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased antiviral effect, or some other beneficial effect of the combination compared with the individual components.
[0058] “Pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of the basic residues. The pharmaceutically acceptable salts include the conventional quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 1,2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.
Synthesis
[0059] Scheme 1 shows a route to racemic doxazosin that uses chemistry from U.S. Pat. No. 4,188,390 (Campbell), J. Med. Chem. 1987, 30, 49-57 (Campbell, et al.), and J. Org. Chem., 2002, 67, 8284-8286 (Andrus, et al.).
[0000]
[0060] Scheme 2 shows how various deuterated starting materials and intermediates from Scheme 1 can be accessed and used to make deuterated doxazosin analogs. A person skilled in the art of organic synthesis will recognize that these reactions and these materials may be used in various combinations to access a variety of deuterated doxazosins. The use of commercial perdeuterated catechol 1 or the dideuterated catechols 2 or 3 in the known reaction shown in equation (1) will produce 4, 5, or 6. If 4 is used in the chemistry of Scheme 1, doxazosin with R 22 -R 25 =D will result. If 5 is used in the chemistry of Scheme 1, doxazosin with R 23 -R 24 =D will result. If 6 is used in the chemistry of Scheme 1, doxazosin with R 22 =R 25 =D will result. The use of the deuterated dibromide 7 in equation (2) will give 8. If 8 is used in the chemistry of Scheme 1, doxazosin with R 15 =R 16 =D will result. Note that the hydrogen atom next to the carbonyl group in 8 was originally a deuterium atom, a result due to the various reaction conditions used. The use of commercial 9 or known 10 in the condensation reaction shown in equation (3) will produce 11 or 12. If 11 is used in the chemistry of Scheme 1, doxazosin with R 11 -R 18 =D will result. If 12 is used in the chemistry of Scheme 1, doxazosin with R 11 , R 12 , R 15 , R 16 =D will result. The latter compound could also be designated R 13 , R 14 , R 17 , R 18 =D; they are equivalent. Base-catalyzed exchange can be used to make 13 as shown in equation (4). If 13 is used in the chemistry of Scheme 1, doxazosin with R 19 =D will result. The nitro-acid used in Scheme 1 can be made by the chemistry shown in equations (5)-(7) in Scheme 2. If the deuterated starting materials 14, 16, and 18 are used under the conditions shown, 15, 17, and 19 result. (Note that 14 and 16 are commercially available.) If 15 is used in the chemistry of Scheme 1, doxazosin with R 3 -R 4 and R 5 -R 10 =D will result. If 17 is used in the chemistry of Scheme 1, doxazosin with R 3 -R 4 =D will result. If 19 is used in the chemistry of Scheme 1, doxazosin with R 5 -R 10 =D will result. Again, a person skilled in the art of organic synthesis will recognize that combinations of these processes will afford even more deuterated analogs of doxazosin.
[0000]
EXAMPLES
[0061] Table 1 provides compounds that are representative examples of the present invention. When one of R 1 -R 25 is present, it is selected from H or D.
[0000]
1
2
3
4
5
6
7
8
[0062] Table 2 provides compounds that are representative examples of the present invention. Where H is shown, it represents naturally abundant hydrogen.
[0000]
9
10
11
12
13
14
15
16
[0063] Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein. | The present application describes deuterium-enriched doxazosin, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. | 2 |
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a method and devices for the implantation of artificial meshwork into the eye of a human or animal. The implant is performed on eyes with glaucoma so as to relieve the intraocular pressure in the diseased eye. More specifically, the present invention relates to devices used for implanting an artificial meshwork within an eye to lower the intraocular pressure while avoiding hypotony and a method of using the devices.
Description of the Related Art
Glaucoma is a disease of the eye that occurs most commonly in people over the age of fifty. Two million patients have been diagnosed with glaucoma. One million more have glaucoma but are not aware of it.
In glaucoma, the pressure within the eye increases and destroys the visual nerve fibers. A sharp anatomic angle exists at the junction between the iris and the inner surface of the cornea. At this angle, the fluids of the eye, which are called the aqueous humor, filter out of the anterior chamber of the eye and into the capillaries. In one type of glaucoma, the opening at the junction between the iris and the inner surface of the cornea where filtration occurs closes and aqueous humor builds up in the eye. Due to the excess of the aqueous humor in the eye, the pressure within the eyeball increases. If this increased pressure is sustained for long periods of time, then the optic nerve fibers can be permanently damaged and blindness will result.
For years, doctors have performed sclerotomy operations to relieve the intraocular pressure. The operations usually include a wide incision and a small opening is bored through the scleral tissue, which allows fluid to filter out and thereby lessen the pressure within the eyeball. Similar surgery can be performed less invasively with a laser.
When surgery is not an option, eye drops of a solution containing 0.25 to 5 percent of pilocarpine nitrate is dropped into the eye in the evenings and the mornings. This drug causes the pupil to contract, thus drawing the iris away from the cornea and opening the angle for filtration. This treatment may be continued for days or years. Another drug prescribed to patients is timolol maleate.
Both of these methods have complications.
The surgical process described above is generally not effective for more than five years. Postoperative complications associated with such surgical techniques, such as functional bleb failure due to scarring may occur. These scars are believed to be caused by the procedure's invasiveness and morbidity as well as a relatively long operation time. The usual surgery, generally known as trabeculectomy, lasts for more than half an hour.
Often patients still require glaucoma drugs. In complex cases, the patient is either submitted to a regimen involving daily subconjunctival injections of 5-FU for about two weeks or treated intraoperatively with topical applications of mitomycin C before opening the channel. This must be done in order to minimize the natural wound healing response which ultimately closes, by forming scars, the channel formed in surgery. Another problem is that the operation is less effective for patients with hyper-vascularization.
Approximately 37,000 eyes underwent surgeries involving incisions for glaucoma in 1987. The cost for each procedure is high, including postoperative care, in the first postoperative year alone. By the fifth postoperative year, about half of the eyes will require a second filtering operation. Further, the costs of glaucoma medications are quite expensive, and patient compliance with a doctor recommended regimen is quite low.
Some recently issued patents describe the use of tubes and tubes with valves to regulate the pressure in the anterior chamber of the eye. The surgery to perform these usually require removal of tissue in the eye and the tubes can become clogged as time passes. U.S. Pat. No. 4,936,825 teaches the use of a porous strand which is sewed and tied in the scleral tissue by using a needle. The pores in the string must run substantially the length of the strand. Since these pores are long and narrow, they may become easily blocked.
SUMMARY OF THE INVENTION
There is a need for a method and device that may be used in an operation that is non-traumatic to the eye. The operation of inserting the implant must be quick with no removal of eye tissue. The present invention provides for an artificial meshwork which is similar to living tissue which eliminates the scarring due to cutting of large amounts of tissue and the rejection of foreign substances by the body.
The method of insertion involves the use of a special guide knife which inserts the implant in less than a minute. Once the implant is in place, the patient does not need to use medicinal eye drops and the pressure in the eye is reduced by the release of aqueous humor through the short pore holes of the artificial meshwork of the implant.
The present invention includes devices which assist the surgeon during the operation. These devices are a prismatic contact lens with C-shaped vacuum ring to magnify the anterior chamber where a portion of the implant will protrude and the vacuum helps to stabilize the eye during the implant operation.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of the scalpel provided in accordance with the invention;
FIG. 2 is a front view of the scalpel;
FIG. 3 is a view of the polymer matrix used in the implant;
FIG. 4 is a front view of the folded polymer matrix which forms the implant;
FIG. 5 is a cross-sectional side view of the folded polymer matrix;
FIG. 6 is a cross-sectional top view of the folded and welded polymer matrix;
FIG. 7 shows the guide knife, C-shaped vacuum and prismatic contact lens being used in an operation in accordance with the present invention;
FIG. 8A-8F are diagrams show the steps of inserting the folded polymer matrix during the operation;
FIG. 9 shows the implant in place and functioning after the operation has been completed;
FIG. 10 is a side view of the prismatic contact lens with a C-shaped vacuum ring;
FIG. 11 is a top view of the prismatic contact lens with a C-shaped vacuum ring;
FIG. 12A-12B illustrate another embodiment of the guide knife of the invention;
FIG. 13A-13C show implants with a securing mechanism;
FIG. 14A-14D show implants with ta securing mechanism and perforations in the mesh to increase outflow;
FIG. 15A is a side elevational view of a plunger in the blade in accordance with the invention;
FIG. 15B is a plan view of the plunger in the blade;
FIG. 15C shows a slide mechanism for finger actuated release of the implant; and
FIG. 15D shows a reusable handle and disposable blade with an implant release mechanism.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1 and 2, the guide knife 10 is used to insert an implant (not shown) into the eye. The guide knife comprises a handle 16, a blade 12 and a flange 14. The blade portion has a sharp point 26 and a sharp edge 22 running from the point of the blade to the side of the guide knife. The flange 14 is substantially parallel to the inner surface of the handle forming a gap 20. The handle also has a window 18 which allows light to pass through the middle portion of the handle.
Referring to FIG. 3, the hydrophobic porous polymer film is a polymer matrix which can be made from the same material used in general surgery for tissue replacement, such as products sold under the trademark of Gore-Tex, Proplast and Impra. This hydrophobic porous polymers becomes wetted when implanted into the eye. In particular, several PTFE porous films are custom made by France Chirurgie Instrument for use as a keratoprosthesis material. These polymers were found to be very biocompatible with eye tissues.
Experiments have shown that although body fluids can pass across the polymer matrix, cellular in-growth in 250 μm thick polymer films having 20 μm pores was extremely slow. It usually takes longer than 6 months for cellular in-growth to occur. Eventually, fibrocyte cells, which have a diameter of approximately 6 μm, will invade the implant and obstruct flow. By further reducing the pore size to 1-5 μm, the cellular in-growth is prevented. Another consideration is that the pores must be larger than 1 μm in order to prevent the forming of proteinic aggregates, which are naturally found in aqueous humor of non-inflamed human eyes. The length of the pore has to be small, less than 200 μm to prevent accumulation of proteins and subsequent flow obstruction. The pore's surface must be lippophobic to prevent cell and protein adherence.
In response to all of these considerations, the polymer film 30 is used. As shown in FIG. 3, the polymer film has many micro-channels 32 which are around 1-5 μm in diameter. The micro-channels are separated by thin walls which are around 1-5 μm thick.
Referring to FIG. 4, a sheet of the polymer film 30 is cut to approximately the size of 2-3.5 mm wide and 20 mm long. The sheet is folded in the width direction to form the implant 38. The implant is made of a back section 32 which is longer than a front section 34 and a bend section 36. The back section and front section are welded together to form a seam 44 at the end. FIG. 5 is cross-sectional side view along the line 5--5 in FIG. 4. This side view shows the gap 46 formed between the front section 34 and back section 32. FIG. 6 is a cross-sectional top view along the line marked 6--6 in FIG. 4. This top view shows the seam 44 of welded or heat-sealed ends and the gap 46 formed between the front and back section.
At this point, the fold section, which will be positioned in anterior chamber of the eye, is treated to prevent a protein adhesion. A surface treatment such as Heparinization will prevent protein adhesions. To minimize a "foreign body" immunologic reaction which might limit aqueous flow, the pores in the front and back section of the implant are filled with a biodegradable polymer 5-FU matrix.
Referring to FIG. 7, an eye is prepared for the operation to insert an implant. The eye 50 is shown with a lens 52, an iris 54, a anterior chamber 56, a conjunctiva 58, a cornea 60 and sclera 62. A prismatic contact lens with C-shaped vacuum ring 70 is placed on the cornea of the eye. This device assists the surgeon in viewing the anterior chamber of the eye by the reflected image 84.
The prismatic contact lens with C-shaped vacuum ring is shown in greater detail in FIG. 10 and 11. Referring to FIG. 10, the gonioprism 74 is made of a clear substance such as plastic (PMMA, etc.), crystal (quartz, sapphire, etc.), or glass. A mirror 72 or highly reflective surface is attached to the flat section of the gonioprism 66. The gonioprism also has a concave surface 76 which has a curvature similar to that of the cornea of an eye. A convex surface 78 magnifies the reflected image of the anterior chamber. The prismatic contact lens' optics helps the surgeon to locate the angle of anterior chamber and see the location of the implant. This enables the surgeon to see when the bend section 36 of the implant emerges from the cornea into the anterior chamber 56.
The C-shaped ring is attached to the back portion of the mirror. The ring 82 is made of pliable material which will conform to the shape of the cornea. A tube 80 is attached to the C-shaped ring at one end and the other end of the tube is attached to a conventional vacuum (not shown in the diagram). By adjusting the vacuum, the prismatic contact lens adheres to the eye surface. The level of suction is controlled with a floor-switch activated pump equipped with a 0-700 mmHg regulator and a solenoid valve for fast release to atmosphere.
Referring to FIG. 8A, the implant 38 is fitted onto the guide knife 10. Once the eye is stabilized by using the vacuum attached to the handle of the C-shaped vacuum ring, the surgeon may begin the operation. The flange 14 of the guide knife fits into the gap 46 of the implant. The flange is tapered on the edges so that the seam does not interfere with slipping the implant onto the guide knife. When the implant is in place, the front section 34 of the implant is in the gap 20 of the guide knife and the tip of the flange 14 is near the bend 36 of the implant.
Referring to FIG. 8B, the surgical implantation begins when the guide knife has passed through the conjunctiva 58 and is penetrating the cornea 60 of the eye. In FIG. 8C, the guide knife has been inserted far enough so that the bend section 36 of the implant is completely through the cornea and is touching the aqueous humor of the anterior chamber. At this point the surgeon can look through the window 18 of the guide knife and the prismatic contact lens with C-shaped vacuum ring 70 to see that the bend section 36 of the implant has penetrated into the anterior chamber.
Next, as shown in FIG. 8D, the guide knife is slowly withdrawn from the cornea. The implant remains located in the cornea and begins to squeeze together as the knife slides over the outer portion of the front section.
Referring to FIG. BE, the knife is completely removed and the implant is in place in FIG. 8F. Inserting this implant takes about one minute.
Referring to FIG. 9, the implant is in place. The aqueous humor 86 passes through the micro-channels located in the front, back and bend section of the implant. The aqueous humor then travels down the gap 46 to the subconjunctival space where it is reabsorbed into the body.
In FIG. 12B, a front view of a guide knife with a different shape is shown, with corresponding reference numbers, incremented by one hundred, designating corresponding parts. The blade of this guide knife has a curved edge. In FIG. 12A, a side view of the same guide knife is shown.
In FIGS. 13 and 14 other shapes suitable for the implant are shown, with corresponding reference numbers, incremented by one hundred, designating corresponding parts. Each embodiment of the implant 138 is largest at the bend 136, which serves to prevent the implant from being forced out of the anterior chamber 56. The outflow and tissue pressure prevents the implant from migrating into the anterior chamber 56. The welded or heat-sealed edges 144 are shown in each embodiment.
In FIG. 13A, an implant which has a hook at the fold section is shown. When this fold section is inserted into the anterior chamber, the hook shaped fold section will prevent the implant from sliding out with the retreating guide knife. This also helps keep the implant in place until the body heals around the wound.
In FIG. 13B, an implant with a larger end at the fold section is also shown. This shape will also assist in preventing the implant from sliding out with the retreating guide knife.
In FIG. 13C, an implant which has a tapered shape is shown. The fold section is wider in width than the bottom section of the implant. This design also helps in preventing the implant from sliding out with the retreating guide knife.
FIGS. 14A-14C are implants having one (FIG. 14A) or two (FIGS. 14B and 14C) sections 146 of the bent material cut out to increase outflow.
FIG. 14D has several small perforations 148 made at the bent section.
FIG. 15A is an elevational view and FIG. 15B is a plan view of a plunger 150 in the blade and handle for ejecting the implant. FIG. 15C shows a slide mechanism 152 for finger actuated release of the implant. A spring may be provided to return the actuator to its proximal, inoperative position.
FIG. 15D shows a reusable handle 210 and disposable blade 212 with a cooperating implant release mechanism 252. The disposable blade tip may be coupled to the handle in any suitable manner such as with a luer type coupling. When the blade and handle are coupled, displacement of a plunger 254 in the handle 210 with finger actuator 256 displaces plunger 258 in the blade 212 which ejects the implant. Spring 260 is provided to automatically re-cock the plunger 254 in the handle 210.
While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments but on the contrary is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. | A method and device which is used to insert an implant in order for treating an eye with glaucoma in order to lower the intraocular pressure of the eye. The implant is an artificial meshwork. The implant is attached to a guide knife which is inserted into the anterior chamber of the eye. The knife is then removed leaving the implant in place. During the operation, a prismatic lens with c-shaped vacuum ring is used to help assist the surgeon in viewing the anterior chamber of the eye and stabilizing the eye. | 0 |
RELATED APPLICATIONS
This application claims benefit of provisional application U.S. Ser. No. 60/955,985, filed Aug. 15, 2007, herein incorporated by reference.
FIELD OF THE INVENTION
The present invention relates 6-substituted sulfonyl-1,3,3-trialkyl-6-azabicyclo[3.2.1]octane compounds useful to inhibit 11β-hydroxysteroid dehydrogenase type-I, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the expression of 11β-hydroxysteroid dehydrogenase type-I using such compounds or pharmaceutical compositions.
BACKGROUND OF THE INVENTION
Glucocorticoids are steroid hormones that regulate many metabolic and homeostatic processes, including fat metabolism, function and distribution. Glucocorticoids also have profound and diverse physiological effects on development, neurobiology, inflammation, blood pressure, metabolism and programmed cell death.
Glucocorticoid action is dependent on the following factors: 1) circulating levels of glucocorticoid; 2) protein binding of glucocorticoids in circulation; 3) intracellular receptor density inside target tissues; and 4) tissue-specific pre-receptor metabolism by glucocorticoid-activating and glucocorticoid-inactivating enzymes collectively known as 11-beta-hydroxysteroid dehydrogenase (11-β-HSD). Two distinct isozymes of 11-β-HSD have been cloned and characterized. These two isozymes, known as 11-β-HSD type I and 11-β-HSD type II, respectively, catalyze the interconversion of active and inactive forms of various glucocorticoids. For example, in humans, the primary endogenously-produced glucocorticoid is cortisol. 11-β-HSD type I and 11-β-HSD type II catalyze the interconversion of hormonally active cortisol and inactive cortisone. 11-β-HSD type I is widely distributed in human tissues and its expression has been detected in lung, testis, central nervous system and most abundantly in liver and adipose tissue. Conversely, 11-β-HSD type II expression is found mainly in kidney, placenta, colon and salivary gland tissue.
Up-regulation of 11-β-HSD type I can lead to elevated cellular glucocorticoid levels and amplified glucocorticoid activity. This, in turn, can lead to increased hepatic glucose production, adipocyte differentiation and insulin resistance. In type II diabetes, insulin resistance is a significant pathogenic factor in the development of hyperglycemia. Persistent or uncontrolled hyperglycemia in both type 1 and type 2 diabetes has been associated with increased incidence of macrovascular and/or microvascular complications including atherosclerosis, coronary heart disease, peripheral vascular disease, stroke, nephropathy, neuropathy and retinopathy. Insulin resistance, even in the absence of profound hyperglycemia, is a component also of metabolic syndrome, which is characterized by elevated blood pressure, high fasting blood glucose levels, abdominal obesity, increased triglyceride levels and/or decreased HDL cholesterol. Further, glucocorticoids are known to inhibit the glucose-stimulated secretion of insulin from pancreatic beta-cells. Inhibition of 11-β-HSD type I is, therefore, expected to be beneficial in the treatment of metabolic syndromes, obesity, obesity-related disorders, hypertension, atherosclerosis, lipid disorders, type-II diabetes, insulin resistance, pancreatitis and associated conditions.
Mild cognitive impairment is a common feature of aging that may be ultimately related to the progression of dementia. Chronic exposure to glucocorticoid excess in certain brain subregions has been proposed to contribute to the decline of cognitive function. Inhibition of 11-β-HSD type I is expected to reduce exposure to glucocorticoids in the brain and protect against deleterious glucocorticoid effects on neuronal function, including cognitive impairment, dementia and/or depression, especially in connection with Alzheimer's Disease.
Glucocorticoids also have a role in corticosteroid-induced glaucoma. This particular pathology is characterized by a significant increase in intra-ocular pressure, which unresolved can lead to partial visual field loss and eventually blindness. Inhibition of 11-β-HSD type I is expected to reduce local glucocorticoid concentrations and, thus, intra-ocular pressure, producing beneficial effects in the management of glaucoma and other visual disorders.
Finally, glucocorticoids can have adverse effects on skeletal tissues. Continued exposure to excess glucocorticoids can produce osteoporosis and increased risk of fractures. Inhibition of 11-β-HSD type I should reduce local glucocorticoid concentration within osteoblasts and osteoclasts, producing beneficial effects for management of bone disease, including osteoporosis.
In view of the foregoing, there is a clear and continuing need for new compounds that target 11-β-HSD type I.
SUMMARY OF THE INVENTION
In its many embodiments, the present invention provides a novel class of heterocyclic compounds as inhibitors of 11β-hydroxysteroid dehydrogenase type-I, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the expression of 11β-hydroxysteroid dehydrogenase type-I using such compounds or pharmaceutical compositions.
In one aspect, the present application discloses a compound, or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound, said compound having the general structure shown in Formula I:
wherein:
R 1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl; and R 2 -R 4 independently represent alkyl;
with the exception of those compounds wherein:
R 2 -R 4 each represent methyl; and R 1 represents phenyl substituted by substituted alkoxycarbonyl, substituted alkylcarbonyloxy, substituted sulfonylamino, substituted carbonylamino, or unsubstituted or substituted aminocarbonyl;
and excluding the following compounds:
1,3,3-trimethyl-6-[(phenylmethyl)sulphonyl]-6-azabicyclo[3.2.1]octane; 6-[(3,4-difluorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(4-aminophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 1,3,3-trimethyl-6-[[4-(5-phenyl-2-oxazolyl)phenyl]sulfonyl]-6-azabicyclo[3.2.1]octane; 6-[(2-methyl-5-tert-butylphenyl)sulfonyl]-6-azabicyclo[3.2.1]octane; 6-[[3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[[5-2,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)phenoxy]-2-hydroxyphenyl]sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 1,3,3-trimethyl-6-[[5-[2-[[2-(2-oxo-1-imidazolidinyl)ethyl]amino]-4-pyrimidinyl]-2-thienyl]sulfonyl]-6-azabicyclo[3.2.1]octane; 6-[(4-ethoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 1,3,3-trimethyl-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-6-azabicyclo[3.2.1]octane; 6-[(2,3-dichlorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 3-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid; 3-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid methyl ester; 1,3,3-trimethyl-6-[(3-nitrophenyl)sulfonyl]-6-azabicyclo[3.2.1]octane; 4-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid; 1,3,3-trimethyl-6-[(2,3,5,6-tetramethylphenyl)sulfonyl]-6-azabicyclo[3.2.1]octane; 1,3,3-trimethyl-6-[(2-nitrophenyl)sulfonyl]-6-azabicyclo[3.2.1]octane; 6-[(4-acetylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(2,5-dimethylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(4-methoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(5-bromo-2-ethoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(2,5-dibromophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(2,4-difluorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(5-bromo-6-chloro-3-pyridinyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 6-[(2,5-dichlorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; 1,3,3-trimethyl-6-phenylsulfonyl-6-azabicyclo[3.2.1]octane; 6-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)benzo[d]oxazol-2(3H)-one; 6-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)benzo[cd]indol-2(1H)-one; 3-((1R,5S)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)-1H-pyrazolo[3,4-b]pyridine; 2,2,2-trifluoro-1-(8-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone; 6-[(4-tert-butylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane; and 6-[(3-aminophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane.
The compounds of Formula I, including those excepted and excluded, as well as salts, solvates, esters and prodrugs thereof, are inhibitors of 11β-hydroxysteroid dehydrogenase type-I, and can be used in the treatment of metabolic syndromes, obesity, obesity-related disorders, hypertension, atherosclerosis, lipid disorders, type-II diabetes, insulin resistance, pancreatitis and associated conditions.
Alternatively, the present invention provides for a method for treating a metabolic syndrome in a patient in need thereof which comprises administering to said patient a therapeutically effective amount of at least one compound of the Formula I:
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof;
wherein:
R 1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl; and R 2 -R 4 independently represent alkyl.
A further embodiment of the present invention is a method for treating obesity or an obesity-related disorder in a patient in need thereof which comprises administering to said patient a therapeutically effective amount of at least one compound of the Formula I:
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof;
wherein:
R 1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl; and R 2 -R 4 independently represent alkyl.
Another embodiment of the present invention is a method for treating type-II diabetes in a patient in need thereof which comprises administering to said patient a therapeutically effective amount of at least one compound of the Formula I:
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof;
wherein:
R 1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl; and R 2 -R 4 independently represent alkyl.
Another embodiment of the present invention is a method for treating atherosclerosis in a patient in need thereof which comprises administering to said patient a therapeutically effective amount of at least one compound of the Formula I:
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof;
wherein:
R 1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl; and R 2 -R 4 independently represent alkyl.
DETAILED DESCRIPTION
In one embodiment, the present invention discloses certain heterocyclic compounds which are represented by structural Formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, wherein the various moieties are as described above.
In another embodiment, the present invention embodies compounds of the Formula I, as well as salts, solvates, esters and prodrugs thereof, wherein:
R 1 represents phenyl, naphthyl, benzyl, stryryl, furanyl, thienyl, pyrazolyl, pyridyl, oxazolyl, benzothienyl or benzooxadiazolyl, each of which is optionally substituted by one or more substituents selected from the group consisting of alkyl, halogen, alkoxy, alkylcarbonyl, alkylsulphonyl, cyano, nitro, aryl, heteroaryl, aryloxy, carboxyl, alkoxycarbonylalkyl, cycloalkyl and morpholino; and R 2 -R 4 each represent alkyl.
Table 1 shows structures of representative compounds of this invention. The table and the compounds therein are not intended, nor should they be construed, to limit this invention in any manner whatsoever.
TABLE 1
COMPOUND NO.
STRUCTURE
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
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
68
69
70
71
72
73
74
75
76
77
78
79
80
81
As used above, and throughout this disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:
“Patient” includes both human and animals.
“Mammal” means humans and other mammalian animals.
“Alkyl” means an aliphatic hydrocarbon group which may be straight or branched and comprising about 1 to about 20 carbon atoms in the chain. Preferred alkyl groups contain about 1 to about 12 carbon atoms in the chain. More preferred alkyl groups contain about 1 to about 6 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl, are attached to a linear alkyl chain. “Lower alkyl” means a group having about 1 to about 6 carbon atoms in the chain which may be straight or branched. “Alkyl” may be unsubstituted or optionally substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, oxime (e.g., ═N—OH), —NH(alkyl), —NH(cycloalkyl), —N(alkyl) 2 , —O—C(O)-alkyl, —O—C(O)-aryl, —O—C(O)-cycloalkyl, carboxy and —C(O)O-alkyl. Non-limiting examples of suitable alkyl groups include methyl, ethyl, n-propyl, isopropyl and t-butyl.
“Alkenyl” means an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched and comprising about 2 to about 15 carbon atoms in the chain. Preferred alkenyl groups have about 2 to about 12 carbon atoms in the chain; and more preferably about 2 to about 6 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl, are attached to a linear alkenyl chain. “Lower alkenyl” means about 2 to about 6 carbon atoms in the chain which may be straight or branched. “Alkenyl” may be unsubstituted or optionally substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, alkyl. aryl, cycloalkyl, cyano, alkoxy and —S(alkyl). Non-limiting examples of suitable alkenyl groups include ethenyl, propenyl, n-butenyl, 3-methylbut-2-enyl, n-pentenyl, octenyl and decenyl.
“Alkylene” means a difunctional group obtained by removal of a hydrogen atom from an alkyl group that is defined above. Non-limiting examples of alkylene include methylene, ethylene and propylene.
“Alkynyl” means an aliphatic hydrocarbon group containing at least one carbon-carbon triple bond and which may be straight or branched and comprising about 2 to about 15 carbon atoms in the chain. Preferred alkynyl groups have about 2 to about 12 carbon atoms in the chain; and more preferably about 2 to about 4 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl, are attached to a linear alkynyl chain. “Lower alkynyl” means about 2 to about 6 carbon atoms in the chain which may be straight or branched. Non-limiting examples of suitable alkynyl groups include ethynyl, propynyl, 2-butynyl and 3-methylbutynyl. “Alkynyl” may be unsubstituted or optionally substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of alkyl, aryl and cycloalkyl.
“Aryl” means an aromatic monocyclic or multicyclic ring system comprising about 6 to about 14 carbon atoms, preferably about 6 to about 10 carbon atoms. The aryl group can be optionally substituted with one or more “ring system substituents” which may be the same or different, and are as defined herein. Non-limiting examples of suitable aryl groups include phenyl and naphthyl.
“Heteroaryl” means an aromatic monocyclic or multicyclic ring system comprising about 5 to about 14 ring atoms, preferably about 5 to about 10 ring atoms, in which one or more of the ring atoms is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. Preferred heteroaryls contain about 5 to about 6 ring atoms. The “heteroaryl” can be optionally substituted by one or more “ring system substituents” which may be the same or different, and are as defined herein. The prefix aza, oxa or thia before the heteroaryl root name means that at least a nitrogen, oxygen or sulfur atom respectively, is present as a ring atom. A nitrogen atom of a heteroaryl can be optionally oxidized to the corresponding N-oxide. “Heteroaryl” may also include a heteroaryl as defined above fused to an aryl as defined above. Non-limiting examples of suitable heteroaryls include pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N-substituted pyridones), isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,4-thiadiazolyl, pyrazinyl, pyridazinyl, quinoxalinyl, phthalazinyl, oxindolyl, imidazo[1,2-a]pyridinyl, imidazo[2,1-b]thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl, thienopyrimidyl, pyrrolopyridyl, imidazopyridyl, isoquinolinyl, benzoazaindolyl, 1,2,4-triazinyl, benzothiazolyl and the like. The term “heteroaryl” also refers to partially saturated heteroaryl moieties such as, for example, tetrahydroisoquinolyl, tetrahydroquinolyl and the like.
“Aralkyl” or “arylalkyl” means an aryl-alkyl-group in which the aryl and alkyl are as previously described. Preferred aralkyls comprise a lower alkyl group. Non-limiting examples of suitable aralkyl groups include benzyl, 2-phenethyl and naphthalenylmethyl. The bond to the parent moiety is through the alkyl.
“Alkylaryl” means an alkyl-aryl-group in which the alkyl and aryl are as previously described. Preferred alkylaryls comprise a lower alkyl group. Non-limiting example of a suitable alkylaryl group is tolyl. The bond to the parent moiety is through the aryl.
“Cycloalkyl” means a non-aromatic mono- or multicyclic ring system comprising about 3 to about 10 carbon atoms, preferably about 5 to about 10 carbon atoms. Preferred cycloalkyl rings contain about 5 to about 7 ring atoms. The cycloalkyl can be optionally substituted with one or more “ring system substituents” which may be the same or different, and are as defined above. Non-limiting examples of suitable monocyclic cycloalkyls include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. Non-limiting examples of suitable multicyclic cycloalkyls include 1-decalinyl, norbornyl, adamantyl and the like.
“Cycloalkylalkyl” means a cycloalkyl moiety as defined above linked via an alkyl moiety (defined above) to a parent core. Non-limiting examples of suitable cycloalkylalkyls include cyclohexylmethyl, adamantylmethyl and the like.
“Cycloalkenyl” means a non-aromatic mono or multicyclic ring system comprising about 3 to about 10 carbon atoms, preferably about 5 to about 10 carbon atoms which contains at least one carbon-carbon double bond. Preferred cycloalkenyl rings contain about 5 to about 7 ring atoms. The cycloalkenyl can be optionally substituted with one or more “ring system substituents” which may be the same or different, and are as defined above. Non-limiting examples of suitable monocyclic cycloalkenyls include cyclopentenyl, cyclohexenyl, cyclohepta-1,3-dienyl, and the like. Non-limiting example of a suitable multicyclic cycloalkenyl is norbornylenyl.
“Cycloalkenylalkyl” means a cycloalkenyl moiety as defined above linked via an alkyl moiety (defined above) to a parent core. Non-limiting examples of suitable cycloalkenylalkyls include cyclopentenylmethyl, cyclohexenylmethyl and the like.
“Halogen” means fluorine, chlorine, bromine, or iodine. Preferred are fluorine, chlorine and bromine.
“Ring system substituent” means a substituent attached to an aromatic or non-aromatic ring system which, for example, replaces an available hydrogen on the ring system. Ring system substituents may be the same or different, each being independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, heterocyclyl, —O—C(O)-alkyl, —O—C(O)-aryl, —O—C(O)-cycloalkyl, oxo, —C(═N—CN)—NH 2 , —C(═NH)—NH 2 , —C(═NH)—NH(alkyl), oxime (e.g., ═N—OH), Y 1 Y 2 N—, Y 1 Y 2 N-alkyl-, Y 1 Y 2 NC(O)—, Y 1 Y 2 NSO 2 − and —SO 2 NY 1 Y 2 , wherein Y 1 and V 2 can be the same or different and are independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, and aralkyl. “Ring system substituent” may also mean a single moiety which simultaneously replaces two available hydrogens on two adjacent carbon atoms (one H on each carbon) on a ring system. Examples of such moiety are methylene dioxy, ethylenedioxy, —C(CH 3 ) 2 — and the like which form moieties such as, for example:
In a preferred embodiment, R 1 represents a phenyl group optionally substituted with one or more ring substituents. In one especially preferred embodiment, a ring substituent is bonded at the para-position of the phenyl ring. In another especially preferred embodiment, the ring substituent is a branched alkyl group. In another especially preferred embodiment, the ring substituent contains a hydroxyl group or an ether linkage.
“Heteroarylalkyl” means a heteroaryl moiety as defined above linked via an alkyl moiety (defined above) to a parent core. Non-limiting examples of suitable heteroaryls include 2-pyridinylmethyl, quinolinylmethyl and the like.
“Heterocyclyl” means a non-aromatic saturated monocyclic or multicyclic ring system comprising about 3 to about 10 ring atoms, preferably about 5 to about 10 ring atoms, in which one or more of the atoms in the ring system is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. There are no adjacent oxygen and/or sulfur atoms present in the ring system. Preferred heterocyclyls contain about 5 to about 6 ring atoms. The prefix aza, oxa or thia before the heterocyclyl root name means that at least a nitrogen, oxygen or sulfur atom respectively is present as a ring atom. Any —NH in a heterocyclyl ring may exist protected such as, for example, as an —N(Boc), —N(CBz), —N(Tos) group and the like; such protections are also considered part of this invention. The heterocyclyl can be optionally substituted by one or more “ring system substituents” which may be the same or different, and are as defined herein. The nitrogen or sulfur atom of the heterocyclyl can be optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Non-limiting examples of suitable monocyclic heterocyclyl rings include piperidyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, 1,4-dioxanyl, tetrahydrofuranyl, tetrahydrothiophenyl, lactam, lactone, and the like. “Heterocyclyl” may also mean a single moiety (e.g., carbonyl) which simultaneously replaces two available hydrogens on the same carbon atom on a ring system. Example of such moiety is pyrrolidone:
“Heterocyclylalkyl” means a heterocyclyl moiety as defined above linked via an alkyl moiety (defined above) to a parent core. Non-limiting examples of suitable heterocyclylalkyls include piperidinylmethyl, piperazinylmethyl and the like.
“Heterocyclenyl” means a non-aromatic monocyclic or multicyclic ring system comprising about 3 to about 10 ring atoms, preferably about 5 to about 10 ring atoms, in which one or more of the atoms in the ring system is an element other than carbon, for example nitrogen, oxygen or sulfur atom, alone or in combination, and which contains at least one carbon-carbon double bond or carbon-nitrogen double bond. There are no adjacent oxygen and/or sulfur atoms present in the ring system. Preferred heterocyclenyl rings contain about 5 to about 6 ring atoms. The prefix aza, oxa or thia before the heterocyclenyl root name means that at least a nitrogen, oxygen or sulfur atom respectively is present as a ring atom. The heterocyclenyl can be optionally substituted by one or more ring system substituents, wherein “ring system substituent” is as defined above. The nitrogen or sulfur atom of the heterocyclenyl can be optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Non-limiting examples of suitable heterocyclenyl groups include 1,2,3,4-tetrahydropyridinyl, 1,2-dihydropyridinyl, 1,4-dihydropyridinyl, 1,2,3,6-tetrahydropyridinyl, 1,4,5,6-tetrahydropyrimidinyl, 2-pyrrolinyl, 3-pyrrolinyl, 2-imidazolinyl, 2-pyrazolinyl, dihydroimidazolyl, dihydrooxazolyl, dihydrooxadiazolyl, dihydrothiazolyl, 3,4-dihydro-2H-pyranyl, dihydrofuranyl, fluorodihydrofuranyl, 7-oxabicyclo[2.2.1]heptenyl, dihydrothiophenyl, dihydrothiopyranyl, and the like. “Heterocyclenyl” may also mean a single moiety (e.g., carbonyl) which simultaneously replaces two available hydrogens on the same carbon atom on a ring system. Example of such moiety is pyrrolidinone:
“Heterocyclenylalkyl” means a heterocyclenyl moiety as defined above linked via an alkyl moiety (defined above) to a parent core.
It should be noted that in hetero-atom containing ring systems of this invention, there are no hydroxyl groups on carbon atoms adjacent to a N, O or S, as well as there are no N or S groups on carbon adjacent to another heteroatom. Thus, for example, in the ring:
there is no —OH attached directly to carbons marked 2 and 5.
It should also be noted that tautomeric forms such as, for example, the moieties:
are considered equivalent in certain embodiments of this invention.
“Alkynylalkyl” means an alkynyl-alkyl-group in which the alkynyl and alkyl are as previously described. Preferred alkynylalkyls contain a lower alkynyl and a lower alkyl group. The bond to the parent moiety is through the alkyl. Non-limiting examples of suitable alkynylalkyl groups include propargylmethyl.
“Heteroaralkyl” means a heteroaryl-alkyl-group in which the heteroaryl and alkyl are as previously described. Preferred heteroaralkyls contain a lower alkyl group. Non-limiting examples of suitable aralkyl groups include pyridylmethyl, and quinolin-3-ylmethyl. The bond to the parent moiety is through the alkyl.
“Hydroxyalkyl” means a HO-alkyl-group in which alkyl is as previously defined. Preferred hydroxyalkyls contain lower alkyl. Non-limiting examples of suitable hydroxyalkyl groups include hydroxymethyl and 2-hydroxyethyl.
“Acyl” means an H—C(O)—, alkyl-C(O)— or cycloalkyl-C(O)—, group in which the various groups are as previously described. The bond to the parent moiety is through the carbonyl. Preferred acyls contain a lower alkyl. Non-limiting examples of suitable acyl groups include formyl, acetyl and propanoyl.
“Aroyl” means an aryl-C(O)— group in which the aryl group is as previously described. The bond to the parent moiety is through the carbonyl. Non-limiting examples of suitable groups include benzoyl and 1-naphthoyl.
“Alkoxy” means an alkyl-O— group in which the alkyl group is as previously described. Non-limiting examples of suitable alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy. The bond to the parent moiety is through the ether oxygen.
“Aryloxy” means an aryl-O— group in which the aryl group is as previously described. Non-limiting examples of suitable aryloxy groups include phenoxy and naphthoxy. The bond to the parent moiety is through the ether oxygen.
“Aralkyloxy” means an aralkyl-O— group in which the aralkyl group is as previously described. Non-limiting examples of suitable aralkyloxy groups include benzyloxy and 1- or 2-naphthalenemethoxy. The bond to the parent moiety is through the ether oxygen.
“Alkylthio” means an alkyl-S— group in which the alkyl group is as previously described. Non-limiting examples of suitable alkylthio groups include methylthio and ethylthio. The bond to the parent moiety is through the sulfur.
“Arylthio” means an aryl-S— group in which the aryl group is as previously described. Non-limiting examples of suitable arylthio groups include phenylthio and naphthylthio. The bond to the parent moiety is through the sulfur.
“Aralkylthio” means an aralkyl-S— group in which the aralkyl group is as previously described. Non-limiting example of a suitable aralkylthio group is benzylthio. The bond to the parent moiety is through the sulfur.
“Alkoxycarbonyl” means an alkyl-O—CO— group. Non-limiting examples of suitable alkoxycarbonyl groups include methoxycarbonyl and ethoxycarbonyl. The bond to the parent moiety is through the carbonyl.
“Aryloxycarbonyl” means an aryl-O—C(O)— group. Non-limiting examples of suitable aryloxycarbonyl groups include phenoxycarbonyl and naphthoxycarbonyl. The bond to the parent moiety is through the carbonyl.
“Aralkoxycarbonyl” means an aralkyl-O—C(O)— group. Non-limiting example of a suitable aralkoxycarbonyl group is benzyloxycarbonyl. The bond to the parent moiety is through the carbonyl.
“Alkylsulfonyl” means an alkyl-S(O 2 )— group. Preferred groups are those in which the alkyl group is lower alkyl. The bond to the parent moiety is through the sulfonyl.
“Arylsulfonyl” means an aryl-S(O 2 )— group. The bond to the parent moiety is through the sulfonyl.
The term “substituted” means that one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency under the existing circumstances is not exceeded, and that the substitution results in a stable compound. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By “stable compound” or “stable structure” is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.
The term “optionally substituted” means optional substitution with the specified groups, radicals or moieties.
The term “purified”, “in purified form” or “in isolated and purified form” for a compound refers to the physical state of said compound after being isolated from a synthetic process (e.g. from a reaction mixture), or natural source or combination thereof. Thus, the term “purified”, “in purified form” or “in isolated and purified form” for a compound refers to the physical state of said compound after being obtained from a purification process or processes described herein or well known to the skilled artisan (e.g., chromatography, recrystallization and the like), in sufficient purity to be characterizable by standard analytical techniques described herein or well known to the skilled artisan.
It should also be noted that any carbon as well as heteroatom with unsatisfied valences in the text, schemes, examples and Tables herein is assumed to have the sufficient number of hydrogen atom(s) to satisfy the valences.
When a functional group in a compound is termed “protected”, this means that the group is in modified form to preclude undesired side reactions at the protected site when the compound is subjected to a reaction. Suitable protecting groups will be recognized by those with ordinary skill in the art as well as by reference to standard textbooks such as, for example, T. W. Greene et al, Protective Groups in Organic Synthesis (1991), Wiley, New York.
When any variable (e.g., aryl, heterocycle, R 2 , etc.) occurs more than one time in any constituent or in Formula I, its definition on each occurrence is independent of its definition at every other occurrence.
As used herein, the term “composition” is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.
Prodrugs and solvates of the compounds of the invention are also contemplated herein. A discussion of prodrugs is provided in T. Higuchi and V. Stella, Pro - drugs as Novel Delivery Systems (1987) 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design , (1987) Edward B. Roche, ed., American Pharmaceutical Association and Pergamon Press. The term “prodrug” means a compound (e.g, a drug precursor) that is transformed in vivo to yield a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate or solvate of the compound. The transformation may occur by various mechanisms (e.g., by metabolic or chemical processes), such as, for example, through hydrolysis in blood. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as Novel Delivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.
For example, if a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate or solvate of the compound contains a carboxylic acid functional group, a prodrug can comprise an ester formed by the replacement of the hydrogen atom of the acid group with a group such as, for example, (C 1 -C 8 )alkyl, (C 2 -C 12 )alkanoyloxymethyl, 1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms, 1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms, alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms, 1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms, 1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms, N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms, 1-(N-(alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms, 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, di-N,N—(C 1 -C 2 )alkylamino(C 2 -C 3 )alkyl (such as β-dimethylaminoethyl), carbamoyl-(C 1 -C 2 )alkyl, N,N-di(C 1 -C 2 )alkylcarbamoyl-(C 1 -C 2 )alkyl and piperidino-, pyrrolidino- or morpholino(C 2 -C 3 )alkyl, and the like.
Similarly, if a compound of Formula (I) contains an alcohol functional group, a prodrug can be formed by the replacement of the hydrogen atom of the alcohol group with a group such as, for example, (C 1 -C 6 )alkanoyloxymethyl, 1-((C 1 -C 6 )alkanoyloxy)ethyl, 1-methyl-1-((C 1 -C 6 )alkanoyloxy)ethyl, (C 1 -C 6 )alkoxycarbonyloxymethyl, N—(C 1 -C 6 )alkoxycarbonylaminomethyl, succinoyl, (C 1 -C 6 )alkanoyl, α-amino(C 1 -C 4 )alkanyl, arylacyl and α-aminoacyl, or α-aminoacyl-α-aminoacyl, where each α-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH) 2 , —P(O)(O(C 1 -C 6 )alkyl) 2 or glycosyl (the radical resulting from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate), and the like.
If a compound of Formula (I) incorporates an amine functional group, a prodrug can be formed by the replacement of a hydrogen atom in the amine group with a group such as, for example, R-carbonyl, RO-carbonyl, NRR′-carbonyl where R and R′ are each independently (C 1 -C 10 )alkyl, (C 3 -C 7 ) cycloalkyl, benzyl, or R-carbonyl is a natural α-aminoacyl or natural α-aminoacyl, —C(OH)C(O)OY 1 wherein Y 1 is H, (C 1 -C 6 )alkyl or benzyl, —C(OY 2 )Y 3 wherein Y 2 is (C 1 -C 4 ) alkyl and Y 3 is (C 1 -C 6 )alkyl, carboxy(C 1 -C 6 )alkyl, amino(C 1 -C 4 )alkyl or mono-N— or di-N,N—(C 1 -C 6 )alkylaminoalkyl, —C(Y 4 )Y 5 wherein Y 4 is H or methyl and Y 5 is mono-N— or di-N,N—(C 1 -C 6 )alkylamino morpholino, piperidin-1-yl or pyrrolidin-1-yl, and the like.
One or more compounds of the invention may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and it is intended that the invention embrace both solvated and unsolvated forms. “Solvate” means a physical association of a compound of this invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. “Solvate” encompasses both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like. “Hydrate” is a solvate wherein the solvent molecule is H 2 O.
One or more compounds of the invention may optionally be converted to a solvate. Preparation of solvates is generally known. Thus, for example, M. Caira et al, J. Pharmaceutical Sci., 93(3), 601-611 (2004) describe the preparation of the solvates of the antifungal fluconazole in ethyl acetate as well as from water. Similar preparations of solvates, hemisolvate, hydrates and the like are described by E. C. van Tonder et al, AAPS PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham et al, Chem. Commun., 603-604 (2001). A typical, non-limiting, process involves dissolving the inventive compound in desired amounts of the desired solvent (organic or water or mixtures thereof) at a higher than ambient temperature, and cooling the solution at a rate sufficient to form crystals which are then isolated by standard methods. Analytical techniques such as, for example I. R. spectroscopy, show the presence of the solvent (or water) in the crystals as a solvate (or hydrate).
“Effective amount” or “therapeutically effective amount” is meant to describe an amount of compound or a composition of the present invention effective in inhibiting the above-noted diseases and thus producing the desired therapeutic, ameliorative, inhibitory or preventative effect.
The compounds of Formula I can form salts which are also within the scope of this invention. Reference to a compound of Formula I herein is understood to include reference to salts thereof, unless otherwise indicated. The term “salt(s)”, as employed herein, denotes acidic salts formed with inorganic and/or organic acids, as well as basic salts formed with inorganic and/or organic bases. In addition, when a compound of Formula I contains both a basic moiety, such as, but not limited to a pyridine or imidazole, and an acidic moiety, such as, but not limited to a carboxylic acid, zwitterions (“inner salts”) may be formed and are included within the term “salt(s)” as used herein. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, although other salts are also useful. Salts of the compounds of the Formula I may be formed, for example, by reacting a compound of Formula I with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization.
Exemplary acid addition salts include acetates, ascorbates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, fumarates, hydrochlorides, hydrobromides, hydroiodides, lactates, maleates, methanesulfonates, naphthalenesulfonates, nitrates, oxalates, phosphates, propionates, salicylates, succinates, sulfates, tartarates, thiocyanates, toluenesulfonates (also known as tosylates,) and the like. Additionally, acids which are generally considered suitable for the formation of pharmaceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use . (2002) Zurich: Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D.C. on their website). These disclosures are incorporated herein by reference thereto.
Exemplary basic salts include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases (for example, organic amines) such as dicyclohexylamines, t-butyl amines, and salts with amino acids such as arginine, lysine and the like. Basic nitrogen-containing groups may be quarternized with agents such as lower alkyl halides (e.g. methyl, ethyl, and butyl chlorides, bromides and iodides), dialkyl sulfates (e.g. dimethyl, diethyl, and dibutyl sulfates), long chain halides (e.g. decyl, lauryl, and stearyl chlorides, bromides and iodides), aralkyl halides (e.g. benzyl and phenethyl bromides), and others.
All such acid salts and base salts are intended to be pharmaceutically acceptable salts within the scope of the invention and all acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of the invention.
Pharmaceutically acceptable esters of the present compounds include the following groups: (1) carboxylic acid esters obtained by esterification of the hydroxy groups, in which the non-carbonyl moiety of the carboxylic acid portion of the ester grouping is selected from straight or branched chain alkyl (for example, acetyl, n-propyl, t-butyl, or n-butyl), alkoxyalkyl (for example, methoxymethyl), aralkyl (for example, benzyl), aryloxyalkyl (for example, phenoxymethyl), aryl (for example, phenyl optionally substituted with, for example, halogen, C 1-4 alkyl, or C 1-4 alkoxy or amino); (2) sulfonate esters, such as alkyl- or aralkylsulfonyl (for example, methanesulfonyl); (3) amino acid esters (for example, L-valyl or L-isoleucyl); (4) phosphonate esters and (5) mono-, di- or triphosphate esters. The phosphate esters may be further esterified by, for example, a C 1-20 alcohol or reactive derivative thereof, or by a 2,3-di(C 6-24 )acyl glycerol.
Compounds of Formula I, and salts, solvates, esters and prodrugs thereof, may exist in their tautomeric form (for example, as an amide or imino ether). All such tautomeric forms are contemplated herein as part of the present invention.
The compounds of Formula (I) may contain asymmetric or chiral centers, and, therefore, exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of Formula (I) as well as mixtures thereof, including racemic mixtures, form part of the present invention. In addition, the present invention embraces all geometric and positional isomers. For example, if a compound of Formula (I) incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the invention.
Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and/or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Also, some of the compounds of Formula (I) may be atropisomers (e.g., substituted biaryls) and are considered as part of this invention. Enantiomers can also be separated by use of chiral HPLC column.
It is also possible that the compounds of Formula (I) may exist in different tautomeric forms, and all such forms are embraced within the scope of the invention. Also, for example, all keto-enol and imine-enamine forms of the compounds are included in the invention.
All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds (including those of the salts, solvates, esters and prodrugs of the compounds as well as the salts, solvates and esters of the prodrugs), such as those which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, and diastereomeric forms, are contemplated within the scope of this invention, as are positional isomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example, if a compound of Formula (I) incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the invention. Also, for example, all keto-enol and imine-enamine forms of the compounds are included in the invention.) Individual stereoisomers of the compounds of the invention may, for example, be substantially free of other isomers, or may be admixed, for example, as racemates or with all other, or other selected, stereoisomers. The chiral centers of the present invention can have the S or R configuration as defined by the IUPAC 1974 Recommendations. The use of the terms “salt”, “solvate”, “ester”, “prodrug” and the like, is intended to equally apply to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or prodrugs of the inventive compounds.
The present invention also embraces isotopically-labelled compounds of the present invention which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 17 O, 31 P, 32 P, 35 S, 18 F, and 36 Cl, respectively.
Certain isotopically-labelled compounds of Formula (I) (e.g., those labeled with 3 H and 14 C) are useful in compound and/or substrate tissue distribution assays. Tritiated (i.e., 3 H) and carbon-14 (i.e., 14 C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e., 2 H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Isotopically labelled compounds of Formula (I) can generally be prepared by following procedures analogous to those disclosed in the Schemes and/or in the Examples hereinbelow, by substituting an appropriate isotopically labelled reagent for a non-isotopically labelled reagent.
Polymorphic forms of the compounds of Formula I, and of the salts, solvates, esters and prodrugs of the compounds of Formula I, are intended to be included in the present invention.
The compounds according to the invention have pharmacological properties; in particular, the compounds of Formula I can be inhibitors of 11β-hydroxysteroid dehydrogenase type I.
The term “obesity” as used herein, refers to a patient being overweight and having a body mass index (BMI) of 25 or greater. In one embodiment, an obese patient has a BMI of 25 or greater. In another embodiment, an obese patient has a BMI from 25 to 30. In another embodiment, an obese patient has a BMI greater than 30. In still another embodiment, an obese patient has a BMI greater than 40.
The term “obesity-related disorder” as used herein refers to: (i) disorders which result from a patient having a BMI of 25 or greater; and (ii) eating disorders and other disorders associated with excessive food intake. Non-limiting examples of an obesity-related disorder include edema, shortness of breath, sleep apnea, skin disorders and high blood pressure.
The term “metabolic syndrome” as used herein, refers to a set of risk factors that make a patient more susceptible to cardiovascular disease and/or type 2 diabetes. A patient is said to have metabolic syndrome if the patient has one or more of the following five risk factors:
1) central/abdominal obesity as measured by a waist circumference of greater than 40 inches in a male and greater than 35 inches in a female; 2) a fasting triglyceride level of greater than or equal to 150 mg/dL; 3) an HDL cholesterol level in a male of less than 40 mg/dL or in a female of less than 50 mg/dL; 4) blood pressure greater than or equal to 130/85 mm Hg; and 5) a fasting glucose level of greater than or equal to 110 mg/dL.
A preferred dosage is about 0.001 to 5 mg/kg of body weight/day of the compound of Formula I. An especially preferred dosage is about 0.01 to 5 mg/kg of body weight/day of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound.
In one embodiment, the present invention provides methods for treating a Condition in a patient, the method comprising administering to the patient one or more compounds of Formula I, or a pharmaceutically acceptable salt or solvate thereof and at least one additional therapeutic agent that is not a compound of Formula I, wherein the amounts administered are together effective to treat or prevent a Condition.
Non-limiting examples of additional therapeutic agents useful in the present methods for treating or preventing a Condition include, anti-obesity agents, antidiabetic agents, any agent useful for treating metabolic syndrome, any agent useful for treating a cardiovascular disease, cholesterol biosynthesis inhibitors, cholesterol absorption inhibitors, bile acid sequestrants, probucol derivatives, IBAT inhibitors, nicotinic acid receptor (NAR) agonists, ACAT inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, low-denisity lipoprotein (LDL) activators, fish oil, water-soluble fibers, plant sterols, plant stanols, fatty acid esters of plant stanols, or any combination of two or more of these additional therapeutic agents.
Non-limiting examples of anti-obesity agents useful in the present methods for treating a Condition include CB1 antagonists or inverse agonists such as rimonabant, neuropeptide Y antagonists, MCR4 agonists, MCH receptor antagonists, histamine H 3 receptor antagonists or inverse agonists, metabolic rate enhancers, nutrient absorption inhibitors, leptin, appetite suppressants and lipase inhibitors.
Non-limiting examples of appetite suppressant agents useful in the present methods for treating or preventing a Condition include cannabinoid receptor 1 (CB 1 ) antagonists or inverse agonists (e.g., rimonabant); Neuropeptide Y (NPY1, NPY2, NPY4 and NPY5) antagonists; metabotropic glutamate subtype 5 receptor (mGluR5) antagonists (e.g., 2-methyl-6-(phenylethynyl)-pyridine and 3[(2-methyl-1,4-thiazol-4-yl)ethynyl]pyridine); melanin-concentrating hormone receptor (MCH1 R and MCH2R) antagonists; melanocortin receptor agonists (e.g., Melanotan-II and Mc4r agonists); serotonin uptake inhibitors (e.g., dexfenfluramine and fluoxetine); serotonin (5HT) transport inhibitors (e.g., paroxetine, fluoxetine, fenfluramine, fluvoxamine, sertaline and imipramine); norepinephrine (NE) transporter inhibitors (e.g., desipramine, talsupram and nomifensine); ghrelin antagonists; leptin or derivatives thereof; opioid antagonists (e.g., nalmefene, 3-methoxynaltrexone, naloxone and nalterxone); orexin antagonists; bombesin receptor subtype 3 (BRS3) agonists; Cholecystokinin-A (CCK-A) agonists; ciliary neurotrophic factor (CNTF) or derivatives thereof (e.g.; butabindide and axokine); monoamine reuptake inhibitors (e.g., sibutramine); glucagon-like peptide 1 (GLP-1) agonists; topiramate; and phytopharm compound 57.
Non-limiting examples of metabolic rate enhancers useful in the present methods for treating or preventing a Condition include acetyl-CoA carboxylase-2 (ACC2) inhibitors; beta adrenergic receptor 3 (133) agonists; diacylglycerol acyltransferase inhibitors (DGAT1 and DGAT2); fatty acid synthase (FAS) inhibitors (e.g., Cerulenin); phosphodiesterase (PDE) inhibitors (e.g., theophylline, pentoxifylline, zaprinast, sildenafil, aminone, milrinone, cilostamide, rolipram and cilomilast); thyroid hormone β agonists; uncoupling protein activators (UCP-1, 2 or 3) (e.g., phytanic acid, 4-[(E)-2-(5,6,7,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid and retinoic acid); acyl-estrogens (e.g., oleoyl-estrone); glucocorticoid antagonists; 11-beta hydroxy steroid dehydrogenase type 1 (11β HSD-1) inhibitors; melanocortin-3 receptor (Mc3r) agonists; and stearoyl-CoA desaturase-1 (SCD-1) compounds.
Non-limiting examples of nutrient absorption inhibitors useful in the present methods for treating or preventing a Condition include lipase inhibitors (e.g., orlistat, lipstatin, tetrahydrolipstatin, teasaponin and diethylumbelliferyl phosphate); fatty acid transporter inhibitors; dicarboxylate transporter inhibitors; glucose transporter inhibitors; and phosphate transporter inhibitors.
Non-limiting examples of cholesterol biosynthesis inhibitors useful in the present methods for treating or preventing a Condition include HMG-CoA reductase inhibitors, squalene synthase inhibitors, squalene epoxidase inhibitors and mixtures thereof.
Non-limiting examples of cholesterol absorption inhibitors useful in the present methods for treating or preventing a Condition include ezetimibe and other compounds suitable for the same purpose. In one embodiment, the cholesterol absorption inhibitor is ezetimibe.
HMG-CoA reductase inhibitors useful in the present methods for treating or preventing a Condition include, but are not limited to, statins such as lovastatin, pravastatin, fluvastatin, simvastatin, atorvastatin, cerivastatin, CI-981, resuvastatin, rivastatin, pitavastatin, rosuvastatin or L-659,699 ((E,E)-11-[3′R-(hydroxy-methyl)-4′-oxo-2′R-oxetanyl]-3,5,7R-trimethyl-2,4-undecadienoic acid).
Squalene synthesis inhibitors useful in the present methods for treating or preventing a Condition include, but are not limited to, squalene synthetase inhibitors; squalestatin 1; and squalene epoxidase inhibitors, such as NB-598 ((E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3′-bithiophen-5-yl)methoxy]benzene-methanamine hydrochloride).
Bile acid sequestrants useful in the present methods for treating or preventing a Condition include, but are not limited to, cholestyramine (a styrene-divinylbenzene copolymer containing quaternary ammonium cationic groups capable of binding bile acids, such as QUESTRAN® or QUESTRAN LIGHT® cholestyramine which are available from Bristol-Myers Squibb), colestipol (a copolymer of diethylenetriamine and 1-chloro-2,3-epoxypropane, such as COLESTID® tablets which are available from Pharmacia), colesevelam hydrochloride (such as WelChol® Tablets (poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide) which are available from Sankyo), water soluble derivatives such as 3,3-ioene, N-(cycloalkyl) alkylamines and poliglusam, insoluble quaternized polystyrenes, saponins and mixtures thereof. Suitable inorganic cholesterol sequestrants include bismuth salicylate plus moritmorillonite clay, aluminum hydroxide and calcium carbonate antacids.
Probucol derivatives useful in the present methods for treating or preventing a Condition include, but are not limited to, AGI-1067 and others disclosed in U.S. Pat. Nos. 6,121,319 and 6,147,250.
IBAT inhibitors useful in the present methods for treating or preventing a Condition include, but are not limited to, benzothiepines such as therapeutic compounds comprising a 2,3,4,5-tetrahydro-1-benzothiepine 1,1-dioxide structure such as are disclosed in International Publication No. WO 00/38727.
Nicotinic acid receptor agonists useful in the present methods for treating or preventing a Condition include, but are not limited to, those having a pyridine-3-carboxylate structure or a pyrazine-2-carboxylate structure, including acid forms, salts, esters, zwitterions and tautomers, where available. Other examples of nicotinic acid receptor agonists useful in the present methods include nicotinic acid, niceritrol, nicofuranose and acipimox. An example of a suitable nicotinic acid product is NIASPAN® (niacin extended-release tablets) which are available from Kos Pharmaceuticals, Inc. (Cranbury, N.J.).
ACAT inhibitors useful in the present methods for treating or preventing a Condition include, but are not limited to, avasimibe, HL-004, lecimibide and CL-277082 (N-(2,4-difluorophenyl)-N-[[4-(2,2-dimethylpropyl)phenyl]-methyl]-N-heptylurea). See P. Chang et al., “Current, New and Future Treatments in Dyslipidaemia and Atherosclerosis”, Drugs 2000 July; 60(1); 55-93, which is incorporated by reference herein.
CETP inhibitors useful in the present methods for treating or preventing a Condition include, but are not limited to, those disclosed in International Publication No. WO 00/38721 and U.S. Pat. No. 6,147,090, which are incorporated herein by reference.
LDL-receptor activators useful in the present methods for treating or preventing a Condition include, but are not limited to, include HOE-402, an imidazolidinyl-pyrimidine derivative that directly stimulates LDL receptor activity. See M. Huettinger et al., “Hypolipidemic activity of HOE-402 is Mediated by Stimulation of the LDL Receptor Pathway”, Arterioscler. Thromb. 1993; 13:1005-12.
Natural water-soluble fibers useful in the present methods for treating or preventing a Condition include, but are not limited to, psyllium, guar, oat and pectin.
Fatty acid esters of plant stanols useful in the present methods for treating or preventing a Condition include, but are not limited to, the sitostanol ester used in BENECOL® margarine.
Non-limiting examples of antidiabetic agents useful in the present methods for treating a Condition include insulin sensitizers, β-glucosidase inhibitors, DPP-IV inhibitors, insulin secretagogues, hepatic glucose output lowering compounds, antihypertensive agents, sodium glucose uptake transporter 2 (SGLT-2) inhibitors, insulin and insulin-containing compositions, and anti-obesity agents as set forth above.
In one embodiment, the antidiabetic agent is an insulin secretagogue. In one embodiment, the insulin secretagogue is a sulfonylurea.
Non-limiting examples of sulfonylureas useful in the present methods include glipizide, tolbutamide, glyburide, glimepiride, chlorpropamide, acetohexamide, gliamilide, gliclazide, gliquidone, glibenclamide and tolazamide.
In another embodiment, the insulin secretagogue is a meglitinide.
Non-limiting examples of meglitinides useful in the present methods for treating a Condition include repaglinide, mitiglinide, and nateglinide.
In still another embodiment, the insulin secretagogue is GLP-1 or a GLP-1 mimetic.
Non-limiting examples of GLP-1 mimetics useful in the present methods include Byetta-Exanatide, Liraglutinide, CJC-1131 (ConjuChem, Exanatide-LAR (Amylin), BIM-51077 (Ipsen/LaRoche), ZP-10 (Zealand Pharmaceuticals), and compounds disclosed in International Publication No. WO 00/07617.
Other non-limiting examples of insulin secretagogues useful in the present methods include exendin, GIP and secretin.
In another embodiment, the antidiabetic agent is an insulin sensitizer.
Non-limiting examples of insulin sensitizers useful in the present methods include PPAR activators or agonists, such as troglitazone, rosiglitazone, pioglitazone and englitazone; biguanidines such as metformin and phenformin; PTP-1 B inhibitors; and glucokinase activators.
In another embodiment, the antidiabetic agent is a β-Glucosidase inhibitor.
Non-limiting examples of β-Glucosidase inhibitors useful the present methods include miglitol, acarbose, and voglibose.
In another embodiment, the antidiabetic agent is an hepatic glucose output lowering agent.
Non-limiting examples of hepatic glucose output lowering agents useful in the present methods include Glucophage and Glucophage XR.
In yet another embodiment, the antidiabetic agent is insulin, including all formualtions of insulin, such as long acting and short acting forms of insulin.
Non-limiting examples of orally administrable insulin and insulin containing compositions include AL-401 from Autoimmune, and the compositions disclosed in U.S. Pat. Nos. 4,579,730; 4,849,405; 4,963,526; 5,642,868; 5,763,396; 5,824,638; 5,843,866; 6,153,632; 6,191,105; and International Publication No. WO 85/05029, each of which is incorporated herein by reference.
In another embodiment, the antidiabetic agent is a DPP-IV inhibitor.
Non-limiting examples of DPP-IV inhibitors useful in the present methods include sitagliptin, saxagliptin, denagliptin, vildagliptin, alogliptin, alogliptin benzoate, Galvus (Novartis), ABT-279 and ABT-341 (Abbott), ALS-2-0426 (Alantos), ARI-2243 (Arisaph), BI-A and BI-B (Boehringer Ingelheim), SYR-322 (Takeda), MP-513 (Mitsubishi), DP-893 (Pfizer) and RO-0730699 (Roche).
In a further embodiment, the antidiabetic agent is a SGLT-2 inhibitor.
Non-limiting examples of SGLT-2 inhibitors useful in the present methods include dapagliflozin and sergliflozin, AVE2268 (Sanofi-Aventis) and T-1095 (Tanabe Seiyaku).
Non-limiting examples of antihypertensive agents useful in the present methods for treating a Condition include β-blockers and calcium channel blockers (for example diltiazem, verapamil, nifedipine, amlopidine, and mybefradil), ACE inhibitors (for example captopril, lisinopril, enalapril, spirapril, ceranopril, zefenopril, fosinopril, cilazopril, and quinapril), AT-1 receptor antagonists (for example losartan, irbesartan, and valsartan), renin inhibitors and endothelin receptor antagonists (for example sitaxsentan).
In one embodiment, the antidiabetic agent is an agent that slows or blocks the breakdown of starches and certain sugars.
Non-limiting examples of antidiabetic agents that slow or block the breakdown of starches and certain sugars and are suitable for use in the compositions and methods of the present invention include alpha-glucosidase inhibitors and certain peptides for increasing insulin production. Alpha-glucosidase inhibitors help the body to lower blood sugar by delaying the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. Non-limiting examples of suitable alpha-glucosidase inhibitors include acarbose; miglitol; camiglibose; certain polyamines as disclosed in WO 01/47528 (incorporated herein by reference); voglibose. Non-limiting examples of suitable peptides for increasing insulin production including amlintide (CAS Reg. No. 122384-88-7 from Amylin; pramlintide, exendin, certain compounds having Glucagon-like peptide-1 (GLP-1) agonistic activity as disclosed in International Publication No. WO 00/07617.
Other specific additional therapeutic agents useful in the present methods for treating or preventing a Condition include, but are not limited to, rimonabant, 2-methyl-6-(phenylethynyl)-pyridine, 3[(2-methyl-1,4-thiazol-4-yl)ethynyl]pyridine, Melanotan-II, dexfenfluramine, fluoxetine, paroxetine, fenfluramine, fluvoxamine, sertaline, imipramine, desipramine, talsupram, nomifensine, leptin, nalmefene, 3-methoxynaltrexone, naloxone, nalterxone, butabindide, axokine, sibutramine, topiramate, phytopharm compound 57, Cerulenin, theophylline, pentoxifylline, zaprinast, sildenafil, aminone, milrinone, cilostamide, rolipram, cilomilast, phytanic acid, 4-[(E)-2-(5,6,7,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid, retinoic acid, oleoyl-estrone, orlistat, lipstatin, tetrahydrolipstatin, teasaponin and diethylumbelliferyl phosphate.
In one embodiment, the present combination therapies for treating or preventing diabetes comprise administering a compound of formula (I), an antidiabetic agent and/or an antiobesity agent.
In another embodiment, the present combination therapies for treating or preventing diabetes comprise administering a compound of formula (I) and an antidiabetic agent.
In another embodiment, the present combination therapies for treating or preventing diabetes comprise administering a compound of formula (I) and an anti-obesity agent.
In one embodiment, the present combination therapies for treating or preventing obesity comprise administering a compound of formula (I), an antidiabetic agent and/or an antiobesity agent.
In another embodiment, the present combination therapies for treating or preventing obesity comprise administering a compound of formula (I) and an antidiabetic agent.
In another embodiment, the present combination therapies for treating or preventing obesity comprise administering a compound of formula (I) and an anti-obesity agent.
In one embodiment, the present combination therapies for treating or preventing metabolic syndrome comprise administering a compound of formula (I) and one or more additional therapeutic agents selected from: anti-obesity agents, antidiabetic agents, any agent useful for treating metabolic syndrome, any agent useful for treating a cardiovascular disease, cholesterol biosynthesis inhibitors, sterol absorption inhibitors, bile acid sequestrants, probucol derivatives, IBAT inhibitors, nicotinic acid receptor (NAR) agonists, ACAT inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, low-denisity lipoprotein (LDL) activators, fish oil, water-soluble fibers, plant sterols, plant stanols and fatty acid esters of plant stanols.
In one embodiment, the additional therapeutic agent is a cholesterol biosynthesis inhibitor. In another embodiment, the cholesterol biosynthesis inhibitor is an HMG-CoA reductase inhibitor. In another embodiment, the HMG-CoA reductase inhibitor is a statin. In another embodiment, the statin is lovastatin, pravastatin, simvastatin or atorvastatin.
In one embodiment, the additional therapeutic agent is a cholesterol absorption inhibitor. In another embodiment, the cholesterol absorption inhibitor is ezetimibe. In another embodiment, the cholesterol absorption inhibitor is a squalene synthetase inhibitor. In another embodiment, the cholesterol absorption inhibitor is a squalene epoxidase inhibitor.
In one embodiment, the additional therapeutic agent comprises a cholesterol absorption inhibitor and a cholesterol biosynthesis inhibitor. In another embodiment, the additional therapeutic agent comprises a cholesterol absorption inhibitor and a statin. In another embodiment, the additional therapeutic agent comprises ezetimibe and a statin. In another embodiment, the additional therapeutic agent comprises ezetimibe and simvastatin.
In one embodiment, the present combination therapies for treating or preventing metabolic syndrome comprise administering a compound of formula (I), an antidiabetic agent and/or an antiobesity agent.
In another embodiment, the present combination therapies for treating or preventing metabolic syndrome comprise administering a compound of formula (I) and an antidiabetic agent.
In another embodiment, the present combination therapies for treating or preventing metabolic syndrome comprise administering a compound of formula (I) and an anti-obesity agent.
In one embodiment, the present combination therapies for treating or preventing a cardiovascular disease comprise administering one or more compounds of formula (I), and an additional agent useful for treating or preventing a cardiovascular disease.
When administering a combination therapy to a patient in need of such administration, the therapeutic agents in the combination, or a pharmaceutical composition or compositions comprising the therapeutic agents, may be administered in any order such as, for example, sequentially, concurrently, together, simultaneously and the like. The amounts of the various actives in such combination therapy may be different amounts (different dosage amounts) or same amounts (same dosage amounts).
In one embodiment, the one or more compounds of Formula I are administered during a time when the additional therapeutic agent(s) exert their prophylactic or therapeutic effect, or vice versa.
In another embodiment, the one or more compounds of Formula I and the additional therapeutic agent(s) are administered in doses commonly employed when such agents are used as monotherapy for treating a Condition.
In another embodiment, the one or more compounds of Formula I and the additional therapeutic agent(s) are administered in doses lower than the doses commonly employed when such agents are used as monotherapy for treating a Condition.
In still another embodiment, the one or more compounds of Formula I and the additional therapeutic agent(s) act synergistically and are administered in doses lower than the doses commonly employed when such agents are used as monotherapy for treating a Condition.
In one embodiment, the one or more compounds of Formula I and the additional therapeutic agent(s) are present in the same composition. In one embodiment, this composition is suitable for oral administration. In another embodiment, this composition is suitable for intravenous administration.
The one or more compounds of Formula I and the additional therapeutic agent(s) can act additively or synergistically. A synergistic combination may allow the use of lower dosages of one or more agents and/or less frequent administration of one or more agents of a combination therapy. A lower dosage or less frequent administration of one or more agents may lower toxicity of the therapy without reducing the efficacy of the therapy.
In one embodiment, the administration of one or more compounds of Formula I and the additional therapeutic agent(s) may inhibit the resistance of a Condition to these agents.
In one embodiment, when the patient is treated for diabetes or a diabetic complication, the additional therapeutic agent is an antidiabetic agent which is not a compound of Formula I. In another embodiment, the additional therapeutic agent is an agent useful for reducing any potential side effect of a compound of Formula I. Such potential side effects include, but are not limited to, nausea, vomiting, headache, fever, lethargy, muscle aches, diarrhea, general pain, and pain at an injection site.
The pharmacological properties of the compounds of this invention may be confirmed by a number of pharmacological assays. The exemplified pharmacological assays which are described later have been carried out with the compounds according to the invention and their salts.
The invention is also directed to pharmaceutical compositions which comprise at least one compound of Formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound and at least one pharmaceutically acceptable carrier.
The term “pharmaceutical composition” is also intended to encompass both the bulk composition and individual dosage units comprised of more than one (e.g., two) pharmaceutically active agents such as, for example, a compound of the present invention and an additional agent selected from the lists of the additional agents described herein, along with any pharmaceutically inactive excipients. The bulk composition and each individual dosage unit can contain fixed amounts of the afore-said “more than one pharmaceutically active agents”. The bulk composition is material that has not yet been formed into individual dosage units. An illustrative dosage unit is an oral dosage unit such as tablets, pills and the like. Similarly, the herein-described method of treating a patient by administering a pharmaceutical composition of the present invention is also intended to encompass the administration of the afore-said bulk composition and individual dosage units.
For preparing pharmaceutical compositions from the compounds described by this invention, inert, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets and suppositories. The powders and tablets may be comprised of from about 5 to about 95 percent active ingredient. Suitable solid carriers are known in the art, e.g., magnesium carbonate, magnesium state, talc, sugar or lactose. Tablets, powders, cachets and capsules can be used as solid dosage forms suitable for oral administration. Examples of pharmaceutically acceptable carriers and methods of manufacture for various compositions may be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18 th Edition, (1990), Mack Publishing Co., Easton, Pa.
Liquid form preparations include solutions, suspensions and emulsions. As an example may be mentioned water or water-propylene glycol solutions for parenteral injection or addition of sweeteners and opacifiers for oral solutions, suspensions and emulsions. Liquid form preparations may also intranasal administration.
Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutically acceptable carrier, such as an inert compressed gas, e.g. nitrogen.
Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration. Such liquid forms include solutions, suspensions and emulsions.
The compounds of the invention may also be deliverable transdermally.
The transdermal compositions can take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as are conventional in the art for this purpose.
The compounds of this invention may also be delivered subcutaneously.
Preferably the compound is administered orally.
Preferably, the pharmaceutical preparation is in a unit dosage form. In such form, the preparation is subdivided into suitable sized unit doses containing appropriate quantities of the active component, e.g. an effective amount to achieve the desired purpose.
The quantity of active compound in a unit dose of preparation may be varied or adjusted from about 1 mg to about 100 mg, preferably from about 1 mg to about 50 mg, more preferably from about 1 mg to about 25 mg, according to the particular application.
The actual dosage employed may be varied depending upon the requirements of the patient and the severity of the condition being treated. Determination of the proper dosage regimen for a particular situation is within the skill of the art. For convenience, the total daily dosage may be divided and administered in portions during the day as required.
The amount and frequency of administration of the compounds of the invention and/or the pharmaceutically acceptable salts thereof will be regulated according to the judgment of the attending clinician considering such factors as age, condition and size of the patient as well as severity of the symptoms being treated. A typical recommended daily dosage regimen for oral administration can range from about 1 mg/day to about 500 mg/day, preferably 1 mg/day to 200 mg/day, in two to four divided doses.
Another aspect of this invention is a kit comprising a therapeutically effective amount of at least one compound of Formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound and a pharmaceutically acceptable carrier, vehicle or diluent.
Yet another aspect of this invention is a kit comprising an amount of at least one compound of Formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound and an amount of at least one therapeutic agent listed above, wherein the amounts of the two or more ingredients result in a desired therapeutic effect.
The invention disclosed herein is exemplified by the following preparations and examples which should not be construed to limit the scope of the disclosure. Alternative mechanistic pathways and analogous structures will be apparent to those skilled in the art.
Where NMR data are presented, 1 H spectra were obtained on either a Variant VXR-200 (200 MHz, 1 H), Varian Gemini-300 (300 MHZ), Varian Mercury VX-400 (400 MHz), or Bruker-Biospin AV-500(500 MHz), and are reported as ppm with number of protons and multiplicities indicated parenthetically. Where LC/MS data are presented, analyses was performed using an Applied Biosystems API-100 mass spectrometer and C18 column, 10-95% CH 3 CN—H 2 O (with 0.05% TFA) gradient. The observed parent ion is given.
The following solvents and reagents may be referred to by their abbreviations in parenthesis:
Me=methyl Et=ethyl Pr=propyl Bu=butyl Ph=phenyl Ac=acetyl μl=microliters AcOEt or EtOAc=ethyl acetate AcOH or HOAc=acetic acid ACN=acetonitrile atm=atmosphere Boc or BOC=tert-butoxycarbonyl DCE=dichloroethane DCM or CH 2 Cl 2 =dichloromethane DIPEA=diisopropylethylamine DMAP=4-dimethylaminopyridine DMF=dimethylformamide DMS=dimethylsulfide DMSO=dimethyl sulfoxide EDCI=1-(3-dimethylaminopropyl)-3-ethylcarbodiimine Fmoc or FMOC=9-fluorenylmethoxycarbonyl g=grams h=hour hal=halogen HOBt=1-hydroxybenzotriazole LAH=lithium aluminum hydride LCMS=liquid chromatography mass spectrometry min=minute mg=milligrams mL=milliliters mmol=millimoles MCPBA=3-chloroperoxybenzoic acid MeOH=methanol MS=mass spectrometry NMR=nuclear magnetic resonance spectroscopy RT or rt=room temperature (ambient, about 25° C.) TEA or Et 3 N=triethylamine TFA=trifluoroacetic acid THF=tetrahydrofuran TLC=thin layer chromatography TMS=trimethylsilyl Tr=triphenylmethyl
EXAMPLES
The compounds of this invention can be prepared as generally described in the Preparation Scheme, and the following examples.
Preparation Scheme
Polystyrene DIEA resin (47 mg, 0.045 mmol) was added to 40-wells of a deep well polypropylene microtiter plate followed by a MeCN/THF (2:1) stock solution (1 mL) of 1,3,3-trimethyl-6-azabicyclo-[3.2.1]octane X (8.0 mg, 0.05 mmol). Then 0.5 M stock solutions of each of the individual sulfonyl chlorides (R 1-45 SO 2 Cl) (0.210 mL, 0.10 mmol) were added to the wells, which was then sealed and shaken at 25° C. for 20 h. The solutions were filtered thru a polypropylene frit into a 2 nd microtiter plate containing polystyrene isocyanate resin (103 mg, 3 equivalents, 1.52 mmol/g) and polystyrene trisamine resin (74 mg, 6 equivalents, 4.23 mmol/g). After the top plate was washed with MeCN (0.5 mL), the plate was removed, the bottom microtiter plate sealed and shaken at 25° C. for 16 hrs. Then the solutions were filtered thru a polypropylene frit into a 96-well collection plate. The wells of the top plate were then washed with MeCN (2×0.5 mL), and the plate removed. Then the resultant solutions in the collection plate were transferred into vials and the solvents removed in vacuo via a SpeedVac to provide the sulfonamides.
Using this Preparation Scheme, the inventive compounds can be prepared.
Compound No. 1
To a solution of 1,3,3-trimethyl-6-azabicyclo-[3.2.1]octane (0.06 mL, 0.33 mmol) in CH 2 Cl 2 (3.3 mL) was added diisopropylethyl amine (0.17 mL, 0.99 mmol) followed by the sulfonyl chloride (0.49 mmol). The reaction was stirred at RT under nitrogen for 21 h after which it was quenched with 1 N HCl and extracted with CH 2 Cl 2 . The organics were dried over MgSO 4 , filtered and concentrated to give crude material. Purification by PTLC (15% EtOAc/hexanes) afforded the desired sulfonamide Compound No. 1 (115 mg, 100%).
Compound Nos. 2, 3, 47, 48, 51-67, 76-81 and N-(4-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)phenyl)acetamide, a compound purchased from TRIPOS, were prepared using commercially available sulfonyl chlorides in a similar manner as described for the synthesis of Compound No. 1.Yields ranged from 40 to 100%.
Separation of Compound No. 23
Compound No. 23 was prepared in the same manner as Compound No. 1.
About 90 mg of Compound No. 23 was dissolved in 5% IPA/hexanes (1.2 mL) and injected onto a chiralpak AS prep HPLC column (5 cm×50 cm) and eluted with 5% IPA/hexanes at 100 mL/min. Detection at 254 nm. 45 mg of Compound No. 54 (isomer 1, retention time=30.1 min) and 45 mg of a mixture of isomer 1 and 2 were obtained. The mixture (45 mg) was dissolved in 25% IPA/hexanes and injected onto the chiralpak AS prep column for the second time and eluted with 3% IPA/hexanes at 50 mL/min. 20.5 mg of Compound No. 55 (isomer 2, retention time=−67 min) was obtained.
Separation of Compound No. 16
Compound No. 16 was prepared in the same manner as Compound No. 1.
About 240 mg of Compound No. 16 was dissolved in 5% IPA/hexanes (1.2 mL) and injected onto a chiralpak AS prep HPLC column (5 cm×50 cm) and eluted with 15% IPA/hexanes at 75 mL/min. Detection at 254 nm. 81.3 mg of Compound No. 67 (isomer 1, retention time=46.4 min) and 102 mg of a mixture of isomer 1 and 2 were obtained. The mixture (102 mg) was dissolved in 25% IPA/hexanes and injected onto the chiralpak AS prep column for the second time and eluted with 15% IPA/hexanes at 50 mL/min. 44.0 mg of Compound No. 66 (isomer 2, retention time=86.9 min) was obtained.
Reduction of Compound No. 67
To a solution of Compound No. 67 (0.039 g, 0.12 mmol) in MeOH (1.5 mL) was added sodium borohydride (0.012 g, 0.32 mmol) at 0° C. in (ice bath). After stirring at room temperature for 1 h, the reaction was quenched with saturated ammonium chloride solution and extracted with CH 2 Cl 2 . The organic fractions were combined, dried over MgSO 4 , filtered, and concentrated to give the crude material. Purification by PTLC (2% MeOH/CH 2 Cl 2 ) yielded the desired reduction product Intermediate A as a mixture of enantiomers (33 mg, 85%).
Separation of Compound No. 67
About 18 mg of Intermediate A from the previous example was dissolved in 20% IPA/hexanes (1.0 mL) and injected onto a chiralpak AD semi-prep HPLC column and eluted with 10% IPA/hexanes at 10 mL/min. Detection at 254 nm. 7.9 mg of Compound No. 73 (isomer 1, retention time=19.1 min) and 7.3 mg of Compound No. 72 (isomer 2, retention time=22.6 min) were obtained.
Separation of Compound No. 66
Intermediate B was prepared from Compound No. 66 in the same manner as Intermediate A was prepared from Compound No. 67. Compound No. 71 (isomer 3, retention time=18.8 min, 95%) and Compound No. 70 (isomer 4, retention time=22.8 min, 5%) were prepared in the same manner as Compound No. 72 and Compound No. 73.
Preparation of Compound No. 81
To a solution of Compound No. 67 (34 mg, 0.10 mmol) in THF (2 mL) was added methylmagnesium bromide (3M in ether, 0.18 mL, 0.40 mmol). The reaction was stirred at room temperature for 1.5 h after which it was quenched with saturated ammonium chloride solution and extracted with CH 2 Cl 2 . The organic fraction was dried (MgSO 4 ), filtered, and concentrated to give a crude material. Purification by preparative TLC (25% EtOAc/Hexanes) afforded the desired compound Compound No. 81 (20.9 mg, 60%).
Compound No. 80 was prepared in the same manner as Compound No. 81 from Compound No. 66.
Preparation of Compound No. 79
NaH (6 mg, 0.25 mmol) was added to a solution of Compound No. 81 (18.2 mg, 0.050 mmol) in DMF (1 mL) at 0° C. After 15 min., iodomethane (0.01 mL, 0.10 mmol) was added and the reaction was warmed to room temperature. After 1.75 hours, the reaction was quenched with water and extracted with EtOAc. The combined organics were washed with water, dried over MgSO 4 , filtered and concentrated to give the crude material. Purification by PTLC (20% EtOAc/Hexanes) yielded the Compound No. 79 (9.0 mg, 48%).
Compound No. 78 was prepared in a similar manner as Compound No. 79 from Compound No. 80.
In vitro 11β-HSD1 activity assay
Preparation of 11β-HSD1 membranes
Human 11β-HSD1 with N-terminal myc tag was expressed in Sf9 cells using baculovirus Bac-to-Bac expression system (Invitrogen) according to manufacturer's instructions. Cells were harvested three days after infection and washed in PBS before frozen. To make membranes, the cells were resuspended in buffer A (20 mM Tris-HCl, pH7.4, 100 mM NaCl, 2 mM EDTA, 2 mM EGTA and Complete™ protease inhibitor tablets (Roche Molecular Biochemicals)), and lysed in a nitrogen bomb at 900 psi. The cell lysate was centrifuged at 600 g for 10 min to remove nuclei and large cell debris. The supernatant was centrifuged at 100,000 g for 1 hr. The membrane pellet was resuspended in buffer A, flash-frozen in liquid nitrogen and stored at −70° C. before use.
Measurement of 11β-HSD1 activity
11β-HSD1 enzymatic activity was measured in a 50 μl reaction containing 20 mM NaPO 4 pH 7.5, 0.1 mM MgCl 2 , 3 mM NADPH (prepared fresh daily), 125 nM 3 H-cortisone (American Radiochemicals) and 0.5 μg membrane. The reaction was incubated at room temperature for 1 hr before it was stopped by addition of 50 μM buffer containing 20 mM NaPO 4 pH 7.5, 30 μM 18β-glycyrrhetinic acid, 1 μg/ml monoclonal anti-cortisol antibody (Biosource) and 2 mg/ml anti-mouse antibody coated scintillation proximity assay (SPA) beads (Amersham Bioscience). The mixture was incubated at room temperature for 2 hrs with vigorous shaking and analyzed on TopCount scintillation counter.
Compounds according to the present invention showed activity against 11β-HSD1 in this assay.
In Vivo Screen for Inhibition of 11β-HSD-1
Lean male C57BI/6N mice were orally dosed with a solution of dexamethasone (0.5 mg/kg) and test agent or vehicle (20% HPβCD (10 ml/kg)). One hour later, cortisone was administered (1 mg/kg sc in sesame oil). One hour after cortisone administration, animals were euthanized for blood collection, and plasma cortisol levels were determined with a commercially available ELISA.
Compounds according to the present invention inhibited 11β-HSD1 in this screen.
Table 2 shows 11β-HSD-1 activity of representative compounds of this invention. The table and the compounds therein are not intended, nor should they be construed, to limit this invention in any manner whatsoever.
TABLE 2
Mouse cort.
Human
Mouse
challenge
11β-HSD-1
11β-HSD-1
% I
Compound No.
IC 50 (nM)
IC 50 (nM)
@ 30 mpk
29
5714
13266
76
126
1819
10
2509
3167
39
268
686
12
1415
28195
13
407
2483
5
3006
18247
6
247
670
4
3392
7926
74
5714
11136
75
126
5937
32
2509
3167
48
268
686
3
407
1875
64
340
217
61
415
165
25
169
364
63
111
305
62
96
309
9
190
420
17
67
127
1
31
71
30
23
28
19
26
65
372
950
68
55
112
16
139
732
44
16
67
63
45
19
27
16
46
10
87
50
7
43
43
49
23
11
19
69
30
68
While the present invention has been described in conjunction with the specific embodiments set forth above, many alternatives, modifications and other variations thereof will be apparent to those of ordinary skill in the art. All such alternatives, modifications and variations are intended to fall within the spirit and scope of the present invention. | In its many embodiments, the present invention relates to a novel class of 6-substituted sulfonyl-1,3,3-trialkyl-6-azabicyclo[3.2.1]octane compounds useful to inhibit 11β-hydroxysteroid dehydrogenase type-I, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the expression of 11β-hydroxysteroid dehydrogenase type-I using such compounds or pharmaceutical compositions. | 2 |
FIELD OF THE INVENTION
[0001] This invention relates generally to an apparatus for storing trading cards.
BACKGROUND OF THE INVENTION
[0002] Trading cards are an especially popular collector's item across all age groups. In addition to traditional sports cards such as baseball cards, children may collect and trade cards representing characters in role-playing games or popular animated television programs. Typically children will bring their cards to school or to a friend's house to trade or to play role-playing games. However, through use and transportation cards are subject to wear. A card's value in a trade or as collector's items may be reduced by wear and tear.
[0003] Prior storage means, such as a conventional box increase the risk of damage to trading cards and are not readily accessible. For example, a conventional box may snugly store trading cards during transportation. However, when removing the cards, only the edges of the cards may be gripped, resulting in excess wear at the edges, which are vulnerable to delamination and fraying. Alternatively, an entire box may be dumped out, which may be inconvenient when only a single card is needed.
[0004] Accordingly, it would be an advancement in the art to provide a container for storing and transporting trading cards that enabled ready removal of the cards from the container.
SUMMARY OF THE INVENTION
[0005] A box for storing cards includes an outer case having an upper and a lower end, the upper end defining an opening for insertion of cards and the like. A lid is sized to cover the opening and hingedly secures to an upper end of the outer case. An inner platform fits within the box and has a lower portion conforming to the lower end of the outer case, portion of the outer case proximate the lower end thereof. One or more vertical standoffs extend upwardly from the lower portion and secure to the lid by means of a linkage that lifts the platform from the box as the lid is opened.
[0006] The linkage may include a plate extending from the lid and pivotally coupling to the vertical standoff. In some embodiments, the plate secures to a front flap secured to a free end of the lid. A retention mechanism may retain the lid in a closed or open position. In one embodiment, the retention mechanism is a raised portion secured to the standoff and a depression secured to the linkage and positioned to receive the raised portion in at least one orientation of the linkage.
[0007] As will be readily appreciated from the foregoing summary, the invention provides a storage box for storing trading cards and provides a platform that is automatically raised on opening of the lid to facilitate removal of cards from the box.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] Preferred and alternative embodiments of the present invention are described in detail below with reference to the following drawings.
[0009] FIG. 1 is a perspective view of a lid-actuated card dispensing box in an open configuration, in accordance with an embodiment of the present invention;
[0010] FIG. 2 is a perspective view of an inner sleeve, in accordance with one embodiment of the present invention;
[0011] FIG. 3 is a cut-away front view of a linkage, in accordance with an embodiment of the present invention;
[0012] FIG. 4A is a side view of a lid-actuated card dispensing box in a closed configuration, in accordance with one embodiment of the present invention;
[0013] FIG. 4B is a side view of a is a lid-actuated card dispensing box in an open configuration, in accordance with one embodiment of the present invention; and
[0014] FIG. 5 is a rear quarter perspective view of a lid-actuated card dispensing box having a carrying clip, in accordance with one embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0015] Referring to FIG. 1 , a box 10 may include an outer box 12 having a lid 14 hingedly secured to an edge thereof. The outer box 12 and lid 14 may be formed of cardboard, steel, plastic, or other material sufficiently rigid to maintain a box shape. The outer box 12 and lid 14 may be covered in a wear resistant or decorative material, such as genuine or imitation leather, plastic, or the like. The outer box 12 and lid 14 may be lined to protect the outer box 12 and to inhibit wear on the contents of the box 10 . In the illustrated embodiment, the outer box 12 and lid 14 are lined with a nylon fabric.
[0016] Referring to FIG. 2 , while still referring to FIG. 1 , an inner sleeve 16 may be positioned within the outer box 12 . The inner sleeve 16 may include one or more vertical standoffs 18 extending upwardly from a platform 20 . The platform 20 may occupy a substantial portion of the bottom of the outer box 12 . The platform 20 is typically slightly smaller than the horizontal cross section of the outer box 12 to facilitate movement of the platform 20 within the outer box 12 . The vertical standoffs 18 extend upwardly from the platform 20 and secure to the lid 14 by means of a linkage 22 .
[0017] The linkage 22 transfers force from the manual raising of the lid 14 to the platform 20 , thereby raising cards and the like within the outer box 12 to a more accessible position. A retention member 24 engages the linkage 22 to selectively prevent relative motion between the lid and the standoffs 18 . The retention member 24 may serve to maintain the lid 14 in an open position with the platform 20 raised. The retention member 24 may also maintain the lid 14 in a closed position with the platform 20 lowered into the outer box 12 . In some embodiments, the retention member 24 serves to lock the lid 14 in both open and closed positions.
[0018] In the illustrated embodiment, the standoffs 18 are embodied as sides 26 a, 26 b forming the inner sleeve 16 . The sides 26 a, 26 b may extend substantially along the entire inner lateral walls of the outer box 12 while still sliding readily within the outer box 12 . A back 28 may extend between the sides 26 a, 26 b to define, along with the platform 20 , the sleeve 16 for holding cards, and the like.
[0019] The linkage 22 may include at least one plate 32 extending from the lid 14 to the standoff 18 . In the illustrated embodiment, two plates 32 extend from the lid. The plates 32 may independently secure to the lid 14 or may be angled end portions of a plate securing to the lid 14 . The plate 32 may secure to the standoff 18 by means of a pivot 34 , such as a rivet, such that as the lid is raised, the plate 32 pivots with respect to the standoff 18 . In the illustrated embodiment, the plate 32 may secure to the lid 14 by means of a front flap 36 rigidly or hingedly secured to the free end of the lid 14 .
[0020] Referring to FIG. 3 , the retention member 24 may be embodied as a raised portion 38 secured to the standoff 18 that engages a depression 40 secured to the plate 32 . Alternatively, the raised portion 38 may be secured to the plate 32 whereas the depression 40 is secured to the standoff 18 . The raised portion 38 may be forced into the depression 40 such that deformation of the plate 32 , standoff 18 , or both is required to remove the raised portion from the depression 40 . In the illustrated embodiment, the raised portion 38 is a rivet head and the depression is embodied as the crimped end of a hollow rivet shaft. In other embodiments, the raised portion 38 and depression 40 are formed by locally deforming the standoff 18 and plate 32 , respectively. Embodying the raised portion 38 and depression 40 as rivets may facilitate manufacture of a linkage 22 , inasmuch as a single tool is needed to form the pivot 34 , the depression 40 , and raised portion 38 .
[0021] Referring to FIG. 4A , in a closed configuration of the lid 14 , the inner sleeve 16 is pushed down into the outer box 12 . The plate 32 is positioned having the depression 40 aligned with the raised portion 38 such that the lid 14 is retained in the closed position. In some embodiments, a cutaway portion 48 may be formed in the outer box 12 adjacent the plate 32 to enable the plates 32 to secure the outside surfaces of the sides 26 a, 26 b, which may be spread apart by a distance substantially equal the interior width of the box 12 .
[0022] Referring to FIG. 4B , when opening the box 10 , the user swings the lid 14 upwardly from the outer box 12 causing the plate 32 to move upward and to pivot with respect to the sides 26 a, 26 b. Pivoting of the plate 32 forces the raised portion 38 out of the depression 40 . As the plate 32 is raised, the inner sleeve 16 is drawn out of the outer box 12 due to coupling of the plate 32 to the standoffs 18 by means of the pivot 34 . In some embodiments, a tongue 52 secures to a front side of the outer box 12 and extends upwardly therefrom. The tongue 52 may serve to retain cards when the lid is an open position. In the illustrated embodiment, the tongue 52 secures to the front of the outer box 12 and extends from the cutaway portion 48 to near the top of the outer box 12 . The tongue 52 may be formed from materials similar to those forming the outer box 12 . The tongue 52 may be formed monolithically with the front panel of the outer box 12 or may secure to the outer box 12 by means of glue, stitching, or other fastening means.
[0023] FIG. 5 , in some embodiments, a fastener 56 , such as a clip, belt loop, or like structure secures to a back panel of the outer box 12 . The fastener 56 may enable a user to secure the box 10 to a belt in order to transport the box 10 . The fastener 56 may pivot in a plane parallel to the back panel of the outer box 12 . In some embodiments, a detent mechanism retains the fastener 56 in specific orientations. In the illustrated embodiment, the detent mechanism retains the fastener 56 in vertical and horizontal orientations. The detent mechanism may also retain the fastener 56 in intermediate orientations.
[0024] While the preferred embodiment of the invention has been illustrated and described, as noted above, many changes can be made without departing from the spirit and scope of the invention. Accordingly, the scope of the invention is not limited by the disclosure of the preferred embodiment. Instead, the invention should be determined entirely by reference to the claims that follow. | A lid-actuated card-dispensing box is disclosed. An outer box having a lid receives an inner sleeve having a platform and at least one standoff coupled to the lid by means of a linkage. The linkage includes a plate secured to a front flap of the lid and pivotally connected to the standoff. A retention system resists movement of the plate relative to the standoff when the lid is in a closed position. | 0 |
BACKGROUND OF THE INVENTION
The invention relates to a sealing cap for the fuel tank pipe for motor vehicles, with an outer cap and an inner cover portion, held in torsion-proof relationship therein, whereby the inner cover portion being cup-shaped, having a peripheral flange at its side which faces the outer cap and bearing packing means for the sealing of the pipe and comprising fastening means for engagement with the pipe, the outer cap at its reverse side, facing the inner cover portion, including an integrally molded rib of a synthetic material, having at its free end at least one inwardly-directed radial lug engaging the inner cover portion, and the outer cap being adapted to snap off from the inner cover portion whenever the outer cap is affected by forces such as they occur during a motor vehicle accident.
THE PRIOR ART
A sealing cap of this type is known from German Patent Specification No. 26 57 747 Volkswagenwek AG. The rib portion of the outer cap has an annular lug, or several lugs, arranged at a distance from each other in the direction of the circumference and radially outwardly directed, and there is provided at the inner cover portion a sheet metal ring which is radially inward beaded in the direction of the outer cap and adjacent thereto, the beads having a C-shaped cross-section the lug or lugs of the rib reaching behind the beaded rim which is radially open towards the inside in order to connect the outer cap with the inner cover portion. In order to ensure that the outer cap can snap off in motor vehicle accidents, without undoing the tight seating of the inner cover portion on the fuel tank pipe, parts of this outer cap and certainly its rib, as well as the lug or lugs are manufactured from a weakly resilient material so that the lug or lugs may snap out of the beaded rim of the ring of the inner cover portion. Such desirable breakage under the influence of extremely strong forces affecting the outer cap should, however, be impossible under normal operating conditions.
During normal use of the cap, the connection between the outer cap and the inner cover portion must not only be tight enough to prevent a separation of the two parts, but the lug or lugs must be held tightly enough within the beaded rim of the inner cover portion so that the frictional engagement results in a sufficiently torsion-proof connection between the two. For this purpose, the rib with its lug or lugs must be held in the beaded rim under great radial prestress, and the rib as well as the lug or lugs must be highly stable so that they are not destroyed during mounting or when affected by forces resulting from normal operations, as well as the extremely high forces occurring in a motor vehicle accident. These parts must, therefore, be manufactured from a high-quality, tough, resilient synthetic material. The necessary use of such a high-quality synthetic material entails a corresponding expenditure for the synthetic material as well as for a more difficult processing thereof. In addition, the strong radial stress of the rib may lead to fatigue of the synthetic material, which means that after a certain working life, a secure connection between the outer cap and the inner cover portion, safeguarding against a snapping-off of the outer cap and against torsion between the outer cap and the inner cover portion, is no longer guaranteed.
OBJECT OF THE INVENTION
The invention is based on further developing economically a sealing cap of the initially described type in such a manner, that under normal operating stresses, a secure connection between outer cap and the inner cover portion is guaranteed while, at the same time, it is possible for the outer cap to snap off under the stress of extreme forces during motor vehicle accidents, without impairing the leakproof seating of the inner cover portion within the pipe.
The invention proposes to solve this problem by providing a sealing cap, of the initially described type, giving a sufficiently low stability to the radial lug so that it breaks off under the influence of forces acting upon the outer cap, and by providing positive locking means for a torsion-proof connection between the outer cap and the inner cover portion.
SUMMARY OF THE INVENTION
In the sealing cap of the invention, the lug of the rib constitutes a predetermined breaking point, where the outer cap separates from the inner cover portion under the influence of extremely high forces. Inasmuch as the lug is of relatively minor strength, the outer cap, if manufactured from a synthetic substance, may be made out of a synthetic material of not too high a quality and of relatively minor rigidity, which may also easily be processed or, alternatively, when using a high-quality synthetic material, a relatively minor thickness may be chosen for the area of the rib and for the lug, resulting in a reduced expenditure. Since separate positive-locking coupling means are provided for the torsion-proof connection between the outer cap and the inner cover portion, the lug at the inner cover portion does not have to be subjected to radial prestress in order to achieve a frictional engagement, so that, in this respect also, only a minor stability is required for the rib and for the lug, thereby excluding any material fatigue of these parts.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is hereinafter described in detail with reference to the accompanying drawings:
FIG. 1 shows a first embodiment of a sealing cap according to the invention in longitudinal section;
FIG. 2 shows a section through the sealing cap of FIG. 1 taken on line II--II of FIG. 1;
FIG. 3 shows a second embodiment of a sealing cap according to the invention, in longitudinal section, and
FIG. 4 shows a section through the sealing cap according to FIG. 3, taken on the line IV--IV of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The sealing cap as shown in FIGS. 1 and 2 comprises an outer cap 10 and an inner cover portion 12, held torsion-proof therein. The inner cover portion 12 is cup-shaped and includes (i) a bottom 14, located at its rear end, facing away from the outer cap 10, (ii) an approximately cylindrical wall section 16 adjacent thereto, and (iii) a flange 18 adjoining at the side which faces the outer cap 10, said flange protruding radially outward and extending around the circumference, manufactured out of sheet metal. The reverse side of the flange 18 has a sealing ring 20 to keep the fuel tank (not shown) sealed. Located within the interior space of the inner cover portion 12 in the area of the wall 16, there is a bayonet bridge 22 which is prestressed in the direction of the outer cap 10 by means of a helical pressure spring 24, fixed between said bridge and the bottom 14, said bayonet bridge with its free ends 26 protruding radially outward through openings 28 provided in the wall of the inner cover portion 12, to achieve fastening within the pipe by means of curves provided at the inner rim of the pipe (not shown).
The outer cap 10 is made of synthetic material which is not too high in quality, while its stability still permits the absorption of the forces occurring during manual operation. It comprises a slightly outward bulging mid-section 30, a rim 32, extending concentrically to the flange 18 and at a distance from it towards the rear and beyond the surface of said flange, as well as radial extensions 34, with spaces provided between them for manual operation and twisting of the cap between a closed and an open position. The outer cap 10 also includes a rib 36, located at the reverse side of the wall mid-section 30 facing the inner cover portion and molded as one piece therewith and, therefore, also being made of synthetic material, the rib 36 being annular, the radial wall thickness of said rib 36 being small as compared to the thicknesses of the wall mid-section 30, the rim 32 and the extensions 34. The rib 36 has several radially inward directed lugs 38 whose radial and axial cross-sectional dimensions are small as compared to the thicknesses of the wall mid-section 30 and the lugs 34; the extensions 38 at their upper surface which faces the wall mid-section 30 each providing an arcuate support surface 40 in a plane normal to the axis of the outer cap 10.
The inner cover portion 12, at the side which faces the outer cap 10, carries an insert 42 made of synthetic material. It includes a plane disc 44 with an outer diameter equal to the diameter of the flange 18 which rests against the flange 18 next to an inserted sealing ring 46.
In order to maintain the insert 42 in an axially fixed and torsion-proof position with respect to the flange 18 the rim 48 of said flange is provided with a bead of C-shaped cross-section lying tightly against the outer rim 50 of the disc 44, said outer rim 50 being bevelled facing the outer cap 10. The rim 48 also interlocks with recesses provided in the outer rim 50 in a manner which is not shown in detail.
In addition, the insert 42 comprises a flange 52, connected in one piece with the disc 44 and extending into the inner area of the rib 36, and a lip 54, radially extending outward at the free end of said flange 52 and engaging the lugs 38. The lip 54 is bevelled at the side which faces the outer cap 10 in order to facilitate the mounting of the insert 42 within the outer cap 10, while its reverse side is annular in shape and in a plane normal to the axis of the cap so that it rests against the support surfaces 40 of the lugs 38. Even though the axial and radial dimensions of the lip 54 are the same as for the lugs 38, the lip 54 is more stable than the lugs, inasmuch as it extends continuously into the direction of the circumference, and a severance of the outer cap 10 from the inner cover portion 12 is only possible by a breaking of the lugs 38 which are intended to have a relatively minor stability by reason of the material and the dimensions selected for them.
The outer radius of the flange 52 of the insert 42, in the unassembled state of the shaped piece, is identical with the inner radius of the lugs 38. The outer diameter of the lip 54, in the unassembled state of the insert 42 is identical, with the inside diameter of the rib 36. Thus, after the assembly of the insert 42 in the outer cap 10, the extension 52 and the lip 54 do not put any radial stress on the lugs 38 and on the rib 36. In order to make it possible that, during the assembly of the insert 42, the lip 54 may lock behind the lugs 38, without the lugs 38 breaking off during the necessary radial yield of the rib 30 and/or the flange 52, the radial dimensions of the lip 54 and of the lugs 38 are very small as compared to the outer diameter of the flange 18.
Flange 52 of the insert 42 is cylindrical. At the inside of flange 52, several cams 52 are provided at a distance from each other, in the direction of the circumference, which cams extend approximately as far as the reverse side of the mid-section 30 of the outer cap 10 and are formed in one piece with the disc 44. Their radially inner and outer surfaces are located along concentric circles while their radial flanks, facing each other and pointing in the direction of the circumference, are precisely radial. In addition, at the reverse side of the mid-section 30 of the outer cap 10, there is provided an identical number of cams 58, extending approximately as far as the disc 44 of the insert 42 and occupying with their cross-section each space between two neighbouring cams 56 of the insert 42 around the circumference; as can be seen from FIG. 2, the inner radius and the outer radius of the cams 58 are identical to that of the cams 56, while the flanks of the cams 58, facing each other and pointing in the direction of the circumference, are also precisely radial, so that one flank each of a cam 56 adjoins one flank each of a neighboring cam 58. In this manner, a torsion-proof positively locking connection between the outer cap 10 and the inner cover portion 12 has been created, while there is no frictional engagement between the extensions 38 and the section 52 or its annular flange 54.
In a variation of the embodiment shown, the inner cover portion 12 could be of a closed design and, as a connecting means, it could be provided with an outer thread in the area of the wall sector 16. In this case, the sealing ring 46 might be superfluous. If however as shown in the illustrated embodiment a bridge 22 is provided, which presupposes the existence of openings 28, it is possible that fuel may enter the inner area of the inner cover portion 12. In order to prevent this fuel from escaping into the outer cap 10, the inner cover portion 12 must be leakproof. This leakproof closure is achieved by means of the insert 42, the sealing ring 46 and the above-described mounting of the insert 42 in the rim 48 of the flange 18.
In the embodiment as shown in FIGS. 3 and 4, identical or equal parts are given the same reference symbols as in FIGS. 1 and 2. Thus, the inner cover portion 12 is cup-shaped, with a flange 18. However, at the elevation of the flange, there is a leakproof seal formed against the outer cap 10 by means of a wall portion 60. Also, the rim 48 of the flange is beaded radially inward towards the outer cap and adjacent thereto, the beads having a C-shaped cross-section, but there is also a ring 62 adjoining the radially inward pointing leg, said ring extending axially to the mid-section 30 of the outer cap 10 and being slightly widened at its free end.
In the embodiments shown in FIG. 3, and 4, the rim 48 directly serves as a mounting for the outer cap 10. In this case, the flange 64 provided at the reverse side of the outer cap 10 has an outer diameter which in the unassembled state is equal to the inside diameter of the ring 62 of the flange rim 48, so that in the assembled state the ring 62 lies against the outer diameter of the flange 64 without exerting any radial stress. At its free end, the hollow-cylindrical wall portion has a lip 66 which, in this case, extends radially towards the outside and engages the beaded rim 48. Between the rear free end of the flange 64 and the flange 18 there is a resilient ring 68 which largely prevents any axial motion of the extension 66 within the rim 48. While the ring 68 exerts a minor axial pressure on the extension 66 in the direction of the beaded leg of the rim 48, the resulting radial force affecting the flange 64 is very small. As a consequence, the outer cap may be snapped off from the inner cover portion 12 only by a breakage of the extension 66 along a sufficiently large portion of the circumference.
For the purpose of a positive-locking and torsion-proof coupling between the outer cap 10 and the inner cover portion 12, the beaded rim 48, including its ring 62, has a cut-out recess 70 of a width which is less than the length of the circumference, and the hollow-cylindrical flange 64 is provided with a cam 72, extending radially outward into said recess 70. The rim 48 which extends the ring 62 in the axial direction thereby enlarges the effective supporting surfaces between the rim 48 and the cam 72 along the circumference. | In a sealing cap for fuel tank pipes of motor vehicles with an outer cap (10) and an inner cover portion (12), the outer cap (10) has, at its inner side, a rib (36), made of synthetic material, which bears at least one radial lug (38) at its open end to serve as connection with the inner cover portion (12). In order to obtain a secure, torsion-proof connection between the outer cap (10) and the inner cover portion (12) during normal use and in order to facilitate a snapping off of the outer cap (10) in the case of motor vehicle accidents, the strength of the lug (38) is calculated to be low, and the torsion-proof connection between the outer cap (10) and the inner cover portion (12) is achieved by a separate positive-locking coupling (56, 58). | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a rotatable guide sleeve, and more particularly, to an improved rotatable sleeve for guiding wire strands over a rotatable shaft and the like.
2. Description of the prior art
In the prior art, rotatable sleeves for guiding a plurality of wire strands are typified by those used in material cutting machines having a web with a plurality of wires. Rotatable sleeves with grooves for spacing the plurality of wires a predetermined distance from one another are provided in the material cutting machine on a plurality of elongated, parallel, cylindrical rotatable shafts. The plurality of wires between the shafts form a web or wires, wherein a predetermined portion of the web defines a cutting area. Prior art guide sleeves, which are press fitted to the shafts are made of a synthetic material, such as plastics, into which the plurality of grooves are machined. The accuracy of the wire-cutting machine is due to the precise spacing of the wires by the grooves of the rotatable sleeves.
During the cutting operation, the rotatable sleeve is subjected to radial stress by the web of wires which causes transverse expansion and eventually cold flow of the synthetic sleeve into a distorted shape. The dimensional instabilities of the synthetic sleeve result in a considerable deterioration of the cutting accuracy of the material cutting machine after a relatively short period of time. Stress relaxation and fluctuations in operating temperatures may also cause dimensional instabilities in the synthetic sleeve. To maintain the accuracy of the material cutting machine, the synthetic sleeve on the shafts must be periodically changed.
In order to improve the dimensional stability of the rotatable sleeve relatively hard plastics have been used. However, hard plastics have a much lower abrasion resistance than softer plastics and therefore tend to wear out quickly.
For the foregoing and other shortcomings and problems, there has been a long felt need for an improved rotatable guide sleeve.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide an improved rotatable sleeve for guiding one or more wire strands that is dimensionally stable under radial stress.
It is a further object of the present invention to provide an improved rotatable sleeve for guiding one or more wire strands that exhibits a high degree of abrasion resistance.
It is a still further object of the present invention to provide an improved rotatable sleeve for guiding a plurality of wire strands that accurately spaces them a predetermined distance from one another.
It is yet a further object of the present invention to provide an improved rotatable sleeve for guiding one or more wire strands that has a longer usable life than prior art rotatable sleeves.
In accordance with the present invention, the aforementioned problems and shortcomings of the prior art are overcome and the stated and other objects are attained by an improved rotatable sleeve adapted to guide at least one strand of material, for example, wire strands, which includes a tubular, dimensionally stable inner member, a tubular outer member embracing the inner member, and means for imparting dimensional stability from the inner member to the outer member. The outer member, receiving its dimensional stability from the inner member can now be made of a less dimensionally stable material that possesses a high degree of abrasion resistance. Grooves are machined into the outer member for spacing a plurality of wire strands at a predetermined distance from one another. The rotatable sleeve can subsequently be fixedly mounted to a rotatable shaft or a similar device.
According to another feature of the invention, a rotatable sleeve adapted to guide a plurality of wire strands includes a tubular first member, a tubular dimensionally stable second member embracing the first member, a tubular third member embracing the second member and spacing a plurality of wire strands at a predetermined distance from one another, and means for imparting dimensional stability from the second member to the first and third members. The tubular first member, being less dimensionally stable than the second member, can be made of any practical material selected to enable a press fitted mounting of the rotatable sleeve to a rotatable shaft.
Additional features, objects and advantages of the rotatable guide sleeve in accordance with the present invention will be more clearly apprehended from the following detailed description together with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a rotatable guide sleeve in accordance with the present invention.
FIG. 2 is a sectional view taken substantially along the line 2--2 of FIG. 1.
FIG. 3 is a perspective view of a rotatable guide sleeve of the prior art.
FIG. 4 is a partial view of the material cutting machine showing a web with a plurality of wires between three elongated, parallel, cylindrical rotatable shafts.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1, a rotatable guide sleeve 20 for use in a material cutting machine is illustrated that includes a tubular first member 23, a tubular, dimensionally stable second member 22 embracing the first member 23, and a tubular third member 21 embracing the second member 22. The rotatable guide sleeve 20 further includes a plurality of grooves 24 on the outer surface of the third member 21 for spacing a plurality of wire strands at a predetermined distance from one another. Means are provided for imparting dimensional stability from the second member 22 to the first and third members 23 and 21. For example, the members 21, 22 and 23 can be pre-formed of predetermined materials and then cemented together such that they are fixedly secured to one another. The rotatable guide sleeve 20 can also be constructed by casting the first and third members 23 and 21 onto the second member 22.
In FIG. 2, the cross sectional view illustrates more clearly one form of the present invention. The second member 22 is made of a dimensionally stable and hard material, for instance, a metallic material. The first and third members 23 and 21, receiving dimensional stability from the second member 22, can be made from a wide variety of materials which need not possess a high degree of dimensional stability or hardness. The materials for the first and third members 23 and 21 can be selected to have a high degree of abrasion resistance in order to increase the usable life of the rotatable guide sleeve. For example, the second member 22 is preferably made of a steel alloy, such as INVAR, and the first and third members 23 and 21 are preferably made of 95 shore "A" polyurethane. The INVAR is selected for its hardness, its low thermal expansion coefficient and its relatively low degree of transverse expansion when subjected to radial stress, as evidenced by its relatively low Poisson's ratio of approximately 0.30. The polyurethane is selected for its high degree of abrasion resistance. Although the polyurethane is relatively dimensionally unstable, as evidenced by its relatively high Poisson's ratio of approximately 0.45, the polyurethane is imparted dimensional stability by being fixedly secured to the second member 22. The polyurethane first and third members 23 and 21 are preferably cast to the second member 22 to provide an excellent bond between the INVAR and the polyurethane.
The dimensional stability imparted from the second member 22 to the first and third members 23 and 21 can be further enhanced by indentations or protrusions, such as longitudinal or radial ribs, on the surfaces of the second bushing 22. The protrusions provide additional coupling between the three members 21, 22 and 23 to further strengthen the bond and limit the transverse expansion of the first and third members 23 and 21 due to radial stress.
Next, grooves 24 are machined into the outer surface of the rotatable guide sleeve 20 for spacing a plurality of wires at a predetermined distance from one another. The grooves are precisely spaced so that the material cutting machine accurately cuts as many as two hundred wafers simultaneously from a piece of material, such as quartz, silicon, or ceramics. The thickness of the third member 21 is kept as thin as possible, while still accomodating the grooves 24, to decrease the volume of material and thus decrease the transverse expansion experienced when subjected to radial stress.
In FIG. 3, a prior art synthetic sleeve 25 is shown which is made of hard plastic, such as nylon, DELRIN or polyethylene. Grooves 24 are machined into the plastic sleeve 25 for spacing a plurality of wires at a predetermined distance from one another. The plastic sleeve 25, being made of one of the relatively hard plastics which have a relatively low degree of abrasion resistance, experiences significantly more wear than the rotatable guide sleeve 20 of the present invention. The plastic sleeve 25 is also relatively dimensionally unstable as compared to the rotatable guide sleeve 20 of the present invention. The plastic sleeve 25 undergoes transverse expansion when subjected to radial stress during the cutting operation and cold flows in the transverse direction after a relatively short period of use. The resultant transverse distortion of the plastic sleeve 25 causes considerable inaccuracy in the spacing of the plurality of wires, resulting in wafers that do not meet tolerance specifications. These and other problems of the prior art have been overcome by the improved rotatable guide sleeve 20 of the present invention.
Referring to FIG. 4, the rotatable guide sleeve 20 in accordance with the present convention can be advantageously utilized in a material cutting machine which has a web, generally designated 35, with a plurality of wires between elongated, parallel, cylindrical rotatable shafts 36, 37 and 38, wherein a predetermined portion of the web 35 defines a cutting area 40. Such a machine is more fully described in U.S. Pat. No. 3,824,982, entitled "Machine for Cutting Brittle Materials," by J. L. Bowman, U.S. Pat. No. 3,831,576, entitled "Machine and Method For Cutting Brittle Materials Using a Reciprocating Cutting Wire," by H. W. Mech, and U.S. Pat. No. 3,841,297, entitled "Machine for Cutting Brittle Materials," by H. W. Mech. In this machine a piece of material (not illustrated) is passed through the cutting area 40 to produce a large number of uniform wafers of predetermined thickness controlled by the spacing of the wires. For example, as many as two hundred wafers are simultaneously cut from a piece of material, such as quartz, silicon or ceramics. Rotatable guide sleeves 20 are press fitted onto the rotatable shafts 36, 37 and 38 and accurately space the plurality of wires in the web 35 at a predetermined distance from one another. The web of wires 35 subjects the rotatable sleeves 26 to radial stress and abrasive wear. Because of its improved dimensional stability and abrasion resistance, the rotatable guide sleeve 20 of the present invention has a usable life that is three to four times greater than that of prior art synthetic sleeves 25. The material cutting machine is not only more accurate but also more efficient with the rotatable guide sleeve 20 of the present invention since the time consuming process of changing the sleeves 20 is not required as often.
A rotatable guide sleeve 20 in accordance with the present invention can be generally applied to any device in which one or more wire strands are accurately guided over a pulley or the like. It is to be understood that, in practicing the present invention, only the second member 22 and the third member 21 need be included in the rotatable guide sleeve 20. In addition, any number of concentric tubular members can be included in the rotatable guide sleeve 20 without departing from the spirit and scope of the present invention.
The foregoing embodiments have been intended as illustrations of the principles of the present invention. Accordingly, other modifications, uses and embodiments can be devised by those skilled in the art without departing from the spirit and scope of the principles of the present invention. | A rotatable sleeve for guiding at least one strand of wire, for example, includes a tubular outer member bonded to a tubular, dimensionally stable inner member which is press fitted onto a rotatable shaft. Dimensional stability is imparted from the inner member to the outer member which undergoes radial stress from the wire strand. For spacing a plurality of wire strands at a predetermined distance from one another, grooves are machined into the outer member of the rotatable sleeve. A further feature provides another tubular member inside the inner member for optimizing the press fit of the rotatable sleeve to the shaft. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] Not Applicable,
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
MICROFICHE/COPYRIGHT REFERENCE
[0003] Not Applicable.
FIELD
[0004] This disclosure relates to safety equipment and harnesses, and in more particular applications, to fall protection equipment in the form of safety harnesses that are worn by people who are at risk of falling from an elevated location.
BACKGROUND
[0005] Safety harnesses are commonly used as part of a fall protection system for persons subjected to the potential of a fall from a height. In the workplace, full-body safety harnesses are generally used. Such harnesses, which typically include both an upper torso portion (having, for example, shoulder straps) and a lower torso portion (having, for example seat straps and leg straps), can be designed in many alternative manners.
[0006] Many currently available full-body safety harnesses are manufactured from relatively inelastic, woven webbing materials such as nylon or polyester. A flexible and elastic harness, as described in U.S. Pat. No. 6,006,700, has been introduced that greatly improves the comfort of the user during normal use of the safety harness. A safety harness with blunted edges for further increasing the comfort of the user is disclosed in U.S. Pat. No. 6,739,427. These documents can be referenced for an understanding of the materials and constructions of some examples of harness with which the features disclosed herein can be employed.
[0007] Although the comfort of safety harnesses during normal use and even during a fall arrest has been greatly improved in the above-described harnesses, problems can still arise in the case that a harness user is suspended in a safety harness for a substantial period of time after a fall. In that regard, orthostatic intolerance/suspension trauma, including unconsciousness and even death, may be experienced by an individual using a fall protection safety harness if the individual remains suspended in the harness for a length of time. Typically, a person suspended in a fall protection system is suspended in an upright static position in which venous pooling can lead to orthostatic intolerance/suspension trauma. For example, pooling of blood can occur in the legs do to the pressure created by the leg straps of a harness while supporting the weight of the victim, with this pooling of blood subsequently restricting the flow of blood to the brain and other major organs which may cause unconsciousness. Thus, venous pooling and orthostatic intolerance can lead to a serious injury and even death as the brain and other vital organs are deprived of oxygen.
[0008] For the above reasons, it is recommended that individual in a safety harness should not work alone, and, in the case of suspension after a fall, the suspended individual should be rescued as soon as possible. It is further recommended, for example, that an individual using a harness be trained to try to move their legs while suspended in the harness and to push against any available footholds in an attempt to prevent venous pooling.
[0009] Because the average fall rescue time is 15 minutes, the need arises for victim to be able to relieve the pressure of the leg straps around the legs to avoid succumbing to suspension trauma.
[0010] One prior solution is shown in US 2005/0194211 A1, which discloses a pair of footholds that can be used to remove pressure/load from the leg straps of a safety harness. Two of them are required for proper use. This is a secondary product that may be purchased and added onto a harness if the end user so desires to do so, however at least one manufacturer provides a harness than includes such a feature,
SUMMARY
[0011] In accordance with one feature of this disclosure, a safety harness is provided to be worn by a person. The safety harness includes at least one of a pair of leg straps, each adapted to encircle a respective leg of a person wearing the harness, each of the leg straps moveable between a first position where the leg strap encircles an upper thigh portion of a leg of a person wearing the strap and a second position wherein the strap encircles a lower thigh portion of the leg of the person; and a seat strap adapted to extend across the buttocks of a person wearing the harness and operatively connected to the leg straps, the seat strap moveable from a first position extending across or above the upper buttocks of a person wearing the harness and a second position extending across or below the lower buttocks of a person wearing the harness. The harness further includes at least one hand engageable member operatively connected to the at least one of the pair of leg straps and the seat strap to allow a person wearing the harness to move the at least one of the pair of leg straps and the seat strap between the first and second positions with the harness bearing the weight of the person.
[0012] As one feature, the at least one hand engageable member is a loop extending from the at least one of pair of leg straps and the seat strap and adapted for engagement by a hand a person wearing the harness. In a further feature, the loop includes a strap fixed to the at least one of the leg straps and seat strap. In yet a further feature, the loop is a thumb or finger loop sized to accept a thumb of a person wearing the harness but not the remainder of a hand of the person.
[0013] In one feature, the at least one hand engageable member is a pair of loops operatively connected to the at least one of the leg straps and the seat strap, the loops located on the harness to be positioned on opposite sides of a buttocks from each other on a person wearing the safety harness. In a further feature, each of the loops is a thumb or finger loop sized to accept a thumb of a person wearing the harness but not the remainder of a hand of the person
[0014] According to one feature, the at least one of the leg straps and the seat strap includes the seat strap, and the at least one hand engageable member is operatively connected to the seat strap to allow a person wearing the harness to move the seat strap from the first position to the second position. In a further feature, the at least one hand engageable member is a pair of loops operatively connected to the seat strap, the loops located on the harness to be positioned on opposite sides of a buttocks from each other of a person wearing the safety harness.
[0015] As one feature, the at least one of the leg straps and the seat strap includes the leg straps, and the at least one hand engageable member is operatively connected to the leg straps to allow a person wearing the harness to move the leg straps from the first position to the second position. In a further feature, the at least one hand engageable member is a pair of loops operatively connected to the leg straps, the loops located on the harness to be positioned on opposite sides of a buttocks from each other on a person wearing the safety harness. In yet a further feature, the at least one of the leg straps and seat strap further includes the seat strap, with each of the loops being fixed to the seat strap and to a corresponding one of the leg straps to allow a person wearing the harness to move the seat strap and the leg straps from the first positions to the second positions. In yet a further feature, each of the loops includes a strap fixed to the seat strap and a corresponding one of the leg straps. As an additional feature, each of the loops is sized to accept a thumb of a person wearing the harness but not the remainder of a hand of the person. As yet a further feature, the leg straps, the seat strap and the at least one hand engageable member define a lower seat portion of the harness, and the harness further includes an upper torso portion operatively connected to the lower seat portion and adapted to secure the harness to the upper torso of a person wearing the harness. As an additional feature, the upper torso portion includes a pair of shoulder straps operatively connected to the lower seat portion, each of the shoulder straps configured to extend over a respective shoulder of a person wearing the strap.
[0016] In accordance with one feature of this disclosure, a method is provided for manipulating a safety harness to alleviate the potential effects of orthostatic intolerance in a person wearing the harness while suspended thereby. The method includes the steps of loading a safety harness with a weight of a person wearing the harness; and while the safety harness is loaded with the weight of the person wearing the harness, selectively repositioning a strap of the harness from a first position where the strap extends across an upper portion of a lower torso of the person wearing the harness and a second position where the strap extends across a lower portion of the lower torso of the person wearing the harness.
[0017] As a one feature, the step of selectively repositioning includes the step of selectively repositioning at least one leg strap of the harness from a first position where the strap extends around an upper thigh of a leg of the person wearing the harness to a lower position on the thigh of the leg of the person.
[0018] In one feature, the step of selectively repositioning includes the step of selectively repositioning a seat strap of the harness from a first position where the strap extends across or above an upper portion of a buttocks of the person wearing the harness to a lower portion of the buttocks or thighs of the person wearing the harness.
[0019] According to one feature, the step of selectively repositioning includes the step of engaging each hand of the person with a corresponding harness member extending from the strap and using the hands to move the strap to the second position. In a further feature, the engaging step includes inserting one of a finger or thumb of each hand of the person into a corresponding loop extending from the strap.
[0020] Other features and advantages will become apparent from a review of the entire specification, including the appended claims and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is a somewhat diagrammatic front view of a person wearing the safety harness of FIG. 3 ;
[0022] FIG. 2 is a somewhat diagrammatic rear view of a person wearing the safety harness of FIG. 3 ;
[0023] FIG. 3 is a somewhat diagrammatic illustration of a safety harness embodiment of this disclosure;
[0024] FIG. 4 is an enlarged rear view of a person wearing the safety harness of FIGS. 1-3 and better illustrating selected features of the harness of FIG. 1 ;
[0025] FIG. 5 is a perspective view from the right rear side of a person wearing the harness of FIGS. 1-4 , with the harness bearing the weight of the person;
[0026] FIG. 6 is a view similar to FIG. 5 , but showing the person engaging selected components of the harness so as to reposition selected straps of the harness on the body of the person;
[0027] FIG. 7 is a view similar to FIGS. 5 and 6 , but showing the selected straps of the harness after they have been repositioned on the body of the person while the harness bears the weight of the person and the person is still engaging the selected components of the harness; and
[0028] FIG. 8 is a view similar to FIG. 7 , but with the person no longer engaging the selected components of the harness.
DETAILED DESCRIPTION
[0029] Referring to FIG. 1 , an embodiment of a full-body safety harness 10 of the present disclosure is discussed below. The overall structural design of safety harness 10 corresponds generally, for example, to the DURAFLEX ULTRA Model safety harness, model E650QC-UGN, available from Miller By Honeywell. Safety harness 10 includes an upper torso portion comprising first and second shoulder straps 20 and 30 for extending over the shoulders of the user and a chest strap 40 (see FIGS. 1-2 ) for extending over a portion of the chest of the user to secure the harness 10 to the upper torso of the user.
[0030] As illustrated in FIG. 2 , a first end of each of the shoulder straps 20 and 30 extends down over the back of the user to form first and second generally longitudinal back straps 22 and 32 , respectively. Longitudinal back straps 22 and 32 of shoulder straps 20 and 30 cross through and connect to a typical D-ring 50 as known in the art. D-ring 50 includes a harness connection portion 52 and an anchor portion 54 . Harness connection portion 52 enables fastening of D-ring 50 to safety harness 10 via longitudinal back straps 22 and 32 . Anchor portion 54 is adapted to be connected to a nylon rope, a chain, webbing or other connector which may be used to anchor the person wearing safety harness 10 .
[0031] In the embodiment illustrated in FIG. 2 , after crossing and passing through D-ring 50 , shoulder straps 20 and 30 are connected via a generally latitudinal back strap 60 . As illustrated in FIG. 2 , latitudinal back strap 60 passes generally latitudinally over a portion of the back of the user.
[0032] A second end of each of shoulder straps 20 and 30 extends downward over the front of the user as illustrated in FIG. 1 to from generally longitudinal first and second front straps 24 and 34 , respectively. As best seen in FIG. 3 , a first chest strap portion 42 is preferably attached to front strap 24 and a second chest strap portion 44 is attached to front strap 34 . Each of first and second chest straps 42 and 44 have cooperating fastening members 46 and 48 on the ends thereof to enable attachment of first and second chest straps 42 and 44 to form chest strap 40 . As known in the art, first and second chest straps 42 and 44 , respectively, are preferably attached via an adjustable mating buckle mechanism, including, for example, cooperating fastening members 46 and 48 .
[0033] First and second front straps 24 and 34 extend further downward and preferably include adjustment members 26 and 36 (for example, adjustable buckles) as known in the art for adjustment of the fit of safety harness 10 on the upper torso of the user. Extending still further downward as illustrated in FIG. 1 , extensions 24 a and 34 a of first and second front straps 24 and 34 converge and meet generally centrally to form a seat strap or sub-pelvic portion 70 . As illustrated in FIGS. 2 and 3 , first and second front extension straps 24 a and 34 a pass to the rear of the user and seat strap 70 passes under the pelvis and behind the buttocks of the user.
[0034] As shown in the illustrated embodiment, attached to and extending from seat strap 70 are a first and a second leg strap 80 and 90 , respectively. Each of first and second leg straps 80 and 90 pass around the upper leg or thigh of a corresponding leg of the user to be attached to the distal end of first and second longitudinal back straps 22 and 32 , respectively. The distal ends of each of first and second leg straps 80 and 90 and the distal ends of each of longitudinal back straps 22 and 32 thus preferably comprise cooperating fastening members ( 82 and 92 and 28 and 38 , respectively) such as adjusting buckle members as known in the art.
[0035] It will be appreciated by those skilled in the art that, in the illustrated embodiment, the straps 20 , 22 , 24 , 30 , 32 , 34 , 40 , and 60 define an upper torso portion 96 of the harness 10 that secures the harness 10 to the upper torso of a person, while the straps 70 , 80 , and 90 define a lower torso portion 98 of the harness 10 that secures the harness 10 to the lower torso of a person.
[0036] In the design of FIGS. 1-3 , the bottom portion of safety harness 10 can, for example, be fabricated from a single, integral length of material. In that regard, the length of material as described above begins at first end 94 a on leg strap 90 . The material then travels downward through fastening member 92 and then travels upward toward seat portion 70 , thereby forming leg strap 90 . Upon reaching seat portion 70 , the material travels along the path identified by the left side of seat portion 70 , forming the back side thereof. The material travels to adjustment member 36 at which point it is preferably looped around or through adjustment member 36 . The material then travels downward (doubling itself) over the lower portion of longitudinal front strap 34 and the left side of seat portion 70 . The material the travels across the center of seat portion 70 and upward along the path defined by the right side of seat, portion 70 . Upon reaching adjustment member 26 , the material is preferably looped around or through adjustment member 26 . After looping through adjustment member 26 , the material travels downward (doubling itself) under the lower portion of longitudinal front strap 24 and the right side of seat portion 70 . Before reaching the center of seat portion 70 , the material breaks away from the path of seat portion 70 to extend downward to from leg strap 80 . The material preferably loops through fastening member 82 and terminates at second end 94 b . Over those areas of doubling, the material is preferably held together via, for example, several stitching areas ( 100 ), as is common in safety harnesses.
[0037] According to this disclosure, the harness 10 advantageously includes a pair of hand engageable members, which are shown in the illustrated embodiment as suspension trauma loops 102 , that are each fixed to both the seat strap 70 and a corresponding one of the leg straps 80 and 90 , such as by the stitching areas 100 , as best seen in FIG. 3 . The loops 102 are located on the harness 10 to be positioned on opposite sides from each other on the buttocks of a person wearing the harness 10 , as best seen in FIGS. 2 and 4 . The loops 102 extend from the seat strap 70 and leg straps 80 and 90 so that each of the loops 102 can be engaged by a corresponding hand of a person wearing the harness to allow the person to move or reposition the seat strap 70 and leg straps 80 and 90 from first positions shown in FIGS. 5 and 6 to second positions shown in FIGS. 7 and 8 (leg strap 90 not visible in FIGS. 7 and 8 ). More specifically, as shown in FIG. 5 , the seat strap 70 has a first position where the seat strap 70 extends across or above the buttocks of the person and the leg straps 80 and 90 have a first position where the leg straps encircle an upper thigh portion of the person, and after the person uses the trauma loops 102 to manually move the straps 70 , 80 , and 90 to the second positions shown in FIGS. 7 and 8 , the seat strap 70 extends across or below the lower buttocks of the person and the leg straps 80 and 90 encircle a lower thigh portion of the person. In the illustrated embodiment and as best seen in FIGS. 6 and 7 , each of the trauma loops 102 are advantageously sized so that a thumb or finger of the corresponding hand of the person can be inserted through the loop 102 so the loop 102 encircles the thumb or finger to provide the person with additional grip or purchase on the loop 102 when moving the straps 70 , 80 , and 90 , with the sizing of the loop 102 preventing the remainder of the hand to be inserted into the loop 102 . It should be understood that the loops 102 are also functional to allow the person to move the straps 70 , 80 , and 90 from the second positions shown in FIGS. 7 and 8 to the first positions shown in FIGS. 5 and 6 . It should also be understood that, while the loops 102 are shown in the illustration as being sized to prevent the remainder of a hand from being inserted into each of the loops 102 , in some applications, it may be desirable for each of the loops 102 to be sized to allow additional parts of the hand, or the entire hand, of a user to be inserted into each of the loops 102 .
[0038] As shown in FIGS. 5-8 and described above, the suspension trauma loops 102 enable the user to manipulate his or her posture while hanging in the harness 10 into a seated position all the while staying in the safety of the harness 10 . Changing the position of the leg straps 80 and 90 from the upper inner thigh area to the bottom mid thigh area will alleviate the pressure on the arteries thus allowing blood to circulate throughout your body. Changing the position of the seat strap 70 from the upper buttocks area to the lower buttocks and/or upper thigh area also helps to alleviate the pressure on the arteries and improve blood circulation while helping to remove body load from the remainder of the harness 10 by accepting more of the body load. In the illustrated embodiments, the suspension trauma loops 102 will be attached to a harness from the factory, are reusable, and do not require any assembly or re-assembly after a fall has occurred.
[0039] To use the illustrated suspension trauma loops 102 , a person wearing the harness would:
[0040] 1. Insert thumbs into loops;
[0041] 2. Push down and forward on loops while lifting up legs;
[0042] 3. Position legs straps about mid thigh;
[0043] 4. Remove thumbs; and
[0044] 5. Reposition as necessary.
[0045] While one embodiment of a harness 10 and hand engageable members 102 have been described above, it should be understood that this disclosure anticipates variations from the illustrated embodiments. For example, the hand engageable members 102 can be provided in other forms than the loops 102 that would still allow a person wearing the harness to grasp the hand engageable members 102 and move the straps 70 , 80 , and 90 as discussed above. As a further example, while the illustrated embodiment shows two hand engageable members 102 , it may be possible and desirable in some applications to provide a single hand engageable member 102 or more than two hand engageable members 102 . As yet a further example, while the illustrated embodiment shows each of the loops 102 fixed to both the seat strap 70 and the corresponding leg strap 80 and 90 , in some applications it may be desirable to fix each of the loops 102 to just the corresponding leg strap 80 and 90 with no connection between the seat strap 70 and the loops 102 , while in other applications it may be desirable to fix each of the loops 102 to just the seat strap 70 with no connection between the legs straps 80 and 90 and the loops 102 . By way of further example, it may be desirable to incorporate the hand engageable members 102 on other specific embodiments of safety harnesses, many of which are known and which include either a seat strap or leg straps, or both seat straps and leg straps. As another example, while the embodiment disclosed herein includes both an upper portion 96 for securing the harness 10 to the upper torso of a person and a lower portion 98 for securing the harness 10 to the lower torso of a person, in some applications, it may be desirable for the harness 10 to just include a lower portion 98 without the upper portion 96 , such as harnesses used for climbing. In view of the many possible variations within the scope of this disclosure, only some of which have been discussed above, it should be understood that there is no intention to claim a specific structure shown or described herein unless it is expressly recited in a claim. | A safety harness ( 10 ) is provided to be worn by a person and to allow the person to manipulate the harness ( 10 ) to alleviate the potential effects of orthostatic intolerance in the person while suspended by the harness ( 10 ). The harness ( 10 ) includes one or more hand engageable members ( 102 ) allow the person to selectively repositioning a strap ( 70, 80, 90 ) of the harness ( 10 ) from a first position where the strap ( 70, 80, 90 ) extends across an upper portion of a lower torso of the person and a second position where the strap ( 70, 80, 90 ) extends across a lower portion of the lower torso of the person. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates to a crutch.
For those who are handicapped in their lower limbs, the crutch is a vital and indispensable instrument which they cannot leave even for a moment in their daily lives.
The most serious problem common to all crutched persons resides in the trouble concerning the disposal or storage of the crutch when it is not used, rather than the difficulty in the handling of the same for the walking or the like purposes.
Unfortunately, the modern society is leaning to exclude the crutches in its all aspects. Thus, the crutches are becoming hardly accepted.
SUMMARY OF THE INVENTION
It is therefore a major object of the invention to provide a crutch which can conveniently be folded into a short length when not used.
It is another object of the invention to provide a crutch having an upper and a lower portions which are pivotally secured to each other for a 180° rotation.
It is still another object of the invention to provide a crutch having a mechanism for locking the upper and lower portions against the relative pivotal movement when the crutch is to be presented for use.
It is a further object of the invention to provide a crutch having a locking mechanism which can be handled without difficulty.
These and other objects, as well as advantageous features of the invention, will become more clear from the following description of preferred embodiments taken in conjunction with the accompanying drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a front elevational view of a crutch in accordance with the invention,
FIG. 2 is a side elevational view of the crutch as shown in FIG. 1,
FIG. 3 is a side elevational view of the crutch in the folded state,
FIG. 4 is a front elevational view of the crutch in the folded state,
FIG. 5 is an enlarged perspective view of the crutch in the locked state, specifically showing the connecting portion of the upper and lower parts of the crutch,
FIG. 6 is an enlarged perspective view of the crutch in the unlocked and slightly folded state, specifically showing the same portion as that shown in FIG. 5,
FIG. 7 is an enlarged perspective view of the connecting portion with the constituents of the locking mechanism removed,
FIG. 8 is an exploded perspective view of the locking mechanism, showing the constituents of the same, and
FIG. 9 is a sectional view taken along the line IX--IX of FIG. 5.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to the drawings, a crutch embodying the present invention has an upper portion 1 and a lower portion 2 of substantially equal lengths. The upper portion 1 is provided with a handle or a hand-retaining bar 3. The lower end of the upper portion 1 has a pair of forked or U-shaped portions 1a. Each U-shaped portion 1a has a groove 1b extending in the longitudinal direction of the upper portion 1 and at a right angle to the breadthwise direction of the latter.
On the other hand, the lower portion 2 is provided with a pair of projections 2a formed on its upper end. These projections 2a are received by the grooves 1b of corresponding U-shaped portions 1a.
As will be seen most clearly from FIG. 7, the U-shaped portion 1a and the projection 2 have lateral extensions which are shown, in FIG. 7, to project downwardly from the upper and lower portions 1, 2. Mutually aligned through bores 4 are formed in these lateral extensions of the U-shaped portions 1a and the projections 2a.
The common axis X--X of the through bores 4 extends in the breadthwise direction of the crutch and at a right angle to the longitudinal axis of the crutch.
As will be seen from FIG. 2, the center X of the through bore 4 is slightly deviated outwardly from the side edges 1c, 2c of the upper and lower portions 1, 2 of the crutch.
The upper portion 1 and the lower portion 2 are pivotally connected to each other through a rod 5 which is inserted into the through bores 4. Thus, the lower portion 2 can be swung by 180° around the axis of the rod 5, from the folded position as shown in FIGS. 3, 4 in which it extends in parallel with the upper portion 1 to the stretched position as shown in FIGS. 1, 2 in which it is linearly extended from the upper portion 1.
The arrangement is such that the ends 1d of each U-shaped portion 1a abut shoulders 2d formed at both sides of each projection 2a, when the lower portion 2 is rotated by 180° into the stretched position, thereby to prevent the lower portion 2 from being further rotated beyond 180°. It is also possible to prevent the rotation of the lower portion 2 beyond 180° by the abutment of the end surface of each projection 2a and the bottom surface of the corresponding groove 1b.
A locking mechanism generally designated at a reference numeral 6 includes a locking bore 7 formed in the U-shaped portion 1a and another locking bore 8 formed in the projection 2a. These locking bores 7, 8 are so arranged that they are brought into alignment with each other when the lower portion 2 is in the stretched position.
Guide pipes 9 are fixed to the opposing surfaces of two U-shaped portions 1a, 1a, in axial alignment with respective locking bores 7. Each guide pipe 9 slidably holds a locking pin 10. Each locking pin 10 is fixed to an operation plate 11. These operation plates 11 are fixed to respective pipes 12 which are slidable along the rod 5. A collar 13 is fixed by suitable means to the center of the rod 5. A coiled spring 14 is disposed on each side of the collar 13. These coiled springs 14 are adapted to bias respective operation plates toward the corresponding U-shaped portions 1a, so as to drive the locking pins into the locking bores 7, 8. Two operation plates 11, 11 are spaced apart from each other by such a distance that these operation plates can easily be brought together by fingers of single hand.
In use, the lower portion 2 of the crutch in accordance with the invention is locked at the stretched position as shown in FIGS. 1 and 2, with the locking pins 10 received by corresponding locking bores as shown in FIG. 5.
For folding the crutch, two operation plates 11, 11 are brought together by fingers as shown in FIG. 6, so that the locking pins 10, 10 may be disengaged at least from the locking bores 8, 8. Then, the lower portion 2 is simply pivoted with respect to the upper portion 1 to the folded position as shown in FIGS. 3, 4.
Since the length of the crutch is reduced to half by the folding, the crutch in the folded state can be handled quite easily and can conveniently be stored even in an extremely limited space.
Further, the folded crutch can support itself and, therefore, can conveniently be used as a temporary stool, by flattening the lower end of the crutch in the folded state as shown in FIG. 3.
Various modifications in structure and/or function may be made to the disclosed embodiments by one skilled in the art without departing from the scope of the invention as defined by the claims. | A foldable crutch having an upper portion and a lower portion of substantially equal lengths, connecting means adapted for pivotally connecting the adjacent ends of the upper and lower portions, and a locking mechanism adapted to hold the upper and lower portions in the linearly stretched state against the pivotal movement. | 0 |
[0001] The contents of this application are related to those provisional applications having Ser. Nos. 60/227,165, 60/227,161, and 60/226,866, filed Aug. 22, 2000, and a provisional application having Ser. No. 60/262,541, filed Jan. 16, 2001. The present application claims priority to these related provisional patent applications and their contents are hereby incorporated by reference in their entirety into the present disclosure. The contents of this application are also related to several nonprovisional patent applications being filed concurrently herewith. These nonprovisional patent applications are hereby incorporated by reference in their entirety and have the following attorney docket reference numerals: 510015-263, 510015-264, 510015-265, 510015-266, 510015-268, 510015-269, 510015-270, 510015-271, and 510015-272.
[0002] This invention was made with the support of the United States Government under Grant No. MDA972-98-1-0001, awarded by the Department of Defense (DARPA). The Government has certain rights in this invention under 35 U.S.C. §202.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] The invention relates in general to a vertical cavity surface emitting laser (VCSEL). More particularly, the invention relates to growth methods and structures for distributed Bragg reflectors (DBRs) utilized in VCSELs.
[0005] 2. General Background and State of the Art
[0006] Semiconductor lasers are widely used in optical applications, in part because semiconductor fabrication techniques are relatively inexpensive and yield reliable, consistent results. Also, they are easily packaged into current microelectronics. A relatively new class of semiconductor lasers, vertical cavity surface emitting lasers (VCSELs), has been developed through the evolution of this technology. Unlike conventional edge emitting lasers that emit light in a direction parallel to the semiconductor substrates where the lasers are formed, VCSELs have optical cavities perpendicular to the substrate, and thus emit optical radiation in a direction perpendicular to the substrate. In addition to various performance and application-adaptable improvements created thereby, VCSELs simply require reduced complexity in their fabrication and testing, as compared to conventional edge emitting semiconductor lasers.
[0007] Vertical cavity surface emitting lasers (VCSELs) have been proven to be solutions for low-cost transmitters for high-speed data communications at 980 nm and 850 nm and have shown great potential for cost-effective telecommunication systems at longer wavelengths as well, such as 1.55 μm and 1.3 μm. These long wavelength VCSELs will satisfy increasing demand for high speed data transmission over tens of kilometers. 10-Gigabit Ethernet is one example, which requires inexpensive transmitters with a data rate of 10 G bit per second (Gbps) and up to 40 km reach over single-mode fiber.
[0008] VCSELs are semiconductor lasers having a semiconductor layer of optically active material, such as gallium arsenide or indium gallium arsenide or the like, sandwiched between highly-reflective layers of metallic material, dielectric material, epitaxially-grown semiconductor dielectric material or combinations thereof, most frequently in stacks. These stacks are known as distributed Bragg reflectors, or DBRs. DBRs are used to reflect emitted light back into the active material of a VCSEL. As is conventional, one of the mirror stacks is partially reflective so as to pass a portion of the coherent light built up in the resonating cavity formed by the mirror stack/active layer sandwich. Laser structures require optical confinement and carrier confinement to achieve efficient conversion of pumping electrons to stimulated photons (a semiconductor may lase if it achieves population inversion in the energy bands of the active material.)
[0009] The development of vertical-cavity surface-emitting lasers (VCSELs) at the telecommunications-important wavelength of 1.55 μm has been hindered by the absence of a substrate that is suitable for both technologically-developed distributed Bragg reflectors (DBRs) and quantum well active regions. In fact, despite the demonstration of VCSELs grown on a single substrate, the best results have been obtained through the fusion of InP-based active regions and AlGaAs-based DBRs.
[0010] To overcome mirror limitations on InP, several groups have examined AlGaAsSb-based DBRs, which have a refractive index contrast that is similar to AlGaAs-based DBRs at this wavelength. The high index contrast leads to a lower penetration depth than traditional InGaAsP-based DBRs and, therefore, implies lower optical loss in the structure. Only optically-pumped VCSELs using such DBRs, however, have been demonstrated.
[0011] While both short wavelength and long wavelength VCSELs have proven to offer excellent solutions for many applications in the evolving optical applications marketplace, they also have certain limitations and drawbacks that are well known in the art. Some of these drawbacks are inherent to the conventional materials used in the fabrication of Bragg mirrors for VCSELs grown on InP substrates. For example, the accuracy and reproducibility of an As, Sb composition in a AlGaAsSb semiconductor system is very difficult to achieve in DBR fabrication. While such materials have conventionally been considered and used as the best selection for the mirrors, they do not effectively optimize high reflectivity, good electrical conduction and low thermal resistance.
INVENTION SUMMARY
[0012] The present invention provides a method of growing a distributed Bragg reflector for use in a VCSEL using molecular beam epitaxy. The present invention also provides a method of fabricating a distributed Bragg reflector (DBR) in which the amount of particular semiconductor materials used in the DBR are controlled in the molecular beam epitaxy process.
[0013] The present invention provides a DBR for use in vertical cavity surfave emitting laser (VCSEL) having an Sb-based semiconductor material. The present invention further provides a method of enhancing thermal properties in a DBR by growing AlGaAsSb layers and InP layers on a substrate to form the DBR. A method of fabricating DBRs using these two types of layers is also provided.
[0014] One aspect of the present invention provides a method for controlling material composition in a distributed Bragg reflector. The method includes applying reflection high-energy electron diffraction (RHEED) oscillations in molecular beam epitaxy to a substrate, measuring the intensity of antinomy (Sb) atoms present in the substrate in response to the RHEED oscillations, and calibrating the amount of Sb to be incorporated into the susbtrate, with the amount depending upon the frequency of the RHEED oscillations induced by the Sb atoms.
[0015] Accordingly, one object of the present invention is to provide a method of controlling material composition in a distributed Bragg reflector for use in a VCSEL. It is another object of the present invention to provide a method of fabricating a distributed Bragg reflect for use in a VCSEL incorporating the above method of controlling material composition. It is still another object of the present invention to provide a VCSEL and method of fabrication of a VCSEL which enhances the thermal and reflective characteristics of the VCSEL.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] [0016]FIG. 1 is a flowchart overview of the process of forming a DBR using one embodiment of the present invention;
[0017] [0017]FIG. 2 is a plot of the intensity of RHEED oscillations over time when induced by Sb atoms on a substrate;
[0018] [0018]FIG. 3 is a diagrammatic representation of atoms on a substrate during standard molecular beam epitaxy;
[0019] [0019]FIG. 4 is a diagrammatic representation of atoms on a substrate during mixed group V molecular beam epitaxy;
[0020] [0020]FIG. 5 is a plot of Sb composition in GaAsSb, AlAsSb, and GaAsSb layers as a function of calibrated incorporation rates of Sb normalized with the incorporation rate of Ga;
[0021] [0021]FIG. 6 is a plot of the room-temperature photoluminescence spectra of AlGaAsSb/AlAsSb DBRs and AlGaInAs/AlAsSb DBRs;
[0022] [0022]FIG. 7 is a schematic representation of a VCSEL having an Sb-based DBR;
[0023] [0023]FIG. 8 is an additional schematic representation of a VCSEL having showing Sb-based DBRs of specific periods;
[0024] [0024]FIG. 9 is a plot of L-I and I-V for a VCSEL having an etched pillar of 25 μm
[0025] [0025]FIG. 10 is a schematic representation of a VCSEL with a DBR having an AlGaAsSb/InP material composition;
[0026] [0026]FIG. 11 is a flowchart overview of the process of forming a DBR using InP;
[0027] [0027]FIG. 12 is a plot of differences in band alignment between arsenide-antimonide (AsSb) alloys and InP;
[0028] [0028]FIG. 13 is a plot of current density versus voltage characteristics of an Al 0.1 GaAsSb/InP DBR in a growth direction;
[0029] [0029]FIG. 14 is a table of thermal conductivity measurements of AsSb compounds in bulk layers and in DBRs; and
[0030] [0030]FIG. 15 is a plot of calculated and experimental spectra of a 20.5 period AlGaAsSb/InP DBR.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0031] [0031]FIG. 1 is a flowchart describing the process of growing a DBR in one embodiment. Block 12 shows the step of providing a substrate on which DBR materials are grown. Block 14 shows the step of growing semiconductor material on the substrate. As described herein, molecular beam epitaxy is used in this embodiment to grow the materials on the substrate. Block 16 shows the step of observing RHEED oscillations to monitor the composition of group V elements such as antimony (Sb) in the semiconductor material. The RHEED oscillations occur simultaneously as semiconductor material is being grown on the substrate. Growth continues as measurements are taken of the RHEED oscillations.
[0032] The RHEED oscillations are used to monitor the amount of a group V element's atoms being to the substrate. Block 18 shows the next step, in which measurements of the oscillation frequencies are taken and used to control the amounts of the group V elements incorporated into the semiconductor material. Additionally, the RHEED oscillations are used to monitor the amount of group III elements such as Ga. A valve or other control mechanism, such as temperature, is used to control the rate of Sb reaching the substrate. Frequencies of the RHEED oscillations indicate the valve setting to control the composition rate of Sb. Block 20 shows the step of calibrating the amount of group V element-based material based upon the measurements taken in Block 18 and as described herein.
[0033] As semiconductor materials are being applied to the substrate, Ga and Sb are simultaneously hitting the substrate. However, because it is desirable to control the amount of Sb (or another similar group V element such as arsenic (As)), the flow of Sb must monitored. Beginning with a condition in which there are fewer Ga atoms on the substrate than there are Sb atoms, oscillations registering a frequency change will occur when the amount of Ga atoms exceeds the amount of Sb atoms. Because it is the incorporation rate of the group V, or Sb atoms that are being controlled, a shutter is used to limit the flow of Ga atoms to the substrate when Ga atoms begin to exceed Sb atoms, since too many Ga atoms can swamp the process of accurately controlling Sb composition. This step of controlling the amount of Ga atoms hitting the substrate is shown in Block 22 of FIG. 1. This process of determining valve settings for proper Sb incorporation rates, and controlling the flow of Ga atoms to measure the frequency of oscillations, repeats until an appropriate composition rate of Sb has been reached.
[0034] In the present invention, all the growths of arsenide-antimonide compounds on InP substrates have been made using calibrations at a substrate temperature of 470° C. The composition of Sb in the Al x Ga 1-x As 1-y Sb y layers is set with regard to the total group-III growth rate. The modifications of growth rates according to the different atoms surface density between GaAs, GaSb and InP are also contemplated, since the calibrations were done on GaAs and GaSb, and the grown layer has the same lattice as InP. In order to maintain a V/III ratio higher than unity, the As flux is always slightly higher than the calibrated value for 1-y As composition.
[0035] [0035]FIG. 2 is a plot of frequencies of group-V induced reflection high-energy electron diffraction (RHEED) oscillations 10 used to monitor the incorporation of Sb and As in ternary compounds GaAsSb and AlAsSb as well as the quaternary compound AlGaAsSb. The calibration of the group-V composition is achieved by correlating the Sb incorporation rate with beam equivalent pressure (BEP). An equivalent in situ technique using gas-source molecular beam epitaxy (MBE) is also used to control the group-V compositions of InGaAsP alloys.
[0036] Substrate growths are performed in an MBE system equipped with solid source cracking effusion cells producing As 2 and Sb 2 species on the surface. Conventional RHEED oscillations of group-III species under As 2 overpressure are applied on a GaAs substrate to calibrate the growth rates. The Sb and As incorporation rates have been measured also by RHEED oscillations while maintaining an overpressure of Ga during the growth. When an excess of the group-III element is formed at the surface, for example by growth using a high III/V flux ratio, the oscillation period corresponds to the growth of a monolayer, but it is not related to the group-III element flux. Instead it relates to the group-V flux as a product of this flux and the sticking coefficient of the group-V element. The As-induced oscillations have been observed on GaAs layers, and on the same substrate the Sb-induced RHEED oscillations have been performed on a thick totally smooth GaSb layer. FIG. 2 shows an example of such Sb-induced RHEED oscillations at a substrate temperature of 420° C. Before t=1.5 s the surface is under Sb flux, and at t=1.5 s the Ga shutter is opened. The behavior of the RHEED intensity is characteristic of a group-III stabilized surface: the specular beam brightness drops rapidly during the first few monolayers and oscillates with a shorter period than the following Sb-induced oscillations. At t=4 s the oscillations caused by the Sb atoms begin while being rapidly damped due to the degradation of the Ga-stabilized surface.
[0037] Molecular beam epitaxy is a method of growing high-purity epitaxial layers of compound semiconductors. It has evolved into a popular technique for growing group III-V compound semiconductors as well as several other materials. MBE can produce high-quality layers with very abrupt interfaces and good control of thickness, doping, and composition. Because of the high degree of control possible with MBE, it is a valuable tool in the development of sophisticated electronic and optoelectronic devices.
[0038] In MBE, the constituent elements of a semiconductor in the form of “molecular beams” are deposited onto a heated crystalline substrate to form thin epitaxial layers. The “molecular beams” are typically from thermally evaporated elemental sources, but other sources include metal-organic group III precursors (MOMBE), gaseous group V hydride or organic precursors (gas-source MBE), or some combination (chemical beam epitaxy or CBE). To obtain high-purity layers, it is critical that the material sources be extremely pure and that the entire process be done in an ultra-high vacuum environment. Another important feature is that growth rates are typically on the order of a few Å/s and the beams can be shuttered in a fraction of a second, allowing for nearly atomically abrupt transitions from one material to another.
[0039] Calibration of the growth rate is essential for the proper tuning of resonant-cavity devices. There are several in-situ techniques which can be used in MBE. One way to measure the growth rate is to use the BEP gauge. This measurement is dependent on factors such as the geometry of the system and ionization efficiency of the material being measured, but for a given system and material, the BEP reading is proportional to the flux at the sample surface and hence the growth rate. Unlike other techniques, a BEP measurement does not require that any epitaxial layers be grown. Growing epitaxial layers requires an approximate knowledge of the flux beforehand, so the BEP is particularly useful for effusion cells which are being used for the first time. For the Varian Gen II, a BEP reading in the mid to high 10 −7 Torr range gives Ga growth rates of about 1 μm/hour. However, the technique is not a direct measure of the growth rate, so some other in-situ or ex-situ technique must still be used to relate the BEP to a growth rate.
[0040] One such technique includes RHEED intensity oscillations, which are used as an accurate, quick, direct measure of the growth rates in MBE. When growth is initiated on a smooth GaAs surface, the intensity of the RHEED pattern, especially the specular reflection, starts to oscillate. The oscillation frequency corresponds to the monolayer growth rate, where a monolayer (ML) is the thickness of one full layer of Ga and one full layer of As atoms. When a layer starts it is smooth and the specular spot is bright, but as the layer nucleates, islands form on the surface, and the specular spot dims. As the layer finishes, the islands coalesce into a flat layer, and the specular spot intensity increases. The oscillation of the specular spot intensity has been attributed to the oscillating roughness of the layers changing the diffuse scattering, but the incident angle dependence of the oscillations suggest that interference between electrons scattering from the underlying layer and the partially grown layer contribute to these oscillations.
[0041] [0041]FIG. 3 and FIG. 4 are diagrammatic representations of atoms 26 on a substrate. FIG. 3 shows the atoms 26 during standard molecular beam epitaxy, while FIG. 4 shows the atoms 26 during mixed group V molecular beam epitaxy including Sb atoms 28 . MBE typically utilizes group V overpressure and assumes that all group III elements will stick. However, when two group V elements (such as As and Sb) are included in the overpressure, the composition must be determined as described herein.
[0042] [0042]FIG. 5 is a plot showing the resulting Sb composition measured in GaAsSb, AlAsSb and AlGaAsSb layers grown on InP as a function of the Sb incorporation rate calibrated as described above. Some of these layers are near to InP lattice-matched compositions (x sb ≈0.5) and other growths were performed with x sb ≈0.8. Over the whole composition range the experimental Sb composition depends linearly on the normalized Sb flux as y≅x. The mean deviation of Sb composition from the fit is 0.0186 (maximum deviation=0.039). The best linearly dependent fit can be obtained with y=1.4x and a mean deviation of 0.0095 (maximum deviation=0.02).
[0043] In order to demonstrate the good quality of the AlGaAsSb layers, two DBRs containing 10.5 periods of Al 0.2 Ga 0.8 AsSb/AlAsSb were grown on InP. The main difference between the mirrors is that one was grown with Al 0.2 GaAsSb quaternary bulk layers and the other with a digital-alloy (AlAsSb) 0.2 (GaAsSb) 0.8 . By using such digital alloys we can eliminate growth pauses at each mirror interface because of group-III cell temperature changes when only one Al cell is available o the MBE system. FIG. 6 is a plot of photoluminescence measurements at room temperature performed on both AlGaAsSb/AlAsSb DBRs and AlGaInAs/AlAsSb DBRs. The signals measured for AlGaAsSb in the mirrors are very intense but the digital quaternary alloy shows more intensity than the analog AlGaAsSb. The full-widths at half maximum are respectively 65 meV for the digital quaternary alloy and 54 meV for the analog one. As a comparison the photoluminescence signal observed for a 10.5 periods Be-doped AlGaInAs/AlAsSb is also depicted in FIG. 6. The wavelength at the maximum of both peaks is 1222 nm which corresponds to the calculated band-gap wavelength of Al 0.17 Ga 0.83 AsSb close to the 20% Al expected.
[0044] [0044]FIG. 7 is a schematic representation of another aspect of the present invention, in which an electrically-pumped, Sb-based vertical-cavity laser 30 operating at 1.55 μm is produced in a single epitaxial growth. The laser 30 employs AlGaAsSb DBRs 32 and 34 and an AlInGaAs-based active region 36 , and has a room temperature threshold current density of 1.4 kA/cm 2 and an external quantum efficiency of 18%. The DBRs 28 and 30 employ a plurality of layers of semiconductor material, each alternating layer having the material composition of AlGaAsSb. In another embodiment, the DBRs 28 and 30 have a plurality of layers of semiconductor material, only one of which includes the element antimony (Sb).
[0045] The VCSEL 30 is grown by a molecular beam epitaxy on an n-doped (Sn) InP substrate 38 . The active region 36 includes a 1λ cavity in which five strain-compensated AlInGaAs quantum wells are grown. A thin, heavily-doped tunnel junction 40 , using CB r4 as the p-type dopant and Si as the n-type dopant, is placed at a standing-wave null of the mode to provide electron-hole conversion from the top n-DBR.
[0046] [0046]FIG. 8 is a schematic representation of one embodiment of the present invention in which the bottom DBR 34 includes 23 pairs of AlAs 0.56 Sb 0.44 and Al 0.2 Ga 0.8 As 0.58 Sb 0.42 λ/4-layers lattice-matched to InP. The calculated reflectivity for this mirror is 99.6%. The top DBR 32 , which has a calculated reflectivity of 99.9%, includes 30 periods of the same material combination plus a phase-matching layer for a metal contact 42 . Both DBRs 32 and 34 have linearly graded interfaces between the low- and high-index layers and are uniformly n-type doped with the donor tellurium (Te) using PbTe (n≅10 18 /cm 3 in AlAsSb). Two n-type DBRs are chosen to reduce both the voltage drop and optical losses in the VCSEL.
[0047] In general the DBRs 32 , 34 can include alternating layer pairs of Al a Ga 1-a As b Sb 1-b which are approximately lattice-matched to InP. The subscript “a” can be greater than 0.9 in one layer of the alternating layer pairs and less than 0.3 in the other layer of the alternating layer pairs. In the higher-index layers with “a” less than 0.3, “a” should still be large enough such that the layer is substantially transparent to lasing light. Here “b” can be a positive number and preferably greater than approximately 0.5.
[0048] More specifically, the DBRs 32 , 34 can consist, respectively, of preferably twenty-three and thirty-two pairs of Al a1 Ga 1-a1 As x Sb 1-x and Al a2 Ga 1-a2 As x Sb 1-x (a1>0.9, a2<0.3, x>0.5) λ/4-layers, lattice-matched to the InP cladding layers. Lattice-matching is achieved by using previously-calibrated group-V induced reflection high-energy electron diffraction oscillations and then growing at conditions with near-unity antimony incorporation rates. As an alternative, only the top cladding layer or the bottom cladding layer may be present in the VCSEL. A small amount of Ga is generally added to the AlAsSb reflecting surfaces so as to stabilize these surfaces chemically, and make them more resistive to degradation without substantially increasing their index of refraction.
[0049] The cavity mode has a reflectivity spectrum of 1.55 μm measured after growth, which is centered on a >140 nm stopband (reflectivity >99%). Other embodiments can have an approximate range between 1.3 and 1.6 microns. The top DBR 32 is then removed in order to examine the photoluminescence (PL) of the quantum wells. The PL peak is at ˜1580 nm, placing the cavity mode on the broad, short-wavelength shoulder of the PL spectrum. The mode and PL peak can be aligned by lowering the operation temperature.
[0050] Pillars with diameters ranging from 10 to 100 μm are then fabricated by reactive ion etching using the top metal contact as an etch mask. Contacts may also deposited on the substrate 38 backside.
[0051] [0051]FIG. 9 is a plot of the L-I and I-V results from a VCSEL having a 25 μm diameter pillar operated in pulsed-mode at room temperature. The threshold current is 7 mA, corresponding to the current density of 1.4 kA/cm 2 . The external differential quantum efficiency of this device was 18% and the maximum power was 2 mW. Lasing is achieved up to 45° C. with a threshold current of 15.5 mA.
[0052] [0052]FIG. 9 also shows that the devices exhibit a high voltage that most likely is attributable to both a high contact resistance in this processing run and to the DBRs which have a relatively low doping level. By increasing the doping a few periods away from the cavity or by using intra-cavity contacts, it is anticipated that this voltage drop may be reduced significantly without introducing additional optical losses.
[0053] In accordance with another aspect of the present invention, FIG. 10 is schematic representation of a VCSEL 44 having DBRs 46 including InP and AlGaAsSb respectively as low-refractive index and high-refractive index quarter-wavelength layers. The DBRs 46 have alternating layers of semiconductor material, where on layer is AlGaAsSb and the next layer is InP. The introduction of InP layers in the DBRs 46 leads to numerous benefits such as easier epitaxial growth of a binary alloy, and intrinsic low thermal resistivity and high electrical conductivity of the InP material. In particular, InP has the unique property of combining a low refractive index (n=3.17) and a direct bandgap in the near-infrared (E Γ ≡0.92 μm). For the 1.55 μm DBRs, this avoids carrier transfers between Γ and X valleys, existing with other low refractive index materials (AlAsSb and AlInAs).
[0054] In one embodiment, the DBRs 46 include 21 pairs of Al 0.1 Ga 0.9 As 0.52 Sb 0.48 /InP N-doped with tellerium (Te) at approximately 3×10 18 cm −3 . This value was obtained from a Hall measurement on the DBR itself, grown on a semi-insulated (SI) InP substrate, and reflects an effective doping level because of the different activation efficiencies between the quaternary alloy and InP. The DBRs are grown by solid source molecular beam epitaxy (SSMBE) using valved cracker cells for As, Sb and P species. All the AlGaAsSb layers are nominally lattice-matched on InP.
[0055] For electrical characterizations, etched mesas defined by reactive ion etching (RIE) with a mixed flow of chlorine and argon were incorporated in the VCSEL. After etching, NiAuGe contacts were deposited in order to form transmission line model (TLM) test patterns.
[0056] [0056]FIG. 11 is a flowchart of steps in the process of fabricating a DBR 46 using this aspect of the present invention. Block 48 shows the step of providing a substrate on which a DBR structure will be grown. Block 50 shows the step of determining lattice-matching conditions for AlGaAsSb material. The lattice matching conditions are determined by observing and measuring RHEED oscillations on the substrate. Because the substrate and alternating layers of the DBR structure are composed of InP, which is a binary alloy having a static lattice constant, the primary concern in lattice matching the DBR layers is the composition of the elements in the AlGaAsSb layers of the DBR structure. Each of the elements of the AlGaAsSb structure has an influence on the overall lattice constant. Al and Ga (both group III elements) have a large effect on the refractive index, so their proportions are design selections for the DBR. Therefore, given a selected amount of the group III elements, the relative amounts of As and Sb, both group V elements, must be determined to match the lattice constant with that of the InP layers and substrate. RHEED oscillations are then observed and measured to determine proper proportions of As and Sb to arrive at the appropriate lattice constant to lattice match the AlGaAsSb layers to the InP layers and to the InP substrate.
[0057] Block 52 shows the step of growing a lattice-matched AlGaAsSb layer of semiconductor material on the substrate. AlGaAsSb layers are lattice-matched to both the substrate and to the InP layers. Block 54 shows the step of growing an InP layer of semiconductor material on the substrate. Finally, Block 56 shows the step of doping the AlGaAsSb and InP layers on the substrate. The doping step occurs simultaneously with the growth of the AlGaAsSb and InP layers on the substrate, since dopants are introduced to the substrate as these semiconductor materials are being grown.
[0058] [0058]FIG. 12 is a plot of the differences in band alignment between arsenide-antimonide alloys and InP. The conduction band offset is quite important between AlAsSb and AlGaAsSb previously used. A drastic reduction of this offset can be achieved by substituting InP for AlAsSb. Another significant improvement is to avoid the scattering mechanisms encountered in the electron transport between direct and indirect bandgap materials. The InP/Al 0.1 Ga 0.9 As 0.52 Sb 0.48 heterostructure thus obtained is of type II, with a barrier height of 310 meV for the electrons. According to this, conduction band offset is higher than for InGaAsP/InP (186 meV) but lower than for AlGaInAs/AlInAs (381 meV).
[0059] [0059]FIG. 13 is a plot of the current density versus voltage characteristics of an Al 0.1 GaAsSb/InP DBR in the growth direction. As expected from the band diagram discussed above, the voltage drop is low; typically 10 mV per period is measured at a current density of 1 kA/cm 2 . From the modeling of the conduction band, depicted in the inset of the FIG. 13, the calculated thermionic component of the current leads to a voltage of 8 mV per pair. Again, if this result is compared to other systems used on InP, the voltage in AlGaAsSb/InP is the smallest. In an actual VCSEL structure including two AlGaAsSb/InP DBRs of 25 pair each, the total voltage due to the DBRs would be only 0.5 V.
[0060] [0060]FIG. 14 is a table of thermal conductivity measurements of AsSb compounds in bulk layers and in DBRs. Generally speaking, the only lattice-matched alloys to InP are ternary and quaternary alloys, and so their thermal conductivities are limited. This comes from the phonon scattering in a lattice with different atoms. The best way to maximize the thermal properties of a DBR is to use InP. In FIG. 14, the difference between InP and ternary or quaternary alloys is clearly demonstrated. An improvement of a factor two was obtained for InP-containing DBRs. By reasoning as an equivalent electric circuit, one can deduce the relation between the thermal conductivities of the DBR and the constituting layers 1 and 2 -as
( d 1 +d 2 )/ K DBR =d 1 /k 1 +d 2 /k 2
[0061] where d is the layer thickness and k the thermal conductivity.
[0062] The conductivity of the DBRs calculated from the experimental data of bulk layers is equal to the measured values, even for AlGaAsSb/AlAsSb or AlGaAsSb/InP. This indicates that phonon scattering occurs predominantly in the quaternary alloy rather than at the interfaces.
[0063] [0063]FIG. 15 shows the experimental and calculated reflectivity spectra. A good correlation is obtained for the high reflectivity stop-band and the higher wavelengths sidelobes. Whereas, at shorter wavelengths, we observe the incidence on the reflectivity curve of the AlGaAsSb absorption below the bandgap (E Γ [Al 0.1 Ga 0.9 As 0.52 Sb 0.48 ]≡1.4 μm). At the center-wavelength located at 1.47 μm, the refractive index contrast used in the calculation was 1.135 with the refractive indices, n=3.61 and n=3.18, respectively for Al 0.1 Ga 0.9 As 0.52 Sb 0.48 and InP, leading to a maximum reflectivity of 0.994. One can also note the important width of the stop-band of about 100 nm.
[0064] It is to be understood that other embodiments may be utilized and structural and functional changes may be made without departing from the scope of the present invention. The foregoing descriptions of embodiments of the invention have been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Accordingly, many modifications and variations are possible in light of the above teachings. For example, a distributed Bragg reflector according to the present invention may utilize alternating layers of semiconductor material having the element antimony, or it may utilize one layer of material having antimony in the mirror design. It is therefore intended that the scope of the invention be limited not by this detailed description. | A distributed Bragg reflector (DBR) for a vertical cavity surface emitting laser (VCSEL) includes alternating layers of different semiconductor materials to improve thermal and electrical characteristics for the VCSEL. Use of particular materials reduces the thermal resistivity of the DBR and allows heat to dissipate quickly during operation of the VCSEL. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates in general to tubular hydroforming and more particularly to method and device for forming a tubular work into a shaped hollow product by using hydroforming process. More specifically, the present invention relates to method and device for producing an automotive hollow part, such as front pillar, center pillar, roof rail or the like, by using tubular hydroforming process.
2. Description of the Prior Art
Tubular hydroforming process is a novel process that has recently gained much attention due to its cost-effective application particularly in the automotive industry. As is known, the tubular hydroforming is of a process that includes major steps wherein ends of a tubular work in a net shape die unit are sealed and a hydraulic fluid is pumped in the tubular work and pressurized to deform cross-sections of the work to conform to a cross section of the net shape die. Usually, before the major steps, a pre-forming is made wherein for obtaining a pre-defined shape of the tube that closely resembles the final component (viz., hollow product), a die closing is gradually carried out while receiving a relatively low hydraulic fluid in the work. While, in a so-called bulging process in the tubular hydroforming, axial feed is provided along the longitudinal axis of the tubular work in the net shape die while receiving the hydraulic fluid in the work. When employing this bulging process, a tube wall thinning during the hydroforming process can be reduced.
However, due to the nature of deformation of the material of the tubular work during the hydroforming process, it has been difficult to provide a hydroformed hollow product that gives users satisfaction. In fact, in the pre-forming step, even when aluminum and/or high strength steel tube is used as the tubular work, a crack tends to appear at a portion that has been subjected to a wall thinning during the expansion of the work. Furthermore, in the pre-forming step, a corner portion remote from the center of the work is particularly attacked by such wall thinning. In the bulging process, wall thickening throughout the length of the tubular work is readily made, however wall thickening at a specified or needed portion, such as a corner portion or the like, is not readily made, and thus, reduction in weight of the hydroformed hollow product has not been satisfactorily achieved particularly in the field of automotive industry.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a method for forming a tubular work into a shaped hollow product by using hydroforming process, which method is free of the above-mentioned drawbacks.
It is further an object of the present invention to provide a hydroforming device which is suitable for practically carrying out the method of the present invention.
It is further an object of the present invention to provide a hydroforming method by which a specified or needed portion of a shaped hollow product can be exclusively thickened.
According to the present invention, there is provided a method for forming a tubular work into a shaped hollow product by using hydroforming process. In the method, female and male dies are prepared. The female die has a longitudinally extending cavity which has a polygonal cross section when receiving the male die. The tubular work is placed into the cavity of the female die. The interior of the tubular work is then fed with a hydraulic fluid, and the pressure of the fluid is increased to a given level. The given level is smaller than a critical level that causes a bulging of the tubular work. The male die is then pressed against the tubular work to deform the same while keeping the hydraulic fluid at the given level, thereby forming a shaped hollow product that has a polygonal cross section that conforms to that of the cavity. The pressing work is continued until a circumferential length of the shaped hollow product becomes shorter than that of the tubular work.
According to the present invention, there is further provided a hydroforming device for forming a tubular work into a shaped hollow product by using a hydroforming process. The device comprises a fixed female die having a longitudinally extending cavity, the cavity being sized to receive therein the tubular work; a male die having a work surface, the male die being movably received in the female die in such a manner that the work surface of the male die faces the cavity to cause the cavity to be enclosed and have a polygonal cross section; at least one projection formed on a lateral end of the work surface, the projection having a sloped surface angled relative to the work surface and an actuator which actuates the male die to press against the tubular work.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a longitudinally sectional view of a hydroforming device used for practically carrying out a method of a first embodiment of the present invention;
FIG. 2 is a view similar to FIG. 1, but showing a different or pressing condition of the device;
FIG. 3 is a perspective view of the hydroforming device for carrying out the method of the first embodiment;
FIG. 4 is a schematically illustrated laterally sectional view of the hydroforming device of FIG. 3;
FIG. 5 is a sectional view of a shaped hollow product provided by the method of the first embodiment;
FIG. 6 is a schematic illustration showing a test for examining a mechanical strength of the shaped hollow product;
FIG. 7 is a graph showing the results of the test;
FIG. 8 is a graph showing results of other test;
FIG. 9 is a schematically illustrated female die used in a hydroforming device which is used for carrying out a method of a second embodiment of the present invention;
FIG. 10 is a partial sectional view of a female die used in a hydroforming device which is used for carrying out a method of a third embodiment of the present invention;
FIG. 11 is a graph showing results of a test for finding a desired angle of an extra slanted wall possessed by the female die of FIG. 10;
FIG. 12 is a longitudinally sectional view of a hydroforming device used for carrying out a method of a fourth embodiment of the present invention;
FIG. 13 is a view similar to FIG. 12, but showing a different or pressing condition of the device;
FIG. 14 is a sectional view of a shaped hollow produced provided by the method of the fourth embodiment;
FIG. 15 is a laterally sectional view of a hydroforming device used for carrying out a method of a fifth embodiment of the present invention;
FIG. 16 is a graph showing results of a test for examining the thickness increasing rate relative to male die pressing stroke;
FIG. 17 is a laterally sectional view of a hydroforming device used for carrying out a method of a sixth embodiment of the present invention;
FIG. 18 is a laterally sectional view of a hydroforming device used for carrying out a method of a seventh embodiment of the present invention;
FIG. 19 is a laterally sectional view of a hydroforming device used for carrying out a method of an eighth embodiment of the present invention;
FIG. 20 is a laterally sectional view of a hydroforming device used for carrying out a method of a ninth embodiment of the present invention;
FIG. 21 is a sectional view of a shaped hollow product provided by the method of the ninth embodiment;
FIG. 22 is a laterally sectional view of a hydroforming device used for carrying out a method of a tenth embodiment of the present invention;
FIG. 23 is a sectional view of a shaped hollow product provided by the method of the tenth embodiment;
FIG. 24 is a laterally sectional view of a reference hydroforming device which was used for proving improvement achieved by the tenth embodiment of the invention;
FIG. 25 is a sectional view of a shaped hollow product provided by the device of FIG. 24;
FIG. 26 is a laterally sectional view of a hydroforming device used for carrying out a method of an eleventh embodiment of the present invention;
FIG. 27 is a sectional view of a shaped hollow product provided by the method of the eleventh embodiment;
FIG. 28 is an enlarged sectional view of one of four corner portions of the shaped hollow product shown in FIG. 27;
FIG. 29 is a graph showing results of a measurement for measuring the thickness of various positions of the corner portion;
FIG. 30 is a laterally sectional view of a hydroforming device used for carrying out a method of a twelfth embodiment of the present invention;
FIG. 31 is an enlarged view of a part of the device of FIG. 30, showing a pressing condition of the device;
FIG. 32 is a sectional view of a shaped hollow product provided by the method of the twelfth embodiment;
FIG. 33 is an enlarged sectional view of one of four projected round corner portions of the product of FIG. 32;
FIG. 34 is a laterally sectional view of a reference hydroforming device which was used for proving improvement achieved by the method of the twelfth embodiment;
FIG. 35 is an enlarged view of a part of the device of FIG. 34, showing a pressing condition of the device;
FIG. 36 is a graph showing results of a measurement for measuring the thickness of various portions of the projected round corner portion of the product of FIG. 32; and
FIG. 37 is a perspective view of an automotive body and frame construction having front pillars, center pillars, side roof rails and the like which can be provided by tubular hydroforming process.
DETAILED DESCRIPTION OF THE EMBODIMENTS
In the following, the present invention will be described in detail with reference to the drawings.
For ease of understanding, directional terms, such as upper, lower, right, left, vertical, horizontal, upward, downward, and the like are used in the description. However, it is to be noted that such terms are to be understood with respect to only a drawing or drawings on which the corresponding parts or structures are illustrated.
Referring to FIGS. 1 to 8 , particularly FIGS. 1 to 4 , there is shown a hydroforming device 1 with which a method of a first embodiment of the present invention is practically carried out.
As will become apparent as the description proceeds, the explanation will be made with respect to a process for producing an automotive side roof rail S (see FIG. 37) as an example of the final component or a shaped hollow product.
As is seen from FIGS. 1 to 4 , the hydroforming device 1 comprises generally a female die 2 which has a cavity 2 a formed therein, two sealing tools 3 which seal both open ends of a tubular work W, two supporting members 4 which stably support both end portions of the tubular work W while having a major portion of the tubular work W put in the cavity 2 a of the female die 2 , two feeding tubes 5 which feed and draw a hydraulic fluid into and from an interior Wa of the tubular work W whose ends are sealed by the sealing tools 3 and a male die 6 which presses the tubular work W in the cavity 2 a of the female die 2 . During pressing of the tubular work W by the male die 6 , the interior Wa of the work W is kept filled with the hydraulic fluid of pressure P. For pressing the male die 6 against the work W, a ram R extending from a hydraulic actuator is connected to the male die 6 .
As is seen from FIG. 4, the cavity 2 a of the female die 2 is defined by two mutually facing vertical walls 2 b , a bottom wall 2 c and two slanted walls 2 d each extending between the bottom wall 2 c and the vertical wall 2 b . The male die 6 is arranged to move upward and downward in the cavity 2 a of the female die 2 . The male die 6 comprises a work pressing main surface 6 a and two projected side surfaces 6 b which are located at lateral ends of the main surface 6 a . As shown, each projected side surface 6 b is generally perpendicular to the vertical wall 2 b of the female die 2 .
For producing the automotive side roof rail S from the tubular work W by using the above-mentioned hydroforming device 1 , the following steps were carried out.
First, the tubular work W was set in the cavity 2 a of the female die 2 and held stably by the supporting members 4 . The tubular work W had a wall thickness of about 2.2 mm. More specifically, the work W was made of a steel of 370 MPa type, that is, a carbon steel tube of STKM11A specified by JIS (Japanese Industrial Standard) G 3445. Then, the sealing tools 3 were put into the open ends of the tubular work W to seal the same. Then, a hydraulic fluid was led into the interior Wa of the work W through the feeding tubes 5 and the interior of the work W was kept at a given pressure P that was 50 MPa. The pressure P was kept lower than a value that would induce expansion of the work W.
Then, as is seen from FIGS. 1 and 2 with the interior pressure P kept at 50 MPa, the male die 6 was lowered into the cavity 2 a of the female die 2 to press the tubular work W at the work pressing main surface 6 a . With these steps, the automotive side roof rail S was produced, which had a depressed hexagonal cross section as is understood from FIG. 5 .
As is seen from FIG. 5, the depressed hexagonal cross section of the side roof rail S thus produced had a circumferential length that was smaller than that of the tubular work W. While, the thickness of the produced side roof rail S became greater than that of a corresponding portion of the tubular work W except a bottom wall Sc of the rail S and its neighboring portion. That is, as is seen from FIG. 5, by applying the hydroforming process of the invention to the work W, the thickness of each vertical wall Sb of the rail S increased by about 9%, the thickness of each corner portion Se defined between the vertical wall Sb and a horizontal upper wall Sa increased by over 25% and even each rounded portion Sf defined between the vertical wall Sb and the slanted wall Sd showed a little increase in thickness.
In addition to the above, by using the above-mentioned hydroforming device 1 , substantially identical hydroforming process was applied to a tubular work which was made of a steel of 590 MPa type and had a wall thickness of about 2.0 mm. Also, in this case, each rounded portion Sf defined between the vertical wall Sb and the slanted wall Sd showed a certain increase in thickness. This fact has revealed that even a tube of less malleable steel can be used as the work for the hydroforming process of the present invention.
For examining a mechanical strength of the side roof rail S thus produced, a test was carried out. That is, as is seen from FIG. 6, an elongate test piece S′ was cut from the rail S, and two I-type steel blocks 7 were welded to respective ends of the test piece S′ to provide an elongate test piece unit. The elongate test piece unit was put on two holders 8 which were spaced by 500 mm. Then, a center of the test piece unit was pressed down by a rounded pusher 9 of R 50 . That is, a load applied to the center of the test piece unit was gradually increased by the rounded head of the pusher 9 .
FIG. 7 is a graph showing the results of the test in terms of a relation between the load applied by the rounded pusher 9 and a stroke of the pusher 9 . For comparison, similar test was applied to a reference test piece which showed no increase in thickness. As is seen from this graph, the test piece S′ produced in accordance with the present invention exhibited the maximum flexural rigidity (viz., about 4200 Kgf) that is greater than that (viz., about 2600 Kgf) of the reference test piece by about 64%. Other tests revealed that as is seen from the graph of FIG. 8, when the thickness of the vertical walls Sb increased by over 3%, the mechanical strength showed a satisfied value.
Referring to FIG. 9, there is schematically shown a female die 22 employed in a hydroforming device 21 with which a method of a second embodiment of the present invention is carried out.
As is seen from the drawing, the female die 22 is formed with an axially extending stepped portion 22 g between each vertical wall 22 b and the adjacent slanted wall 22 d . Preferably, the size of the stepped portion 22 g is smaller than the thickness of the tubular work W and greater than one tenth (viz., {fraction (1/10)}) of the thickness of the work W. Denoted by numeral 22 a is a cavity defined by the female die 22 . Several tests have revealed that the presence of such stepped portions 22 g lessens the possibility of producing undesired buckling of the tubular work W during the forming process. Furthermore, the tests have revealed that the presence of the stepped portions 22 g assuredly reduces the stroke length of the male die.
Referring to FIGS. 10 and 11, particularly FIG. 10, there is shown but partially and in a sectional manner a female die 32 employed in a hydroforming device 31 with which a method of a third embodiment of the present invention is carried out.
As is seen from FIG. 10, in this female die 32 , there is formed, between each vertical wall 32 b and the corresponding slanted wall 32 d , with an extra slanted wall 32 g that defines an angle “θ” relative to the vertical wall 32 b . Preferably, the angle “θ” is within a range from 0 to 45°. Denoted by numeral 32 a is a cavity defined by the female die 32 . Tests have revealed that due to presence of such extra slanted walls 32 g , the friction inevitably produced between the wall of the female die 32 and the male die 6 can be reduced and the pressing load applied by the male die 6 is evenly transmitted to the entire construction of the work W.
For finding a desired value of the angle “θ” in case wherein the hydroforming process reduces the circumferential length of the tubular work W by 3%, a test was carried out. In this test, many tubular works were subjected to the hydroforming process by using many female dies 32 that had different values of the angle “θ”, and the rate of increase in thickness of the vertical wall Sb of each product (viz., side rail roof S) was measured.
The result of this test is depicted in FIG. 11 . As is see from this graph, when the angle “θ” exceeded about 50°, the rate of increase in thickness of the vertical wall Sb of the product S became lower than 3%.
Referring to FIGS. 12 and 13, there is schematically shown a hydroforming device 41 with which a method of a fourth embodiment of the present invention is carried out. This forming device 41 is designed to make a hydroformed product SA having a rectangular cross section, as shown in FIG. 14 .
In this fourth embodiment, two male dies 46 are employed, which are arranged to move toward and away from each other in a cavity 42 a formed in a female die 42 . Two sealing tools 3 , two supporting members 4 and two feeding tubes 5 are arranged in substantially the same manner as in the case of the above-mentioned first embodiment 1 of FIGS. 1 and 2.
For producing the product SA, a tubular work W was prepared. The tubular work W was the same as the work W used in the above-mentioned first embodiment. The tubular work W was set in the cavity 42 a and held stably by the supporting members 4 . Then, the sealing tools 3 were put into the open ends of the tubular work W to seal the same. Then, a hydraulic fluid was led into the interior Wa of the work W through the feeding tubes 5 and the interior of the work W was kept at a given pressure that was 50 MPa.
Then, as is seen from FIG. 13, with the interior pressure kept constant, the two male dies 46 were moved toward each other to press the tubular work W from both sides. With these steps, the product SA as shown in FIG. 14 was provided, which had a rectangular cross section.
As is seen from FIG. 14, the product SA had a circumferential length that was smaller than that of the tubular work W. While, the thickness of each vertical wall SAb became greater than that of a corresponding portion of the tubular work W. In fact, the thickness of each vertical wall SAb was much greater than that of the vertical wall Sb of the product S produced in the above-mentioned first embodiment. That is, the thickness of each vertical wall SAb increased by about 20%. Furthermore, no reduction in thickness at the four corners SAe was found. That is, the thickness of each corner SAe increased by about 30%.
In addition to the above, substantially identical hydroforming process was applied to a tubular work which was made of a steel of 590 MPa type and had a wall thickness of about 2.0 mm. Also in this case, sufficient increase in thickness of the product was found. This fact has revealed that even a tube of less malleable steel can be used as the work for the hydroforming process of the present invention.
Referring to FIG. 15, there is schematically shown a hydroforming device 51 with which a method of a fifth embodiment of the present invention is carried out.
Similar to the device 1 for the above-mentioned first embodiment, the hydroforming device 51 for this fifth embodiment comprises generally a female die 53 and a male die 52 . The female die 53 has a generally U-shaped cross section and has a cavity 53 a formed therein. The male die 52 is connected to a ram R (see FIG. 3) of a hydraulic actuator, so that the male die 52 can move up and down in the cavity 53 a of the female die 53 .
As shown in the drawing, the male die 52 is formed at lateral ends of its major work surface 52 a with respective projections 52 b that project into the cavity 53 a . Each projection 52 b has a triangular cross section and has a sloped work surface 52 c that faces the cavity 53 a . Furthermore, each projection 52 b has a leading edge that is rounded. Preferably, the radius of curvature of the rounded edge is about a half of the thickness of a tubular work W. In the illustrated embodiment, the radius of curvature is about 1 mm.
For finding a desired shape of the male die 52 to produce a satisfied hollow product M 1 from the tubular work W, four male dies 52 were prepared. These male dies 52 were different in shape of the projections 52 b . That is, the length “L” of the sloped work surface 52 c and the angle “α” defined by the sloped work surface 52 c relative to a vertical wall 53 b of the female die 53 were different in the four male dies 52 .
By taking the following steps, four products M 1 were provided from respective tubular works W through the hydroforming process using the four male dies 52 .
First, each tubular work W was set in the cavity 53 a of the female die 53 and stably held. Each tubular work W was made of a steel of 370 MPa type and was 101.6 mm in diameter and 2.0 mm in thickness. Then, the interior of the tubular work W was filled a hydraulic fluid and kept at 20 MPa. Then, the male die 52 was lowered into the cavity 53 a to press the tubular work W. With these steps, the four products M 1 were provided, each product M 1 having a depressed octagonal cross section as is seen from the drawing. In these four products M 1 , the thickness of two sloped upper portions M 1 a was measured for investigating a thickness change of the portions M 1 a due to the hydroforming process. These two sloped upper portions M 1 a were mainly shaped by the projections 52 b of the male die 52 .
The result of the investigating is shown in TABLE-1. As is seen from the table, when using the first male die 52 (viz., α=141°, D=5.0), the thickness of each sloped upper portion M 1 a increased by 30%, and when using the second male die 52 (viz., α=153°, D=5.6), the thickness of the portion M 1 a increased by 15% and when using the third male die 52 (viz., α=153°, D=6.7), the thickness of the portion M 1 a increased by 10%. In case of the first, second and third male dies 52 , it was further found that with increase of the pressing stroke of the male die 52 , the circumferential length of the product M 1 decreased and the thickness of each sloped upper portion M 1 a increased. While, when using the fourth male die 52 (viz., α=124°, D=9.0), the sloped upper portions M 1 a of the product M 1 showed creases. That is, in case of this fourth male die 52 , with increase of the pressing stroke of the male die 52 , creases gradually appeared at the two sloped upper portions M 1 a of the product M 1 .
FIG. 16 is a graph showing the result in case of using the second male die 52 (viz., α=153°, D=5.6). That is, the graph plots the thickness increasing rate of the sloped upper portions M 1 a relative the pressing stroke of the second male die 52 . As is seen from this graph, with increase of the pressing stroke of the second male die 52 , the thickness of the two sloped upper portions M 1 a increased and at the same time, the thickness of two vertical wall portions M 1 b (see FIG. 15) of the product M 1 increased. The two vertical wall portions M 1 b were mainly shaped by the vertical walls 53 b of the female die 53 . As is seen, once the pressing stroke of the male die 52 exceeded 20 mm, the thickness increasing rate of the sloped upper portions M 1 a sharply increased as compared with that of the vertical wall portions M 1 b . That is, the thickness of the wall portions M 1 a that were mainly shaped by the projections 52 b of the male die 52 increased exclusively.
Referring to FIG. 17, there is schematically shown a hydroforming device 61 with which a method of a sixth embodiment of the present invention is carried out.
As shown, the device 61 of this embodiment comprises generally a female die 64 and two male dies 62 and 63 which are arranged to move toward and away from each other in a cavity 64 a of the female die 64 . Although not shown in the drawing, the two male dies 62 and 63 are powered by a hydraulic actuator.
The male die 62 is formed at lateral ends of its major work surface 62 a with respective projections 62 b that project into the cavity 64 a . Each projection 62 b has a triangular cross section and has a sloped work surface 62 c that faces the cavity 64 a . The length “L1” of the sloped work surface 62 c is 11.2 mm and the angle “α1” defined by the sloped work surface 62 c relative to a vertical wall 64 b of the female die 64 is 153°.
The other male die 63 is formed at lateral ends of its major work surface 63 a with respective projections 63 b that project into the cavity 64 a . Each projection 63 b has a triangular cross section and has a sloped work surface 63 c . The length “L2” of the sloped work surface 63 c is 11.2 mm and the angle “α2” defined by the sloped work surface 63 c relative to the vertical wall 64 b of the female die 64 is 117°.
By using the hydroforming device 61 , a tubular work W was subjected to a hydroforming process. The work W was the same as that used in the above-mentioned fifth embodiment. The tubular work W was set in the cavity 64 a of the female die 64 and stably held. Then, the interior of the work W was filled with a hydraulic fluid and kept at a certain pressure that did induce a free bulging of the work W. The certain pressure was lower than a critical level that is calculated from the following equation:
CL=t 0 × Sy ×1.6 (1)
Wherein:
CL: critical level (MPa)
t 0 : thickness of tubular work (mm)
Sy: yield strength (MPa)
Then, the two male dies 62 and 63 are moved toward each other to press the tubular work W.
With these steps, a hollow product M 2 was provided that had a depressed octagonal cross section as is seen from the drawing.
The thickness of two sloped upper portions M 2 a and that of two sloped lower portions M 2 b of the product M 2 were measured for investigating the thickness change of those portions M 2 a and M 2 b due to the hydroforming process.
The result of the investigating is shown in TABLE-2. As is seen from this table, due to the hydroforming process using the hydroforming device 61 of the sixth embodiment, the thickness of the upper sloped portions M 2 a and that of the lower sloped portions M 2 b increased by 10% and 20% respectively. More specifically, the thickness of the portions M 2 a and M 2 b that were mainly shaped by the projections 62 b and 63 b of the upper and lower male dies 62 increased exclusively. In addition to this, it was further found that due to the hydroforming process by the device 61 , the thickness of vertical walls M 2 c of the product M 2 increased also.
Because the increase in thickness of the specified portions induces a work-hardening of the same, the mechanical strength of the product M 2 is remarkably increased due to combination of the thickness increase and work-hardening.
If the product M 2 thus provided is put into the hydroforming device 61 and set in the cavity 64 a with the two walls M 2 c thereof facing the upper and lower male dies 62 and 63 , pressing of the product M 2 by the two male dies 62 and 63 can provide the product M 2 with a generally square cross section. Furthermore, with this process, the neighboring walls of the product M 2 can have different thickness.
Referring to FIG. 18, there is schematically shown a hydroforming device 71 with which a method of a seventh embodiment of the present invention is carried out.
The device 71 of this seventh embodiment is substantially the same as the device 51 of the above-mentioned fifth embodiment of FIG. 15 except that in the seventh embodiment the male die 72 is formed with only one projection 72 b . That is, the projection 72 b is provided at one lateral end of the major work surface 72 a of the male die 72 . The projection 72 b has a triangular cross section and has a sloped work surface 72 c . The male die 72 moves in a cavity 73 a of the female die 73 . The length “L” of the sloped work surface 72 c is 11.2 mm and the angle “α” defined by the sloped work surface 72 c relative to a vertical wall 73 b of the female die 73 is 153°.
By using the hydroforming device 71 , a tubular work W was subjected to a hydroforming process. The work W was the same as that used in the above-mentioned fifth embodiment. The work W was set in the cavity 73 a of the female die 73 and stably held. Then, the interior of the work W was filled with a hydraulic fluid and kept at a pressure that did make a substantial promotion of a free bulging of the work W. Then, the male die 72 was lowered to press the work W. With these steps, a product M 3 was provided that had a depressed heptagonal cross section as is seen from the drawing.
The thickness of a sloped upper portion M 3 a of the product M 3 was measured for investigating the thickness change of that portion M 3 a due to the hydroforming process.
The result of the investigating is shown in TABLE-3. As is seen from this table, due to the hydroforming process using the hydroforming device 71 of the seventh embodiment, the thickness of the sloped supper portion M 3 a increased by 10%. In addition, it was found that due to the hydroforming process by the device 71 , the thickness of vertical walls M 3 b of the product M 3 increased also.
Referring to FIG. 19, there is schematically shown a hydroforming device 81 with which a method of an eighth embodiment of the present invention is carried out.
The device 81 of this eighth embodiment is substantially the same as the device 61 of the above-mentioned sixth embodiment of FIG. 17 except that in the eighth embodiment each of the upper and lower male dies 82 and 83 is formed with only one projection 82 b or 83 b . As shown, the projections 82 b and 83 b are positioned at opposite sides with respect to a center axis of the device 81 and each projection 82 b or 83 b is provided at one lateral end of the major work surface 82 a or 83 a of the male die 82 or 83 . The projection 82 b or 83 b has a triangular cross section and has a sloped work surface 82 c or 83 c . The upper and lower male dies 82 and 83 move toward and away from each other in a cavity 84 a of the female die 84 . The length “L1” of the sloped work surface 82 c of the upper male die 82 is 11.2 mm and the angle “α1” defined by the sloped work surface 82 c relative to a vertical wall 84 b of the female die 84 is 153°. While, the length “L2” of the sloped work surface 83 c of the lower male die 83 is 11.2 mm and the angle “α2” defined by the sloped work surface 83 c relative to a vertical wall 84 b of the female die 84 is 117°.
By using the hydroforming device 81 , a tubular work W was subjected to a hydroforming process. That is, the work W was set in the cavity 84 a of the female die 84 and held stably. Then, the interior of the work W was filled with a hydraulic fluid and kept at a certain pressure that did not make a substantial promotion to a free bulging of the work W. Then, the two male dies 82 and 83 are moved toward each other to press the tubular work W. With these steps, a product M 4 was provided that had a depressed hexagonal cross section as is seen from the drawing.
The thickness of a sloped upper portion M 4 a and that of a sloped lower portion M 4 b of the product M 4 were measured for investigating the thickness change of these portions M 4 a and M 4 b due to the hydroforming process.
The result of this investigation is shown in TABLE-4. As is seen from this table, due to the hydroforming process using the hydroforming device 81 , the thickness of the upper and lower sloped portions M 4 a and M 4 b increased by 10% and 20% respectively. More specifically, the thickness of the portions M 4 a and M 4 b that were mainly shaped by the projections 82 b and 83 b of the male dies 82 and 83 increased exclusively. In addition to this, it was further found that due to the hydroforming process by the device 81 , the thickness of vertical walls M 4 c of the product M 4 increased also.
Referring to FIG. 20, there is schematically shown a hydroforming device 91 with which a method of a ninth embodiment of the present invention is carried out.
The device 91 used in this ninth embodiment is substantially the same as the device 61 of the above-mentioned sixth embodiment of FIG. 17 except that in the ninth embodiment the projections 93 b of the lower male die 93 are different from those 63 b of the lower male die 63 of the sixth embodiment. That is, in the ninth embodiment, the length “L2” of each sloped work surface 93 c is 11.2 mm, but the angle “α2” defined by the sloped work surface 93 c relative to the vertical wall 94 b of the female die 94 is 153° which is the same as the sloped work surface 92 c of each projection 92 b of the upper male die 92 .
By using the hydroforming device 91 , a tubular work W was subjected to a hydroforming process. The work W used in this embodiment was substantially the same as that used in the fifth embodiment except that in this ninth embodiment the work W was made of a steel of 590 MPa type. The tubular work W was set in the cavity 94 a of the female die 94 and stably held. Then, the interior of the work W was filled with a hydraulic fluid and kept at about 20 MPa. Then, the two male dies 92 and 93 are moved toward each other to press the tubular work W. During this pressing, the hydraulic pressure in the work W increased. However, by using a leak-off valve (not shown), rapid increase of the pressure was suppressed. For this pressing, the maximum pressing stroke of each male die 92 or 93 was so determined as to cause a product M 5 (see FIG. 21) to have a circumferential length smaller than that of the non-pressed tubular work W. At the maximum pressing stroke of each male die 92 or 93 , the pressure of the fluid in the work W showed a level above 30 MPa.
With these steps, the product M 5 was provided that had a depressed octagonal cross section as is seen FIG. 21 .
The thickness of two sloped upper portions M 5 a , the thickness of two sloped lower portions M 5 b and the thickness of two vertical portions M 5 c of the product M 5 were measured, which were 2.30 mm, 2.30 mm and 2.20 mm respectively. That is, the sloped upper portions M 5 a increased by 15%, the sloped lower portions M 5 b increased 15% and the vertical portions M 5 C increased by 10% in thickness. It was further found that portions (viz., upper and lower horizontal wall portions) other than the above-mentioned portions M 5 a , M 5 b and M 5 c showed no change in thickness.
Referring to FIG. 22, there is schematically shown a hydroforming device 101 with which a method of a tenth embodiment of the present invention is carried out.
The device 101 used in this tenth embodiment is substantially the same ad the device 81 of the above-mentioned eighth embodiment of FIG. 19 except that in the tenth embodiment the projection 103 b of the lower male die 103 is different from that 83 b of the lower male die 83 of the eighth embodiment. That is, in the tenth embodiment, the length “L2” of the sloped work surface 103 c is 11.2 mm, but the angle “α2” defined by the sloped work surface 103 c relative to the vertical wall 104 b of the female die 104 is 153° which is the same as the sloped work surface 102 c of the projection 102 b of the upper male die 102 .
By using the hydroforming device 101 , a tubular work W was subjected to a hydroforming process. The work W used in this embodiment was the same as that used in the above-mentioned ninth embodiment. The tubular work W was set in the cavity 104 a of the female die 104 and stably held. The interior of the work W was filled with a hydraulic fluid and kept at about 20 MPa. Then, the two male dies 102 and 103 are moved toward each other to press the tubular work W. For this pressing, the maximum pressing stroke of each male die 102 or 103 was so determined as to cause a product M 6 (see FIG. 23) to have a circumferential length smaller than that of the non-pressed tubular work W. At the maximum pressing stroke of each male die 102 or 103 , the pressure of the fluid in the work W showed a value above 30 MPa.
With these steps, the product M 6 was provided that had a depressed hexagonal cross section, as is seen from FIG. 23 .
The thickness of a sloped upper portion M 6 a , that of a sloped lower portion M 6 b and that of two vertical portions M 6 c and M 6 d of the product M 6 were measured, which were 2.24 mm, 2.24 mm, 2.16 mm and 2.20 mm respectively. That is, the sloped upper portion M 6 a increased by 12%, the sloped lower portion M 6 b increased by 12%, the vertical portion M 6 c increased by 8% and the other vertical portion M 6 d increased by 10% in thickness. It was further found that portions (viz., upper and lower horizontal wall portions) other than the above-mentioned portions M 6 a , M 6 b , M 6 c and M 6 d showed no change in thickness.
Referring to FIG. 24, there is shown a reference hydroforming device 111 , which was provided for proving the improvement achieved by the present invention.
The device 111 is substantially the same as the device 51 used in the above-mentioned fifth embodiment of FIG. 15 except that in this reference device 111 a cavity 113 a of the female die 113 has an entirely flat bottom 113 c , as shown. The length “L” of the sloped work surface 112 c of each projection 112 b is 11.2 mm and the angle “α” defined by the sloped work surface 112 c relative to the vertical wall 113 b of the female die 113 is 153°.
By using the reference device 111 , a tubular work was subjected to a hydroforming process. The work W was the same as the work W used in the above-mentioned ninth and tenth embodiments. Steps of the hydroforming process were substantially the same as those of the ninth and tenth embodiments.
With these steps, a product M 7 was provided, that had a depressed hexagonal cross section, as is seen from FIG. 25 .
The thickness of a right side sloped upper portion M 7 a and that of a left side vertical wall M 7 c of the product M 7 were measured, which were 2.30 mm and 2.20 mm respectively. That is, these portions M 7 a and M 7 c increased by 15% and 10% in thickness respectively. However, it was found that portions other than those portions M 7 a and M 7 b showed no change in thickness. That is, in case of this reference device 111 , the product M 7 failed to have continuous vertical and sloped portions that were both increased in thickness.
For the above, it has been revealed that if the sloped surface 92 c , 93 c , 102 c or 103 c of each projection 92 b , 93 b , 102 b or 103 b of the male die 92 , 93 , 102 or 103 is constructed to satisfy the following equations, a desired result is expected for producing the shaped hollow product M 5 or M 6 .
4≦ L/t 0 ≦7.5 (2)
α≧10×( L/t 0 )+68 (3)
wherein:
L: length of the sloped surface
t 0 : initial thickness of the tubular work
α: angle between the sloped surface and the vertical wall.
Referring to FIG. 26, there is schematically shown a hydroforming device 121 with which a method of an eleventh embodiment of the present invention is carried out. As will be described in detail hereinafter, the device 121 of this embodiment is constructed to shape a tubular work W into a hollow square product M 8 (see FIG. 27) with four rounded corners M 8 a.
As is seen from FIG. 26, the device 121 used in this eleventh embodiment comprises generally fixed lower and upper dies 122 and 123 which are mounted on each other to define therebetween a longitudinally extending cavity 121 a . Each fixed die 122 or 123 is formed at laterally spaced internal portions with longitudinally extending concave surfaces 122 a or 123 a . These concave surfaces 122 a and 123 a are used for shaping the four rounded corners M 8 a of the product M 8 .
The two fixed dies 122 and 123 are respectively formed with vertical slots 122 b and 123 b in which lower and upper male dies 124 and 125 are movably received. The two fixed dies 122 and 123 are vertically spaced from each other to define therebetween horizontal slots 126 a and 126 b in which left and right male dies 127 and 128 are movably received. These four male dies 124 , 125 , 127 and 128 are used for shaping the four flat wall portions M 8 b of the product M 8 .
As is seen from FIG. 26, each slot 122 b , 123 b , 126 a or 126 b is exposed to the cavity 121 a at longitudinally extending ridges P 1 that constitute circumferentially terminal ends of the corresponding concave surfaces 122 a and 123 a . That is, each ridge P 1 constitutes an inside edge of the corresponding slot 122 b , 123 b , 126 a or 126 b.
It is now to be noted that in this eleventh embodiment 121 , the ridges P 1 are shaped and sized to satisfy the following geometrical conditions.
That is, an imaginary straight line “T1” that passes through neighboring two ridges P 1 and P 1 of each slot extends outside of the cavity 121 a defined by the lower and upper female dies 122 and 123 . In other words, the imaginary straight line “T1” does not pass any area of the cavity 121 a . When the male dies 124 , 125 , 127 and 128 are brought to their frontmost work positions, the flat work surface (no numeral) of each male die 124 , 125 , 127 or 128 becomes coincident with the corresponding imaginary straight line “T1”. In this condition, the work surface of each male die 124 , 125 , 127 or 128 is smoothly mated with the ridges P 1 , that is, the circumferentially terminal ends of the concave surfaces 122 a and 123 a.
By using the hydroforming device 121 , a tubular work W was subjected to a hydroforming process. The work W was made of a steel of 370 MPa type and was 123 mm in diameter and 2 mm in thickness. That is, the work W was set in the cavity 121 a of the fixed dies 122 and 123 , and the male dies 124 , 125 , 127 and 128 were moved to their rest position and then, the work W was stably held in the cavity 121 a . Then, the interior of the work W was filled with a hydraulic fluid and the pressure in the work W was increased to and kept at 10.1 MPa. Then, the male dies 124 , 125 , 127 and 128 were moved to their work or press positions to press the work W. During this pressing, the pressure in the work W gradually increased, and at the maximum pressing stroke of each male die, the pressure in the work W was increased to a level of 24.8 MPa.
With these steps, a hollow square product M 8 was provided that had a square cross section with four rounded corners, as is seen from FIG. 27 . The radius of curvature of each corner M 8 a was 8 mm, the height was 100 mm and the width was 100 mm.
The thickness of various portions “a to j” of one rounded corner M 8 a and its neighboring flat wall portion M 8 b of the product M 8 was measured, as is seen from FIG. 28 .
FIG. 29 is a graph showing the result of the thickness measuring, that plots the thickness of such portions “a to j”. For comparison, the result provided by a conventional hydroforming device having no moving dies is also plotted. As is seen from this graph, in the conventional one, the thickness of the rounded corner M 8 a reduced by 20% at most, while in case of the product M 8 of the invention, the thickness of such corner M 8 a increased by 20% at most. That is, by using the hydroforming device 121 of the eleventh embodiment, undesired thickness reduction in the corner was suppressed.
Referring to FIG. 30, there is schematically shown a hydroforming device 131 with which is a method of a twelfth embodiment of the present invention is carried out. As will be described in detail hereinafter, the device 131 of this embodiment is constructed to shape a tubular work W into a hollow square product M 9 (see FIG. 32) with four projected round corners M 9 a.
As is seen from FIG. 30, the device 131 used in this twelfth embodiment comprises generally fixed lower and upper dies 133 and 134 which are mounted on each other to define therebetween a longitudinally extending cavity 131 a.
Each fixed die 133 or 134 is formed at laterally spaced internal portions with longitudinally extending concave surfaces 133 a or 134 a.
The two fixed dies 133 and 134 are respectively formed with vertical slots 133 b and 134 b in which lower and upper male dies 135 and 136 are movably received. The two fixed dies 133 and 134 are vertically spaced from each other to define therebetween horizontal slots 137 a and 137 b in which left and right male dies 138 and 139 are movably received.
As shown, each male die 135 , 136 , 138 or 139 is formed at lateral ends of the work surface 135 a , 136 a , 138 a or 139 a with respective concave recesses 135 b , 136 b , 138 b or 139 b . As is understood from FIG. 31, one concave surface 134 a or 133 a of the fixed female die 134 or 133 and neighboring two concave recesses 136 b and 138 b , 136 b and 139 b , 138 b and 135 b or 135 b and 139 b of the corresponding male dies 136 , 138 , 139 and 135 are used for shaping one projected round corner M 9 a of the product M 9 .
As is seen from FIG. 30, each slot 133 b , 134 b , 137 a or 137 b is exposed to the cavity 131 a at longitudinally extending ridges P 2 that constitute circumferentially terminal ends of the corresponding concave surfaces 133 a and 134 a . That is, each ridge P 2 constitutes an inside edge of the corresponding slot 133 b , 134 b , 137 a or 137 b.
It is now to be noted that in this twelfth embodiment 131 , the ridges P 2 are so shaped and sized as to satisfy the following geometrical conditions.
That is, as is seen from FIG. 30, an imaginary straight line “T2” that passes through neighboring two ridges P 2 and P 2 of each slot extends outside of the cavity 131 a defined by the lower and upper fixed female dies 133 and 134 . In other words, the imaginary straight line “T2” does not pass any area of the cavity 131 a . As is seen from FIG. 31, when the male dies 136 , 138 , 135 and 139 are brought to their frontmost work positions, the outside edge of each concave recess 136 b , 138 b , 135 b or 139 b becomes coincident with the corresponding imaginary straight line “T2”. In this condition, the outside edge of each concave recess 136 b , 138 b , 135 b or 139 b is smoothly mated with the ridges P 2 , that is, the circumferentially terminal ends of the concave surfaces 134 a and 133 a.
By using the hydroforming device 131 , a tubular work W was subjected to a hydroforming process. The work W was made of a steel of 370 MPa type and was 140 mm in diameter and 2 mm in thickness. That is, the work W was set in the cavity 131 a of the fixed dies 133 and 134 , and the male dies 135 , 136 , 138 and 139 were moved to their rest positions and then, the work W was stably held in the cavity 131 a . Then, the interior of the work W was filled with a hydraulic fluid and the pressure in the work W was increased to and kept at 10.1 MPa. Then, the male dies 135 , 136 , 138 and 139 were moved toward their work or press positions to press the work W while keeping the internal pressure of the work W at 20.2 MPa. At the maximum pressing stroke of each male die, the pressure in the work W was increased to a level of 24.8 MPa.
With these steps, a hollow square product M 9 was provided, that had a generally square cross section with four projected round corners, as is seen from FIG. 32 . The radius of curvature of each corner M 9 a was 10 mm, the height was 100 mm and the width was 100 mm.
The thickness of various portions “a to j” of one projected round corner M 9 a and its neighboring flat wall portion M 9 b of the product M 9 was measured, as is seen from FIG. 33 .
FIG. 36 is a graph showing the result of the thickness measuring, that plots the thickness of such portions “a to j”.
For proving the improvement achieved by the method of the twelfth embodiment, a reference method was carried out by using a hydroforming device 141 shown in FIG. 34 .
As is shown in the drawing, the device 141 comprises fixed lower and upper dies 143 and 144 , lower and upper male dies 145 and 146 and left and right male dies 148 and 149 which are arranged in substantially the same manner as those of the above-mentioned device 131 of the twelfth embodiment of FIG. 30 .
Each fixed die 143 or 144 is formed at laterally spaced internal portions with longitudinally extending concave surfaces 143 a or 144 a.
Each male die 145 , 146 , 148 or 149 is formed with a flat work surface 145 a , 146 a , 148 a or 149 a.
As is seen from FIGS. 34 and 35, each slot 143 b 144 b , 147 a or 147 b is exposed to the cavity 141 a at longitudinally extending ridges P 3 that constitute circumferentially terminal ends of the corresponding concave surfaces 143 a and 144 a . That is, each ridge P 3 constitutes an inside edge of the corresponding slot 143 b , 144 b , 147 a or 147 b.
In this reference device 141 , the ridges P 3 are so shaped and sized as to satisfy the following geometrical conditions.
That is, as is seen from FIG. 34, an imaginary straight line “T3” that passes through neighboring two ridges P 3 and P 3 of each slot extends inside (not outside) of the cavity 141 a defined by the lower and upper fixed female dies 144 and 144 . In other words, the imaginary straight line “T3” passes through the projected part of the cavity 121 a , which is defined by the concave surface 144 a or 143 a of the female die 144 or 143 . When the male dies 145 , 146 , 148 and 149 are brought to their frontmost work positions, the flat work surface 145 a , 146 a , 148 a or 149 a of each male die becomes coincident with the corresponding imaginary straight line “T3”. In this condition, the work surface 145 a , 146 a , 148 a or 149 a of each male die is mated with the ridges P 3 , as is seen from FIG. 35 .
By using the reference device 141 , a tubular work W was subjected to a hydroforming process. The work W and the hydroforming steps were the same as those used in the above-mentioned twelfth embodiment. With this, a hollow square product MR was provided, that was similar in construction to the product M 9 provided according to the twelfth embodiment. The thickness of various portions “a to j” of the product MR was measured. The result of the thickness measurement is plotted in the graph of FIG. 36 .
As is seen from this graph, in the product M 9 according to the twelfth embodiment, the thickness of the projected round corner M 9 a increased by about 15%, while in the product MR according to the reference device 141 , thickness increase was now found and a crack was produced at the portion “g”.
The entire contents of Japanese Patent Applications 11-083658 (filed Mar. 26, 1999), 11-183920 (filed Jun. 29, 1999), 11-366894 (filed Dec. 24, 1999) and 2000-49476 (filed Feb. 25, 2000), are incorporated herein by reference.
Although the invention has been described above with reference to the embodiments, the invention is not limited to such embodiments as described hereinabove. Various modifications and variations of such embodiments may be carried out by those skilled in the art, in light of the above description.
TABLE 1
Length
of
Angle
sloped
Increasing
Hydraulic
of pro-
work
Initial
Ratio
rate of
forming
jection
surface
thickness
(D)
thickness
device
α(°)
L (mm)
t 0 (mm)
(L/t 0 )
10D ÷ 68
(%)
FIG. 15
141
10.0
2.0
5.0
118
3
153
11.2
2.0
5.6
124
15
153
13.4
2.0
6.7
135
10
124
18.0
2.0
9.0
158
(Creases
appeared)
TABLE 2
Length
In-
of
creasing
Angle
sloped
rate of
Hydraulic
of pro-
work
Initial
Ratio
thick-
forming
jection
surface
thickness
(D)
ness
device
α(°)
L (mm)
t 0 (mm)
(L/t 0 )
10D ÷ 68
(%)
FIG.
62b
α1:153
L1:11.2
2.0
5.6
124
10
17
63b
α2:117
L2:11.2
2.0
5.6
124
2
TABLE 3
Length
of
Angle
sloped
Increasing
Hydraulic
of pro-
work
Initial
Ratio
rate of
forming
jection
surface
thickness
(D)
thickness
device
α(°)
L (mm)
t 0 (mm)
(L/t 0 )
10D ÷ 68
(%)
FIG. 18
153
11.2
2.0
5.6
124
10
TABLE 4
Length
In-
of
creasing
Angle
sloped
rate of
Hydraulic
of pro-
work
Initial
Ratio
thick-
forming
jection
surface
thickness
(D)
ness
device
α(°)
L (mm)
t 0 (mm)
(L/t 0 )
10D ÷ 68
(%)
FIG.
82b
α1:153
L1:11.2
2.0
5.6
124
10
19
83b
α2:117
L2:11.2
2.0
5.6
124
2 | For forming a tubular work into a shaped hollow product by using hydroforming process, a method and a device are described. In the method, female and male dies are prepared. The female die has a longitudinally extending cavity which has a polygonal cross section when receiving the male die. The tubular work is placed into the cavity of the female die. The interior of the tubular work is then fed with a hydraulic fluid, and the pressure of the fluid is increased to a given level. The given level is smaller than a critical level that causes a bulging of the tubular work. The male die is then pressed against the tubular work to deform the same while keeping the hydraulic fluid at the given level, thereby forming a shaped hollow product that has a polygonal cross section that conforms to that of the cavity. The pressing work is continued until a circumferential length of the shaped hollow product becomes shorter than that of the tubular work. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is the national phase of PCT application PCT/NL2010/050138 having an international filing date of 17 Mar. 2010, which claims benefit of European application No. 09155380.0 filed 17 Mar. 2009. The contents of the above patent applications are incorporated by reference herein in their entirety.
REFERENCE TO SEQUENCE LISTING SUBMITTED VIA EFS-WEB
The entire content of the following electronic submission of the sequence listing via the USPTO EFS-WEB server, as authorized and set forth in MPEP §1730 II.B.2(a)(C), is incorporated herein by reference in its entirety for all purposes. The sequence listing is identified on the electronically filed text file as follows:
File Name
Date of Creation
Size (bytes)
313632012100Seqlist.txt
Dec. 9, 2011
266,182 bytes
FIELD OF THE INVENTION
This invention is related to the field of enzymatic digest of carbohydrate polymers, more specifically enzymatic modification, conversion and degradation of ligno-cellulose and (hemi-)cellulose containing substrates.
BACKGROUND ART
Carbohydrates constitute the most abundant organic compounds on earth. However, much of this carbohydrate is sequestered in complex polymers including starch (the principle storage carbohydrate in seeds and grain), and a collection of carbohydrates and lignin known as lignocellulose. The main carbohydrate components of lignocellulose are cellulose, hemicellulose, and glucans. These complex polymers are often referred to collectively as lignocellulose. Cellulose is a linear polysaccharide composed of glucose residues linked by beta-1,4 bonds. The linear nature of the cellulose fibers, as well as the stoichiometry of the beta-linked glucose (relative to alpha) generates structures more prone to interstrand hydrogen bonding than the highly branched alpha-linked structures of starch. Thus, cellulose polymers are generally less soluble, and form more tightly bound fibers than the fibers found in starch. Hemicellulose is a complex polymer, and its composition often varies widely from organism to organism, and from one tissue type to another. In general, a main component of hemicellulose is beta-1,4-linked xylose, a five carbon sugar. However, this xylose is often branched as beta-1,3 linkages, and can be substituted with linkages to arabinose, galactose, mannose, glucuronic acid, or by esterification to acetic acid. Hemicellulose can also contain glucan, which is a general term for beta-linked six carbon sugars. The composition, nature of substitution, and degree of branching of hemicellulose is very different in dicot plants as compared to monocot plants. In dicots, hemicellulose is comprised mainly of xyloglucans that are 1,4-beta-linked glucose chains with 1,6-beta-linked xylosyl side chains. In monocots, including most grain crops, the principle components of hemicellulose are heteroxylans. These are primarily comprised of 1,4-beta-linked xylose backbone polymers with 1,3-beta linkages to arabinose, galactose and mannose as well as xylose modified by ester-linked acetic acids. Also present are branched beta glucans comprised of 1,3- and 1,4-beta-linked glucosyl chains. In monocots, cellulose, heteroxylans and beta glucans are present in roughly equal amounts, each comprising about 15-25% of the dry matter of cell walls.
The sequestration of such large amounts of carbohydrates in plant biomass provides a plentiful source of potential energy in the form of sugars, both five carbon and six carbon sugars that could be utilized for numerous industrial and agricultural processes. However, the enormous energy potential of these carbohydrates is currently under-utilized because the sugars are locked in complex polymers, and hence are not readily accessible for fermentation. Methods that generate sugars from plant biomass would provide plentiful, economically-competitive feedstocks for fermentation into chemicals, plastics, and fuels. Current processes to generate soluble sugars from lignocellulose are complex. A key step in the process is referred to as pretreatment. The aim of pretreatment is to increase the accessibility of cellulose to cellulose-degrading enzymes, such as the cellulase mixture derived from fermentation of the fungus Trichoderma reesei . Current pretreatment processes involve steeping lignocellulosic material such as corn stover in strong acids or bases under high temperatures and pressures. Such chemical pretreatments degrade hemicellulose and/or lignin components of lignocellulose to expose cellulose, but also create unwanted by-products such as acetic acid, furfural, hydroxymethyl furfural and gypsum. These products must be removed in additional processes to allow subsequent degradation of cellulose with enzymes or by a co-fermentation process known as simultaneous saccharification and fermentation (SSF). The conditions currently used for chemical pretreatments require expensive reaction vessels, and are energy intensive. Chemical pretreatment occurring at high temperatures and extreme pH conditions (for example 160° C. and 1.1% sulfuric acid at 12 atm. pressure) are not compatible with known cellulose-degrading enzymes. Further, these reactions produce compounds that must be removed before fermentation can proceed. As a result, chemical pretreatment processes currently occur in separate reaction vessels from cellulose degradation, and must occur prior to cellulose degradation.
Thus, methods that are more compatible with the cellulose degradation process, do not require high temperatures and pressures, do not generate toxic waste products, and require less energy, are desirable. For these reasons, efficient methods are needed for biomass conversion.
Filamentous fungi are efficient producers of a large variety of enzymes, and, therefore, they are exploited already for decades for the production of enzymes at industrial scale. Numerous hydrolytic activities have been identified for hydrolysis of starch, (hemi)cellulose and inulin. For many of these enzymes industrial processes have been developed.
Based on extensive research on these carbohydrolytic enzymes, besides catalytic domains also domains involved in substrate binding have been identified. For fungal enzymes in particular, most of the lignocellulose and (hemi-)cellulose degrading enzymes are characterized by having a cellulose binding domain, denominated as CBM1 (se also www.cazy.org/fam/acc_CBM.html. Interestingly, in particular for CBM1, which is unique to fungi, proteins with completely different catalytic activities have been identified. Besides different types of (hemi)cellulases, xylanases, pectinases, esterases, chitinases and lipases amongst others also CBM-1 proteins with unknown activity have been identified. The largest gene family of this latter class is the GH61 protein/gene family. However, there is still need for further enzymes involved in lignocellulose and (hemi-)cellulose degradation.
SUMMARY OF THE INVENTION
The inventors have now discovered two novel gene families of lignocellulose active enzymes, sharing a hitherto unknown domain (sometimes in addition to a CBM1 domain). Therefore the invention comprises a lignocellulose and/or (hemi-)cellulose active protein comprising the domain with the amino acid sequence
(SEQ ID NOS: 1-2) [DN]-P-[IVL]-[MAIV]-X-[PAF]-[GNQ]-X 3-4 -[SAP]-X 1-2 -H-X-H-X 3 -G-X 16-21 - C-[ST]-[ST]-X5-D-X-S-[AN]-Y-[YW]-X-[AP]-X-[LVM]-X 2-9 -G
or a sequence that has an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98% with said amino acid sequence. Preferably said protein comprises the sequence
DPLVFPGAM QSPHVHQIVG GNMFNVTMDP NRHNIGEEAT CTTCTFSEDF SNYWTAILYF RARNGTLIRV PQRPNIDFDG ARGGGMTVYY TATYQNHKPT AFQPGFRMIV GNPMYRTQAE ASRYRQMTFT CLETLSTRTG ETTEMPKQPC REGIMSNVRF PTCWDGKTLD PPDHSSHVAY PSSGTFESGG PCPASHPVRI PQLFYEVLWD TRRFNDRSLW PEDGSQPFVW SYGDYTGYGT HGDYVFGWKG I (SEQ ID NO: 4), or, alternatively, the sequence GAPSVHAVLR FSCSELVTER LDPLVFPGAM QSPHVHQIVG GNMFNVTMDP NRHNIGEEAT CTTCTFSEDF SNYWTAILYF RARNGTLIRV PQRPNIDFDG ARGGGMTVYY TATYQNHKPT AFQPGFRMIV GNPMYRTQAE ASRYRQMTFT CLETLSTRTG ETTEMPKQPC REGIMSNVRF PTCWDGKTLD PPDHSSHVAY PSSGTFESGG PCPASHPVRI PQLFYEVLWD TRRFNDRSLW PEDGSQPFVW SYGDYTGYGT HGDYVFGWKG DSLQRAMDAN CDFYCPQLKT QSIATGNQCR QNQKVAENID1 GPFDRLPGNV EITGPQPGAS (SEQ ID NO: 5)
or a sequence that has an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98% with said amino acid sequences. Said protein is preferably selected from the group consisting of the proteins with the NCBI accession no. XP — 001907658.1 (SEQ ID NO:16), XP — 001904981.1 (SEQ ID NO:17), XP — 001911253.1 (SEQ ID NO:18), XP — 001911467.1 (SEQ ID NO:19), XP — 001908261.1 (SEQ ID NO:20), XP — 001907671.1 (SEQ ID NO:21), XP — 001906312.1 (SEQ ID NO:22), XP — 001912166.1 (SEQ ID NO:23), XP — 001904033.1 (SEQ ID NO:24), XP — 001905336.1 (SEQ ID NO:25), XP — 001904002.1 (SEQ ID NO:26), XP — 001905175.1 (SEQ ID NO:27), XP — 001911617.1 (SEQ ID NO:28), XP — 001907672.1 (SEQ ID NO:29), XP — 001903756.1 (SEQ ID NO:30), XP — 001903833.1 (SEQ ID NO:31), XP — 001904389.1 (SEQ ID NO:32), XP — 001904303.1 (SEQ ID NO:33), XP — 001903094.1 (SEQ ID NO:34), XP — 001904583.1 (SEQ ID NO:35), XP — 001904957.1 (SEQ ID NO:36), XP — 001906851.1 (SEQ ID NO:37), XP — 001903754.1 (SEQ ID NO:38), XP — 001911708.1 (SEQ ID NO:39), XP — 001907931.1 (SEQ ID NO:40), and XP — 001903118.1 (SEQ ID NO:41) from Podospora anserina , BAE61525.1 (SEQ ID NO:42), BAE54784.1 (SEQ ID NO:43) and BAE66576.1 (SEQ ID NO:44) from Aspergillus oryzae , CAK38435.1 (SEQ ID NO:45) and CAK40357.1 (SEQ ID NO:46) from Aspergillus niger and three proteins from Trichoderma reesei (proteins 108655 (SEQ ID NO:47), 37665 (SEQ ID NO:48) and 102735 (SEQ ID NO:49) from the T. reesei protein database at JTI, genome.jgi-psforg/Trire2/Trire2.home.html). Also preferred is a protein according to the invention that additionally comprises a CBM1 domain, preferably wherein said CBM1 domain comprises the consensus sequence C-G (2) -X (4-7) -G-X (3) -C-X (4,5) -C-X (3-5) -[NHGS]-X-[FYWMI]-X (2) -Q-C (SEQ ID NO:9), more preferably wherein said protein is the protein from Podospora anserina with the NCBI accession no. CAP68330.1 (SEQ ID NO:81).
In another embodiment, the invention comprises a lignocellulose and/or (hemi-)cellulose active protein comprising the domain with the amino acid sequence
[GA]-[ST]-[IV]-[ILV]-W-[DS]-G-[RIFS]-F-[ND]-[DS]-X 2 -[TS]-X 2 -D-[LIF]-[ND]- K-W-S-W-[GSA]-N-Q-[IV]-[GP]-[PS]-[YW]-X 0-4 -Q-[YW]-Y-I-H-G-S-X 2 -[VT]-X 2 - Y-[ILV]-X[ILV]-S-X 2 -[FY]-K-N-P-X 5-7 -Q-G-X-[KR]-I-T-[LI]-D-X-[ST]-[AS]-X-W- N-G-Q-[NT]-M-X-R-[IST]-E-L-I-P-Q-T-X 6-13 -G-X-[KLV]-[FY]-Y-H-F-S-[ILV]-X 5 - N-A-P-X 4 -E-H-Q-[ILV]-[AC]-F-F-E-X 0-13 -S-H-F-T-E-[LM]-K-[YST]-G-W-X 0-2 -G- X 6-33 -[LF]-X 1-24 -I-D-F-[ASD]-X 3-8 -V-[FL]-[FWY]-X-S-[ENT]-G-X 2-5 -[AP]-L-X 2-4 - [AV]-[AV]-X-[PAN]-X 3-5 -[ANS]-[AT]-[AFS]-[ST]-[DN]-[GS]-[AQ]-D-[FW]-H- {FILV}-G-[EIQV]-L-[ERK]-[ILV]-P-X 8-18 -E-D-[FWY]-[FY]-[FW]-S-G-[IV]-[FY]- [IV]-E (SEQ ID NOS: 6-7)
or a sequence that has an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98% with said amino acid sequence. Preferably such a protein comprises the sequence
(SEQ ID NO: 3) GT ILWDGRFNDM TSSADLNKWS WGNQVGPYQY YIHGSSPVSA YVNLSPDYKN PADTGSRQGA KITLDNTAYW NGQNMRRTEL IPQTTAAINQ GKVYYHFSLM RKDINAPATT REHQIAFFES HFTELKSGWL SGAPGISDTL LRWCIDFAAG TVGFWHSTGS DPLTRKVAPV KTSTSSNGAD WHVGVLELPR SGYPDSNEDF YWSGVYIESG SLTTSVAGPG QPIPGDGG
or a sequence that has an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98% with said amino acid sequence. Preferably said protein is selected from the group consisting of the proteins from Podospora anserina with the NCBI accession numbers XP — 001903534.1 (CAP61309.1) (SEQ ID NO:50) and XP — 001907960.1 (CAP68633.1) (SEQ ID NO:51), from Aspergillus flavus (EED52126.1 (SEQ ID NO:52) and EED54304.1 (SEQ ID NO:53)), from Aspergillus fumigatus (XP — 751054.2 (SEQ ID NO:54), XP — 755877.1 (SEQ ID NO:55) and EDP49742.1 (SEQ ID NO:56)), Aspergillus clavatus (XP — 001275827.1) (SEQ ID NO:57), Aspergillus oryzae (XP — 001825707.1) (SEQ ID NO:58), Aspergillus terreus (XP — 001211584.1) (SEQ ID NO:59), Aspergillus nidulans (XP — 680867.1) (SEQ ID NO:60), Aspergillus niger (XP — 001392581.1) (SEQ ID NO:61), Magnaporthe griseae (XP — 362641.1 (SEQ ID NO:62) and XP — 001408874.1 (SEQ ID NO:63)), Phaeosphaeria nodorum (XP — 001793212.1 (SEQ ID NO:64) and XP — 001799980.1 (SEQ ID NO:65)), Neurospra crassa (XP — 958348.1 (SEQ ID NO:66) and XP — 956768.1 (SEQ ID NO:67)), Pyrenophora tritici - repentis (XP — 001932168.1 (SEQ ID NO:68) and XP — 001931381.1 (SEQ ID NO:69)), Neosartorya fischeri (XP — 001258287.1 (SEQ ID NO:70) and XP — 001261005.1 (SEQ ID NO:71)), Chaetomiun globosum (XP — 001228503) (SEQ ID NO:72), Botryotinia fuckeliana (XP — 001546653.1) (SEQ ID NO:73), Sclerotinia sclerotiorum (XP — 001593519.1) (SEQ ID NO:74), Moniliophthora perniciosa (EEB91913.1) (SEQ ID NO:75) and Coprionopsis cinerea (XP — 001835742) (SEQ ID NO:76).
In another embodiment, said protein additionally comprises a CBM1 domain, and is preferably selected from the group consisting of the proteins with NCBI accession no. CAP61309.1 (SEQ ID NO:77), BAE64574.1 (SEQ ID NO:78) and CAK45436.1 (SEQ ID NO:79).
In a preferred embodiment the protein from the invention is from fungal origin, preferably wherein the fungus is chosen from the group consisting of Aspergillus, Neurospora, Sclerotina, Gibberella, Coniothyrium, Psiticum, Magnaporthe, Podospora, Chaetomium, Phaeosphaeria, Botryotinia, Neosartorya, Pyrenophora, Panicum, Aureococcus, Trichoderma Penicillium and Chrysosporium.
Also part of the invention is a nucleic acid encoding a protein according to the invention, a vector comprising said nucleic acid and a host cell capable of expressing a protein according to the invention by harbouring said nucleic acid or vector.
Further, also comprised in the invention is the use of a protein according to the invention in the modification of a raw carbohydrate, preferably lignocellulose and/or (hemi-)cellulose, most preferably non-soluble cellulose, preferably wherein the protein has or enhances cellulase activity.
LEGENDS TO THE FIGURES
FIG. 1 . SDS PAGE of proteins produced by A. niger transformants transgenic for CAP68330 and CAP61309. M indicates marker lane.
DETAILED DESCRIPTION
The term “sequence identity,” as used herein, is generally expressed as a percentage and refers to the percent of amino acid residues or nucleotides, as appropriate, that are identical as between two sequences when optimally aligned. For the purposes of this invention, sequence identity means the sequence identity determined using the well-known Basic Local Alignment Search Tool (BLAST), which is publicly available through the National Cancer Institute/National Institutes of Health (Bethesda, Md.) and has been described in printed publications (see, e.g., Altschul et al., J. MoI. Biol, 215(3), 403-10 (1990)). Preferred parameters for amino acid sequences comparison using BLASTP are gap open 11.0, gap extend 1, Blosum 62 matrix. Protein analysis software matches similar sequences using measures of homology assigned to various substitutions, deletions and other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.
The term “signal peptide” or “signal sequence” as used herein, refers to an amino acid sequence, typically located at the amino terminus of an immature protein or polypeptide (e.g., prior to secretion from a cell and associated processing and cleavage), which directs the secretion of the protein or polypeptide from the cell in which it is produced. The signal peptide typically is removed from an immature protein or polypeptide prior to or during secretion and, thus, is not present in the mature, secreted polypeptide.
As used herein, the term “recombinant nucleic acid molecule” refers to a recombinant DNA molecule or a recombinant RNA molecule. A recombinant nucleic acid molecule is any synthetic nucleic acid construct or nucleic acid molecule containing joined nucleic acid molecules from different original sources or and not naturally occurring or attached together and prepared by using recombinant DNA techniques.
The term “recombinant host cell” as used herein, refers to a host cell strain containing nucleic acid not naturally occurring in that strain and which has been introduced into that strain using recombinant DNA techniques.
The term “nucleic acid” as used herein, includes reference to a deoxyribonucleotide or ribonucleotide polymer, i.e. a polynucleotide, in either single- or double-stranded form, and unless otherwise limited, encompasses known analogues having the essential nature of natural nucleotides in that they hybridize to single-stranded nucleic acids in a manner similar to naturally occurring nucleotides (e.g., peptide nucleic acids). A polynucleotide can be full-length or a subsequence of a native or heterologous structural or regulatory gene. Unless otherwise indicated, the term includes reference to the specified sequence as well as the complementary sequence thereof. Thus, DNAs or RNAs with backbones modified for stability or for other reasons are “polynucleotides” (a polymeric form of nucleotides, either ribonucleotides or deoxyribonucleotides, double- or single-stranded of any length) as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritylated bases, to name just two examples, are polynucleotides as the term is used herein. It will be appreciated that a great variety of modifications have been made to DNA and RNA that serve many useful purposes known to those of skill in the art. The term polynucleotide as it is employed herein embraces such chemically, enzymatically or metabolically modified forms of polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including among other things, simple and complex cells.
Every nucleic acid sequence herein that encodes a polypeptide also, by reference to the genetic code, describes every possible silent variation of the nucleic acid. The term “conservatively modified variants” applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refer to those nucleic acids which encode identical or conservatively modified variants of the amino acid sequences due to the degeneracy of the genetic code.
The term “degeneracy of the genetic code” refers to the fact that a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are “silent variations” and represent one species of conservatively modified variation.
The term “gene”, as used herein, refers to a nucleic acid sequence containing a template for a nucleic acid polymerase, in eukaryotes, RNA polymerase II. Genes are transcribed into mRNAs that are then translated into protein.
“Expression” refers to the transcription of a gene into structural RNA (rRNA, tRNA) or messenger RNA (mRNA) with subsequent translation into a protein.
The term “complementary”, as used herein, refers to a sequence of nucleotides which forms a hydrogen-bonded duplex with another sequence of nucleotides according to Watson-Crick base-paring rules. For example, the complementary base sequence for 5′-AAGGCT-3′ is 3′-TTCCGA-5′. As used herein, “substantially complementary” means that two nucleic acid sequences have at least about 40, preferably about 50% more preferably at least 55%, more preferably about 60%, more preferably about 70%, more preferably about 80%, even more preferably 90%, and most preferably about 98%, sequence complementarity to each other.
The term “hybridise” refers to the process by which single strands of nucleic acid sequences form double-helical segments through hydrogen bonding between complementary nucleotides.
As used herein, the term “expression control sequence” refers to a nucleic acid sequence that regulates the transcription and translation of a gene to which it is operatively linked. An expression control sequence is “operatively linked” to a gene when the expression control sequence controls and regulates the transcription and, where appropriate, translation of the gene. The term “operatively linked” includes the provision of an appropriate start codon (e.g. ATG), in front of a polypeptide-encoding gene and maintaining the correct reading frame of that gene to permit proper translation of the mRNA.
As used herein, the term “operably linked” refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. A control sequence “operably linked” to another control sequence and/or to a coding sequence is ligated in such a way that transcription and/or expression of the coding sequence is achieved under conditions compatible with the control sequence. Generally, operably linked means that the nucleic acid sequences being linked are contiguous and, where necessary to join two protein coding regions, contiguous and in the same reading frame.
The term “vector” as used herein, includes reference to an autosomal expression vector and to an integration vector used for integration into the chromosome.
The term “expression vector” refers to a DNA molecule, linear or circular, that comprises a segment encoding a polypeptide of interest under the control of (i.e., operably linked to) additional nucleic acid segments that provide for its transcription. Such additional segments may include promoter and terminator sequences, and may optionally include one or more origins of replication, one or more selectable markers, an enhancer, a polyadenylation signal, and the like. Expression vectors are generally derived from plasmid or viral DNA, or may contain elements of both. In particular an expression vector comprises a nucleotide sequence that comprises in the 5′ to 3′ direction and operably linked: (a) a fungal-recognized transcription and translation initiation region, (b) a coding sequence for a polypeptide of interest, and (c) a fungal-recognized transcription and translation termination region. “Plasmid” refers to autonomously replicating extrachromosomal DNA which is not integrated into a microorganism's genome and is usually circular in nature.
An “integration vector” refers to a DNA molecule, linear or circular, that can be incorporated in a microorganism's genome and provides for stable inheritance of a gene encoding a polypeptide of interest. The integration vector generally comprises one or more segments comprising a gene sequence encoding a polypeptide of interest under the control of (i.e., operably linked to) additional nucleic acid segments that provide for its transcription. Such additional segments may include promoter and terminator sequences, and one or more segments that drive the incorporation of the gene of interest into the genome of the target cell, usually by the process of homologous recombination. Typically, the integration vector will be one which can be transferred into the host cell, but which has a replicon which is nonfunctional in that organism. Integration of the segment comprising the gene of interest may be selected if an appropriate marker is included within that segment.
“Transformation” and “transforming”, as used herein, refers to the insertion of an exogenous polynucleotide into a host cell, irrespective of the method used for the insertion, for example, direct uptake, transduction, f-mating or electroporation. The exogenous polynucleotide may be maintained as a non-integrated vector, for example, a plasmid, or alternatively, may be integrated into the host cell genome.
By “host cell” is meant a cell which contains a vector or recombinant nucleic acid molecule and supports the replication and/or expression of the vector or recombinant nucleic acid molecule. Host cells may be prokaryotic cells such as E. coli , or eukaryotic cells such as yeast, fungus, plant, insect, amphibian, or mammalian cells. Preferably, host cells are fungal cells.
The term “fungus” or “fungi” includes a wide variety of nucleated, spore-bearing organisms which are devoid of chlorophyll. Examples of fungi include yeasts, mildews, molds, rusts and mushrooms. Preferred fungi in aspects of the present invention are organisms of the genera Aspergillus, Neurospora, Sclerotina, Gibberella, Coniothyrium, Psiticum, Magnaporthe, Podospora, Chaetomium, Phaeosphaeria, Botryotinia, Neosartorya, Pyrenophora, Panicum, Aureococcus Penicillium and Chrysospsorium.
The terms “isolated” or “purified” as used herein refer to a nucleic acid or protein or peptide that is removed from at least one component with which it is naturally associated. In the present invention, an isolated nucleic acid can include a vector comprising the nucleic acid. Purified as used herein to describe a polypeptide produced by cultivation of a recombinant host cell refers to removing that polypeptide from at least one component with which it is naturally associated in the host cell or culture medium.
The CBM1 domain that is present in many of the proteins that are held to have activity on cellulose, chitin, sepharose, xylan has a consensus amino acid sequence that can be denoted as:
C-G (2) -X (4-7) -G-X (3) -C-X (4-5) -C-X (3-5) [NHGS]-X-[FYWMI]- x (2) -Q-C (SEQ ID NO: 9)
in which the amino acids between square brackets are alternatives on that position, and X n denotes a series of n freely chosen amino acids. Alternatively, the CBM1 domain is a sequence that has a high identity with the above consensus sequence. However, no or only very limited catalytic activity has been shown to reside in or be linked to said CBM1 domain.
Now, the inventors have discovered two novel classes of starch active proteins wherein the first class shares a common domain of unknown function (D-U-F), also called the DUF1996 domain, partly represented by the consensus sequence:
[DN]-P-[IVL]-[MAIV]-x-[PAF]-[GNQ]-X 3-4 -[SAP]-X 1-2 -
H-X-H-X 3 -G-X 16-21 -C-[ST]-[ST]-X 5 -D-X-S-[AN]-Y-[YW]-
X-[AP]-X-[LVM]-X 2-9 -G (SEQ ID NOS: 1-2)
in which the amino acids between square brackets are alternatives at the same position and X n denotes a series of n freely chosen amino acids, or an amino acid sequence that has a high degree of identity with said consensus sequence.
An example of such a domain is the sequence:
DPLVFPGAM QSPHVHQIVG GNMFNVTMDP NRHNIGEEAT CTTCTFSEDF SNYWTAILYF RARNGTLIRV PQRPNIDFDG ARGGGMTVYY TATYQNHKPT AFQPGFRMIV GNPMYRTQAE ASRYRQMTFT CLETLSTRTG ETTEMPKQPC REGIMSNVRF PTCWDGKTLD PPDHSSHVAY PSSGTFESGG PCPASHPVRI PQLFYEVLWD TRRFNDRSLW PEDGSQPFVW SYGDYTGYGT HGDYVFGWKG I (SEQ ID NO: 4),
and also the sequence:
GAPSVHAVLR FSCSELVTER LDPLVFPGAM QSPHVHQIVG GNMFNVTMDP NRHNIGEEAT CTTCTFSEDF SNYWTAILYF RARNGTLIRV PQRPNIDFDG ARGGGMTVYY TATYQNHKPT AFQPGFRMIV GNPMYRTQAE ASRYRQMTFT CLETLSTRTG ETTEMPKQPC REGIMSNVRF PTCWDGKTLD PPDHSSHVAY PSSGTFESGG PCPASHPVRI PQLFYEVLWD TRRFNDRSLW PEDGSQPFVW SYGDYTGYGT HGDYVFGWKG DSLQRAMDAN CDFYCPQLKT QSIATGNQCR QNQKVAENID1 GPFDRLPGNV EITGPQPGAS (SEQ ID NO: 5)
or an amino acid sequence that has a high degree of identity with said sequences. A high degree of identity is herein defined as an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98%.
Species of proteins with this new domain are 26 proteins from Podospora anserina (accession numbers XP — 001907658.1 (SEQ ID NO:16), XP — 001904981.1 (SEQ ID NO:17), XP — 001911253.1, (SEQ ID NO:18) XP — 001911467.1 (SEQ ID NO:19), XP — 001908261.1 (SEQ ID NO:20), XP — 001907671.1 (SEQ ID NO:21), XP — 001906312.1 (SEQ ID NO:22), XP — 001912166.1 (SEQ ID NO:23), XP — 001904033.1 (SEQ ID NO:24), XP — 001905336.1 (SEQ ID NO:25), XP — 001904002.1 (SEQ ID NO:26), XP — 001905175.1 (SEQ ID NO:27), XP — 001911617.1 (SEQ ID NO:28), XP — 001907672.1 (SEQ ID NO:29), XP — 001903756.1 (SEQ ID NO:30), XP — 001903833.1 (SEQ ID NO:31), XP — 001904389.1 (SEQ ID NO:32), XP — 001904303.1 (SEQ ID NO:33), XP — 001903094.1 (SEQ ID NO:34), XP — 001904583.1 (SEQ ID NO:35), XP — 001904957.1 (SEQ ID NO:36), XP — 001906851.1 (SEQ ID NO:37), XP — 001903754.1 (SEQ ID NO:38), XP — 001911708.1 (SEQ ID NO:39), XP — 001907931.1 (SEQ ID NO:40), XP — 001903118.1 (SEQ ID NO:41), BAE61525.1 (SEQ ID NO:42), BAE54784.1 (SEQ ID NO:43) and BAE66576.1 (SEQ ID NO:44) from Aspergillus oryzae , CAK38435.1 (SEQ ID NO:45) and CAK40357.1 (SEQ ID NO:46) from Aspergillus niger and three proteins from Trichoderma reesei (proteins 108655 (SEQ ID NO:47), 37665 (SEQ ID NO:48) and 102735 (SEQ ID NO:49) from the T. reesei protein database at JTI, genome.jgi-psforg/Trire2/Trire2.home.html, see Martinez, D. et al., 2008 , Nature Biotechnology 26, 553-560).
This new class of proteins has been discovered in the search for proteins with CBM1 domains. It appeared that several of the proteins, especially those from fungal origin contained the above conserved DUF1996 domain next to the CBM1 domain. Further search for more proteins that also comprised the conserved DUF1996 domain has led to the proteins of the present invention. It is submitted that for all currently known proteins with said domain that are listed above and/or in the experimental part no function was hitherto known from any of these proteins. A species of a protein with both CBM1 and DUF1996 domains is CAP68330.1 from Podospora anserine (SEQ ID NO:81).
A further new class of proteins concerns proteins that have the domain with the consensus sequence:
[GA]-[ST]-[IV]-[ILV]-W-[DS]-G-[RIFS]-F-[ND]-[DS]-X 2 -[TS]-X 2 -D-[LIF]-[ND]- K-W-S-W-[GSA]-N-Q-[IV]-[GP]-[PS]-[YW]-X 0-4 -Q-[YW]-Y-I-H-G-S-X 2 -[VT]-X 2 - Y-[ILV]-X[ILV]-S-X 2 -[FY]-K-N-P-X 5-7 -Q-G-X-[KR]-I-T-[LI]-D-X-[ST]-[AS]-X-W- N-G-Q-[NT]-M-X-R-[IST]-E-L-I-P-Q-T-X 6-13 -G-X-[KLV]-[FY]-Y-H-F-S-[ILV]-X 5 - N-A-P-X 4 -E-H-Q-[ILV]-[AC]-F-F-E-X 0-13 -S-H-F-T-E-[LM]-K-[YST]-G-W-X 0-2 -G- X 6-33 -[LF]-X 1-24 -I-D-F-[ASD]-X 3-8 -V-[FL]-[FWY]-X-S-[ENT]-G-X 2-5 -[AP]-L-X 2-4 - [AV]-[AV]-X-[PAN]-X 3-5 -[ANS]-[AT]-[AFS]-[ST]-[DN]-[GS]-[AQ]-D-[FW]-H- {FILV}-G-[EIQV]-L-[ERK]-[ILV]-P-X 8-18 -E-D-[FWY]-[FY]-[FW]-S-G-[IV]-[FY]- [IV]-E (SEQ ID NOS: 6-7)
or an amino acid sequence that has a high degree of identity with this sequence. Particularly, the domain comprises the sequence
(SEQ ID NO: 3) GT ILWDGRFNDM TSSADLNKWS WGNQVGPYQY YIHGSSPVSA YVNLSPDYKN PADTGSRQGA KITLDNTAYW NGQNMRRTEL IPQTTAAINQ GKVYYHFSLM RKDINAPATT REHQIAFFES HFTELKSGWL SGAPGISDTL LRWCIDFAAG TVGFWHSTGS DPLTRKVAPV KTSTSSNGAD WHVGVLELPR SGYPDSNEDF YWSGVYIESG SLTTSVAGPG QPIPGDGG
or an amino acid sequence that has a high degree of identity therewith. A high degree of identity is herein defined as an identity of more than 70%, preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98%. Species of a protein with this new domain are two proteins from Podospora anserina with accession numbers XP — 001903534.1 (CAP61309.1) and XP — 001907960.1 (CAP68633.1), wherein CAP61309 comprises the sequence
19 GTILWDGRFNDMTSSADLNKWSWGNQVGPYQYYIHGSSPVSAYVNLSPDYKNPADTGSRQ 79 GAKITLDNTAYWNGQNMRRTELIPQTTAAINQGKVYYHFSLMRKDINAPATTREHQIAFF 139 ESHFTELKSGWLSGAPGISDTLLRWCIDFAAGTVGFWHSTGSDPLTRKVAPVKTSTSSNG 199 ADWHVGVLELPRSGYPDSNEDFYWSGVYIESGSLTTSVAGPGQPIPGDGG 248 (SEQ ID NO: 10)
and CAP68633 comprises the sequence
19
GAVLWDGRFNDFTSSADLNKWSWANQVGPYPFTNKEYYIHGSGTVNRYINLSPDYKNPND
79
TVSKQGARFTLDSTAYWNGQTMRRIELIPQTKAAINRGKVFYHFSISRRDTNAPSVNKEH
139
QICFFESHFTELKYGWISGEQGAANPALQWMTNQRTQWKLSEWKANVWHNFAYEIDFSGN
199
RVGLWYSEGGADLKQVVAPVGGVSTSSNGQDWHLGVLELPRSGYPNTNEDYYFSGVFIED
259
GAITTKIGGPGE (SEQ ID NO: 11)
270
Other examples of this new class of proteins are hitherto hypothetical proteins with unknown function from Aspergillus flavus (EED52126.1 (SEQ ID NO:52) and EED54304.1 (SEQ ID NO:53)), from Aspergillus fumigatus (XP — 751054.2 (SEQ ID NO:54), XP — 755877.1 (SEQ ID NO:55) and EDP49742.1 (SEQ ID NO:56)), Aspergillus clavatus (XP — 001275827.1) (SEQ ID NO:57), Aspergillus oryzae (XP — 001825707.1) (SEQ ID NO:58), Aspergillus terreus (XP — 001211584.1) (SEQ ID NO:59), Aspergillus nidulans (XP — 680867.1) (SEQ ID NO:60), Aspergillus niger (XP — 001392581.1) (SEQ ID NO:61), Magnaporthe griseae (XP — 362641.1 (SEQ ID NO:62) and XP — 001408874.1 (SEQ ID NO:63)), Phaeosphaeria nodorum (XP — 001793212.1 (SEQ ID NO:64) and XP — 001799980.1 (SEQ ID NO:65)), Neurospra crassa (XP — 958348.1 (SEQ ID NO:66) and XP — 956768.1 (SEQ ID NO:67)), Pyrenophora tritici - repentis (XP — 001932168.1 (SEQ ID NO:68) and XP — 001931381.1 (SEQ ID NO:69)), Neosartorya fischeri (XP — 001258287.1 (SEQ ID NO:70) and XP — 001261005.1 (SEQ ID NO:71)), Chaetomiun globosum (XP — 001228503) (SEQ ID NO:72), Botryotinia fuckeliana (XP — 001546653.1) (SEQ ID NO:73), Sclerotinia sclerotiorum (XP — 001593519.1) (SEQ ID NO:74), Moniliophthora perniciosa (EEB91913.1) (SEQ ID NO:75) and Coprionopsis cinerea (XP — 001835742) (SEQ ID NO:76).
This second new class of proteins has also been discovered in the search of proteins with CBM1 domains. It appeared that several of the proteins, especially those from fungal origin contained the above conserved new domain next to the CBM1 domain. Further search for more proteins that also comprised the conserved new domain has led to the proteins of the present invention. It is submitted that all currently known proteins with said domain or a domain which is highly identical thereto are listed in the experimental part and that no function was hitherto known from any of these proteins. Species of the proteins with both domains are CAP61309.1 (SEQ ID NO:77) from Podospora anserina , BAE64574.1 (SEQ ID NO:78) from Aspergillus oryzae , CAK45436.1 (SEQ ID NO:79) from Aspergillus niger and AN7598.2 from Aspergillus nidulans (SEQ ID NO:80).
The proteins of the invention are generally derived from fungi.
Also part of the invention is a nucleotide sequence encoding one or more of the lignocellulose or (hemi-)cellulose active proteins described above. Such a nucleotide sequence can be any nucleotide sequence that encodes said protein(s), but preferably it is the natural coding sequence found in the organisms from which the lignocellulose or (hemi-)cellulose active proteins are derived. However, if these nucleotide sequences are meant for expression in a different host organism, the nucleotide sequence(s) may be adapted to optimize expression is said host organism (codon optimization). For expression purposes, the nucleotide sequence is included in an expression vector that also provides for regulatory sequences, operably linked with the coding nucleotide sequence.
The proteins of the invention can be used in isolated form for addition to a raw carbohydrate (lignocellulose or (hemi-)cellulose) substrate, alone or together with other lignocellulose or (hemi-)cellulose degrading enzymes, such as (hemi)cellulase, xylanase and/or pectinase. The proteins of the invention may yield a lignocellulose or (hemi-)cellulose hydrolytic activity per se, or they increase the accessibility of the lignocellulose or (hemi-)cellulose by other lignocellulose or (hemi-)cellulose degrading enzymes.
In another embodiment, the proteins of the invention can be (over)expressed in a host cell. Overexpression of the proteins of the present invention can be effected in several ways. It can be caused by transforming a host cell with a gene coding for a protein of the invention. Alternatively, another method for effecting overexpression is to provide a stronger promoter in front of and regulating the expression of said gene. This can be achieved by use of a strong heterologous promoter or by providing mutations in the endogenous promoter. An increased expression of the protein can also be caused by removing possible inhibiting regulatory proteins, e.g. that inhibit the expression of such proteins. The person skilled in the art will know other ways of increasing the activity of the above mentioned starch active proteins.
In another aspect of the invention, host cells overexpressing at least one of the above mentioned nucleotide sequences, encoding at least one lignocellulose or (hemi-)cellulose active protein of the invention, are produced and used, for production of said protein(s).
Host cells used in the invention are preferably cells of filamentous fungi, yeasts and/or bacteria, such as, but not limited to, Aspergillus sp., such as the fungi A. terreus, A. itaconicus and A. niger, Aspergillus nidulans, Aspergillus oryzae or Aspergillus fuminagates, Trichoderma, Penicillium Chrysosporium, Ustilago zeae, Ustilago maydis, Ustilago sp., Candida sp., Yarrowia lipolytica, Rhodotorula sp. and Pseudozyma antarctica , the bacterium E. coli and the yeast Saccharomyces cerevisiae . Especially preferred are host cells that also produce one or more lignocellulose degrading enzymes, such as (hemi)cellulase, xylanase or pectinase.
Recombinant host cells described above can be obtained using methods known in the art for providing cells with recombinant nucleic acids. These include transformation, transconjugation, transfection or electroporation of a host cell with a suitable plasmid (also referred to as vector) comprising the nucleic acid construct of interest operationally coupled to a promoter sequence to drive expression. Host cells of the invention are preferably transformed with a nucleic acid construct as further defined below and may comprise a single but preferably comprises multiple copies of the nucleic acid construct. The nucleic acid construct may be maintained episomally and thus comprise a sequence for autonomous replication, such as an ARS sequence. Suitable episomal nucleic acid constructs may e.g. be based on the yeast 2μ or pKD1 (Fleer et al., 1991, Biotechnology 9: 968-975) plasmids. Preferably, however, the nucleic acid construct is integrated in one or more copies into the genome of the host cell. Integration into the host cell's genome may occur at random by illegitimate recombination but preferably the nucleic acid construct is integrated into the host cell's genome by homologous recombination as is well known in the art of fungal molecular genetics (see e.g. WO 90/14423, EP-A-0 481 008, EP-A-0 635 574 and U.S. Pat. No. 6,265,186). Most preferably for homologous recombination the ku70Δ/ku80Δ technique is used as described for instance in WO 02/052026.
Transformation of host cells with the nucleic acid constructs of the invention and additional genetic modification of the fungal host cells of the invention as described above may be carried out by methods well known in the art. Such methods are e.g. known from standard handbooks, such as Sambrook and Russel (2001) “Molecular Cloning: A Laboratory Manual (3rd edition), Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, or F. Ausubel et al, eds., “Current protocols in molecular biology”, Green Publishing and Wiley Interscience, New York (1987). Methods for transformation and genetic modification of fungal host cells are known from e.g. EP-A-0 635 574, WO 98/46772, WO 99/60102 and WO 00/37671.
In another aspect the invention relates to a vector comprising a nucleotide sequence encoding a starch active protein as defined above and usable for transformation of a host cell as defined above. In the nucleic acid construct, the coding nucleotide sequences preferably is/are operably linked to a promoter for control and initiation of transcription of the nucleotide sequence in a host cell as defined below. The promoter preferably is capable of causing sufficient expression of the starch active protein described above, in the host cell. Promoters useful in the nucleic acid constructs of the invention include the promoter that in nature provides for expression of the coding genes. Further, both constitutive and inducible natural promoters as well as engineered promoters can be used. Promoters suitable to drive expression of the genes in the hosts of the invention include e.g. promoters from glycolytic genes (e.g. from a glyceraldehyde-3-phosphate dehydrogenase gene), ribosomal protein encoding gene promoters, alcohol dehydrogenase promoters (ADH1, ADH4, and the like), promoters from genes encoding amylo- or cellulolytic enzymes (glucoamylase, TAKA-amylase and cellobiohydrolase). Other promoters, both constitutive and inducible and enhancers or upstream activating sequences will be known to those of skill in the art. The promoters used in the nucleic acid constructs of the present invention may be modified, if desired, to affect their control characteristics. Preferably, the promoter used in the nucleic acid construct for expression of the genes is homologous to the host cell in which genes are expressed.
In the nucleic acid construct, the 3′-end of the coding nucleotide acid sequence(s) preferably is/are operably linked to a transcription terminator sequence. Preferably the terminator sequence is operable in a host cell of choice. In any case the choice of the terminator is not critical; it may e.g. be from any fungal gene, although terminators may sometimes work if from a non-fungal, eukaryotic, gene. The transcription termination sequence further preferably comprises a polyadenylation signal.
Optionally, a selectable marker may be present in the nucleic acid construct. As used herein, the term “marker” refers to a gene encoding a trait or a phenotype which permits the selection of, or the screening for, a host cell containing the marker. A variety of selectable marker genes are available for use in the transformation of fungi. Suitable markers include auxotrophic marker genes involved in amino acid or nucleotide metabolism, such as e.g. genes encoding ornithine-transcarbamylases (argB), orotidine-5′-decarboxylases (pyrG, URA3) or glutamine-amido-transferase indoleglycerol-phosphate-synthase phosphoribosyl-anthranilate isomerases (trpC), or involved in carbon or nitrogen metabolism, such e.g. niaD or facA, and antibiotic resistance markers such as genes providing resistance against phleomycin, bleomycin or neomycin (G418). Preferably, bidirectional selection markers are used for which both a positive and a negative genetic selection is possible. Examples of such bidirectional markers are the pyrG (URA3), facA and amdS genes. Due to their bidirectionality these markers can be deleted from transformed filamentous fungus while leaving the introduced recombinant DNA molecule in place, in order to obtain fungi that do not contain selectable markers. This essence of this MARKER GENE FREE™ transformation technology is disclosed in EP-A-0 635 574, which is herein incorporated by reference. Of these selectable markers the use of dominant and bidirectional selectable markers such as acetamidase genes like the amdS genes of A. nidulans, A. niger and P. chrysogenum is most preferred. In addition to their bidirectionality these markers provide the advantage that they are dominant selectable markers that, the use of which does not require mutant (auxotrophic) strains, but which can be used directly in wild type strains.
Optional further elements that may be present in the nucleic acid constructs of the invention include, but are not limited to, one or more leader sequences, enhancers, integration factors, and/or reporter genes, intron sequences, centromers, telomers and/or matrix attachment (MAR) sequences. The nucleic acid constructs of the invention may further comprise a sequence for autonomous replication, such as an ARS sequence. Suitable episomal nucleic acid constructs may e.g. be based on the yeast 2μ or pKD1 (Fleer et al., 1991, Biotechnology 9: 968-975) plasmids. Alternatively the nucleic acid construct may comprise sequences for integration, preferably by homologous recombination (see e.g. WO98/46772). Such sequences may thus be sequences homologous to the target site for integration in the host cell's genome. The nucleic acid constructs of the invention can be provided in a manner known per se, which generally involves techniques such as restricting and linking nucleic acids/nucleic acid sequences, for which reference is made to the standard handbooks, such as Sambrook and Russel (2001) “Molecular Cloning: A Laboratory Manual (3rd edition), Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, or F. Ausubel et al, eds., “Current protocols in molecular biology”, Green Publishing and Wiley Interscience, New York (1987).
In a further aspect the invention relates to fermentation processes in which the transformed host cells of the invention are used for the conversion of a lignocellulose or (hemi-)cellulose substrate. A preferred fermentation process is an aerobic fermentation process. The fermentation process may either be a submerged or a solid state fermentation process.
In a solid state fermentation process (sometimes referred to as semi-solid state fermentation) the transformed host cells are fermenting on a solid medium that provides anchorage points for the fungus in the absence of any freely flowing substance. The amount of water in the solid medium can be any amount of water. For example, the solid medium could be almost dry, or it could be slushy. A person skilled in the art knows that the terms “solid state fermentation” and “semi-solid state fermentation” are interchangeable. A wide variety of solid state fermentation devices have previously been described (for review see, Larroche et al., “Special Transformation Processes Using Fungal Spores and Immobilized Cells”, Adv. Biochem. Eng. Biotech., (1997), Vol 55, pp. 179; Roussos et al., “Zymotis: A large Scale Solid State Fermenter”, Applied Biochemistry and Biotechnology, (1993), Vol. 42, pp. 37-52; Smits et al., “Solid-State Fermentation—A Mini Review, 1998), Agro-Food-Industry Hi-Tech, March/April, pp. 29-36). These devices fall within two categories, those categories being static systems and agitated systems. In static systems, the solid media is stationary throughout the fermentation process. Examples of static systems used for solid state fermentation include flasks, petri dishes, trays, fixed bed columns, and ovens. Agitated systems provide a means for mixing the solid media during the fermentation process. One example of an agitated system is a rotating drum (Larroche et al., supra). In a submerged fermentation process on the other hand, the transformed fungal host cells are fermenting while being submerged in a liquid medium, usually in a stirred tank fermenter as are well known in the art, although also other types of fermenters such as e.g. airlift-type fermenters may also be applied (see e.g. U.S. Pat. No. 6,746,862).
Preferred in the invention is a submerged fermentation process, which is performed fed-batch. This means that there is a continuous input of feed containing a carbon source and/or other relevant nutrients in order to improve protein yields. The input of the feed can, for example, be at a constant rate or when the concentration of a specific substrate or fermentation parameter falls below some set point.
Further comprised in the invention is the use of an active protein according to the invention for modification of raw carbohydrate substrate (lignocellulose or (hemi-)cellulose). Preferably said use encompasses hydrolysis of the carbohydrate substrate. Also included in this use is the modification of the substrate by the active protein, thereby allowing other carbohydrate substrate hydrolyzing enzymes to approach the substrate more easily and exert their function in resulting in improved hydrolysis.
EXAMPLES
Examples
Expression of Genes Encoding Lignocellulose and/or (Hemi-)Cellulose Active Proteins in Aspergillus niger
In order to unambiguously establish that the discovered proteins aid to the increased saccharification of beta-glucan containing plant derived substrates, a host naturally not expressing these genes was (co-)transformed with the respective genes under control of a suitable promoter.
(I) Gene Design
Synthetic (codon-optimized) full length gene copies from two selected Podospora anserine genes were generated
CAP 61309: CBM1 Protein
A synthetic gene was designed by back translation from the reannotated protein for further reference called CAP61309, originally deposited under number XM — 001903499.1, with codon bias for Aspergillus niger . The start codon of the protein is part of a BspHI site, so as to fit to the NcoI cloning site of vector pAN52-5doubleNotamdS. At the 3′ end of the gene two consecutive stop codons were introduced, followed by a BamHI cloning site.
KpnI BspHI 1 GGTACCTC ATG AAGTTCCACGTCCTCTCCGGCCTCGTCGCCCAGGTCCTCTCCGTTAGCG 1 M K F H V L S G L V A Q V L S V S 61 CCGGCACCATTCTCTGGGATGGCCGCTTCAACGATATGACCTCCTCCGCCGATCTCAACA 18 A G T I L W D G R F N D M T S S A D L N 121 AGTGGTCCTGGGGCAACCAGGTCGGCCCCTACCAGTACTATATCCACGGCTCCTCCCCGG 38 K W S W G N Q V G P Y Q Y Y I H G S S P 181 TGTCCGCCTACGTCAACCTGTCCCCCGATTACAAGAACCCCGCCGATACCGGCTCCCGCC 58 V S A Y V N L S P D Y K N P A D T G S R 241 AGGGCGCCAAGATCACCCTCGATAACACCGCCTACTGGAACGGCCAGAACATGCGCCGCA 78 Q G A K I T L D N T A Y W N G Q N M R R 301 CCGAGCTGATCCCCCAGACTACCGCCGCTATCAACCAGGGCAAGGTCTACTACCACTTCA 98 T E L I P Q T T A A I N Q G K V Y Y H F 361 GCCTCATGCGCAAGGATATCAACGCCCCTGCCACCACCCGCGAGCACCAGATCGCTTTCT 118 S L M R K D I N A P A T T R E H Q I A F 421 TCGAGTCCCACTTCACCGAGCTGAAGTCCGGCTGGCTCTCCGGCGCTCCCGGCATCTCCG 138 F E S H F T E L K S G W L S G A P G I S 481 ATACCCTGCTCCGCTGGTGCGTCGGCGGCCAGACCCAGTGGTCCGTCGAGTGGGCCGCTG 158 D T L L R W C V G G Q T Q W S V E W A A 541 ATGTCTGGCACAACGTCGCCTACGAGATCGATTTCGCCGCTGGCACCGTCGGTTTCTGGC 178 D V W H N V A Y E I D F A A G T V G F W 601 ACTCCACCGGCTCCGACCCCCTCACCCGCAAGGTCGCCCCCGTCAAGACCAGCACCAGCT 198 H S T G S D P L T R K V A P V K T S T S 661 CCAACGGTGCTGACTGGCACGTCGGCGTCCTCGAGCTGCCCCGCTCCGGCTACCCCGATT 218 S N G A D W H V G V L E L P R S G Y P D 721 CCAACGAGGATTTCTACTGGTCCGGCGTCTACATCGAGTCCGGCTCCCTCACCACCTCCG 238 S N E D F Y W S G V Y I E S G S L T T S 781 TCGCTGGTCCTGGCCAGCCCATCCCTGGTGACGGCGGCTCCTCCAGCTCCAGCTCCTCCT 258 V A G P G Q P I P G D G G S S S S S S S 841 CCTCCGTCCCTTCCTCCACCTCCACCCGCGTGTCCAGCACCTCCACCCCTGCCCCCGTGT 278 S S V P S S T S T R V S S T S T P A P V 901 CCTCCACAACCCTCGTTACCAGCACCACTCGCGTCAGCTCCACCTCTACCTCCAGCGCCG 298 S S T T L V T S T T R V S S T S T S S A 961 CTCCCGTCCAGACCACCCCCTCCGGCTGCACCGCTGGCCAGTACGCCCAGTGCGACGGCA 318 A P V Q T T P S G C T A G Q Y A Q C D G 1021 TCGGCTTCTCCGGCTGCAAGACCTGCGCCGCTCCCTACACCTGCAAGTACGGCAACGATT 338 I G F S G C K T C A A P Y T C K Y G N D BamHI SacI 1081 GGTACTCCCAGTGCCTC TGATGA GGATCCGAGCTC (SEQ ID NO: 12) 358 W Y S Q C L * * (SEQ ID NO: 13)
CAP 68330 DUF1996-CBM1 Protein
A synthetic gene was designed by back translation from the reannotated protein, for further reference called CAP68330, deposited originally under number XM — 001907623.1, with codon bias for Aspergillus niger . Since the start of the coding sequence thus obtained (MHSRN . . . ) can not be comprised in a restriction enzyme recognition site that is compatible with NcoI (that serves as the 5′ cloning site in vector pAN52-5doubleNotamdS) it was decided to include at the 5′ end of the synthetic gene the 3′ end of the Aspergillus specific gpdA promoter sequence (from SalI to NcoI). SalI is the nearest unique site upstream of NcoI in vector pAN52-5doubleNotamdS. At the 3′ end of the gene two consecutive stop codons were introduced, followed by a BamHI cloning site.
KpnI SalI 1 GGTACCGTCGACCCATCCGGTGCTCTGCACTCGACCTGCTGAGGTCCCTCAGTCCCTGGT 61 AGGCAGCTTTGCCCCGTCTGTCCGCCCGGTGTGTCGGCGGGGTTGACAAGGTCGTTGCGT 121 CAGTCCAACATTTGTTGCCATATTTTCCTGCTCTCCCCACCAGCTGCTCTTTTCTTTTCT 181 CTTTCTTTTCCCATCTTCAGTATATTCATCTTCCCATCCAAGAACCTTTATTTCCCCTAA 241 GTAAGTACTTTGCTACATCCATACTCCATCCTTCCCATCCCTTATTCCTTTGAACCTTTC 301 AGTTCGAGCTTTCCCACTTCATCGCAGCTTGACTAACAGCTACCCCGCTTGAGCAGACAT 361 CACC ATG CACTCCCGCAACGTCCTCGCCGCTGCCGTCGCTCTCGCTGGCGCCCCTTCCGT 1 M H S R N V L A A A V A L A G A P S V 421 CCACGCCGTCCTCCGCTTCAGCTGCTCCGAGCTGGTCACCGAGCGCCTCGACCCCCTCGT 20 H A V L R F S C S E L V T E R L D P L V 481 GTTCCCTGGCGCCATGCAGTCCCCCCACGTCCACCAGATCGTCGGCGGCAACATGTTCAA 40 F P G A M Q S P H V H Q I V G G N M F N 541 CGTCACTATGGACCCCAACCGCCACAACATCGGCGAGGAAGCCACCTGCACCACCTGTAC 60 V T M D P N R H N I G E E A T C T T C T 601 CTTCTCCGAGGATTTCTCCAACTACTGGACCGCCATCCTCTACTTCCGCGCTCGCAACGG 80 F S E D F S N Y W T A I L Y F R A R N G 661 CACCCTCATCCGCGTCCCCCAGCGCCCCAATATCGATTTCGATGGCGCTCGCGGCGGTGG 100 T L I R V P Q R P N I D F D G A R G G G 721 CATGACCGTCTACTACACCGCCACCTACCAGAACCACAAGCCCACCGCCTTCCAGCCCGG 120 M T V Y Y T A T Y Q N H K P T A F Q P G 781 CTTCCGCATGATCGTCGGCAACCCCATGTACCGCACCCAGGCCGAGGCTTCCCGCTACCG 140 F R M I V G N P M Y R T Q A E A S R Y R 841 CCAGATGACCTTCACCTGCCTCGAAACCCTCTCCACCCGCACCGGCGAAACCACCGAGAT 160 Q M T F T C L E T L S T R T G E T T E M 901 GCCCAAGCAGCCCTGCCGCGAGGGCATCATGTCCAACGTCCGCTTCCCCACCTGCTGGGA 180 P K Q P C R E G I M S N V R F P T C W D 961 TGGCAAGACCCTCGATCCCCCCGATCACTCCTCCCACGTCGCCTACCCGTCCTCCGGCAC 200 G K T L D P P D H S S H V A Y P S S G T 1021 CTTCGAGTCCGGCGGTCCCTGCCCTGCTTCCCACCCTGTCCGCATCCCCCAGCTGTTCTA 220 F E S G G P C P A S H P V R I P Q L F Y 1081 CGAGGTCCTCTGGGATACCCGCCGCTTCAACGATCGCTCCCTCTGGCCCGAGGATGGCTC 240 E V L W D T R R F N D R S L W P E D G S 1141 CCAGCCCTTCGTCTGGTCCTACGGCGATTACACCGGCTACGGCACCCACGGCGATTACGT 260 Q P F V W S Y G D Y T G Y G T H G D Y V 1201 GTTCGGCTGGAAGGGCGATTCCCTCCAGCGCGCTATGGATGCCAACTGCGATTTCTACTG 280 F G W K G D S L Q R A M D A N C D F Y C 1261 CCCCCAGCTCAAGACCCAGTCTATCGCCACCGGCAACCAGTGCCGCCAGAACCAGAAGGT 300 P Q L K T Q S I A T G N Q C R Q N Q K V 1321 CGCCGAGAACATCGATGGCCCCTTCGATCGCCTCCCTGGTAACGTCGAGATCACCGGCCC 320 A E N I D G P F D R L P G N V E I T G P 1381 TCAGCCTGGCGCCTCCAACCCCAACCCCGGCAATGGCGGTGGCTCTACTCAGACTCCTGT 360 Q P G A S N P N P G N G G G S T Q T P V 1441 CCAGCCCACCCCCGTCCCTAACCCTGGCAACGGTGGCGGCTGCTCCGTCCAAAAGTGGGG 380 Q P T P V P N P G N G G G C S V Q K W G 1501 CCAGTGCGGCGGTCAGGGCTGGTCCGGTTGCACCGTCTGCGCCTCCGGCTCCACCTGCCG 400 Q C G G Q G W S G C T V C A S G S T C R BamHI SacI 1561 CGCTCAGAACCAGTGGTACTCCCAGTGCCTC TGATGA GGATCCGAGCTC (SEQ ID NO: 14) 420 A Q N Q W Y S Q C L * * (SEQ ID NO: 15)
(II) Overexpression of Synthetic Genes Copies
The synthetic gene copies were inserted in an expression vector based on the A. nidulans gpdA promoter, carrying also the amdS selection marker. This Aspergillus expression vector pAN52-4-amdSdoubleNotI was derived by cloning the Aspergillus selection marker amdS and an additional NotI cloning site into the Aspergillus expression vector pAN52-4 (EMBL accession #Z32699).
The resulting expression vectors were introduced in a protease deficient A. niger host strain AB1.13 (Punt et al., 2008). AmdS+ transformants were selected using acrylamide selection.
(III) Protocol MicroTiterPlate Cultivation of Aspergillus
For cultivation of the strains, standard round bottom 96-well microtiter plates (Corning #3799) were used using a Multitron shaker (Infors) designed for the use with MTP.
Volume: 200 μl MM Aspergillus medium per well (MM+casamino acids+vitamins)
Each separate well was inoculated with spores (from colonies on plates), using toothpicks. MTP was incubated for 48 hours at 33° C., 850 rpm Good growth was confirmed by visual inspection MTP was centrifuged 10 min 3500 rpm to allow biomass separation.
(IV) DNS-CMCase Method in MTP
Reagents:
Carboxymethyl cellulose sodium salt (CMC), Avicel or non soluble cellulose 3-5, dinitrosalicylic acid, sodium salt (DNS)
Potassium/sodium tartrate (tetrahydrate)
Sodium hydroxide
Glacial acetic acid
Reagent Preparation Protocol:
1. 0.05 M NaAc, pH 4.8: Add 2.85 ml of glacial acetic acid to 900 ml of distilled water, adjust the pH to 4.8 with 50% Sodium hydroxide. Bring to total volume of one liter with distilled water.
2. 1% CMC substrate solution: Add 1 gm CMC to 99 ml NaAc buffer, pH4.8. Keep at 4° C. for at least 1 hour before using. The solution is stable for 3 days at 4° C.
3. 10.67% (w/v) Sodium hydroxide solution: add 32 gm of sodium hydroxide pellets to 300 ml of distilled water.
4.1% 3-5, dinitrosalicylic acid, sodium salt (DNS): suspend 2 gram of DNS in 100 ml of distilled water and gradually add 30 ml of the 10.67% sodium hydroxide solution while mixing. Warm the suspension in water bath set at 50° C. until the solution is clear. Gradually add 60 gm of potassium/sodium artrate (tetrahydrate) to the solution with continuous mixing. Dilute the solution to 200 ml with distilled water. The solution is stable for 2 months. The solution must be clear when used.
Assay Procedure Protocol:
Making Standard Curve
Choose a lot of cellulase preparation as a standard
Standard curve: dilute the standard using acetate buffer such that the absorbance (at 540 nm) is between 0.1 and 0.5.
Blank solution: use acetate buffer 0.05M NaAc, pH 4.8 as a blank solution
1. Mix 10 μl of each sample with 90 μl buffer 0.05M NaAc, pH 4.8 using a 1.1 ml volume, 96-deep well Micro Titer Plate (Oxygen; cat. no. P-DW-11-C). At the same time prepare the standard in the same MTP in duplicate. 2. pre-equilibrate the CMC substrate in a (plastic test plate) in a water bath set at 50° C. for 5 minutes 3. At 20 second intervals, add 100 μl of the CMC substrate (pre-equilibrated at 50° C.) to the enzyme dilution using a multichannel pipette (12 channel). Mix and incubate at 50° C. for 10 minutes. (Incubation time can be adjusted depending on activity level of parental strain). 4. at the same time interval as in step 3, add 300 μl of DNS solution and mix 5. boil the reaction mixture+DNS for exactly 5 minutes by placing the test microtiterplate in a boiling water bath. Cover the tops to prevent evaporation during boiling. As a blanc for remaining glucose in the samples prior to incubation also a duplicate MTP is included in which the reaction is terminated by boiling directly upon addition of the cellulase substrate. All samples, standard and blanks should be boiled together. After boiling, cool the plate in an ice bath 6. Measure the absorbance of the enzyme samples, standard and blancs at 540 nm in a Tecan Infinite 200 microplate reader
(Measurement range 0-3 OD)
(V) Cellulose Binding Assay
For qualitative evaluation of cellulose binding capacity the following assay was used:
Incubate 1 ml fermentation samples 1 hour with 10 mg Avicel at 4° C. with gentle mixing. Centrifuge 10 min, 3000 g Wash the cellulose once with 0.5 ml of 50 mM sodium phosphate pH 7.0 Elute the bound protein by boiling the cellulose pellet for 10 min in 50 μl of 10% SDS Subject 20 μl to SDS-PAGE gel.
(VI) Transformant Screening
For a number of transformants obtained from each of the two expression vectors described MTP cultures were performed.
For both the CAP68330 and CAP61309 transformants the culture supernatant was used in a DNS-CMCase activity assay to identify the transformants with the highest activity level. For each expression vector transformants with increased CMCase activity were identified
(VII) Fermentation
Transformants selected from the transformant screening were cultivated in standard fed-batch fermentation and the lignocellulose and/or (hemi-)cellulose active proteins produced were analyzed in various cellulase related assays
VIII Analysis of A. niger Transformants In Controlled Fermentation
Medium samples during the various fermentations were taken and samples at the end of fermentation (around 70-100 h) were analyzed for cellulase related activity using both soluble (CMC) and non-soluble (non-soluble cellulose, avicel) cellulase substrates. In addition, as the produced CAP68330 or CAP61309 proteins could also be non-enzymatic accessory proteins potentiating cellulase activity also an assay was performed in the presence of a fixed amount of a commercial cellulase preparation and samples from the culture fluid of the CAP68330 and CAP61309 strains was added
Results of these assays are shown in the table below
Substrate
non-soluble cellulose
Avicel
Strains
CMC
−cellulase
+cellulase
−cellulase
+cellulase
Blanc
ND
ND
0.07
ND
1.00
cap68330#4
0.25
0.15
0.26
1.92
2.06
cap61309#8
0.22
0.21
0.23
1.90
2.09
CONTROL
0.31
0.17
0.21
1.53
1.86
As shown in the table the activity towards CMC and non-soluble cellulose was not increased compared to the control strain not expressing CAP68330 or CAP61309 protein. The background activity level observed in the Control strain originates from native Aspergillus proteins releasing reducing sugar equivalents from the various substrates.
In contrast as shown in the table, with Avicel as a substrate the cellulase-related activity was higher for the CAP68330/61309 strains than for the control, indicating the presence of cellulase and/or cellulase enhancing activity due to the presence of the CAP68330 or CAP61309 protein.
IX SDS PAGE and Cellulose Binding Analysis
In addition to activity assays also SDS PAGE was carried out with concentrated fermentation samples. In addition cellulose binding analysis followed by SDS PAGE analysis was carried out. As shown in FIG. 1 for CAP61309 protein an additional protein band was observed in SDS PAGE. This band was also identified by binding to Avicel | Methods to digest carbohydrates, especially lignocelluloses and hemicelluloses, using fungal proteins previously not recognized as having this activity are described. | 2 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application claims the benefit of and priority to U.S. Provisional Application Ser. No. 60/620,068, filed on Oct. 18, 2004, the entire contents of which being incorporated herein by reference.
BACKGROUND
[0002] 1. Technical Field
[0003] The present disclosure relates to surgical fasteners and more particularly to surgical fasteners coated with wound treatment materials.
[0004] 2. Description of Related Art
[0005] Generally, coatings for medical devices are useful to create a water absorbent and lubricious coating for surgical instruments, for in-dwelling biomaterials such as stents, screws and internal splints, and for tubing, catheters, wire guides, and the like. Such coatings minimize the trauma of contact of the medical device with tissues and biological fluids. In particular, coatings have been used to provide a slippery and lubricious coating for reducing the coefficient of friction of a surface of a medical device to facilitate movement and maneuverability of the device. Lubricious coatings made from hydrophilic polymers are well-known in the art.
[0006] Medical devices such as surgical fasteners and staples have replaced suturing when joining or anastomosing various body structures, such as, for example, the bowel or bronchus. The surgical stapling devices employed to apply these staples are generally designed to simultaneously cut and seal an extended segment of tissue in a patient, thus vastly reducing the time and risks of such procedures.
[0007] Linear or annular surgical stapling devices are employed by surgeons to sequentially or simultaneously apply one or more linear rows of surgical fasteners, e.g., staples or two-part fasteners, to body tissue for the purpose of joining segments of body tissue together and/or for the creation of anastomosis. Linear surgical stapling devices generally include a pair of jaws or finger-like structures between which body tissue to be joined is placed. When the surgical stapling device is actuated and/or “fired,” firing bars move longitudinally and contact staple drive members in one of the jaws, and surgical staples are pushed through the body tissue and into/against an anvil in the opposite jaw thereby crimping the staples closed. A knife blade may be provided to cut between the rows/lines of staples. Examples of such linear surgical stapling devices are Models “GIA™”, “Endo GIA™” and “Premium Multi-fire TA™” instruments available from United States Surgical, a Division of Tyco Health-Care Group, LP, Norwalk, CT and disclosed in, inter alia, U.S. Pat. No. 5,465,896 to Allen et al., U.S. Pat. No. 6,330,965 to Milliman et al., and U.S. Pat. No. 6,817,508 to Racenet et al., the entire contents of each of which are incorporated herein by reference.
[0008] Annular surgical stapling devices generally include an annular staple cartridge assembly including a plurality of annular rows of staples, typically two, an anvil assembly operatively associated with the annular cartridge assembly, and an annular blade disposed internal of the rows of staples.
[0009] Another type of surgical stapler is an end-to-end anastomosis stapler. An example of such a device is a Model “EEA™” instrument available from United States Surgical, a Division of Tyco Health-Care Group, LP, Norwalk, Conn. and disclosed in, inter alia, U.S. Pat. No. 5,392,979 to Green et al., the entire contents of which is incorporated herein by reference. In general, an end-to-end anastomosis stapler typically places an array of staples into the approximated sections of a patient's bowels or other tubular organs. The resulting anastomosis contains an inverted section of bowel which contains numerous “B” shaped staples to maintain a secure connection between the approximated sections of bowel.
[0010] In addition to the use of surgical staples, sealants, e.g., biological sealants, can be applied to the surgical site to guard against leakage. Typically, the biological sealants are manually applied to the outer surface of the staple line by a physician by spraying on, brushing on, swabbing on, or any combinations thereof. This manual application of biological sealant can lead to non-uniformity of the thickness of sealant across the staple line and/or omitting a portion of the intended coverage area due to inability to see or reach the desired location.
[0011] A need exists for surgical fasteners and the like for delivering wound treatment material to a target surgical site without adding additional steps or complications to the surgical procedure.
SUMMARY
[0012] The present disclosure relates to surgical fasteners and more particularly to surgical fasteners coated with wound treatment materials.
[0013] According to an aspect of the present disclosure, a surgical fastener for use in combination with a surgical fastener applying apparatus is provided. The surgical fastener includes a pair of legs; a crown interconnecting the pair of legs; and a wound treatment material coating at least a portion of the legs and/or crown.
[0014] The wound treatment material may be at least one of an adhesive, a sealant, a hemostat, and a medicament. In an embodiment, the surgical fastener is a staple. In another embodiment, the surgical fastener is a two-part fastener.
[0015] The legs and crown of the surgical fastener may be fabricated from at least one of a non-absorbable and a bio-absorbable material. It is envisioned that the non-absorbable material is at least one of stainless steel and titanium. The bio-absorbable material may be at least one of a homopolymers, copolymers, and a blend of monomers selected from the group consisting of glycolide, glycolic acid, lactide, lactic acid, p-dioxanone, α-caprolactone and trimethylene carbonate. The bio-absorbable material may also be at least one of Polyglycolic Acid (PGA) and Polylactic Acid (PLA).
[0016] The wound treatment material may be a sealant selected from the group consisting of acrylate, methacrylate functional hydrogels in the presence of a biocompatible photoinitiator, alkyl-cyanoacrylates, isocyanate functional macromers with or without amine functional macromers, succinimidyl ester functional macromers with amine or sulfhydryl functional macromers, epoxy functional macromers with amine functional macromers, mixtures of proteins or polypeptides in the presence of aldehyde crosslinkers, Genipin, water-soluble carbodiimides, and anionic polysaccharides in the presence of polyvalent cations.
[0017] The wound treatment material may also be a sealant selected from the group consisting of isocyanate terminated hydrophilic urethane prepolymers derived from organic polyisocyanates and oxyethylene-based diols or polyols; alpha-cyanoacrylate based adhesives; alkyl ester based cyanoacrylate adhesives; adhesives based on biocompatible cross-linked polymers formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and cross-linking in situ; two part adhesive systems including those based upon polyalkylene oxide backbones substituted with one or more isocyanate groups in combination with bioabsorbable diamine compounds, or polyalkylene oxide backbones substituted with one or more amine groups in combination with bioabsorbable diisoycanate compounds; and isocyanate terminated hydrophilic urethane prepolymers derived from aromatic diisocyanates and polyols.
[0018] It is envisioned that the wound treatment material is a hemostat selected from the group consisting of fibrin-based, collagen-based, oxidized regenerated cellulose-based and gelatin-based topical hemostats.
[0019] It is contemplated that the wound treatment material is a medicament selected from the group consisting of drugs, enzymes, growth factors, peptides, proteins, pigments, dyes, diagnostic agents or hemostasis agents, monoclonal antibodies, or any other pharmaceutical used in the prevention of stenosis.
[0020] In an embodiment, the wound treatment material may be impregnated into the legs and the crown. In another embodiment, the wound treatment material completely coats the legs and the crown.
[0021] It is envisioned that each leg includes a sharpened distal end. It is further envisioned that the crown is linear or non-linear.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a perspective view of a surgical fastener in accordance with an embodiment of the present disclosure;
[0023] FIG. 2 is a longitudinal cross-sectional view of the surgical fastener of FIG. 1 ;
[0024] FIG. 3 is a longitudinal cross-sectional view of a surgical fastener according to another embodiment of the present disclosure;
[0025] FIG. 4 is a longitudinal cross-sectional view of a surgical fastener according to yet another embodiment of the present disclosure; and
[0026] FIG. 5 is a perspective view of an exemplary two-part fastener constructed in accordance with the present disclosure.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0027] Embodiments of the presently disclosed surgical fasteners will now be described in detail with reference to the drawing figures wherein like reference numerals identify similar or identical elements. As used herein and as is traditional, the term “distal” refers to that portion which is farthest from the user while the term “proximal” refers to that portion which is closest to the user.
[0028] With reference to FIGS. 1 and 2 , a surgical fastener, in the form of a surgical staple, is generally shown as 100 . Surgical staples of the present disclosure typically include any metallic staple used to join together tissue parts and/or adjacent tissues. Surgical staples 100 may be made of metal, such as, for example, stainless steel or titanium, or any other material known by one having skill in the art. For example, surgical staples 100 may also be fabricated from bio-absorbable material or the like.
[0029] Bio-absorbable materials used for surgical staples 100 include, and are not limited to, those fabricated from homopolymers, copolymers or blends obtained from one or more monomers selected from the group consisting of glycolide, glycolic acid, lactide, lactic acid, p-dioxanone, α-caprolactone and trimethylene carbonate. Other bio-absorbable materials include and are not limited to, for example, Polyglycolic Acid (PGA) and Polylactic Acid (PLA).
[0030] With continued reference to FIGS. 1 and 2 , surgical staple 100 includes a pair of legs 102 , 104 which are interconnected to one another by a crown or backspan 106 extending between first ends 102 a, 104 a, respectively, thereof. As seen in FIGS. 1 and 2 , crown 106 is substantially perpendicular to legs 102 , 104 . However, it is envisioned that crown 106 may take on any shape and/or form as needed and/or desired and may have any orientation relative to legs 102 , 104 . For example, crown 106 may include two sections which extend angularly from legs 102 , 104 and are connected at an apex (not shown).
[0031] As seen in FIGS. 1 and 2 , respective distal ends 102 b, 104 b of legs 102 , 104 are sharpened to facilitate penetration of legs 102 , 104 into tissue or the like.
[0032] In accordance with the present disclosure, surgical staple 100 is coated with a wound treatment material “W”. It is envisioned that wound treatment material “W” may be applied to the entirety of surgical staple 100 (as seen in FIGS. 1 and 2 ), or may be applied to any specific area of surgical staple 100 that is to come into contact with tissue of the like. For example, wound treatment material “W” may be applied solely to legs 102 , 104 (see FIG. 3 ); solely to one of legs 102 , 104 (not shown); solely to crown 106 (not shown); or any portion thereof. It is further envisioned that wound treatment material “W” may be impregnated into legs 102 , 104 and crown 106 of surgical staple 100 , as seen in FIG. 4 .
[0033] In one embodiment, surgical staples 100 may be fabricated from a bio-absorbable material which is desirably impregnated with wound treatment material “W”. Accordingly, in use, the wound treatment material component of surgical staples 100 may function to retard any bleeding which may occur from the tissue, in the manner of a sealant, and to secure the approximated tissue together, in the manner of an adhesive. The bio-absorbability of surgical staples 100 allows for the at least a portion of surgical staples 100 to be absorbed into the body after a predetermined amount of time. For example, surgical staples 100 may remain in place in the body for approximately 2-3 weeks in order for the anastomosis to sufficiently heal prior to surgical staples 100 being absorbed into the body.
[0034] As mentioned above and as shown in FIG. 3 , it is envisioned that surgical staples 100 may be impregnated with a wound treatment material “W” which is a pre-cured adhesive or sealant. The pre-cured sealant or adhesive will react with the moisture and/or heat of the body tissue to thereby activate the sealing and/or adhesive properties of the sealant or adhesive. It is envisioned that the pre-cured sealant or adhesive may be a hydro-gel or the like.
[0035] It is contemplated that the wound treatment material “W” is any material for joining, healing, sealing or otherwise treating tissue. In a preferred embodiment, the wound treatment material is a bio-compatible sealant, including, and not limited, to sealants which cure upon tissue contact, sealants which cure upon exposure to ultraviolet (UV) light, sealants which are two-part systems which are kept isolated from one another and are combined or any combinations thereof. Any known suitable adhesive may be used. In one embodiment, it is contemplated that such sealants and/or adhesives are curable. For example, sealants may have a cure time of from about 10 to 15 seconds may be used. In preferred embodiments, the sealant and/or adhesive is a bioabsorbable and/or bio-resorbable material. In another embodiment, it is contemplated that a sealant and/or adhesive having a cure time of about 30 seconds may be used. It is further envisioned that wound treatment material “W” may be a pre-cured adhesive or sealant.
[0036] In certain preferred embodiments, the wound treatment material “W” comprises a sealant. Such a sealant is desirably a PEG-based material. Examples of classes of materials useful as the sealant and/or adhesive include acrylate or methacrylate functional hydrogels in the presence of a biocompatible photoinitiator, alkyl-cyanoacrylates, isocyanate functional macromers with or without amine functional macromers, succinimidyl ester functional macromers with amine or sulfhydryl functional macromers, epoxy functional macromers with amine functional macromers, mixtures of proteins or polypeptides in the presence of aldehyde crosslinkers, Genipin, or water-soluble carbodiimides, anionic polysaccharides in the presence of polyvalent cations, etc.
[0037] Some specific materials which may be utilized include isocyanate terminated hydrophilic urethane prepolymers derived from organic polyisocyanates and oxyethylene-based diols or polyols, including those disclosed in U.S. Pat. Nos. 6,702,731 and 6,296,607 and U.S. Published Patent Application No. 2004/0068078; alpha-cyanoacrylate based adhesives including those disclosed in U.S. Pat. No. 6,565,840; alkyl ester based cyanoacrylate adhesives including those disclosed in U.S. Patent No. 6,620,846; adhesives based on biocompatible cross-linked polymers formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and cross-linking in situ, including those disclosed in U.S. Pat. No. 6,566,406; two part adhesive systems including those based upon polyalkylene oxide backbones substituted with one or more isocyanate groups in combination with bioabsorbable diamine compounds, or polyalkylene oxide backbones substituted with one or more amine groups in combination with bioabsorbable diisoycanate compounds as disclosed in U.S. Published Patent Application No. 2003/0032734, the contents of which are incorporated by reference herein; and isocyanate terminated hydrophilic urethane prepolymers derived from aromatic diisocyanates and polyols as disclosed in U.S. Published Patent Application No. 2004/0115229, the contents of which are incorporated by reference herein.
[0038] It is envisioned and within the scope of the present disclosure that wound treatment material “W” may include one or a combination of adhesives, hemostats, sealants, or any other tissue or wound-treating material. Surgical biocompatible wound treatment materials “W”, which may be used in accordance with the present disclosure, include adhesives whose function is to attach or hold organs, tissues or structures, sealants to prevent fluid leakage, and hemostats to halt or prevent bleeding. Examples of adhesives which can be employed include protein derived, aldehyde-based adhesive materials, for example, the commercially available albumin/glutaraldehyde materials sold under the trade designation BioGlue™ by Cryolife, Inc., and cyanoacrylate-based materials sold under the trade designations Indermil™ and Derma Bond™ by Tyco Healthcare Group, LP and Ethicon Endosurgery, Inc., respectively. Examples of sealants, which can be employed, include fibrin sealants and collagen-based and synthetic polymer-based tissue sealants. Examples of commercially available sealants are synthetic polyethylene glycol-based, hydrogel materials sold under the trade designation CoSeal™ by Cohesion Technologies and Baxter International, Inc. Examples of hemostat materials, which can be employed, include fibrin-based, collagen-based, oxidized regenerated cellulose-based and gelatin-based topical hemostats, as well as aluminum alum (i.e., ammonium alum or aluminum ammonium sulfate). Examples of commercially available hemostat materials are fibrinogen-thrombin combination materials sold under the trade designations CoStasis™ by Tyco Healthcare Group, LP, and Tisseel™ sold by Baxter International, Inc. Hemostats herein include astringents, e.g., aluminum sulfates, and coagulants. A further example of a hemostat includes “Quick Clot™”, commercially available from Z-Medica, Inc., Newington, Conn..
[0039] The medicament may include one or more medically and/or surgically useful substances such as drugs, enzymes, growth factors, peptides, proteins, dyes, pigments, diagnostic agents or hemostasis agents, monoclonal antibodies, or any other pharmaceutical used in the prevention of stenosis. The medicament may be disposed on structure 100 or impregnated into structure 100 .
[0040] Wound treatment material “W” may include visco-elastic film forming materials, cross-linking reactive agents, and energy curable adhesives. It is envisioned that wound treatment material “W”, and in particular, adhesive may be cured with the application of water and/or glycerin (1, 2, 3, -pranatetriol, also known as glycerol or glycerine) thereto. In this manner, the water and/or glycerin cure the adhesive and hydrate the wound.
[0041] It is further contemplated that wound treatment material “W” may include, for example, compositions and/or compounds which accelerate or beneficially modify the healing process when particles of the composition and/or compound are applied to or exposed to a surgical repair site. For example, the wound treatment material “W” may be a therapeutic agent which will be deposited at the repair site. The therapeutic agent can be chosen for its antimicrobial properties, capability for promoting repair or reconstruction and/or new tissue growth. For example, the wound treatment material “W” may comprise “SilvaSorb™”, commercially available from AcryMed, Inc, Portland, Oreg.. Antimicrobial agents such as broad spectrum antibiotic (gentamycin sulfate, erythromycin or derivatized glycopeptides) which are slowly released into the tissue can be applied in this manner to aid in combating clinical and sub-clinical infections in a tissue repair site. To promote repair and/or tissue growth, wound treatment material “W” may include one or several growth promoting factors, e.g., fibroblast growth factor, bone growth factor, epidermal growth factor, platelet derived growth factor, macrophage derived growth factor, alveolar derived growth factor, monocyte derived growth factor, magainin, and so forth. Some therapeutic indications are: glycerol with tissue or kidney plasminogen activator to cause thrombosis, superoxide dimutase to scavenge tissue damaging free radicals, tumor necrosis factor for cancer therapy or colony stimulating factor and interferon, interleukin-2 or other lymphokine to enhance the immune system.
[0042] It is further envisioned and within the of the present disclosure for wound treatment material “W” to include any microbial agent, analgesic, growth factor, and anti-inflammatory agent known by one having skill in the art or any combination thereof.
[0043] Those skilled in the art will recognize that the successful surface treatment of surgical staple 100 , prior to the application of wound treatment material “W”, may include pre-cleaning surgical staple 100 and controlling the moisture at the surface of surgical staple 100 in order to ensure complete and/or proper coating of surgical staple 100 . Multi-step cleaning and drying operations can therefore be used to provide a clean surface and to control moisture. Once the surface of surgical staple 100 is treated, as described above, a solution containing wound treatment material “W” is applied to the treated surgical staple 100 .
[0044] It is contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to be used in connection with linear-type surgical staplers, non-linear-type surgical stapler, annular-type surgical staples, endoscopic-type surgical staplers, skin-type surgical staplers and the like.
[0045] It is further contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to have equal length legs, un-equal length legs, a relatively short crown as compared to the length of the legs, a relatively long crown as compared to the length of the legs, a symmetrical transverse cross-sectional profile in at least one of the legs and the crown, and an asymmetrical transverse cross-sectional profile in at least one of the legs and the crown. For example, each leg and/or the crown may have a cross-sectional profile which is polygonal, such as, triangular, rectangular, hexagonal any combination thereof or the like. Moreover, each leg and/or the crown may have a cross-sectional profile which is circular, ovular or the like. It is further envisioned that the crown may be either linear of non-linear.
[0046] It is still further contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to include legs which do not lie in the same plane as one another. In other words, one leg and the crown of the surgical staple 100 define a first plane, and the other leg of the surgical staple 100 lies in a second plane which is non-coplanar, or transverse to the first plane.
[0047] As seen in FIG. 5 , a surgical fastener, in the form of a two-part fastener, is generally shown as 200 . The physical structure of an exemplary surgical fastener 200 is shown and described in U.S. Pat. No. 4,534,352, the entire content of which is incorporated herein by reference. Generally, surgical fastener 200 includes a retainer member 210 and fastener member 202 , which has two prongs or legs 204 that are driven through tissue (not shown) to engage apertures 212 in retainer member 210 . Prongs 204 each include a barb 206 attached to a shank 208 .
[0048] In accordance with the present disclosure, surgical fastener 200 , including retainer member 210 and fastener member 202 may be constructed from any of the materials disclosed hereinabove either identically (constructed from the same materials) or uniquely (i.e., constructed from different materials) from one another.
[0049] It should be understood that various changes in form, detail and application of the support structures of the present disclosure may be made without departing from the spirit and scope of the present disclosure. | The present disclosure relates to surgical fasteners and more particularly to surgical fasteners coated with wound treatment materials. According to an aspect of the present disclosure, a surgical fastener for use in combination with a surgical fastener applying apparatus is provided. The surgical fastener includes a pair of legs; a crown interconnecting the pair of legs; and a wound treatment material coating at least a portion of the legs and crown. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of provisional patent application Ser. No. 61/483,450 filed May 6, 2011.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
None.
BACKGROUND OF THE INVENTION
The present disclosure relates to a cushioning, shock absorbing device adaptable for use in a variety of situations to cup and support a user's heel or heels, suspending the heel above an associated shoe or shoes, for example, when weight is applied to the device. While the device is described in particular detail to the human foot heel, those skilled in the art will recognize the wider application of the inventive concepts disclosed hereinafter.
When people stand, walk or run they exert pressure on their heel. The device disclosed takes pressure off the heel, thereby diminishing or eliminating pain and discomfort many people experience while standing, walking or running. Prior heel support devices typically provide flexible cushioning materials as a part of a shoe and/or as an insert to a particular type of shoe. Other prior devices provide shoes that contain an integral and non-removable foot support structure that is installed as a unit into a shoe which is not transferable to other shoes. Still other prior art devices typically use spring structures of various forms constructed as part either the shoe insole itself or as a supplemental insert positioned adjacent to the insole.
There is a need for an adjustable heel support for supporting the heel independently of the shoe insole. There also is a need for a heel support device which is transferable between various shoes and is adaptable to fit various widths of shoes. There is a need for such a support device which is also adjustable longitudinally to provide adjustability of support along the length of the user's foot. A need also exists for a device in which the cushioning member is replaceable and adjustable in applicational use.
BRIEF SUMMARY OF THE INVENTION
In accordance with this disclosure, generally stated, a support and cushioning device having a simplified construction is provided which includes a flexible support member having a predetermined shape, the flexible member being designed for insertion into a second article, the second article conventionally being used to support the heel equivalent of a limb. A flexible cushioning member is provided having a plurality of ends, at least two of said ends being attached to the flexible member in a manner to cushion the heel and prevent and/or reduce contact of the heel with the second article in the application and use of the device. The support member is compatible with a plurality of second articles, and both the support member and the cushioning member preferably are adjustable in use. For the purposes of this disclosure the support and cushioning device is denominated as a “heel jack.”
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
In the accompanying drawings which form part of the specification:
FIG. 1 is a view in perspective of one illustrative embodiment of heel jack of the present disclosure;
FIG. 2 is a view in side elevation of the embodiment shown in FIG. 1 ;
FIG. 3 is a top plan view illustrating the flex pattern of the device shown in FIG. 1 ;
FIG. 4 is a view rear elevation of the heel jack of FIG. 1 ;
FIG. 5 is a view in perspective of one illustrative embodiment of the flexible heel support employed with the embodiment of FIG. 1 ;
FIG. 6 is a front plan view of a second illustrative embodiment of the heel jack of the present invention;
FIG. 7 is a plan view of a second illustrative embodiment of the flexible heel support employed with the embodiment of FIG. 6 ;
FIG. 8 is a view and perspective of the second illustrative embodiment of the heel jack of the present invention shown in FIG. 6 ;
FIG. 9 is an enlarged view taken about the line 9 - 9 of FIG. 8 ;
FIGS. 10 a and 10 b show a third illustrative third embodiment of the heel jack of the present invention; and
FIG. 11 is a view in perspective, partly broken away, illustrating one application for the heel jack of this invention.
Corresponding reference numerals indicate corresponding parts throughout the several figures of the drawings.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The following detailed description illustrates the invention by way of example and not by way of limitation. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what I presently believe is the best mode of carrying out the invention. As various changes could be made in the described constructions without departing from the scope of the invention, it is intended that all matter contained in the following description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
Referring now to FIG. 1 , one illustrative embodiment of heel jack of the present invention is shown preferably to comprise a support structure or element 1 and a heel support or cushion 2 ( FIG. 5 ).
The support a structure 1 includes, in the embodiment illustrated, a pair of opposed wing members 3 and 4 respectively. The wing members preferably are constructed from a moldable material, and various forms of plastic or other synthetic material, for example, polypropylene, latex, rubber or other similar moldable and/or thermoplastic materials work well. Those skilled in the art will recognize that materials other than the materials listed may be used, if desired. The wing members 3 and 4 preferably are interchangeable with one another, and may be formed from a single mold during manufacture. In addition, the wings themselves may be coated with a soft coating of a non abrasive material not shown, for example, a latex or foam rubber coating to increase the comfort level of the structure 1 in use. The wing members 3 and 4 define an open mouth 5 generally sized to accept the heel portion of the user's foot, as latter described in greater detail.
Each of the wing members 3 and 4 has a plurality of generally parallel spaced apart channels 10 formed in it. The channels 10 also preferably have a plurality of serrations 11 formed in them. The outward facing area between the spaced channels 10 are intended to receive elongated strips of a hook and loop fastening (Velcro®) material 13 . The material 13 is attached to the wing members by any convenient method. Adhesive works well, for example. Other fastening devices and methods will be apparent to those skilled in the art, and another novel method is described in greater detail below.
A plurality of support arms 20 extend from and between the wings 3 and 4 . Each of the support arms 20 have respective first and second ends which engage the channels 10 in respective ones of the wing members 3 and 4 . In the embodiment illustrated, preferably one of the support arms 20 assumes a shape corresponding to the contour of a typical shoe of the wearer. As will be appreciated, other shapes may be employed if desired.
The support arms 20 may be constructed from a variety of materials. I have found that the spring steel works well, but those skilled in the art will recognize that other materials may be employed for the arms 20 in other embodiments of the support element 1 .
Each end of the members 20 have a plurality of protrusions 25 formed in them, which are sized both for reception in the channels 10 and for frictional engagement with the serrations 11 of the respective wing members 3 and 4 .
The support element 1 is adjustable for reception in a number of various size shoes, and may be transferred between shoes by the user. For example, as shown in FIGS. 2 and 3 , the support element 1 is adjustable axially along the members 20 through the engagement of various ones of the protrusions 25 and the serrations 11 . Because the position of the members 3 and 4 with respects to the length of the members 20 control the stiffness or flexibility of the members 20 , the relative position of the members 20 and the wing members 3 , 4 also controls the flexibility of the heel jack. Thus movement of the members 20 provides both adjustment of the mouth 5 thereby making a larger heel silhouette insertable in the support element 1 while also permitting the heel jack to support and cushion a longer portion of the heel as the arm 20 movement adjusts the length and width provided by the support element 1 at the same time. At least some adjustment is an important aspect of the present disclosure in that it enables the support 1 to be used in a plurality of different shoe sizes and shoe designs, merely by making the adjustment between the support arms 20 and the wings 3 and 4 varies the flexibility of the design as illustratively shown by a plurality of positions along the spread angles 100 . As later described, and shown in FIG. 3 , even without adjustment between the wings and the support members 20 , the members 20 themselves provided rotational movement about a length or longitudinal axis along the spread angles 100 , regardless of whether or not the additional adjustment provided by axial movement of the arms 20 and the wings is provided in a particular embodiment of the disclosure.
As illustrated in FIG. 5 , one illustrative embodiment of heel supporting member or cushion 3 is shown to have an elongated T-shape, delineated by a first arm 31 , a second arm 32 and a third arm 33 . Each end of the arms 31 , 32 , and 33 has conventional hook and eye 35 material attached to them, enabling the heel support 30 to be removably secured to the support element 1 . Again, attachment of the material 35 to the member 2 may be accomplished by any conventional method. Through the material 35 , the arms 31 , 32 may be mounted to the hook and eye material 13 along the wings 3 and 4 , while the arm 33 may be attached to itself around at least one of the members 20 to provide a heel supporting a position for the combined components. It should be appreciated by those skilled in the art the heel support 3 may be adjusted along the channels 13 to vary the height of the member 2 with respect to the wings of 3 and 4 , while the end 33 may be adjusted along the support members 20 to position the heel support 2 properly with respect to and in consideration of a user's physical characteristics and/or the intended use of the device. While the heel supporting member or cushion 3 in the embodiments illustrated is described as being or having a “T” shape, a variety of other design silhouettes are compatible with the broader aspects of the disclosure.
Referring now to FIGS. 6, 8 and 9 , a second attachment method of the heel support or cushion 2 is shown in greater detail. As there shown, the wings 3 and 4 again have a plurality of support arms 20 extending between them. In this embodiment, however, the arms 20 are encapsulated within the support wings 3 and 4 . While this embodiment is not as adjustable as the embodiment of FIG. 1 , the arms 20 still are flexible enough to vary the size of the mouth 5 to accommodate the need of the user. The heel support or cushion 2 again preferably is T-shaped, but the ends of the arms 31 and 32 are crimped to provide a rail 50 . The rail 50 then is inserted along a mating channel 60 formed in the wings 3 and 4 , as best seen in FIG. 9 . The end 33 of the heel support 3 , in the embodiment illustrated, may use a hook and eye fastening system for attachment to and release from a selected one of the arms 20 . However, other fastening methods, including various conventional clips or a simple hook type fastener or hanger type hook may be used, if desired.
FIGS. 10 a and 10 b illustrate a third illustrative embodiment of the heel jack of the present invention. In the embodiment of FIG. 10 , the wings 3 and 4 have a pair of members 20 associated with the wings. One of the members 20 is preferably integrally formed with the wings. A second member 20 is pivotally mounted to wings 3 and 4 at a pivot point 70 and 71 respectively. The integrally formed member 20 , in the embodiment shown in FIG. 10 b has a plurality of teeth 75 formed in it. The second member 20 , which as indicated above is rotatably mounted to the rings 3 and 4 , has a groove or channel 80 formed it which is sized to receives a teeth 75 in a friction fit. The channel 80 /teeth 75 interaction permits the heel support member 2 to be crimped between the rotatable member 20 and the lower member 20 or to slide into a channel on the under portion of the second member 20 . While a friction fit between the arm members 20 is described,
As shown in the various embodiments, the support structure or element 1 is generally U-shaped; however it may take any shape, such as oval, square or a rectangle. The support structure 1 is intended to make contact with the heel counter on the inner portion of the shoe of the user, for example. It may be further secured to the heel counter of the shoe with hook and eye material (Velcro®), although in the embodiments shown in FIGS. 1 and 8 , the spring material utilized for the support arms 20 enable the device to be frictionally engaged with the inner portion of the shoe in a friction fit. The preferred U-shape coupling component is the shape of a person's heel. (See FIG. 11 ) As indicated above, at least the wings can be molded, contoured or indented depending on the shoe needed. As further indicated above, it is preferable that the support element 1 is adjustable, to accommodate a range of length, but as shown in FIG. 8 and FIG. 11 , a single length device may be provided, if desired.
The support element 1 function is to support and suspend the flexible member 2 when weight is supplied by a person's heel. While various materials may be in employed in construction, the support element 1 should be strong enough to withstand forces applied to it. As will be appreciated by those skilled in the art, this will vary from one person to another depending on weight, age, shoe size and type and whether the device is used merely for standing, walking or running. In any event, the support 1 should not be allowed to invert, bend, crack or break. The flexible heel support or cushion 2 is used to cushion the heel. That is accomplished in the various embodiments by keeping the member 2 suspended between the wings 3 and 4 and the support arms 20 forming the U-shape. As best seen in FIG. 11 , the flexible member 2 function is to cup and support the person's heel, suspend the heel and keep the heel generally from touching the shoe when weight it applied to it by the user. Various materials may be used for the heel support or cushion 2 , but I have found that a latex material works well for the intended purpose. While the intent of the support 1 is to eliminate contact between the heel and the shoe, for example, some contact may be acceptable depending of the physical characteristics of the user and/or the condition being treated through use of the support element 1 . As will be appreciated, the member 2 is intended to be replaceable, and the flexibility of the member 2 may be varied to accomplish the intended use.
As indicated above, the support element 1 fits inside the shoe against the heel counter. It cups the outer edges of the person's heel. The flexible member 2 in turn is supported during application use. The support element 1 and flexible member 2 are all necessary for proper function. As will be appreciated by those skilled in the art, additional ankle stabilization elements can be added for use with the above described structural elements, if desired. An ankle stabilization element will be necessary if there is no heel counter in application use or if the device is used in other areas or other medical purposes.
Numerous variations within the scope of the appended claims will be apparent to those skilled in the art. In addition to the various examples given throughout the description, it will be apparent that various dimensions, materials and shapes may be altered in other embodiments. For example, the cushion 2 may have differing thicknesses associated with it to facilitate use of the device described. While a latex construction for the cushion 2 is preferred, other elastic or flexible materials are compatible with the broader aspects of the disclosure. In view of the above, it will be seen that the several objects and advantages of the present invention have been achieved and other advantageous results have been obtained. | An improved construction for a device intended to raise the heel or heels of a user up off an associated shoe to diminish or eliminate pain and discomfort. The device is adjustable to accommodate a variety of applications and is transferable between those applications. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a seed layer for improving the pinning field of a spin valve sensor and more particularly to a seed layer structure that improves the pinning field between pinning and pinned layers and promotes a higher magnetoresistive coefficient of a spin valve sensor.
2. Description of the Related Art
A spin valve sensor is employed by a read head for sensing magnetic signal fields from a moving magnetic medium, such as a rotating magnetic disk. The sensor includes a nonmagnetic electrically conductive first spacer layer sandwiched between a ferromagnetic pinned layer and a ferromagnetic free layer. An antiferromagnetic pinning layer interfaces the pinned layer for pinning a magnetic moment of the pinned layer 90° to an air bearing surface (ABS) wherein the ABS is an exposed surface of the sensor that faces the magnetic disk. First and second leads are connected to the spin valve sensor for conducting a sense current therethrough. A magnetic moment of the free layer is free to rotate upwardly and downwardly with respect to the ABS from a quiescent or bias point position in response to positive and negative magnetic field signals from a rotating magnetic disk. The quiescent position, which is preferably parallel to the ABS, is the position of the magnetic moment of the free layer with the sense current conducted through the sensor in the absence of signal fields.
The thickness of the spacer layer is chosen so that shunting of the sense current and a magnetic coupling between the free and pinned layers are minimized. This thickness is typically less than the mean free path of electrons conducted through the sensor. With this arrangement, a portion of the conduction electrons are scattered at the interfaces of the spacer layer with the pinned and free layers. When the magnetic moments of the pinned and free layers are parallel with respect to one another scattering is minimal and when their magnetic moments are antiparallel scattering is maximized. Changes in scattering changes the resistance of the spin valve sensor as a function of cos θ, where θ is the angle between the magnetic moments of the pinned and free layers. The sensitivity of the sensor is quantified as magnetoresistive coefficient dr/R where dr is the change in the resistance of the sensor as the magnetic moment of the free layer rotates from a position parallel with respect to the magnetic moment of the pinned layer to an antiparallel position with respect thereto and R is the resistance of the sensor when the magnetic moments are parallel.
A read head in a magnetic disk drive of a computer includes the spin valve sensor as well as nonconductive nonmagnetic first and second read gap layers and ferromagnetic first and second shield layers. The spin valve sensor is located between the first and second read gap layers and the first and second read gap layers are located between the first and second shield layers. In the construction of the read head the first shield layer is first formed followed by formation of the first read gap layer, the spin valve sensor, the second read gap layer and the second shield layer. Spin valve sensors are classified as a top or a bottom spin valve sensor depending upon whether the pinning layer is located at the bottom of the sensor next to the first read gap layer or at the top of the sensor closer to the second read gap layer. Spin valve sensors are further classified as simple pinned or antiparallel pinned depending upon whether the pinned layer structure is one or more ferromagnetic layers with a unidirectional magnetic moment or a pair of ferromagnetic layers that are separated by a coupling layer with magnetic moments of the ferromagnetic layers being antiparallel. Spin valve sensors are still further classified as single or dual wherein a single spin valve sensor employs only one pinned layer and a dual spin valve sensor employs two pinned layers with the free layer structure located therebetween.
Because of the interfacing of the pinning and pinned layers the pinned layer is exchange coupled to the pinning layer. A unidirectional orientation of the magnetic spins of the pinning layer pins the magnetic moment of the pinned layer in the same direction. The orientation of the magnetic spins of the pinning layer are set by applying heat close to or above a blocking temperature of the material of the pinning layer in the presence of a field that is directed perpendicular to the ABS. The blocking temperature is the temperature at which all of the magnetic spins of the pinning layer are free to rotate in response to an applied field. During the setting, the magnetic moment of the pinned layer is oriented parallel to the applied field and the magnetic spins of the pinning layer follow the orientation of the pinned layer. When the heat is reduced below the blocking temperature the magnetic spins of the pinning layer pin the orientation of the magnetic moment of the pinned layer. The pinning function is effective as long as the temperature remains substantially below the blocking temperature.
In the presence of some magnetic fields the magnetic moment of the pinned layer can be rotated antiparallel to the pinned direction. The question then is whether the magnetic moment of the pinned layer will return to the pinned direction when the magnetic field is relaxed. This depends upon the strength of the exchange coupling field and the coercivity of the pinned layer. If the coercivity of the pinned layer exceeds the exchange coupling field between the pinning and pinned layers the exchange coupling field will not be strong enough to bring the magnetic moment of the pinned layer back to the original pinned direction. Until the magnetic spins of the pinning layer are reset the read head is rendered inoperative. Accordingly, there is a strong felt need to increase the exchange coupling field between the pinning layer and the pinned layer so that the spin valve sensor has improved thermal stability.
Another parameter that indicates the performance of the pinning of the pinned layer is the pinning field H p between the pinning and pinned layers. The pinning field, which is somewhat dependent upon the exchange coupling field H ex , is the applied field at which the magnetic moment of the pinned layer commences to rotate in a substantial manner. If the pinning field H p is low the orientation of the pinned layer will not be controlled thereby degrading performance of the read head. Accordingly, it is desirable to maximize the pinning field H p .
SUMMARY OF THE INVENTION
I have provided a seed layer structure for the pinning layer which increases the pinning field H PIN between the pinning layer and the pinned layer. In an example, which will be described in detail hereinafter, I obtained a pinning field H PIN of 600 Oe which is excellent in the spin valve sensor art. In the example the seed layer structure included a first seed layer of cobalt iron boron (CoFeB), a second seed layer of nickel manganese oxide (NiMnO) and a third seed layer of aluminum oxide (Al 2 O 3 ) with the first seed layer interfacing the pinning layer and the second seed layer being located between the first and third seed layers. My invention also includes employing a seed layer structure which includes only the first seed layer of cobalt iron boron (CoFeB) since it directly interfaces the pinning layer and is primarily responsible for the improvement in the pinning field H PIN . The pinned layer can be a single pinned layer or an antiparallel (AP) pinned layer structure. The cobalt iron boron (CoFeB) seed layer provides a second significant function of at least partially counterbalancing the demagnetizing field from the pinned layer. Accordingly, the seed layer improves readback asymmetry of the read head by promoting a centering of a bias point of the spin valve sensor on its transfer curve. As will also be seen from the following example the spin valve sensor with the seed layer structure provided a magnetoresistive coefficient of 8.8% which is excellent in the spin valve art.
An object is to provide a seed layer for a spin valve sensor which improves the pinning field H PIN between pinning and pinned layers and the magnetoresistive coefficient dr/R of the sensor.
Another object is to provide a seed layer for a spin valve sensor which improves the texture of layers constructed on the seed layer for improving performance of the spin valve sensor.
A further object is to accomplish the aforementioned objectives while employing the seed layer to provide a sense current field for counterbalancing a demagnetization field from a pinned layer or pinned layer structure of the spin valve sensor.
Other objects and attendant advantages of the invention will be appreciated upon reading the following description taken together with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a planar view of an exemplary magnetic disk drive;
FIG. 2 is an end view of a slider with a magnetic head of the disk drive as seen in plane 2 — 2 ;
FIG. 3 is an elevation view of the magnetic disk drive wherein multiple disks and magnetic heads are employed;
FIG. 4 is an isometric illustration of an exemplary suspension system for supporting the slider and magnetic head;
FIG. 5 is an ABS view of the slider taken along plane 5 — 5 of FIG. 2;
FIG. 6 is a partial view of the slider and a piggyback magnetic head as seen in plane 6 — 6 of FIG. 2;
FIG. 7 is a partial view of the slider and a merged magnetic head as seen in plane 7 — 7 of FIG. 2;
FIG. 8 is a partial ABS view of the slider taken along plane 8 — 8 of FIG. 6 to show the read and write elements of the piggyback magnetic head;
FIG. 9 is a partial ABS view of the slider taken along plane 9 — 9 of FIG. 7 to show the read and write elements of the merged magnetic head;
FIG. 10 is a view taken along plane 10 — 10 of FIGS. 6 or 7 with all material above the coil layer and leads removed;
FIG. 11 is an isometric ABS illustration of an exemplary read head which employs a spin valve sensor longitudinally biased by hard biasing layers;
FIG. 12 is an ABS illustration of a first embodiment of the present spin valve sensor; and
FIG. 13 is an ABS illustration of a second embodiment of the present spin valve sensor.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Magnetic Disk Drive
Referring now to the drawings wherein like reference numerals designate like or similar parts throughout the several views, FIGS. 1-3 illustrate a magnetic disk drive 30 . The drive 30 includes a spindle 32 that supports and rotates a magnetic disk 34 . The spindle 32 is rotated by a spindle motor 36 that is controlled by a motor controller 38 . A slider 42 supports a combined read and write magnetic head 40 and is supported by a suspension 44 and actuator arm 46 that is rotatably positioned by an actuator 47 . A plurality of disks, sliders and suspensions may be employed in a large capacity direct access storage device (DASD) as shown in FIG. 3 . The suspension 44 and actuator arm 46 are moved by the actuator 47 to position the slider 42 so that the magnetic head 40 is in a transducing relationship with a surface of the magnetic disk 34 . When the disk 34 is rotated by the spindle motor 36 the slider is supported on a thin (typically, 0.05 μm) cushion of air (air bearing) between the surface of the disk 34 and the air bearing surface (ABS) 48 . The magnetic head 40 may then be employed for writing information to multiple circular tracks on the surface of the disk 34 , as well as for reading information therefrom. Processing circuitry 50 exchanges signals, representing such information, with the head 40 , provides spindle motor drive signals for rotating the magnetic disk 34 , and provides control signals to the actuator for moving the slider to various tracks. In FIG. 4 the slider 42 is shown mounted to a suspension 44 . The components described hereinabove may be mounted on a frame 54 of a housing 55 , as shown in FIG. 3 .
FIG. 5 is an ABS view of the slider 42 and the magnetic head 40 . The slider has a center rail 56 , which supports the magnetic head 40 , and side rails 58 and 60 . The rails 56 , 58 and 60 extend from a cross rail 62 . With respect to rotation of the magnetic disk 34 , the cross rail 62 is at a leading edge 64 of the slider and the magnetic head 40 is at a trailing edge 66 of the slider.
FIG. 6 is a side cross-sectional elevation view of a piggyback magnetic head 40 , which includes a write head portion 70 and a read head portion 72 , the read head portion employing a spin valve sensor 74 of the present invention. FIG. 8 is an ABS view of FIG. 6 . The spin valve sensor 74 is sandwiched between nonmagnetic electrically insulative first and second read gap layers 76 and 78 , and the read gap layers are sandwiched between ferromagnetic first and second shield layers 80 and 82 . In response to external magnetic fields, the resistance of the spin valve sensor 74 changes. A sense current I s conducted through the sensor causes these resistance changes to be manifested as potential changes. These potential changes are then processed as readback signals by the processing circuitry 50 shown in FIG. 3 .
The write head portion 70 of the magnetic head 40 includes a coil layer 84 sandwiched between first and second insulation layers 86 and 88 . A third insulation layer 90 may be employed for planarizing the head to eliminate ripples in the second insulation layer caused by the coil layer 84 . The first, second and third insulation layers are referred to in the art as an “insulation stack”. The coil layer 84 and the first, second and third insulation layers 86 , 88 and 90 are sandwiched between first and second pole piece layers 92 and 94 . The first and second pole piece layers 92 and 94 are magnetically coupled at a back gap 96 and have first and second pole tips 98 and 100 which are separated by a write gap layer 102 at the ABS. An insulation layer 103 is located between the second shield layer 82 and the first pole piece layer 92 . Since the second shield layer 82 and the first pole piece layer 92 are separate layers this head is known as a piggyback head. As shown in FIGS. 2 and 4, first and second solder connections 104 and 106 connect leads from the spin valve sensor 74 to leads 112 and 114 on the suspension 44 , and third and fourth solder connections 116 and 118 connect leads 120 and 122 from the coil 84 (see FIG. 10) to leads 124 and 126 on the suspension.
FIGS. 7 and 9 are the same as FIGS. 6 and 8 except the second shield layer 82 and the first pole piece layer 92 are a common layer. This type of head is known as a merged magnetic head. The insulation layer 103 of the piggyback head in FIGS. 6 and 8 is omitted.
FIG. 11 is an isometric ABS illustration of a read head 72 which has a spin valve sensor 130 with a pinning layer 132 which is typically nickel oxide (NiO). First and second hard bias and lead layers 134 and 136 are connected to first and second side edges 138 and 140 of the spin valve sensor. This connection is known in the art as a contiguous junction and is fully described in commonly assigned U. S. Pat. No. 5,018,037. The first hard bias and lead layers include a first hard bias layer 140 and a first lead layer 142 and the second hard bias and lead layers 136 include a second hard bias layer 144 and a second lead layer 146 . The hard bias layers 140 and 144 cause magnetic flux to extend longitudinally through the spin valve sensor 130 for stabilizing magnetic domains of the free layer. The spin valve sensor 130 and the first and second hard bias and lead layers 134 and 136 are located between nonmagnetic electrically insulative first and second read gap layers 148 and 150 . The first and second read gap layers 148 and 150 are, in turn, located between first and second shield layers 152 and 154 .
The Invention
The read head embodiment 400 shown in FIG. 12 includes a spin valve sensor 402 which may be constructed on the first read gap layer 148 . The spin valve sensor 402 includes a nonmagnetic conductive spacer layer (S) 404 which is located between a free layer structure 406 and a pinned layer (P) 408 . The pinned layer 408 is exchange coupled to an antiferromagnetic (AFM) pinning layer 410 . The pinning layer 410 pins a magnetic moment 412 of the pinned layer perpendicular to the ABS in a direction away from the ABS, as shown in FIG. 12, or optionally toward the ABS.
The free layer structure 406 includes a free layer (F) 414 and a nanolayer (NL) 416 with the nanolayer located between the spacer layer 404 and the free layer 414 for increasing the magnetoresistive coefficient dr/R of the spin valve sensor. The free layer structure has a magnetic moment 418 which is directed parallel to the ABS from left to right, as shown in FIG. 12, or optionally from right to left. The magnetic moment 418 is rotated upwardly and downwardly by signal fields from the rotating magnetic disk. When the sense current Is is conducted through the spin valve sensor a rotation of the magnetic moment 418 upwardly decreases the resistance of the sensor and a rotation of the magnetic moment 418 downwardly increases the resistance of the sensor which resistance changes are processed as playback signals by the processing circuitry 50 in FIG. 3. A cap layer 420 is located on the free layer 414 for protecting it from subsequent processing steps.
A seed layer structure 422 was provided for the spin valve sensor which included 10 Å of cobalt iron boron (CoFeB) for a first seed layer 424 , 30 Å of nickel manganese oxide (NiMnO) for a second seed layer 426 and 30 Å of aluminum oxide (Al 2 O 3 ) for a third seed layer 428 with the second seed layer located between the first and third seed layers. The spin valve sensor 402 is located on the seed layer structure 422 with the pinning layer 410 interfacing the first seed layer 424 .
The thicknesses and materials of the layers of the spin valve sensor 402 are 250 Å of platinum manganese (PtMn) for the pinning layer 410 , 35 Å of cobalt iron (CoFe) for the pinned layer 408 , 20 Å of copper (Cu) for the spacer layer 404 , 15 Å of cobalt iron (CoFe) for the nanolayer 416 , 45 Å of nickel iron (NiFe) for the free layer 414 and 50 Å of tantalum (Ta) for the cap layer 420 .
Upon testing the embodiment 400 shown in FIG. 12 the magnetoresistive coefficient dr/R of the spin valve sensor was 8.8% and the pinning field H PIN between the pinning layer 410 and the pinned layer 408 was 600 Oe. Both of these values are considered to be excellent in the spin valve sensor art.
Another embodiment of the present invention is illustrated in FIG. 13 which is same as the embodiment 400 in FIG. 12 except an antiparallel (AP) pinned layer structure 502 is substituted for the pinned layer 408 in FIG. 12 . The AP pinned layer structure 502 includes first and second AP pinned layers (AP 1 ) and (AP 2 ) 504 and 506 with an AP coupling layer 508 located between the first and second AP pinned layers. The first and second AP pinned layers 506 and 508 have first and second magnetic moments 510 and 512 which are antiparallel with respect to one another. Because of this relationship the AP pinned layer structure 502 produces a net demagnetizing field which is less than the demagnetizing field of the pinned layer 408 in FIG. 12 . Exemplary thicknesses and materials for the AP pinned layer structure are 23 Å of cobalt iron (CoFe) for the first AP pinned layer 504 , 26 Å of cobalt iron (CoFe) for the second AP pinned layer 506 and 8 Å of ruthenium (Ru) for the AP coupling layer 508 .
Discussion
The percentage composition of the various elements of the materials are Co 88 Fe 9 B 3 , Ni 50 Mn 50 O, Pt 50 Mn 50 , Co 90 Fe 10 and Ni 82 Fe, 18 . All of the layers embodiments shown in FIGS. 12-15 were deposited in situ except for the first gap layer 148 wherein in situ means that all of the layers are deposited in a ion beam sputtering chamber without breaking the vacuum.
The spin valve sensors 402 and 502 in FIGS. 12 and 13 are bottom spin valve sensors since the pinning layer 410 is located at the bottom of the spin valve sensor closer to the first read gap layer 408 than the free layer structure 406 is to the first read gap layer. It should be understood that the thicknesses for the various layers are exemplary and can be varied. Further, while cobalt iron (CoFe) is preferred for the pinned and nanolayers, cobalt (Co) could be substituted therefor. Still further, while platinum manganese (PtMn) is preferred for the pinning layers, other metallic antiferromagnetic materials may be employed such as iridium manganese (IrMn), nickel manganese (NiMn), iron manganese (FeMn), palladium platinum manganese (PdPtMn) and nickel manganese (NiMn).
Clearly, other embodiments and modifications of this invention will occur readily to those of ordinary skill in the art in view of these teachings. Therefore, this invention is to be limited only by the following claims, which include all such embodiments and modifications when viewed in conjunction with the above specification and accompanying drawings. | A seed layer is provided for a pinning layer which increases the pinning field H PIN between a pinning layer and a pinned layer of a spin valve sensor. In an example the seed layer structure included a first seed layer of cobalt iron boron (CoFeB), a second seed layer of nickel manganese oxide (NiMnO) and a third seed layer of aluminum oxide (Al 2 O 3 ) with the first seed layer interfacing the pinning layer and the second seed layer being located between the first and third seed layers. A pinning field between the pinning and pinned layers was 600 Oe and the magnetoresistive coefficient of the spin valve sensor was 8.8%. The pinned layer can be a single pinned layer or an antiparallel (AP) pinned layer structure. If the pinned layer structure is a single pinned layer the cobalt iron boron (CoFeB) first seed layer provides a second significant function of at least partially counterbalancing the demagnetizing field from the pinned layer. | 1 |
FIELD OF THE INVENTION
[0001] The invention relates to the general field of GMR recording heads for magnetic disk systems with particular reference to design of the free layer.
BACKGROUND OF THE INVENTION
[0002] Read-write heads for magnetic disk systems have undergone substantial development during the last few years. In particular, older systems in which a single device was used for both reading and writing, have given way to configurations in which the two functions are performed by different structures. An example of such a read-write head is schematically illustrated in FIG. 1. The magnetic field that ‘writes’ a bit at the surface of recording medium 15 is generated by a flat coil, two of whose windings 14 can be seen in the figure. The magnetic flux generated by the flat coil is concentrated within pole pieces 12 and 13 which, while being connected at a point beyond the top edge of the figure, are separated by small gap 16 . Thus, most of the magnetic flux generated by the flat coil passes across this gap with fringing fields extending out for a short distance where the field is still powerful enough to magnetize a small portion of recoding medium 15 .
[0003] The present invention is directed towards the design of read element 20 which can be seen to be a thin slice of material located between magnetic shields 11 and 12 ( 12 doing double duty as a pole piece, as just discussed). The principle governing the operation of read sensor 20 is the change of resistivity of certain materials in the presence of a magnetic field (magneto-resistance). Most magnetic materials exhibit anisotropic behavior in that they have a preferred direction along which-they are most easily magnetized (known as the easy axis). The magneto-resistance effect manifests itself as a decrease in resistivity when the material is magnetized in a direction perpendicular to the easy axis, said decrease being reduced to zero when magnetization is along the easy axis. Thus, any magnetic field that changes the direction of magnetization in a magneto-resistive material can be detected as a change in resistance.
[0004] It is widely known that the magneto-resistance effect can be significantly increased by means of a structure known as a spin valve. The resulting increase (known as Giant magneto-resistance or GMR) derives from the fact that electrons in a magnetized solid are subject to significantly less scattering by the lattice when their own magnetization vectors (due to spin) are parallel (as opposed to anti-parallel) to the direction of magnetization of the solid as a whole.
[0005] The key elements of a spin valve structure are shown in FIG. 2. In addition to a seed layer 22 on a substrate 21 and a topmost cap layer 27 , these key elements are two magnetic layers 24 and 26 , separated by a non-magnetic layer 25 . The thickness of layer 25 is chosen so that layers 24 and 26 are sufficiently far apart for exchange effects to be negligible (i.e. the layers do not influence each other's magnetic behavior at the atomic level) but are close enough to be within the mean free path of conduction electrons in the material. If, now, layers 24 and 26 are magnetized in opposite directions and a current is passed though them along the direction of magnetization (such as direction 28 in the figure), half the electrons in each layer will be subject to increased scattering while half will be unaffected (to a first approximation). Furthermore, only the unaffected electrons will have mean free paths long enough for them to have a high probability of crossing over from 24 to 26 (or vice versa). However, once these electrons ‘switch sides’, they are immediately subject to increased scattering, thereby becoming unlikely to return to their original side, the overall result being a significant increase in the resistance of the entire structure.
[0006] In order to make use of the GMR effect, the direction of magnetization of one of the layers 24 and 26 is permanently fixed, or pinned. In FIG. 2 it is layer 24 that is pinned. Pinning is achieved by first magnetizing the layer (by depositing and/or annealing it in the presence of a magnetic field) and then permanently maintaining the magnetization with an undercoat of a layer of antiferromagnetic material, or AFM, (layer 23 in the figure). Layer 26 , by contrast, is a “free layer” whose direction of magnetization can be readily changed by an external field (such as that associated with a bit at the surface 15 of a magnetic disk).
[0007] The structure shown in FIG. 2 is referred to as a bottom spin valve because the pinned layer is at the bottom. It is also possible to form a ‘top spin valve’ structure where the pinned layer is deposited after the pinning layer.
[0008] Ultra-thin free layers as well as MR ratio are very effective to obtain high output spin valve GMR heads for over 30 Gb/in 2 magnetic recording. In general, magneto-resistive devices have a characteristic response curve such that their sensitivity initially increases with the applied field, then is constant with applied field, and then decreases to zero for even higher fields. It is therefore standard to provide a biasing field to keep the sensor operating in the linear range where it is also at its most sensitive. However, as the free layer thickness decreases, it becomes difficult to obtain a controllable bias point, high GMR ratio and good magnetic softness all at the same time. Synthetic antiferromagnets (SyAF) are known to reduce magneto-static fields in a pinned layer, but a large bias point shift due to sense current fields remains a problem for practical use of an ultra-thin free layer. To overcome this problem, the spin-filter spin valve (SFSV) was invented.
[0009] In a SFSV, the free layer is placed between the Cu spacer and an additional high-conductance-layer (HCL). SFSV reduces sense current fields in the free layer by shifting the sense current center toward the free layer, resulting in a smaller bias point shift by sense current fields. High GMR ratio is maintained even in the ultra-thin free layer because the HCL improves the mean free path of a spin-up electron while maintaining the mean free path difference between spin-up and spin-down electrons.
[0010] As discussed earlier, spin valve GMR heads may be either top or bottom types. The GMR sensor track is defined by a patterned longitudinal biasing layer in the form of two bias stripes. These are permanently magnetized in a direction parallel to the surface. Their purpose is to prevent the formation of multiple magnetic domains in the free layer. The most commonly used longitudinal bias for the bottom spin valve is with contiguous (abutted) junction hard bias. The problem with the abutted junction is the existence of a “dead zone” at the sensor ends. A MR sensor track defined by continuous spacer exchange bias (similar to that for the DSMR) does not have the “dead zone”. This may be critical for a very narrow track for ultra-high density recording application.
[0011] A routine search of the prior art was performed. The following references of interest were found. U.S. Pat. No. 5,637,235 (Kim et al.) shows a SV with a capping layer. U.S. Pat. No. 5,896,252 (Kanai) shows a SV with a free magnetic layer composed of a CoFe and NiFe sublayers while U.S. Pat. No. 5,648,885 (Nishioka et al.) teaches a SV with CoFe free layer.
SUMMARY OF THE INVENTION
[0012] It has been an object of the present invention to provide a spin-filter synthetic antiferromagnetic bottom spin valve that is suitable for ultra-high density magnetic recording applications.
[0013] Another object of the invention has been to provide suitable longitudinal biasing leads for this structure.
[0014] A further object of the invention has been to provide processes for the manufacture of these structures.
[0015] These objects have been achieved in a structure made up the following layers:
[0016] NiCr/MnPt/CoFe/Ru/CoFe/Cu/(free layer)/Cu/Ta or TaO. A key feature is that the free layer is made of thin CoFe plus a CoFe/NiFe composite layer in which CoFe is thinner than NiFe. Experimental data confirming the effectiveness of this structure is provided, together with a method for manufacturing it and the longitudinal bias leads.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] [0017]FIG. 1 is a schematic representation of a read-write head for a magnetic disk system.
[0018] [0018]FIG. 2 shows the cross-sectional structure of a spin valve according to the teachings of the prior art.
[0019] [0019]FIG. 3 shows the cross-sectional structure of a spin-filter spin valve according to the teachings of the present invention.
[0020] [0020]FIG. 4 illustrates how the structure of FIG. 3 is modified in order to apply longitudinal bias leads to it.
[0021] [0021]FIG. 5 shows the structure of FIG. 3 after longitudinal bias leads have been added to it.
[0022] [0022]FIG. 6 shows a plan view of the structure of which FIG. 5 is a cross-section.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] Relative to NiFe, sputter-etching of tantalum or tantalum oxide (TaO) is 3 times slower. In the present invention, the Ta or TaO capping layer of the bottom spin valve can be removed by using a carbon tetrafluoride reactive ion etching (RIE) process. The process for sputter etching the underlying Cu and partially etching of NiFe is controllable. These factors cause our process for forming an ultra-thin free layer bottom spin valve to be suitable for manufacturing.
[0024] Advantages of the processes and structures that we will disclose below include the following:
[0025] Bottom spin valves made by this invention have larger output signal amplitude.
[0026] The process for sputter-etching of the underlying Cu and (partially) etching NiFe for the continuous spacer exchange bias is controllable.
[0027] With the above design considerations in mind, we have worked out a structure and fabrication process to form a SF-SyAF bottom spin valve head with a very thin free layer. The GMR sensor track is defined by using a continuous exchange spacer bias.
[0028] Using the CVC GMR sputtering system, bottom SF-SyAF spin valves having: NiCr/MnPt/CoFe(I)/Ru/CoFe(2)/Cu/CoFe+NiFe(free layer)/Cu/Ta or TaO/configuration were made. Free layers of the present work are made of a very thin CoFe/NiFe composite layer. TaO in the present structure is formed by first depositing a thin (e.g. 10-15 Å) Ta film on the NiFe free layer, and then oxidizing it by oxygen plasma ashing.
[0029] We now describe the process of the present invention for both spin valves and read heads. In the course of this description, the structure of the present invention will also become clear.
[0030] Referring now to FIG. 3, the process for manufacturing a spin valve begins with the provision of substrate 21 onto which there is deposited magneto-resistance-enhancing seed layer 22 . Pinning layer 33 is then deposited onto layer 22 . This pinning layer is between about 100 and 200 Angstroms thick. Our preferred material has been MnPt but similar materials such as InMn, MnNi, ot MnPtPd could also have been used. This is followed by pinned layer 34 , a synthetic antiferromagnetic material that is actually a laminate details not shown), deposited as follows:
[0031] first a layer of cobalt-iron, between about 12 and 25 Angstroms thick, then a layer of ruthenium, between about 6 and 9 Angstroms thick, and last a second layer of cobalt-iron, between about 12 and 25 Angstroms thick. It is a requirement that these two cobalt-iron layers differ in thickness by between about 2 and 10 Angstroms.
[0032] Next, non-magnetic copper spacer layer 25 , between about 18 and 25 Angstroms thick, is deposited onto layer 34 .
[0033] In a key feature of the invention, free layer 35 is then deposited. This free layer is actually a composite of a cobalt-iron layer, having a thickness between about 3 and 15 Angstroms and a nickel-iron layer that is between about 10 and 35 Angstroms thick, the CoFe being deposited first.
[0034] Next, high conductance copper layer 36 , between about 5 and 15 Angstroms thick, is deposited on free layer 35 . This is followed by the deposition of a specular reflection layer of either tantalum that may be left unchanged at a thickness between about 10 and 20 Angstroms or that is converted to tantalum oxide layer 37 through plasma oxidation, as discussed earlier. This tantalum oxide layer has a thickness between about 15 and 30 Angstroms. Then, capping layer of aluminum oxide 38 , between about 100 and 300 Angstroms thick, is deposited on layer 37 .
[0035] The process is then completed by annealing. This takes the form of heating in the presence a magnetic field of between about 5,000 and 10,000 Oe, in a transverse direction, at a temperature between about 250 and 280° C. for between about 5 and 10 hours.
[0036] The process for manufacturing a read head begins with the provision of a bottom spin valve structure that includes an ultra-thin specular free layer as described immediately above. First, capping layer 38 is removed by wet etching, thereby uncovering tantalum or tantalum oxide layer 37 onto which a layer of photoresist (comprising soluble underlayer 40 a and insoluble top layer 40 b ), suitable for later lift-off, is applied arid then patterned to define the shape of a pair of conductor leads. This can be seen in FIG. 4.
[0037] Then, all tantalum or tantalum oxide that is not protected by photoresist is removed by reactive etching in carbon tetrafluoride. This results in the uncovering of high conductance copper layer 15 , which layer serves as an effective etch stop layer. Etching, by sputter-etching, then continues until all uncovered high conductance copper 36 has been removed, as well as a certain amount of nickel iron from free layer 35 . The removed nickel iron is then refilled with a layer of ferromagnetic material such as NiFe or CoFe, to a slightly greater thickness than the removed material (because of some uncertainty in the thickness control). This is followed by deposition of a layer of antiferromagnetic material.
[0038] Continuing our reference to FIG. 4, biasing layer 41 is then deposited on layer 35 (i.e. the refilled nickel-iron) to a thickness between about 100 and 150 Angstroms. The biasing layer may be either an exchange bias layer made of manganese-platinum or a similar material such as InMn, MnNi, or MnPtPd. This is followed by deposition of a layer of conductive material 42 . Our preferred material for the layer of conductive material has been Ta/Au/Ta, but similar materials, such as Cr/Rh/Cr could also have been used. It is deposited to a thickness between about 300 and 400 Angstroms.
[0039] At this point the liftoff process is invoked so that all photoresist, together with all material on the resist's surface, is removed, giving the structure the appearance shown in FIG. 5. A plan view, of which FIG. 5 is a cross-section, is shown in FIG. 6.
[0040] The process is completed by annealing. This involves heating in the presence a magnetic field of between about 100 and 200 Oe in the longitudinal direction, at a temperature between about 250 and 280° C. for between about 2 and 5 hours.
[0041] Experimental Verification of the Invention:
[0042] For comparison purposes, SF-SyAF top spin valves having: NiCr/Cu/NiFe+CoFe (free layer)/Cu/CoFe1/Ru/CoFe2/MnPt/NiCr configurations with equivalent layer thicknesses were also made.
[0043] To characterize free layer anisotropy, free layer structures made of 55 NiCr/20 Cu/2 CoFe-34 NiFe/15 Cu/TaO/Al 2 0 3 and 55 NiCr/15 Cu/34 NiFe-2 CoFe/20 Cu/NiCr, respectively (where all numbers are thicknesses in Angstroms), for the bottom and top SFSV were also studied.
[0044] After forming free layer and GMR stacks, the deposited structures were first given a standard 6000 Oe transverse field 280° C.-5 hrs annealing. The high field annealing set up the pinned layer direction. After removing Al 2 O 3 capping by wet etching, the GMR and the free layer stacks, were further given a low field (100 Oe) 250° C.-5 hrs annealing to reset the free layer in the sensor direction. This low field annealing was used to simulate the exchange bias annealing process.
[0045] Comparisons of the top and bottom spin valve free layer magnetic properties are illustrated in Table I.
TABLE I Free layer structure: 80.9% NiFe B s H c H k R s Dr/r Oe to close HA CZB55/Cu15/NiFe32/CoFe3/Cu20/CZB50 Top 0.28 10.23 15.84 24.12 0.54 9 Oe CZB55/Cu20/CoFe3/NiFe32/Cu15/TaO Bottom 0.28 6.77 14.67 25.85 0.65 4 Oe
[0046] As illustrated in TABLE I, the free layer of the bottom spin valve shows softer magnetic properties (i.e. lower H c and H k than that of the top spin valve. To close the hard axis (HA) loops for the free layers, applied longitudinal fields of 9 and 4 Oe are needed for the top and the bottom spin valve respectively.
[0047] Magnetic performance properties of the top and bottom SF-SyAF spin valves are listed in TABLE II. For the top spin valve with (55 NiFe/5 CoFe) free layer, GMR ratio (Dr/r)=9.54% and output amplitude (Dr)=1.20 ohm/sq. Dr/r and Dr for the bottom spin valve are 10% higher. Also H c and H k are lower.
TABLE II Structure: (80.9% NiFe/MP43%-2mt) B s H c H e H k R s Dr/r Dr FOM CZB55/Cu15/NiFe55/CoFe5/Cu20/CoFe23/Ru 1 0.52 8.47 16.2 9.94 12.6 9.54 1.20 0.65 7.5/CoFe18/MP150/CZB30/Al 2 O 3 CZB55/MP150/CoFe18/Ru7.5/CoFe23/Cu20/ 2 0.51 5.34 13.5 6.77 12.7 10.5 1.33 0.73 CoFe5/NiFe55/Cu15/Ta10/OL/Al 2 O 3 CZB55/Cu15/NiFe34/CoFe2/Cu19/CoFe23/Ru 3 0.28 7.20 13.5 7.44 14.6 9.74 1.42 1.33 7.5/CoFe18/MP150/CZB30/Al 2 O 3 CZB55/MP150/CoFe18/Ru7.5/CoFe23/Cu20/ 4 0.29 6.05 4.56 2.20 15.5 10.7 1.66 1.45 CoFe2/NiFe34/Cu15/Ta10/OL/Al 2 O 3 CZB55/MP150/CoFe18/Ru7.5/CoFe23/Cu20/ 5 0.27 5.92 8.53 4.07 15.9 12.8 2.03 1.89 CoFe10/NiFe20/Cu10/Ta10/Al 2 O 3
[0048] For ultra-high density recording, the free layer of the bottom spin valve is made of a very thin CoFe/NiFe composite layer having a magnetic moment equivalent to that of a 37 Å thick NiFe layer. See Cell 3 and Cell 4/Cell 5, respectively, for the top and the bottom spin valves with ultra-thin free layer. Figure-of-merit (FOM) for the (2 Å CoFe/34 Å NiFe) spin valves is about 2×greater than that with (5 Å CoFe/55 Å NiFe) free layer. The difference between Cell 4 and Cell 5, is that the composite free layer in cell 5 has a thicker CoFe component. The FOM for the (10 Å CoFe/20 Å NiFe) spin valve with 1 Å Cu HCL is about 2.5×greater than that of the (5 ÅCoFe/55 Å NiFe) spin valve with 15 Å Cdu HCL. Besides having greater FOM, the bottom spin valve has shown softer magnetic properties than the top spin valve. These results indicate that a bottom spin valve head gives higher sensor sensitivity to yield even higher output signal.
[0049] While the invention has been particularly shown and described with reference to the preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the spirit and scope of the invention. | A high performance specular free layer bottom spin valve is disclosed. This structure made up the following layers: NiCr/MnPt/CoFe/Ru/CoFe/Cu/free layer/Cu/Ta or TaO/Al 2 O 3 . A key feature is that the free layer is made of a very thin CoFe/NiFe composite layer. Experimental data confirming the effectiveness of this structure is provided, together with a method for manufacturing it and, additionally, its longitudinal bias leads. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the priority of Taiwanese patent application No. 104135487, filed on Oct. 28, 2015, which is incorporated herewith by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to a peptide, and more particularly, to provide a peptide having effects on promoting wound healing, collagen production, angiogenesis, activation of immunocytes.
[0004] 2. The Prior Arts
[0005] After injury and surgery, most patients need a long time and certain food to recovery wound and energy. In early rehabilitation of patients, it is common method to get the proper foods, nutrients and drug which can help them heal fast and efficiently form injury.
SUMMARY OF THE INVENTION
[0006] As such, the present invention provides an effective peptide selected from the group consisting of SEQ ID NO:1-SEQ ID NO:11, and validates the effective peptides having the ability of promoting wound healing, collagen production, angiogenesis, activation of immunocytes.
[0007] A primary objective of the present invention is to provide a method for promoting wound healing, collagen production, angiogenesis, activation of immunocytes in a subject in need thereof, comprising administering to the subject an effective amount of a peptide, wherein the peptide is selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:11 or a combination thereof.
[0008] Another objective of the present invention is to provide a method for increasing the mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in a cell, comprising contacting the cell with an effective amount of a peptide, wherein the peptide is selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:11 or a combination thereof.
[0009] A further objective of the present invention is to provide a composition comprising: a core comprising a peptide; and a layer of natural polymeric material enveloping the core, wherein the peptide is selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:11 and a combination thereof.
[0010] According to an embodiment of the present invention, the peptide activates the mRNA levels of interleukin-1β (IL-1β).
[0011] According to an embodiment of the present invention, the peptide activates the mRNA levels of tumor necrosis factor-α (TNF-α).
[0012] According to an embodiment of the present invention, the cell is an infected cell or inflamed cell, and the cell is obtained from a wound tissue, an inflamed tissue or an infected tissue.
[0013] According to an embodiment of the present invention, the core further comprises an additive or pharmacological acceptable excipient, and the additive is citric acid, taurine, vitamins, pantothenic acid or nicotinic acid
[0014] According to an embodiment of the present invention, the composition is in the form of tablet.
[0015] According to an embodiment of the present invention, the composition is filled in a capsule.
[0016] According to an embodiment of the present invention, the composition is used as a food or pharmaceutical composition.
[0017] Accordingly, the present invention provides some embodiments to validate that the peptides can induce interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) overexpression to have the ability of anti-virus and bacteria, reduce infections, clean necrotic tissue, and promote debridement so as to facilitate wound healing. And other embodiments also validate that the peptides can induce interleukin-8 (IL-8) and chemokine (C-X-C motif) ligand 12 (CXCL12) overexpression to circulate immune cells to appear in the wound and active immune cells; still other embodiments also validate that the peptides can induce interleukin-10 (IL-10) down-expression to promote fibrous tissue to secrete collagen so as to facilitate wound repair and healing. The present invention further provides some embodiments to validate that the peptides can induce IL-1β and TNF-α overexpression to activate fibroblasts and keratinocyte so as to stimulate angiogenesis.
[0018] According to the effect of the peptides, the present invention further provides a method for promoting wound healing, collagen production, angiogenesis, activation of immunocytes in a subject in need thereof, comprising administering to the subject an effective amount of the peptides.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The present invention will be apparent to those skilled in the art by reading the following detailed description of a preferred embodiment thereof, with reference to the attached drawings, in which:
[0020] FIG. 1 is a histogram illustrating the effect of the peptides of the bass extract on interleukin-1β (IL-1β) mRNA expression in LPS induced inflammation model;
[0021] FIG. 2 is a histogram illustrating the effect of the peptides of the bass extract on tumor necrosis factor-α (TNF-α) mRNA expression in LPS induced inflammation model;
[0022] FIG. 3 is a histogram illustrating the effect of the peptides of the bass extract on interleukin-8 (IL-8) mRNA expression in LPS induced inflammation model;
[0023] FIG. 4 is a histogram illustrating the effect of the peptides of the bass extract on chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA expression in LPS induced inflammation model;
[0024] FIG. 5 is a histogram illustrating the effect of the peptides of the bass extract on interleukin-10 (IL-10) mRNA expression in LPS induced inflammation model;
[0025] FIG. 6 is a histogram illustrating the effect of the peptides of the bass extract on IL-1β mRNA expression in LPS induced inflammation model; and
[0026] FIG. 7 is a histogram illustrating the effect of the peptides of the bass extract on TNF-α mRNA expression in LPS induced inflammation model.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0027] The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.
[0028] In the present embodiment is to obtain the peptides of the bass extract. First, a prepared bass sample is treated with acid solution and extracted with water to obtain a bass mixture; then, the bass mixture is digested with enzyme complex to obtain a digested product; finally, the digested product is filtered and purified to obtain the peptides of the present invention. The examples below show the sequences of the peptides and its effects, the present invention is described in detail below.
EXAMPLE 1
Preparation of Bass Extract
[0029] First, cutting a bass into about 2 to 6 cm in size with slicer as raw material, wherein the bass comprises fish skin, scales, bone and meat. And washing the raw material with 2 to 5-fold of reverse osmosis (RO) water for 2 to 3 times to remove blood and impurities, obtaining a prepared bass sample.
[0030] Then, treating the prepared bass sample with an acid solution at a ratio of 1:5 (w/v), wherein the concentration of the acid solution is 1% to 5% hydrochloric acid, sulfuric acid or phosphoric acid. Soaking the acid treated bass sample in 15° C. to 20° C. for 10 to 48 hr, and washing the acid treated bass sample with 2 to 5-fold of RO water for 2 to 3 times to remove the acid solution, finally adjusting the pH value between 4 and 8 with calcium carbonate to obtain a bass mixture.
[0031] After preparing the bass mixture, extracting the bass mixture with 55° C. to 100° C. hot water for 1 to 6 hr to obtain an extracted bass mixture; centrifuging the extracted bass mixture at 3000 rpm for 10 min and filtering the impurities. Purifying the extracted bass mixture with 0.2% to 1% calcium carbonate or limestone, then filtering the extracted bass mixture with 1 to 10 μm filter membrane and ion exchange resin column to remove impurities and limestone, further, to isolate and purify an effective peptide from the extracted bass mixture. Treating the effective peptide with activated carbon to deodorize and decolorize, and concentrating the effective peptide under reduce pressure to a volume of 1/10 to 1/20 at 50° C. to 60° C.
[0032] Next, digesting the effective peptide with an enzyme complex at 40° C. to 60° C. for 1 to 5 hr to obtain a digested product, wherein the enzyme complex comprises 0.01% to 0.1% keratinase and bromelain, 0.1% to 5% papain, trypsin, pepsin, alcalase, neutrase, protamex and flavourzyme. After digesting, denaturing the enzyme in the digested product at 85° C. to 95° C. for 10 to 30 min, and cooling. Filtering the digested product with diatomaceous earth and activated carbon for two times; sterilizing the digested product with ultra-high temperature (UHT) at 135° C. to 140° C. for 3 to 5 sec; and filtering the digested product with 0.2 μm filter membrane to sterilize and remove small impurities, further, to obtain the peptides of the bass extract in the present invention.
EXAMPLE 2
The Sequence of the Peptides of the Bass Extract
[0033] After appropriate dilution, the peptides of the bass extract are centrifuged at 13,000 rpm for 2 min to obtain 200 μL supernatant. The supernatant is desalted and concentrated using C18-Zip Tip (MILLPORE, MA) and dissolved in water taking a half volume to perform multiple LC-MS/MS analysis. All MS/MS spectra are processed using Mascot Distiller and database search is performed by Mascot Search engine.
[0034] Reaction condition:
Mass Spectrometer: LTQ XL (Thermo Scientific) LC system: Agilent 1200 Series Buffer A: ddH 2 O/0.1% formic acid Buffer B: 100% ACN/0.1% formic acid Analytical column: C18 reverse phase column
[0000]
TABLE 1
Gradient table
Time (min)
B %
0.00
5
10.02
5
10.05
5
45.00
40
50.00
85
60.00
85
63.00
5
75.02
5
75.05
5
90.00
5
[0040] After sequencing these peptides, there are 11 peptides in the bass extract, as shown in Table 2.
[0000]
TABLE 2
The sequence of the peptides
of the bass extract
SEQ ID
Sequence
SEQ ID NO: 1
VPGPMGPMGPRGPPGPSGSPGPQG
SEQ ID NO: 2
VPGPMGPMGPRGPPGPS
SEQ ID NO: 3
VPGPMGPMGPRGPPGPSGS
SEQ ID NO: 4
ISVPGPMGPM
SEQ ID NO: 5
VPGPMGPMGPRGPPGPSGSPGPQG
SEQ ID NO: 6
VPGPMGPMGPRGPPGPSGS
SEQ ID NO: 7
PGSSGEQGAPGPSGPAGPRGPPGS
SGSTGKDGVNGLPGPIGPPGPRGR
NGDV
SEQ ID NO: 8
PAGNVGAPGPKGTRGAAG
SEQ ID NO: 9
PQMSYGYDEKSAGISVPGPMGPM
SEQ ID NO: 10
GSTGESGRPGEPGLPGA
SEQ ID NO: 11
GAPGF
EXAMPLE 3
The Gene Expression of Immunocytes
[0041] Human monocytic (THP-1) cells are cultured in 6-well plate (5×10 5 ), and separated into 4 groups, each experimental group is treated with lipopolysaccharide (LPS) for LPS induced inflammation model, as shown in Table 3.
[0000]
TABLE 3
The treatment and reaction time of each group
Group
Treatment
Reaction Time
Control group
No
No
LPS comparable group
LPS
27 hr, 9 hr, 6 hr
The peptides of the
1% peptides
THP-1 cells are induced by LPS
bass extract
of the bass
prior to the peptides treatment (3 hr
(low concentration)
extract +
minimum), and THP-1 cells are
LPS
treated with the peptides of the
bass extract for 24 hr, 6 hr and
3 hr, respectively.
The peptides of the
2% peptides
THP-1 cells are induced by LPS
bass extract
of the bass
prior to the peptides treatment (3 hr
(High concentration)
extract +
minimum), and THP-1 cells are
LPS
treated with the peptides of the
bass extract for 24 hr, 6 hr and
3 hr, respectively.
[0042] Collecting THP-1 cells with different treatment and reaction time, extracting RNA of THP-1 cells using RNA isolation kit (GeneMark), reverse transcribing RNA to cDNA using Transcriptor First Strand cDNA Synthesis Kit (Roche), detect target gene using SYBR Green Master Mix (KAPA), and analyzing the gene expression using Step One Software (Applied Biosystems) to identify the impact and effect of the peptides of the bass extract on the immunocytes, which are shown in FIG. 1 to FIG. 7 .
[0043] Referring to FIG. 1 , there is shown a histogram illustrating the effect of the peptides of the bass extract on interleukin-1β (IL-1β) mRNA expression in LPS induced inflammation model. As show in FIG. 1 , IL-1β mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 6 hr model, IL-1β mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 3 hr is increased 4.8 and 7.9 fold compared to control group (LPS_6 hr); in LPS induced inflammation for 9 hr model, IL-1β mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 6 hr is increased 4.3 and 8.7 fold compared to control group (LPS_9 hr).
[0044] Referring to FIG. 2 , there is shown a histogram illustrating the effect of the peptides of the bass extract on tumor necrosis factor-α (TNF-α) mRNA expression in LPS induced inflammation model. As show in FIG. 2 , TNF-α mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 6 hr model, TNF-αmRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 3 hr is increased 3 and 3.5 fold compared to control group (LPS_6 hr); in LPS induced inflammation for 9 hr model, IL-1β mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 6 hr is increased 2.3 and 4 fold compared to control group (LPS_9 hr). IL-1β and TNF-α overexpression are important mediators of inflammation to have the ability of anti-virus and bacteria, to reduce infections, clean necrotic tissue, and to promote debridement so as to facilitate wound healing.
[0045] Referring to FIG. 3 , there is shown a histogram illustrating the effect of the peptides of the bass extract on interleukin-8 (IL-8) mRNA expression in LPS induced inflammation model. As show in FIG. 3 , IL-8 mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 6 hr model, IL-8 mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 3 hr is increased 7.6 and 6.3 fold compared to control group (LPS_6 hr); in LPS induced inflammation for 9 hr model, IL-8 mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 6 hr is increased 4.7 and 7.9 fold compared to control group (LPS_9 hr).
[0046] Referring to FIG. 4 , there is shown a histogram illustrating the effect of the peptides of the bass extract on chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA expressions in LPS induced inflammation model. As show in FIG. 4 , CXCL12 mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 6 hr model, CXCL12 mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 3 hr is increased 1.9 and 3 fold compared to control group (LPS_6 hr); in LPS induced inflammation for 9 hr model, CXCL12 mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 6 hr is increased 1.7 and 3.2 fold compared to control group (LPS_9 hr). IL-8 and CXCL12 overexpression can stimulate immune system circulating immune cells to appear in the wound and active immune cells.
[0047] Referring to FIG. 5 , there is shown a histogram illustrating the effect of the peptides of the bass extract on interleukin-10 (IL-10) mRNA expression in LPS induced inflammation model. As show in FIG. 5 , IL-10 mRNA expression in THP-1 cells induced by LPS is decreased. In LPS induced inflammation for 27 hr model, IL-10 mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 24 hr is decreased 54% and 30% compared to control group (LPS_27 hr). IL-10 down-expression can promote fibrous tissue to secrete collagen so as to facilitate wound repair and healing.
[0048] Referring to FIGS. 6 and 7 , there are shown histograms illustrating the effect of the peptides of the bass extract on IL-1β and TNF-α mRNA expressions in LPS induced inflammation model. As show in FIG. 6 , IL-1β mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 27 hr model, IL-1β mRNA expression in THP-1 cells treated with 1% and 2% respectively the peptides of the bass extract for 24 hr is increased 3.3 and 5.1 fold compared to control group (LPS_27 hr). As show in FIG. 7 , TNF-α mRNA expression in THP-1 cells induced by LPS is increased. In LPS induced inflammation for 27 hr model, TNF-α mRNA expression in THP-1 cells treated with 2% the peptides of the bass extract for 24 hr is increased 2.3 fold compared to control group (LPS_27 hr). IL-1β and TNF-α overexpression can activate fibroblasts and keratinocyte to stimulate angiogenesis.
[0049] Therefore, according to above-mentioned the impact of IL-1β, TNF-α, IL-8, IL-10 and CXCL12 expressions in LPS induced inflammation model, which validates that the peptides of the present invention can circulate immune cells to appear in the wound and active immune cells, have the ability of anti-virus and bacteria, reduce infections, clean necrotic tissue, and promote debridement so as to facilitate wound healing. Also, the peptides of the present invention can promote fibrous tissue to secrete collagen so as to facilitate wound repair and healing. Additionally, IL-1β and TNF-α overexpression can activate fibroblasts and keratinocyte to stimulate angiogenesis.
[0050] According to the effect of the peptides, the present invention further provides a method for promoting wound healing, collagen production, angiogenesis, activation of immunocytes in a subject in need thereof, comprising administering to the subject an effective amount of the composition or stable aqueous composition containing the peptides. The composition or stable aqueous composition can be tablet, capsule, liquid, gel, slurry, suspension, power, dressing, lotion, spray and film, but not limited thereto. Moreover, the composition comprising: a core comprising the peptides of the present invention; and a layer of natural polymeric material enveloping the core, wherein the core further comprises an additive or pharmacological acceptable excipient, and the additive is citric acid, taurine, vitamins, pantothenic acid or nicotinic acid. The stable aqueous composition comprising: the peptides of the present invention; and a solubilizing agent. The composition or stable aqueous composition further can be a food or pharmaceutical composition as a healthcare-related product, or be an external application as auxiliary product.
[0051] Although the present invention has been described with reference to the preferred embodiments thereof, it is apparent to those skilled in the art that a variety of modifications and changes may be made without departing from the scope of the present invention which is intended to be defined by the appended claims. | The present invention provides 11 peptides represented as SEQ ID NO: 1-11. The peptides have the ability of anti-virus and bacteria, and can reduce infections, clean necrotic tissue, and promote debridement so as to facilitate wound healing. Moreover, the peptides can also induce collagen secretion and activate fibroblasts and keratinocytes so as to stimulate angiogenesis. Thus, the peptides of the present invention are suitable for development as a health caring product to help an individual enhance recovery and immunity. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 13/229,717, filed Sep. 10, 2011, which is a continuation of PCT application PCT/US2011/044591, filed on Jul. 19, 2011, which claims the benefit of U.S. Provisional Application 61/365,761, filed Jul. 19, 2010. Each application is incorporated by reference in its entirety.
BACKGROUND
[0002] 1. Field of the Invention
[0003] This disclosure relates generally to a personal aircraft configured to provide safe operations while achieving robust control. In particular, the described invention includes an aircraft with vertical takeoff and landing capability, and which provides vertical and horizontal thrust in a controlled fashion for hover, transition and cruise flight.
[0004] 2. Description of Related Art
[0005] Taking off and landing vertically, instead of using a runway to develop sufficient velocity on the ground for wings to provide adequate lift, requires an aircraft to provide both vertical and forward thrust. Thrust produced in the vertical direction provides lift to the vehicle; thrust produced horizontally provides forward movement. A vertical takeoff and landing (VTOL) aircraft can produce both vertical and horizontal thrust, and is able to control these forces in a balanced fashion.
[0006] The rotary wing aircraft, or helicopter, is one common type of VTOL aircraft. Helicopters have large rotors that provide both vertical and horizontal thrust. In order for the rotors to perform this dual function across a range of airspeeds, the rotors are typically quite complex. Depending on the vehicle flight condition, the rotor blades must be at different orientation angles around the 360 degrees of azimuth rotation to provide the needed thrust. Therefore, rotors have both collective and cyclic variation of the blade orientation angle. Collective varies the angle of each blade equally, independent of the 360-degree rotation azimuth angle. Cyclic varies the blade angle of attack as a function of the 360-degree rotation azimuth angle. Cyclic control allows the rotor to be tilted in various directions and therefore direct the thrust of the rotor forwards, backwards, left or right. This direction provides control forces to move the helicopter in the horizontal plane and respond to disturbances such as wind gusts.
[0007] Helicopter rotors are large and unprotected from hitting nearby obstacles. Additionally, they utilize mechanically complex systems to control both the collective and cyclic blade angles. Such rotors are mechanically complex and require maintenance. The rotors generally rotate at a low speed; this results in heavy transmissions between the rotor and motor. The transmissions, or gearboxes, decrease the vehicle payload potential, as well as vehicle safety. Because of the mechanical complexity across the entire vehicle system, many parts are single points of failure. Because of this lack of redundancy, frequent inspections and maintenance are required to keep the vehicle safe.
SUMMARY
[0008] The described embodiments provide a personal aircraft with a configuration that is safe, quiet, and efficient, as well as easy to control, highly compact, and which is able to accomplish vertical takeoff and landing with transition to and from forward flight. In one embodiment, the aircraft configuration includes multiple rotors oriented to provide vertical thrust for lift and control during takeoff, transition to and from forward flight, and landing. The rotors are located longitudinally along the port and starboard sides of the fuselage, with two or more rotors located on each side.
[0009] The fuselage carries a variable-weight payload. The aircraft has tandem wings at the front and rear of the vehicle with a combined center of lift near the center of gravity (CG) of the aircraft. The wings provide lift and control during cruise, with one or more aft-located propellers to provide forward thrust. The combination of vertical lift rotors and front and rear tandem wings bound the rotors, permitting movement in the aircraft's center of gravity while still enabling the vehicle to maintain vertical and horizontal flight control. The forward and rear wings are also located to provide a boundary to avoid foreign object damage (FOD) to the lift rotors. The control surfaces, which include elevator and ailerons, are usable to compensate for changes in CG of the aircraft during flight by adjusting the center of lift, in addition to changing angle of attack and attitude. The vertical lift rotors are arranged around the CG, and the thrust of each rotor is adjustable, which permits the relocation of the center of lift in vertical flight if the CG shifts.
[0010] Due to the multiple number and independence of the vertical lift rotors, the vertical thrust is redundant and thrust and control remain available even with the failure of any single rotor. Since there are multiple vertical rotors that provide large control forces, the rotors are able to be smaller, with faster response rates for operation even in gusty wind conditions. In one embodiment a separate electric motor and controller powers each vertical lift rotor, in order to provide lift system redundancy from failure of one or more lifting rotors. In some embodiments, the vertical thrust rotors are embedded in ducts that conceal them and provide increased lift. In other embodiments, protective shrouding guards against contact with other objects and prevent FOD to the rotors. The protective shielding in combination with in-line vertical lift rotors provide low cruise drag for efficient flight. Low tip speed vertical lift rotors are used in various embodiments to produce low community noise levels during takeoff, transition, and landing. Embodiments with a low front wing and high rear wing with winglets provide high aerodynamic efficiency while also providing yaw stability for the aircraft. In some embodiments, the wings fold to provide a compact vehicle footprint when in hover or while on the ground. Some embodiments of the wing have control surfaces only on the inner part of the wing fold so that no articulating control linkages are required. Since the lift rotors that are used for vertical lift are separate from the forward thrust propellers, each is optimized for its specific operating conditions. Such a vehicle can be used for either piloted or unpiloted embodiments across a range of occupant sizes or payloads.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a top view of a personal aircraft vehicle in accordance with one embodiment.
[0012] FIG. 2 illustrates a second view of a personal aircraft vehicle in accordance with one embodiment.
[0013] FIG. 3 illustrates a front view of a personal aircraft vehicle in accordance with one embodiment of the present invention.
[0014] FIG. 4 illustrates a view of the left side of a personal aircraft vehicle in accordance with one embodiment.
[0015] FIG. 5 illustrates a view of a personal aircraft with ducted rotors in accordance with one embodiment.
[0016] FIG. 6 illustrates a view of a personal aircraft with ducted rotors in accordance with an alternative embodiment.
[0017] FIGS. 7A and 7B illustrate two views of a personal aircraft with folded wings in accordance with one embodiment.
DETAILED DESCRIPTION
[0018] FIG. 1 illustrates a personal aircraft 100 in accordance with one embodiment. Aircraft 100 includes vertical lift rotors 101 ; forward flight propellers 103 ; a forward wing 104 ; a rear wing 105 having winglets 106 ; protective shroud 102 (also known as a fence); and a fuselage 107 . Fuselage 107 also includes landing gear and power source (not shown). FIG. 2 illustrates a second view of personal aircraft 100 , including port-side main landing gear and nose landing gear 205 . FIG. 3 illustrates a front view of personal aircraft 100 , in which port landing gear, starboard landing gear and nose gear 205 are visible. FIG. 4 illustrates a view of the left (port) side of aircraft 100 in accordance with one embodiment.
[0019] In various embodiments, aircraft 100 is sized to accommodate a single pilot and personal cargo. For example, in various embodiments the length of the aircraft from nose to its aft-most surface is between 15 and 20 feet, and its wingspan is between 15 and 20 feet. In alternative embodiments, the aircraft may be longer or shorter, wider or narrower, as will be appreciated by those of skill in the art, without departing from the principles described here.
[0020] Aircraft 100 is constructed in various embodiments primarily of a composite material. Fuselage 107 and wings 104 , 105 are made from carbon fiber composite material. In alternative embodiments, the wings may have metal fittings and ribs attached to the inside and outside of a carbon fiber composite wing skin. In some embodiments the wing skins may comprise composite materials made of carbon fiber combined with other composite materials such as Kevlar. In other alternative embodiments, the fuselage may comprise a metal truss made from material such as but not limited to steel or aluminum with a composite skin that covers the truss. The composite fuselage skin in this embodiment may be made of carbon fiber, Kevlar, or other composite materials as understood by those of skill in the art. The cockpit windows in one embodiment are polycarbonate, though other lightweight clear plastics may also be used. In some embodiments, fences 110 are made from a Kevlar and carbon fiber composite. In alternative embodiments, they are made only from carbon fiber or only from Kevlar or similar fibers.
[0021] Rotors 101 in one embodiment have a 16 inch radius, and are made from carbon fiber composite material, and in an alternative embodiment from carbon fiber composite blades attached to an aluminum hub. In other embodiments, rotors are made from wood blades attached to an aluminum hub, or wood blades attached to a carbon fiber composite hub. The rotors may be a single piece that bolts onto the motor assembly.
[0022] Aircraft 100 includes a forward wing 104 and an aft wing 105 . The aft wing is swept back and has winglets 106 at its ends. The winglets provide lateral stability and decrease the drag due to lift on the aft wing. Sweeping the wing back improves the pitch stability of the aircraft and increases the benefits of the winglets on lateral stability. In some embodiments the aft wing can fold, and thus maintain the same overall vehicle length as an aircraft with an unswept aft wing. Additionally, the sweep of the aft wing provides more space for the rotors to fit into. Forward wing 104 is also attached to fuselage 107 at a point substantially lower than is aft wing 105 in various embodiments. A non-planar wing lifting system enables the wings to develop efficient lift during cruise flight. The vertical separation between the two wings is chosen to be as large as possible, given the constraint of attaching to the fuselage. By maximizing the wing vertical separation, the negative aerodynamic interaction between the front wing and the rear wing is reduced. Thus, the drag due to lift of the vehicle is significantly decreased, for example by 15-20% compared to a single in-plane wing lifting system.
[0023] The winglets 106 are located at the tip of rear wing 105 to provide decreased drag due to lift on the rear wing, as well as yaw or directional stability and control. The particular winglet shape is established for adequate stability, as will be understood by those skilled in the art. In some embodiments the winglets extend downward and provide improved controllability by reducing the coupling between the sideslip angle of the aircraft and the yawing moment that the airflow produces on the aircraft. In other embodiments, as illustrated in FIG. 2 , the winglets 106 extend upwards.
[0024] In one embodiment, the tandem wing system has joints where the wingtips on each wing fold, allowing aircraft 100 to fit in a constrained space. For example, in one embodiment folding the wings enables the aircraft 100 to be stored an 8′ by 7′ by 16′ space, or the space provided by a typical single car garage. In one embodiment the rear wing 105 has a dihedral angle of 8.4 degrees. In other embodiments the dihedral ranges between −10 and 10 degrees.
[0025] Vertical lift rotor assemblies 101 are mounted on each side of aircraft 100 . In one embodiment, a propulsion boom 114 is secured to each side of the fuselage 107 . Vertical lift rotor assemblies 101 are installed on top of the booms 114 . Propulsion booms 114 are attached to the fuselage 107 with struts 116 . The struts 116 are positioned so that the downwash from the rotors does not impinge on the struts. In some embodiments there are 3 struts connecting each boom to the fuselage. In alternative embodiments there are 2 or 1 struts connecting each boom to the fuselage. In other embodiments the struts may be swept forward, aft, up, or down to improve the attachment of the booms to the fuselage. In one embodiment, a vertically oriented support structure provides increased bending stiffness from the vertical lift rotor loads during hover.
[0026] Each vertical lift rotor assembly 101 includes a rotor and a motor. The rotor may comprise blades attached to a hub, or may be manufactured as a single piece with an integral hub. The hub provides a central structure to which the blades connect, and in some embodiments is made in a shape that envelops the motor. The motor includes a rotating part and a stationary part. In one embodiment the rotating part is concentric to the stationary part, known as a radial flux motor. In this embodiment the stationary part may form the outer ring of the motor, known as an inrunner motor, or the stationary part may form the inner ring of the motor, known as an outrunner motor. In other embodiments the rotating and stationary parts are flat and arranged in opposition to each other, known as an axial flux motor. The rotor is attached to the rotating part of the motor. The stationary part of the motor is attached to the propulsion boom 114 . In some embodiments the motor is a permanent magnet motor and is controlled by an electronic motor controller. The electronic motor controller sends electrical currents to the motor in a precise sequence to allow the rotor to turn at a desired speed or with a desired torque.
[0027] As noted, aircraft 100 includes multiple rotor assemblies 101 per side. The vertical lift rotors are configured to generate thrust that is independent of the thrust generated by the forward flight propellers 103 during horizontal cruise. The vertical lift rotors provide enough thrust to lift the aircraft off the ground and maintain control. In one embodiment, each rotor generates more, e.g., 40% more, thrust than is needed to hover, to maintain control in all portions of the flight envelope. The rotors are optimized by selecting the diameter, blade chord, and blade incidence distributions to provide the needed thrust with minimum consumed power at hover and low speed flight conditions. In various embodiments, half of the rotors rotate in one direction, and the other half rotate in the opposite direction to balance the reaction torque on aircraft. In the embodiment illustrated in FIG. 1 , four vertical lift rotor assemblies 101 per side are shown. In alternative embodiments more or fewer vertical lift rotors provide the vertical lift and control. When at least two rotors per side are present, the ability to produce a vertical force with equilibrium about the center of gravity is retained even when one rotor fails. This is achieved by decreasing the thrust on the opposite quadrant to the failed rotor. When three rotors per side are present, control about all three axes, or directions of flight, is available. As the number of rotors per side increases, the loss of any one rotor results in a decreasing overall loss of vertical thrust. However, with each extra pair of rotors there is increasing complexity and probability that a failure would result, as well as increased cost and weight.
[0028] In one embodiment, two vertical lift rotor assemblies 101 per side are located in front of the CG and two are located behind the CG. In this manner, the center of lift of the rotors in hover is co-located with the center of gravity of the aircraft 100 . This arrangement permits a variation of longitudinal or lateral positioning of the payload in the fuselage 107 because each independent vertical lift rotor is able to modify its thrust to provide a balanced vertical lift or, alternatively, unbalanced lift to provide control.
[0029] Forward flight propellers 103 provide the thrust for transition to forward flight, climb, descent, and cruise. In one embodiment two or more forward thrust propellers 103 are mounted along the span of the rear wing 105 . Alternatively, a single forward thrust propeller is mounted on the aft portion of the fuselage 107 at the center of the span. The propellers can be rotated in opposite directions so that the torque required to turn them does not produce a net torque on the airplane. Also, the thrust of the two propellers can be varied differentially to provide a yaw control moment. Positioning on the wing results in less inflow disturbance to the propellers. Use of a single propeller on the fuselage permits fewer components and less weight, but with a different-sized motor and with the inflow including disturbances from the fuselage. In one embodiment a single propeller is used in a hybrid-electric system having a small hyrdrocarbon-based fuel engine to provide power in forward flight and/or to recharge the battery system.
[0030] The fuselage 107 provides payload volume near the vehicle center of gravity as well as the attachment structure for the vertical lift rotors 101 , forward wing 104 , and the rear wing 105 . Forward flight propellers 103 are also attached to the aft portion of the fuselage. Other embodiments have a protective shroud or the ducts attached to the fuselage in a fashion to provide the least interference with the rotor airflow, while resisting bending loads.
[0031] The vertical lift rotors and the forward propellers are driven by electric motors that are powered by a power system. In one embodiment the power system includes a battery that is attached to one motor controller for each motor. The battery provides a DC voltage and current that the motor controllers turn into the AC signals that make the motors spin in response to control input from the flight computer or other source. In alternative embodiments, the rotors and propellers are powered by a power system that includes a hybrid-electric system with a small hydrocarbon-based fuel engine and a smaller battery. The hydrocarbon engine provides extended range in forward flight and can recharge the battery system.
[0032] The vertical lift rotor assemblies 101 in various embodiments are protected by either ducts or protective shrouds 102 to avoid accidental blade strikes. In one embodiment, as illustrated in FIG. 5 , the rotor blades are completely and tightly surrounded by a duct 502 that also provides incremental lift. This additional lift is generated by suction forces on the duct surface, due to the increased velocity of the air in front of the rotors. In another embodiment, the rotor is loosely surrounded by only a protective shroud 102 or fence. Referring to FIG. 6 , in those embodiments that use vertical lift ducts, the ducts have embodiments either with or without duct covers 601 that seal the ducts from airflow during cruise flight to decrease the vehicle drag.
[0033] The vertical lift rotors 101 generate thrust that is independent from the thrust generated by the forward flight rotors 103 during horizontal cruise. In some embodiments this permits fixed pitch to be used for both the rotors and propellers. This independence of thrust generation as opposed to having the same rotors generating both the vertical and horizontal thrust, permits the rotors 101 to be optimized for zero-airspeed flight performance and low noise, without the need for a variable pitch mechanism. The rotors are optimized by designing for a single pitch blade setting at the hover and low speed flight conditions. The forward flight propellers 103 are optimized for cruise airspeed flight performance, also without the need for a variable pitch mechanism. These blades are designed with the optimum pitch, twist, taper, and rpm for cruise operation. Since the rotor and propellers are completely separate, they are able to have different characteristics, such as tip speed, rpm, and diameter so that they are optimal at their specific operating conditions. This decreases the mechanical complexity of the propulsion system.
[0034] Longitudinal arrangement of multiple vertical lift rotors 101 permits pitch, roll, and yaw moments as well as vertical force to be generated directly through a combination of direct thrust or differential torque across the combination of rotors. By varying the thrust of rotors in different locations on the vehicle, the control moments are created. By varying thrust on some of the rotors, the altitude can be controlled. The use of direct thrust and differential torque provides predictable control forces. The result is more rapid response rates and gust responsiveness, which is enhanced by the low moments of inertia of the small diameter vertical lift rotors 101 and the high torque and response rates of electric motors. Combined, this system enables a control system that is accurate and responsive to the pilot control inputs.
[0035] As noted, the use of multiple independently controlled rotors provides a redundant lift system. For example, a system that includes six or more rotors permits hover and vertical ascent with safe operation without forward airspeed, even if one or several individual components fail.
[0036] The vertical lift rotors 101 are arranged longitudinally along the aircraft direction of travel in-line to reduce the cruise drag. Other embodiments have the rotors offset in other ways, either to align with the body airflow, or to provide a more compact footprint. One embodiment has an in-line arrangement with a horizontally oriented support structure that attaches to the fuselage 107 .
[0037] As noted, wing 104 and 105 fold in some embodiments. Some embodiments have a wing fold that is positioned at a location where the loads are small, outboard of 50% of the span, for example, to permit a lighter weight hinge. In other embodiments, the forward wing does not fold. In other embodiments, the wings fold so the aircraft can fit into an 8′ wide space, such as a typical single car garage. Alternative embodiments also include folding the forward wing in other ways, such as in a scissor motion underneath the fuselage or along the side of the fuselage. This scissor folding is accomplished through pivot and pin at the center of the front wing that permits a rotation backwards about that center pivot point. This embodiment permits wing articulation about a single point to reduce weight at a location where the wing structural depth is largest, as well as enabling the front wing to be folded completely away to the side of the vehicle by an electro mechanical actuator to promote better pilot visibility while in hover or on the ground. In an embodiment including a scissor-fold front wing, the landing gear includes a single front wheel with two main rear landing gear wheels.
[0038] The rear wing 105 also provides a portion of the aircraft lift during forward flight. In one embodiment, and referring to FIGS. 7A and 7B , the rear wing fold 302 permits the rear wing structure to articulate downward to permit ground operation or storage in a more compact footprint. Folding downward permits the winglet 303 to fit into the small door opening or parking storage space, both in terms of the vehicle width and height. In other embodiments, the rear wing does not fold. Alternative embodiments also include folding the rear wing in other ways, such as upward and on top of the rear wing if longer spans are desired and not capable of folding while clearing the ground.
[0039] In one embodiment, aircraft 100 is capable of taking off and landing with the front and rear wings folded. Taking off and landing with the wings folded in vertical flight decreases the gust response of the vehicle due to unsteady wind conditions through decreased wing lift performance and shorter wing spans. Since the wing lift is not required in hover flight, but only in forward flight, is it possible to wait to unfold the wings until sufficient altitude is achieved away from ground. Avoiding ground wing unfolding is advantageous for some operations where the ground takeoff and landing space available and wind conditions are not favorable. An electromechanical actuator provides the actuation force to unfold the wing before commencing forward flight.
[0040] In one embodiment, control surfaces are located on the inner portion of the front wing fold 301 and rear wing fold 302 to permit folding without control lines required outboard of the folding hinge mechanism to provide less mechanical complexity through fewer moving parts. The control surfaces provide pitch, roll, and yaw control during forward flight aerodynamically so that the vertical lift rotors are not required for control except at low or zero forward speed. Other embodiments that require greater forward flight control responsiveness also have control surfaces outboard of the wing fold mechanism. Other embodiments only have control surfaces on the outboard section of the wing.
[0041] Landing gear 205 is provided with wheels to permit the aircraft to move while on the ground. One forward 204 and two rear 202 main landing gear provide lower drag and less lift interference on the front wing. In other embodiments the landing gear is a skid and has no wheels, since the aircraft is capable of takeoff and landing without forward movement. Alternative embodiments include two forward and one rear main landing gear to permit the front landing gear to be widely separated for ground stability. In some embodiments, some or all of the wheels are fitted with electric motors that allow the wheels to be driven. Such motors allow the vehicle to be self-propelled while on the ground.
[0042] In addition to the embodiments specifically described above, those of skill in the art will appreciate that the invention may additionally be practiced in other embodiments. For example, in an alternative embodiment, aircraft 100 is designed to accommodate two or more occupants. In such an embodiment, the wingspan is larger, the rotors have a larger diameter, and the fuselage 107 is wider. In an alternative embodiment, aircraft 100 is an unmanned vehicle that is capable of flight without a pilot or passengers. Embodiments without passengers have additional control systems that provide directional control inputs in place of a pilot, either through a ground link or through a predetermined flight path trajectory.
[0043] Although this description has been provided in the context of specific embodiments, those of skill in the art will appreciate that many alternative embodiments may be inferred from the teaching provided. Furthermore, within this written description, the particular naming of the components, capitalization of terms, etc., is not mandatory or significant unless otherwise noted, and the mechanisms that implement the described invention or its features may have different names, formats, or protocols.
[0044] Finally, it should be noted that the language used in the specification has been principally selected for readability and instructional purposes, and may not have been selected to delineate or circumscribe the inventive subject matter. Accordingly, the disclosure is intended to be illustrative, but not limiting, of the scope of the invention. | A safe, quiet, easy to control, efficient, and compact aircraft configuration is enabled through the combination of multiple vertical lift rotors, tandem wings, and forward thrust propellers. The vertical lift rotors, in combination with a front and rear wing, permits a balancing of the center of lift with the center of gravity for both vertical and horizontal flight. This wing and multiple rotor system has the ability to tolerate a relatively large variation of the payload weight for hover, transition, or cruise flight while also providing vertical thrust redundancy. The propulsion system uses multiple lift rotors and forward thrust propellers of a small enough size to be shielded from potential blade strike and provide increased perceived and real safety to the passengers. Using multiple independent rotors provides redundancy and the elimination of single point failure modes that can make the vehicle non-operable in flight. | 1 |
RELATED APPLICATION
This is a continuation of copending application Ser. No. 07/957,509 filed on Oct. 5, 1992 now abandoned which application is a continuation-in-part of co-pending and allowed U.S. application Ser. No. 07/722,886 filed Jun. 28, 1991 by applicants herein and allowed for issuance Oct. 6, 1992 as U.S. Pat. No. 5,152,749.
BACKGROUND OF THE INVENTION
The present invention relates to a surgical apparatus for the placement of an instrument within a body cavity. More particularly, the invention relates to an apparatus, device and method for end-to-end instrument placement.
Suprapubic catheters and instruments are used in many clinical settings including cases involving female incontinence, transurethral resection of the prostate where continuous irrigation is used, neurogenic bladders, spinal cord injury and other cases where bladder drainage and/or healing are desired. Additionally suprapubic instruments are used for inspection and therapy of the bladder, prostate, and/or ureter. Suprapubic catheterization offers a number of advantages over transurethral catheterization. These advantages include increased patient comfort, minimization of infection, improved irrigation and drainage during and after resection of the prostate, easier replacement and superior convenience during long-term catheterization, and improved evaluation of voiding and residual urine when applicable. Also, the suprapubic site is a convenient access route for instruments to observe and treat various conditions, the design, shape, and size of the instrument not being restricted by the shape and size of the urethra or concerns of urethral injury.
U.S. Pat. No. 4,684,369 discloses a needle for introducing a suprapubic bladder drainage instrument through the urethra. The needle is adapted to be attached at its rear end to a catheter which follows the needle through the urethra.
Current methods of placing suprapubic catheters are the "outside-to-inside" method and the less common "inside-to-outside" method. With the outside-to-inside approach, a sharp trocar or catheter-obturator combination is used to pierce from outside the body through the lower abdomen and into the bladder to create a passageway for pushing the catheter into the bladder. By comparison, the inside-to-outside method employs a grasping tool which is passed into the bladder via the urethra and, after positioning, can be pressed through the bladder and abdominal wall near the symphysis. Then grasping the catheter, it is used to pull the catheter into the bladder where the catheter may be released and left in a suprapubic placement.
While complications are rare, difficulties have been reported with percutaneous outside-to-inside suprapubic catheterization using a trocar. For example, the catheter may be placed accidentally outside of the bladder. The standard method of using a trocar/catheter arrangement does not always provide the accuracy and control needed for correct placement of the catheter. Also, outside-to-inside catheterization presents risk of injury to the floor of the bladder or damage to the bowel. Uncertainties in trocar alignment, orientation, or insertion distance can lead to such injuries. Thus, poor alignment or variable depth can result in perforation of the peritoneum, incomplete bladder entry, or penetration of the posterior bladder wall. Furthermore, due to a limited choice of catheter sizes and types, inadequate catheter lumen size may result. Finally, inappropriate suprapubic puncture size may result in extravasation of urine around the catheter or into the retroperitoneum.
Use of the inside-to-outside technique can minimize the above problems, but the lack of well designed devices for performing the procedure has limited its adoption. With the inside-to-outside method, a curved grasping tool is passed through the urethra and its tip is pushed against the bladder dome and anterior abdominal wall. Suprapubic palpation enables the practitioner to select a desired penetration site. The curved tool is pressed against the bladder dome and in some cases forced through the bladder, fascia, and abdominal wall. In other techniques, an incision is extended from the exterior abdominal wall on to the instrument tip permitting its advancement. Once outside the abdomen, the device is coupled to the drainage tube in some fashion so that the tube is guided into the bladder. Once within the bladder, the drainage tube is released. The device is then removed by way of the urethra.
While various instruments which utilize the inside-to-outside approach exist, none have coordinated the penetration, coupling, and release functions. Currently used instruments include the Lowsley retractor, uterine packing forceps (for females), and modified urethral sound. In general, these instruments require many steps, lack uniformity, and are not always readily available. Use of such instruments often results in ineffective penetration, inadvertent loss of the catheter, and poor sealing between the catheter and bladder wall.
Improvements in the suprapubic instrument placement may be applied to other medical applications. For example, in substantially non-invasive methods of internal operations, e.g. laproscopic surgery, the practitioner accesses internal organs through small incisions and working sheaths. The instruments used in such operations are generally elongate and adapted for use by way of these small incisions or sheaths. Accordingly, improvements in placement of suprapubic instruments, which are generally elongate instruments, may be applied to such substantially noninvasive operations.
Placing in-dwelling drainage tubes such as ureteral stents can be difficult due to their lack of column strength, frictional forces, and the fact that direct control of their proximal end is typically lost once the stent entirely enters a body lumen. Various placement techniques have been employed to overcome these problems, but without providing the extent of instrument placement control a practitioner would desire. Such placement techniques include stent placement over a guidewire using a pushing tube to advance the stent; stent placement on a wire where the stent, guidewire and pusher advance as one; and stent placement alongside a wire using a guide-eye where the stent is pushed internally or externally at its distal tip. In use of guidewire instrument placement methods, it is desirable to leave the guidewire as free as possible because the guidewire constitutes the primary instrument access route.
U.S. Pat. No. 4,824,435 issued Apr. 25, 1989 to Jerry D. Giesy and Matthew W. Hoskins, inventors herein, shows a guide-eye instrument guidance system wherein elongate flexible elements are guided into place within a tortuous body passage by providing the elements with annular guides adjacent their distal ends and sliding the elements over a guidewire within the passage. Column strength to move the elements through the body passage may be provided by a tubular pusher slidably received on the guidewire. Several instruments, each including an annular guide at its distal end, may be sequentially or simultaneously guided into place over a single guidewire.
Under the technique and apparatus disclosed in U.S. Pat. No. 4,824,435 the instrument to be placed is slidably coupled at its distal end to a guidewire. Such slidable coupling may include a loop formation at the distal end of the instrument to be placed. For tubular instruments, a lateral cut or slot in the tube wall near the distal end slidably receives the guidewire. To mount the instrument, the guidewire is threaded into the open distal end of the tube and then out the wall opening provided by the lateral cut or slot. In either case, the instrument to be placed is slidably coupled at its distal end to the guidewire. If the instrument itself has sufficient column strength, the instrument may be positioned by application of force at its proximal end as its distal end slides along the access pathway provided by the guidewire. For instruments having insufficient column strength, a tubular pusher may be slidably and concentrically received upon the guidewire. The distal end of the pusher engages the slidably mounted distal end of the instrument to be placed to move the instrument to be placed along the guidewire and into position.
While the apparatus and method of the system shown in U.S. Pat. No. 4,824,435 has proven useful in many cases, it lacks certain instrument positioning control desired by many practitioners. In particular, the disclosed system is generally limited to pushing of instruments along a guidewire. The practitioner has limited additional positioning control over the instrument to be placed, e.g., the practitioner typically cannot retract the instrument along the guidewire.
Various technologies have also been developed to address access problems in placement of instruments within a body lumen. These technologies include higher-column strength stents, hydrophilic-coated stents, stents of hybrid materials, locking devices to lock the stent, guidewire and pusher as one.
No one instrument placement method and apparatus provides complete and versatile positioning control, i.e., pushing, pulling, and twisting, of the instrument to be placed especially in the context of guidewire instrument placement. Furthermore, those instrument placement methods available often limit the practitioner in use of other associated instrument placement methods. Present positioning systems suffer certain limitations.
In a trailing suture design, i.e., a Lubri-Flex (Registered Trademark of Surgitek) hydrophilic-coated stent, the suture trails the stent and provides retraction control during placement. Once positioning is complete the suture can be cut and pulled out or left in for use later in removing the stent. This provides reasonable control, but can be cumbersome and makes desirable a more simple coupling system.
The Speed Lok (TM) ureteral stent set available from Boston Scientific Corporation under the Registered Trademark Microvasive, is limited to one pass placement. The guidewire, stent, and pusher are designed specifically to be pre-coupled as a placement system, and cannot be employed in connection with a separate or pre-existing guidewire. The system does not offer a clean release between the pusher or positioner device and the instrument to be placed. Removal of instrument placement components can affect the position of the instrument placed. Accordingly, upon removal of the placement system following positioning of the instrument to be placed, the instrument placed may have been dislodged from its desired position.
The Kwart retro-inject (TM) stent sets require different pusher/inserter sizes for stents of different sizes. As understood, the Kwart retro-inject system coaxially mounts a stent inserter sleeve, release sleeve, and the stent upon a guidewire. Manipulation of the stent, i.e., positioning of the stent, is provided by the frictional inter-relationship among the coaxially mounted elements. Once the stent is positioned, one of the coaxially mounted elements is removed from the system to frictionally disengage the stent from the remaining portions of the system. The remaining portions of the system are then withdrawn from the stent. Thus, the Kwart retro-inject system is not an end-to-end coupling mechanism, the elements are used in coaxial relation. Furthermore, because the various components must be specifically sized relative to one another in order to achieve the desired frictional relationship, the system lacks versatility with respect to stent diameters. For any given stent diameter, a separate placement system dedicated to that diameter is required.
It is desirable, therefore, that a guidewire instrument placement method and apparatus provide a broader range of positioning control capability across a broader range of instrument placement methods and devices. It is particularly desirable that better grasp and release features be available for instrument placement over an in-place guidewire.
SUMMARY OF THE INVENTION
In accordance with a preferred embodiment of the present invention, end-to-end coupling between a placement instrument and an instrument to be placed is provided in the context of guidewire assisted instrument placement. The distal end of the instrument to the place is slidably captured upon the guidewire and an elongate positioner engages in end-to-end relation the proximal end of the instrument to be placed. The practitioner enjoys improved control over the positioning of the instrument to be placed, and may attach several such systems slidably upon the guidewire. Once the instrument to be placed is suitably positioned, the end-to-end coupling arrangement allows quick and complete detachment between the instrument to be placed and the placement instrument. This insures that the instrument to be placed remains in its position without being dislodged by the removal of the positioning instrument.
According to one embodiment of the invention, the end-to-end coupling arrangement is formed by a loop resting within a slot and a stylet resting coaxially within the instrument whereby the stylet locks the loop within the slot formation. In a second embodiment of the present invention, a collapsible loop captures a tail formation of the other instrument in order to accomplish end-to-end coupling. In a third embodiment of the invention, a flared distal end of an inner sleeve captures a tail formation of the instrument to be placed between the inner sleeve and an outer sleeve to accomplish end-to-end coupling.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more particularly described with reference to preferred embodiments as illustrated in the accompanying drawings, in which:
FIG. 1 is an exploded perspective view of a suprapubic instrument placement device in accordance with the present invention.
FIG. 2 illustrates a suprapubic instrument placement device similar to that of FIG. 1, but with an alternative handle shape and assembled to illustrate its coupling relationship to a catheter having a mating coupling means thereon.
FIGS. 3 and 4 are detailed views of coupling means for releasably coupling and locking together the instrument placement device and the instrument to be drawn into the bladder.
FIGS. 5A-5F illustrate suprapubic instrument placement according to the method of the present invention.
FIG. 6 illustrates an alternative coupling means in accordance with the present invention.
FIG. 7 is a needle and sheath arrangement adapted for placement within the male urethral sound.
FIG. 8 illustrates an instrument placement system for use in conjunction with a guidewire.
FIGS. 9 and 10 illustrate the uncoupling of the instrument placement system of FIG. 8.
FIGS. 11A-11C illustrate in-dwelling stent placement for coupling a kidney and a bladder by use of a guidewire and cystoscope according to the embodiment of FIG. 8.
FIGS. 12-14 illustrate a second instrument placement system for use in conjunction with a guidewire.
FIG. 15 illustrates a handle locking arrangement for the proximal end of the instrument placement system of FIGS. 12-14.
FIGS. 16 and 17 show an alternative locking arrangement for the distal end of the instrument placement system of FIGS. 12-14.
DETAILED DESCRIPTION OF THE INVENTION
Instrument placement as applied to suprapubic instrument placement uses a placement device comprising a needle similar in shape to that of the urethral sound, slidably disposed within a sheath sized to suitably dilate the puncture made by the needle. The distal tip of the needle coupling means adjacent thereto configured such that it accepts and couples with a mating coupling means attached to the instrument, e.g., catheter to be pulled into the bladder. The preferred structure of the coupling means on the needle and the instrument to be pulled into the bladder is such that the instruments cannot be pulled apart in the direction of their longitudinal axis, yet may be disengaged in response to lateral forces. To more fully secure the needle and instrument while drawing the instrument into the bladder, the sheath is advanced over the tip of the needle to prevent the instrument coupling means from releasing from the needle tip coupling means.
In FIG. 1 of the drawings, a suprapubic instrument placement device 10 includes a handle 12 with a central slot 14 therein. A luer lock hub 16 is mounted upon handle 12 between the proximal end 12a of the handle and the proximal end 14a of the slot. At the distal end 14b of the slot, an aperture 18 coaxial to hub 16 passes from the distal end 12b of the handle to the distal end 14b of the slot. A rigid needle 20 is accommodated within aperture 18 and couples at its proximal end 20a to the hub 16 at the proximal end 14a of slot 14 In the illustrated embodiment needle 20 is substantially straight but includes a bend 20c to provide a distal end portion which makes an angle of approximately 15 degrees with the main portion of the needle whereby needle 20 conforms generally in shape to that of a urethral sound.
A flexible sheath 22 slidably mounts upon needle 20 and conforms to the shape of needle 20. A proximal end 22a of sheath 22 threadably connects to a thumb piece 24 at a threaded aperture 25 thereof. An O ring 23 is interposed between the proximal end 22a of sheath 22 and thumb piece 24 for sealably coupling sheath 22, thumb piece 24, and needle 20. Thumb piece 24 is slidably positionable within the slot 14 with a smaller diameter portion of aperture 25 (not shown) closely receiving needle 20 for slidable mounting thereon. The aperture 25 of thumb piece 24 is desirably of two diameters, a larger diameter threaded portion closest to distal slot end 14b adapted to receive the proximal end 22a of sheath 22 and the above-mentioned lesser diameter portion closest to proximal slot end 14a adapted for slidably receiving the needle 20. A spring 26 mounts coaxially upon the needle 20 near its proximal end 20a and is located between the thumb piece 24 and proximal slot end 14a to bias thumb piece 24 toward the distal slot end 14b.
The needle 20 is rigidly affixed to the handle 12 at hub 16. Thumb piece 24 is slidably positioned upon the portion of the needle 20 residing within slot 14. Also, spring 26 biases thumb piece 24 toward the distal end 14b of slot 14. The O ring 23 slides down the length of needle 20 and into slot 14 for positioning within the aperture 25 of thumb piece 24. Sheath 22 is then positioned upon needle 20 by inserting the distal end 20b of needle 20 through the proximal end 22a of sheath 22 whereby the proximal end 22a of sheath 22 may be threadably mounted within the aperture 25 of thumb piece 24. Accordingly, sheath 22 may be selectively mounted and dismounted from the device 10. It is contemplated that several such sheaths 22 may be provided of various diameters whereby a suitable sheath diameter may be selected corresponding to the diameter of the instrument to be suprapubicly placed. In this manner, sheath 22 performs a dilating function to closely match the diameter of the passageway provided between the bladder and the abdominal wall with the diameter of the instrument to be suprapubicly placed.
The proper relative length of needle 20 and sheath 22 as compared to the length of slot 14, i.e., range and movement for thumb piece 24, enables the user of device 10 to selectively expose the distal end 20b of needle 20 beyond the distal end 22b of sheath 22 by operation of thumb piece 24 within slot 14.
FIG. 2 illustrates a suprapubic instrument placement device 10 in its assembled configuration, but having a T shaped handle 12'. In other respects, the devices 10 of FIGS. 1 and 2 can be identical. The shape of handle 12 and handle 12' provides the practitioner with a reference for orientation of the distal end 20b of needle 20. A practitioner familiar with the shape and orientation of handle 12 relative to the orientation of needle 20 more accurately positions the distal end 20b of needle 20 during suprapubic instrument placement. In operation, needle 20 remains fixed relative to handle 12', but sheath 22 moves relative to handle 12' by movement of thumb piece 24 within slot 14. More particularly, movement of thumb piece 24 as indicated by arrows 30 corresponds to movement of the distal end 22b of sheath 22 relative to the distal end 20b of needle 20 as indicated by arrows 32. In this manner, the distal end 20b of needle 20 may be selectively exposed at the distal end 22b of sheath 22.
FIG. 2 also illustrates a catheter 40 including an inlet opening 42 for passage of fluids through catheter 40 to the proximal end 40a of catheter 40. The distal end 40b of catheter 40 includes a loop 44 comprising a length of filament material forming a closed loop and passing through a solid portion of the tip, i.e. the end 40b, of catheter 40. Loop 44 thereby provides a secure structure for attachment to an indentation or notch 46 adjacent to the distal end 20b of needle 20.
FIG. 3 is a detailed view of the end 40b of catheter 40 and distal end 20b of needle 20. FIG. 3 illustrates the coupling of the loop 44 and indentation 46. As shown in FIG. 3, the distal end 20b of needle 20 extends, by operation of thumb piece 24, beyond the distal end 22b of sheath 22 to expose the indentation 46. Indentation 46 receives the loop 44 of catheter 40 for coupling needle 20 and catheter 40. With reference to FIG. 4, once the loop 44 is positioned and retained within the indentation 46, the distal end 22b of sheath 22 may be advanced by movement of thumb piece 24 (FIG. 2), beyond the distal end 20b of needle 20. In such configuration, the loop 44 is drawn into sheath 22 and lockingly engaged with indentation 46.
FIGS. 5A-5F illustrate suprapubic instrument placement by use of the device 10 and catheter 40. In FIG. 5A, the device 10 has been inserted through the urethra 60 to position the distal end 22b of sheath 22 within bladder 62. When placing device 10 within bladder 62 the thumb piece 24 is extended to the distal end 14b of slot 14 whereby sheath 22 shrouds the distal end 20b of needle 20. In FIG. 5B, device 10 is lifted against the dome 62a of bladder 62. The practitioner places his or her fingers 64 on the abdomen above the bladder to verify by palpation the positioning of the distal end 22b of device 10. More particularly, the practitioner must position the distal end 22b of device 10 just above the pubic bone 66 and just below the peritoneum 68.
Once the position of device 10 is verified as suitable for suprapubic instrument placement, the thumb piece 24 is drawn back to expose the distal end 20b of needle 20. The point of needle 20, i.e., the distal end 20b, may then be pushed, substantially longitudinally, through the fascia and abdominal wall 70 to the exterior of the abdominal wall 70 as shown in FIG. 5C. In certain cases, a small suprapubic incision may be made to assist advancement of the device 10 through the anterior abdominal wall 70. As shown in FIG. 5C, the distal end 20b of device 10 now protrudes out of the abdominal wall 70 exposing the indentation 46.
The loop 44 of catheter 40 is then coupled to the indentation 46 of device 10. Operation of thumb piece 24 then moves sheath 22 back over the distal end 20b of needle 20 to fully secure the catheter 40 and device 10. Referring now to FIG. 5D, the catheter 40 is then drawn through the abdominal wall 70 and into the bladder 62. Control of catheter location within the bladder is enhanced as traction can be applied at either end of the device assembly until the correct location is determined and the catheter released.
Turning to FIG. 5E, once the end 40b of catheter 40 is suitably positioned within bladder 62, thumb piece 24 is again actuated to expose the distal end 20b of needle 20. Lateral forces applied to the device 10 relative to the catheter 40 release the loop 44 of catheter 40 from the indentation 46. Device 10 may then be removed from the bladder 62 by way of the urethra 60. FIG. 5F shows final positioning of the catheter 40 within bladder 62. More particularly, in the illustrated example the catheter is a J-curve catheter which may be curled into the shape shown in FIG. 5F by withdrawing and securing a string 72 of catheter 40. Once so configured within the bladder 62, catheter 40 is operational.
Thus, the device and method of suprapubic instrument placement according to the present invention avoids many potential hazards of suprapubic instrument placement. For example, before penetrating the bladder wall or abdominal wall, the practitioner may accurately determine the location of the proposed site of catheterization by locating the instrument tip as illustrated in FIG. 5B. This insures that a proper instrument placement site is established.
The nature of the coupling mechanism between the instrument 10 and catheter 40 effects quick and convenient coupling and decoupling, yet provides a very secure coupling while drawing the catheter into the bladder. More particularly, the notch and loop configuration of the coupling means of device 10 and catheter 40 allow convenient coupling and decoupling of these devices, but because the sheath 22 may be positioned over the tip of needle 20, the loop 44 is securely held within the indentation 46. Once the catheter 40 is positioned within the bladder 62, exposing the needle tip and therefore the loop 44 and indentation 46 allows the practitioner to easily decouple the devices.
Additional features of the apparatus of the present invention offer the following benefits. Extravasation is minimized as the catheter size and sheath diameter may be closely matched, by selecting among a variety of sheaths 22, to improve the catheter-bladder seal. The control permitted by the apparatus facilitates its use under local anesthesia. Also, the apparatus may be adapted to place other instruments in the bladder such as cystotomy access tubes, cystourethroscopes, cystolithotriptors and instruments for the treatment of conditions of the bladder prostate urethra, and ureter.
FIG. 6 illustrates an alternative embodiment wherein the instrument coupling means comprises a ball 80 attached to the tip of a catheter 40 by a stem 81. A cavity 82 and groove 83 adjacent the distal end 20b of needle 20 receive the ball 80 and stem 81, respectively. To secure the catheter 40 of FIG. 6 and the device 10 of FIG. 6, the ball 80 is positioned within the cavity 82 and the stem within the groove 83. The sheath 22 may then be moved over the distal end 20b of needle 20 to fully secure the ball 80 within the cavity 82. The arrangement of FIG. 6 thereby provides convenient coupling and decoupling while providing a secure locking together of the device 10 and catheter 40 while drawing the catheter 40 into the bladder.
While a J-curve type catheter has been shown for use in connection with the device 10, many forms of catheter and other instruments, e.g. obturators, suitable for suprapubic instrument placement may be used in accordance with the present invention. For example, the types of suprapubic catheters applicable to the present invention include Foleys, Malecots, pigtails and loop-types. The ability to select and align the penetration site and pathway compared to actual penetration minimizes accidental perforation and catheter misplacement.
In the illustrated embodiments of FIGS. 1-5, the sheath-needle assembly comprises a 25 cm length, 13 gauge needle, which is shaped for a female urethra. FIG. 7 illustrates a configuration more suitable for the male urethra. In FIG. 7, needle 20 is shown extended approximately one inch beyond the distal end 22b of sheath 22. As previously described, the needle 20 is desirably a substantially rigid element while the sheath 22 is a flexible member adapted to conform in shape to that of needle 20 while being slidably disposed thereon. In this regard, rigidity in needle 20 may be achieved by use of a stepped-gauge or tapered-gauge needle. A central length portion 20c of needle 20 is approximately 2.5 inches, or 6.35 centimeters. The proximal length portion 20d of needle 20 is approximately three inches, or 7.62 centimeters, and aligned at approximately 20 degrees relative to length portion 20c. A distal length portion 20e of needle 20 is curved along a radius of approximately 2.625 inches, or 6.67 centimeters, extending from the central length portion 20c to the straight distal length portion 20f. The curvatures provided in the needle 20 maintain each length portion of needle 20 within a common plane, with the curvature of portion 20d relative to portion 20c being opposite that of the curvature of portion 20e relative to 20c, i.e., in opposite half-planes as defined by portion 20c. The configuration of needle 20 and sheath 22 as illustrated in FIG. 7 conforms to male anatomy while permitting proper angulation to select suprapubic placement and provide good transfer of longitudinal energy forces.
Suprapubic procedures, as made more available and practical by the present invention, offer many advantages. Suprapubic catheters provide increased patient comfort and minimization of infection in comparison to urethral catheters. Transurethral resection of prostate (TURP) irrigation via a suprapubic tube has been found to maximize visibility and speed resection time. Reduced morbidity and hospital stay can occur when percutaneous bladder procedures are used over open operations. Improving the ease and safety of suprapubic catheter and instrument placement encourages their broader use and allows their benefits to be more fully realized.
Inside-to-outside suprapubic instrument placement in accordance with the illustrated embodiments further provides full control over catheter placement; accurate suprapubic puncture location and orientation protection of penetrating element (needle); compatibility with a variety of catheter sizes and types; and coordination of puncture diameter with catheter size. Other benefits of suprapubic instrument placement as shown herein include the capability to fill or drain the bladder, via the needle. It is also possible to inject a local anesthetic through the needle, offering the potential for bedside placement of suprapubic catheters.
Limitations in the application of the apparatus and method of the present invention are few.
For example, in suprapubic instrument placement, urethral obstruction would not permit inside-to-outside access to the bladder. Obesity requires an assistant to pull up on the pannus and then depress down and toward the head. Control of catheter location is enhanced as traction can be applied at either end of the device assembly until the correct location is determined and the catheter is released. The apparatus in accordance with the present invention provides additional benefits such as minimization of extravasation since the catheter diameter and dilating sheath diameter can be closely matched to improve the catheter-bladder wall seal. Catheter loss during placement is substantially minimized the secure coupling between the placement device and the instrument to be placed. Thus, the illustrated devices offer practitioners, in various surgical fields, a less demanding, and more reliable option for the performance of suprapubic instrument placement.
In addition to the specific embodiments described and illustrated herein, other embodiments are contemplated within the scope of the invention. For example, a rigid sheath may be employed in combination with a flexible needle, or even two rigid components if applicable, wherein the shape of the sheath corresponds to a given anatomy. The coupling mechanism of the present invention is not limited to the inside-to-outside method as it is equally applicable to outside-to-inside methods. Also, the coupling means of the device may be located on the sheath as an alternative to a coupling means on the needle. Transfer tubes, catheters, stents, wire guides, scopes, and other instruments to permit diagnosis and operation may be modified for placement in accordance the present invention. Furthermore, by selecting a different placement site, a variety of instrument devices can be placed, e.g., for cardiovascular, gastroenterology laparoscopy and other situations where indirect means are employed.
Finally, the reliability and control of inside-to-outside suprapubic instrument placement as provided by the present invention will likely generate increased use of suprapubic devices and, therefore, further advance the art of urologic treatment.
FIG. 8 illustrates an instrument placement system for positioning a stent 100 in a body lumen, e.g., as an in-dwelling stent coupling a kidney and a bladder. The placement system of FIG. 8 includes a guidewire 102 which provides an access route along a selected body lumen. An internal stylet 104 rests coaxially within the stent 100 and engages at its distal end 104a the distal end 100a of stent 100 in pushing fashion. The stylet 104 frictionally engages the stent 100, or may engage a formation (not shown) of the stent 100, in order to provide a pushing force on the stent 100 and thereby drive the stent 100 along the guidewire 102. The stylet 104 also provides a stiffening function within the stent 100 to maintain the stent 100 in a substantially straight configuration.
The instrument placement system of FIG. 8 further includes a proximal positioner 106. The distal end 106a of the positioner 106 abuts in end-to-end relation the proximal end 100b of stent 100. The distal end 106a of positioner 106 includes a loop 110. The proximal end 100b of stent 100 carries slot 108. Loop 110 is of sufficient size to rest within the slot formation 108. The stent 100 is then locked end-to-end to the positioner 106 by positioning the loop 110 within slot 108 and sliding the stylet 104 coaxially through both the positioner 106 and the stent 100. The stylet 104 thereby captures the loop 110 within the slot 108 as illustrated in FIG. 8. The positioner 106 and stylet 104 are coupled at their proximal ends 106b and 104b by luer lock 105. More particularly, the proximal end 106b of positioner 106 terminates in and attaches to the portion 105a of lock 105. Stylet 104 rests coaxially within and slidably through portion 105a. The proximal end 104b of stylet 104 terminates in and attaches to the portion 105b of luer lock 105. The stylet 104 may be solid, or may include a central bore for passage of fluid therethrough in accordance with known practice.
FIGS. 9 and 10 illustrate the unlocking of positioner 106 and stent 100 following placement of the stent 100. In FIG. 9, the stylet 104 is retracted as indicated by the arrow 112 by decoupling and separating portions 105a and 105b of lock 105. In FIG. 10, the stylet 104 is retracted until a marker 114 emerges from the portion 105b of lock 105. The emergence of marker 114 corresponds to the passage of the distal end 104a of stylet 104 past the slot formation 108. Once the distal end 104a of stylet 104 passes the slot 108, the loop 110 is free to move out of the slot 108 as indicated by the arrow 116. The stent 100 may be preloaded to naturally assume a curled configuration upon the removal of the stylet 104. This natural curling of the stent 100 helps bring the loop 110 out of the slot 108 when the stylet 104 exits the stent 100. Also, it is suggested that the slot 108 be angled with respect to the longitudinal axis of stent 100 in such manner to better facilitate the removal of loop 110 therefrom, e.g., the deepest portion of slot 108 being most removed longitudinally from loop 110.
FIGS. 11A-11C illustrate in-dwelling placement of the stent 100 for coupling a kidney 120 and a bladder 122. In FIG. 11A, a cystoscope 124 has been positioned within the urethra 126 and terminates in the bladder 122. The guidewire 102 rests coaxially within the cystoscope 124 and extends from the distal end of the cystoscope 124 up through the ureter 128 and into the kidney 120. The distal end 100a of stent 100 is slidably mounted upon the guidewire 102. The stent 100 is coupled to the positioner 106 as shown in FIG. 8 and the stylet 104 rests coaxially within the positioner 106 and the stent 100 as shown in FIG. 8. The luer lock 105 is joined together to lock the stylet 104 and positioner 106 in fixed relative longitudinal position.
The placement system is then ready for sliding along the guidewire 102 through the cystoscope 124 and into the desired position. Movement of the system along the guidewire 102 is facilitated by the column strength provided by the stylet 104 and the coupling of stylet 104 and positioner 106 at the lock 105. As may be appreciated, and as discussed in U.S. Pat. No. 4,824,435, the disclosure of which is incorporated fully herein by reference, a separate pusher can be slidably mounted on the guidewire 102 and engage the distal end 100a of stent 100 in order to slide the stent 100 along the guidewire 102.
FIG. 11B shows the placement system after having pushed the stent 100 into position within ureter 128 to better fluidly couple the kidney 120 and bladder 122. The distal end 100a of stent 100 has been pushed off the distal end 102a of guidewire 102 thereby making the placement system free of the guidewire 102. Guidewire 102 can be removed at this time, or left in place for other uses. The stent 100 then has its distal end 100a within the kidney 120 and its proximal end 100b within the bladder 122. The system is now ready for uncoupling. Uncoupling is accomplished by retraction of the stylet 104 as indicated by arrow 112, i.e., uncoupling and separation of luer lock 105. As discussed above in connection with FIGS. 9 and 10, the stylet is retracted until the marker 114 (FIG. 10) emerges from the portion 105a of lock 105. This indicates that the distal end 104a of stylet 104 has passed the slot 108. Turning to FIG. 11C, the stylet has passed the slot 108, the loop 110 falls from slot 108, and stent 100 assumes its natural curled configuration. Stent 100 is thereby decoupled from the positioner 106 as shown in FIG. 11C. The stylet 104 is then completely removed from the positioner 106, and the positioner 106 can be removed from the cystoscope 124. The stent 100 is now in operational position coupling the kidney 120 and the bladder 122. The guidewire 102 and cystoscope 124 may then be used for other associated procedures, or may be removed if no longer needed.
FIGS. 12-15 illustrate a second instrument placement system for use in conjunction with a guidewire. In FIG. 12, a stent 140 rests coaxially upon a guidewire 142. The proximal end 140b of stent 140 carries a tail 144, in this particular embodiment a tail 144 defining a ball 144a and stem 144b. In other implementations of the present invention, the tail at the proximal end 140b of stent 140 may simply be an extension of the stent wall structure, or soft material well captured by a collapsible loop 152 of the positioner system 146. For example, the tail 172 illustrated in FIGS. 16 and 17 could be used in connection with the loop 152 of the embodiment of FIGS. 12-14. A positioner system 146 rests coaxially upon the guidewire 142. The positioner system 146 includes an inner sleeve 148 and an outer sleeve 150. The sleeves 148 and 150 are allowed relative longitudinal sliding movement. Loop 152 at the distal end of sleeve 148 is attached at one end 152a and at the other end 152b to the inner sleeve 148, extending through apertures 154 of outer sleeve 150. Thus, the loop 152 may be collapsed against the outer surface of sleeve 150 by relative movement between the sleeves 148 and 150.
FIGS. 13 and 14 illustrate the locking procedure for coupling together in end-to-end relation the stent 140 and the positioner system 146. In FIG. 13, the sleeves 148 and 150 are positioned relative to one another such that the loop 152 is expanded. The inner sleeve 148 is brought into abutment with the proximal end 140b of stent 140 and the tail 144 is inserted through the loop 152. The system is now ready for locking together in end-to-end relation the stent 140 and the positioner system 146.
In FIG. 14, the inner sleeve 148 is retracted within outer sleeve 150 for relative longitudinal movement of the inner sleeve 148 as indicated by the arrow 158, i.e., retracting movement of sleeve 148 relative to sleeve 150. Such relative longitudinal movement of sleeves 148 and 150 collapses the loop 152 against the outside of sleeve 150 and thereby captures the tail 144 at the loop 152.
FIGS. 15A and 15B illustrate a locking arrangement for the positioning system 146. In FIGS. 15A and 15B, outer sleeve 150 attaches to a handle 152. Inner sleeve 148 extends slidably into a cavity 154 of handle 153 and attaches to a locking inner handle 156 slidably disposed within the cavity 154. Handle 156 includes a resilient portion 156a carrying a catch 158. Resilient portion 156a may be pressed downward to allow sliding of the locking inner handle 156 into the cavity 154 to thereby fully expand the loop 152. By retracting the handle 156 from the cavity 154, the catch 158 engages a rear edge of handle 153 and prevents handle 156 from re-entering cavity 154. By suitably dimensioning the handle 153, handle 156, and positioning of catch 158, the loop 152 may be suitably closed upon engagement of catch 158 at the rear edge of handle 153. Furthermore, the locking arrangement of FIG. 15 may accommodate a central bore for accommodating the guidewire 142 therethrough. As may be appreciated, the locking arrangement can be operated, i.e., locked, by manipulation at the distal ends of sleeves 148 and 150. The practitioner need not manipulate handles 153 and 156 when loading a stent.
The positioner system 146 is thereby positively locked to the stent 140 to provide pushing and pulling control over the stent 140 as well as twisting control over the stent 140. The extent of twisting control is determined by the specific configuration of the tail 144. In the particular embodiment illustrated, to the extent that the length of stem portion 144b can be minimized, the twisting control over stent 140 may be increased.
A typical problem encountered by the practitioner is limited guidewire length available at the proximal, exposed end of the guidewire. The instrument placement system illustrated in FIGS. 12-15 addresses this problem. In use of the instrument placement system of FIGS. 12-14, once the guidewire 142 is positioned, the stent 140 is positioned on the guidewire 142 by sliding the stent coaxially along the guidewire 142. This requires, at most, only enough exposed guidewire 142 length to cover slightly more than the length of stent 140. In other words, if the available guidewire length is slightly greater than the stent 140, then the length of stent 140 may be slidably and coaxially mounted upon the guidewire 140 while maintaining contact with the guidewire 140. In this manner, the guidewire 140 does not migrate in positioning of the stent 140 thereon.
Once the stent 140 is positioned along the guidewire 142, then the placement system 146 is slidably and coaxially mounted upon the guidewire 142 and locked to the stent 140 as discussed above. Once the system is so locked, the stent 140 may be positioned as desired. Once so positioned, the guidewire 142 is retracted from the instrument placement system. Once the wire 142 is removed, the stent 140 is decoupled from the placement system 146 by operation of handle 152 (FIG. 15).
FIGS. 16 and 17 illustrate an alternative locking arrangement for the instrument placement system of FIGS. 12-15. In FIG. 16, the inner sleeve 148 includes at its distal end 148a a flared end configuration to provide an adjacent relatively smaller diameter recess 170. The stent 140 includes a tail 172 integrally formed as an extension of the wall structure of stent 140. The system generally operates in the same fashion as described above. The stent 140, inner sleeve 148 and outer sleeve 150 each rest coaxially relative to the guidewire 142 with the stent in end-to-end relation to the sleeves 148 and 150. Locking of the stent 140 to the sleeves 148 and 150 is accomplished by placing the stent 140 in end-to-end abutment relative to the proximal end 148a of sleeve 148 such that the tail 172 may rest within the recess formation 170. By then retracting the sleeve 148 within the sleeve 150, the tail 172 is captured within the recess formation 170 by the inner surface of the sleeve 150, as illustrated in FIG. 17.
Thus, an improved end-to-end coupling arrangement has been shown and described for use in connection with guidewire instrument placement. The end-to-end coupling arrangement provides a reliable coupling between a positioning system and an instrument to be positioned whereby pushing, pulling, and twisting capabilities are desired. While the illustrated system provides a positive lock between the instrument to be placed and the positioning system, such positive engagement can be easily and completely disengaged to establish a clean break between the instrument to be placed and the positioning system. Thus, the practitioner making use of the illustrated system can precisely achieve the desired instrument position, then completely disengage the positioning system and leave the positioned instrument undisturbed in the desired position. More particularly, in removing the positioning system from the body lumen the positioning system is completely decoupled and cannot affect the established instrument position. The illustrated system can be provided prepackaged with a guidewire, or may be used in connection with a separate guidewire previously positioned within a body lumen. | A surgical apparatus for the placement of an instrument within a body cavity which comprises a placement device including an elongate element with an exposable tissue piercing tip, a first coupling means adjacent to the tip, and means for selectively exposing the tip; and an elongate instrument for placement including a second coupling means adapted to be coupled to the first coupling means to effect an end to end coupling of said device and said instrument whereby said instrument is positioned within said body cavity. Preferably the instrument is a suprapubic instrument for placement within a bladder. A method for placement of a suprapubic instrument is also disclosed. Also shown is a method and apparatus for end-to-end instrument coupling in the context of guidewire instrument placement. End-to-end coupling is accomplished by loop and slot arrangements, a tail and collapsing loop arrangement, and a tail captured between two slidably disposed sleeves. | 0 |
FIELD OF THE INVENTION
The present invention relates to a vehicle trailer hitch and more particularly to a vehicle hitch system which can detect a jackknife condition and warn the vehicle operator.
BACKGROUND OF THE INVENTION
It is well known that backing up a vehicle with a trailer for many drivers is often difficult and frustrating. Even individuals with considerable driving experience often have little opportunity to develop the skill required to back up a trailer. Much of the difficulty associated with backing up a trailer results from the fact that it is not intuitive for many drivers to sense the jackknifing situation before it is too late a nd from the fact that many drivers do not know how to steer properly in order to align the trailer back to avoid a jackknifing situation. It is the purpose of this invention to provide such assistance to the driver by the early detection of vehicle-trailer jackknifing tendency and provide steering direction assistance to avoid a jackknifing situation.
In general, vehicle-trailer backing up is by nature an unstable motion, unless an experienced driver in the loop stabilizes it with timely and proper steering and/or braking. Jackknife occurs when a vehicle-trailer is approaching away from its equilibrium position, a position intended by the driver through his/her steering input, and thus becomes unstable. In other words, the relative angle between vehicle and trailer is diverging from the driver's intended target angle, and usually increases if proper steering and/or braking action are not taken. This is typically out of control by the driver, either due to lack of sufficient driving skill, or the condition is too severe. Therefore, a driver's capability in controlling the motion of vehicle-trailer combination is one of the key elements in this invention.
The prior art can be found through U.S. Pat. No. 6,268,800 and U.S. Pat. No. 5,912,626 related to this invention. Both of these systems use hitch articulation position as the sole criteria to detect a potential jackknifing situation. While systems provide satisfactory functioning for a vehicle towing a trailer, they may not function during the backing up of a trailer. More particularly, neither of them takes into account the operator and vehicle-trailer combination into consideration. Furthermore the articulation rate (as how fast the jackknife is to happen) during the detection of jackknife situation is not used in their calculations.
SUMMARY OF THE INVENTION
The jackknifing warning system of the present invention utilizes vehicle steering wheel angle sensor signal, vehicle travel speed and hitch articulation angle to evaluate system stability. Based on a hitch angle equilibrium position, hitch angle rate and some predetermined criteria, the system utilizes an algorithm to determine if the motion of vehicle-trailer combination is stable or not with driver in the loop. When instability is detected, a critical hitch angle will be calculated as a function of hitch angle rate, a predetermined maximum critical hitch angle and a predetermined tolerant time period to determine if and how the vehicle-trailer is approaching jackknifing. If the vehicle-trailer surpasses the critical angle, a proper warning signal is issued with varying intensity as the severity varies. The algorithm also provides steering direction assistance in order for the driver to steer to avoid jackknifing.
This invention can apply to vehicle with either two-wheel steer or four-wheel steer with a trailer. Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will become more fully understood from the detailed description and the accompanying drawings, wherein:
FIG. 1 depicts an algorithm to determine a potential jackknife situation during back-up of a vehicle-trailer, and
FIG. 2 shows a schematic of a vehicle-trailer system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.
With reference to FIG. 1 , the system according to the present invention first determines the instability of the vehicle and trailer with driver in the loop. For example, whether or not the vehicle-trailer combination is under control. After updating a system clock, the system begins when a controller reads steering wheel angle δ sw from steering wheel angle sensor and vehicle traveling speed from speed sensor at input point 10 . In order to detect system instability, at process block 12 an equilibrium position in terms of hitch angle is calculated based on the input of vehicle steering wheel angle, vehicle speed along with some geometric parameters of the vehicle and trailer. The equilibrium position of the hitch angle, {overscore (θ)} eq , can be calculated as below:
θ _ eq = tan - 1 ( y x ) = f ( δ f δ r , Γ ) , ( 1 )
Where
δ f = δ sw r gearRatio
is the front-wheel angle, and δ r =K f δ sw is the rear-wheel angle if four-wheel steer vehicle. r gearRatio is the gear ratio in front steering system while K f is the ratio between steering wheel to rear-wheel angle for four-wheel steer vehicle. Γ represents the geometric parameters of vehicle-trailer combination where
x = h - L 1 tan δ r tan δ f - tan δ r
y = YL 2 x Y 2 - x 2 + x 2 Y 2 - x 2 Y 2 + L 2 2 - x 2 , and
Y = ( L 1 tan δ f - tan δ r + T 2 ) 2 + ( h - L 1 tan δ r tan δ f - tan δ r ) 2 - L 2 2
A measured hitch angle is taken at input block 14 . The measured hitch angle is then compared with the equilibrium position in terms of hitch angle at query block 16 based on criteria (2) to determine if the measured hitch angle is approaching to the equilibrium position:
if θ( n )>{overscore (θ)} eq ( n ) then (2)
Δθ( n )=θ( n+ 1)−θ( n )<0
else
Δθ( n )=θ( n+ 1)−θ( n )>0
If the criteria (2) are not met, the measured hitch angle is diverging from the equilibrium position, therefore, the instability is detected. Then the hitch angle rate is estimated at block 26 and then proceeds to block 24 . Otherwise, it proceeds to query block 18 below.
If the criteria (2) are met in query block 16 , the difference |Δθ(n)|=|{overscore (θ)} eq (n)−θ(n)| between the current hitch angle θ (through hitch angle sensor) and {overscore (θ)} eq is calculated in query block 18 and checked to see if it is bounded to a small value. If it is bounded, then the hitch angle rate is estimated at block 20 and checked to see if it is approaching to zero (or bounded to a small value numerically) at the neighborhood of the equilibrium position based on the criteria (3), for early distinction between convergence and divergence of hitch angle towards the equilibrium position:
|Δθ( n )|=|{overscore (θ)} eq ( n )−θ( n )|<Δ{overscore (θ)}*( n ) (3)
|{dot over (θ)}( n )|<{dot over({overscore (θ)})}*( n )
Therefore, if both criteria (2) and (3) are met, the current hitch angle θ is determined to approach the equilibrium angle, and the stability of vehicle-trailer with drive in the loop can be determined. If Δθ is not bounded at query block 18 , it restarts at point 8 with time clock updated. If {dot over (θ)} is not bounded at query block 22 , the instability is detected. It proceeds to block 24 to calculate the critical hitch angle.
When the instability is detected, the system will check the current vehicle and trailer relative position and compare with a predetermined critical angle under the current estimated hitch angle rate based on equation (4). If the measured hitch angle is larger than the critical angle, the jackknifing status is detected and a warning message is issued a nd transmitted to the driver via some audio and/or video signals.
θ . ( n ) ≈ θ ( n + 1 ) - θ ( n ) Δ t ( 4 )
The critical hitch angle can vary depending on the hitch angle rate, as the larger of hitch angle rate, the smaller critical angle can be tolerated. As shown in query block 22 , if a is bounded by a small value (or approaching to zero), the system is stable and returns to start point 8 . If the condition of query block 22 is not met, the system continues with process block 24 . Similarly from query block 16 , should the current hitch angle 0 not approach the equilibrium angle, the hitch angle rate is estimated approximately in process block 26 based on equation (4).
Given a predetermined maximum critical hitch angle {overscore (θ)} cr0 at static (hitch angle rate equals to zero), and the predetermined tolerant time period, {overscore (τ)}*, to achieve the consistent tolerable time period, the critical hitch angle θ cr *(n) at hitch angle rate {dot over (θ)}( n ) can be determined in process block 24 as:
θ cr *( n )={overscore (θ)} cr0 *−{overscore (τ)}*·{dot over (θ)}( n ) (5)
If in query block 28 the current hitch angle is smaller than the critical hitch angle, then the system is not seen as a jackknife situation and restarts at start point 8 . If in query block 28 the current hitch angle is larger than the critical hitch angle, the vehicle-trailer motion is considered to be approaching to a jackknife situation:
|θ( n )|>{overscore (θ)} cr *( n ) (6)
The difference Δθ(n)=|θ(n)|−{overscore (θ)} cr *(n) can be used to determine how severe the potential jackknife situation is. An intensity-varying audio device, such as frequency-varying audio (beep) signal generator, for instance, can be used to generate a signal with lower frequency corresponding to a less severe situation, and higher frequency when the jackknife situation is worse.
Furthermore, when a potential jackknife situation is detected, the system will instruct the driver, based on the current hitch position, as to which direction to steer with maximum steering amount at the fastest steering rate in order to avoid the jackknife. In process block 30 , the steering command δ sw can be determined by:
if θ( n )>0, then (7)
δ sw *<0 (steering right)
else
δ sw *>0 (steering left)
Where positive steering means steering left in this invention. With the same device, such information can be passed to the driver through left or right speaker equipped respectively in the original vehicle audio system, or can use light emitting devices. It is envisioned either the amplitude or frequency of the audible signal can be adjusted to alert the operator.
FIG. 2 represent a schematic of the system according to the teachings of the present invention. Shown is a controller 40 coupled to an associated memory unit 42 . The controller 40 is coupled to a system I/O module 44 which is configured to accept signals from a number of wheel angle and vehicle traveling speed sensors 46 as well as a hitch articulation sensor 48 . The I/O module 44 is coupled to an occupant warning system 50 which can take the form of an audible, visual or tactile information system. The warning system FIG. 50 is configured to convey to the vehicle's operator if a jackknife condition exists and further recommend to the vehicle's operator how to avoid a jackknife condition. The detail procedure can be described as follows:
1. The controller 40 reads the sensor signals of vehicle speed, vehicle steering wheel angle δ sw , and calculates the front wheel angle
δ f ( n ) = δ sw r gearRatio
and rear wheel angle δ r (n)=K f δ sw (n) if any.
2. The controller 40 then calculates the hitch angle equilibrium position {overscore (θ)} eq (n) based on equation (1); 3. The I/O module 44 reads the sensor signal of hitch angle θ( n ) and the controller 40 compares it with {overscore (θ)} eq (n); 4. The controller 40 then determines if θ( n ) is approaching to equilibrium position {overscore (θ)} eq (n) based on the criteria (2); 5. If θ( n ) is not approaching to {overscore (θ)} eq (n) the vehicle-trailer motion is considered to be unstable. Then, the controller 40 goes to step 7 ; 6. If θ( n ) is approaching to {overscore (θ)} eq (n) further determine if hitch angle and hitch angle rate are bounded from block 18 , 20 and 22 based on the criteria (3). If yes, the vehicle-trailer motion is considered to be stable. The controller 46 starts detection over again by going back to step 1 ; 7. When instability is detected, the critical hitch angle is then calculated based on equation (5) by the controller 40 , which is a function of the current hitch angle rate, a predetermined maximum critical hitch angle and a predetermined tolerant time period; 8. If the controller 40 determines that the current hitch angle is larger than the critical hitch angle, the vehicle-trailer motion is considered to be approaching the jackknifing situation; 9. The controller 40 uses the difference Δθ=|θ(n)|−θ cr *(n) to determine the severity of the potential jackknife situation. A different audio signal is generated accordingly; and 10. The steering instruction δ sw * as how to steer to avoid the jackknife is determined based on criteria (7), and passed to the driver accordingly through either right or left speaker 50 , for instance.
The system assumes that the roll and pitch of the vehicle and trailer is small and can be neglected; furthermore, the system assumes that the tire slip is negligible. It is envisioned that the above parameters can be modified to incorporate the vehicle and trailer pitch and is well as tire slip should this information become available through systems such as traction control or and anti-lock braking systems.
The description of the invention is merely exemplary in nature and, thus, variations that do not depart from the gist of the invention are intended to be within the scope of the invention. Such variations are not to be regarded as a departure from the spirit and scope of the invention. | This invention provides a system to detect in real time the condition of jackknifing tendency during vehicle-trailer backing up, and to provide steering direction assistance. The system utilizes rates of change of a vehicle-trailer articulation angle to determine a critical articulation angle. | 1 |
BACKGROUND OF THE INVENTION
This invention relates to cord winding devices and more particularly to carriage returns on printers or typewriters.
Moving paper carriage printers and typewriters have, in the past, utilized carriage returns in the form of power driven cord reels or tape drums depending on the force transmission member chosen. Patents which deal with the release or the termination of operation of the carriage return drive mechanism include U.S. Pat. Nos. 909,539 to Burlingame, 1,386,387 to Waldheim, 2,647,609 to Sagner and 3,263,793 to Brignole, Jr. U.S. Pat. No. 909,539 is exemplary of a device where the electrical motor power for the carriage return mechanism is interrupted by a mechanical movement caused by the engagement of the left margin stop on the carriage with a follower to effectively break the electrical circuit.
Waldheim discloses a device which is tension governed such that upon the completion of the carriage return movement, the cord tension overcomes spring forces sufficient to pull an electrical switch contact apart, thus preventing further driving by the electrical motor.
Sagner, U.S. Pat. No. 2,647,609, utilizes a mechanical stop member as does Brignole, Jr., 3,263,793, to disengage the driving clutches as a result of the engagement of a knock-off latch by a carriage return stop.
With the exception of the Waldheim reference, all three other references require the carriage return to be returned to the leftmost position on the print line to engage the margin stop with the knock-off mechanism. This requires a complete carriage return and does not allow for carriage jams or other inadvertent blocking of the carriage return and could then cause a burning of the clutch, overloading of the motor, or a breakage of parts. Waldheim permits the disengagement of the motor upon the overcoming of the spring tensions by the carriage return tape. The Waldheim device will, of necessity, require sufficient spring tensions in the spring holding the switch closed to prevent a premature disconnection of the motor contacts. This will, of course, accommodate high initial cord tension and also very high cord tensions in order to accomplish the disconnecting of the motor upon the completion of the carriage return.
All of the above references would require a very substantially sized motor in order to overcome the acceleration forces during the initial phase of carriage return and generate adequate forces to terminate carriage drive.
OBJECTS OF THE INVENTION
It is an object of the invention to automatically disengage the carriage return clutch whenever the carriage return cord tension exceeds a preselected value.
It is another object of the invention to automatically disengage the carriage return clutch whenever the carriage has reached its normal limit of travel or ceases to move, thus raising the carriage return cord tension past a predetermined level.
It is another object of the invention to absorb initial acceleration loadings to prevent premature disengagement of the carriage return clutch.
It is still a further object of the invention to absorb initial loadings and eliminate peak forces to reduce the requirement for motor size on the carriage return function.
It is still another object of this invention to smooth out and minimize the variations in the carriage return velocity.
The shortcomings of the prior art are overcome and the objects of the invention are accomplished by the incorporation into the carriage return clutch module of a shock unloader prestressed spring member, which also acts as a resilient torque transmission member, and a cord tension responsive latch control to disconnect the clutch and allow the clutch to disengage upon the reaching of some predetermined cord tension value. The carriage return control module includes a coil spring torque transmission member which is pretensioned to absorb the initial forces necessary to accelerate the carriage. After the forces have been absorbed, the driving hub of the carriage return control is then resiliently coupled to the driving arbor and continues to rotate the arbor. The shock absorbing capacities insure (1) that a smaller motor may be utilized inasmuch as peak loads are diminished and (2) that the cord tension sensing knock-off control is not inadvertently activated early in the operational cycle prior to a complete carriage return operation being accomplished. The cord tension sensing device is moved when the cord tension reaches a predetermined threshold and then, through linkages, unlatches or disengages the clutch pawl from the clutch lug, thereby allowing the controlled spring clutch to relax and disengage the driven arbor and the cord drum.
A more complete understanding of the function, structure and operation of the carriage return control may be had from the accompanying drawings and the detailed description to follow.
FIG. 1 illustrates a typewriter having a moving carriage and a carriage return mechanism as described in the remainder of the figures.
FIG. 2 illustrates the carriage return drive and control apparatus in its assembled state.
FIG. 3 is an exploded view of the components of the carriage return apparatus displaced from each other for clarity.
FIG. 4 illustrates the cord tension sensing mechanism found in FIG. 2 from the opposite side and generally illustrates its relationship to the carriage return module.
FIG. 5 illustrates the interior of the hub driven by the drive belt.
FIG. 6 is a graph depicting the cord tension experienced in a carriage return system with and without a shock unloader in the system.
DESCRIPTION OF THE INVENTION
Referring to FIG. 1, typewriter 10 is the type of typewriter where the moving paper carriage 12 translates past the print element 14 to define a writing line on the page 16. The movement of carriage 12 is in a leftward direction, thus displacing the print point along the writing line on page 16 toward the right, in an escapement operation. The mechanisms by which that is accomplished form no part of this invention and, therefore, are not included in the drawings.
In order to translate carriage 12 toward the right, thereby repositioning the print point at the left end of the print line, a carriage return mechanism 18 is disclosed in the right portion of typewriter 10. Carriage return mechanism 18 is powered by drive motor 20 by timing belt 22.
Referring to FIG. 2, timing belt 22 is wrapped around and engages timing gear 24. Timing gear 24 is conveniently molded into the periphery of a drive hub 26. Further detail as to the internal construction of hub 26 is found in FIGS. 3 and 5. Hub 26 is provided with a raised partial annular member 28 on the interior of the cavity of hub 26. Further, hub 26 is provided with a bearing surface 30 for engagement with shaft 32. Depressed into interior end face of hub 26 is a relief 29 to accommodate the end of arbor 36 and provide driving surface 31 engageable with rim 37.
Further referring to FIG. 3, extending through the central axis of the carriage return control module 18 is shaft 32 which further acts to support and provide the axis of rotation for component parts of the module as well as a mounting means with respect to the typewriter frame 34 shown on the right end of shaft 32 in FIG. 2. Surrounding shaft 32 is arbor 36. Arbor 36 is provided with a channel or groove 38 formed in the cylindrical periphery thereof and at one end.
At the opposite end of arbor 36 is a partial annular protruding rim 37 extending outward from the cylindrical surface of arbor 36. This rim 37 is dimensioned to fit into the interior of hub 26. It is also dimensioned to engage surface 31 which is formed into the interior of hub 26. Rim 37 and surface 31 will engage one or the other end thereof when hub 26 is rotated with respect to arbor 36 and, thus, become a solid driving connection. When the other or opposite end of rim 37 is engaged with surface 25, it becomes a stop surface which prevents arbor 36 from rotating in the biased direction.
Surrounding arbor 36 is resilient torque transmission member with form of a coil spring 39 having two end tangs 40 and 42. Tang 40 is inwardly disposed to engage in and be trapped by slot 38. Tang 42 is outwardly disposed to be engaged by and driven by the interior surfaces of hub 26, specifically the end of 28.
Also concentric with shaft 32 is clutch spring 50 having inwardly disposed tang 52 and outwardly disposed tang 54. Tang 52 is engaged with slot 38 for purposes of deriving motion from the rotation of arbor 36. As arbor 36 is rotated, clutch spring 50 will be rotated about its axis and freely about arbor 56 which is rotationally mounted on shaft 32. Shaft 32 extends freely through arbor 56, cord drum 58 and clock spring housing 60. Clock spring housing 60 contains a clock spring 61 illustrated in FIG. 2 which will act to spring bias the cord drum 58. Cord drum 58 and arbor 56 are fixedly attached to each other to provide a driving relationship between arbor 56 and drum 58. In order to retain spring 50 with inwardly disposed tang 52 engaged with slot 38 of arbor 36, spring clip 62 is engaged with the outer periphery of clutch spring 50. Spring clip 62 grasps the outer cylindrical surface of clutch spring 50 and retains it frictionally on arbor 36. A supplemental function of clip 62 is to also contain on the arbor 36 resilient torque transmission member 39, thus preventing it from sliding axially off the arbor 36. Resilient torque transmission member 39 performs a shock unloading function to absorb and subsequently unload the shock of initial acceleration forces.
Spring 50 has an upwardly or outwardly extending tang 54 engageable with tang slot 66. Tang slot 66 is formed into clutch sleeve 68. Clutch sleeve 68 has on its exterior a cylindrical surface into which slip ring 70 is engaged. Slip ring 70 is further provided with lug 72 through which a screw 74 is threadedly engaged. Screw 74 may be provided with a spring 78 coaxial therewith as better illustrated in FIG. 2. Screw 74 and spring 78 in conjunction with slip ring 70 provides a tensioning or frictional adjustment. Slip ring 70 carries clutch lug 76 on its periphery. Clutch spring 50 is contained within the interior of clutch sleeve 68. Clock spring housing 60 contains a clock spring 61 which will be wound during the normal operation of the paper carriage in moving from right to left during printing and spacing escapements. The clock spring thus is wound to insure that a tension sufficient to prevent slack is maintained on carriage return cord 80 at all times.
Referring to FIGS. 2 and 4, FIG. 4 being a perspective view of the clutch latch control from the opposite direction of that illustrated in FIG. 2, and with the carriage return control module removed for visibility sake, a clutch pawl 82 is provided in proximity to the periphery of slip ring 70 which frictionally engages the exterior of clutch slip ring 68. Sleeve 70 carries clutch lug 76 which extends outwardly therefrom, and clutch pawl 82 is positioned to be insertable into the path of lug 76 as illustrated in FIG. 2.
Clutch pawl 82 is pivotally supported on support pin 84 which is shown mounted on the typewriter frame 86 in FIG. 4. Typewriter frame 86 in FIG. 4 is not similarly illustrated in FIG. 2 for visibility. Clutch pawl 82 is formed as a single piece member or bellcrank and is further comprised of a main body section 87 and a lower arm 88. Extending from the main body section 86 is a pivotal support member 90 which carries on it in a pivotal fashion latch pawl 92. Main body section 87 of clutch pawl 82 further has a spring retainer 94 for mounting a tension spring 96 between spring retainer 94 and pawl 92. Pawl 92 is normally biased by spring 96 into engagement with its adjacent face of main body section 87 of clutch pawl 82.
To provide movement for clutch pawl 82, link 98 is engaged with the lower arm 88 of clutch pawl 82. Link 98, on its opposite end, is connected into a bellcrank 100 which is in turn spring biased by tension spring 102 attached to typewriter frame 86. Under the influence of spring 102, link 98 will provide a normal biasing force toward engagement of pawl 82 into the path of lug 76.
Movement of bellcrank 100 is permitted due to the motion slot 104 in pulley arm 106. Connecting link 108 is engaged with lost motion slot 104 and bellcrank 100, thus permitting a limited amount of movement of link 108 and bellcrank 100 without encountering the resistance of pulley arm 106. Pulley arm 106 is attached likewise to the typewriter frame 86 by means of fulcrum pin 110 and biased with respect to the typewriter frame 86 by a tension spring 112.
Mounted on arm 106 as a cord direction change means is pulley 114. Pulley 114 acts to direct the carriage return cord 80 in a direction perpendicular to the plane of the cord takeup spool 58.
Referring to FIGS. 2 and 3, link 108 is illustrated in the position where clutch pawl 82 has engaged lug 76 in order to cause engagement of clutch spring 50 with arbor 56 of FIG. 3 and the cord tension in cord 80 has not risen to the point sufficient to displace pulley 114 against the force of spring 112 and thus rotate arm 106 in a counterclockwise direction as in FIG. 2.
FIG. 4 illustrates this same linkage in a position where the pulley 114 has been translated rightwardly by cord tension sufficient to cause the lost motion slot 104 to engage in a forcible connection with link 108.
Referring to FIGS. 2 and 4, with particular attention to FIG. 4, pivot pin 120, supported on frame 86 pivotally supports trigger mechanism 122. Trigger 122 is in the form of a bellcrank having one arm 124 engaged by a link to the keyboard 126. Two other separate arms of the bellcrank 128 and 130 are also formed thereon. Arms 128 and 130 serve as latch surfaces for engagement with the tip of pawl 92.
Link 126 extending toward the front of the typewriter 10 is connected to bellcrank 132 which in turn may be oscillated by carriage return button 134 shown in FIG. 1. The movement of keybutton 134 is thus transferred through bellcrank 132 and link 126 to trigger bellcrank 122. As trigger mechanism 122 is oscillated in FIG. 4 in a clockwise direction in response to carriage return button 134 and its depression, the arms 130 and 128 will be moved downward. The movement of arm 130 downward will cause it to disengage from the tip of latch pawl 92 thus allowing spring 102 to move the bellcrank 100, link 98 and clutch pawl 82 in such a direction as to engage clutch pawl 82 with lug 76 on the slip ring 70 upon its next revolution. This will effectively engage the carriage return clutch control mechanism 18 to begin to effect the drawing in of carriage return cord 80 and the shifting of carriage 12 rightward as depicted in FIG. 1.
Pawl 92 will remain disengaged from arm 130 so long as the carriage return mechanism is operative. Upon the completion of the carriage return, the action of pulley 114 under the increasing tension cord 80 will cause the arm 106 in FIG. 4 to rotate in a clockwise direction effecting a pulling on link 98 through link 108 and bellcrank 100 and a counterclockwise rotation of clutch pawl 82 about its support shaft 84. As it is retracted, pawl 92 is retracted along with pawl 82. In the event that the carriage return button has been released, pawl 92 will engage arm 130 and will cam away from pawl 82 until it has been adequately withdrawn for pawl 92 to clear arm 130 and reposition itself against pawl 82.
Upon the relaxation of the cord tension due to the disengagement of the clutch by withdrawal of pawl 82, spring 112 will act to relieve forcible engagement of lost motion slot 104 against link 108 permitting spring 102 to move pawl 82 generally toward engagement. As pawl 92 reengages arm 130, pawl 82 will be stopped. Arm 128 is provided so that in the event the operator's finger remains on the carriage return key 134 and link 126 remains displaced such that arm 130 is not in a position to reengage pawl 92, arm 128 is capable of trapping pawl 92. Upon the restoration of bellcrank 122 to its normal at rest position, arm 128 will disengage by rotating out of engagement with pawl 92 and permit pawl 92 to engage arm 130 in preparation for the next operation.
Should the operator desire a repeat index function after the normal carriage return, carriage return key 134 may be further depressed to prevent both arm 130 and 128 from engaging pawl 92 upon its return and, therefore, allow clutch pawl 82 to again reengage clutch lug 76. By doing this, the cord tension will be increased and with the carriage return cord 80 engaged with the line feed mechanism as is highly conventional, the platen 8 on carriage 12 will be indexed through a line feed movement and then the cord tension will increase to again disable the clutch through the tension sensing control.
A typical sequence of operations for this device would be for the operator to depress the carriage return key 134. Depression of the carriage return key 134 will effect translational movement of link 126, thereby rotating bellcrank 122 to displace arm 130 downward and thus disengage pawl 92. As arm 130 is depressed and disengages pawl 92, clutch pawl 82 will move inward toward engagement with lug 76, a condition illustrated in FIG. 2. This movement of the clutch pawl 82 is effected by the force exerted by spring 102 on bellcrank 100. As lug 76 engages pawl 82, the outer sleeve 70 stops rotating and the friction between slip ring 70 and clutch sleeve 68 sufficient to at least momentarily stop clutch sleeve 68. As sleeve 68 stops, slot 66 will act to prevent further rotation of tang 54 of clutch spring 50. Clutch spring 50 will then begin to wrap down onto arbor 56. As clutch spring 50 engages the periphery of arbor 56 and attempts to rotate cord drum 58, a resistance is encountered by the drive chain of parts comprising hub 26, shock spring 39, arbor 36, clutch spring 50 and arbor 56. As this resistance to movement is transferred from arbor 56 back through the chain of drive, hub 26 will continue to rotate under the influence of drive belt 22 in a clockwise direction as shown in FIG. 3. This movement will continue and will act to wind spring 39 through the action of member 28 on tang 42. As this energy is stored, a portion of the energy is transmitted by tang 40 to arbor 36 for further driving of the carriage return drive. The initial shocks are absorbed by spring 39, thus preventing a high tension in cord 80 during the portion of operation where carriage 12 is being accelerated.
At the time that the carriage 12 completes its return movement and stop surface 31 within the interior of hub 26 engages the end of rim 37, thus forming a solid drive connection for further driving of the arbor 36.
Sleeve 70 having lug 76 formed as a part thereof is provided with an adjustment means primarily two lugs 72 and adjusting screw 74 coupled with spring 78. This device provides a means for controlling the frictional drag between the slip ring 70 extending around sleeve 68. This arrangement permits sleeve 68 to rotate after clutch spring 50 has fully wrapped down onto arbor 56 and it is necessary for clutch spring 50 to continue to rotate.
FIG. 6 illustrates a typical cord tension versus time graph showing on curve A the peaks encountered during acceleration, where the shock absorbing spring member 38 is not found in the mechanism and where there is a direct drive from the hub 26 to arbor 36.
Curve B illustrates the effect of putting the shock absorbing torque transmission member 38 between drive hub 26 and arbor 36 and the absorbing of the initial acceleration peaks. The cord tension necessary to release the clutch pawl 82 from engagement with lug 76 and allow disengagement of the clutch spring 50 from arbor 56 may be controlled by the strength of spring 112. It is highly advantageous to limit the amount of force required to extend spring 112 to the minimum necessary for reliable function.
The predetermined cord tension necessary to operate the pulley arm 106 and thus the trigger 122 to disengage the clutch spring 50 is sized to exceed the tensions experienced during acceleration but as low as reliable. Spring 112 is the controlling factor in setting the predetermined cord tension.
Therefore, it is also desirable to limit the cord tension during the initial acceleration phase of operation, thereby reducing the chances of mechanical wear and failure due to cord breakage or overloading of the clutch mechanism. Additionally, by reducing the necessary cord tension during the acceleration phase, a lower knock-off cord tension may be utilized, thus reducing the load on the motor.
It is also highly beneficial to the operation of the carriage return control and function that the shock unloader spring 39 further acts to dampen the oscillations in the velocity of the carriage 12 during carriage return, since this allows the drive motor 20 to operate under a smoother load and permits a better design of the machine, having predictable timing. | A carriage return device utilizing a spring clutch and shock unloader spring is disclosed in conjunction with a cord tension sensing mechanism for detecting the cord tension increases when the paper carriage of a typewriter ceases to move and the carriage return drive mechanism continues to operate. It is desirable to disengage the drive mechanism at that point rather than to cause frictional wear or overloading of the motor pending a predetermined amount of driving time prior to disengagement. Upon the cord tension reaching a preset value, the clutch pawl will disengage the drive clutch and prevent further wear of the clutching arrangement. To prevent premature disengagement of the clutch, a shock unloading pretensioned spring is incorporated in the drive unit to absorb the initial shocks of clutch engagement and the forces experienced during acceleration of the paper carriage. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
The present application claims priority under 35 U.S.C. §119 to Japanese Patent Application No. 2006-148142, filed May 29, 2006, the entire contents of which are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to vehicle instrument panel devices and in particular to a vehicle instrument panel device having a main switch including an ignition switch.
2. Description of Background Art
Motorcycles, all terrain vehicles (hereinafter referred to as “ATVs”) and other vehicles include an instrument panel device generally housing a speed meter and an odometer. There is known an example in which a main switch including an ignition switch as well as instruments such as a speed meter and an odometer is integrally arranged in such an instrument panel device. Japanese Patent Laid-Open No. 2005-280577 discloses an ATV attached with an instrument panel device including a main switch in which the central axis of a key cylinder, namely, a direction of taking a key in and out, is set to a direction almost-vertically to an instrument panel.
An effort has been made to reduce the thickness of the entire instrument panel device (a size in a direction perpendicular to an instrument panel) by employing a liquid crystal display panel or the like as an instrument panel installed in the instrument panel device.
A key cylinder may be arranged almost vertically to an instrument panel like the instrument panel device described in Japanese Patent Laid-Open No. 2005-280577. In this case, a cover of the instrument panel device needs to cover at least a length of the key cylinder extending from the surface of the instrument panel. However, this opposes the technique of downsizing the instrument panel device by reducing the thickness of the entire instrument panel device. Thus, a technique is desired which can downsize the instrument panel device without the effect of the length of the key cylinder.
It is an object of the present invention to provide an instrument panel device that can be downsized while being equipped with a main switch having a key cylinder.
SUMMARY AND OBJECTS OF THE INVENTION
To achieve the above object, according to a first aspect of the present invention, a vehicle instrument panel device includes: an instrument panel having an instrument and a screen displaying display information of the instrument; a main switch including a key cylinder; and a meter cover which covers the instrument panel and the main switch; the main switch is attached to an side wall portion of the meter cover and the key cylinder projects obliquely downwardly from the side wall portion in the meter cover.
According to a second aspect of the present invention, an inclined surface formed to have a downward angle with respect to an upper surface of the instrument panel is provided in the side wall portion of the meter cover and the inclined surface is provided with an attachment hole adapted to receive the key cylinder passing therethrough.
According to a third aspect of the present invention, the inclined surface is arranged in the side wall portion of the meter cover and at a position close to a rear portion of a vehicle mounted with the vehicle instrument panel device.
According to a fourth aspect of the present invention, the inclined surface is formed with a stepped surface at a position recessed inwardly of the meter cover from an outermost circumferential portion of the side wall portion.
According to a fifth aspect of the present invention the inclined surface is formed to have a further inclined angle so that the key cylinder which passes through the attachment hole for attachment thereto is oriented toward the screen of the instrument panel.
The effects of the invention include the following:
According to the first aspect of the present invention, unlike, for example, the structure of a key cylinder extending vertically from the upper surface of a meter cover, the key cylinder is arranged to extend obliquely downwardly from the side surface of the meter cover. Therefore, the depth extending downward from the upper surface of the meter cover can be reduced. Consequently, the instrument panel device can be entirely downsized. In addition, since the depth of the meter cover is reduced, the position of the instrument panel can be lowered accordingly, contributing to lowering of the gravity center of the entire vehicle.
According to the second aspect of the present invention, since the main switch is attached to the inclined surface formed in the meter cover, the projecting direction of the key cylinder can be defined accurately.
According to the third aspect of the present invention, since the main switch is disposed close to the rear end portion of the meter cover, the operator can operate switches without stretching her or his arm widely. In addition, since the amount of the meter cover projecting from the main switch toward the operator is reduced, the space around the main switch can be enlarged during operation, thereby enhancing operability.
According to the fourth aspect of the present invention, since the inclined surface serving as an attachment surface for the main switch is set at a position recessed by one step, the entire instrument panel device can be further downsized. In addition, the amount of the key projecting from the meter cover can be reduced, the key being inserted into the key cylinder.
According to the fifth aspect of the present invention, since the key cylinder extends toward the screen of the instrument panel, protrusion of the meter cover can be reduced, thereby further downsizing the entire instrument panel device.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which are given by way of illustration only, and thus are not limitative of the present invention, and wherein:
FIG. 1 is a perspective view of an essential portion of a vehicle front portion including an instrument panel device according to an embodiment of the present invention;
FIG. 2 is a side view of the essential portion of the vehicle front portion shown in FIG. 1 ;
FIG. 3 is a side view of an ATV as an example of the vehicle mounted with the instrument panel device;
FIG. 4 is a perspective view of a meter cover;
FIG. 5 is a plan view of the meter cover; and
FIG. 6 is a front view of the meter cover.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
An embodiment of the present invention will be hereinafter described with reference to the drawings. FIG. 3 is a side view of an ATV mounted with an instrument panel device according to the embodiment of the present invention. The ATV 1 includes a body frame 2 , a 4-cycle engine 3 , a power transmission device 4 , a front cushion 5 and a rear cushion 6 . The engine 3 is disposed at a central lower portion of the body frame 2 . The power transmission device 4 is connected to the output shaft of the engine 3 . The front and rear cushions 5 and 6 carry the front and rear, respectively, of the power transmission device 4 swingably with respect to the body frame 2 .
The body frame 2 includes a main frame 12 , a pair of left and right front frames 13 and rear frames 14 . The front frames 13 are connected by a bracket 15 and a cross member 16 . A front guard 17 and a front carrier 18 are attached to the front portion of the front frame 13 . A fender 10 composed of a front cover 33 and a rear cover 34 is attached to the body frame 2 . A pair of left and right headlights 21 are attached to the front portion of the vehicle body.
The power transmission device 4 includes a transmission 24 , a gear shift pedal 25 , a front drive shaft 26 and a rear drive shaft 27 . The front drive shaft 26 is connected to a front reduction gear 28 and the rear drive shaft 27 is connected to a rear reduction gear 29 . A pair of left and right front wheels 7 and rear wheels 8 (only left-hand front and rear wheels 7 and 8 are illustrated) are attached to the power transmission device 4 . A steering device 9 is connected to the front wheels 7 . The steering device 9 includes a steering shaft 31 attached to the main frame 12 with a shaft holder 30 and a handlebar 32 attached to the steering shaft 31 .
A passenger seat 11 is provided above the engine 3 . An oil pan 35 is disposed below the engine 3 . A cooling fan 36 which forcibly cools the engine and a lubricating oil mechanism 37 are disposed forward of the engine 3 . An instrument panel device 38 is provided on the upper portion of the steering device 9 .
The instrument panel device 38 is described in detail. FIGS. 1 and 2 are a perspective view and a right side view, respectively, illustrating an upper portion of the steering device 9 with the front cover 33 removed. A support plate 39 with an almost-horizontal surface is fixedly attached to an upper end of the steering shaft 31 . A lower-half block 40 A constituting part of a handlebar support block 40 is fastened to the upper surface of the support plate 39 with a bolt 41 . An upper-half block 40 B is, from above, fitted together with and fastened to the lower-half block 40 A with bolts 42 . The upper surface of the lower-half block 40 A and the lower surface of the upper-half block 40 B are each formed with a semi-circular groove conforming to the shape of the handlebar 32 .
The handlebar 32 is composed of a central horizontal portion, almost-vertical portions extending upward from both the ends of the central horizontal portion and both-end horizontal portions contiguous to the almost-vertical portions. The central horizontal portion of the handlebar 32 is sandwiched from above and below by the upper-half block 40 B and the lower-half block 40 A, respectively. The semi-circular grooves come into contact with the outer circumference of the handlebar 32 . The lower-half block 40 A and the upper-half block 40 B are fastened with the bolts 42 , whereby the handlebar 32 is secured to the handlebar support block 40 .
The instrument panel device 38 is disposed above the central horizontal portion of the handlebar 32 , namely, above a portion lowered by one step from both-end portions of the handlebar 32 . The instrument panel device 38 includes an instrument panel (panel main body) 43 provided with instruments indicating the conditions of the ATV, such as a speed meter, a rotating meter, a fuel meter, an odometer, etc. and with a liquid crystal display panel indicating information. The panel main body 43 is supported by a stay 45 connected to a bracket 44 secured to the support block 40 and by a stay 47 connected to a pipe member 46 which is secured to the front surface of the plate 39 and extends upward.
A meter cover 48 is provided to cover the central portion of the handlebar 32 including the panel main body 43 . The stay 47 extends so as to reach an attachment boss 487 formed inside the meter cover 48 . The meter cover 48 is supported by the handlebar 32 by passing a setscrew 49 through the stay 47 from below and fastening it to the attachment boss 487 . Attachment bosses (see FIGS. 5 and 6 ) are provided at the rear portion of the meter cover 48 and are secured to the extension of the stay 45 with setscrews (not shown).
The meter cover 48 is composed of an upper surface portion 481 covering the panel main body 43 from above and a front surface portion 482 which is contiguous to the front portion of the upper surface portion 481 and extends downward. The upper surface of the panel main body 43 is viewed from a window 483 formed in the upper surface portion 481 .
A main switch 50 is attached to a right side portion of the upper surface portion 481 of the meter cover 48 . The main switch 50 has a function of opening and closing a main circuit which feeds electric power from a battery to an electrical system provided in the ATV 1 and an ignition switch function of driving an ignition device of the engine.
A key cylinder 50 A of the main switch 50 is not arranged parallel or vertically to the upper surface of the panel main body 43 . The key cylinder 50 is arranged so that its key insertion slot side end portion 50 B and bottom portion are located on the upside and downside, respectively. That is to say, the key cylinder 50 A is arranged obliquely relative to the upper surface of the panel main body 43 . Since the key cylinder 50 is arranged obliquely relative to the upper surface of the panel main body 43 , the depth D of the meter cover 48 (a dimension in a direction perpendicular to the upper surface of the panel main body 43 ) can be reduced as shown in FIG. 2 . If the key cylinder 50 A is arranged parallel to the panel main body 43 , the depth D can be further reduced. Taking into consideration the height of the operator's eyes when she or he inserts the key into the key cylinder 50 A, however, it is advantageous that the key insertion slot of the key cylinder 50 A slightly faces the upside. Thus, the key cylinder 50 A is oriented obliquely so that the depth D is almost equal to the thickness of the panel main body 43 .
The handlebar 32 is provided with grips 51 and 52 at left and right ends thereof, respectively. A combination switch 53 is provided adjacently to the left grip 51 . The combination switch 53 includes a plurality of switches including a shift-up switch, a shift-down switch, an engine stop switch, a winker switch and a dimmer switch. A throttle lever 54 , a throttle lever operation angle sensor 55 , a brake lever 56 , a brake oil reservoir 57 and the like are provided in the vicinity of the right grip 52 .
The meter cover 48 is subsequently described in detail. FIG. 4 is a perspective view of the meter cover 48 , FIG. 5 is a plan view of the meter cover 48 and FIG. 6 is a front view (as viewed from the rear of the vehicle body). The meter cover 48 can be integrally cast from a resin material such as polyethylene. The meter cover 48 is formed with the large rectangular window 483 at the upper surface portion 481 as described above and with a circular hole 484 adapted to receive the key cylinder 50 A inserted thereinto. The circular hole 484 is formed in an inclined surface 485 having an angle with respect to a plane including the window 483 . The inclined surface 485 has an angle with respect to a plane including the window 483 and is provided along the plane including the window 483 at a minute angle β with respect to the upper and lower sides of the window 483 . The inclined surface 485 is formed as a surface recessed from the outermost circumferential portion of the meter cover 48 . Specifically, the inclined surface 485 is disposed at a position lowered by one step from the side surface 488 of the meter cover 48 through a boundary surface 489 .
In this way, the inclined surface 485 is lowered by one step from the outermost circumferential portion of the meter cover 48 . Therefore, a portion of the surface of the key cylinder 50 A or a portion of the key 50 A inserted into the key cylinder 50 A (indicated with the two-dot chain line in FIG. 5 ) which projects outwardly from the meter cover 48 can be reduced.
Preferably, the position of the key cylinder 50 A, namely, the forming position of the circular hole 484 is set at the aftermost portion of the meter cover 48 , that is, at a position in vicinity to the end face of the meter cover 48 close to the rear of the vehicle body. This intends to facilitate the operator's operation by bringing the key cylinder 50 A closer to the operator.
The meter cover 48 is formed on the inside thereof with a plurality of ribs 486 used for reinforcement and with attachment bosses 487 adapted to receive setscrews 49 fastened thereto for securing the meter cover 48 .
The present invention has been described thus far according to the embodiment but is not limited to the embodiment. The invention may be modified or altered in various ways. For instance, the vehicle mounted with the instrument panel device is not limited to the ATV and the present invention can be applied to overall saddle-ride type vehicles such as motorcycles and three wheelers. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims. | An instrument panel device includes an instrument panel incorporating a speed meter, an odometer, a main switch and a meter cover covering the instrument panel and the main switch. The main switch is provided with a key cylinder projecting inwardly from the side surface of the meter cover. An inclined surface is formed on the side surface of the meter cover so that the projecting direction of the key cylinder is oriented obliquely downwardly. The inclined surface is formed at a position lowered by one step from the outermost circumferential surface of the meter cover. The resulting configuration reduces the size of the instrument panel device by reducing the depth of the instrument panel device incorporating the main switch with the key cylinder. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of, and hereby incorporates by reference, U.S. patent application Ser. No. 12/001,080, filed Dec. 7, 2001, which, in turn, claims priority under 35 U.S.C. §119(e) to, and hereby incorporates by reference, U.S. Provisional Application No. 60/874,212, filed Dec. 11, 2006.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to the printing industry and, in particular, this invention relates to devices for curing ultraviolet sensitive inks printed on substrate.
[0004] 2. Background
[0005] Ultraviolet-sensitive ink is used widely in the printing industry. One reason for its use is that ultraviolet-sensitive ink can be quickly cured by being irradiated with ultraviolet light. Such irradiation is accomplished by directing a light beam, containing high proportions of ultraviolet light, at the printed substrate.
[0006] Lamps used to generate light for this purpose also generate considerable amounts of other energy in the form of heat. This heat is usually of little consequence when a printing press is operating, because the light and heat are directed toward the substrate which is in motion during the printing process. However, if the heat and light generated by the lamp is directed at a nonmoving substrate for a sufficient amount of time, the substrate is damaged, often to the point of the ignition. Additionally, other nonmoving components of the printing press may be damaged by the high amount of heat generated from the lamps. When the printing press operation must be halted, for example to Clear obstructions or replenish ink supplies, the light generated by the lamp must be prevented from impinging the substrate. One way to prevent irradiating nonmoving substrate is to power down the lamp. However, considerable time is necessary for the lamp to generate sufficient irradiation to cure the ultraviolet-sensitive ink when power is restored. Consequently, preventing irradiation from impinging nonmoving substrate when a printing press is halted has been accomplished by housing the lamp in a structure having shutters, which can be opened to allow irradiation or closed to prevent irradiation from leaving the structure.
[0007] As stated above, intense heat is generated by the UV lamp during operation. These high-energy lamps require high-voltage and fairly high current, some requiring 3000 volts and 17 amps and may generate temperatures of 1000 degrees Fahrenheit during operation. Consequently, the structures housing these high-energy lamps are subjected to periods of the extremely high temperatures. These high temperatures inescapably cause the metal components of these structures to expand and warp. One consequence of this expansion and warpage is failure of these structures to properly operate.
[0008] There is then a need for an ultraviolet module, which can dependably operate when subjected to the intense heat generated by high-energy ultraviolet lamps.
SUMMARY OF THE INVENTION
[0009] This invention substantially meets the aforementioned needs of the industry by providing an ultraviolet module capable of functioning when components of the module are expanded and warped by heat generated during operation and which can be readily adjusted without extensive or undue effort or time expenditure.
[0010] A cassette style shutter drive assembly has been developed, which operates efficiently when subjected to extremely high heat generated by high-energy ultraviolet lamps. One embodiment has two shutter drive assemblies, each incorporating a clutch, drive train, and other associated components to eliminate problems associated with shutter warpage, drive train component misalignment, as well as other tolerance issues.
[0011] Each of a plurality of, e.g., two, shutter drive assemblies incorporates a clutch as well as a set of features designed to eliminate problems associated with shutter warpage, drive train component misalignment, and other malfunctions due to incorrect tolerances. The shutter drive train operates both shutter drive assemblies simultaneously.
[0012] A shutter shaft sleeve bearing used as a component of one embodiment of this invention includes integral internal dynamic seal glands and integral external static seal glands. The two external seals are arranged with a coolant drainway therebetween, working in conjunction with a drain port integral to the connection end cap to provide a visual leak path and indicator.
[0013] A ball-drive pin engages a slot in the shutter end cap to drive the shutter. Several degrees of freedom are provided by this pin and the shutter end cap slot arrangement, thereby allowing the shutter to warp and change length without inducing undesirable forces on the drive train components. The shutter arm assembly contributes thusly to reliable shutter functionality.
[0014] A pair of “indexing” clutches (e.g., one clutch per shutter) has been designed to prevent drive train binding and subsequent drive motor overload. Each clutch is bi-directional, having an adjustable break-point torque to enable automatic re-engagement. The instant clutch also allows for shutter retiming (synchronization). Each worm gear may be positively secured to a shutter shaft using a special two-piece clamp collar and a drive pin, which engages the worm gear. An angled shoulder on the collar abuttingly mates to an angled rib on the shutter shaft. These two features cooperate to function as a circumferential wedge. When the clamp fasteners are tightened, the worm gear is firmly secured in place. Loosening the fasteners on both shutter drive assemblies accordingly allows the gears to be oriented as required to time or synchronize the shutters to work together properly.
[0015] The worm gear is secured to the shutter shaft in a positive manner by using a two-piece clamp collar and a drive pin. The two-piece collar clamps securely to the shutter shaft. The drive pin protrudes from the collar to engage a slot in the worm gear. The collar also features an angled shoulder which mates to an angled rib integral to the shutter shaft. These two features serve as a circumferential wedge. As the fasteners securing the two-piece collar to the shutter shaft are tightened, the worm gear is wedged toward a bearing-retaining nut. The gear is then tightly clamped between the clamp collar and the nut. The combination of the two-piece clamp collar, drive pin, and wedge-induced clamping action serves to firmly secure the worm gear in place and correctly positions the worm gear relative to the worm. This arrangement allows all worm gear teeth remain fully intact and functional so that the worm gear may rotate fully in accordance to the requirements for proper clutch operation.
[0016] The shutter shafts and the exhaust shutter pivot shafts function as bearing surfaces for the shutter end cap bearings as well as for O-rings and sealing surfaces for the shutter end cap bearing seals.
[0017] An integral stop is built into the center of the lower end cap to prevent either of the shutters from over-traveling or contacting the UV lamp. The stop works equally well for all contemplated manual and automatic operations.
[0018] A pair of sensors monitors the “open” and “closed” positions of each shutter. These sensors are activated by a magnet embedded in the shutter shaft arm and are mounted so as to minimize contact with hot module components. The sensor/magnet arrangement provides for a range of sensor sensitivity. Once the sensitivity of the sensor/magnet arrangement is adjusted as desired, sensitivity is unaffected by changes in shutter length, shutter axial position, shutter radial position, or shutter warpage.
[0019] A drain hole in the connection end cap assembly may be ported outside the instant module, thereby visually indicating the existence of an internal leak. The drain hole may also direct leaking coolant away from electrical components to reduce the likelihood of detrimental high-energy short circuits.
[0020] The water poppet valve may have a double-seal arrangement. Accordingly, the instant water poppet valve may be essentially drip-free during module installation, removal, and post-removal. This high-flow valve fits into a restricted amount of space and functions in conjunction with a rotating shutter shaft and its integral coolant passageway.
[0021] Shutter end cap material is matched to the shutter extrusion material to minimize galvanic and corrosive effects. The shutter end cap includes a special coolant passageway, which doubles as a reservoir and cooperates with other features to cool the stem of the UV lamp, as well as other components.
[0022] The bearing/seal arrangement in the shutter end caps allows for nominal flexing, thermal expansion/contraction, warpage, and dimensional variations of the shutter assembly without sacrificing fluid-tight integrity or inducing adverse forces on seals and shutter drive train components. The instant bearing features a narrow, centrally located load-bearing surface that is sealed on either side by a pair of integral seal glands fitted with O-rings. The O-rings help to distribute the bearing loads and the outer seal also serves as a wiper. The bearing arrangement also provides for important freedom of motion for the shutter assembly relative to these shutter shafts. The bearing further acts as a heat sink and a heat transfer element further cooling the stem of the UV lamp and other components.
[0023] In one embodiment, the lamp connector of this invention is a two-piece assembly, thereby allowing easier and more reliable assembly of the high-voltage socket and lead wire. Additional insulation may be present around the high-voltage wire entryway and around the socket opening. The increased insulation results in a longer and a less direct electrical leak path to thereby reduce the chance of a high-energy short circuit.
[0024] Both lamp connector assemblies may be spring-loaded against the lamp. This spring-loading encourages higher and more consistent electrical conductivity, maintains full pin-socket engagement during aggressive module installations, allows for more relaxed dimensional tolerances for manufacturing the UV bulb, and minimizes high-energy short circuits.
[0025] Special non-conductive, screw-ferrules may be used as a mechanical backup to thereby secure the high voltage pin and socket connectors into the electrical connection block. The ferrules also allow for easier pin and socket servicing.
[0026] Coolant plugs with integral sacrificial zinc anodes may be installed directly in the coolant flow path inside the module to prevent corrosion in the coolant passage ways. The anodes may be shaped to reduce flow restrictions.
[0027] The shutter end caps may have a relieved reflector mounting surface. This feature provides better UV protection for the ring located in the shutter body/shutter end cap interface and eliminates the need for custom-fit reflector strips.
[0028] The reflectors may be removed and installed without removing the shutter end caps and without breaking the fluid-tight integrity of the shutter assembly. Only the retaining strip needs to be removed to exchange a reflector.
[0029] The design of the instant module produces a full length, uninterrupted, properly shaped reflector supporting surface. This design further provides for quicker reflector replacement and allows the use of convenient pre-cut reflectors.
[0030] In one embodiment, the original female V-shaped reflector retainer profile has been modified to include a shallow U-shaped channel. This helps to prevent shutter-to-shutter binding when the shutters are closed. The U-shaped channel does not reduce the effectiveness of how well the closed shutters block light.
[0031] The coolant cross over feature may be incorporated into the upper module of this invention to facilitate easier and less expensive manufacturing and assembly. The cross over cavity doubles as a substantial reservoir to provide better component cooling.
[0032] A slide-out mount for the electrical connection assembly is located in the connection block and may be easily removed to provide better and quicker service. Special three-dimensional locating features provide the precise alignment required for optimum module performance.
[0033] The dove-tailed edge design of the shutter drive train access doors allows the doors to be easily removed with a minimum of module disassembly.
[0034] The stub bayonet shafts act as precision two-dimensional locating dowel to provide optimum functionality to the poppet valves and electrical connections.
[0035] The latch rod has locating features at the latch-end and provides accurate axial positioning of the poppet valve components and the electrical connections.
[0036] The spring-loaded latch provides precise axial alignment of the instant module to the connection block of this invention. When combined with the stub bayonets and the latch rod left, a precise three-dimensional module-to-module connection block docking is easily achieved to provide for optimum module performance.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] FIG. 1 is a top isometric view of one embodiment of the UV module of this invention.
[0038] FIG. 2 is a bottom view of the UV module of FIG. 1 .
[0039] FIG. 3 is a top, isometric view of the connection block of this invention.
[0040] FIG. 4 is a perspective view of the module of FIG. 1 docked to the connection block of FIG. 3 .
[0041] FIG. 5 is a sectional view depicting portions of the instant shutter shaft seal arrangement and bearing arrangement.
[0042] FIG. 6 is an oblique sectional view of the UV module of FIG. 1 with the shutters in an open position.
[0043] FIG. 7 is an oblique sectional view of the UV module of FIG. 1 with the shutters in a closed position.
[0044] FIG. 8 is a perspective view of one embodiment of the instant shutter shaft assembly.
[0045] FIG. 9 is a perspective view of the shutter shaft assembly of FIG. 8 and a shutter end cap of this invention, shown disengaged.
[0046] FIG. 10 is a perspective view of one embodiment of the shutter drive train of this invention.
[0047] FIG. 11 is a partial sectional view of the shutter drive pin/slot, depicting freedoms of motion thereof.
[0048] FIG. 12 is a perspective view of one embodiment of the instant clutch, having the shutter arm thereof in phantom view.
[0049] FIG. 13 is an oblique sectional view showing the instant shutters “out of time” (unsynchronized).
[0050] FIG. 14 is a perspective view of the lower end cap showing an integral stop of one embodiment of the module of this invention.
[0051] FIG. 15 is a perspective view depicting shutter position sensors of this invention as mounted in the instant connection end cap assembly.
[0052] FIG. 16 is a sectional view of one embodiment of the poppet valve of this invention, prior to docking.
[0053] FIG. 17 is a sectional view of the poppet valve of FIG. 16 during mid-docking.
[0054] FIG. 18 is a sectional view of a poppet valve of FIG. 16 fully docked.
[0055] FIG. 19 is a sectional view of the connection end of the shutter end cap bearing/seal arrangement of this invention.
[0056] FIG. 20 is a sectional view of the exhaust end of one embodiment of the shutter end cap bearing/seal arrangement of this invention.
[0057] FIG. 21 is an isometric view of one embodiment of the lamp connector assembly of this invention.
[0058] FIG. 22 is a sectional view of the lamp connector assembly of FIG. 21 .
[0059] FIG. 23 is an isometric view of one embodiment of the ferrules and high-voltage pin connector of this connection.
[0060] FIG. 24 is a sectional view of the ferrules and high-voltage pin assembly of FIG. 23 .
[0061] FIG. 25 is a perspective view of one embodiment of the coolant plugs with integral sacrificial anodes of this invention.
[0062] FIG. 26 is a sectional view of the coolant plugs with integral sacrificial anodes of FIG. 25 .
[0063] FIG. 27 is a perspective view of one embodiment of the shutter end cap of this invention showing a relieved reflector mounting surface.
[0064] FIG. 28 is a perspective view of the shutter end cap of FIG. 27 installed in the module of FIG. 1 .
[0065] FIG. 29 is a perspective view of one embodiment of the cross-over location callout of this invention.
[0066] FIG. 30 is a perspective view of one embodiment of the upper module cover of this invention with cross-over details.
[0067] FIG. 31 is a perspective view of one embodiment of the UV module of this invention showing slide-out mount detail.
[0068] FIG. 32 is a perspective view of one embodiment of the slide-out mount of this invention shown removed from one embodiment of the connection block of this invention.
[0069] FIG. 33 is a perspective view of the slide-out mount of FIG. 31 .
[0070] FIG. 34 is a perspective view of one embodiment of the UV module of this invention, with an access door location.
[0071] FIG. 35 is a perspective view of the UV module embodiment of FIG. 34 , the access door thereof depicted as positioned for removal.
[0072] FIG. 36 is a perspective view of one embodiment of an access door of this invention.
[0073] FIG. 37 is a sectional view of one embodiment of the connection cap assembly with the access door of this invention removed.
[0074] FIG. 38 is a perspective view of one embodiment of the stub bayonet of this invention.
[0075] FIG. 39 is a sectional view of one embodiment of a three-axis module docking/locating feature of this invention.
[0076] FIG. 40 is a perspective view of one embodiment of a latch/latch-rod assembly of this invention.
[0077] FIG. 41 is a perspective view of a latch side of one embodiment of the connection end cap assembly of this invention.
[0078] FIG. 42 is a sectional view of one embodiment of a spring-loaded lamp connector of this invention, biased against a lamp.
[0079] FIG. 43 is a sectional view of one embodiment of a high voltage pin/socket arrangement of this invention.
[0080] FIG. 44 is a side view of the UV module of this invention depicting another embodiment of the positive and negative retaining strips of this invention.
[0081] FIG. 45 is a sectional view along line A-A of FIG. 44 .
[0082] FIG. 46 is a sectional view along line B-B of FIG. 44 .
[0083] FIG. 47 is a cross-section of the clutch arm of this invention depicting the ball spring plungers engaged to shutter shaft grooves.
[0084] FIG. 48 is a cross-section of the clutch arm of this invention depicting the ball spring plungers disengaged to the shutter shaft grooves.
[0085] It is understood that the above-described figures are only illustrative of the present invention and are not contemplated to limit the scope thereof.
DETAILED DESCRIPTION
[0086] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below.
[0087] Any references to such relative terms as front and back, right and left, top and bottom, upper and lower, horizontal and vertical, or the like, are intended for convenience of description and are not intended to limit the present invention or its components to any one positional or spatial orientation.
[0088] Each of the additional features and methods disclosed herein may be utilized separately or in conjunction with other features and methods to provide improved devices of this invention and methods for making and using the same. Representative examples of the teachings of the present invention, which examples utilize many of these additional features and methods in conjunction, will now be described in detail with reference to the drawings. This detailed description is merely intended to teach a person of skill in the art further details for practicing preferred aspects of the present teachings and is not intended to limit the scope of the invention. Therefore, combinations of features and methods disclosed in the following detailed description may not be necessary to practice the invention in the broadest sense, and are instead taught merely to particularly describe representative and preferred embodiments of the invention.
[0089] One embodiment of the ultraviolet (UV) module of this invention is shown in FIGS. 1 and 2 , and particularly in FIG. 4 , at 100 and includes an optional connection block assembly 102 , a connection end cap assembly 104 , a shutter assembly 106 , and an exhaust end cap assembly 108 .
[0090] Referring now to FIGS. 3 , 31 , 32 , and 33 , the connection block assembly 102 has a connection block 120 , a slide-out mount 122 , an electrical (or socket) connection subassembly 124 , a poppet valve connection block 126 , and stub bayonets 130 , 132 .
[0091] As best seen in FIG. 32 , the connection block 120 defines a stepped opening 140 , with horizontal surfaces 142 , 144 facing vertical surfaces 146 , 148 (not shown) and a lower horizontal surface 150 . Locating structures such as extensions 152 , 154 from the horizontal surfaces 142 , 144 and extensions 156 , 158 (not shown) from the vertical surfaces 146 , 148 may be present.
[0092] Referring to FIGS. 3 and 31 , an optional attachment block 160 is depicted. The attachment block 160 , in the embodiment shown, has fluid attachment features (e.g., fittings) 162 , 164 and an electrical attachment fixture 166 . One of the fluid attachment fixtures 162 , 164 connects to a source of ingressing fluids to cool the instant UV module during use and the other of the fluid attachment fixtures 162 , 164 serves as a conduit for egressing coolant fluids therefrom. When attached to the connection block assembly 102 , the attachment block 160 provides for electrical and fluid supply to the UV module of this invention. While shown oriented generally horizontally to the instant UV module, a person of ordinary skill in the art will readily recognize that the coolant and electrical attachment fittings 162 , 164 , 166 may be vertically oriented as well, due to space constraints and the like. Moreover, a person of ordinary skill in the art will readily recognize that fluids and electricity may be supplied to the UV module of this invention by other means as well. A person of ordinary skill in the art would further recognize that UV modules without a system or assembly for circulating coolant are also within the scope of this invention, for example, if sources of UV radiation are used which do not generate appreciable amounts of heat. One example of such a UV source is an LED emitter.
[0093] As seen in FIG. 33 , the slide-out mount 122 includes an upper member 172 and unitary (or otherwise integral) extensions 174 , 176 extending from the upper member 172 . An electrical connection assembly mounting face 178 is defined by the extensions 174 , 176 and a lower portion of the upper member 172 . Locating features are functionally defined as slots 180 , 182 , each defined in a lower portion of the upper member 172 adjacent each extension 174 , 176 . Further locating features include slots 184 , 186 (slot 186 not shown) defined in outboard surfaces of the extensions 174 , 176 . Threaded apertures 188 , 190 , 192 , 194 are present in the extensions 174 , 176 .
[0094] The instant slide-out mount for electrical connection assembly, located in the connection block docking with the module, may be conveniently attached to and removed from the attachment block 160 to facilitate assembly and disassembly. Due to the facilitated attachment and removal, the slide-out mount also significantly reduces servicing time. Locating features in this slide-out mount provide the precise three-dimensional alignment required for optimum module-to-connection block interface performance ( FIGS. 31 , 32 , 33 ).
[0095] As viewed in FIGS. 3 , 15 , 33 39 , 42 , and 43 , and especially in FIGS. 32 and 43 , the socket connection block subassembly 124 has a housing 200 , which encloses sockets 202 , 204 and ferrules 206 , 208 . In one embodiment, the ferrules 206 , 208 are made from a non-conductive material and are threaded into openings in the connection block housing 200 , thereby securing the sockets 202 , 204 within the housing 200 . The sockets 202 , 204 are accessed by means of openings 210 , 212 in the housing 200 . The socket connection block 124 is secured to the slide-out mount 122 by threading fasteners through apertures 214 , 216 , 218 , 220 present in the housing 200 and into the apertures 188 , 190 , 192 , 194 (present in the slide-out mount extensions 174 , 176 ). While two sockets 202 , 204 are depicted and described, a person of ordinary skill in the art would readily recognize that more sockets may be present, e.g., to accommodate other voltages. As seen in FIG. 43 , at least one, e.g., a pair of elastomeric elements, such as O-rings 228 . are optionally disposed between the electrical connection block subassembly 124 and the slide out mount 122 when the electrical connection block subassembly 124 is attached to the slide out block 122 using fasteners, such as shoulder screws 230 . While O-rings 228 are depicted as being secured by each of the shoulder screws 230 , this may not be the case in other embodiments of this invention. For example, one or more of the 0 228 -rings may be secured in a pair of diagonal or opposing corners. The elasticity of the O-rings enables the connection block subassembly 124 to move slightly during docking. Consequently, the elastomeric characteristics of the O-rings, when present, maintain the electrical connection subassembly 124 , hence the connection block assembly 102 , in a position such that the sockets are centered or positioned to receive the pins when connecting the connection block assembly 102 to the remainder of the instant UV module. as more fully described below. Upon engagement of the connection block assembly to the remainder of the module, the elasticity of the O-rings 228 ensures that the electrical connection pins can slide into their respective sockets without misalignment due to the ability of the electrical connection subassembly 124 to displace within the limits of the elasticity of the O-rings 228 . Accordingly, initial misalignments of the sockets and pins are corrected during connection or docking or whenever the connection block assembly 102 is not completely engaged to the remainder of the UV module. In UV modules of the prior art, the absence of the elastically enabled or self-correcting alignment sometimes resulted in misalignment of pins and sockets when connecting the connection block assembly to the remainder of the UV module. Consequently, the pins were not completely seated in the sockets and the electrical connections were incomplete and arcing sometimes occurred between the misaligned sockets and pins. Additionally, the sockets and/or pins were bent or damaged due to the misalignment. In other embodiments of the prior art, the connection assembly was spring mounted, thereby resulting in an attenuated ability to maintain the desired centered position. Consequently, the pins were sometimes ejected from their mounts when engaging the sockets. Ejection of pins often caused mechanical damage to the pins or sockets, arcing, and occasionally fires from the arcing. The foregoing self-centering feature of the instant electrical connection subassembly functions in conjunction with the precision dowel feature of the stub bayonets (described below) of the UV module of this invention to ensure that connecting elements of the connection block assembly 104 are properly aligned with corresponding elements of the remainder of the instant UV module.
[0096] Referring to FIGS. 32 , 33 the rear surface of the electrical connection subassembly 124 contacts the electrical connection assembly mounting face 178 of the slide-out mount 122 . The modular slide-out mount 122 is attached to the connection block 120 by disposing the slide-out mount 122 into the opening 140 , such that extensions 152 , 154 are disposed in slots 180 , 182 and such that extensions 156 , 158 are located in slots 184 , 186 . When the slide-out mount 122 is disposed in the opening 140 as described, apertures 188 , 190 in the slide-out mount 122 are aligned with threaded apertures 224 , 226 (defined from surfaces 142 , 144 of the connection block 120 ). Accordingly, the slide out mount 122 can be secured in place by threading fasteners through the foregoing aligned apertures. While the connection block of this invention is depicted as having electrical connection sockets, it should be appreciated that electrical pins could be present in place of the sockets, so that electrical connection pins shown below as present in the pin connector assembly could be replaced by sockets.
[0097] As seen in FIG. 32 , the poppet valve connection block 126 includes high flow water poppet valves 240 , 242 , which are housed in the connection block 120 . Referring now to FIGS. 16 , 17 , and 18 , each of the poppet valves 240 , 242 (poppet valve 240 shown) has a water stem 243 axially retained within a water sleeve 244 . A water stem seal 245 is disposed about an inner surface of the water sleeve 244 . An exterior seal 246 is disposed about a central portion of the water sleeve 206 . A spring (not shown), also present within the water sleeve 206 , urges the water sleeve 244 to the right (from the perspective of FIG. 12 ).
[0098] The water poppet valve of this invention has a double seal arrangement provided by seals 245 , 246 ( FIGS. 3 , 5 , 16 - 18 ). The double seal provides a virtually drip-free connection during module installation, as well as a drip-free connection when the instant module is undocked. Stated otherwise, all components are closed during initial module engagement to the connection block and again closed prior to final disengagement from the connection block. Accordingly, very little, or no, fluid escapes the valve when the instant module is being installed or removed. The instant poppet valve, in contrast to other known poppet valves, functions in conjunction with a rotating shutter shaft, the rotating shutter shaft doubling as a coolant passage way.
[0099] FIGS. 3 , 32 , and 38 depict the present stub bayonets 130 , 132 , which may unitarily (or otherwise integrally) have six cylindrical portions. A first cylindrical portion 250 adjoins a second cylindrical portion 252 , the second cylindrical portion 252 with a greater diameter. A third cylindrical portion 254 has a smaller diameter than either of flanking portions 252 , 256 . The increased diameter of the cylindrical portion 256 produces a tapered (or stepped) “precision dowel surface,” as more fully explained below. A diameter of the stub bayonets 130 , 132 continues to decrease (taper) at cylindrical portions 258 , 260 . A latch mating surface 262 is defined by facing surfaces 264 , 266 (surface 266 not shown) and 268 . The function of the latch mating surface 262 is more fully described below. The cylindrical portion 260 is secured within the connection block 120 , as depicted in FIG. 3 .
[0100] The two stub bayonet shafts guide, support and dock the connection block assembly as it is attached to, and functions with, the remainder of the instant UV module. Due to the close concentric tolerances required for optimum functionality of the water poppet valves and the electrical connections, a short section of the stub bayonets is slightly increased in diameter to act as a pair of precision locating dowel pins. This feature accurately docks the module to the connection block. The two-dimensional (up/down and side-to-side) mating precision resulting from this dowel effect enables increased flow through the water poppet valves and eliminates the pin and socket ejection problems associated with misalignment. When the precision dowel locating effect is combined with the axial (in/out) positional control gained from the instant latch rod and the instant spring-loaded docking latch (as more fully explained below), optimum functionality of the poppet valves and the electrical connections are achieved ( FIGS. 3 , 38 - 41 ).
[0101] Referring to FIGS. 1 , 2 , 4 , 5 , 10 and 16 , the connection end cap assembly 104 is enclosed in a housing 280 and includes a shutter drive train assembly 282 , a connection end cap valve assembly 283 , an end cap electrical assembly 284 , and an end cap latch assembly 286 .
[0102] As best viewed in FIG. 10 , the shutter drive train (assembly) 282 includes a connection end cap 290 (as seen in FIG. 14 ), a drive gear motor 292 , first and second spur gears 294 , 296 , a worm shaft 298 , and left and right shutter drive subassemblies 300 , 302 . However, in some embodiments, the instant drive train may be considered to include connection shutter end caps 570 , 172 (discussed below). The drive gear motor 292 rotates the spur gear 294 which, in turn, rotates the spur gear 296 . The spur gear 296 is attached to, and rotates, the worm shaft 298 . The worm shaft 298 has respective left and right hand segments 304 , 306 , which, in turn, rotate the shutter drive subassemblies 300 , 302 , as more fully explained below. However, a person of ordinary skill in the art will recognize that the shutter shafts 332 may be directly rotated by the motor 292 or that other combinations of gears to comprise the instant drive train are within the scope of this invention. As seen in FIG. 15 , also included in each of the left and right shutter drive subassemblies 300 , 302 are sensor mounts 308 , 309 and a pair of sensors 310 .
[0103] Within the instant connection end cap assembly is a geared drive motor. Via a set of spur gears, this geared drive motor turns a worm shaft having left-hand and right-hand thread segments. Each of these worm shaft segments turns a worm gear secured to a shutter shaft. The gear motor spins the worm to open or close both shutters simultaneously.
[0104] As seen in FIGS. 8 , 9 , 10 , 11 , 12 , 40 , and 41 , respective left and right shutter drive subassemblies 300 , 302 are rotatably attached to the shutter shafts 332 and have clutch pin drive assemblies 316 , 318 , and worm gears 324 , 326 , as well as substantially identical (or similar) shutter shafts 332 , collars 334 , (hex) nuts 336 , ball bearings 338 , and worm gear drive pins 340 . The left and right clutch pin drive assemblies 316 are rotatably attached to each end of the shutter shafts 332 and 318 respectively include shutter arms 350 , 352 and shutter arm extensions 354 , 356 , the other components described below being substantially identical or similar. Referring now to FIGS. 8 , 9 , 11 , 12 , 40 , and 41 , a ball headed drive pin 358 axially extends from each of the shutter arm extensions 354 , 356 . Each of the ball headed drive pins 358 has a shank 360 with a longitudinal axis 361 and terminating in a head 362 . A cross sectional dimension, such as a diameter 364 of the head 362 is greater than a cross sectional dimension such as a diameter 366 of the shank 360 .
[0105] A sensor magnet 372 is housed in each of the shutter arms 352 , 354 generally opposite the shutter arm extensions 354 , 356 . At least one or a plurality of, e.g., four, adjustable ball spring plungers 374 are disposed in each of the shutter arms 350 , 352 . A plurality, e.g., pair, of shutter position sensors 376 , 378 are also attached to each of the shutter arms 350 , 352 , the shutter position sensor 376 attached so as to be aligned with a sensor magnet 372 , thereby detecting when the shutters are in an open or closed position. The shutter position sensor 378 is attached approximately radially midway between the shutter position sensor 376 and one of the shutter arm extensions 354 , 356 , to thereby detect when the shutters are in a closed position. The two pairs of sensors (one pair for each shutter) monitor the open and closed position of each shutter. The sensors may be reed switches activated by a magnetic field and are mounted so as to minimize contact with module components directly exposed to high temperatures found in the instant UV module. The magnets are stronger than those previously used to ensure sensor activation. A variety of magnet lengths (thus, a variety of magnetic field strengths) may be used to finely adjust shutter sensor sensitivity. The magnets are present in the shutter shaft arms which are, in turn, mounted on the shutter shafts. Accordingly, the sensitivity of the shutter position sensors is unaffected by shutter warpage, changes in shutter length, or changes in the axial positioning of the shutter assemblies relative to the module body of this invention. The sensors themselves may be also micro-positioned within their mounting brackets to more finely adjust sensor sensitivity ( FIGS. 8 , 10 , 11 ).
[0106] Referring more particularly to FIGS. 47 and 48 , each of the ball spring plungers 374 includes a slotted cap 380 , which closes a threaded housing 382 . A spring 384 is disposed within the housing 382 and a ball 386 partially protrudes from the housing 382 , the spring 384 biasing the ball 386 away from the slotted cap 380 .
[0107] As seen in FIGS. 11 and 12 , each of the shutter shafts 332 has at least one or a plurality of, e.g., six, axial bores 390 and an angled rib 392 is circumferentially and integrally formed from an exterior surface thereof. A plurality of axially aligned grooves (slots) 394 are formed on the exterior of the shutter shafts 332 so as to coincide with the position of the shutter arms 350 , 352 . The shutter shaft of this invention has been extended to extend through the connection block and the associated seal arrangement has been designed to greatly reduce the chance of a coolant leak. If a leak were to occur, a tale-tale weep hole ported to the atmosphere, not only indicates the existence of a leak, but directs any leaking coolant away from the internal spaces of the connection block and module and, in particular, any coolant leakage is directed away from electrical connections and components, thereby minimizing chances of any coolant-induced electrical shortages and any damages to the instant module therefrom.
[0108] A pair of “indexing” clutches (one per shutter) prevents drive train binding and subsequent drive overload ( FIGS. 8-12 , 47 - 48 ). Within the clutch of this invention, a plurality of ball spring plungers are mounted within the shutter shaft arm and may be adjusted as required to produce the desired “breakpoint” torque, the amount of torque required to disengage the clutch as seen in FIG. 47 and during normal operation with each shutter clutch engaged, the spring plunger balls 386 are forced into the grooves 394 formed in the shutter shaft 332 , thereby effectively “locking” the shutters to the drive train. The optimum “breakpoint” allows the clutch to disengage before the drive motor draws sufficient heat-producing current to be damaged, yet still operates the shutters during normal operation. As shown in FIG. 48 , when disengaged, the balls 386 are no longer seated in the grooves 394 of the shutter shaft 332 . When properly adjusted, the present clutch in the “disengaged” mode allows the shutter drive train to continue operating in a powered-up condition for an unlimited amount of time without damaging drive train components. While under power and disengaged, the clutch can “free wheel” in a manner somewhat similar to a spring-loaded pawl and ratchet arrangement. The clutch will always automatically reengage by virtue of the “indexing” configuration integral to the shutter shaft, shutter shaft arms, and spring plungers. Stated otherwise, regardless of the position of the shutters, a disengaged clutch of this invention will always attempt to reengage. The clutch arrangement of this invention also allows the shutters to be individually repositioned by hand. Suitable ball spring plungers are available in several ranges of spring force values. These devices may have threaded bodies allowing them to be threaded into or out of the shutter shaft arm to respectively increase or decrease the torque required to reach the “breakpoint” of the clutch. The combination of the spring forces and the extent to which the threaded bodies are threaded into the clutch allows the clutch “breakpoint” to be thus readily adjustable. Due to the action of the springs, a disengaged clutch will continually attempt to reengage and will reengage automatically as soon as the applied torque in the shutter drive train system falls below the “breakpoint” torque, or as soon as the drive motor is deenergized. When a shutter is repositioned by hand, the clutch will reengage as soon as the shutter is released. The design of the clutch components is such that the clutch is bidirectional and will disengage at approximately the same “breakpoint” torque value regardless of whether the shutters are being opened or closed. The clutch operates silently when fully engaged. When operating under power in the “disengaged” mode, the clutch admits a series of subdued clicking sounds to thereby alert personnel that the clutch is disengaged and is attempting to reengage.
[0109] The instant clutch also facilitates shutter synchronization. During module assembly the two shutters may be moved to their fully open positions and synchronized to mate the positive and negative reflector retaining strips. In any condition in which either or both of the shutter clutches undergo disengagement, loss of shutter timing may occur. To re-synchronize the shutters, the condition causing the clutches to disengage must often be first corrected. The shutters may then automatically reacquire the correct shutter synchronization when they are moved, either manually or via the drive motor to their fully open positions. In this situation, the module body extrusion acts as a hard stop for both shutters. When both shutters have been moved to their fully opened positions (and the drive motor, if in use, has been deenergized), both shutter clutches will automatically reengage and the shutters will again be properly timed and engaged to their respective shutter shafts ( FIGS. 6 , 7 , 13 ).
[0110] As shown in FIGS. 8 , 9 , and 11 , the worm gears 324 , 326 are secured to the shutter shafts 332 using the two piece clamp collar 334 and the drive pin 340 . Individual pieces ( 396 , 400 ) of the clamp collar 334 clamp securely to the shutter shaft 332 and the drive pin 340 protrudes from the collar 334 to engage a slot (not shown) in each of the worm gears 324 , 326 . When thusly secured, an angled shoulder 400 of the collar 334 abuts the angled rib 392 of the shutter shaft 332 . As fasteners 402 secure the two-piece collar 334 to the shutter shaft 332 , one of the worm gears 324 , 326 is wedged toward the bearing-retaining nut 336 . Each of the worm gears 324 , 326 is then tightly clamped in place between the clamp collar 334 and the hex nut 336 and is positioned to fully mesh with the left and right hand segments 304 , 306 of the worm shaft 298 .
[0111] As best seen in FIG. 15 , the sensor mounts 308 are mounted to the connection end cap 290 secure shutter position sensors 310 in place.
[0112] Referring to FIGS. 14 and 15 , a lower end cap 406 includes an optionally integral (or unitary) hard integral stop 408 in one embodiment of this invention. The integral stop is positioned at the center of the lower end cap cover to prevent either of the shutters from over traveling and contacting the UV lamp. In the event of clutch disengagement, the shutter may be forced past the normal “shutter closed” position. In this event, the shutter shaft arm will contact the integral stop before any portion of the shutter assembly can move sufficiently to contact the lamp. Thus, this integral stop prevents UV lamp contact whether the shutters are overdriven via the drive motor or by manual manipulation and will prevent lamp-to-shutter contact, regardless of the axial position of the shutter relative to the module body ( FIGS. 13-15 ).
[0113] As can be seen in FIGS. 5 , 16 , 17 , and 18 , a second bearing 420 may be used in conjunction with a ball bearing 422 to support the shutter shafts 332 . In one embodiment, the second bearing 420 is a bronze, flanged, sleeve bushing. However, other suitable materials may be used for other embodiments. The bearing 420 may include integral internal dynamic seal glands 430 , 432 and integral external static seal glands 434 , 436 . These glands may be outfitted to accommodate seals, such as O-rings 440 , 442 , 446 , 448 to provide fluid-tight integrity. The two external seals 446 , 448 have a coolant drainway 452 therebetween. The coolant drainway 452 drains to a drain port 454 , which is integral to the connection end cap 290 , to provide a path for coolant leakage. For each of the two shutter drive assemblies, the second bearing (e.g., bronze, flanged, sleeve bushing type) is used in conjunction with a single ball bearing to provide full and solid support to the shutter shaft. The sleeve bearing may include integral internal dynamic seal glands and integral external static seal glands. These glands accommodate seals, e.g., O-rings, to provide a high degree of fluid-tight integrity. The two external seals are arranged with a coolant drainway therebetween and function in conjunction with a drain port integral to the connection end cap to provide a telltale leak path in the event of a failed primary static bearing seal.
[0114] Referring to FIGS. 16 , 17 , and 18 , one embodiment of the connection end cap valve assembly of this invention 283 has a striker plate 456 , a valve disc 457 , a sleeve 458 with a plurality of outboard slots 459 , and a compression (coil) spring 460 (spring 460 not shown). The striker plate 456 accommodates internal O-rings 461 , 462 about a fluid passageway 463 and an inboard O-ring 464 to seal the junction between the connection end cap valve assembly 283 and the bearing 596 (more fully described below). An open volume 465 is defined in an inboard portion of the striker plate 456 and is also bounded by the sleeve 458 and the bearing 596 . The spring 460 is disposed in the sleeve 458 and biases the valve disc 457 toward the left (as viewed from the perspective of FIG. 16 ) such that the valve disc 457 is in a fluid tight engagement with the O-ring 462 , thereby preventing fluid egress from the valve assembly 283 . FIG. 16 depicts what may be considered as a first stage of docking the connection block assembly 102 to the connection end cap assembly 104 , wherein the connection block poppet valve 240 and the connection end cap valve assembly 283 are both closed to fluid egress. As seen in FIG. 17 , the opening 463 of the striker plate snugly accommodates a positive end 466 of the water sleeve 244 , such that the O-rings 461 , 462 sealingly contact said positive end 466 . As the cooperation between the connection block poppet valve 240 and the connection end cap valve assembly 283 progresses toward the disposition depicted in FIG. 18 , the positive end 466 of the water sleeve 244 abuts and displaces the valve disc 457 (to the right as viewed from the perspective of FIGS. 17 and 18 ), thereby compressing the spring 460 . As viewed in FIG. 18 , the valve disc 457 is fully displaced, no longer in a sealing position, thereby allowing fluid to flow through the poppet about 240 and into the valve assembly 283 . Coolant thusly flows around the valve this 457 , though the slots 459 and sleeve 458 in two the shutter shaft 332 . A person of ordinary skill in the art will readily recognize that when undocking the connection block assembly 102 from the connection end cap assembly 104 , the connection block poppet valve 240 and the connection end cap valve assembly 283 are sealed to prevent fluid egress by events essentially the reverse of the foregoing description.
[0115] As may be viewed in FIGS. 15 , 21 , 22 , 23 , 24 and 42 , the end cap electrical assembly 284 includes a UV lamp 468 , a lamp connector 470 , a pin connector assembly 472 , and a board 474 . The UV lamp 468 fits into, and is secured in place by, the lamp connector 470 . Referring to FIGS. 21 and 22 , the lamp connector 470 , in turn, has a high-voltage cable 480 , a two-piece housing 482 , a fastener mechanism 484 , an insulating membrane 486 , and socket 488 . The two-piece housing 482 depicted in this embodiment may include two housing components 492 , 494 , which house the high voltage socket 488 , the insulating membrane 486 and a ring terminal 496 . As best shown in FIG. 22 , a plurality of connectors, e.g., two, sex bolts 498 attach and secure the high voltage cable 480 to the ring terminal 496 . As seen in FIG. 15 , the conductors within the high voltage cable 480 (not shown) may be connected directly to the pin connector 472 , or connected to the pin connector 472 via the connector board 474 . When the lamp connector 470 is secured in place, a spring 502 (as best shown in FIG. 42 ) biases the lamp connector 470 toward the lamp 468 .
[0116] As best viewed in FIGS. 15 , 23 , 24 , and 42 , the pin connector assembly 472 , in the embodiment shown, includes an electrical connection block 510 , ferrules 512 , 514 , and high voltage connection pins 516 , 518 . The nonconductive ferrules 512 , 514 threadably secure and connect conductors to the high voltage pins 516 , 518 when disposed in openings 520 , 522 of the connection block 510 . As best shown in FIG. 42 , additional high voltage pins (and sockets), such as high-voltage connection pin 524 may be present, e.g., to accommodate three phase electrical current. However, a person of ordinary skill in the art will readily recognize that any number of the present high voltage connection pins (as well as sockets 202 , 204 ) may be present. The instant two-piece socket housing allows easier, more consistent, and more reliable assembly of the high-voltage socket and lead wire; and the lamp socket housing is designed to provide better electrical insulating properties. These better insulating properties are accomplished by providing more insulating material around the high-voltage wire entry way and by adding an additional partial membrane around the socket opening. With a UV lamp installed in the instant module, this membrane creates a longer, more tortuous path to reduce the likelihood of a high-energy short circuit between the lamp connection and the surrounding housing.
[0117] Both lamp connectors (a lamp connector in each of the connection and exhaust ends) are substantially identical in one embodiment of this invention. Additionally, both are spring-loaded against the UV lamp ( FIG. 42 ). The spring action thus encourages higher electrical conductivity through the lamp, socket-pin connections by maintaining full pin-two-socket engagement; prevents the lamp pin from becoming unseated from the socket during aggressive module installation; allows more relaxed dimensional tolerances for manufacturing the UV bulb; and reduces the likelihood of arcing between the pin-to-socket connections and the surrounding end caps.
[0118] Special non-conductive screw-in type ferrules are used as a mechanical back-up to maintain the high-voltage pin and socket connectors better secured in their respective electrical blocks. The pin and socket connectors, normally depending solely on a press-fit into the connection blocks, have, in the past, become unseated or ejected during aggressive module installations. The instant ferrules also permit easier pin and socket replacement in the instance that a conductor is damaged ( FIGS. 23 , 24 , 43 ).
[0119] Referring now to FIGS. 38 , 39 , 40 , and 41 , one embodiment of the latch assembly of this invention 286 includes a latch 530 and torsion spring 532 axially secured to a latch rod 534 by retaining rings 536 . The latch 530 defines a retaining groove 538 , within which one arm 540 of the torsion spring 532 is disposed. When secured to the stub bayonets 130 , 132 , the latch 530 is disposed in the latch mating surface 262 , as described above. When the latch 536 is thusly secured, the bayonets 130 , 132 , hence connection block assembly 102 , are secured in place. Pressing the latch 530 inwardly (as seen in FIG. 41 ) displaces the latch from the latch mating surface 262 of each of the stub bayonets 130 , 132 and allows removal of the connection block assembly 102 .
[0120] The latch rod 534 of this invention has retaining clip grooves 542 at the latch end thereof, rather than at the handle end. With the instant module docked to the connection block of this invention, the retaining clips provide more accurate axial positioning of the water poppet valve components and the electrical connections. As stated above, optimum axial positioning of the water poppet valves provides for maximum coolant flow through the module. Optimum axial positioning of the electrical connections further ensures reliable current flow and minimizes chances for electrical arcing ( FIGS. 38-41 ).
[0121] The spring-loaded docking latch has been widened to transmit more easily over the small gaps between bayonet junctions. The latch features an integral, linear groove designed to retain one leg of the latch torsion spring, thereby providing more consistent assembly and latch operation. Accordingly, the instant latch provides precise axial alignment of the module of this invention to the instant connection block. When utilized with the instant stub bayonets and the instant latch rod, the overall result of the cooperation of these mechanical features results in a precision three-dimensional module-to-connection docking arrangement necessary for optimum module performance ( FIGS. 3 , 38 - 41 ).
[0122] As can be seen in FIGS. 15 and 39 , lateral connection end cap passageways 546 , 548 are laterally defined in the connection end cap 290 and accommodate the stub bayonets 130 , 132 . The increased diameter of the tapering portion 256 of each of the stub bayonets 130 , 132 is snugly accommodated within the passageways 546 , 548 . However, the more distal portions, e.g., 254 , 252 , of the stub bayonets 130 , 132 have a smaller diameter and, thus, slide easily into the connection passageways 546 , 548 . Consequently, the stub bayonets 130 , 132 are easily placed within the passageways 546 , 548 but are laterally secured therewithin due to the quite close tolerance between the diameter of the bayonet sections 256 and the diameter of, and distance between, the passageways 546 , 548 .
[0123] One embodiment of the shutter assembly 106 of this invention includes left and right connection shutter end caps 570 , 572 , ( FIG. 10 ), left and right exhaust shutter end caps 574 , 576 ( FIG. 25 ), a module body 578 ( FIG. 6 ), left and right shutters (extrusions) 580 , 582 ( FIG. 6 ), negative and positive retainers 584 , 586 ( FIG. 6 ), a crossover module 588 and cover 590 ( FIGS. 29 , 30 , and 31 ), an access door 592 ( FIGS. 34 and 35 ), and connection end and exhaust end bearings 596 , 598 ( FIGS. 16 and 20 ).
[0124] Perspectives of the shutter end caps of this invention may be viewed in FIGS. 10 , 25 , 27 , and 28 and are either identical or are mirror images. Consequently, the right connection shutter end cap 572 will be further explained, corresponding features in the other shutter end caps being either identical or in mirror image. Referring now to FIG. 9 , the exterior of the shutter end cap 572 is shaped to receive and secure in place the shutter 582 . An exterior opening 612 is defined, and extends from, an exterior surface of the shutter end cap 572 . The opening 612 is dimensioned and disposed to receive a bearing 596 , which will be more fully described below. The bearing, in turn, snugly receives the shutter shaft 332 therewithin. A drive pin slot 614 , with a longitudinal axis 615 , is also defined in a lower outboard portion of the shutter end cap 572 . As can be seen in FIG. 11 , the drive pin slot 614 is dimensioned to snugly accommodate the drive pin head 362 , as will be more fully explained below. Accordingly, on each of the two cassette-style shutter drive assemblies, a ball headed drive pin is mounted to a shutter shaft arm at the connection end of the module. During operation, the head of this pin engages a drive pin slot in the shutter end cap to rotate each shutter. The ball diameter is larger than the shank diameter of the pin to prevent the shank from contacting any portion of the slot. As shown in FIG. 11 , several degrees of freedom are therefore provided by the interface of this pin and the shutter end cap slot to allow the shutter to warp and change length without inducing undesired, adverse forces on drive train components. The slot and pin are configured to provide minimal backlash throughout the normal radial swing of the shutter arm and drive pin. Additionally, the slot/pin arrangement of this invention provides for these freedoms of motion: the pin may rotate df 1 along its axis inside the slot 614 ; the pin may slide df 2 into the slot at various depths; the pin may tilt df 3 relative to the centerline of the pin; and the drive pin may contact virtually any portion of the walls of the slot without loss of functionality while nonetheless rotating the shutters. Stated otherwise, the pin-and-slot configuration of this invention allows the shutter end cap to “wobble” and slide along the pin as the shutter assembly warps, expands, and contracts in length. Consequently, binding problems in the drive train components due to imperfect shutter configurations are eliminated or greatly reduced. The variable orientation of the slot relative to the drive pin also relaxes a variety of dimensional and tolerance requirements for pertinent components. This design further prevents damage from occurring to the drive train during rough handling of the instant module, for example, when being lifted or carried by the shutters. The instant drive-pin configuration functions in conjunction with the shutter shaft, exhaust shutter pivot shafts, and shutter end cap bearings to accomplish this functionality.
[0125] Referring now to FIGS. 16 , 17 , and 18 , the opening 612 extends into a reservoir 616 . As seen in FIG. 19 , the reservoir 616 opens into a vertical passageway 618 which, in turn, opens into a horizontal passageway 620 . Accordingly, coolant flowing from the shutter shaft 332 flows horizontally into the reservoir 616 , then flows vertically through the vertical passageway 618 , then flows horizontally through the horizontal passageway 620 . From the horizontal passageway 620 , the coolant flows through a passageway in each of the shutters, as will be described more fully below. Referring now to FIG. 27 , the interior surface of the shutter end cap 572 defines an O-ring gland 622 surrounding the opening of the horizontal passageway 620 and a relieved surface 624 . The relieved surface (slot) 624 accommodates and secures reflectors in place.
[0126] The shutter end caps include a relieved reflector mounting surface. This feature provides better UV protection for the O-ring located in the shutter body-shutter end cap interface. This feature further allows the length tolerances of the replaceable reflector strips to be less critical. By using the instant shutter end caps, reflectors may now be removed and installed without removing the shutter end cap and without breaking the fluid-tight integrity of the shutter assembly. Only the retaining strip needs to be removed to exchange a reflector. In-situ, carefully made reflector fitment is no longer necessary because convenient pre-cut reflectors may be used. With the end caps of this invention assembled to the shutter extrusion, the relieved surfaces of the end caps fit flush to the inner surface of the shutter extrusion to produce an uninterrupted, full length, properly shaped reflector supporting surface ( FIGS. 27 , 28 ). Accordingly, printing press down time may be greatly reduced, due to the advantages of the quick change feature present in the reflectors of this invention. Using the instant reflectors may also be an important factor of the efficiency of the UV curing process. It has been reported that, with the use of clean and properly shaped reflectors, somewhere between 60% and 80% of the UV light striking the substrate is reflected light.
[0127] The present shutter end caps are made from aluminum, rather than stainless steel previously used. Accordingly, the instant shutter caps minimize galvanic and corrosive action occurring when the instant shutter end caps are mounted to the extruded aluminum shutter body. Shutter end caps are further fabricated from a single piece of material, rather than the multiple pieces previously used. Fashioning the instant shutter end caps eliminates several intricate welding operations previously necessary. The shutter end caps of this invention are fabricated using custom made tools to produce a special coolant passageway. This passageway includes an integral reservoir, which helps cool the stem of the UV lamp. The stem of the UV lamp must be maintained several hundred degrees cooler than the main body of the lamp ( FIGS. 18 , 27 ).
[0128] As seen in FIGS. 1 , 2 , 4 , 6 , 7 , and 13 , the module body 578 unitarily, or otherwise integrally, defines an upper member 630 and lateral members 632 , 634 , which depend from the upper member 630 . The lateral members 632 , 634 respectively define module body lateral passageways 636 , 638 , which are continuous with the respective passageways 546 , 548 of the connection end cap assembly 102 and which accommodate the stub bayonets 130 , 132 therein ( FIG. 15 ). As seen in FIG. 39 , defined in a central portion of the module body 578 are coolant passageways 640 , 642 . Referring again to FIGS. 6 and 7 , the upper portion of the module body 578 defines a crossover module opening 644 , which accommodates the crossover module 588 as more fully explained below.
[0129] As best viewed in FIGS. 6 , 7 , and 13 , the shutters 580 and 582 attach to the end caps and have therewithin coolant passageways 650 , 652 . The coolant passageways 650 , 652 align with, and receive coolant from, the horizontal passageways 620 of the instant shutter end caps. Attached to lower edges of the shutters 580 , 582 are respective negative (female) and positive (male) reflector retainers 584 , 586 . The negative reflector retainer 584 terminates in extensions 650 , 652 , thereby defining a gap 654 . The positive reflector retainer 586 terminates in a beveled tip 660 . Reflector mounts 662 , 664 , are formed at the inboard ends of the shutters 580 , 582 and reflector mounts 666 , 668 are formed at the outboard ends of the retainers 584 , 586 . These mounts secure The reflectors utilized during operation by securing the edges of the reflectors therewithin. To replace these reflectors, the retainers 584 , 586 are removed by removing the fasteners used to secure them in place, the reflectors are then removed from the mounts 662 , 664 , replacement reflectors are installed, and the retainers are then secured in place as shown by the fasteners.
[0130] Previously, each shutter assembly was outfitted with either a “male” or “female” reflector retainer strip mounted to the outer edge of the shutter extrusion. When the shutters were closed, the male and female profiles of the retainer strips mated together to effectively block the direct path of light out of the module. In the design of this invention, the original female V-shaped (negative) reflector retainer profile is modified to define a shallow U-shaped channel. This new shape prevents shutter-to-shutter binding when closed shutters are warped from heat or from other causes of shutter-to-shutter misalignment ( FIGS. 6 , 7 ). The male, V-shaped “positive” reflector retainer profile retains its original profile. Consequently, when the shutters are closed and the shutter retainer profiles are mated together, the U-shaped channel does not affect the ability of the closed shutters to block light.
[0131] Referring now to FIGS. 29 and 30 , the crossover module 588 defines a coolant reservoir 670 opening into coolant ports 672 , 674 . Lateral portions of the crossover module 588 define passageways 676 , 678 , which are continuous with the module body passageways 636 , 638 in assembly end cap passageways 546 , 548 to thereby accommodate the stub bayonets 130 , 132 . The horizontal, planar portion 682 of the crossover module 588 defines a plurality of, e.g., eight threaded apertures 680 . Operationally, the crossover module 588 is disposed within the crossover module opening 644 of the module body 578 . The module body cover 590 conforms to the shape of the horizontal planar portion 682 of the crossover module 588 and defines a plurality of, e.g., eight apertures 686 . The apertures 686 align with the apertures 680 present in the crossover module 588 . Accordingly, the module body cover 590 is secured in place by extending fasteners through the apertures 686 and threading the fasteners into the apertures 680 .
[0132] The coolant crossover feature is incorporated into the upper module cover to ease manufacturing and assembly issues. The crossover cavity features a substantial reservoir to better cool the lamp seal, shutter sensors, lamp socket assembly and shutter assemblies ( FIGS. 29 , 30 ).
[0133] FIGS. 34 , 35 , and 36 show an access 690 and access door 592 of this invention. The access 690 is defined at lower portions of each lateral side of the connection end cap assembly 104 . The access door includes respective upper and lower dovetailed edges 694 , 696 , which terminate about midway at 698 , 700 . A worm shaft access hole 702 is defined in the access door 592 as well. Proximate upper and lower peripheries of the access 690 are complementary, slotted portions 704 , 706 . The dovetailed edges 694 , 696 are accommodated, and slide within, the slotted portions 704 , 706 .
[0134] The shutter drive train access doors have been designed to allow them to be removed with a minimum of module disassembly. A portion of the upper and lower dove tail edges of the access doors has been removed, thereby allowing the doors to be removed after being slid a short distance. Accordingly, the only component necessary for removal prior to access door removal is the module bottom cover in one embodiment. Once the doors are removed, the shutter drive assemblies may be “timed” (synchronized) as required without further disassembly of other module components ( FIGS. 34-37 ). The fasteners securing the two-piece collar to the shaft are easily accessible. Initial timing of the shutters may be quickly accomplished with the shutter drive assembly in place and without extensive disassembly of module components. After removing the access doors, an Allen wrench inserted through access holes can quickly loosen and retighten the fasteners on the collars or worm shaft to provide quick and easy shutter timing adjustments. Each of the two shutter drive assemblies may be independently adjusted in this manner to help simplify and finely adjust shutter timing adjustments as desired ( FIGS. 8 , 34 - 37 ).
[0135] As shown in FIG. 9 , the bearing 596 is disposed in the opening 612 of the connection and exhaust shutter end cap shown of this invention. FIG. 19 depicts the bearing 596 disposed in the right connection shutter end cap 572 and FIG. 20 shows the bearing 596 disposed in the right exhaust shutter end cap 576 . The orientation of the bearing 596 in the right exhaust shutter end cap 576 is rotated 180 degrees from the orientation of the bearing 596 in the right connection shutter end cap 572 . In either case, the bearing 596 has a housing 710 defining respective outer and inner glands 712 , 714 and a bearing surface 716 therebetween. Respective outer and inner seals 718 , 720 are accommodated within the outer and inner glands 712 , 714 . In the case of the left and right connection shutter end cap shown 570 , 572 each of the bearings 596 receives one of the shutter shafts 332 to achieve a fluid tight connection as the connection end caps are rotated during operation.
[0136] The bearing arrangement of this invention provides for nominal flexing, thermal expansion/contraction, warpage, and dimensional variations of the shutter assembly without sacrificing fluid-integrity or inducing undesired forces on seals and shutter drive train components. The instant bearing features a narrow, centrally located load-bearing surface that is sealed on either side by a pair of integral seal glands fitted with O-rings. By virtue of their elasticity, these O-rings also provide a mechanical means to distribute the bearing loads. The outer O-ring 718 also serves as a wiper to prevent debris from entering the bearing and seal areas.
[0137] The shutter shafts and the exhaust shutter pivot shafts function as bearing surfaces for the shutter end cap bearings and as O-ring sealing surfaces for the shutter end cap bearing seals. In both cases, the shutter end cap shown may be displaced with several degrees of freedom.
[0138] The instant bearing arrangement provides several degrees of freedom for the shutter and caps as more fully described above. The instant bearing also functions as a heat sink and a heat transfer element, again cooperating with other features to maintain module components at cooler temperatures ( FIGS. 5 , 19 , 20 ).
[0139] FIGS. 20 , 25 , 26 , and 28 depict the exhaust end cap assembly 108 of the instant invention, including a lamp connector 730 , a lamp connection assembly 731 , an exhaust shutter shaft 732 , a fluid passageway including a sacrificial anode 738 , and an end plate 740 . The lamp connector 730 may be substantially identical to the lamp connector 470 as shown in FIGS. 21 and 22 . In FIG. 28 , the lamp connector 730 is shown operably mounted between the exhaust end caps 574 , 576 . The exhaust shutter shaft is rotatably disposed within the bearing 596 of each of the exhaust shutter end caps 574 , 576 . The exhaust shutter shaft opens into the reservoir of each of the exhaust shutter end caps 574 , 576 , as well, then opening into a vertical passageway 734 . The vertical passageway 734 extends upwardly joining a horizontal passageway 736 . The horizontal passageway 736 opens into one of the module body passageways 640 , 642 . The sacrificial anode 738 functions as a coolant plug and threads into a lower portion of the vertical passageway 734 .
[0140] In one embodiment, the coolant plugs in the module exhaust end cap are modified (shortened) sacrificial zinc (or manganese) anodes to combat corrosion in coolant passageways. The sacrificial anodes are installed directly in the flow path inside the module for maximum effectiveness and have a chamfered or radiused end for maximum exposure to coolant flow ( FIGS. 25 , 26 ). The contemplated coolant utilized in the instant invention, as well as other UV modules, is either locally available water or water-polyethylene glycol mixtures. Locally available water is often an electrical conductor due to concentrations of sodium, calcium, magnesium, and iron cations. Water-polyethylene glycol mixtures are electrical conductors as well. Accordingly, galvanic corrosion presents an ongoing problem by causing corrosion of the coolant conductive passageways. Moreover, the high temperatures present during operation accelerate the chemical reactions of galvanic corrosion, resulting in coolant leakage where corrosion reactions have eroded coolant passageways. Coolant leakages, especially in proximity to the UV lamp or electrical connections, can cause extensive damage due to electrical arcing. Galvanic corrosion occurs when a first metal contacts a second metal, both exposed to an electrolyte. Since both the first and second metals are conductors, the first metal will corrode preferentially if the first metal has a greater (more negative) galvanic potential than the second metal. In the case in point, zinc has a greater galvanic potential than aluminum, the predominant metal exposed to the instant coolant solution. Therefore, the zinc anode of this invention will corrode preferentially to any aluminum components of the coolant pathway. Because the instant zinc anode may be provided in the form of a threaded plug, the instant zinc anode may be easily and quickly replaced periodically when sufficiently corroded to ensure that the predominant aluminum pathways remain intact, uncorroded, and leakage free.
[0141] In one embodiment, a coolant pathway present in the instant UV module begins when coolant enters the right fitting 164 and exits the left fitting 162 . However, entry via the left fitting 162 and exit via the right fitting 164 or alternating the foregoing two alternatives are contemplated to be within the scope of the instant invention. In any of the foregoing scenarios the coolant pathway would encounter elements described above, albeit in different sequences. In the first scenario, the coolant enters the right fitting 164 ( FIG. 4 ) and flows through the right poppet valve 240 ( FIG. 16 ). From the right poppet valve 240 , the coolant flows through the sleeve bushing 420 , then through the right shutter shaft 332 ( FIG. 5 ). From the right shutter shaft 332 , the coolant then flows through the right connection shutter end cap reservoir 616 ( FIG. 16 ), then through the right connection shutter end cap vertical and horizontal passageways 618 , 620 ( FIG. 19 ), then through the right shutter passageway 652 ( FIG. 6 ). From the right shutter passageway 652 , the coolant flows through the right exhaust shutter end cap horizontal and vertical passageways and into the reservoir thereof (not shown). From the right exhaust shutter end cap reservoir, the coolant flows through the right exhaust shutter shaft 732 , though the vertical and horizontal passageways 734 , 736 ( FIG. 26 ) and into the module body coolant passageway 642 ( FIG. 39 ). After flowing through the module body coolant passageway 642 , the coolant flows through the crossover module 588 , though port 674 , reservoir 670 and port 672 ( FIG. 30 ) and into the module body passageway 640 ( FIG. 39 ) to begin a passageway in the left components of the instant UV module which is essentially a reverse of the passageway to the right components thereof In this reverse passageway, the coolant flows through the module body passageway 640 ( FIG. 39 ) and into the left horizontal and vertical passageways (not shown). While many of the components of the left fluid passageways are not depicted, these components are substantially similar or identical to those shown with respect to right fluid passageways. From the vertical passageway 734 , the coolant flows through the left exhaust shutter shaft and into the left exhaust shutter end cap, where the coolant flows through the end cap reservoir and vertical and horizontal passageways. From the left exhaust shutter end cap horizontal passageway, the coolant then flows through the left shutter passageway 650 ( FIG. 6 ) and into the left connection shutter end cap reservoir (not shown). After flowing through the left connection shutter end cap reservoir, the coolant then flows through the horizontal and vertical passageways thereof and into the left shutter shaft 332 (not shown). From the left shutter shaft 332 , the coolant then flows through the sleeve bushing 420 , poppet valve 240 , and exits via the left fitting 162 (not shown).
[0142] Referring now to FIGS. 44 , 45 , 46 , and 47 , another embodiment of the instant shutter assembly of this invention is depicted at 750 , having respective negative (female) and positive (male) retainers 752 , 754 . The other components of the shutter assembly 750 may be similar or substantially identical to those discussed previously. The negative retainers 752 defines a terminal C-channel or slot 760 in a similar manner to the negative retainer 584 discussed above. However, in contrast to the positive retainer 586 , the positive male retainers have a plurality of alternate respective lower and upper cutouts 762 , 764 straddling the tip 766 thereof. As can be seen, the remaining, or non-cutout portions 768 , 770 of the positive retainer 754 abut the upper or lower extensions 772 , 774 of the negative retainers 752 , thereby leaving a gap between the tip 766 of the positive retainer 754 and the surface of the C-channel 760 to allow airflow into the interior of the shuttle assembly from the exterior, to thereby further assist in cooling. Stated otherwise, the gap between the lower cutout 762 and the lower extensions 772 , 774 may be considered as a lower channel portion 778 ; the gap between the positive retainer tip 766 and the surface of the C-channel 760 may be considered as an intermediate channel portion 780 ; and the gap between upper cutout 764 and the upper extensions 772 may be considered as an upper channel portion 782 . The lower, intermediate, and upper channel portions 778 , 780 , 782 being continuous, a plurality of air channels are thereby defined to further assist in cooling the interior of the instant UV module of this invention.
[0143] When a printing press is operating, the shutters of this invention are rotated to an open position by the shutter drive train ( FIG. 6 ). The very high energy light (a combination of visible, infrared, and ultraviolet wavelengths) is generated from a lamp. A proportion of the light is reflected and another proportion directly impinges the inked substrate. The shutters are designed with a special shape to reflect and aim as much light energy toward the substrate as possible so that the UV wavelengths will “cure” (dry) the UV-reactive ink.
[0144] Under certain conditions, the shutters must be closed ( FIG. 7 ). The outer edges of each of the shutters are equipped with either a positive (male) or a negative (female) profile. These profiles mate together when the shutters are closed to block the passage of light to the substrate being printed by the press. A shutter assembly that has stalled in a non-fully-closed position (usually due to shutter warpage, drive train bind-up, or motor failure) has been known to allow a powered-up lamp to ignite the substrate.
[0145] During normal operation, a water or water/glycol coolant mixture is circulated through the module body and through both shutter assemblies to remove excess heat and control the amount of shutter warpage and expansion. The instant module body and shutter assemblies are made from extruded aluminum with integral coolant passageways. There are numerous places throughout the module assembly where static and dynamic O-rings seals may be used to attempt to prevent the coolant from leakage. In the past, leakage problems have been fairly common. In the module design of this invention, the O-ring seal and gland designs eliminate, or greatly reduce, coolant leakages. However, most coolants are good conductors of electricity and due to the close proximity of leakages to the high-voltage electrical connections within the module of the prior art, these leakages have often caused and escalated component damage due to electrical arcing.
[0146] The special high-energy UV lamps require high-voltage and fairly high current, e.g., up to 3000 volts and up to 17 amps. The electrical connections conducting this electrical current must retain electrical conduction properties and must be well insulated from surrounding components ( FIGS. 21-24 , 42 , 43 ). In the past coolant leakages, electrical leakages, pin and socket erosion and pin-to-socket alignment problems between the module and the connection block have been causes of failure in the electrical connections.
[0147] Because numerous modifications of this invention may be made without departing from the spirit thereof, the scope of the invention is not to be limited to the embodiments illustrated and described. Rather, the scope of the invention is to be determined by the appended claims and their equivalents. | A UV module of this invention has connection block (optional), connection end cap, shutter, and exhaust end cap assemblies. The connection block has doweled or tapered bayonets for facilitated installation and removal of the UV module. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. 37 C.F.R. §1.72(b). | 2 |
CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/075,018, filed Feb. 18, 1998.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to dental instruments. More specifically, the invention is directed to a plurality of heated orthodontic pliers with jaws having various configurations. The pliers are used for producing various configurations of bumps, logos and cuts on and pinching of a retainer fabricated from thermoplastic co-polymer blends. To achieve this end, the pliers are heated to a sufficiently high temperature and then placed on the retainer to reshape it at a specific location.
2. Description of Related Art
In the field of orthodontics it is useful to form differently shaped bumps and cuts in a thermoplastic retainer in order for the dental retainer to apply appropriate corrective pressure to a patient's teeth. Another problem is the looseness of a fastener incorporated in a retainer. To this point, once the retainers are manufactured, it is difficult for the individual orthodontist to reshape the retainer to meet the changing needs of his patient. Additionally, the only known method of forming these bumps is by using a heated rod that works like a soldering iron to form a cylindrical bump in the retainer. This method is not as effective as the present invention because it can only result in limited forms of bumps. The soldering iron must be heated electrically and works effectively only on specific thermoplastic materials, rather than on all thermoplastic materials as does the present invention.
What is needed is an assortment of orthodontic pliers that are capable of easily and accurately forming different shaped ramps, imprinted logos, logo pockets, fluoride and bleach pockets, bite plates, rectangular shapes for retention of blocks on any thermoplastic retainer and pinching down on loose fasteners when heated to a sufficient temperature. This will allow orthodontists to make the minor modifications that are often necessary in a cost effective manner. A discussion of the related art of which the present inventor is aware, and its differences and distinctions from the present invention is provided below. No patent discloses the necessity to heat the dental pliers for forming bumps or pinching loosely held fasteners in the thermoplastic retainer.
U.S. Pat. No. 5,538,421 issued on Jul. 23, 1996, to Thomas E. Aspel describes an assortment of dental pliers comprising a lower jaw longer or shorter than the upper jaw for removing orthodontic brackets, bands, buttons, cleats, bonding materials, and braces from teeth. The pliers are distinguishable for being limited to jaws designed for cutting and removing unwanted dental materials from the patient's teeth and to prevent luxation (tipping) of the tooth to minimize pain while using the pliers.
U.S. Pat. No. 3,911,583 issued on Oct. 14, 1975, to Robert Hoffman describes a dental pliers having an upper jaw having an upwardly and inwardly tapered concave shaped sides and front for forming gripping edges in removing metal bands cemented to teeth and the removal of cement on teeth. The pliers are distinguishable for being limited to removal of cemented dental bands and cement.
U.S. Pat. No. 5,395,236 issued on Mar. 7, 1995, to Suhail A. Khouri describes an orthodontic pliers for forming a wire on teeth to effect gingivally directed bends in the distal ends of the arch wire. The jaws of the pliers have perpendicular free ends which render the plier structurally distinguishable from the present invention.
U.S. Pat. No. 5,084,935 issued on Feb. 4, 1992, to Ferdinand Kalthoff describes a multiple-purpose wire shaping and cutting tool. It further describes means of forming certain commonly known wire shapes used in the orthodontic profession. There are opposing convex and concave surfaces on its inner jaws in order for the tool to perform its intended function. One handle has a hole while the other handle has a disc-shaped guide for forming labial bows in a wire. The wire shaping tool is distinguishable for lacking any means of forming shapes in thermoplastic retainers, nor is there disclosure of any heating of the tool to facilitate wire formation.
U.S. Pat. No. 3,727,316 issued on Apr. 17, 1973, to Louis Goldberg describes an orthodontic pliers used for bending wire into desired open or closed loop sizes, and for forming and modifying the arch curve in the wire. The pliers possess male and female conical dies (including a recess on one jaw) and a wire cutter on opposing surfaces of the inner jaws. No means of heating the pliers or use of the pliers on thermoplastics is disclosed in Goldberg. The orthodontic pliers are distinguishable for its limitation to manipulating and cutting wire.
U.S. Pat. No. 5,197,880 issued on Mar. 30, 1993, to Leeland M. Lovaas describes a tool for crimping a metal endodontic file. The tool has opposing convex and concave surfaces on its inner jaws to perform its intended function. Unlike the present invention, the inner surfaces of the jaws are parallel to one another when the tool is in its closed position. The file crimping tool of FIG. 8 is distinguishable because the tool cannot be used for the formation of bumps in thermoplastic retainers.
U.S. Pat. No. 4,310,305 issued on Jan. 12, 1982, to Jacob Frajdenrajch describes a mechanical device for holding elastic articles such as small orthodontic rubber bands. One embodiment of the invention describes the device having jaws which are curved at their ends to facilitate the use of the device in tight spaces. The orthodontic tool does not suggest the use of the curved-jaw device for imparting pressure on a thermoplastic surface. Additionally, the curved jaw assembly is structurally unlike that of the present invention.
U.S. Pat. No. 5,588,832 issued on Dec. 31, 1996, to Farrokh Farzin-Nia describes a method of fabricating orthodontic pliers and the stainless steel or titanium alloy pliers made by the process. The manufacturing process of making these pliers minimizes the grinding and cutting of the pliers once the two nearly identical halves are made into the two scissor parts. The orthodontic pliers are distinguishable for having conventional needle-nose jaws.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.
SUMMARY OF THE INVENTION
The present invention is a heated orthodontic pliers comprising two components in a first embodiment that are subapically and pivotally joined. Each of these elongated pieces are irregular in shape, unequal in length and possess asymmetrical jaws relative to each other. The lower jaw of one plier is curved in an arc to ensure that the only part of the lower jaw of the plier that comes in contact with the thermoplastic retainer is the bump forming end of that jaw when the jaws are closed around the retainer. The heated pliers are used for producing different shaped bumps on a thermoplastic retainer. A second embodiment of pliers have equal length jaws for different purposes such as tightening the retainer about its fittings enclosed or otherwise.
To achieve the shaping of retainers, the pair of pliers are heated to a temperature range of approximately 325 to 350° F. or the appropriate softening temperature for a specific thermoplastic material, and then placed on the retainer to reshape it. It is noted that the orthodontist will wear insulated gloves when handling the heated pliers. The reshaping end of the lower jaw of the pliers can be shaped in various ways so that it will create a smooth, evenly shaped bump in the retainer that is comfortable for the patient to wear. After the bumps are created, the retainer is permitted to cool and stabilize, i.e., harden. The specially reshaped retainer may then be placed in the patient's mouth to impart corrective pressure to the desired tooth. The various configured shapes formed by the specific orthodontic pliers of the present invention are an elliptical bump, a square bump, a rectangular bump, a tear shaped bump, ramps of different sizes, circular and square logos, logo attaching apertures, fluoride and bleach pockets, horizontal and vertical hooks, a bite-plate, and square or rectangular bumps for inserting blocks for connecting the blocks with wires, tubes, elastic chains, and springs. Other uses include specially configured pliers with heated jaws of equal length for crimping encapsulated expansion screws or the like.
Accordingly, it is a principal object of the invention to provide a pair of orthodontic pliers for the purpose of accurately forming bumps or pinching loosely encapsulated fasteners in thermoplastic retainers when the pliers are sufficiently heated to a temperature range of approximately 325 to 350° F. or the appropriate softening temperature for a specific thermoplastic material.
It is another object of the invention to be able to form the bumps of different shapes on the retainer, depending on the specific needs of the patient, by changing the shape of the bumpforming end of the jaws of the pliers having unequal length.
It is a further object of the invention to crimp encapsulated expansion screws and the like in thermoplastic retainers that make the retainer comfortable for the patient to wear with heated pliers having jaws of equal length but different configurations.
It is still another object of the invention to provide an assortment of orthodontic pliers with unequal jaw length which will provide various configured shapes as an elliptical bump, a square bump, a rectangular bump, a tear shaped bump, ramps of different sizes, circular and square logos, logo retaining apertures, fluoride pockets, horizontal and vertical hooks, a bite-plate, and square or rectangular bumps for inserting blocks for connecting the blocks with wires, tubes, elastic chains, and springs.
It is an object of the invention to provide improved elements and arrangements thereof in an orthodontic tool for the purposes described which is inexpensive, dependable and fully effective in accomplishing its intended purposes.
These and other objects of the present invention will become readily apparent upon further review of the following specification and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an environmental, perspective view of a first embodiment of an orthodontic pliers for forming a bump and a thermoplastic retainer according to the present invention.
FIG. 2 is a partial perspective view of the FIG. 1 pliers in an open position.
FIG. 3 is a partial side elevational view of the jaws of the FIG. 1 pliers in a closed position with the apertured jaw partially cross-sectioned to demonstrate the manner in which the jaws fit together.
FIG. 4 is a top plan view of the jaws of the FIG. 1 pliers.
FIG. 5 is an elevational side view of the jaws of a second embodiment of a pliers for increasing an undercut in a thermoplastic retainer.
FIG. 6 is a partial elevational side view of the jaws of a third embodiment of a smaller ramp forming pliers required for the lower anterior teeth portion of a thermoplastic retainer.
FIG. 7A is a partial elevational side view of the jaws of a fourth embodiment of a pliers for reducing the size of an oversized ramp in a thermoplastic retainer.
FIG. 7B is an elevational front end view of the jaws of the FIG. 7A embodiment.
FIG. 8A is an elevational side view of a thermoplastic retainer depicting the logo impressed on it by a logo pliers of a fifth embodiment.
FIG. 8B is a partial plan view of the underside of the upper jaw of the pliers of the fifth embodiment.
FIG. 8C is a partial plan view of the underside of the lower jaw of the pliers of the fifth embodiment.
FIG. 8D is a partial elevational side view of the jaws of the pliers of the fifth embodiment.
FIG. 9A is a front elevational view of a thermoplastic retainer with a logo insert in a holder made by a circular logo pliers of a sixth embodiment.
FIG. 9B is a sectional elevational view of the thermoplastic retainer with the configuration made with the circular logo pliers of the sixth embodiment.
FIG. 9C is a sectional elevational view of the thermoplastic retainer with a hole made with a puncher of a smaller diameter than the circular bump with the pliers of the FIG. 9B embodiment.
FIG. 9D is a sectional elevational view of the thermoplastic retainer with a logo insert in place in the sixth embodiment.
FIG. 9E is a partial side elevational view of the jaws of the circular logo forming pliers of the sixth embodiment.
FIG. 10A is a front elevational view of the thermoplastic retainer provided with fluoride pockets made by the pliers of a seventh embodiment.
FIG. 10B is a partial plan view of the underside of the upper jaw of the fluoride pocket forming pliers of the seventh embodiment.
FIG. 10C is a partial plan view of the underside of the lower jaw of the fluoride pocket forming pliers of the seventh embodiment.
FIG. 10D is a partial elevational side view of the open jaws of the pliers of the seventh embodiment.
FIG. 11A is a front elevational view of a thermoplastic retainer with a pair of horizontal hooks for an elastic band oriented to open outwardly and made initially by ramps formed by a pliers of the eighth embodiment.
FIG. 11B is a partial plan view of the underside of the upper jaw of the horizontal hook forming pliers of the eighth embodiment.
FIG. 11C is a partial plan view of the underside of the lower jaw of the horizontal hook forming pliers of the eighth embodiment.
FIG. 11D is a partial side elevational view of the closed jaws of the eighth embodiment pliers.
FIG. 12A is a front elevational view of a thermoplastic retainer with a pair of vertical hooks open upwardly for attaching an elastic band; and the ramps made initially formed by a pliers of a ninth embodiment.
FIG. 12B is a partial plan view of the underside of the upper jaw of the ninth embodiment pliers.
FIG. 12C is a partial plan view of the underside of the lower jaw of the ninth embodiment pliers.
FIG. 12D is a partial elevational side view of the closed jaws of the ramp forming pliers of the ninth embodiment.
FIG. 13A is an elevational side view of a bite-plate portion of a thermoplastic retainer shown schematically positioned on a lower tooth; the bite-plate portion made by a bite-plate forming pliers of the tenth embodiment.
FIG. 13B is a partial plan view of the underside of the upper jaw of the tenth embodiment pliers.
FIG. 13C is a partial plan view of the underside of the lower jaw of the tenth embodiment pliers.
FIG. 13D is a partial elevational side view of the open jaws of the bite-plate forming pliers of the tenth embodiment.
FIG. 14A is an elevational front view of a thermoplastic retainer formed in two sections but joined by horizontally positioned wires, elastic chains, tubes and/or springs in blocks inserted in the rectangular or square receptacles made by the pliers of an eleventh embodiment.
FIG. 14B is a schematic side view of a portion of a thermoplastic retainer impressed with the rectangular or square receptacle containing a horizontally apertured block in the eleventh embodiment.
FIG. 14C is a partial plan view of the underside of the upper jaw of the eleventh embodiment pliers.
FIG. 14D is a partial plan view of the underside of the lower jaw of the eleventh embodiment pliers.
FIG. 14E is a partial elevational side view of the open jaws of the pliers of the eleventh embodiment.
FIG. 15 is a partial plan view of a teardrop forming pliers in a closed position of a twelfth embodiment.
FIG. 16 is a partial plan view of an inverted teardrop forming pliers in a closed position of a thirteenth embodiment.
FIG. 17A is an elevational side view of a “dolphin” beaked pliers for crimping encapsulated fasteners of a fourteenth embodiment.
FIG. 17B is a top plan view of the pliers of the fourteenth embodiment.
FIG. 17C is a sectional view of a retainer with an expansion screw being crimped by the heated dolphin beak pliers in a direction adjacent to the retainer in the fourteenth embodiment.
FIG. 18A is a partial side view of the pliers' jaws for forming a bleaching pocket in a retainer of pliers of a fifteenth embodiment. The pliers is capable of utilizing blocks of various sizes.
FIG. 18B is a partial plan view of the female jaw's underside of the pliers of the fifteenth embodiment.
FIG. 18C is a partial plan view of the underside of the male jaw of the pliers of the fifteenth embodiment.
FIG. 18D is a sectional view of a retainer on a tooth with the bleaching pocket formed by the pliers of a seventeenth embodiment.
FIG. 19 is an elevational side view of an alternative crimping pliers positioned perpendicular to a retainer in a sixteenth embodiment, wherein a partially sectioned retainer encapsulates an expansion screw on a tooth.
Similar reference characters denote corresponding features consistently throughout the attached drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is a heated pair of orthodontic pliers used for forming bumps in thermoplastic retainers. In the field of orthodontics, a retainer is generally individually produced to fit an patient's mouth. However, over time a patient's needs may change, thus making it is necessary to slightly modify the retainers. The generic components of an orthodontic plier typically comprise a first handle 10 having a first jaw 14 , a second handle 12 having a second jaw 16 , which are subapically and pivotally joined by a pivot pin 18 connecting the handle and jaw assembly, as suggested by FIG. 1, which is drawn to a first embodiment pliers 20 of the present invention. A thermoplastic retainer 22 is illustrated ready for bump formation by a bump forming projection 24 of the first jaw 14 which pushes the pertinent portion of the retainer 22 into the elliptical throughbore 26 of the second jaw 16 .
As shown in FIGS. 2, 3 and 4 , the first jaw 14 is curved to ensure that the only part of the first jaw 14 that comes in contact with the thermoplastic retainer 22 is the bump forming projection 24 of the first jaw 14 when the jaws are closed around the retainer 22 . It should be noted that the space between the bump forming projection 24 and the elliptical throughbore 26 shown in FIG. 4 would be the thickness of the bump in the retainer 22 .
The bump forming projection 24 of the first jaw 14 can be shaped differently depending on the shape that the orthodontist wants to create in the retainer. Alternatively, the shape of the elliptical throughbore 26 can be teardrop shaped (not shown) to create a smooth surfaced ramp (similar to ramps shown in FIGS. 6 and 13C) in the thermoplastic retainer 22 which imparts even pressure to the appropriate tooth and is comfortable for the patient to wear. The teardrop shape allows for a gradation of corrective pressure to be imparted to the desired tooth as the patient bites down. The teardrop throughbore can be inverted to apply the same sort of varying pressure as the teardrop. However, the inverted teardrop faces in a diametrically opposite direction than the teardrop of the above embodiment in order to account for the orthodontic needs of different patients.
A second embodiment directed to an undercut increasing orthodontic plier 28 is illustrated in FIG. 5 with a first jaw 14 having a square shaped projection 30 and a second jaw 16 having a square shaped blind bore 32 with a slightly larger size to accommodate the retainer 22 being shaped to form the undercut. The purpose of using this plier 28 is to increase the undercuts in the thermoplastic overlay retainer. The significance of increasing the undercuts is that the undercut holds the overlay retainer on the teeth. The increased retention prevents the retainer from being easily dislodged. There are situations where additional retention over and above that available from the plaster work model that the retainer is made from would be advantageous to the wearer.
In FIG. 6, a small ramp plier 34 is shown as a third embodiment for use on the lower anterior teeth in the retainer 22 , as the anterior teeth are smaller on the lower jaw than in the upper jaw. Thus, the ramp 36 has a longer projection 37 (nearest the end of the jaw 12 ), which when heated pushes the warmed retainer portion through a throughbore 38 , sized to exceed the dimensions of the ramp 36 , to form a correspondingly shaped ramp projection in the retainer 22 .
FIGS. 7A and 7B are directed to a fourth embodiment of an orthodontic plier 40 designed for reducing the size of an oversized ramp in a thermoplastic retainer. The oversized ramp may be pushing a tooth too far out of alignment, or, may be determined by the clinician to have been formed in the laboratory too large for proper fit and placement in the patient's mouth. Plier 40 has a shorter first jaw 14 with a slightly concave, cross-sectional surface 42 which is inserted inside the retainer 22 and which cooperates with a slightly convex, cross-sectional surface 44 of the second jaw 16 , placed against the outside the retainer 22 . The use of pliers 40 results in the saving of a new retainer.
In FIGS. 8A, 8 B, 8 C, and 8 D, a fifth embodiment of the invention is shown, wherein the bump forming end is shaped to provide an identification means on the retainer, either on the outside surface as shown, or alternatively, on the inside surface. For example, the shape can be that of a logo of a company or an ornamental design. In FIG. 8A, the square logo 46 with four equal sized segments on the outside of a retainer 22 consists of a decorative design of a circle 48 , a rectangle 50 , a triangle 52 , and a cylinder 54 . In FIG. 8B, the pliers 58 have the shorter first jaw 14 defining a protruding block 47 including raised or depressed features of logo 46 . In FIG. 8C, the longer second jaw 16 has a square blind bore 56 of slightly greater dimensions than that of the block 47 to receive the front portion of the thermoplastic retainer receiving the logo impression.
In FIGS. 9A, 9 B, 9 C, 9 D, and 9 E, a sixth embodiment of the invention shows a retainer 60 (FIG. 9A) with a circular logo insert 61 held in a circular cutout 62 made within a circular rimmed retention area 63 which was formed by a circular bump forming pliers 64 (FIG. 9 E), wherein the male jaw 14 has a circular ridge 65 at the end of the projection 66 which cooperates with the circular throughbore 67 in the female jaw 16 .
In FIG. 9B, shows a sectional profile of the thermoplastic retainer 60 showing the rim 68 formed by a peripheral ridge 65 on the male bump 66 of the male jaw 14 being inserted in the throughbore 67 of the female jaw 16 (FIG. 9 E). A specially made punch (not shown) can be used to punch out a circle having a diameter less than the depression 70 to form the internal circular flange 72 (FIG. 9C) required to cooperate with the recess 74 in the circular logo insert 61 to retain the insert in the retainer 60 as shown in FIG. 9 D.
The indicia 68 shown as “LOGO” in FIG. 9A, is representative of a plurality of items such as the patient's name, company logos, or ornamental designs. Ornamental designs can be any color, plastic or metal, or glow in the dark material. This design allows an otherwise bland clear retainer 60 to be decorated in a way that will be pleasing to pre-teenagers and teenagers. A version of this design will allow the patient to change the colors as they wish to match one's mood, fashion, or for a special occasion. The logo insert does not interfere with the functioning of the retainer 60 and does not make the retainer uncomfortable.
In FIG. 10A, a thermoplastic retainer 78 containing a plurality of fluoride pockets 76 made by a pocket forming pliers 80 of a seventh embodiment is illustrated. The pockets 76 are formed to contain a fluoride paste and have a circular shaped top portion 81 to follow the outline of the gingiva (gums) and cover the upper third region of the enclosed tooth. The reason for adding fluoride is for treating etched areas of the tooth enamel to replace lost calcium oxide molecules with fluoride molecules. The pocket depth can vary from 1 to 4 mm.
FIGS. 10B and 10C depict the undersides of the jaws 14 and 16 , respectively, of the pocket forming pliers 80 showing the pocket projection 82 in jaw 14 and the pocket shaped throughbore 84 in jaw 16 .
In FIGS. 11A, 11 B, 11 C, and 11 D, a horizontal hook forming embodiment 86 (eighth embodiment) is illustrated to provide hooks 88 oriented horizontally and opened in opposite positions for attaching an elastic band 90 horizontally (in shadow) on a retainer 92 . The horizontal hook forming pliers 94 have a shorter male first jaw 14 with an elongated perpendicular projection 96 at its end perpendicular to the longitudinal axis of the jaw. The female second jaw 16 has an elongated throughbore 98 at its end having an adequate space provided for the portion of the retainer 92 being bumped. The male projection 96 is bent downward at a right angle to the male first jaw 14 to align with the throughbore 98 . The pair of elliptical shaped bumps or hooks 88 are opened up on outside edges by a dental drill for accommodating the elastic band 90 in a horizontal position.
Similarly, FIGS. 12A, 12 B, 12 C, and 12 D illustrate a vertical hook forming embodiment 100 (ninth embodiment) to provide vertically oriented hooks 102 open upwards by subsequent cutting of the top surface for attaching an elastic band 90 (in shadow) on a retainer 104 . The vertical hook forming pliers 106 have a shorter male first jaw 14 with an elongated projection 108 at its end and a female second jaw 16 with an elongated throughbore 110 at its end having space provided for the portion of the retainer 104 being bumped. The male projection 108 is formed at a right angle to the male first jaw 14 .
In FIGS. 13A, 13 B, 13 C, and 13 D, a tenth embodiment 112 of the invention shows a bite-plate forming pliers 114 for forming a horizontal ledge or bump 116 in a rear portion of a retainer 118 . As shown in FIG. 13B, the forming end or projection 120 of the shorter first jaw 14 is ramp shaped and has an inner surface 122 that extends perpendicular to the horizontal surface of the jaw 14 (FIG. 13 D), such that it forms a horizontal ledge or bump 116 in the retainer 118 (FIG. 13A) when the pliers 114 are closed thereon in cooperation with the elongated throughbore 124 in jaw 16 (FIG. 13 C). The horizontal ledge 116 provides a surface against which the lower teeth 126 can rest at some distance away from the tongue side of the upper front teeth.
In FIGS. 14A, 14 B, 14 C, and 14 D, a square or rectangular bump forming pliers 128 of an eleventh embodiment forms bumps 140 for the optional inclusion of metal or plastic blocks 132 with throughbores 134 for supporting other orthodontic fasteners such as elastic bands, wires, tubes or springs. The bumps 140 can be left unfilled with apertures 135 made in its sides as shown in FIG. 14A. A retainer 136 formed from two halves is shown with wires 138 connecting the rectangular bumps 140 . Two horizontal hooks 88 are shown as a further securement by attaching an elastic band (not shown). In FIG. 14B, a block 132 is shown in shadow inside with a throughbore 134 through the block and the bump 140 . of the longer second jaw 16 (FIGS. 14D and 14E) to form the bump 140 . Subsequently, a dental drill can form apertures 134 in the bumps 140 and the blocks 132 for attachment of the various aforementioned tensioning agents.
FIGS. 15 and 16 are drawn to a twelfth embodiment of forming teardrop bumps in a thermoplastic retainer to individually fit a patient's mouth more efficiently. In FIG. 15, the teardrop bump 148 of the shorter jaw 14 of the orthodontic pliers 150 has its pointed end 152 directed inward in the pliers. The throughbore 154 of the jaw 16 is similarly shaped but allows space 156 for the heated thermoplastic retainer. FIG. 16 depicts an inverted teardrop bump 158 forming pliers 160 with the point directed outward. It should be noted that these pliers as others can be utilized with either jaw 14 or 16 inside the retainer to produce a desired conforming bump.
FIGS. 17A, 17 B, and 17 C are directed to a fifteenth embodiment of a crimping pliers 162 . In FIG. 17A, the pliers 162 have a first top jaw 164 and a second bottom jaw 166 of equal length and both jaws shaped like a dolphin's nose with aligned narrow beaks 168 . The first top jaw 164 has a first handle 10 . The second top jaw 166 has a second handle 12 joined to the first handle 10 by a pivot pin 18 . FIG. 17B shows a top view of the pliers 162 with the aligned narrow beaks 168 . FIG. 17C depicts the crimping action of the heated pliers 162 sealing the thermoplastic retainer 22 on a lower tooth 126 at the location of an expansion screw 170 or the like. It should be noted that the beaks 168 are placed adjacent the retainer 22 for maximum crimping benefit.
FIG. 19 illustrates an alternative to the crimping of an encapsulated expansion screw 170 or the like by crimping perpendicular to the surface of the retainer 22 on a tooth 126 with the heated crimping pliers 186 as a sixteenth embodiment. In this embodiment, the first and second jaws 14 , 16 , respectively, are equal in length and similar in having an arcuate shape.
FIGS. 18A, 18 B, 18 C, and 18 D are directed to a seventeenth embodiment of a bleaching pocket forming pliers 172 for placing bleaching chemicals in the pockets 174 of a retainer 22 to bleach a tooth 126 to a lighter color. The pocket 174 should be approximately the size of the tooth being bleached. Therefore, the male projection of the first jaw 14 (FIG. 18C) should be approximately the size of the tooth being treated (FIG. 18D) in order to avoid unbleached areas being present. Consequently, as seen in FIG. 18A, an interchangeable block 176 of adequate size can be held by a screw 178 in the socket 180 of the first jaw 14 . The throughbore 182 of the second jaw 16 (FIG. 18B) can accommodate a certain tolerance in the size differences of the interchangeable block 174 . The rounded edge 184 of the block 176 coincides with the gum line for accurate bleaching.
Thus, the present invention of an assortment of bump forming and reforming heated pliers utilized by an orthodontist can economically form various configured and sized bumps to modify a thermoplastic retainer for a better fit to the teeth of a patient.
It is to be understood that the present invention is not limited to the embodiments described above, but encompasses any and all embodiments within the scope of the following claims. | Orthodontic pliers comprised of two asymmetrical components that are subapically and pivotally joined in a first main embodiment. Each of these elongate pieces is irregular in shape, unequal in length and the jaws are asymmetrical jaws relative to each other. The pliers when heated are used for producing or modifying bumps on a thermoplastic retainer. One of the jaws has a throughbore or blind bore for receiving the bump forming end of the other jaw. The jaw with the bump forming end is shorter and curvilinear so that the only part of that jaw that comes in contact with the retainer is the bump forming end. Additionally, the bump forming end may be of different shapes in order to produce different shaped bumps such as ramps, logos, logo pockets, fluoride pockets, bite plates, rectangular shapes for the retention of blocks to be wired, and hooks for elastic banding, depending on the needs of the individual patients. The pliers are heated to a temperature range of approximately 325° F. to 350° F., or the appropriate temperature for a specific thermoplastic material, to facilitate the formation of the bump in the thermoplastic retainer. A second main embodiment includes a system of pliers with jaws of equal and symmetrical shape for crimping a warmed retainer having an encapsulated expansion screw. | 0 |
[0001] This application claims the benefits under 35 USC §119 (e) of U.S. provisional application No. 62/169,722 filed 2 Jun. 2015, incorporated by reference in its entirety.
[0002] This invention is related to visible-light photoinitiators and their uses for producing contact lenses capable of blocking ultra-violet (“UV”) radiation and optionally (but preferably) violet radiation with wavelengths from 380 nm to 440 nm, thereby protecting eyes to some extent from damages caused by UV radiation and potentially by high energy violet light (HEVL).
BACKGROUND
[0003] Most commercially-available non-silicone hydrogel contact lenses are produced according to a conventional cast molding technique involving use of disposable plastic molds and a mixture of vinylic monomers and crosslinking agents. There are several disadvantages with the conventional cast-molding technique. For example, a traditional cast-molding manufacturing process often includes lens extraction in which unpolymerized monomers must be removed from the lenses by using an organic solvent. Use of organic solvents can be costly and is not environmentally friendly. In addition, disposable plastic molds inherently have unavoidable dimensional variations, because, during injection-molding of plastic molds, fluctuations in the dimensions of molds can occur as a result of fluctuations in the production process (temperatures, pressures, material properties), and also because the resultant molds may undergo non-uniformly shrinking after the injection molding. These dimensional changes in the mold may lead to fluctuations in the parameters of contact lenses to be produced (peak refractive index, diameter, basic curve, central thickness etc.) and to a low fidelity in duplicating complex lens design.
[0004] The above described disadvantages encountered in a conventional cast-molding technique can be overcome by using the so-called Lightstream Technology™ (CIBA Vision), which involves (1) a lens-forming composition being substantially free of monomers and comprising a substantially-purified, water-soluble prepolymer with ethylenically-unsaturated groups, (2) reusable molds produced in high precision, and (3) curing under a spatial limitation of actinic radiation (e.g., UV), as described in U.S. Pat. Nos. 5,508,317, 5,583,163, 5,789,464, 5,849,810, 6,800,225, and 8,088,313. Lenses produced according to the Lightstream Technology™ can have high consistency and high fidelity to the original lens design, because of use of reusable, high precision molds. In addition, contact lenses with high quality can be produced at relatively lower cost due to the short curing time, a high production yield, and free of lens extraction and in an environmentally friendly manner because of use of water as solvent for preparing lens formulations.
[0005] However, the Lightstream Technology™ has not been applied to make UV-absorbing contact lenses, largely because of the lack of water-soluble photoinitiator which can efficiently initiate curing (polymerization) of an aqueous lens formulation using a visible light having a wavelength from 380 to 460 nm. Examples of known efficient visible-light photoinitiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), 2,4,6-trimethylbenzoylethoxy-phenylphosphine oxide (TPO-L), and bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO), acylgermanium compounds described in U.S. Pat. No. 7,605,190 (herein incorporated by reference in its entirety). But, those available photoinitiators are insoluble in water and cannot be used in the production of contact lenses from an aqueous lens formulation according to the Lightstream Technology™. Some attempts have been made to prepare more hydrophilic phosphine oxide photoinitiators (Majima, Tetsuro; Schnabel, W.; Weber, W. Makromolekulare Chemie 1991, 192(10), 2307-15; De Groot, J. H.; et. al. Biomacromolecules 2001, 2, 1271). The phosphine oxide photoinitiators reported in those studies either have a limited solubility in water or have a much reduced efficiency in initiating polymerization (i.e., prolonging the cure times).
[0006] Therefore, there are still needs for a new water-soluble photoinitiator that is active and efficient in curing an aqueous lens formulation in wavelengths from 390 to 500 nm and for making UV-absorbing contact lenses from an aqueous lens formulation according to the Lightstream Technology™.
SUMMARY
[0007] In one aspect, the invention provides an acyl germanium photoinitiator of formula (I)
[0000]
[0000] in which: R 1 and R 1 ′ are C 1 to C 6 alkyl; one or two of R 2 , R 3 , R 4 , R 5 , and R 6 are a hydrophilic group selected from the group consisting of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 , —CH 2 (OCH 2 CH 2 ) n1 —OH,
[0000]
[0000] and -L 1 -SO 3 H while the others of R 2 , R 3 , R 4 , R 5 , and R 6 independent of one another are hydrogen, methyl, or methoxy, wherein in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10), L 1 is a direct bond or methylene diradical (—CH 2 —), L 2 is ethylene diradical (—C 2 H 4 —) or propylene diradical (—C 3 H 6 —), L 3 is hydrogen or a C 1 -C 4 alkyl, R 10 is methyl or ethyl.
[0008] In another aspect, the invention provides a method for producing UV-absorbing contact lenses, comprising the steps of: (1) obtaining an aqueous lens formulation, wherein the aqueous lens formulation comprises (a) at least one UV-absorbing vinylic monomer or a water-soluble UV-absorbing prepolymer (which comprises UV-absorbing moieties attached covalently thereonto) or a combination thereof, and (b) at least one acyl germanium photoinitiator of formula (I) as defined above; (2) introducing the aqueous lens formulation into a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; and (3) irradiating the aqueous lens formulation in the mold by using the light source including a light in a region of from 390 nm to 500 nm, so as to crosslink the lens-forming materials to form the UV-absorbing contact lens, wherein the formed UV-absorbing silicone hydrogel contact lens comprises an anterior surface defined by the first molding surface and an opposite posterior surface defined by the second molding surface and is characterized by having the UVB transmittance of about 10% or less between 280 and 315 nanometers and a UVA transmittance of about 30% or less between 315 and 380 nanometers and and optionally (but preferably) a Violet transmittance of about 60% or less between 380 nm and 440 nm.
[0009] The invention provides in a further aspect contact lenses obtained according to a method of the invention.
DETAILED DESCRIPTION
[0010] Unless defined otherwise, 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. Generally, the nomenclature used herein and the laboratory procedures are well known and commonly employed in the art. Conventional methods are used for these procedures, such as those provided in the art and various general references. Where a term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are those well known and commonly employed in the art.
[0011] “About” as used herein means that a number referred to as “about” comprises the recited number plus or minus 1-10% of that recited number.
[0012] “Optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.
[0013] An “ophthalmic lens” refers to a contact lens and/or an intraocular lens. A “contact Lens” refers to a structure that can be placed on or within a wearer's eye. A contact lens can correct, improve, or alter a user's eyesight, but that need not be the case. A “silicone hydrogel contact lens” refers to a contact lens comprising a silicone hydrogel material.
[0014] As used in this application, the term “hydrogel” or “hydrogel material” refers to a crosslinked polymeric material which is insoluble in water, but can hold at least 10 percent by weight of water in its three-dimensional polymer networks (i.e., polymer matrix) when it is fully hydrated.
[0015] A “vinylic monomer” refers to a compound that has one sole ethylenically-unsaturated group.
[0016] The term “soluble”, in reference to a compound or material in a solvent, means that the compound or material can be dissolved in the solvent to give a solution with a concentration of at least about 0.1% by weight at room temperature (i.e., a temperature of about 20° C. to about 30° C.).
[0017] The term “insoluble”, in reference to a compound or material in a solvent, means that the compound or material can be dissolved in the solvent to give a solution with a concentration of less than 0.005% by weight at room temperature (as defined above).
[0018] The term “olefinically unsaturated group” or “ethylenically unsaturated group” is employed herein in a broad sense and is intended to encompass any groups containing at least one >C═C< group. Exemplary ethylenically unsaturated groups include without limitation (meth)acryloyl
[0000]
[0000] allyl, vinyl
[0000]
[0000] styrenyl, or other C═C containing groups.
[0019] The term “(meth)acrylamide” refers to methacrylamide and/or acrylamide.
[0020] The term “(meth)acrylamido” refers to an ethylenically-unsaturated group of
[0000]
[0000] in which R 0 is hydrogen or C 1 -C 10 -alkyl.
[0021] The term “(meth)acrylate” refers to methacrylate and/or acrylate.
[0022] A “hydrophilic vinylic monomer”, as used herein, refers to a vinylic monomer which can be polymerized to form a homopolymer that is water-soluble or can absorb at least 10 percent by weight of water.
[0023] A “hydrophobic vinylic monomer” refers to a vinylic monomer which can be polymerized to form a homopolymer that is insoluble in water and can absorb less than 10 percent by weight of water.
[0024] “UVA” refers to radiation occurring at wavelengths between 315 and 380 nanometers; “UVB” refers to radiation occurring between 280 and 315 nanometers; “Violet” refers to radiation occurring at wavelengths between 380 and 440 nanometers.
[0025] “UVA transmittance” (or “UVA % T”), “UVB transmittance” or “UVB % T”, and “violet-transmittance” or “Violet % T” are calculated by the following formula
[0000]
UVA
%
T
=
Average
%
Transmission
between
315
and
380
nm
Luminescence
%
T
100
UVB
%
T
=
Average
%
Transmission
between
280
and
315
nm
Luminescence
%
T
100
Violet
%
T
=
Average
%
Transmission
between
380
and
440
nm
Luminescence
%
T
100
[0000] in which is Luminescence % T is determined by the following formula
[0000] Luminescence % T=Average % Transmission between 780-380 nm.
[0026] As used in this application, the term “macromer” or “prepolymer” refers to a medium and high molecular weight compound or polymer that contains two or more ethylenically unsaturated groups. Medium and high molecular weight typically means average molecular weights greater than 700 Daltons.
[0027] As used in this application, the term “vinylic crosslinker” refers to a compound having at least two ethylenically unsaturated groups. A “vinylic crosslinking agent” refers to a vinylic crosslinker having a molecular weight of about 700 Daltons or less.
[0028] As used in this application, the term “polymer” means a material formed by polymerizing/crosslinking one or more monomers or macromers or prepolymers.
[0029] As used in this application, the term “molecular weight” of a polymeric material (including monomeric or macromeric materials) refers to the weight-average molecular weight unless otherwise specifically noted or unless testing conditions indicate otherwise.
[0030] The term “fluid” as used herein indicates that a material is capable of flowing like a liquid.
[0031] The term “alkyl” refers to a monovalent radical obtained by removing a hydrogen atom from a linear or branched alkane compound. An alkyl group (radical) forms one bond with one other group in an organic compound.
[0032] The term “alkylene divalent group” or “alkylene diradical” or “alkyl diradical” interchangeably refers to a divalent radical obtained by removing one hydrogen atom from an alkyl. An alkylene divalent group forms two bonds with other groups in an organic compound.
[0033] The term “alkyl triradical” refers to a trivalent radical obtained by removing two hydrogen atoms from an alkyl. A alkyl triradical forms three bonds with other groups in an organic compound.
[0034] The term “alkoxy” or “alkoxyl” refers to a monovalent radical obtained by removing the hydrogen atom from the hydroxyl group of a linear or branched alkyl alcohol. An alkoxy group (radical) forms one bond with one other group in an organic compound.
[0035] In this application, the term “substituted” in reference to an alkyl diradical or an alkyl radical means that the alkyl diradical or the alkyl radical comprises at least one substituent which replaces one hydrogen atom of the alkyl diradical or the alkyl radical and is selected from the group consisting of hydroxy (—OH), carboxy (—COOH), —NH 2 , sulfhydryl (—SH), C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio (alkyl sulfide), C 1 -C 4 acylamino, C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, halogen atom (Br or Cl), and combinations thereof.
[0036] A “photoinitiator” refers to a chemical that initiates free radical crosslinking/polymerizing reaction by the use of light.
[0037] A “UV-absorbing vinylic monomer” refers to a compound comprising an ethylenically-unsaturated group and a UV-absorbing moiety which can absorb or screen out UV radiation in the range from 200 nm to 400 nm as understood by a person skilled in the art.
[0038] A “spatial limitation of actinic radiation” refers to an act or process in which energy radiation in the form of rays is directed by, for example, a mask or screen or combinations thereof, to impinge, in a spatially restricted manner, onto an area having a well defined peripheral boundary. A spatial limitation of UV radiation is obtained by using a mask or screen having a radiation (e.g., UV and/or visible light) permeable region, a radiation (e.g., UV and/or visible light) impermeable region surrounding the radiation-permeable region, and a projection contour which is the boundary between the radiation-impermeable and radiation-permeable regions, as schematically illustrated in the drawings of U.S. Pat. No. 6,800,225 (FIGS. 1-11), and U.S. Pat. No. 6,627,124 (FIGS. 1-9), U.S. Pat. No. 7,384,590 (FIGS. 1-6), and U.S. Pat. No. 7,387,759 (FIGS. 1-6), all of which are incorporated by reference in their entireties. The mask or screen allows to spatially projects a beam of radiation (e.g., UV radiation and/or visible radiation) having a cross-sectional profile defined by the projection contour of the mask or screen. The projected beam of radiation (e.g., UV radiation and/or visible radiation) limits radiation impinging on a lens formulation located in the path of the projected beam from the first molding surface to the second molding surface of a mold. The resultant contact lens comprises an anterior surface defined by the first molding surface, an opposite posterior surface defined by the second molding surface, and a lens edge defined by the sectional profile of the projected UV and/or visible beam (i.e., a spatial limitation of radiation). The radiation used for the crosslinking is radiation energy, especially UV radiation (and/or visible radiation), gamma radiation, electron radiation or thermal radiation, the radiation energy preferably being in the form of a substantially parallel beam in order on the one hand to achieve good restriction and on the other hand efficient use of the energy.
[0039] The term “modulus” or “elastic modulus” in reference to a contact lens or a material means the tensile modulus or Young's modulus which is a measure of the stiffness of a contact lens or a material. The modulus can be measured using a method in accordance with ANSI Z80.20 standard. A person skilled in the art knows well how to determine the elastic modulus of a silicone hydrogel material or a contact lens. For example, all commercial contact lenses have reported values of elastic modulus.
[0040] In general, the invention is directed to a class of acyl germanium photoinitiators which have increased solubility in water due to the presence of hydrophilic groups, can be activated with a visible light having a wavelength of from 390 nm to 500 nm to initiate a free radical polymerization reaction, and to the uses of such photoinitiators in making UV-absorbing contact lenses, in particularly, according to the Lightstream Technology™.
[0041] In one aspect, the present invention provides an acyl germanium photoinitiator of formula (I)
[0000]
[0000] in which:
R 1 and R 1 ′ are C 1 to C 6 alkyl, preferably C 1 to C 4 alkyl, more preferably methyl or ethyl; one or two of R 2 , R 3 , R 4 , R 5 , and R 6 are a hydrophilic group selected from the group consisting of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 , —CH 2 (OCH 2 CH 2 ) n1 —OH, -L 1 -SO 3 H,
[0000]
[0000] while the others of R 2 , R 3 , R 4 , R 5 , and R 6 independent of one another are hydrogen, methyl, or methoxy, wherein in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10), L 1 is a direct bond or methylene diradical (—CH 2 —), L 2 is ethylene diradical (—C 2 H 4 —) or propylene diradical (—C 3 H 6 —), L 3 is hydrogen or a C 1 -C 4 alkyl (preferably methyl or ethyl), R 10 is methyl or ethyl.
[0044] Examples of preferred acyl germanium photoinitiators of formula (I) include without limitation:
[0000]
[0000] in which R 1 and R 1 ′ are C 1 to C 6 alkyl (preferably C 1 to C 4 alkyl, more preferably methyl or ethyl), PEG is a monovalent radical of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 or —CH 2 (OCH 2 CH 2 ) n1 —OH in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10).
[0045] An acyl germanium photoinitiator of formula (I) defined above can be prepared from commercially-available starting materials, for example including but not limited to: (1) mono-(chloromethyl)-substituted benzoic acids (e.g., 2-(chloromethyl)benzoic acid, 3-(chloromethyl)benzoic acid, 4-(chloromethyl)benzoic acid, 2-(chloromethyl)-4-methylbenzoic acid, 2-(chloromethyl)-6-methylbenzoic acid, 2-(chloromethyl)-4-methoxybenzoic acid, 2-(chloromethyl)-5-methoxybenzoic acid, 2-(chloromethyl)-6-methoxybenzoic acid, 3-(chloromethyl)-2-methylbenzoic acid, 3-(chloromethyl)-4-methylbenzoic acid, 3-(chloromethyl)-4-methoxybenzoic acid, 5-(chloromethyl)-2-methoxybenzoic acid, 3-(chloromethyl)-2,4-dimethylbenzoic acid, 3-(chloromethyl)-2,4-dimethoxybenzoic acid, 3-(chloromethyl)-2,6-dimethoxybenzoic acid, 3-(chloromethyl)-2,6-dimethylbenzoic acid, 3-(chloromethyl)-2,4,6-trimethylbenzoic acid, 4-(chloromethyl)-3-methoxybenzoic acid, 4-(chloromethyl)-2,5-dimethoxybenzoic acid, 2-(chloromethyl)-4,6-dimethoxybenzoic acid); (2) mono-(bromomethyl)-substituted benzoic acids (e.g., 2-(bromomethyl)benzoic acid, 3-(bromomethyl)benzoic acid, 4-(bromomethyl) benzoic acid, 2-(bromomethyl)-4-methylbenzoic acid, 2-(bromomethyl)-6-methylbenzoic acid, 2-(bromomethyl)-4-methoxybenzoic acid, 2-(bromomethyl)-5-methoxybenzoic acid, 2-(bromomethyl)-6-methoxybenzoic acid, 3-(bromomethyl)-2-methylbenzoic acid, 3-(bromomethyl)-4-methyl benzoic acid, 3-(bromomethyl)-4-methoxybenzoic acid, 5-(bromomethyl)-2-methoxybenzoic acid, 3-(bromomethyl)-2,4-dimethylbenzoic acid, 3-(bromomethyl)-2,4-dimethoxybenzoic acid, 3-(bromomethyl)-2,6-dimethoxybenzoic acid, 3-(bromomethyl)-2,6-dimethylbenzoic acid, 3-(bromomethyl)-2,4,6-trimethylbenzoic acid, 4-(bromomethyl)-3-methoxybenzoic acid, 4-(bromomethyl)-2,5-dimethoxybenzoic acid, 2-(bromomethyl)-4,6-dimethoxybenzoic acid); (3) bis-(chloromethyl)-substituted benzoic acids or bis-(bromomethyl)-substituted benzoic acids (e.g., 3,5-bis(chloromethyl)benzoic acid, 3,5-bis(chloromethyl)-4-methylbenzoic acid, 3,4-bis(chloromethyl)benzoic acid, 2,5-bis(chloromethyl)benzoic acid, 3,5-bis(bromomethyl)benzoic acid, 3,5-bis(bromomethyl)-4-methylbenzoic acid, 3,4-bis(bromomethyl)benzoic acid, 2,5-bis(bromomethyl)benzoic acid); (4) mono-(dimethylamino)-substituted benzoic acids (e.g., 2-(dimethylamino)benzoic acid, 3-(dimethylamino)benzoic acid, 4-(dimethylamino)benzoic acid, 4-(dimethylamino)-2-methylbenzoic acid, 4-(dimethylamino)-3-methylbenzoic acid, 3-(dimethylamino)-4-methoxybenzoic acid); (5) mono-(dimethylaminomethyl)-substituted benzoic acids (e.g., 2-(dimethylaminomethyl)benzoic acid, 3-(dimethylaminomethyl)benzoic acid, 4-(dimethylaminomethyl)benzoic acid, 4-(dimethylaminomethyl)-2-methylbenzoic acid, 4-(dimethylaminomethyl)-3-methylbenzoic acid, 3-(dimethylaminomethyl)-4-methoxybenzoic acid); (6) dialkylgermanium dihydrides (e.g., dimethylgermanium dihydride, diethylgermanium dihydride, dipropylgermanium dihydride, dibutylgermanium dihydride, dipentylgermanium dihydride, dhexylgermanium dihydride); (7) 1,3-propanesultone; (8) alkyl alkylene phosphates (e.g., methyl ethylene phosphates, ethyl ethylene phosphates, methyl propylene phosphates, ethyl propylene phosphates); and (9) poly(ethyleneglycol) monomethyl ethers with various weight average molecular weights.
[0046] An acyl germanium photoinitiator of formula (I) defined above can be prepared from the above-listed starting materials or the likes according to various schemes, for example, such as, the following illustrative methods or the likes.
[0047] An acyl germanium photoinitiator of any one of formula (I-1) to (I-23) can be prepared by reacting a poly(ethylene glycol) monomethyl ether with a mono-(chloromethyl)-substituted benzoic acid, a mono-(bromomethyl)-substituted benzoic acid, a bis-(chloromethyl)-substituted benzoic acid, or a bis-(bromomethyl)-substituted benzoic acid, to substitute the chlorine or bromine atom with a monovalent radical of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 or —CH 2 (OCH 2 CH 2 ) n1 —OH in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10); converting the resultant carboxylic acid group into an acyl chloride according to a known reaction, e.g., by using oxalyl chloride; reacting the resultant acy chloride with a dialkylgermanium dilithium which can be obtained from the reaction of a dialkylgermanium dihydride with tert-butyl lithium, to obtain a photoinitiator of the invention, under conditions known to a person skilled in the art (see, for example, Castel, A; Piviere, P.; Satge, J.; Ko, H. Y. Organometallics 1990, 9, 205, herein incorporated by reference in its entirety), as illustrated in Scheme I.
[0000]
[0048] An acyl germanium photoinitiator of any one of formula (I-24) to (I-35) can be prepared by reacting a dialkylgermanium dilithium with a (dimethylamino)-substituted or (dimethylaminomethyl)-substituted benzoic acid, to a dibenzoyldimethylgermanium compound; reacting the resultant dibenzoyldimethylgermanium compound with 1,3-propane sultone, under conditions known to a person skilled in the art (see, for example, Lascelles, S. F.; Malet, F.; Mayada, R.; Billingham, N. C.; Armes, S. P. Macromolecules 1999, 32(8), 2462, herein incorporated by reference in its entirety), as illustrated in Scheme II, to obtain a photoinitiator of the invention.
[0000]
[0049] An acyl germanium photoinitiator of any one of formula (I-36) to (I-47) can be prepared by reacting a dialkylgermanium dilithium with a (dimethylamino)-substituted or (dimethylaminomethyl)-substituted benzoic acid, to a dibenzoyldimethylgermanium compound; reacting the resultant dibenzoyldimethylgermanium compound with alkyl alkylene phosphate (e.g., methyl ethylene phosphate, ethyl ethylene phosphate, methyl propylene phosphate, or ethyl propylene phosphate), under conditions known to a person skilled in the art, as illustrated in Scheme III, to obtain a photoinitiator of the invention (Makromol. Chem., Rapid Commun. 3, 457-459 (1982).
[0000]
[0050] An acyl germanium photoinitiator of any one of formula (I-48) to (I-57) can be prepared by reacting a dialkylgermanium dilithium with a (dimethylamino)-substituted or (dimethylaminomethyl)-substituted benzoic acid, to a dibenzoyldiethylgermanium compound; reacting the resultant dibenzoyldiethylgermanium compound with methyl bromide or other agents known to form the quaternary salts under conditions known to a person skilled in the art, as illustrated in Scheme IV, to obtain a photoinitiator of the invention. Other counterions can be used instead of bromide. (Journal of Bioactive and Compatible Polymer, 5, 1990, 31 and ThermochimicaActa, 134, (1988), 49-54)
[0000]
[0000] An acyl germanium photoinitiator of any one of formula (I-58) to (I-63) can be prepared by reacting a dialkylgermanium dilithium with a (dithioester)-substituted or (dithioestermethyl)-substituted benzoic acid, to a dibenzoyldiethylgermanium compound; deprotecting the thioester, then oxidizing to the resultant dibenzoyldiethylgermanium compound. Other reagents and conditions can be used by known by persons skilled in the art as illustrated in Scheme V. ( JACS 1963, 85, 1337 ; J. Med. Chem 1985, 28, 328 ; Tetrahedron Letters 2008, 49, 3291)
[0000]
[0051] An acyl germanium photoinitiator of formula (I) as defined above can find use in making UV-absorbing contact lenses, in particularly, according to the Lightstream Technology™, which is another aspect of the invention.
[0052] In another aspect, the invention provides a method for producing UV-absorbing contact lenses, comprising the steps of: (1) obtaining an aqueous lens formulation, wherein the aqueous lens formulation comprises (a) at least one UV-absorbing vinylic monomer or a water-soluble UV-absorbing prepolymer (which comprises UV-absorbing moieties attached covalently thereonto) or a combination thereof, and (b) from about 0.1% to about 2.0% by weight of, preferably from about 0.25% to about 1.75% by weight of, more preferably from about 0.5% to about 1.5% by weight of, even more preferably from about 0.75% to about 1.25% by weight of at least one acyl germanium photoinitiator of formula (I) as defined above; (2) introducing the aqueous lens formulation into a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; and (3) irradiating the aqueous lens formulation in the mold by using the light source including a light in a region of from 390 nm to 500 nm, so as to crosslink the lens-forming materials to form the UV-absorbing contact lens, wherein the formed UV-absorbing silicone hydrogel contact lens comprises an anterior surface defined by the first molding surface and an opposite posterior surface defined by the second molding surface and is characterized by having the UVB transmittance of about 10% or less (preferably about 5% or less, more preferably about 2.5% or less, even more preferably about 1% or less) between 280 and 315 nanometers and a UVA transmittance of about 30% or less (preferably about 20% or less, more preferably about 10% or less, even more preferably about 5% or less) between 315 and 380 nanometers and and optionally (but preferably) a Violet transmittance of about 60% or less, preferably about 50% or less, more preferably about 40% or less, even more preferably about 30% or less) between 380 nm and 440 nm.
[0053] An “aqueous lens formulation” refers to a polymerizable composition which comprises water as solvent or a solvent mixture comprising at least about 60% (preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, most preferably at least about 98%) by weight of water relative to the total amount of the solvent mixture and polymerizable/crosslinkable components, and which can be cured (i.e., polymerized and/or crosslinked) thermally or actinically to obtain a crosslinked/polymerized polymeric material. Polymerizable components for making contact lenses are well known to a person skilled in the art, including, for example, such as, monomers, macromers, prepolymers, or combinations thereof, as known to a person skilled in the art. A lens formulation can further include other components, such as an initiator (e.g., a photoinitiator or a thermal initiator), a visibility tinting agent, UV-absorbing vinylic monomers, photoinitiators, photosensitizers, antimicrobial agents (e.g., Ag-nanoparticles), lubricant/wetting agents, and the like.
[0054] A preferred group of prepolymers are those which are soluble in water or a water-organic solvent mixture and and are ophthalmically compatible. It would be advantageous that an actinically-crosslinkable prepolymer are in a substantially pure form (e.g., purified by ultrafiltration to remove most reactants for forming the prepolymer). Therefore, after crosslinking by actinic radiation, a contact lens may require practically no more subsequent purification, such as in particular complicated extraction of unpolymerized constituents. Furthermore, crosslinking may take place in aqueous solution, so that a subsequent solvent exchange or the hydration step is not necessary.
[0055] Examples of preferred actinically crosslinkable prepolymers include, but are not limited to, a water-soluble actinically-crosslinkable poly(vinyl alcohol) prepolymer described in U.S. Pat. Nos. 5,583,163 and 6,303,687 (incorporated by reference in their entireties); a water-soluble vinyl group-terminated polyurethane prepolymer described in U.S. Patent Application Publication No. 2004/0082680 (herein incorporated by reference in its entirety); a water-soluble prepolymer disclosed in U.S. Pat. No. 5,849,841 (incorporated by reference in its entirety); a water-soluble actinically-crosslinkable polyurea prepolymer described in U.S. Pat. No. 6,479,587 and in commonly owned pending U.S. patent application Ser. No. 10/991,124 filed on Nov. 17, 2004 (herein incorporated by reference in their entireties); a water-soluble actinically-crosslinkable polyacrylamide; a water-soluble actinically-crosslinkable statistical copolymer of vinyl lactam, MMA and a comonomer, which are disclosed in EP 655,470 and U.S. Pat. No. 5,712,356 (herein incorporated by references in their entireties); a water-soluble actinically-crosslinkable copolymer of vinyl lactam, vinyl acetate and vinyl alcohol, which are disclosed in EP 712,867 and U.S. Pat. No. 5,665,840 (herein incorporated by references in their entireties); a water-soluble polyether-polyester copolymer with actinically-crosslinkable side chains which are disclosed in EP 932,635 and U.S. Pat. No. 6,492,478 (herein incorporated by references in their entireties); a water-soluble branched polyalkylene glycol-urethane prepolymer disclosed in EP 958,315 and U.S. Pat. No. 6,165,408 (herein incorporated by references in their entireties); a water-soluble polyalkylene glycol-tetra(meth)acrylate prepolymer disclosed in EP 961,941 and U.S. Pat. No. 6,221,303 (herein incorporated by references in their entireties); and a water-soluble actinically-crosslinkable polyallylamine gluconolactone prepolymer disclosed in PCT patent application WO 2000/31150 and U.S. Pat. No. 6,472,489 (herein incorporated by references in their entireties). Preferred concentrations of the prepolymer in solution are from approximately 15 to approximately 50% by weight, especially from approximately 15 to approximately 40% by weight, for example from approximately 25% to approximately 40% by weight.
[0056] Preferably, the prepolymers used in the process according to the invention are previously purified in a manner known per se, for example by precipitation with organic solvents, such as acetone, filtration and washing, extraction in a suitable solvent, dialysis or ultrafiltration, ultrafiltration being especially preferred. By means of that purification process the prepolymers can be obtained in extremely pure form, for example in the form of concentrated aqueous solutions that are free, or at least substantially free, from reaction products, such as salts, and from starting materials, such as, for example, non-polymeric constituents.
[0057] The preferred purification process for the prepolymers used in the process according to the invention, ultrafiltration, can be carried out in a manner known per se. It is possible for the ultrafiltration to be carried out repeatedly, for example from two to ten times. Alternatively, the ultrafiltration can be carried out continuously until the selected degree of purity is attained. The selected degree of purity can in principle be as high as desired. A suitable measure for the degree of purity is, for example, the concentration of dissolved salts obtained as by-products, which can be determined simply in known manner.
[0058] In a preferred embodiment, an actinically-crosslinkable prepolymer is a water-soluble crosslinkable poly(vinyl alcohol).
[0059] In another preferred embodiment, an actinically-crosslinkable prepolymer is a crosslinkable polyurea as described in U.S. Pat. No. 6,479,587 or in a commonly assigned copending U.S. patent application Ser. No. 10/991,124 filed on Nov. 17, 2004 (herein incorporated by reference in their entireties).
[0060] Any suitable UV-absorbing vinylic monomers, or polymer with UV absorbing capability, can be used in the invention. A UV-absorbing vinylic monomer used in the invention comprises a benzophenone-moiety, preferably a benzotriazole-moiety. In a preferred embodiment, a UV-absorbing vinylic monomer, or polymer with UV absorbing capability, used in the invention is a benzotriazole-containing UV/HEVL absorber that absorbs both ultraviolet light and high-energy violet light (HEVL) and preferably is represented by formula
[0000]
[0000] wherein R 1 ═H or CH 3 ; R 2 ═C 2 -C 10 alkylene divalent group or preferably C 2 -C 4 alkylene divalent group; and R 3 ═H, CH 3 , CH 3 O, F, Cl, Br, I, or CF 3 . Preparation of those UV/HEVL absorbers of the above formula are described in U.S. Pat. No. 8,153,703 and U.S. Pat. No. 8,232,326, which are herein incorporated by references in their entireties. Benzotriazole-containing UV-absorbing vinyl monomers can be prepared according to procedures described in U.S. Pat. Nos. 3,299,173, 4,612,358, 4,716,234, 4,528,311 (herein incorporated by reference in their entireties) or can be obtained from commercial suppliers.
[0061] Examples of preferred benzophenone-containing UV-absorbing vinylic monomers include without limitation 2-hydroxy-4-acryloxy alkoxy benzophenone, 2-hydroxy-4-methacryloxy alkoxy benzophenone, allyl-2-hydroxybenzophenone, 4-acryloylethoxy-2-hydroxybenzophenone (UV2), 2-hydroxy-4-methacryloyloxybenzophenone (UV7), or combinations thereof. Benzophenone-containing UV-absorbing vinyl monomers can be prepared according to procedures described in U.S. Pat. No. 3,162,676 (herein incorporated by reference in its entirety) or can be obtained from commercial suppliers.
[0062] Examples of preferred UV-absorbing and UV/HEVL-absorbing, benzotriazole-containing vinylic monomers include without limitation: 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole, 2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole, 2-(2-hydroxy-3-methacrylamido methyl-5-tert octylphenyl) benzotriazole, 2-(2′-hydroxy-5′-methacrylamidophenyl)-5-chlorobenzotriazole, 2-(2′-hydroxy-5′-methacrylamidophenyl)-5-methoxybenzotriazole, 2-(2′-hydroxy-5′-methacryloxypropyl-3′-t-butyl-phenyl)-5-chlorobenzotriazole, 2-(2′-hydroxy-5′-methacryloxypropylphenyl) benzotriazole, 2-hydroxy-5-methoxy-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-1), 2-hydroxy-5-methoxy-3-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-5), 3-(5-fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-2), 3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-3), 3-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-4), 2-hydroxy-5-methoxy-3-(5-methyl-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-6), 2-hydroxy-5-methyl-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-7), 4-allyl-2-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-6-methoxyphenol (WL-8), 2-{2′-Hydroxy-3′-tert-5′[3″-(4″-vinylbenzyloxy)propoxy]phenyl}-5-methoxy-2H-benzotriazole, phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-ethenyl-(UVAM), 2-(2′-hydroxy-5-methacryloxyethylphenyl) benzotriazole (2-Propenoic acid, 2-methyl-, 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester, Norbloc), 2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole (UV13), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV13), 2-(2′-hydroxy-5-methacrylamidophenyl)-5-methoxybenzotriazole (UV6), 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV9), 2-(2-Hydroxy-3-methallyl-5-methylphenyl)-2H-benzotriazole (UV12), 2-3′-t-butyl-2′-hydroxy-5′-(3″-dimethylvinylsilylpropoxy)-2′-hydroxy-phenyl)-5-methoxybenzotriazole (UV15), 2-(2′-hydroxy-5′-methacryloylpropyl-3′-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16), 2-(2′-hydroxy-5′-acryloylpropyl-3′-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16A), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV23), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole, 2-Methylacrylic acid 3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propyl ester (16-100, CAS#96478-15-8), 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethyl methacrylate (16-102); Phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-methoxy-4-(2-propen-1-yl) (CAS#1260141-20-5); 2-[2-Hydroxy-5-[3-(methacryloyloxy)propyl]-3-tert-butylphenyl]-5-chloro-2H-benzotriazole; Phenol, 2-(5-ethenyl-2H-benzotriazol-2-yl)-4-methyl-, homopolymer (901) (CAS#83063-87-0).
[0063] Examples of more preferred UV-absorbing vinylic monomers include 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV23), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole, 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV13), 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester (Norbloc), 2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole (UV13), or a mixture thereof.
[0064] In a more preferred embodiment, UV-absorbing moieties, such as, benzophenone-moieties or benzotriazole-moieties or combinations thereof are covalently attached to a water-soluble, actinically-crosslinkable prepolymer, for example, such as, actinically-crosslinkable PVA, to make a water-soluble UV-absorbing prepolymer.
[0065] It is understood that the amount of at least one UV-absorbing vinylic monomer, or a water-soluble UV-absorbing polymer, in the aqueous lens formulation is sufficient to render a contact lens, which is obtained from the curing of the lens formulation, ability of blocking or absorbing (i.e., the inverse of transmittance) at least 90% (preferably at least about 95%, more preferably at least about 97.5%, even more preferably at least about 99%) of UVB (between 280 and 315 nanometers), at least 70% (preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%) of UVA transmittance (between 315 and 380 nanometers), and optionally (but preferably) at least 30% (preferably at least about 40%, more preferably at least about 50%, even more preferably at least about 60%) of violet light between 380 nm and 440 nm, which impinge on the lens.
[0066] In accordance with the present invention, the aqueous lens formulation can also comprise a hydrophilic vinylic monomer. Nearly any hydrophilic vinylic monomer can be used in the invention. Suitable hydrophilic vinylic monomers are, without this being an exhaustive list, N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, N-hydroxypropylacrylamide, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-vinylpyrrolidone, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 2-hydroxyethylmethacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), a C 1 -C 4 -alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, methacrylic acid, acrylic acid, and mixtures thereof.
[0067] An aqueous lens formulation of the invention can also comprise a non-silicone hydrophobic monomer (i.e., free of silicone). By incorporating a certain amount of non-silicone hydrophobic vinylic monomer in a lens formulation, the mechanical properties (e.g., modulus of elasticity) of the resultant polymer may be improved. Nearly any non-silicone hydrophobic vinylic monomer can be used in the actinically polymerizable composition for preparing the intermediary copolymer with pendant or terminal functional groups. Examples of preferred non-silicone hydrophobic vinylic monomers include methylacrylate, ethyl-acrylate, propylacrylate, isopropylacrylate, cyclohexylacrylate, 2-ethylhexylacrylate, methylmethacrylate, ethylmethacrylate, propylmethacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate.
[0068] In a preferred embodiment, the aqueous lens formulation may further comprise a crosslinking agent, preferably selected from the group consisting of N,N′-methylene-bis-(meth)acrylamide, N,N′-ethylene-bis-(meth)acrylamide, N,N′-dihydroxyethylene-bis-(meth)acrylamide, 1,3-bis(methacrylamidopropyl)-1,1,3,3-tetramethyldisiloxane, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, glycerol di(meth)acrylate, triallyl isocyanurate, triallyl cyanurate, N-allyl-(meth)acrylamide, tetraethyleneglycol divinyl ether, triethyleneglycol divinyl ether, diethyleneglycol divinyl ether, ethyleneglycol divinyl ether, and combinations thereof.
[0069] An aqueous lens formulation of the invention can further comprise visibility tinting agents (e.g., D&C Blue No. 6, D&C Green No. 6, D&C Violet No. 2, carbazole violet, certain copper complexes, certain chromium oxides, various iron oxides, phthalocyanine green, phthalocyanine blue, titanium dioxides, or mixtures thereof), antimicrobial agents (e.g., silver nanoparticles), a bioactive agent (e.g., a drug, an amino acid, a polypeptide, a protein, a nucleic acid, 2-pyrrolidone-5-carboxylic acid (PCA), an alpha hydroxyl acid, linoleic and gamma linoleic acids, vitamins, or any combination thereof), leachable lubricants (e.g., a non-crosslinkable hydrophilic polymer having an average molecular weight from 5,000 to 500,000, preferably from 10,000 to 300,000, more preferably from 20,000 to 100,000 Daltons), leachable tear-stabilizing agents (e.g., a phospholipid, a monoglyceride, a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, a sphingolipid, a sphingo-glycolipid, a fatty acid having 8 to 36 carbon atoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixture thereof), and the like, as known to a person skilled in the art.
[0070] An aqueous lens formulation can be prepared by dissolving all of the desirable components in water or a mixture of water and an organic solvent known to a person skilled in the art.
[0071] Lens molds for making contact lenses are well known to a person skilled in the art. Methods of manufacturing mold sections for cast-molding a contact lens are generally well known to those of ordinary skill in the art. The process of the present invention is not limited to any particular method of forming a mold. In fact, any method of forming a mold can be used in the present invention. The first and second mold halves can be formed through various techniques, such as injection molding or lathing. Examples of suitable processes for forming the mold halves are disclosed in U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534 to Boehm et al.; U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No. 5,894,002 to Boneberger et al., which are also incorporated herein by reference. Virtually all materials known in the art for making molds can be used to make molds for making contact lenses. For example, polymeric materials, such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene, from Ticona GmbH of Frankfurt, Germany and Summit, N.J.), or the like can be used. Other materials that allow UV light transmission could be used, such as quartz glass and sapphire.
[0072] Preferably, a reusable mold suitable for spatial limitation of radiation is used in the invention, the projected beam of radiation (e.g., radiation from the light source including the light in the region of 360 nm to 550 nm) limits radiation (e.g., UV radiation) impinging on the mixture of the lens-forming materials located in the path of the projected beam from the first molding surface to the second molding surface of the reusable mold. The resultant contact lens comprises an anterior surface defined by the first molding surface, an opposite posterior surface defined by the second molding surface, and a lens edge (with sharp edge and high quality) defined by the sectional profile of the projected radiation beam (i.e., a spatial limitation of radiation). Examples of reusable molds suitable for spatial limitation of radiation include without limitation those disclosed in U.S. Pat. Nos. 6,627,124, 6,800,225, 7,384,590, and 7,387,759, which are incorporated by reference in their entireties.
[0073] For example, a preferred reusable mold comprises a first mold half having a first molding surface and a second mold half having a second molding surface. The two mold halves of the preferred reusable mold are not touching each other, but there is a thin gap of annular design arranged between the two mold halves. The gap is connected to the mold cavity formed between the first and second molding surfaces, so that excess mixture can flow into the gap. It is understood that gaps with any design can be used in the invention.
[0074] In a preferred embodiment, at least one of the first and second molding surfaces is permeable to a crosslinking radiation. More preferably, one of the first and second molding surfaces is permeable to a crosslinking radiation while the other molding surface is poorly permeable to the crosslinking radiation.
[0075] The reusable mold preferably comprises a mask which is fixed, constructed or arranged in, at or on the mold half having the radiation-permeable molding surface. The mask is impermeable or at least of poor permeability compared with the permeability of the radiation-permeable molding surface. The mask extends inwardly right up to the mold cavity and surrounds the mold cavity so as to screen all areas behind the mask with the exception of the mold cavity.
[0076] The mask may preferably be a thin chromium layer, which can be produced according to processes as known, for example, in photo and UV lithography. Other metals or metal oxides may also be suitable mask materials. The mask can also be coated with a protective layer, for example of silicon dioxide if the material used for the mold or mold half is quartz.
[0077] Alternatively, the mask can be a masking collar made of a material comprising a UV-absorber and substantially blocks curing energy therethrough as described in U.S. Pat. No. 7,387,759 (incorporated by reference in its entirety). In this preferred embodiment, the mold half with the mask comprises a generally circular disc-shaped transmissive portion and a masking collar having an inner diameter adapted to fit in close engagement with the transmissive portion, wherein said transmissive portion is made from an optically clear material and allows passage of curing energy therethrough, and wherein the masking collar is made from a material comprising a light-blocker and substantially blocks passage of curing energy therethrough, wherein the masking collar generally resembles a washer or a doughnut, with a center hole for receiving the transmissive portion, wherein the transmissive portion is pressed into the center opening of the masking collar and the masking collar is mounted within a bushing sleeve.
[0078] Reusable molds can be made of quartz, glass, sapphire, CaF 2 , a cyclic olefin copolymer (such as for example, Topas® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene) from Ticona GmbH of Frankfurt, Germany and Summit, N.J. Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, Ky.), polymethylmethacrylate (PMMA), polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from G.E. Plastics, PrimoSpire®, etc. Because of the reusability of the mold halves, a relatively high outlay can be expended at the time of their production in order to obtain molds of extremely high precision and reproducibility. Since the mold halves do not touch each other in the region of the lens to be produced, i.e. the cavity or actual molding surfaces, damage as a result of contact is ruled out. This ensures a high service life of the molds, which, in particular, also ensures high reproducibility of the contact lenses to be produced and high fidelity to the lens design.
[0079] In accordance with the invention, the lens formulation can be introduced (dispensed) into a cavity formed by a mold according to any known methods.
[0080] After the lens formulation is dispensed into the mold, it is polymerized to produce a contact lens. Crosslinking may be initiated upon exposure to a light source including a light in a region between 390 nm to 500 nm, preferably under a spatial limitation of actinic radiation, to crosslink the polymerizable components in the mixture.
[0081] In accordance with the invention, light source can be any ones emitting light in the 390-500 nm range sufficient to activate Germane-based Norrish Type I photoinitiators. Blue-light sources are commercially available and include: the Palatray CU blue-light unit (available from Heraeus Kulzer, Inc., Irvine, Calif.), the Fusion F450 blue light system (available from TEAMCO, Richardson, Tex.), Dymax Blue Wave 200, LED light sources from Opsytec (385 nm, 395 nm, 405 nm, 435 nm, 445 nm, 460 nm), LED light sources from Hamamatsu (385 nm), and the GE 24″ blue fluorescent lamp (available from General Electric Company, U.S.). A preferred blue-light source is the UV LED from Opsytec (those described above).
[0082] The intensity of the light source is preferably from about 4 to about 40 mW/cm 2 , preferably from about 8 to about 16 mW/cm 2 in the 410 nm to 550 nm region is more preferred.
[0083] The crosslinking according to the invention may be effected in a very short time, e.g. in ≦about 120 seconds, preferably in ≦about 80 seconds, more preferably in ≦50 about seconds, even more preferably in ≦about 30 seconds, and most preferably in 5 to 30 seconds.
[0084] Opening of the mold so that the molded lens can be removed from the mold may take place in a manner known per se.
[0085] The molded contact lens can be subject to lens extraction to remove unpolymerized vinylic monomers and macromers. The extraction solvent is preferably water or an aqueous solution. After extraction, lenses can be hydrated in water or an aqueous solution of a wetting agent (e.g., a hydrophilic polymer); packaged in lens packages with a packaging solution which can contain about 0.005% to about 5% by weight of a wetting agent (e.g., a hydrophilic polymer), a viscosity-enhancing agent (e.g., methyl cellulose (MC), ethyl cellulose, hydroxymethylcellulose, hydroxyethyl cellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or a mixture thereof); sterilization such as autoclave at from 118 to 124° C. for at least about 30 minutes; and the like.
[0086] A contact lens of the invention preferably is characterized by having an average Violet-transmittance of about 60% or less (preferably about 50% or less, more preferably about 40% or less) between 380 and 440 nanometers.
[0087] A contact lens of the invention further has a water content of preferably from about 15% to about 80%, more preferably from about 30% to about 70% by weight (at room temperature, about 22° C. to 28° C.) when fully hydrated.
[0088] It should be understood that although in this aspect of the invention various embodiments including preferred embodiments of the invention may be separately described above, they can be combined and/or used together in any desirable fashion to arrive at different embodiments of a contact lenses of the invention.
[0089] Although various embodiments of the invention have been described using specific terms, devices, and methods, such description is for illustrative purposes only. The words used are words of description rather than of limitation. It is to be understood that changes and variations may be made by those skilled in the art without departing from the spirit or scope of the present invention, which is set forth in the following claims. In addition, it should be understood that aspects of the various embodiments may be interchanged either in whole or in part or can be combined in any manner and/or used together, as illustrated below:
1. An acyl germanium photoinitiator of formula (I)
[0000]
[0000] in which:
R 1 and R 1 ′ are C 1 to C 6 alkyl, preferably C 1 to C 4 alkyl; one or two of R 2 , R 3 , R 4 , R 5 , and R 6 are a hydrophilic group selected from the group consisting of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 , —CH 2 (OCH 2 CH 2 ) n1 —OH, -L 1 -SO 3 H,
[0000]
[0000] while the others of R 2 , R 3 , R 4 , R 5 , and R 6 independent of one another are hydrogen, methyl, or methoxy, wherein in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10), L 1 is a direct bond or methylene diradical (—CH 2 —), L 2 is ethylene diradical (—C 2 H 4 —) or propylene diradical (—C 3 H 6 —), L 3 is hydrogen or a C 1 -C 4 alkyl, R 10 is methyl or ethyl.
2. The acyl germanium photoinitiator of invention 1, wherein R 1 and R 1 ′ are C 1 to C 4 alkyl. 3. The acyl germanium photoinitiator of invention 1, wherein R 1 and R 1 ′ are methyl or ethyl. 4. The acyl germanium photoinitiator of invention 1, 2 or 3, wherein n1 is an integer of 3 to 15. 5. The acyl germanium photoinitiator of invention 1, 2 or 3, wherein n1 is an integer of 4 to 10. 6. The acyl germanium photoinitiator of any one of inventions 1 to 5, wherein L 3 is methyl or ethyl. 7. The acyl germanium photoinitiator of any one of inventions 1 to 6, wherein only one of R 2 , R 3 , R 4 , R 5 , and R 6 is a hydrophilic group selected from the group consisting of
[0000]
[0000] —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 , —CH 2 (OCH 2 CH 2 ) n1 —OH, and -L-SO 3 H while the others of R 2 , R 3 , R 4 , R 5 , and R 6 independent of one another are hydrogen, methyl, or methoxy.
8. The acyl germanium photoinitiator of any one of inventions 1 to 6, wherein two of R 2 , R 3 , R 4 , R 5 , and R 6 are a hydrophilic group selected from the group consisting of
[0000]
[0000] —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 , —CH 2 (OCH 2 CH 2 ) n1 —OH, and -L 1 -SO 3 H while the others of R 2 , R 3 , R 4 , R 5 , and R 6 independent of one another are hydrogen, methyl, or methoxy.
9. The acyl germanium photoinitiator of any one of inventions 1 to 8, wherein the hydrophilic group is —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 or —CH 2 (OCH 2 CH 2 ) n1 —OH. 10. The acyl germanium photoinitiator of any one of inventions 1 to 8, wherein the hydrophilic group is
[0000]
11. The acyl germanium photoinitiator of any one of inventions 1 to 8, wherein the hydrophilic group is
[0000]
12. The acyl germanium photoinitiator of any one of inventions 1 to 8, wherein the hydrophilic group is
[0000]
13. The acyl germanium photoinitiator of any one of inventions 1 to 8, wherein the hydrophilic group is -L 1 -SO 3 H in which L 1 is a direct bond or methylene diradical (—CH 2 —).
14. The acyl germanium photoinitiator of any one of inventions 1 to 6, having a formula selected from the group consisting of formula (I-1) to (I-63):
[0000]
in which PEG is a monovalent radical of —CH 2 (OCH 2 CH 2 ) n1 —OCH 3 or —CH 2 (OCH 2 CH 2 ) n1 —OH in which n1 is an integer of 2 to 20 (preferably 3 to 15, more preferably 4 to 10).
15. A method for producing UV-absorbing silicone hydrogel contact lenses, the method comprising the steps of:
(1) obtaining an aqueous lens formulation, wherein the aqueous lens formulation comprises
(a) from about 0.1% to about 2.0% by weight of at least one acyl germanium photoinitiator of any one of inventions 1 to 14, and (b) at least one UV-absorbing vinylic monomer, or a water-soluble UV-absorbing prepolymer (which comprises UV-absorbing moieties attached covalently thereto), and
(2) introducing the aqueous lens formulation into a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; and (3) irradiating the aqueous lens formulation in the mold by using a light source including a light in a region of from 390 nm to 500 nm, so as to crosslink the lens-forming materials to form the UV-absorbing contact lens, wherein the formed UV-absorbing silicone hydrogel contact lens comprises an anterior surface defined by the first molding surface and an opposite posterior surface defined by the second molding surface and is characterized by having a UVB transmittance of about 10% or less between 280 and 315 nanometers and a UVA transmittance of about 30% or less between 315 and 380 nanometers.
16. The method according to invention 15, wherein the aqueous lens formulation comprises from about 0.25% to about 1.75% by weight of (preferably from about 0.5% to about 1.5% by weight of, more preferably from about 0.75% to about 1.25% by weight of) at least one acyl germanium photoinitiator of any one of inventions 1 to 14
17. The method according to invention 15 or 16, wherein the formed UV-absorbing silicone hydrogel contact lens is characterized by having the UVB transmittance of about 5% or less (preferably about 2.5% or less, even more preferably about 1% or less) between 280 and 315 nanometers.
18. The method according to any one of inventions 15 to 17, wherein the formed UV-absorbing silicone hydrogel contact lens is characterized by having the UVA transmittance of about 20% or less (preferably about 10% or less, more preferably about 5% or less) between 315 and 380 nanometers.
19. The method according to any one of inventions 15 to 17, wherein the formed UV-absorbing silicone hydrogel contact lens is characterized by having a Violet transmittance of about 60% or less (preferably about 50% or less, more preferably about 40% or less, even more preferably about 30% or less) between 380 nm and 440 nm.
20. The method according to any one of inventions 15 to 19, wherein the mold is a reusable mold, wherein the step of irradiating is performed under a spatial limitation of actinic radiation, wherein the formed UV-absorbing silicone hydrogel contact lens comprises a lens edge defined by the spatial limitation of actinic radiation.
21. The method according to any one of inventions 15 to 20, wherein the aqueous lens formulation comprises a water-soluble actinically-crosslinkable prepolymer.
22. The method according to invention 21, wherein water-soluble actinically-crosslinkable prepolymer is: a water-soluble actinically-crosslinkable poly(vinyl alcohol) prepolymer; a water-soluble vinyl group-terminated polyurethane prepolymer; a water-soluble actinically-crosslinkable polyurea prepolymer); a water-soluble actinically-crosslinkable polyacrylamide; a water-soluble actinically-crosslinkable statistical copolymer of vinyl lactam, MMA and a comonomer; a water-soluble actinically-crosslinkable copolymer of vinyl lactam, vinyl acetate and vinyl alcohol; a water-soluble polyether-polyester copolymer with actinically-crosslinkable side chains; a water-soluble branched polyalkylene glycol-urethane prepolymer; a water-soluble polyalkylene glycol-tetra(meth)acrylate prepolymer; a water-soluble actinically-crosslinkable polyallylamine gluconolactone prepolymer, or a mixture thereof.
23. The method according to invention 21 or 22, wherein the aqueous lens formulation comprises from about 15% to about 50% by weight, preferably from about 15% to about 40% by weight, more preferably from about 25% to approximately 40% by weight of the water-soluble actinically-crosslinkable prepolymer.
24. The method of any one of inventions 15 to 23, wherein said at least one UV-absorbing vinylic monomer is selected from the group consisting of: 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole; 2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole; 2-(2-hydroxy-3-methacrylamido methyl-5-tert octylphenyl) benzotriazole; 2-(2′-hydroxy-5-methacrylamidophenyl)-5-chlorobenzotriazole; 2-(2′-hydroxy-5′-methacrylamidophenyl)-5-methoxybenzotriazole; 2-(2′-hydroxy-5-methacryloxypropyl-3′-t-butyl-phenyl)-5-chlorobenzotriazole; 2-(2′-hydroxy-5-methacryloxypropylphenyl) benzotriazole; 2-hydroxy-5-methoxy-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-1); 2-hydroxy-5-methoxy-3-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-5); 3-(5-fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-2); 3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-3); 3-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-4); 2-hydroxy-5-methoxy-3-(5-methyl-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-6); 2-hydroxy-5-methyl-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-7); 4-allyl-2-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-6-methoxyphenol (WL-8); 2-{2′-Hydroxy-3′-tert-5-[3″-(4″-vinylbenzyloxy)propoxy]phenyl}-5-methoxy-2H-benzotriazole; phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-ethenyl- (UVAM); 2-(2′-hydroxy-5-methacryloxyethylphenyl) benzotriazole (2-Propenoic acid, 2-methyl-, 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester, Norbloc); 2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole (UV13); 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV13); 2-(2′-hydroxy-5-methacrylamidophenyl)-5-methoxybenzotriazole (UV6); 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV9); 2-(2-Hydroxy-3-methallyl-5-methylphenyl)-2H-benzotriazole (UV12); 2-3′-t-butyl-2′-hydroxy-5′-(3″-dimethylvinylsilylpropoxy)-2′-hydroxy-phenyl)-5-methoxybenzotriazole (UV15); 2-(2′-hydroxy-5′-methacryloylpropyl-3′-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16); 2-(2′-hydroxy-5′-acryloylpropyl-3′-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16A); 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV23), 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28); 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole; 2-Methylacrylic acid 3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propyl ester (16-100, CAS#96478-15-8); 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethyl methacrylate (16-102); Phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-methoxy-4-(2-propen-1-yl) (CAS#1260141-20-5); 2-[2-Hydroxy-5-[3-(methacryloyloxy)propyl]-3-tert-butylphenyl]-5-chloro-2H-benzotriazole; Phenol, 2-(5-ethenyl-2H-benzotriazol-2-yl)-4-methyl-, homopolymer (9CI) (CAS#83063-87-0); and combinations thereof (preferably from the consisting of: 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV23); 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28); 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole; 2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (CF 3 —UV13); 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester (Norbloc); 2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole (UV13); and combinations thereof).
25. The method of any one of inventions 15 to 24, wherein the light source is a light-emitting-device having a peak wavelength of from 400 nm to 480 nm.
[0123] The previous disclosure will enable one having ordinary skill in the art to practice the invention. Various modifications, variations, and combinations can be made to the various embodiment described herein. In order to better enable the reader to understand specific embodiments and the advantages thereof, reference to the following examples is suggested. It is intended that the specification and examples be considered as exemplary.
Example 1
Transmittance
[0124] Contact lenses are manually placed into a specially fabricated sample holder or the like which can maintain the shape of the lens as it would be when placing onto eye. This holder is then submerged into a 1 cm path-length quartz cell containing phosphate buffered saline (PBS, pH ˜7.0-7.4) as the reference. A UV/visible spectrpohotmeter, such as, Varian Cary 3E UV-Visible Spectrophotometer with a LabSphere DRA-CA-302 beam splitter or the like, can be used in this measurement. Percent transmission spectra are collected at a wavelength range of 250-800 nm with % T values collected at 0.5 nm intervals. This data is transposed onto an Excel spreadsheet and used to determine if the lenses conform to Class 1 UV absorbance. Transmittance is calculated using the following equations:
[0000]
UVA
%
T
=
Average
%
T
between
380
-
316
nm
Luminescence
%
T
100
UVB
%
T
=
Average
%
T
between
280
-
315
nm
Luminescence
%
T
100
Violet
%
T
=
Average
%
T
between
440
-
380
nm
Luminescence
%
T
100
[0000] in which Luminescence % T is the average % transmission between 380 and 780.
[0125] Photo-Rheology:
[0126] The photo-rheology experiment measures the elastic (G′) and viscous modulus (G″) as a function of time during curing. The experiment is conducted by using an appropriate light source, optionally cutoff filters to select wavelengths of interest, and a rheometer. The light source is a Mercury bulb in a Hamamatsu light source. The intensity of light source is set by adjusting the shutter opening to get an appropriate intensity measured by a radiometer. The sample is placed between a quartz plate that allows UV light to pass through and the rheometer. The cure time is determined when the elastic modulus (G′) reaches a plateau. | Described herein are acyl germanium photoinitiator for cost-effective and time-efficient method for producing UV-absorbing contact lenses capable of blocking ultra-violet (“UV”) radiation and optionally (but preferably) violet radiation with wavelengths from 380 nm to 440 nm, thereby protecting eyes to some extent from damages caused by UV radiation and potentially from violet radiation. This invention also provides a method for making UV-absorbing contact lenses made by using an acyl germanium photoinitiator of the invention. | 2 |
FIELD OF THE INVENTION
The present invention generally relates to an intravenous catheter and associated flexible tubing for use with a patient and more particularly to a non-kinking tubing adaptor for an intravenous catheter and associate flexible tubing.
BACKGROUND OF THE INVENTION
Intravenous (IV) catheters are well known in the medical field and are used for a wide variety of applications including hydration and administration of medications, feeding and blood transfusions. A typical intravenous infusion system includes a catheter for penetrating the skin and underlining vein of the patient usually in the patient's forearm or hand, a source of fluid and flexible plastic tubing interconnecting the source of fluid and the intravenous catheter. It is common practice to secure the intravenous catheter and a portion of its associated flexible tubing to the limb of the patient to minimize movement of the catheter relative to the limb. This is normally accomplished with adhesive tape. A loop is normally formed in the end of the flexible tubing that connects to the intravenous catheter. It is important that the loop be secured to the limb of the patient in a manner so as to avoid kinking the flexible tubing which would result in a shut-off of the fluid through the tubing. In the past various arrangements have been proposed for securing the catheter and tubing to the patient so as to avoid kinking and unnecessary movement. Examples of various prior art devices are disclosed in U.S. Pat. Nos. 3,059,645, 3,942,528, 4,976,698 and 5,116,324. Such prior art devices require separate apparatus for maintaining the "U" in the flexible tubing. While such prior art devices appear to be successful in maintaining the "U" in the flexible tubing, they have left something to be desired in regard to bulk and comfort of the patient.
It will be understood that the majority of IV placements are made around the areas of the wrist and the back of the hand of the patient. The obtrusiveness of the tubing loop or any separate for maintaining the "U" in the flexible tubing makes the IV placement quite vulnerable due to random movements of the hand and arm. Displacement of the IV catheter can be quite serious, especially when a patient is very ill and available veins for placement of the catheter are at a minimum. It would be desirable to provide the flexible tubing with a rigid U-shaped section for connection to an intravenous catheter. This would eliminate the bulk of any extra apparatus, permit the use of a smaller U-shaped section and still permit the intravenous catheter and associated flexible tubing to be secured to the patient's limb with adhesive tape for a light weight connection.
SUMMARY OF THE INVENTION
In accordance with the present invention there is provided a non-kinking tubing adaptor for an intravenous catheter and associated flexible tubing. The adaptor comprises a rigid tube having a pair of straight tube connections interconnected by a U-shaped tube section. An adaptor is positioned on the free end of one of the straight sections for connection to an intravenous catheter and the end of the other straight section remote from the U-shaped section is adapted for connection to a flexible intravenous tubing. In the preferred form of the invention the rigid tube is J-shaped with the short section of the "J" being provided with an adaptor for connection to an intravenous catheter. The long leg of the J-shaped adaptor may be provided with an adaptor for connection to the flexible intravenous tubing or the flexible intravenous tubing may be bonded directly to the long leg of the J-shaped adaptor.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a non-kinking tubing adaptor for an intravenous catheter and associated flexible tubing in accordance with the present invention shown in position on an intravenous site on the forearm of a patient.
FIG. 2 is a modification of the non-kinking tubing adaptor in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1 there is illustrated an intravenous system embodying the present invention. The system includes the novel non-kinking tubing adaptor 10 which interconnects the intravenous catheter 11 and a flexible plastic IV tubing 12. The non-kinking tubing adaptor 10 comprises a rigid tube, preferably plastic, having a pair of straight sections 10a and 10b interconnected by a U-shaped section 10c. As may be seen in FIG. 1 the rigid tube is preferably J-shaped, the straight tube section 10a being shorter than the other straight tube section 10b. As may be seen from FIG. 1 the term "tube" is used herein in accordance with its ordinary dictionary definition, namely a hollow elongated cylindrical body. The tube section 10a is provided with a male connector 13 for insertion in the female connector portion of the intravenous catheter 11. The other leg 10b of the rigid tube 10 is provided with a female connector 14 for receiving an adaptor or directly connected to the flexible IV tubing 12. The flexible IV tubing 12 is connected to a source of intravenous fluid, not shown.
In practice the intravenous catheter 11 is maintained in place on the patient's forearm or hand by a piece of adhesive tape T. After the connector 13 of the rigid J-shaped tube 10 has been inserted in the intravenous catheter, the tube 10 is held in place on the patient's arm by a second piece of adhesive tape T' applied over the first piece of tape T. With this arrangement, the required loop in the intravenous tubing system will be maintained by virtue of the rigid adaptor 10 and the complete system is readily maintained in position on the patient's arm by the use of adhesive tape. This arrangement provides a simple light weight intravenous system which permits the use of a smaller loop and is comfortable for the patient but at the same time ensures that the loop in the intravenous tubing system will remain unkinked.
Referring to FIG. 2 there is shown another non-kinking tubing adaptor 10' embodying the present invention. In this embodiment, the adaptor 10' is a rigid tube and is similar to the adaptor 10. The adaptor 10' comprises a pair of straight sections 10a' and 10b' interconnected by a U-shaped section 10c'. A connector 13' is positioned on the short leg 10a' of the J-shaped rigid tube. The long leg 10b' of the J-shaped tube instead of being provided with a detachable connector is permanently connected as by bonding to the end of the flexible tubing 12 with a bonding sleeve 14'.
The tubing adaptor's 10 and 10' may be made from any suitable plastic material which may be formed as a rigid tube. The connectors 13 and 14 are conventional press fitting connectors used in intravenous systems. The intravenous tubing 12 is also conventional plastic tubing used in intravenous systems.
From the foregoing it will be seen that the novel tubing adaptor of the present invention not only eliminates the kinking normally inherent in flexible tubing intravenous systems but by reason of its rigid tube construction it permits the use of a smaller loop. A smaller loop is particularly desirable with regard to infants and children and the smallness in size minimizes the vulnerability of displacement of the IV due to random movements of the hand and arm by the patient. As an example of size, the dimension across the U-shaped portion 10c may be as small a 3/4". The dimension of the short leg 10a measured from the end of the adaptor 13 to the top of the U-shaped portion 10c may be in the order of 1" and the length of the longer leg 10b measured from the end of the adaptor 14 to the top edge of the U-shaped portion 10c may be in the order of 2". An adaptor 10 with these dimensions is large enough to be firmly secured to the limb of the patient with adhesive tape but is also small enough to provide for comfort of the patient.
While a preferred embodiment of the invention has been described and illustrated, it is to be understood that further modification thereof will be made within the scope of the appended claims without departing from the spirit of the invention. | A non-kinking tubing adaptor for an intravenous catheter and associated flexible tubing including a rigid tube having a J-shaped configuration, the short end of the J-shaped tube being constructed for connection to an intravenous catheter and the long end of the J-shaped tube being constructed for connection to a flexible intravenous tubing. | 0 |
BACKGROUND OF THE INVENTION
This invention relates to an elongate wiper blade assembly of the kind comprising a yoke structure having a plurality of yokes provided with claw members for supporting backing means carrying two wiper blades. In particular, the invention relates to a wiper blade assembly for motor vehicles.
A known elongate wiper blade assembly of the kind referred to is described in EP-A-0327233 and has a single backing member constituting the said backing means which carries both of the wiper blades. The backing member is specifically designed for carrying two wiper blades and is not interchangeable with backing members intended to be used with wiper blade assemblies having a single wiper blade.
Another known elongate wiper blade assembly of the kind referred to is described in U.S. Pat. No. 4,628,565. In this known wiper blade the backing means consists of two separate backing strips each carrying a different one of the two wiper blades and the claw members are arranged in longitudinally spaced apart pairs for supporting the two backing strips. However the two claw members of each longitudinally spaced apart pair are movable independently of each other so that the two backing strips are supported independently of each other along their lengths.
SUMMARY OF THE INVENTION
The present invention seeks to provide an elongate wiper blade assembly of the kind referred to in which separate backing strips are supported by common claw members along the length of the wiper blade assembly.
According to the present invention an elongate wiper blade assembly of the kind referred to is characterised in that the backing means comprises two separate backing strips each carrying a different one of said two wiper blades and in that each claw member is constructed and arranged to support both of said backing strips.
The two backing strips are thus supported at common positions along their lengths. By employing two separate backing strips, these may be of similar design to backing strips employed in conventional single wiper blade assemblies. This is an important commercial consideration since it is not necessary for manufacturers to manufacture different backing strips for the single and dual wiper blade assemblies or for retailers to stock different replacement backing strips for the two types of wiper blade assembly.
Conveniently each claw member comprises two parallel open channels in which the two backing strips are received. Preferably each open channel has a restricted mouth defined by inwardly extending lip portions designed to be received in opposed open side channels of its associated backing strip.
Preferably the yoke structure and claw members are made of plastics material. Each backing strip is also preferably made of plastics material.
Suitably the wiper blade assembly includes end clip means for engaging a common end of the backing strips and one of the claw members to restrain relative longitudinal movement between the backing strips and the said one claw member. Preferably the end clip means consists of a separate end clip associated with each backing strip. In this case each end clip conveniently comprises means for detachably securing the end clip to one end of its associated backing strip and spaced apart resiliently deflectable legs, at least one of which legs having latching means, e.g. in the form of a recess, for cooperating with said one claw member to restrain said relative longitudinal movement.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the invention will now be described, by way of example, with reference to the accompanying drawings, in which:
FIG. 1 is a perspective view of a yoke structure for an elongate wiper blade assembly according to the invention,
FIG. 2 is a sectional view through part of a wiper blade assembly according to the invention and showing a claw member of the yoke structure shown in FIG. 1 supporting two wiper blades and their associated backing strips,
FIG. 3 is a partly cut away perspective view of one end of an elongate wiper blade assembly according to the invention showing the use of end clips to restrain movement of backing strips relative to an endmost claw member,
FIG. 4 is a side view of the end of the wiper blade assembly shown in FIG. 3 illustrating the end clips affixed to the claw member,
FIG. 5 is a perspective view of one of the end clips shown in FIG. 3 detached from its associated backing strip,
FIGS. 6 and 7 are alternative designs of end clip, and
FIGS. 8 and 9 are schematic views of different yoke designs which can be incorporated in an elongate wiper blade assembly according to the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a yoke structure, generally designated 1, of an elongate wiper blade assembly according to the invention, connected to a wiper arm, generally designated 2, via a pivot pin 4 extending sideways from the wiper arm 2. The yoke structure 1 includes a plastics main yoke 5, plastics secondary yokes 6 articulated to the main yoke 5 and plastics tertiary yokes 7 articulated to the secondary yokes 6. Each secondary yoke 6 has two inner arms joined at their inner ends by a unitary claw member 8. Each tertiary yoke 7 comprises two cradles 7a, 7b each articulated at central regions to an outer end portion of its associated secondary yoke 6 and joined together at their opposite ends by unitary claw members 8. Since the claw members 8 are each of generally the same design they have been identified in the drawings by the same reference numeral.
As can be seen in FIG. 2, each claw member 8 has two spaced apart parallel open channels 10 and 11 having restricted mouths defined by inwardly extending lip portions 10a, 10b and 11a, 11b, respectively. Within each channel 10, 11 there is received an elongate plastics backing strip 12, 13, respectively carrying a wiper element 14, 15, respectively, in the form of a rubber squeegee or the like. Each backing strip 12 (13) has elongate open side channels 12a, 12b (13a, 13b) within which the lip portions 10a, 10b (11a, 11b), respectively, are received to support the backing strips.
Longitudinal movement of the backing strips 12, 13 relative to the outer claw member 8 on one or each of the tertiary yokes 7 is restrained or prevented by end clips 16, 17 (see FIGS. 3 to 5 ) which are attached to one end of the strips 12, 13, respectively, and which interengage with the claw member (only partly shown in FIG. 3 ).
The end clips 16, 17 are of similar design and only one end clip 16, shown in FIGS. 4 and 5, will be described in detail. In particular the end clip 16 has a back wall 19 having spaced apart side walls 20 and 21 connected to opposite ends thereof and a tongue 22 connected to the top of the back wall. Spaced apart legs 23 and 24, having rectangular recesses 25 and 26, respectively, formed in their outer edges, are connected to the side walls 20 and 21, respectively. The side walls 20 and 21 and legs 23 and 24 are normally disposed parallel to each other. However, the side walls 20 and 21 are resiliently connected to the back wall 19 and can be resiliently deflected inwardly on application of inward pressure, e.g. finger pressure, to the side walls 20, 21 to cause the legs 23 and 24 to be moved towards each other. The tongue 12 has a bifurcated peg 27 extending downwardly therefrom with diverging bifurcations which are resiliently deflectable towards each other and which are each of rectangular cross-section.
In order to assemble the windscreen wiper blade assembly, the wiper elements 14 and 15 are slotted into bottom slots 30 and 31, respectively, of the backing strip 12 and 13, respectively, and the end clips 16 and 17 are connected to common ends of the backing strips 12 and 13 by pressing the pegs 27 of the end clips into resilient engagement with recesses 26 formed in the backing strips adjacent one of their ends. In this position the legs 23 and 24 of each end clip lie on top of the associated backing strip and the side walls 20 and 21 of each end clip are spaced apart clear of the side edges of the associated backing strip. The backing strips 12, 13 are then threaded on to each of the claw members 8, starting at the end of each backing strip remote from the end to which the end clip is attached, until the position shown in FIGS. 3 and 4 is reached in which the leg 23 of end clip 16 and the leg 24 of end clip 17 are latched to the claw member 8. The other leg of each end clip--i.e. leg 24 of end clip 16 and leg 23 of end clip 17--is kept resiliently urged inwards by an extended central wall 40 of the claw member 8. The provision of the extended central wall 40 enables both end clips 16, 17 to be released together from the claw member 8 by the application of inwards pressure, e.g. finger pressure, to the two outwardly facing side walls of the end clips 16, 17--i.e. side wall 20 of end clip 16 and side wall 21 of end clip 17 are pressed inwardly to release both end clips from the interlocking engagement with the claw member 8.
As an alternative to providing the extended end wall 40, the design of the two end clips 16 and 17 could be replaced by the end clips 50 and 51 shown in FIGS. 6 and 7, respectively. With these clips, a different one of their two legs is not provided with a latching portion--i.e. the leg 50a, 51a of each end clip 50, 51 which is intended to be positioned inwardly of the claw member 8. However these particular designs of end clip are not preferred since two different end clips 50, 51 have to be manufactured for each wiper blade assembly. Although the end clips 16, 17 and 50, 51 are preferably made of plastics material they could, alternatively, be metallic.
The present invention enables two similar backing strips 12, 13, preferably each of the same design as those used in conventional single wiper blade assemblies, to be employed in a dual wiper blade assembly. This is particularly important for manufacturers who only need to manufacture one design of backing strip for both single and dual wiper blade assemblies and for retailers who only need to stock one design of backing strip for the two types of wiper blade assemblies. The unitary claw members ensure that the two backing strips 12, 13 are held fixed relative to each other, i.e. more rigidly, at spaced locations along their lengths. The use of twin wiper blades provides an improved windscreen wiping effect over a single wiper blade. In particular, the first wiper blade is intended to clear most of the water from the windscreen and the second wiper blade is intended to clear any streaks left by the first wiper blade. Although the invention has been described with particular reference to wiper blade assemblies made of plastics material, it should be realised that the yoke structure, including the claw members, could be metallic, or at least partially metallic. Similarly the backing strips could also be metallic.
FIGS. 8 and 9 schematically illustrate alternative yoke designs which can be incorporated in elongate wiper blade assemblies according to the invention.
It is to be understood that the invention is not considered to be limited to the precise details and constructions set forth in this specification and modifications may be made with in the scope of the appended claims. | An elongate wiper blade assembly comprises a yoke structure provided with a plurality of claw members, each claw member being designed to support a pair of backing strips each adapted to carry a wiper element, | 1 |
FIELD OF THE INVENTION
The present invention relates to molecular-biological diagnostics, and more particularly to a novel method and system for analysing mutations or well-defined genetic events in coding DNA-sequences or corresponding RNA-sequences.
BACKGROUND OF THE INVENTION
The mammalian gene structure is based on coding DNA-sequences (exons) and intervening sequences (introns). Disturbances or changes (mutations) in the coding sequences result in abnormal gene products and thus malfunction and disease. Today, more than 4500 diseases are known which are due to defects in single genes. Such defects may be stable mutations, i.e. they always occur in specific, predictable positions, but may also be unstable genetic events occurring at one or more of a number of different unpredictable locations in the gene. In many cases the cause of a specific genetic disease may be stable or unstable events in any one of a number of exons. Detailed genetic information on an individual will tell about the susceptibility for disease, confirm inherited disorders, confirm disease status and serve as a guidance for more efficient treatment.
In the case of stable and thereby predictable mutations, methods permitting the determination of a specific polynucleotide sequence may be used, whereas the detection of unstable genetic events will require a DNA (or RNA) sequencing operation on the exon or exons in question. It is readily understood that with current methods, the determination of genetic diseases which may be due to one of several possible stable and unstable mutations will be laborious and time-consuming, requiring inter alia a great number of pipetting operations. The reproducibility will therefore be highly dependent on the skill of the operator. Besides, only a few commercial tests are available today for such genetic diseases, which tests, apart from being relatively complicated to perform, have a rather low accuracy.
Co-pending Swedish patent application 9203320-8 discloses a method of performing molecular-genetic reactions using a patrix-matrix type system, wherein the matrix part usually is a microtiter plate and the patrix part is a plate having a plurality of protrusions or extensions, each matching a respective well of the microtiter plate. The extensions are used as solid phase elements, each capable of binding a specific nucleic acid sequence from a solution and then keep it immobilized thereto for further processing or reaction by inserting the assembly of extensions into further microtiter wells. Such a system will permit a plurality of reactions to be performed simultaneously with reduced risk of contamination between reactions. While the use of the system for diagnostics tests is described in general, there is only a specific disclosure of the determination of stable mutations.
SUMMARY OF THE INVENTION
The present invention seeks to provide a novel method and system, respectively, for molecular-biological diagnostics, partially based upon the basic concept of the afore-mentioned Swedish patent application 9203320-8, which are devoid of the disadvantages of the prior art methods for molecular-biological diagnostics and which permit exon-specific determination of both stable and unstable mutations.
Thus, one object of the present invention is to provide an integrated assay format for the analysis of point mutations or well-defined genetic events in exons, i.e. coding DNA-sequences, or corresponding RNA sequences.
Another object is to provide a method and system for exon-specific testing which permit standardisation, high reproducibility and operator-adapted handling routines.
Still another object is to provide a method and system capable of providing all exon-specific testing with very high security (more than 95%) independently of the genetic disease, i.e. stable mutations as well as unstable genetic events.
A further object is to provide a method and system for exon-specific testing which basically are free of pipetting operations.
The above-mentioned objects are achieved with a method and system having the characteristics defined in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be described in more detail with reference to the accompanying drawing wherein the only figure, FIG. 1, is a schematic diagram showing a system for exon-specific genetic tests in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The system illustrated in the figure comprises a processing unit 1 for treating cells from blood (white blood cells) or tissue to obtain a genomic DNA or RNA preparation of a reproducible quality for direct amplification with any of the currently available genetical amplification methods. As an example of a suitable type of processing unit may be mentioned that described in WO 92/02303, in which an upper process microtiter type plate and a lower receiver plate are placed on top of each other, liquid being pressed from the upper plate to the lower plate by the application of gas pressure.
The illustrated system further comprises an amplification unit 2 for amplifying the exons, or more correctly, specific DNA or RNA fragments of interest to analyse with regard to the genetic defects in question (for the sake of simplicity referred to as exons herein). Such units are commercially available and need not be described further here. The specific DNA or RNA fragments may optionally be defined utilizing known intron specific sequences. In such a case the nucleic acid fragment in question will also comprise intron nucleotides at one or both ends.
A basic component of the system of the present invention is a pin member or strip 3 comprising a base portion 4 having a set of, in the illustrated case eight, extensions or pins 5 protruding therefrom in a comb-like fashion. The pins 5 support specific sequencing primers capable of binding to exons specifying a desired diagnosis. The necessary number of pins will depend on the specific exon to be analysed as will be discussed in more detail below. For a more detailed description of the pins 5 it may be referred to the afore-mentioned Swedish patent application 9203320-8.
The term "pin" is to be understood in a broad sense, meaning any kind of protrusion or extension fulfilling the intended purpose.
Preferably, the pin strips 3 are adapted to be assembled side-by-side to form, if desired, a strip assembly having two or more rows of pins 5 and thereby permit the simultaneous handling of a plurality of pin strips 3.
For each pin member, or strip, 3 there is a corresponding matching well member, or strip, 6 comprising a plurality of wells 7 corresponding to the pins 5 of the pin strip 3. Each genetic disorder requires a specific set of pins 5 and wells 7.
For exons containing stable and thereby predictable genetic changes, the wells 7 will contain all the reagents necessary for performing a complete analysis of a specific exon. The well strips 6 are preferably adapted to be assembled to a microtiter plate format 8 as indicated by the dashed lines in the figure.
For exons containing unstable and thereby unpredictable genetic changes, the wells 7 will contain the necessary components for a complete sequencing reaction, such as of the Sanger (dideoxy sequencing) type.
The reagents in the wells are preferably predispensed in dried form as is disclosed in, for example, EP-A-298 669. While the reagents may be in freeze-dried form, reagent mixtures dehydrated in the presence of a glass-forming substance to a glassified state are preferred, e.g. by using a sugar copolymer like Ficoll™, as described in U.S. Pat. No. 5,098,893, or trehalose, as described in U.S. Pat. No. 4,891,319.
Finally, the system comprises detection means 9 and 10, respectively, for the detection of exons identified by the reactions using the pin and well strips 3 and 6, respectively.
For the detection, on one hand, of exons containing stable mutations, the detecting means 9 may be one that is capable of detecting incorporated markers, for example, as suggested in the figure, a conventional fluorometer or the like for measuring incorporated fluorescent markers.
For the detection, on the other hand, of exons which may contain unstable mutations, and optionally of exons which may contain several stable mutations, a sequencer 10 for determining the fine structure of the gene is included in the system. Such a sequencer is advantageously an automated DNA sequencer of the type which records signals generated in adjacent lanes as fluorescently labelled fragments move past a specified point in an electrophoretic sequencing gel. An example of such a sequencer is that described in U.S. Pat. No. 4,707,235 and commercialized as the "A.L.F. DNA Sequencer" by Pharmacia LKB Biotechnology AB, Uppsala, Sweden. This sequencer uses a single fluorescent label, a fixed laser beam, and fixed detectors spaced across the width of the sequencing gel.
The above described system may be used as follows for molecular-biological testing.
First, a genomic DNA or RNA preparation is prepared by lysing cells from blood 11 (white blood cells) or tissue 12 (obtained by biopsy or the like) and applied in specially designed preparation plates adapted for processing in processing unit 1. In the latter, the purification is effected by means of gel-slurries or, preferably, membranes in separation wells of the preparation plates as is per se known in the art. Thus, a preparation plate containing e.g. 24 patient samples is placed on top of a matching receiving plate in the processing unit 1, and the necessary liquids, such as lysing buffer and washing fluid, for the purification process are moved from one plate to the other by the application of air pressure, thereby accomplishing the desired purification. The result will be a genomic DNA or RNA preparation which may be directly used in any one of the commercially available amplification methods.
As an alternative, genomic DNA may be released from the cells by using the method disclosed in WO 91/08308, which comprises subjecting the cells to a temperature of at least 105° C. for a time period of at least 5 minutes. The resulting DNA preparation, containing single-stranded DNA, may be directly used in an amplification process without further purification.
While it may, at least in some cases, be possible to subject the obtained genomic DNA or RNA preparation to a defined cleavage procedure to produce the specific fragments which are to be subsequently analysed with respect to the genetic defects tested for, it is in most cases preferable to produce these specific DNA or RNA fragments by amplification in amplification unit 2. As mentioned above, the specific DNA or RNA fragments may be defined by known intron specific sequences, in which case the fragments will in addition to the exon nucleotides also contain intron nucleotides.
Amplification may be based upon any one of the amplification methods which are commercially available, such as polymerase chain reaction (PCR), nucleic acid sequence-based amplification (NASBA), or self-sustained sequence replication (3SR). The amplification is performed in per se known manner in a number of amplification tubes to which different primers are added to amplify the desired DNA fragments. After completed amplification (usually 20-30 cycles), a selected sample material has been obtained which contains defined DNA or RNA fragments in a sufficient amount for permitting the application of a detection method defining exon-specific genetic changes in detail as will described below.
For simplifying the performance of the amplification procedure, the necessary amplification reagents, such as primers, nucleotides, enzyme and buffer, may be added stabilised on one end of a plastic strip (for example, of the conventional type used for the detection of sugar in urine).
In the next step, the specific reactions required for detecting the exon-specific genetic changes tested for with high reproducibility are performed. This is effected using the pin strip 3 described above which permits pipetting-free handling. Thus, a set of pin strips 3 and well strips 6 specific for a selected genetic disease is provided. As an example, suppose that the genetic disease in question may be due to any one of unstable (and thereby unpredictable) changes in one exon, and stable point mutations in, say, two exons. In this case, two pin strips 3 may be used, one for detecting the stable mutations and one for detecting the unstable mutations. In both cases the individual pins 5 of the pin strip 3 will support exon-specific primers capable of binding to selected exons. Thereby these exons may be fished from the amplified genomic DNA or RNA preparation by introducing the pins 3 into the corresponding amplification tubes.
The necessary number of pins 5 on the pin strip 3 for detecting a stable mutation in an exon will depend on the particular method selected for the detection. Generally, one or two pins 5 per exon will suffice, in many cases only one. However, especially for stable mutations, but also for unstable mutations, it is, in fact, also possible to use one pin for several exons as will be further discussed below.
As an example, the illustrated pin strip 3 which contains eight pins 5 may be prepared to either bind up to eight different exons, or one exon from up to eight different patient samples. In the assumed case of two stable mutations, one pin strip 3 may thus, if desired, be used for testing four different patient samples simultaneously.
The desired detection reactions are then started by dipping the pins 5, having the respective exon or exons bound thereto, into the corresponding wells 7 in well strip 6, which wells contain the necessary reagents predispensed and stabilised.
For detecting stable mutations, several different methods may be used, comprising the incorporation of a detectable marker, e.g. a fluorophore or chromophore. One such method is described in WO 90/09455 and comprises the steps of (i) treating the pin bound exon with an oligonucleotide primer complementary to a portion thereof containing the mutation, extending the bound primer such that the extended product includes a detection element and separation element, separating the extended product into a fraction free of any detectable element which has not been incorporated into the extended product, and assaying this fraction for the detectable element (such as a fluorescent marker), the presence of which indicates presence of the mutation in the exon. This method may be characterized as a mini-sequencing method.
Another method is the oligonucleotide ligation assay (OLA) described in U.S. Pat. No. 4,998,617. In this method the possibility of covalently binding two oligonucleotide probes selected to anneal to immediately adjacent segments is studied, one of the segments having the possible mutation at the linking end. One of the probes has a separation element and the other a detectable element (such as a fluorescent marker). Correct base-pairing is necessary for covalent binding, and if only the mutation will permit correct base-pairing, the presence of the marker in a separated segment is indicative of the mutation.
It is understood that the above methods for detecting stable mutations will permit the use of one and the same pin for several exons. Thus, the pin may support, say, up to five different exons if a corresponding number of markers is used, e.g. five different chromophores. The possible number of exons per strip is therefore dependent on the number of different distinguishable markers available.
In the case of unstable changes, a complete sequencing of the exon in question will be necessary. In case both the DNA strands are to be sequenced, all eight pins 5 have to be used for the same exon, one pin per nucleotide and strand. It may, however, be sufficient to sequence only one strand, and in such a case four pins will be required per exon. This means that two exons may be tested with each pin strip, or alternatively the same exon from two patient samples. However, in the same way as mentioned above for stable mutations, it may also be possible to use one pin for two or more exons, utilizing several different markers.
Of course, sequencing of the exon may also be preferable in the case of an exon containing several stable mutations, as already mentioned above.
Sequencing reactions according to Sanger (dideoxy sequencing), for example, may be performed in per se known manner by dipping the pins into the wells of a corresponding well strip, the wells containing the necessary predispensed reagents (e.g. T7 DNA polymerase, nucleotides, nucleotide analogs, buffer).
If desired, two or more pin strips 3 may be assembled as described above, as may also the corresponding well strips 6. Hereby a test for several exons may be performed simultaneously and/or several patient samples be tested simultaneously.
The final detection of the exons identified by the reactions effected above is then performed.
In the case of stable mutations, the corresponding reaction mixtures in the wells 7 of the respective well strip 6 may be analysed by conventional manner in the fluorometer 9. In the case of the described mini-sequencing method, the result will be a quantification of the different bases incorporated into the sample. Since the incorporation is sequence-specific, it may thus easily be determined whether the patient is homozygous or heterozygous with respect to any one of the detected changes.
In the case of unstable mutations, on the other hand, the reaction contents of the wells 7 of the corresponding well strip(s) 3 are applied to the sequencer 10 for determining the DNA or RNA sequence of the exon. The result will thus be a determination of the fine structure of the exon, thereby permitting the details of complex genetic changes to be detected with great accuracy.
The final diagnosis will be obtained from the combined results of the two types of analyses performed.
A more detailed example of the performance of a test in accordance with the above procedures will now be described.
EXAMPLE
Purification of Genomic DNA
1. Apply <1 ml of blood into the well (on the membrane) of a preparation plate in the processing unit 1.
2. Close the lid of the unit and press the liquid through the membrane, the blood cells remaining on the latter.
3. Add ≈3 ml of wash buffer per well and press the liquid through the membrane. This step will wash away the red blood cells and leave the white cells on the membrane.
4. Add ≈1 ml of lysing buffer and incubate at room temperature.
5. Close the lid and press the liquid through the membrane. The genomic DNA preparation will now remain on the membrane.
6. Add 1-3 ml of wash buffer and press through the membrane.
7. Dissolve the DNA in a minimum amount of water.
8. Transfer 1 reaction volume to amplification tubes for processing in amplification unit 2.
Amplification
1. Add amplification reagent either as a stabilised totally integrated format (e.g. a dip stick having the reagents on one end) or as part components.
2. Incubate corresponding to 20-30 reaction cycles.
Reaction Chemistry
a) Stable Mutations
1. Add 20 μl of water to all wells 7 to be used.
2. Dip the exon-specific pin strip 3 into the amplification tubes as obtained after the amplification step and incubate for 5 minutes (annealing).
3. Lift up the pin strip 3 and dip it into a wash bath, wait for 10 seconds and then remove.
4. Shake off excess liquid with a quick shaking movement.
5. Dip the washed pin strip 3 into the reaction-specific well strip 6.
6. Incubate 5-10 minutes at room temperature (extension).
7. Repeat steps 3 and 4.
8. Measure the fluorescence in fluorometer 9.
b) Unstable Mutations
1. Add 20 μl of water to all wells 7 to be used.
2. Pipette the amplification reaction into 4 tubes in 4 equal volumes (≈20 μl).
3. Dip the exon-specific pin strip 3 into the amplification tubes as obtained after the amplification step and incubate for 5 minutes (annealing).
4. Lift up the pin strip 3 and dip it into a wash bath, wait for 10 seconds and then remove.
5. Shake off excess liquid with a quick shaking movement.
6. Dip the washed pin strip 3 into the reaction-specific well strip 6.
7. Incubate 5-10 minutes at room temperature (extension).
8. Repeat steps 4 and 5.
9. Transfer to stop solution and denature.
10. Apply to DNA sequencer and detect sequence.
The present invention is, of course, not restricted to the embodiments specifically described above and shown in the drawing, but many modifications and changes obvious to the skilled person may be made without departing from the scope of the inventive concept as defined in the following claims. The disclosure of all the patent applications and patents referred to hereinbefore is incorporated by reference herein. | In a method for molecular-biological analysis of genetic material, a genomic DNA or RNA preparation is tested for the presence of mutations. The processed DNA or RNA preparation is contacted with a first set(s) of interconnected solid phase members (5) supporting oligonucleotide primers to bind a defined DNA or RNA fragment that may contain a stable mutation to each solid phase member, and/or with a second set(s) of interconnected solid phase members (5) supporting oligonucleotide primers to bind a defined DNA or RNA fragment that may contain an unstable mutation or several stable mutations to each solid phase member. The solid phase members (5) of the first set(s) are introduced into a matching first set(s) of interconnected receptacles (7) with reaction mixtures for producing products which contain an incorporated marker when a supported DNA or RNA fragment has a mutation. The solid phase members (5) of the second set(s) are introduced into a matching second set(s) of interconnected receptacles (7) containing reaction mixtures for performing sequencing reactions. The contents of the presence of a marker indicating stable mutations is determined from the first set(s) of receptacles, and the sequence for the DNA or RNA fragments is determined from the second set(s) of receptacles. On the bases of these analyses, the genetic status of the genomic DNA or RNA material is determined. A system for performing such analyses is also disclosed. | 2 |
BACKGROUND OF THE INVENTION AND RELATED ART STATEMENT
[0001] The present invention relates to a webbing insertion member, such as a deflection fitting or shoulder anchor, for a shoulder webbing of a seat belt device.
[0002] As well known in the art, a seat belt device is installed in a high-speed vehicle, such as automobile and aircraft, for protecting an occupant by means of a webbing. For example, as for a seat belt device for a front seat of an automobile, the webbing is hooked by a deflection fitting or shoulder anchor disposed on a B-pillar of the automobile.
[0003] A deflection fitting of a known type comprises a plate-like metal body made of metal, a slip piece attached to the metal body, and a synthetic resin mold covering the metal body and the slip piece together.
[0004] The metal body has a bolt hole formed in an upper portion thereof for installation to the B-pillar and a webbing through opening formed in a lower portion thereof.
[0005] The slip piece has a groove in which an edge portion of the through opening is fitted, and a curved surface for guiding the webbing.
[0006] In a state that the edge portion of the webbing through opening is covered by the slip piece, the synthetic resin mold is formed by insert molding, thereby manufacturing a deflection fitting. The synthetic resin may be polyamide, such as nylon.
[0007] The deflection fitting employing such a slip piece has a problem that the slip piece easily slides off or comes off the metal body due to adverse factors, such as vibration, when the metal body with the slip piece is set in a mold for injection molding, especially in case of using an automatic molding apparatus.
[0008] It is an object of the present invention to provide a webbing insertion member with a structure for fixing a slip piece and a metal body and preventing the slip piece from sliding off the metal body even with adverse factors, such as vibration.
SUMMARY OF THE INVENTION
[0009] A webbing insertion member or shoulder anchor of the present invention has an opening through which a webbing is inserted. The webbing insertion member comprises a metal body formed with a through opening, a slip piece attached to an edge of the through opening, and a molding resin for fixing the slip piece to the metal body. In the webbing insertion member, one of the metal body and the slip piece has a first engaging member or convexity thereon, and the other of the metal body and the slip piece has a second engaging member, i.e. concavity or hole, engaging the first engaging member.
[0010] In the webbing insertion member of the present invention, since the convexity formed on one of the metal body and the slip piece is fitted in the concavity or hole formed in the other one, and the convexity is designed to hardly come off the concavity, there is no possibility that the slip piece slides off or comes off the metal body even with adverse factors, such as vibration, after the slip piece is attached to the metal body until the resin molding is completed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] [0011]FIG. 1 is a front view of a deflection fitting for a shoulder webbing as a webbing insertion member according to an embodiment of the present invention;
[0012] [0012]FIG. 2 is a sectional view of the deflection fitting taken along line 2 - 2 in FIG. 1;
[0013] [0013]FIG. 3( a ) is an explanatory view showing a structure of a metal body of the deflection fitting shown in FIG. 1; FIG. 3( b ) is a sectional view taken along line 3 ( b )- 3 ( b ) in FIG. 3( a ); and FIG. 3( c ) is a sectional view taken along line 3 ( c )- 3 ( c ) in FIG. 3( a );
[0014] [0014]FIG. 4( a ) is a perspective view showing a slip piece of the deflection fitting shown in FIG. 1; FIG. 4( b ) is a perspective view of the slip piece from an arrow 4 ( b ) in FIG. 4( a ); FIG. 4( c ) is a bottom view of the slip piece; and FIG. 4( d ) is a sectional view taken along line 4 ( d )- 4 ( d ) in FIG. 4( c ); and
[0015] FIGS. 5 ( a )- 5 ( c ) are explanatory views of the slip piece and the metal body, illustrating the engagement therebetween.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0016] Hereinafter, an embodiment of the present invention will be described with reference to FIG. 1 through FIG. 5.
[0017] [0017]FIG. 1 is a front view of a deflection fitting for a shoulder webbing as a webbing insertion member according to the embodiment of the present invention; FIG. 2 is a sectional view taken along line 2 - 2 in FIG. 1; FIGS. 3 ( a )- 3 ( c ) are explanatory views showing the configuration of a metal body of the deflection fitting; FIGS. 4 ( a )- 4 ( d ) are explanatory views showing the configuration of a slip piece, and FIGS. 5 ( a )- 5 ( c ) are explanatory views showing the engagement between the slip piece and the metal body. In detail, FIG. 3( a ) is a front view of the metal body of the deflection fitting; FIG. 3( b ) is a sectional view taken along line 3 ( b )- 3 ( b ) in FIG. 3( a ); FIG. 3( c ) is a sectional view taken along line 3 ( c )- 3 ( c ) in FIG. 3( a ); FIG. 4( a ) is a perspective view of the slip piece; FIG. 4( b ) is a perspective view taken from a direction of arrow B; FIG. 4( c ) is a bottom view of the slip piece; FIG. 4( d ) is a sectional view taken along line 4 ( d )- 4 ( d ) in FIG. 4( c ); FIG. 5( a ) is an exploded perspective view showing the metal body and the slip piece; FIG. 5( b ) is a perspective view showing the metal body in a state that the slip piece is attached thereto; and FIG. 5( c ) is a sectional view of main parts of the main body and the slip piece, illustrating the engagement therebetween.
[0018] A deflection fitting or shoulder anchor 1 comprises a plate-like metal body 2 made of metal, a slip piece 3 attached to the body 2 , and a synthetic resin mold 4 .
[0019] The metal body 2 has a bolt hole 2 a formed in an upper portion thereof for installation to the B-pillar, and a webbing through opening 2 b formed in a lower portion thereof. The metal body 2 also has a through hole 2 c for allowing communication between both surfaces of the metal body 2 . The synthetic resin mold 4 enters the through hole 2 c so as to increase the strength of connection between the synthetic resin mold 4 and the metal body 2 .
[0020] The slip piece 3 is made of metal or elastic material, such as synthetic resin, and is formed in a semi-cylindrical shape having a C-like section. The slip piece includes a curved surface 3 a at an upper surface, and inward flanges 3 b formed at both lower edges of the curved surface 3 a along the longitudinal direction. The inward flanges 3 b extend in a direction close to each other. Defined between the inward flanges 3 b is a groove 3 c into which an edge of the through opening 2 b is fitted. The slip piece 3 also has a ridge portion 3 d for sliding the webbing thereon, extending on the curved surface 3 a from both lower edges of the slip piece 3 . When the slip piece 3 is attached to the metal body 2 and the metal body 2 with the slip piece 3 is covered by the resin mold 4 , the ridge portion 3 d is not covered by the resin mold 4 to be exposed for forming a sliding portion for the webbing along the edge of the through opening 2 b.
[0021] As shown in FIG. 4( c ), formed on a middle portion of the edge, confronting the groove 3 c , of each of the inward flanges 3 b are small projections 5 and large projections 6 projecting toward the other inward flange 3 b , wherein the small projections 5 and the large projections 6 are alternatively arranged. Boundaries between the small projections 5 and the large projections 6 are recesses 7 , for allowing the large projections 6 to slightly and elastically move in the longitudinal direction of the slip piece 3 .
[0022] In this embodiment, two of the large projections 6 are provided for each inward flange 3 b . Formed between the large projections 6 is a concavity 8 which includes the recesses 7 and the small projection 5 between the large projections 6 . A convexity 9 , described later, of the metal body 2 is fitted into the concavity 8 . In the state before the slip piece 3 is attached to the metal body 2 , the width of the concavity 8 (distance between respective sides, facing each other, of the large projections 6 with the small projection 5 interposed therebetween) is slightly smaller than the width of the convexity 9 . A pair of large projections 6 , with a small projection 5 interposed therebetween, of the other inward flange 3 b are fitted in a concavity 11 , described later, of the metal body 2 in such a manner that the large projections 6 are sandwiched between the convexities 10 , also described later, of the metal body 2 . The distance between oppositely facing respective sides of the pair of the large projections 6 , with the small projection 5 interposed therebetween, (respective outer sides, coming in contact with the respective convexities 10 , of the pair of large projections 6 ) is slightly larger than the width of the concavity 11 .
[0023] The inward flanges 3 b are symmetrical about the groove 3 c so that the small projections 5 and large projections 6 formed on the respective inward flanges 3 b are formed in identical configurations, respectively, and are arranged to face the corresponding ones. The distance between the respective tops of the corresponding large projections 6 is slightly smaller than the distance between the oppositely facing respective tops of the convexities 9 , 10 through the thickness of the metal body 2 .
[0024] The slip piece 3 is attached to the lower edge of the through opening 2 b of the metal body 2 in such a manner that the lower edge of the through opening 2 b enters the groove 3 c of the slip piece 3 .
[0025] As shown in FIGS. 3 ( a )- 3 ( c ), the metal body 2 has the convexities 9 , 10 on both surfaces of a lower end portion below the through opening 2 b thereof at portions corresponding to the inward flanges 3 b when the slip piece 3 is attached. In this embodiment, one convexity 9 is formed on the front surface of the metal body 2 , and two convexities 10 are formed at a predetermined distance away from each other on the rear surface of the metal body 2 . The pair of convexities 10 on the rear surface of the metal body 2 defines the concavity 11 therebetween. When the slip piece 3 is attached to the metal body 2 , the convexity 9 is fitted into the concavity 8 of one of the inward flanges 3 b and the concavity 11 fits with the pair of large projections 6 of the other of the inward flanges 3 b.
[0026] The width of the convexity 9 is slightly larger than the width of the concavity 8 of the slip piece 3 while the width of the concavity 11 is smaller than the space between the oppositely facing respective sides of the projections 6 with the small projection 5 interposed therebetween. The distance between the respective tops of the convexities 9 and 10 through the thickness of the metal body 2 is slightly larger than the distance between the tops of the corresponding large projections 6 with the groove 3 c interposed therebetween. Accordingly, when the slip piece 3 is attached to the metal body 2 , the convexity of the metal body 2 is pressed into the concavity 8 of one of the inward flanges 3 b while the pair of large projections 6 of the other of the inward flanges 3 b is pressed into the concavity 11 of the main body 2 , because of the elasticity of the slip piece 3 . During this, the large projections 6 on both sides of the concavity 8 of the one inward flange 3 b elastically move in the directions apart from each other along the longitudinal direction of the slip piece 3 , whereby the concavity 8 receives the convexity 9 of the metal body 2 .
[0027] On the other hand, the large projections 6 of the other inward flange 3 b move in directions close to each other along the longitudinal direction of the slip piece 3 , whereby the large projections 6 are inserted into the concavity 11 . The large projections 6 on both sides of the concavity 8 receiving the convexity 9 bias the convexity 9 from both sides, while the large projections 6 inserted in the concavity 11 bias the convexities 10 on both sides of the concavity 11 outwardly, whereby the respective convexities hardly come off the respective concavities. As a result of this, the slip piece 3 is prevented from sliding off or coming off the metal body 2 even with adverse factors, such as vibration, after being attached to the metal body 2 .
[0028] After the slip piece 3 is attached to the lower edge of the webbing through an opening 2 b of the metal body 2 , the insert molding is conducted to form the synthetic resin mold 4 , thereby making the deflection fitting. The synthetic resin may be polyamide, such as nylon. Since the slip piece 3 is securely fixed to the metal body 2 as mentioned above, there is no possibility that the slip piece 3 slides off or comes off the metal body 2 due to adverse factors, such as vibration, caused by transportation into the mold for injection molding, after the slip piece 3 is attached to the metal body 2 until the insert molding is finished, thereby manufacturing the deflection fitting in which the molding is achieved with the slip piece 3 securely placed in a desired position.
[0029] As described above, according to the webbing insertion member of the present invention, for example, a deflection fitting as the webbing insertion has a metal body, and a slip piece to be attached to an edge of a webbing through opening of the metal body. One of the metal body and the slip piece has a convexity (or concavity) and the other of the metal body and the slip piece has a concavity (or convexity) for receiving the above convexity, i.e. fitted in the above concavity. The convexity is fitted into the concavity when the slip piece is attached. The configuration is designed such that the convexity hardly comes off the concavity, thereby preventing the slip piece from sliding off or coming off the metal body even with adverse factors, such as vibration, after being attached to the metal body. Therefore, even when the deflection fitting is manufactured by an automatic molding apparatus, the slip piece never slides off or comes off, thereby securely manufacturing the deflection fitting in which the resin molding is made with the slip piece placed in a desired position.
[0030] While the invention has been explained with reference to the specific embodiment of the invention, the explanation is illustrative and the invention is limited only by the appended claims. | A webbing insertion member is formed of a metal body having a through opening with an edge, a slip piece attached to the edge of the through opening for allowing a webbing to pass through the through opening above the slip piece, and a molding resin for fixing the slip piece to the metal body. A first engaging member is formed on one of the metal body and the slip piece, and a second engaging member is formed on the other of the metal body and the slip piece and engages the first engaging member so that the slip piece is securely engaged with the metal body. | 1 |
This invention relates to readmitting air into airtight containers. More specifically, this invention relates to readmitting air into on airtight containers such as Mason jars, using a check valve, that allows air to only flow out the container, an elastomeric seal member, and a retainer member that anchors the elastomeric seal member to the container and compresses the elastomeric seal member sufficiently for the elastomeric seal member to hold a vacuum. Air is readmitted into the container by applying a force on the check valve that sufficiently reduces the pressure on one segment of the elastomeric seal member to greatly accelerate air leakage into the container.
BACKGROUND OF THE INVENTION
People vacuum pack their foods to either retain fresh flavor or preserve food that would otherwise be thrown out. As such, the amortized cost of vacuum packing apparatus must be less than the cost of the food that users are trying to preserve. Further, the net savings must outweigh the inconvenience and time it takes to perform the vacuum packing operation. These economic factors dictate that vacuum packing systems be inexpensive and easy to operate. Further, they should be sufficiently compact to conveniently fit in crowded kitchens. Finally, vacuum packing systems must be reliable and consistently retain vacuums for extended periods.
With the exception of hermetic seals, all seals leak —it's just a matter of how slowly they leak. However, using appropriate materials with compatible lubricants, and applying sufficient sealing pressure, the leakage rate can be controlled to a level acceptable for the particular application.
Although the prior art is replete with simple and reliable mechanisms for evacuating air from containers, it contains few instances of simple and reliable mechanisms for readmitting air into vacuum containers. All air evacuation systems involve some sort of check valve —a generic term for a device that only allows fluids to flow in one direction. In contrast, air reentry systems can readmit air either through the same check valve that exhausted it (internal to the check valve), or through a path external to the check valve. The latter approach is inherently more reliable because making a check valve work in both directions compromises its effectiveness in at least one of the two directions. Further, bi-direction check valves generally require additional mechanisms that make them more complex and more expensive.
The internal and external are reentry approaches are illustrated in the sample of prior art examined in the following paragraphs. The internal air reentry approach embodied in U.S. Pat. No. 4,142,645 by Walton is simple, but cannot work as described. Walton discloses a check valve consisting of a ball 34 residing in an elastomeric nipple 32 featuring a conical bore 42 , and a valve seat 44 having a relatively small slant angle of approximately 5 degrees. A major issue with the Walton device is the plausible impossible approach for readmitting air. Walton postulates that “pinching the nipple 32 immediately below the level of the ball 34 ” will deform the valve seat 44 into an elliptical or oval shape in transverse cross section, thereby creating an air reentry path between the ball and the elastic tube. See FIG. 5 . This postulate is false. Although pressing on a hollow plastic tube will certainly flatten it out, pressing on a plastic tube containing a snugly-fitting ball 34 will not. This is because the ball 34 prevents diametric contraction of the tube in the vicinity of the ball, and diametric contraction in one direction must occur for the tube to expand in the perpendicular direction. Thus the circular tube cross section will remain circular, and the tube will simply compress tighter around the ball 34 . Although an artist can easily draw a ball positioned in an oval-shaped cross section ( FIG. 5 ), no such oval can be physically realized until the ball 34 is pushed out of intimate contact with the nipple 32 . Pressing sufficiently hard on the elastomeric tube can generate axial forces on the ball 34 that act to move the ball 34 up the tube. However, such axial forces will be resisted by atmospheric pressure as well as frictional forces between the nipple 32 and the ball 34 that are especially large if the nipple 32 has a small slant angle. Grossly compressing the nipple 32 can force the ball 34 into a larger conical section of the nipple 32 , but such compression can also pinch the tube completely closed, shutting off the air reentry path. Hence, Walton failed to disclose a combination of geometries and material properties of the nipple 32 and ball 34 that would allow the proposed air reentry method to work as postulated.
U.S. Pat. No. 6,619,493 B2 by Yang is another example of a two-way check valve that readmits air through a path internal to the check valve. The Yang approach is sound mechanically, but overly complex. Yang's approach consists of a curved diaphragm called a membrane piece 41 that rests atop a plurality of air holes 403 that lead to the inside of the container body 2 . Drawing a vacuum causes the membrane piece 41 to lift and allow air to flow out of the container body 2 and through the suction hole 32 . The membrane piece 41 has an integral pull rod 412 that is lifted upward by pressing on a push button 34 attached to the top of the cover 3 . Lifting the pull rod 412 upward unseats the membrane piece 41 allowing air to re-enter the container body 2 . The Yang apparatus for readmitting air will work, but consists of at least nine custom made parts, thereby increasing both complexity and cost. Further the housing 40 must be bonded air tight to the cover 3 , and Yan mentions using a high-frequency welding machine to create such a bond. Hence the complexity and special manufacturing operations drive up cost and thereby diminish the value to would-be users.
U.S. Pat. No. 5,405,038 by Chuang is another example of a two-way check valve that readmits air through a path internal to the check valve. The silicon piece 26 is a diaphragm that naturally opens upward during the air evacuation phase. For the air reentry phase, the user presses on a separate T-shaped button 27 that forces the center of the silicon piece 26 down and its edges up, thereby creating an air leakage path. Once again, the need for a number of additional ancillary components, plus their associated assembly operations, adds complexity and cost to the air reentry mechanism.
U.S. Pat. No. 6,131,753 by Lynch is an example of an air re-entry mechanism that is external to the check valve. The air re-entry path is via a center valve opening 34 . A spring 108 forces a ball 106 against the center valve opening 34 , thereby keeping it closed when the container is under vacuum. The vacuum is released by pulling up on a cable 112 that has one end attached to the ball 106 and the other end attached to a pull ring 104 . Lynch's valve relief assembly 100 consists of at least six different custom parts that must be manufactured and assembled to accomplish the air reentry task. Thus the Lynch device suffers from the same inherent cost penalty as the Yang device.
Air reentry systems must retain vacuums when the air reentry mechanisms are not in operation. Hence, a designer needs a quantitative understanding of how an air reentry system must be designed to preserve a vacuum. A commonly used method for retaining vacuums is to use elastomeric seals. However, to effectively retain a vacuum, the elastomeric seal member must be compressed sufficiently to limit leakage to an acceptable rate. More specifically, the elastomeric seal member must be lubricated and compressed sufficiently, in terms of pounds per linear inch, depending on the material properties of the elastomeric sealing material and the acceptable leak rate. For example, O Rings used as face compression seals typically have a Shore A Hardness of 70 (which represents a compromise between compressibility and durability). Face compression O Rings must be compressed between 20% and 30% to produce a sufficient load, measured in pounds per liner inch, to create long-lasting seals. For an O Ring having a Shore A Hardness 70, and a cross sectional diameter of 0.103 inches, the minimum recommended compression load is approximately 10.3 pounds per linear inch. Accordingly, for a standard AS568A-107 O Ring, that has a mean diameter of 0.309 inches, the total force required to achieve 10.3 pounds per linear inch is 9.99 pounds. This load can be generated by a combination of atmospheric pressure and force applied to the check valve for on external source. In the case of the AS568A-107 O Ring, the maximum load obtainable from atmospheric pressure is 1.1 pounds. This means that 8.9 additional pounds must be applied to the O Ring. This may be done with a spring-like mechanism that anchors the assembly together. This disclosure refers to such a spring-like anchor element as a retainer member. Thus, in the general case, the minimum number of parts to evacuate air from a container using an off-the-shelf check valve is three: a check valve, an elastomeric seal member, and a spring-like retainer member. The objective of this invention is to implement the vacuum release (air re-entry) mechanism with such a minimum number of parts.
Air may be readmitted into a vacuum container outfitted with a check valve and elastomeric seal member in one of three ways. The first way is to install a completely separate mechanism that may be opened and closed, such as a plug that fits into a valve or hole. This method is straight forward but requires two additional parts. A second method is to pull up on the check valve with sufficient force to unseat the elastomeric seal member. There are several disadvantages of this approach. First, a relatively high pulling load is required for even a small elastomeric seal member. For example, as already noted, the AS568A-107 O Ring requires a pre-load of approximately 9 pounds to retain a vacuum, and overcoming this large a force may be difficult for some users. A second disadvantage is the high pulling force may damage the retainer member, check valve, or the container lid. Finally, the check valve might have to be outfitted with a loop or some other pulling device to allow users to get a sufficiently strong grip on the check valve.
A third approach is not to unseat the elastomeric seal member at all, but rather lower the compressive load over a segment of the elastomer seal to allow air to leak between the elastomeric seal member and the container lid or container wall. This is the preferred approach and the one disclosed herein. This approach can be implemented by applying a lateral load to the side of the check valve. Doing so causes the check valve to tilt away from the applied load, thereby increasing compression on the opposite side of the elastomeric seal member, and decreasing compression on the side of the elastomeric seal member where the load is applied. The advantage of this approach is that it requires no additional parts. The only requirements are (1) the elastomeric seal member be sufficiently thick, and the check valve diameter be sufficiently small, to allow the check valve to tilt enough to greatly relieve the pressure on a segment of the elastomer seal, and (2) the retainer member be flexible enough to permit such movement. For example, for an AS568A-107 O Ring having a 0.103 inch thick uncompressed cross section and a 0.309 inch mean diameter, the check valve would have to be free to tilt approximately 7.6 degrees to decompress one segment of the O Ring. Accordingly, the check valve diameter must be small enough not to contact the lid when the check valve is tilted 7.6 degrees, and the retainer member must allow such a range of motion.
Prior art has not considered selectively lowering the contact pressure on one segment of an elastomeric seal member to allow air to leak past the elastomeric seal member. This is because elastomeric seal members such as O Rings are primarily intended to prevent fluid flow, not enhance it. In those instances of the prior art wherein an elastomeric seal member had to act as a switch, allowing fluid to flow past it on command, the conventional practice was to completely unseat the elastomeric seal member by disengaging it from the mating part.
In summary, a reliable and cost-effective method is needed for readmitting air into vacuum containers. The ideal method would not require a separate plug, cover, or any other ancillary part to prevent air from re-entering the vacuumed container. Such a method and apparatus are disclosed in the present invention. The present invention addresses the complexity and cost issues of prior art by devising an air re-entry system that consists of only three parts. Further, all three parts are commonly available, off-the-shelf components that can be supplied by multiple vendors. This not only avoids investments in custom manufacturing tooling, but also allows the present invention to benefit from economies of scale associated with off-the-shelf parts.
BRIEF SUMMARY OF THE INVENTION
This invention is a method and apparatus for inexpensively, and repeatedly, readmitting air into a vacuum container. The vacuum release mechanism consists of three components: a check valve that allows air to flow out the container; an elastomeric seal member, such as an O Ring, that fits between the check valve and the container body or lid; and a retainer member that flexibly anchors the check valve to the container and applies sufficient force to the elastomeric seal to yield a long-lasting seal. Air is readmitted into a vacuumed container by applying a force to the check valve, which decompresses, rather than displaces, a segment of the elastomeric seal member. This decompression is sufficient to allow air to rapidly leak past the elastomer seal member.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the vacuum packing and releasing system in accordance with the present invention;
FIG. 2 is an enlarged view of the check valve, retainer member and cap members in accordance with the present invention;
FIG. 3 shows a check valve mounted on the outside of a container, and in the tilted position that preferentially compresses one segment of an O Ring and decompresses the opposite side of the O Ring
FIG. 4 shows a check valve and O Ring mounted on the inside of a container, with the retainer member mounted on the outside of the container, thereby enabling air to reenter the container by pressing down on the top of the retainer member.
DETAILED DESCRIPTION OF THE INVENTION
This invention readmits air into vacuum containers by shifting an assembly of parts rather than disengaging them. The assembly consists of an elastomeric sealing member, a retainer member, and a check valve.
This invention takes advantage of the inverse relationship between the leakage rate of an elastomeric seal its sealing pressure to simply and reliably readmit air into vacuum containers. The higher the sealing pressure, the less leakage there is between the elastomeric member and its mating surface. Elastomeric seals, such as O Rings, are designed to prevent the flow of air and fluids in both directions by compressing the elastomeric seal against a mating surface with sufficient pressure to inhibit flow between the two components. As such, in conventional systems, air only flows past O Rings when the O Rings are mechanically disengaged from their mating surfaces. The invention disclosed herein uses elastomeric sealing members in a different way so as to create a two-way, on-command valve. In the present invention, the elastomeric sealing member is compressed by the retainer member that holds the assembly together. The present system creates an air reentry path by sufficiently decompressing a segment of the elastomeric seal member to allow it to leak. The elastomeric seal member is decompressed by applying a force to a mating member, such as the check valve, that causes the mating member to shift and thereby decompress a segment of the elastomeric seal member.
In accordance with the previous paragraph, the elastomeric seal member is sandwiched between the check valve and a container wall, or lid. The retainer member holds the assembly together and is flexible enough to allow the check valve to move in both the lateral and vertical directions. Further, the retainer member compresses the elastomeric seal member sufficiently to retain a vacuum when the container is not fully vacuumed, as is the case at the start of the vacuum packing process. Finally, the retainer member contains passageways that provide unobstructed paths for air to reenter the container.
FIG. 1 shows an exploded view a vacuum packing system, comprising a vacuum assembly 1 and a vacuum container 30 . The vacuum assembly 1 is the subject of the present invention and comprises a check valve 2 , an elastomeric seal member 7 , such as O Ring, lid 8 , retainer member 12 , and cap 17 . The check valve 2 features a body 24 , as exhaust port 3 , an inlet port 4 , an inlet stem 5 , and a barb 6 . The check valve body 24 has internal components (not shown) that only allow air to pass from the inlet port 4 through the exhaust port 3 . The compliant elastomeric seal 7 is sandwiched between a lid 8 to prevent air from from reentering the vacuum container 30 through the interface between the check valve 2 and the lid 8 , until the user desires such air reentry to take place. The lid 8 features a circular metal disk 9 , a sealing material 10 bonded to the outer perimeter of the disk 9 , and a hole 11 through which the check valve 2 is inserted. The barb 6 passes freely through the hole 11 . Air is evacuated from the airtight container through the check valve 2 . Air is readmitted into the container by applying a force to the check valve 2 that causes the check valve 2 to tilt or translate away from the applied force. Such motion of the check valve 2 decompresses a segment of the elastomeric seal 7 on the same side of the applied force, thereby causing that segment of the elastomeric seal 7 to noticeably leak. The force on the check valve may be applied, by hand, without using any tools.
FIG. 1 also shows the compliant retainer member 12 that holds the vacuum assembly 1 together by sliding along the inlet stem 5 of the check valve 2 until the bottom edge of the retainer member 12 has traveled past the barb 6 on the inlet stem 5 . The compliant retainer member 12 is made of a flexible material that allows it to expand and slide over the barb 6 in one direction, but resists sliding down the inlet stem 5 in the other direction, unless forcibly removed. The retainer member 12 may be made of any material, including metal coils or spring leaf metal, that latches together the components of the feed through assembly 1 , yet provides an unobstructed air path between the interior of the container 30 and the elastomeric seal 7 . The latching force provided by the retainer member 12 generates enough pressure on the elastomeric seal 7 to prevent air from passing into or out of the container 30 when the seal 7 is properly seated.
FIG. 1 also shows a cap 17 that fits over the retainer member 12 to inhibit fluids and solid particles inside the container 30 from being sucked into the inlet port 4 during the vacuuming process. The cap 17 slides over the retainer member 12 and anchors to it. In the case where the retainer member 12 is made from an elastomeric material, the cap 17 anchors to the retainer member 12 by means of a compression fit. Although the preferred material for the cap 17 is substantially rigid plastic, the cap 17 may also be made of compliant materials.
FIG. 2 shows enlarged views of the check valve 2 , the retainer member 12 , and the cap 17 . The retainer member 12 has a hole 13 running through its entire height, from the top surface 14 to its bottom surface 16 . This hole allows the retainer member 12 to slide over the stem 5 until its bottom surface 16 is restrained by the barb 6 . Another feature of the retainer member 12 is a slot 15 that allows air to freely pass between the interior of the container 30 and the compliant seal 7 . Such free air flow is also enabled by the diameter of the lid hole 11 being larger than the diameter of the stem 5 . The enlarged view of the cap 17 reveals splines 19 that run along its interior and create a compression fit between the cap 17 and the retainer member 12 .
The cap 17 features sloped sides 18 that facilitate installation on the retainer member 12 . The height of the cap 17 is chosen to prevent its top surface 20 from contacting the bottom surface of the lid 8 and restricting air flow into and out of the vacuum container 30 .
FIG. 3 shows the preferred embodiment of the invention wherein the check valve 2 is in the tilted position. Such a tilt is caused by applying a force on the right side of the check valve 2 . As a result, the left side of the O Ring 22 is compressed more than it was when the assembly was in the neutral position with the check valve 2 pointing vertically. Concurrently, the right side of the O Ring 21 is decompressed, but remains in contact with the check valve 2 on one side, and the outside of the vacuum container 91 on the other side. The decompressed segment of the O Ring 21 allows air to reenter the container (not shown), through the interface between the outside of the vacuum container 91 and the decompressed segment of the O Ring 21 . The retainer member 12 is shown in its compressed position.
FIG. 4 shows an alternate embodiment of the invention in which the body of the check valve 2 resides inside the vacuum container (not shown). The O Ring 22 is compressed by the retainer member 12 that resides outside the vacuum container (not shown), and surrounds the exhaust stem 31 of the check valve 2 . The retainer member 12 incorporates passageways, not shown in this figure, that allow air to flow either around the retainer member 12 , or through it were the air not blocked by the compressed O Ring 22 , Air is made to reenter the container by pressing down on the retainer member 12 , thereby relieving the pressure on the O Ring 22 and allowing air to leak through the interface between the O Ring 22 and the inner surface of the container 92 . No force needs be applied to the exhaust port 3 of the check valve 2 because relieving the pressure on the O Ring 22 automatically causes the check valve 2 to move downward, driven by the decompressing O Ring 22 . The main advantage of this embodiment is that it may he easier for some users to apply a downward (axial) force than a lateral force, particularly elderly individuals. Further, some users may find it more intuitive to apply a downward force, rather than a lateral force, to relieve the vacuum, Finally, applying an axial force to the retainer member 12 avoids imparting bending loads to the check valve 2 that might overstress fragile elements such as the inlet stem 5 or the exhaust stem 31 .
Numerous modifications to and alternative embodiments of the present invention will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best modes of carrying out the invention. Details of the system may be varied substantially without departing from the spirit of the invention and the exclusive use of all modifications which come within the scope of the appended claims is reserved. | The present invention is a method and apparatus for readmitting air into vacuum containers, such as canning jars, by incorporating a flexibly-mounted check valve in the container lid or body, and sandwiching an elastomeric seal member, such as an O Ring, between the check valve and the vacuum container's lid or wall. The check valve is flexibly mounted to the airtight container by a retainer member that permits the check valve to move vertically and horizontally and compresses the elastomeric seal member sufficiently to prevent leakage. Air is readmitted into the vacuum container by applying a force to the check valve that sufficiently decompresses a segment of the elastomeric seal member to cause leakage. The displacement force on the check valve may be applied by hand, without using any tools. | 1 |
CROSS-RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application Ser. No. 10/885,878, filed Jul. 8, 2004, which claims priority to PCT/US03/00379, filed Jan. 8, 2003, which claims the benefit of provisional application 60/345,650 filed Jan. 8, 2002, all three of which are hereby incorporated by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to active agent delivery systems and methods for protecting and administering active agents. More specifically, the invention is directed to active agent complexes or conjugates which utilize dendritic encapsulation alone or in combination with other delivery systems to improve and target active agent release.
[0003] In addition to their common meaning the following terms may further be defined as follows. Scaffold: a molecular entity whereby multiple agents can be attached to form a dendritic structure. Dendritic glycopeptide: a construct of multiple polysaccharides covalently attached to a central peptide. Dendrite: multiple polysaccharides branching from a central scaffold. Ligation: the formation of non-covalent bonds between two molecular entities; the energy of the bond being derived from lipophilic interactions, hydrogen bonding, Van der Waals forces or ionic bonding.
[0004] Therapeutic peptide: a pharmaceutically active molecule that is made of amino acids linked through amide bonds. Peptide-drug conjugate: a molecular construct comprised of a peptide and a small molecule covalently bonded. Peptide is meant to include small peptide chains, i.e. 2-10 amino acids, as well as larger oligopeptides and polypeptides.
[0005] Internal release mechanism: a mechanism where a masked nucleophilic moiety in close proximity to an active agent attached to a cleavage site on the same molecule, affects cleavage after the nucleophile is unmasked thereby releasing the active agent.
SUMMARY OF THE INVENTION
[0006] The invention provides for a pharmaceutical composition comprising an active agent bound to a peptide scaffold for dendritic encapsulation wherein said peptide scaffold is covalently attached to a polysaccharide. The peptide scaffold may serve as a ligand for non-covalent binding of an active agent. In one embodiment the active agent is a peptide-drug conjugate. In another embodiment the peptide scaffold serves as a ligand for covalent binding of an active agent. The active agent for instance may also be an azo compound or a nitro compound.
[0007] In another embodiment the active agent is non-covalently incorporated into the higher order structure of the polysaccharide dendrite. In one embodiment of the invention, the non-covalent incorporation is a result of ligand-receptor interaction, lipophilic interactions, Van der Waals forces, ionic bonding, hydrogen bonding.
[0008] In another embodiment the active agent is covalently incorporated into the polysaccharide dendrite. The covalent incorporation may be a result of an azide, amide, thioester, disulfide, ester, carbonate, carbamate or ureide bond. Further, the active agent may be attached to the scaffold via the side chains, the amino terminal residue, the carboxy terminal residue, or combinations thereof. In another embodiment, the non-attached portion of the amino acid, oligopeptide, polypeptide or polysaccharide is in its natural form (e.g. unprotected).
[0009] In another embodiment, an active agent is covalently attached to a peptide and the peptide active agent conjugate is further attached to a polysaccharide dendrite.
[0010] Various embodiments of the invention provide for delivery of the active agent through mediated release under specific body conditions. For instance, the invention may be formulated to release the pharmaceutically active compound in the colon, small intestine, or stomach depending on the formulation. The invention provides for the mediated delivery mechanisms, for instance, following oral, parenterally, injection or inhalation.
[0011] In another embodiment of the invention, the scaffold comprises a plant glycoside. The plant glycoside may be for instance, a glycosylated flavanol, diterpenoid, anthraquinone or like substance. In one embodiment, the plant glycoside serves as a scaffold for covalent attachment of a polysaccharide. In another embodiment, the plant glycoside serves as a scaffold for non-covalent attachment of a peptide active agent conjugate. In other embodiment, the plant glycoside serves as a scaffold for covalent attachment of a peptide active agent conjugate. In another embodiment, the plant glycoside serves as a scaffold for covalent attachment of a small molecule active agent.
[0012] Further, the invention provides for a pharmaceutical composition comprised of a peptide (or oligonucleotide) incorporating polysaccharide dendrites for delivery of a pharmaceutically active compound wherein the peptide (or oligonucleotide) serves as a scaffold for dendritic encapsulation by covalent attachment of polysaccharides. Alternatively, the peptide (or oligonucleotide) scaffold may serve as a ligand for non-covalent binding of a therapeutic peptide (or peptide-drug conjugate). Further, the peptide (or oligonucleotide) scaffold may serve as a point of covalent attachment for the therapeutic peptide (or peptide-drug conjugate).
[0013] The invention also provides for a pharmaceutical composition wherein a therapeutic peptide is bound to the peptide (or oligonucleotide) incorporating polysaccharide dendrites. The therapeutic peptide may be non-covalently (e.g. ligand-receptor interaction, lipophilic interactions, Van der Waals forces, ionic bonding, hydrogen bonding) attached to the scaffold peptide (or oligonucleotide). Alternatively, the therapeutic peptide is covalently attached to the peptide (or oligonucleotide) incorporating polysaccharide dendrites. Further, the therapeutic peptide may be covalently (e.g. azide, amide, thioester, disulfide, ester, carbonate, carbamate or ureide bonds) attached via the side chains and/or the amino terminal and/or carboxy terminal residues of the scaffold.
[0014] The invention also provides for a pharmaceutical composition wherein a peptide containing a pharmaceutically active compound covalently attached to it is attached to the peptide (or oligonucleotide) containing polysaccharide dendrites, (e.g. a peptide-drug conjugate delivered by dendritic encapsulation).
[0015] The invention also provides a pharmaceutical composition comprised of a plant glycoside aglycone (e.g., flavanol, diterpenoid or anthraquinone) which incorporates polysaccharide dendrites for delivery of a pharmaceutically active compound wherein the aglycone serves as a scaffold for dendritic encapsulation by covalent attachment of polysaccharides. Alternatively, the aglycone scaffold may serve as a ligand for non-covalent binding of a therapeutic peptide (or peptide-drug conjugate). The aglycone scaffold may serve as a point of covalent attachment for the therapeutic peptide (or peptide-drug conjugate). Further, the aglycone scaffold may serve as a point of covalent attachment for a small molecule therapeutic agent.
[0016] The invention also provides a pharmaceutical composition comprised of an azo compound or a nitro compound incorporating polysaccharide dendrites for delivery of a pharmaceutically active compound wherein the azo compound or a nitro compound serves as a scaffold for dendritic encapsulation by covalent attachment of polysaccharides. Alternatively, the azo compound or a nitro compound scaffold may serve as a ligand for non-covalent binding of a therapeutic peptide (or peptide-drug conjugate). The azo compound or a nitro compound scaffold may serve also as a point of covalent attachment for the therapeutic peptide (or peptide-drug conjugate). Further, the azo compound or a nitro compound scaffold may serve as a point of covalent attachment for a small molecule therapeutic agent. In another embodiment the azo compound or nitro compound are not scaffolds for dendritic encapsulation.
[0017] The invention provides the ability to design active agent complexes that result in specific delivery of the active agent. For instance active agents may be selectively delivered to the colon via protection of pharmaceutically active agent from enzymatic digestion by stomach and small intestinal enzymes. In another embodiment, the active agent may be protected from serum enzymes, liver metabolism, and elimination by kidneys. Additionally, another embodiment provides protection of pharmaceutically active agent from enzymes in the respiratory tract (e.g. elastase).
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 provides a diagram of a proposed dendritic construct.
[0019] FIG. 2 depicts the structure of A, B and H blood group antigens of mucin.
[0020] FIG. 3 depicts a schematic of Quercitin glycoside covalently attached to a drug via a carbonate linkage.
[0021] FIG. 4 depicts the schematic release of drug conjugated to an azo compound via carbonate linkage.
[0022] FIG. 5 depicts the schematic release of drug conjugated to a nitro compound via a carbonate linkage.
DETAILED DESCRIPTION
[0023] For almost all of the drugs in the Pharmacopoeia the majority of absorption, if not all of it, occurs in the small intestine. For some drugs, however, absorption may occur in the colon (e.g. analgesics); the relative extent of absorption has not been well studied, however. Sustaining the release of drugs would improve their clinical efficacy, especially for drugs requiring multiple dosing or where their therapeutic window is somewhat narrow. For those drugs that could benefit from sustained release pharmacokinetics and are absorbed in the colon, providing additional availability to the colon would be a significant improvement. This increased efficacy is more pronounced by the realization that the transit time in the colon can be as much as ten times that of the small intestine.
[0024] Some of the drugs that are used to treat ulcerative colitis include 5-aminosalicylates (e.g. mesalamine), corticosteroids (e.g. dexamethasone), metronidazole, 6-mercaptopurine, methotrexate and cyclosporine. Delivering these drugs to the colon specifically should improve their efficacy. Delivery of small peptides, such as cyclosporine, to the colon is especially challenging given the peptidase activity in the small intestines. Dexamethasone has been delivered to the colon by combining it with dextran. Furthermore, both metronidazole and celecoxib have been targeted for colonic delivery using guar gum as a carrier.
[0025] Delivery of drugs to certain regions or organs of the body can be accomplished by protecting the drug from decomposition and/or from attachment to binding sites prior to the drug reaching the target site. Micellar encapsulation, polymeric formulation and enteric coating are a few examples of methods used to “protect” a drug in vivo. There a very few examples, however, that exploit the enzymatic specificity in the colon to affect active agent release from the protective agent.
[0026] Perhaps the most appropriate protective agent for colonic delivery is a polysaccharide and for good reason. Polysaccharides are more resistant to hydrolysis in the stomach and small intestines than in the colon. This is because the majority of glycosidases that exist in the animal are actually secreted by bacteria and the colon has, by far, the greatest population of microflora in a healthy animal. It should be pointed out, however, that there are other classes of compounds known to pass through the small intestines into the colon, which include plant glycosides, azo compounds and nitro compounds.
[0027] In dendritic encapsulation ( FIG. 1 ), the therapeutic agent is bound to a core molecular entity, the scaffold. The scaffold can be any multifunctional molecule allowing for attachment of the therapeutic agent and at least one saccharide moiety. The scaffold is selected from a group consisting of amino acids, carbohydrates, purines or combinations thereof. The therapeutic agent can be linked to the scaffold by a covalent bond that is readily hydrolyzed under physiological conditions (i.e. azide, thioester, disulfide, ester, carbonate, carbamate or ureide). Alternatively, the scaffold and the therapeutic agent can be non-covalently bound to each other. In either case, the scaffold serves as a platform to which multiple polysaccharide chains can be affixed. By varying chain length and composition, the polysaccharides will provide a shell enclosing the scaffold and the therapeutic agent. This “shell” prevents absorption of the therapeutic agent and shields peptidic therapeutic agents from digestive enzymes in the stomach and intestines. Microflora in the colon break down the polysaccharide coating exposing the scaffold-therapeutic linkage, making it accessible for hydrolysis and release of the drug.
[0028] The digestive properties of the polysaccharides in different organs can be used to select the polysaccharide portion of the dendritic construct. For example, starch is digested in the small intestines and may not be the ideal polysaccharide for dendritic encapsulation. Non-starch polysaccharides, on the other hand, escape intestinal digestion and thus may be a viable candidate for dendritic encapsulation. Some low molecular weight dietary carbohydrates, such as stachyose and raffinose, are not digested in the small intestines. Even some disaccharides, such as lactulose, palatinose, maltitol and lactitol have been shown to reach the colon in large proportion relative to what was ingested.
[0029] Glycosidases secreted by colonic bacteria are capable of digesting a wide variety of carbohydrates. Most of the carbohydrate source is dietary although a significant portion comes from mucin that is sloughed off from the intestinal wall and is metabolized by mucin oligosaccharide degrading (MOD) bacteria in the colon. Mucin is a complex glycopeptide, where the glycan portion is typically branched and usually consists of reducing sugars, facose, sialic acid and amino sugars. It is important to recognize that the oligosaccharide side chains of mucin help protect the peptide core from proteolytic digestion. Sialic acid confers significant hydrolytic resistance and thus it is a preferred embodiment of this invention that sialic acid be a part of the dendrite composition. Alternatively, A, B, or H blood group antigens ( FIG. 2 ), which are part of mucin, would also confer resistance to hydrolysis in the small intestines. Bifidobacterium , which are a major species in the healthy colon are reported to have unique capabilities to hydrolyze N-acetylhexosamines. Thus it is a further preferred embodiment of this invention that A, B or H blood group antigens make up a portion of or all of the dendrite composition.
A. Dendritic Polysaccharide Encapsulation Platform for Peptide Drug Delivery
[0030] The present invention provides a means for a pharmaceutical composition comprised of a dendritic glycopeptide (i.e. the scaffold and the dendrite) for delivery of a pharmaceutically active compound. The pharmaceutically active compound can be a peptide, oligonucleotide or an active agent covalently bound to a peptide.
[0031] Peptide-based scaffolds are amenable to the preparation of combinatorial libraries by both chemical and recombinant methods. These libraries can in turn be screened to identify candidates that bind the pharmaceutical target through non-covalent/ligand interactions. Thus, peptides provide a powerful means of generating scaffolds suitable for use with peptide and non-peptide therapeutics that are not compatible with an approach that involves chemical/covalent ligation of the therapeutic agent to the scaffold. Thus it is a preferred embodiment of the invention that the peptide serves as a scaffold for dendritic encapsulation through the covalent attachment of polysaccharides. The peptide scaffold also serves as a ligand for non-covalent binding of a therapeutic peptide or peptide-drug conjugate. The therapeutic peptide is non-covalently attached through a ligand-receptor interaction, ionic bonding, or hydrogen bond to the scaffold peptide. Another potential advantage of this approach is that “ligation” reactions can be carried out under mild aqueous conditions, thus preserving the fold and integrity of a peptide therapeutic.
[0032] In another embodiment, the recombinant organism can be genetically engineered to glycosylate the peptide scaffold specifically. This would preclude the need to covalently add the polysaccharide dendrite.
[0033] Further, the peptide scaffold may serve as a point of covalent attachment for the therapeutic peptide or peptide-drug conjugate. The pharmaceutical composition of the present invention allows for the therapeutic peptide to be covalently attached to the dendritic glycopeptide. In this case the therapeutic peptide is covalently attached via an azide, amide, thioester, disulfide, ester, carbonate, carbamate or ureide bond to the side chains and/or the amino terminal and/or carboxy terminal residues of the scaffold.
[0034] In a further embodiment of the invention, the peptide therapeutic agent or therapeutic agent/peptide conjugate is attached to the peptide scaffold via a linker. In this case the linker is covalently attached via an azide, amide, thioester, disulfide, ester, carbonate, carbamate or ureide bond to the side chains and/or the amino terminal and/or carboxy terminal residues of the scaffold. The linker, then, is exposed to cleavage by intestinal enzymes after the polysaccharide dendrite is cleaved off the scaffold by bacterial glycosidases.
[0035] The present invention also embodies a pharmaceutical composition wherein a peptide containing a pharmaceutically active compound covalently attached to it is also attached to a dendritic glycopeptide. For example, a peptide-drug conjugate delivered through the present dendritic encapsulation composition.
B. Dendritic Polysaccharide Encapsulation Platform for Small Molecule Drug Delivery
[0036] Another embodiment of the present invention includes a pharmaceutical composition wherein a pharmaceutically active small molecule is delivered to the colon. One advantage of the present invention is the specific delivery to the colon of pharmaceutically active compounds through protection of the active agent from enzymatic digestion by stomach and enzymes in the small intestine. This allows for improved delivery of the active agents to the colon.
[0037] It is an embodiment of the invention that the pharmaceutically active agent be dendritically encapsulated with a polysaccharide covalently attached to a scaffold. A further embodiment of the invention is that the scaffold is a peptide or oligonucleotide.
[0038] In yet a further embodiment of the invention the scaffold is a flavanol, diterpenoid or anthraquinone. Flavanols (e.g. quercitin), diterpenoids (e.g. stevioside), or anthraquinones (e.g., franguloside) are the aglycone portion of plants glycosides. Some of these plant glycosides are not absorbed in the small intestine and thus make it to the colon. Colonic microflora secrete β-glycosidases that can metabolize plant glycosides releasing the aglycone from the sugar moiety.
[0039] In an embodiment of this invention, an aglycone component of a glycoside can either be covalently attached to the active agent or ligated to the active agent through non-covalent bonding. In the case where the aglycone is covalently attached to the active agent, bacterial glycosidase action will release the aglycone, thus freeing up a hydroxyl group that, in turn, participates in an intramolecular rearrangement releasing the active agent intact. Thus it is a further embodiment of this invention that active agents can be released from a protective agent by an internal release mechanism (IRM) that is available only after enzymatic action occurs on the entire pharmaceutical construct ( FIG. 3 ). In the case where the aglycone is not covalently attached the peptidase action will release the active agent by dissociation and no internal release mechanism is required for active agent release.
[0040] In another embodiment of the invention the scaffold is an azo compound or a nitro compound. Colonic bacteria possess the unique capability of reducing azo groups and nitro groups to amines. An active agent can be covalently attached to a molecule that also has an azo group ( FIG. 4 ) or a nitro group ( FIG. 5 ) in close proximity to the active agent bond. The polysaccharide dendrite is not shown in the figures but can be attached anywhere on the scaffolds. Further, if the azo scaffold or nitro scaffold can pass through the small intestines without being absorbed a polysaccharide dendrite would not be necessary.
[0041] An appropriately designed active agent conjugate will pass through the small intestines to the colon. In the colon, azoreductase or nitroreductase action will reduce the functionality to an amino group, which is now available for intramolecular cleavage of the bond that holds the active agent. Thus, it is a further embodiment of this invention to apply the IRM to masked amino groups as well. It is a preferred embodiment that the masked amino group be an azo compound or a nitro compound.
[0000] C. Dendritic Polysaccharide Encapsulation Platform for Drug Delivery Other than Colonic
[0042] Another embodiment and advantage of the present invention is a pharmaceutical composition wherein a pharmaceutically active compound may be delivered parenterally. The present composition provides protection of pharmaceutically active compounds for example from serum enzymes, liver metabolism, and elimination by kidneys.
[0043] Another advantage and embodiment of the present invention allow for a pharmaceutical composition wherein a pharmaceutically active compound is delivered by inhalation. The present composition provides protection of pharmaceutically active compound from enzymes in the respiratory tract for example, elastase.
[0044] Other embodiments and advantages will be apparent from the non-limiting examples described below.
EXAMPLES
[0045] Hydrocodone, an opioid antagonist, was chosen as a model compound for the hypothesis that conjugates of opioid drugs can afford extended release.
Example 1
Preparation of the Chloroformate of 2,3-O-isopropylidene-1-methoxy-D-ribofuranose
[0046]
[0000]
Reagents
MW
Weight
mmoles
Molar Equivalents
2,3-O-isopropylidene-1-methoxy-D-
204
1.00
g
3.85
1
ribofuranose
20% Phosgene in toluene
—
25
ml
—
—
Chloroformate of 2,3-O-isopropylidene-1-methoxy-D-ribofuranose
[0047] To a stirring solution of 20% phosgene in toluene under an inert atmosphere was added 2,3-O-isopropylidene-1-methoxy-D-ribofaranose via syringe. The resulting clear, colorless solution was stirred at ambient temperature for 30 minutes. After stirring, Ar(g) was bubbled through the solution for approximately 20 minutes to remove any excess phosgene. Solvent was then removed and product dried under vacuum for 18 hours. Product was used without further purification or characterization.
Example 2
Preparation of Ribo-Hydrocodone
[0048]
[0000]
Molar
Reagents
MW
Weight
mmoles
Equivalents
Hydrocodone
299
0.733 g
2.45
1.0
1. LiN(TMS) 2 in THF
1 M
3.68 ml
3.68
1.5
1. DMF
—
8 ml
—
—
2. Ribose Chloroformate
—
—
4.90
2.0
2. DMF
—
3 ml
—
—
3. 1 M HCl
1 M
10 ml
—
—
[0049] To a solution of hydrocodone in DMF was added LiN(TMS) 2 in THF via syringe. The solution was stirred at ambient temperatures for 5 minutes then the chloroformate of ribose in DMF was added via syringe. The resulting solution was stirred at ambient temperatures for 2 hours. A TLC was taken (9:1 CHCl 3 :MeOH; UV and 5% H 2 SO 4 in MeOH; R f(product) =˜0.5). Reaction was neutralized to pH 7 with 1M HCl. Solvent was removed. Crude product was taken up in CHCl 3 (50 ml), washed with water (3×50 ml), dried over MgSO 4 , filtered and solvent removed. Final product was purified using preparative HPLC (10 mM CH 3 COONH 4 /MeCN; 0-20 min: 80/20→0/100). Solid was collected as a clear, colorless glass (0.095 g, 7% yield): 1 H NMR (DMSO-d 6 ) δ 1.26 (s, 3H), 1.39 (s, 3H), 1.50 (m, 2H), 1.89 (s, 4H), 2.08 (m, 2H), 2.29 (s, 4H), 2.40 (m, 2H), 2.88 (d, 1H), 3.08 (m, 1H), 3.25 (s, 3H), 3.73 (s, 3H), 4.12 (m, 2H), 4.28 (t, 1H), 4.58 (d, 1H), 4.72 (d, 1H), 4.97 (s, 1H), 4.98 (s, 1H), 5.70 (s, 1H), 6.66 (d, 1H), 6.75 (d, 1H). MS Calculated mass=529.2 Found=530.4 (M+H).
[0050] To the protected ribose intermediate was added 10 ml of 1M HCl. The resulting solution was stirred at ambient temperatures for 2 hours. Solvent was removed and final product dried under vacuum. Solid was collected as a waxy, slightly yellow solid (0.092 g, quant.): 1 H NMR (DMSO-d 6 ) δ 1.51 (t, 1H), 1.83 (d, 1H), 2.41 (dt, 1H), 2.27 (t, 1H), 2.63 (dd, 1H), 2.80 (s, 3H), 2.96 (m, 2H), 3.20 (m, 1H), 3.75 (s, 3H), 3.82-4.34 (br m, 12H), 5.15 (s, 1H), 5.72 (s, 1H), 6.75 (d, 1H), 6.88 (d, 1H), 11.37 (br s, 1H).
Preparation of the Chloroformate of 1,2:3,4-di-O-isopropylidene-D-galactopyranose
[0051]
[0000]
Molar
Reagents
MW
Weight
mmoles
Equivalents
1,2:3,4-di-O-isopropylidene-
260
1.00
g
3.85
1
D-galactopyranose
20% Phosgene in toluene
—
20
ml
—
—
Chloroformate of 1,2:3,4-di-O-isopropylidene-D-galactopyranose
[0052] To a stirring solution of 20% phosgene in toluene under an inert atmosphere was added 1,2:3,4-di-O-isopropylidene-D-galactopyranose via syringe. The resulting clear, colorless solution was stirred at ambient temperature for 30 minutes. After stirring, Ar(g) was bubbled through the solution for approximately 20 minutes to remove any excess phosgene. Solvent was then removed and product dried under vacuum for 18 hours. Product was used without further purification or characterization.
Preparation of Galacto-Hydrocodone
[0053]
[0000]
Molar
Reagents
MW
Weight
mmoles
Equivalents
1. Hydrocodone
299
0.223 g
0.75
1.0
1. LiN(TMS) 2 in THF
1 M
1.13 ml
1.13
1.5
1. DMF
—
5 ml
—
—
2. Galactose Chloroformate
—
—
1.49
2.0
2. DMF
—
3 ml
—
—
3. 1 M HCl
1 M
30 ml
—
—
3. Acetone
—
20 ml
—
—
Galacto-Hydrocodone
[0054] To a solution of hydrocodone in DMF was added LiN(TMS) 2 in THF via syringe. The solution was stirred at ambient temperatures for 5 minutes then the chloroformate of galactose in DMF was added via syringe. The resulting solution was stirred at ambient temperatures for 2 hours. A TLC was taken (9:1 CHCl 3 :MeOH; UV and 5% H 2 SO 4 in MeOH; R f(product) =˜0.5). Reaction was neutralized to pH 7 with 6M HCl. Solvent was removed. Final product was purified using preparative TLC (0-10% MeOH in CHCl 3 ). Solid was collected as a white powder (0.180 g, 41% yield): 1 H NMR (DMSO-d 6 ) δ 1.28 (2s, 6H), 1.37 (s, 3H), 1.44 (3, 3H), 1.49 (m, 2H), 1.88 (dt, 1H), 2.08 (m, 2H), 2.29 (s, 4H), 2.40 (m, 2H), 2.90 (d, 1H), 3.09 (s, 1H), 3.73 (s, 3H), 3.99 (dd, 1H), 4.14 (t, 1H), 4.26 (dt, 2H), 4.39 (d, 1H), 4.63 (d, 1H), 4.95 (s, 1H), 5.48 (d, 1H), 5.68 (d, 1H), 6.65 (d, 1H), 6.74 (d, 1H); MS Calculated mass=585.6 Found 586.4 (M+H).
[0055] To the protected galactose intermediate was added 30 ml of 1M HCl and 20 ml acetone. The resulting solution was stirred at ambient temperatures for 3 hours. Solvent was removed and final product dried under vacuum. Solid was collected as a white solid: MS Calculated mass=505.5 Found 506.4 (M+H).
[0000]
[0056] The protected mannofaranose (1) has been converted to the trichloroacetimidate (2) as described below. Based on literature precedent, this can in turn be coupled to an orthogonally protected xylose (3), which affords the corresponding disaccharide (4). Disaccharide formation is promoted by the addition of a catalytic amount of acid. Use of an orthogonal protection scheme allows the selective removal of the silyl protecting group using tetrabutyl ammonium fluoride in the presence of the isopropylidene groups, affording the free primary alcohol (5). Employing methods already described in the preparation of galactose and ribose conjugates, this alcohol can then be converted to the chloroformate (6) and in turn coupled to the hydrocodone-enolate (7), resulting in the carbonate (8). Deprotection of (8) using standard protocols affords the hydrocodone-disaccharide conjugate (9)
Preparation of the Trichloroacetimidate of Mannofuranose (2):
[0057] Dissolved 2,3:5,6-Di-O-isopropylidene-D-mannofuranose (1, 0.50 g, 1.9 mmol) in 5 ml of anhydrous dichloromethane. Then, trichloroacetonitrile (0.67 ml, 6.7 mmol) was added to the solution followed by dry K 2 CO 3 (0.54 g, 0 3.8 mmol). The reaction was then allowed to stir over night at room temperature under argon. Qualitative thin-layer chromatography (2:1 hexanes/acetone) of the reaction mixture indicated that the desired trichloroacetimidate had been formed, based on the disappearance of the spot corresponding to the mannofuranose starting material that correlated with the appearance of a new faster-running spot. This is consistent with literature precedence. The reaction was then filtered through fritted glass and the filtrate collected and freed of solvent by rotary-evaporation under high vacuum. This resulted in a viscous oil that solidified with storage over night under high vacuum. | A pharmaceutical composition comprising an active agent bound to a scaffold for dendritic encapsulation wherein said scaffold is covalently or non-covalently attached to a polysaccharide. More specifically, the invention is directed to active agent complexes or conjugates which utilize dendritic encapsulation alone or in combination with other delivery systems to improve and target active agent release. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This non-provisional application claims priority under 35 U.S.C. §119(a) on Patent Application No(s).: 100119583 filed in Taiwan, R.O.C. on Jun. 3, 2011, the entire contents of which are hereby incorporated by reference.
FIELD OF INVENTION
[0002] The present invention relates to a method for preparing a xylose-utilizing Saccharomyces cerevisiae . The preferred recombinant strain contains multiple copies of integrated xylose metabolic genes encoding xylose reductase, xylose dehydrogenase, xylulokinase and transaldolase, and can rapidly ferment xylose to ethanol from synthetic medium and lignocellulosic raw materials. This xylose-utilizing strain can be potentially used for cellulosic, ethanol production and brewing industry.
BACKGROUND OF INVENTION
[0003] Bioethanol is one of the most promising alternatives to petroleum-based fuels. Lignocellulosic biomass, such as woods and agricultural residues, is an attractive feedstock for bioethanol production because of their relatively low cost, great abundance, sustainable supply and without food conflict. Lignocellulosic materials are mainly composed of cellulose, hemicellulose, and lignin. Of these, only cellulose and hemicellulose can be used to produce ethanol by fermentation of monomeric sugars obtained by saccharification including chemical or enzymatic hydrolysis. The cellulose fraction is made up of glucose, which is the most abundant sugar in lignocellulosic biomass, while 20-40% of the biomass is hemicellulose, which consists mostly of xylose. Literature often discloses using Pichia sp. as a strain for xylose fermentation because of its high performance in turning xylose into ethanol. However, Pichia sp. is intolerant to a high ethanol concentration and environmental inhibitors. Therefore, this has resulted in this strain with poor industrial application. Normally, in the pretreatment process of cellulosic raw materials, fermentation inhibitors, such as acetic acid, furfural, and hydroxymethyl furfural, each having a range of concentration levels, are produced, depending on reaction conditions. For example, 0.5˜2.0 g/L of furfural reduces productivity by 29˜95% and growth by 25˜99%, and 1.0-5.0 g/L of hydroxymethyl furfural reduces productivity by 17˜91% and growth by 5˜99%. Hence, lignocellulosic hydrolysates produced in the pretreatment process is usually undergone an overliming process to remove furfural, so as to detoxify the fermentation inhibitors produced in the pretreatment process and thereby ensure the success of the hydrolysate fermentation process. However, the overliming process not only causes a loss of xylose but also contributes to the production of gypsum sludge; hence, the processing and disposal of the resultant gypsum sludge incurs costs and equipment, thereby increasing production costs.
[0004] Saccharomyces cerevisiae is the most attractive ethanol-producing microorganism because of its high ethanol productivity, high inhibitory compounds tolerance and safety as a GRAS organism. However, wild type S. cerevisiae strains rapidly ferment glucose, mannose and galactose, but not xylose. Thus, to achieve economically feasible ethanol fermentation, genetically engineered S. cerevisiae has been developed to improve the capacity for converting xylose into ethanol. A number of metabolic engineering strategies to enhance ethanolic xylose fermentation in S. cerevisiae have been explored. Several approaches have been prospected to express a xylose utilization pathway from naturally pentose-utilizing bacteria and fungi in S. cerevisiae either by introducing genes encoding xylose reductase (XR) and xylitol dehydrogenase (XDH), or by introducing the gene encoding xylose isomerase (XI). Pichia stipitis , a naturally pentose-utilizing fungus, has been chosen as the source of the heterologously expressed enzymes because of its high ethanol yield from xylose, despite only under oxygen limitation. However, the S. cerevisiae strains expressing the XR and XDH from P. stipitis produced xylitol, and the ethanol yield from xylose is low. This is attributed to the cofactor imbalance between XR and XDH. Heterologous expression of bacterial XI genes in S. cerevisiae has been tried for many years. However, less actively expressed XI has been reported. Despite the relatively high activity of Piromyces XI in S. cerevisiae , the expression of this enzyme only enables this strain to grow slowly on xylose, suggesting that the xylose metabolic flux in S. cerevisiae is not only affected by the conversion of xylose to xylulose.
[0005] The flux of metabolism from xylose to ethanol is affected at several levels in the pathway. The transport of xylose in S. cerevisiae occurs through non-specific hexose transporters, but the affinity of xylose is one to two orders of magnitude lower than hexose sugars. Therefore, xylose transport is early considered a rate-controlling step for ethanolic xylose fermentation. In addition, the production of xylitol during xylose consumption by recombinant xylose-utilizing S. cerevisiae is ascribed to the difference in cofactor preferences between the enzymes in the initial xylose utilization pathways. Xylitol formation in recombinant S. cerevisiae has been reduced by expressing mutated XR or XDH with altered cofactor affinity or to increase the NADPH pool by overexpressing the heterologous GADPH enzyme. The fact is that not only the cofactor preferences of the enzymes are involved, but also the levels of the XR and XDH activities affect xylitol formation during xylose fermentation. Increase of the XR and XDH activity, allowing an increased flux in the initial xylose pathway, significantly reduces xylitol accumulation. Increases of the XR and XDH activities have been observed in mutant S. cerevisiae strains with improved xylose utilization. Similarly, high activity of Piromyces XI allows higher xylose fermentation rates than the lower bacterial XI activity. The S. cerevisiae genome contains the gene XKS1 coding for XK, but the XK activity in wild-type S. cerevisiae is too low to support ethanolic xylose fermentation in strains engineered with a xylose metabolic pathway. However, it is only when additional copies of XKS1 are expressed that recombinant xylose utilizing S. cerevisiae produces ethanol from xylose. But, unregulated kinase activity may cause a metabolic disorder. It has experimentally been shown that only fine-tuned expression of XKS1 in S. cerevisiae has improved ethanol fermentation from xylose. Above all, there is not just one rate-limiting step in metabolic flux from xylose to ethanol by S. cerevisiae and therefore, strain engineering for enhanced capacity for xylose fermentation remains a challenge.
SUMMARY OF THE INVENTION
[0006] The present invention describes a method to enhance the ethanol yield and sugar consumption rate from xylose for recombinant S. cerevisiae . This goal is achieved by increasing the extra copies of xylose reductase gene to elevate the enzyme activity, and auto-tune the expression levels of the xylitol dehydrogenase and xylulokinase by dual-transforming two recombinant expression plasmids contained XDH and XK genes. This systematic method could build the S. cerevisiae library with different ratios of xylose metabolic genes, and well-growth colonies with different fermentation capacities of xylose could be further selected. We successfully isolated a recombinant strain with the attractive capacity for xylose fermentation, and then designated it as strain YY5A.
[0007] This invention thus provides new recombinant yeast strains expressing xylose reductase, xylose dehydrogenase, xylulokinase and transaldolase, and can rapidly ferment xylose to ethanol from synthetic medium and lignocellulosic raw materials.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] A detailed description of further features and advantages of the present invention is given below so that a person skilled in the art can understand and implement the technical contents of the present invention and readily comprehend the objectives, features, and advantages thereof by reviewing the disclosure of the present specification and the appended claims in conjunction with the accompanying drawings, in which:
[0009] FIG. 1 shows the restriction map of pB-PGK-XYL2 and the genes cloned within;
[0010] FIG. 2 shows the restriction map of pB-PGK-CXYL1 and the genes cloned within;
[0011] FIG. 3 shows the restriction map of pAURC1 and the genes cloned within;
[0012] FIG. 4 shows the restriction map of p5S-XYL2 and the genes cloned within;
[0013] FIG. 5 shows the restriction map of p5S-XK and the genes cloned within;
[0014] FIG. 6 shows the consumption of xylose by recombinant yeasts during 24 hr fermentation in YPX synthetic medium;
[0015] FIG. 7 shows the accumulation of xylitol by recombinant yeasts during 24 hr fermentation in YPX synthetic medium;
[0016] FIG. 8 shows the accumulation of ethanol by recombinant yeasts during 24 hr fermentation in YPX synthetic medium;
[0017] FIG. 9 is a time-dependent batch fermentation profile of the recombinant yeast YY5A in YPX synthetic medium; and
[0018] FIG. 10 is a time-dependent batch fermentation profile of the recombinant yeast YY5A in lignocellulosic hydrolysate.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0019] Genetically engineered Saccharomyces cerevisiae has been developed to improve the capacity for converting xylose into ethanol because of the potential applicability for the cellulosic ethanol industry. Thus, this invention is aimed at providing a method for enhancing the ethanol yield and sugar consumption rate from xylose for recombinant S. cerevisiae.
[0020] A number of efforts have focused on the initial xylose metabolic pathway in Saccharomyces cerevisiae in view of its critical role in the capability of xylose utilization. Initial xylose metabolic pathways include XR-XDH and XI systems. To make gene acquirement easy, XR-XDH system is used in this invention. Xylose metabolic enzymes of XR-XDH system in the initial xylose metabolism include xylose reductase (XR), xylitol dehydrogenase (XDH) and xylulokinase (XK). Several reports have shown that higher activity of XR increases the xylose consumption rate of S. cerevisiae during the fermentation, but insufficient XDH activity leads to the by-product accumulation of xylitol. XK is prerequisite, but only fine-tuned overexpression of XK gene is capable of improving the xylose metabolic flux. In addition, excess XK activity could result in rapid depletion of ATP and X5P accumulation, and may result in cell toxicity. Cofactor balance between XR and XDH is also important for reducing the xylitol accumulation and improving the xylose utilization. Numerous studies have indicated that efficient utilization of xylose by recombinant S. cerevisiae is directly involved with the specific cofactor usage and the ratio of enzymes activities in xylose metabolic pathway. Therefore, there is not just one rate-limiting step in the xylose metabolic pathway. In order to optimize the XR-XDH system in S. cerevisiae , a novel method is described herein.
[0021] The Saccharomyces cerevisiae strain YY2KL with a lower capability of xylose utilization was used as a parental host for genetic engineering. The genotype of YY2KL contains xylose metabolic genes encoding xylose reductase (XR) from Candida guilliermondii , xylitol dehydrogenase (XDH) from Pichia stipitis , endogenous xylulokinase (XKS1) and transaldolase (TAL) from Pichia stipitis . Except TAL gene is under control of the TEF promoter, the others are of PGK promoter, both of TEF and PGK promoters are constitutive promoters. The parental host used for YY2KL was S. cerevisiae ATCC20270. In order to increase the xylose consumption rate of YY2KL, the strain was integrated with extra copies of cXR gene by transforming with the chromosomal integration plasmid pAURC1 ( FIG. 3 ). The plasmid pAURC1 derived from pAUR101 (TAKARA Bio.) contained cXR gene under control of PGK promoter and aur1 sequence for integrating the expressing plasmids into the chromosome of the strain. Transformed cells were selected on YPD medium with 0.5 mg/L of Aureobasidine A (Takara Bio). The transformants appeared within 3 days at 30° C. The newly recombinant yeast strain was selected and named YYA1. To verify the increased capability of xylose utilization of YYA1, xylose fermentation of the parental strain YY2KL and the genetically modified strain YYA1 was evaluated in 250 ml flask containing 50 ml YPX synthetic medium (1% yeast extracts, 2% peptone, 2% xylose). The result indicates that the xylose consumption rate of YYA1 is increased compared to the parental strain, but the xylitol yield is also increased. Thus, higher activity of XR in S. cerevisiae could increase the xylose consumption rate, but insufficient XDH may result in xylitol accumulation. To reduce the accumulation of the xylitol, the strain was integrated with extra copies of XDH and XK genes by transforming with the chromosomal integration plasmids p5SXDH and p5SXK. The plasmids p5SXDH and p5SXK derived from pGAPZαA (Invitrogen) contained XDH and XKS1 genes respectively, both of the genes were under control of PGK promoter. Both of the plasmids also contained the 5S rDNA sequence from S. cerevisiae ATCC 20270 for integrating the expressing plasmids into the chromosome of the strain. Transformed cells were selected on YPX medium with 400 mg/L of Zeocin (Invitrogen). The transformants appeared within 3 days at 30° C. 14 well-growth colonies with different fermentation capacities of xylose were selected in YPX medium. To verify the xylose utilization capability of the selected strains, xylose fermentation was further evaluated in a 250 ml flask that contains 50 ml YPX synthetic medium. The results indicate that the xylose consumption rates of the selected strains were increased and the xylitol yields were reduced. Consequently, a recombinant strain with an attractive capacity for xylose fermentation was selected, and then designated it as strain YY5A. The yeast S. cerevisiae carries 100-200 copies of the rDNA unit that are randomly repeated on chromosome XII. Because of the expressing plasmids randomly integrating into the sequence sites of 5S rDNA, the recombinant S. cerevisiae library was built with different ratios of enzyme activity in XR-XDH-XK metabolic pathway. The recombinant strains with the correct ratios of enzyme activity grew well on YPX medium than others, thus the optimized strain can be further selected from a culture on YPX medium.
[0022] Ethanolic fermentation of lignocellulose hydrolysates requires that the organism is capable of fermenting in the presence of inhibitory compounds including weak acids, furaldehydes and phenolics. Saccharomyces cerevisiae , which has been the preferred organism for fermentative ethanol production, is also tolerant toward lignocellulose derived metabolic inhibitors. Fermentation by YY5A had also been carried out in non-detoxified rice straw hydrolysate (8.6 g/L glucose, 43.6 g/L xylose, 5.1 g/L arabinose, 1.38 g/L furfural, 1.0 g/L HMF). Although the hydrolysate has a high concentration of furaldehyde inhibitors, the result indicates that YY5A is able to efficiently coferment glucose and xylose of hydrolysate to ethanol simultaneously. Above all, the recombinant yeast YY5A prepared by the method in the present invention could rapidly ferment xylose to ethanol from synthetic medium and lignocellulosic raw materials. Preferred embodiments of the method of the present invention are illustrated by way of the following examples:
Example 1
Construction of the Plasmids pB-PGK-XYL2 and pB-PGK-XYL1
[0023] A. Preparation of a Plasmid pB-PGK-XYL2
[0024] Recombinant plasmid pB-PGK-XYL2 bearing XYL2 gene from Pichia stipitis downstream of the PGK promoter and upstream of ADH1 terminator was constructed. The plasmid was prepared by following the steps of:
[0025] Using P. stipitis chromosome as a template, the XYL2 gene was amplified with primers, Y0811: 5′-TTCACAAGCTTCATATGACTGCTAACCCTTCCTTG-3′ and Y0812: 5′-AAGCGCTGCAGTTACTCAGGGCCGTCAATGAG-3′. HindIII/PstI digested fragment XYL2 was cloned into HindIII/PstI digested plasmid pBluescriptSKII (Stratagene). The resultant recombinant plasmid was pBlue-XYL2.
[0026] Using plasmid pAD-GAL4-2.1 (Stratagene) as a template, the DNA fragment comprising a ADH1 promoter and terminator was amplified with primers, Y0801: 5′-AATTAGGGCCCTCGCGTTGCATTTTTGTTC-3′ and Y0802: 5′-AGAGCGAGCTCATGCTATACCTGAGAAAGC-3′. ApaI/SacI digested fragment comprising a ADH1 promoter and terminator was cloned into ApaI/SacI digested plasmid pBluescriptSKII (Stratagene). The resultant recombinant plasmid was pB-ADH-GAL4AD.
[0027] Using plasmid pB-ADH-GAL4AD as a template, creating a NdeI restriction site with primers, Y0803: 5′-CAATCAACTCCAAGCTTTGCACATATGGATAAAGCGGAATTAATTC-3′ and Y0804: 5′-GAATTAATTCCGCTTTATCCATATGTGCAAAGCTTGGAGTTGATTC-3′. The resultant recombinant plasmid was pB-ADH-GAL4ADN.
[0028] Using a plasmid pGG119 (Rinji Akada, Isao Hirosawa, Miho Kawahata, Hisahi Hoshida and Yoshinori Nishizawa, 2002, “Sets of integrating plasmids and gene disruption cassettes containing improved counter-selection markers designed for repeated use in budding yeast,” Yeast, 19:393-402) as a template, the DNA fragment comprising a PGK promoter was amplified with primers, Y0805: 5′-CCGAACCCGGGCCCGAGGAGCTTGGAAAGATGC-3′ and Y0806: 5′-ACACTCATATGTTCCGATCTTTTGGTTTTATATTTG-3′. ApaI/NdeI digested fragment comprising a PGK promoter was cloned into ApaI/NdeI digested plasmid pB-ADH-GAL4ADN. The resultant recombinant plasmid was pB-PGK-GAL4ADN. Finally, NdeI/PstI digested fragment comprising XYL2 gene was cloned into NdeI/PstI digested plasmid pB-ADH-GAL4ADN. The resultant recombinant plasmid was pB-PGK-XYL2 (see FIG. 1 ).
[0029] B. Preparation of a Plasmid pB-PGK-CXYL1
[0030] Recombinant plasmid pB-PGK-CXYL1 bearing CXYL1 gene from Candida guilliermondii downstream of the PGK promoter and upstream of ADH1 terminator was constructed. The plasmid was prepared by following the steps of:
[0031] Using C. guilliermondii chromosome as a template, the CXYL1 gene was amplified with primers, Y0903: 5′-GCCGCATATGTCTATTACTTTGAACTCAG-3′ and Y0904: 5′-CGCGGAATTCCATGGTTACACAAAAGTTGGAATCTTG-3′. HindIII/PstI digested fragment XYL2 was cloned into HindIII/PstI digested plasmid pBluescriptSKII (Stratagene). The resultant recombinant plasmid was pBlue-CXYL1.
[0032] Finally, NdeI/EcoRI digested fragment comprising CXYL1 gene was cloned into NdeI/EcoRI digested plasmid pB-ADH-GAL4ADN. The resultant recombinant plasmid was pB-PGK-CXYL1 (see FIG. 2 ).
[0033] Construction of the Integrating Plasmids pAURC1, p5SXDH and p5SXK
[0034] Recombinant plasmid pAURC1 bearing CXYL1 gene from Candida guilliermondii downstream of the PGK promoter and upstream of ADH1 terminator was constructed on the basis of pAUR101 shuttle vector (Takara Bio, Kyoto). The sequence of PGK-CXYL1-ADH1 was amplified from pB-PGK-CXYL1 plasmid with primers, PGKKpnlfw: 5′-GGTACCGAGGAGCTTGGAAAGATGCC-3′ and ADH1KpnI/SacIry: 5′-GGTACCCTGGAGCTCATG CTATACCTGAG-3′. KpnI/SacI digested fragment PGK-CXYL1-ADH1 was cloned into KpnI/SacI digested pAUR101 plasmid. The resultant plasmid was pAURC1. Recombinant plasmids p5SXYL2 and p5SXK bearing 5S rDNA from Saccharomyces cerevisiae and coding sequences of XDH and XK from Pichia stipitis respectively were constructed on the basis of the plasmid pGAPZαA (Invitrogen). The sequence of 5s rDNA was amplified from the genomic DNA of S. cerevisiae by using the primers: 5SrDNA-F: 5′-AGATCTGTCCCTCCAAATGTAAAATGG-3′ and 5SrDNA-R: 5′-GGTACCGTAGAAGAGAGGGAAATGGAG-3′. BglII/KpnI digested fragment 5S rDNA was cloned into the BglII/KpnI digested plasmid pGAPZαA. The resultant plasmid was pGAP5S. The sequence of PGK-XYL2-ADH1 was amplified from the plasmids pB-PGK-XYL2 by using the primers: PGKNotlfw-F: 5′-GCGGCCGC GAGGAGCTTGGAAAGATGCC-3′ and ADH1BamHlry-R: 5′-GGATCCCTGGAGCTCATGCTATACCTGAG-3′. The NotI/BamHI digested PGK-XYL2-ADH1 fragment was cloned into the NotI/BamHI digested plasmid pGAP5S. The resultant plasmid was p5SXYL2. The genomic region of Pichia stipitis encompassing the entire coding sequence of XK was amplified with primers, XK-F: 5′-CATATGATGACCACTACCCCATTTG-3′ and XK-R: 5′-CTG CAGTTAGTGTTTCAATTCACTTTCC-3′. The NdeI/PstI digested XK amplified DNA fragments were cloned into the NdeI/PstI digested plasmid p5SXYL2 between the PGK promoter and ADH1 terminator. The resultant plasmid was p5SXK.
Example 2
Transformation
[0035] Yeast transformation of plasmids pAURC1, p5SXK, p5SXYL2 was carried out by the electroporation method. YY2KL was transformed with pAURC1 to become a new transformant named YYA1. YY5A was derived from YYA1 which was transformed with p5SXK and p5SXYL2 simultaneously in a 1:2 mole ratio, and then selected in YPX medium with Zeocin (Invitrogen). For electroporation, pAUR101 was linearized with Stul, p5SXK and p5SXYL2 were linearized with SphI. Culture flasks (250 ml) containing 50 ml YPD medium were inoculated with 1 ml of the overnight inoculum culture and grown for approximately 4-5 hours at 30° C. with shaking to attain an absorbance value of 3 units at 600 nm. Cells were harvested in a clinical centrifuge (4000 rpm) and the pellets resuspended with Lithium Acetate buffer (8 ml sterile water, 1 ml Lithium Acetate, 1 ml 10×TE buffer). Then the resuspended pellets were incubated at 30° C. for 45 min. After incubation, brought the volume to 50 ml with sterile water and washed twice. After washing twice, resuspended the pellets with 0.1 ml 1 M sorbitol that is competent cells. Mixed 40 μl competent cells with 1 μg linearized plasmid. 45 μl mixed sample was subjected to electric shock at 1500 volts and 25 microfarads using a Bio-Rad Gene Pulser Xcell (Richmond, Calif., USA). Following electroporation, cells were immediately plated on selective YPX medium with 400 mg/L of Zeocin (Invitrogen). The transformants appeared within 3 days at 30° C. Well-growth colonies with different fermentation capacities of xylose were selected.
Example 3
Strains and Growing Conditions
[0036] S. cerevisiae BCRC 20270 and recombinant strain YY2KL, YYA1 and YY5A were the Saccharomyces strains used in this study. Yeast strains S. cerevisiae and transformants were grown in YPD medium (0.5% yeast extract, 2% peptone, 2% glucose). For selection of yeast transformants on YPD mediun, 400 mg/L of Zeocin (Invitrogen) or 0.5 ma of Aureobasidine A (Takara Bio) was added. Cultivation of S. cerevisiae was performed at 30° C., 150 rpm.
[0037] E. coli DH5a [F − 80d lacZΔM15 recA1 end1 gyrA96 thi1hsdR 17 (m k − r k − ) supE44 relA1 deoRΔ(lacZYA-argF) U169] was used for subcloning. For selection of E. coli transformants on LB medium (1% tryptone, 0.5% yeast extract, 0.5% NaCl) supplemented with 100 mg/L Ampicillin or 25 ma Zeocin. Cultivation of E. coli was performed at 37° C., 150 rpm.
Example 4
Molecular-Biology Techniques
[0038] Standard cloning techniques were used as described. Genomic DNA of Pichia stipitis and Saccharomyces cerevisiae was isolated using the Wizard® Genomic DNA Purification Kit (Promega, Madi-son, WI, USA). Restriction endonucleases and DNA ligase (New England Biolabs) were used according to the manufacturer specifications. Plasmid isolation from E. coli was performed with the Plasmid Mini kit (Qiagen). PCR-amplification of the fragments of interest was done with ExTaq DNA Polymerase (TAKARA BIO INC.). PCRs were performed in GeneAmp® PCR System 9700 thermocycler (Applied Biosystems). Transformation of the yeast S. cerevisiae by electroporation was carried out as described previously.
Example 5
Fermentation
[0039] For fermentation studies, the seed cultures were grown aerobically in 50 mL of YPD 250-mL Erlenmeyer flask at 30° C. for 16 hr. For ethanol production, 10 mL of seed cultures was used to inoculate into 50 mL of YPX or YPDX medium in a 250-mL Erlenmeyer flask. An initial CDW of 0.4 g/L was used. All fermentations were performed at 30° C. with mild agitation at 150 rpm.
[0040] Ethanol fermentation from xylose by sixteen strains including fourteen selected recombinant strains (pAURC1, p5SXDH, p5SXK), YYA1(pAURC1) and parental strain YY2KL was compared using 20 g/L xylose as the sole carbon source (YPX medium). The results indicate that the parental strain YY2KL and the strain YYA1 consumed 44% and 82% xylose in 24 hours, respectively, whereas the optimized strains were able to consume 88.4%-93.7% xylose. The strain YY5A showed the highest xylose consumption rate (0.78 g/L/h) during the fermentation, and produced ethanol with a yield of 0.3 g/g consumed xylose , xylitol with a yield of 0.1 g/g consumed xylose . However, YY5A fermenting in the medium with higher concentration of xylose (45 g/L) showed the xylose consumption rate of 1.77 g/L/h, and produced ethanol with a yield of 0.34 g/g consumed xylose , xylitol with a yield of 0.02 g/g consumed xylose .
[0041] Fermentation by YY5A has also been carried out in non-detoxified rice straw hydrolysate (8.6 g/L glucose, 43.6 g/L xylose, 5.1 g/L arabinose, 1.38 g/L furfural, 1.0 g/L HMF). YY5A consumed 81% xylose in 48 hours and produced maximum ethanol concentration of 17.1 g/L. The ethanol yield corresponds to 71% of the theoretical yield.
Example 6
Analyses
[0042] Concentrations of ethanol, glucose, xylose, xylitol, glycerol, and acetic acid were determined by high-performance liquid chromatography (HPLC; JASCO, Tokyo) equipped with a refractive index detector. The column used for separation was HPX-87H ion-exclusion column (Bio-Rad Laboratories, Hercules, Calif., USA). The HPLC apparatus was operated with 5 mM H 2 SO 4 at a flow rate of 0.6 ml/min as the mobile phase. Cell growth was monitored by measuring the absorbance at 600 nm using spectrophotometer U-3000 (Hitachi). Cell dry weight was determined thrice by filtering 5 mL of a culture through a pre-weighed hydrophilic polyethersulfone filter (PALL, Life Sciences, Michigan, USA). The average measurements are based on three independent experiments. | A method for preparing a xylose-utilizing strain of Saccharomyces cerevisiae and the Saccharomyces cerevisiae are introduced. The preferred recombinant strain contains multiple copies of integrated xylose metabolic genes, and can rapidly ferment xylose to produce ethanol from synthetic medium and lignocellulosic raw materials. The xylose-utilizing strain is applicable for the cellulosic ethanol production industry and brewing industry. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 09/422,414, filed Oct. 21, 1999 now U.S. Pat. No. 6,551,282, which is a continuation of U.S. application Ser. No. 09/027,754, filed Feb. 23, 1998, now U.S. Pat. No. 5,989,224.
FIELD OF THE INVENTION
The present invention relates generally to seals for use in endoscopic surgery and, more particularly, to a universal seal that seals against different sizes of medical instruments being inserted through a cannula into the body while maintaining insufflation pressure, yet still allowing for side to side motion of the medical instruments.
BACKGROUND OF THE INVENTION
As modern technology has developed, new surgical innovations have followed the technology. One of the techniques of modern surgery that has rapidly grown in the last decade is the use of small openings in the body through which access to the internal organs is obtained. While many different titles to describe this technique have been used, probably the more common titles are laparoscopic surgery or endoscopic surgery. Other people prefer more descriptive titles such as telescopic surgery or minimally invasive surgery. This entire area of surgical techniques probably developed the most in laparoscopic cholecystectomy, which is used to remove gall stones.
For the present application, because the most commonly used and comprehensive term is endoscopic surgery, the term endoscopic surgery will be used in this application to refer collectively to all of these types of surgery. However, it should be realized that other terms can be used to describe the surgical technique.
In endoscopic surgery, a small cut is made in the skin and a sharpened cannula or spike is then inserted through the fascia into a body opening such as the abdominal cavity. After removal of the spike from the cannula, the cannula will then allow access to the body opening such as the abdominal cavity.
Typically, a gas is inserted through the cannula to insufflate the body opening. Once the first opening is made, a camera lens on the end of a fiber optic cable can be inserted through the cannula that will allow the monitoring of the internal parts of the body cavity. It is extremely important that the body organs not be damaged when inserting any cannulas, spikes, or trocars into the body.
After access to the body opening is obtained by the insertion of the cannula, it is also important to maintain a seal along the central opening of the cannula. If not, the gas used for the insufflation of the body cavity-will rapidly escape and it will be difficult to maintain a sufficient cavity opening for the endoscopic surgery.
In the past, various types of seals have been developed to seal the upper part of the cannula opening. An example is shown in U.S. Pat. No. 5,512,053, which patent is owned by the same assignee as the present application. U.S. Pat. No. 5,512,053 provides a lip seal to maintain the insufflation gas in the body cavity. However, once a medical instrument is inserted through the lip seals the gas can leak around the medical instrument and escape into the atmosphere. To provide a back up, a second sliding seal with different size apertures has been provided to engage the medical instrument being inserted into the cannula and through the lip seal. Medical instruments vary in size, and the medical instruments will be moved form side to side during use in endoscopic surgery. This side to side motion causes leakage of the gas around the medical instruments. Some type of seal is needed that will seal around medical instruments of varying sizes and, at the same time, allow for lateral or side to side movement of the medical instrument during endoscopic surgery.
Also, it is important that the seal have a memory to return to its original position after periods of use. In other words, if the doctor during the operation is moving the medical instrument to one side, there should be a continual force trying to urge the medical instrument back to the center of the cannula opening.
To remedy the problem of different size medical instruments being inserted through the cannula, U.S. Pat. No. 4,112,932 shows a laparoscopic cannula that has a rotating seal where different size openings can be selected depending upon the size of instrument being inserted into the cannula. While this is effective to some degree, it does not allow for side to side movement of the medical instrument and it does not allow for the rapid exchange of medical devices without also rotating or spinning the seal.
A common seal that is in use today to seal surgical instruments such as cannulas, trocars, or similar devices is shown in U.S. Pat. No. 5,407,433 to Loomas. The Loomas patent and its related patents allows some side to side movement of the medical instruments, but has a rigid internal ring on the seal that limits its effectiveness. The rigid internal ring does not allow the seal to make a sealing relationship with the medical instrument as well as the present invention. The inflexible nature of the internal ring does not provide as effective an urging force against the medical instrument to return the medical instrument to the center of the cannula. The Loomas seal is also much more complicated and expensive to manufacture than the present universal seal and does not provide as effective sealing as the present invention.
To overcome this problem of accommodating different sizes of medical instruments and to allow for side to side movement, many other United States patents have been issued to seal surgical instruments such as cannulas or trocars. Another example is U.S. Pat. No. 5,342,315 issued to Rowe, which has a whole collection of different types of seals. Each of these seals is much more complicated and expensive to manufacture than the present invention and still is not as effective. The Rowe patent shows all types of reinforcing ribs and slots being cut in the seal, none of which are necessary with the present invention.
Other patents refer to their seal as a “universal seal” such as U.S. Pat. No. 5,628,732 to Antoon or U.S. Pat. No. 5,350,364 to Stephens. Again, both of these patents are much more complicated, expensive, and do not do the job of the present universal seal. Applicants, who are very familiar with the industry, does not know of any other seal that is as economical and inexpensive to manufacture as the present universal seal, but is as effective in allowing different size instrument to be inserted through a cannula and allowing side to side movement of the medical instrument, yet still maintaining air tight contact to hold the insufflation gas inside the body cavity. The need exists for a universal type of seal that can be used for any cannula or trocar device through which access is obtained to body cavities for the purpose of performing endoscopic surgery, particularly while sealing against the surgical instruments being inserted through the cannulas or trocars into the body.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a universal seal.
It is another object of the present invention to provide a seal for cannulas or other devices used in endoscopic surgery.
It is still another object of the present invention to provide for a universal seal that can be used with cannulas or trocars, which universal seal allows for side to side movement with different size surgical instruments when inserted therethrough, yet still maintaining an air tight seal to hold the insufflation gas inside the body.
It is yet another object of the present invention to provide a cannula with an improved seal for sealing against the surgical instruments being inserted through the cannula into the body cavity while still urging the surgical instrument and the seal back to the center of the cannula due to the memory of the elastomeric material.
It is still another object of the present invention to provide a universal seal that can seal against medical instruments of different diameters as they are inserted through a cannula or trocar during endoscopic surgery and still maintain the seal during side to side movement of the medical instrument.
The universal seal is shown in a preferred embodiment in combination with a reusable cannula. The reusable cannula is made from a metal material and is connected to a lip seal housing for a lip seal. An insufflation port connects through the lip seal housing into the central passage of the reusable cannula below the lip seal. Above the lip seal housing is an adapter so that different devices or seals may be attached to the lip seal housing.
Above the adapter is a universal housing, which maintains a universal seal between a top and bottom portion of the universal seal housing. The top and bottom portions form an annulus therebetween that surrounds an insertion port in the universal seal housing. An outer ring of the universal seal is compressed at the outer edge of the annulus between the bottom and top portions of the universal seal housing. An inner ring of the universal seal is free to move back and forth inside of the annulus while maintaining rubbing contact with the top and bottom portions of the universal seal housing which forms the annulus. A small opening is in the center of the universal-seal.
Because the universal seal is made from elastomeric material, as medical instruments of different diameters are inserted through the insertion port into the small opening of the universal seal, the small opening in the universal seal will expand to accommodate the different size medical instruments up to a predetermined limit. If the medical instrument moves from side to side, the center ring of the universal seal will deform and move inside of the annulus to allow for side to side movement of the medical instrument while still maintaining contact with the medical instrument. The universal seal will have a tendency to self center that is caused by a combination of (a) memory of the elastomeric material, (b) gas pressure on the underside of the universal seal, and (c) geometry of the universal seal. This combination creates what could be called an annular spring.
Several different embodiments of the universal seal are shown. Also, the universal seal with the seal housing may be attached to other types of medical devices such as trocars for allowing entry into the body for endoscopic surgery.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded perspective view of the present invention being used with a reusable cannula.
FIG. 2 is a cross-sectional view of FIG. 1 , when assembled, taken along section lines 2 — 2 .
FIG. 3 is an elevated cross-sectional view of the present invention being used with a locking trocar.
FIG. 4 is a partial cross-sectional view of a cannula utilizing the present invention with the medical instrument being moved to the right side.
FIG. 5 is a partial cross-sectional view of a cannula utilizing the present invention with the medical instrument being moved to the left side.
FIG. 6 is an enlarged cross-sectional view of the universal seal as manufactured.
FIG. 7 is a cross-sectional view of the universal seal in its normal position when installed in the universal seal housing.
FIG. 8 is an alternative embodiment of the universal seal of the present invention.
FIG. 9 is another alternative embodiment of the universal seal of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1 and 2 in combination, the universal seal of the present invention is shown in a reusable cannula referred to generally by reference number 10 . The cannula 12 has a slanted cut lower distal end 14 from which a spike or similar instrument (not shown) may extend.
An enlarged upper portion 16 of the cannula 12 has upper internal threads 18 for threadably connecting to lower threads 20 of a lip seal body 22 .
The lip seal body 22 has a port 24 through which insufflation gas is inserted. The insufflation gas 30 is directed downward through the cannula 12 into the body of the patient.
A lip seal 26 is located on an internal shoulder 28 of the lip seal body 22 . A slot 30 is cut in the lip seal 26 , which slot 30 may be opened upon the insertion of medical instruments.
A snap cap 32 snaps onto the upper portion of the lip seal body 22 to securely hold the lip seal 26 in position. The snap cap 32 may be held to the lip seal body by any conventional means such as snap posts (not shown). Around the upper part of the snap cap 32 is an elastomeric ring 34 that provides a good fit with the adapter 36 . The adapter 36 , also called a Chiulli adapter, is used so that access can be obtained to the cannula for the removal of body tissue. It is important not to have to go through any further seals in reaching into the body and removing irregular objects.
While the adapter 36 can be of any particular configuration, in the present preferred embodiment, it is of an elongated shape and has a mating shoulder/edge 38 . The mating shoulder/edge 38 is received into a mating cavity 40 formed in the bottom 42 of the universal seal housing 44 . The connection between the adapter 46 and the bottom 42 of the universal seal housing 44 is an air tight seal that will not allow insufflation gas to escape therethrough. A circular opening 46 is in the top of the bottom 42 of the universal seal housing 44 . The top 48 of the universal seal housing 44 connects to the bottom 42 by any conventional means. Therebetween is located the universal seal 50 , which will be described in more detail subsequently. In this preferred embodiment, the bottom 42 and the top 48 are held together by snap posts 52 snapping into holes 54 to hold the universal seal housing 44 together.
Referring to FIG. 2 , it can be seen that the top portion 48 has an angular undercut 56 formed therein that is just above the circular opening 46 in the bottom 42 of the universal seal housing 44 . The angular undercut 56 with the circular opening 46 forms an annulus in which a roll or bellows 58 of the universal seal 50 is located. An outer ring 60 of the universal seal 50 is pressed between the bottom 42 and the top 48 in a solid sealing relationship. The outer ring 60 is held very securely in place.
An inner ring 62 of the universal seal 50 is located inside of the roll or bellows 58 . The inner ring 62 is free to slide back and forth in sliding contact with the bottom side of the top 48 or the circular opening 46 of the bottom 42 of the universal seal housing 44 . In the middle of the universal seal 50 is located an opening 64 through which medical instruments (not shown) may be inserted. The opening 64 is in alignment with the center of the central passage 66 which extends through the universal seal housing 44 , adapter 36 , snap cap 32 , lip seal body 22 , and cannula 12 .
The inner ring 62 prevents the universal seal 50 from being pushed into the central passage 66 when inserting a large diameter instrument, or from being pulled into the central passage 66 when removing a large diameter instrument.
Referring now to FIGS. 4 and 5 in combination, an elevated partial cross-sectional view of the reusable cannula with the universal seal 50 is shown. A medical instrument 68 is inserted through the opening 64 of the universal seal 50 . As the medical instrument 68 is moved to the right hand side as illustrated in FIG. 4 , the inner ring 62 , while still maintaining sliding contact with the top portion 48 and the bottom portion 42 , moves to the right as the opening 64 moves to the right. The roll or bellows 58 of the universal seal 50 compresses in the right hand direction and elongates in the left hand direction. Also, the inner ring 62 being deformable may deform as the medical instrument 68 moves to the right. The medical instrument 68 will extend down through the opening 64 of the universal seal 50 and through the slot 30 in the lip seal 26 . While it is not shown in the drawings, the slot 30 has a tendency to allow insufflation gas to escape on either end of the slot adjacent to the medical instrument 68 . Therefore, it is important that the universal seal 50 have a good sealing relationship with the medical instrument 68 .
As the medical instrument 68 moves to the left as shown in FIG. 5 , the opening 64 moves to the left. Likewise, the inner ring 62 moves to the left as well. Again, the roll or bellows 58 on the universal seal 50 tends to compress to the left and expand to the right. Again, a good sealing relationship is maintained with the medical instrument 68 .
As can be seen in FIGS. 2 , 3 , 4 and 5 , the universal seal 50 has a downward conical shape 55 that allows for ease of insertion of a medical instrument without tearing or damage. Gas pressure against the downward conical shape 55 also helps insure an air-tight seal against a medical instrument.
While in the present view, the medical instrument is shown as a surgical cutting device, any other type of medical instrument may be inserted such as surgical devices, lens on the end of fiber optic links, clip appliers, just to name a few of the medical instruments.
Referring to FIG. 6 , the universal seal 50 is shown as it comes out of the mold and as it would normally appear. In this enlarged view, the configuration of the outer ring 60 , inner ring 62 , and opening 64 is clearly visible.
As the universal seal 50 is installed in the universal seal housing 44 , it will assume the configuration as shown in FIG. 7 with the roll 58 as clearly shown. The outer ring 60 may be compressed when installed. Otherwise, FIG. 7 is an enlarged representation of the view of the universal seal 50 when in operation.
Referring to FIG. 3 , an alternative use for the universal seal 50 is shown in a trocar arrangement, the trocar being generally referred to with reference number 70 . The trocar 70 as shown in FIG. 3 is a locking trocar that has a molly bolt type of arrangement for an outer cylinder 72 . A molly bolt 74 has a lever 76 that is pivoted up or down, which causes the gear 78 on the molly bolt to pivot. The gears 78 of the molly bolt engages the corresponding outer cylinder gears 80 which are on the top of the outer cylinder 72 .
The outer cylinder 72 moves up and down as the lever 76 is moved down and up. When the outer cylinder 72 is moved down, expandable members 82 extend outward as shown in FIG. 3 . In that manner, the outer skin or fascia of the body in which the trocar 70 is being inserted is maintained solidly in position between the retaining ring 84 and the expandable members 82 . If the outer cylinder 72 is moved up by pivoting the lever 76 down, the expandable members 82 will close so that the outer cylinder 72 appears as an ordinary cylinder.
The outer cylinder 72 is riding on an inner cylinder 86 which is securely mounted into position at the top by housing 88 . The housing 88 may be made from two pieces of injection molded plastic that are fused or snapped together. Inside of the housing 88 is a lip seal housing 90 in which the lip seal 92 is located.
Above the housing 88 and the lip seal housing 90 is located the universal seal 50 and universal seal housing 44 as previously described in connection with FIGS. 1 and 2 . The configuration of the universal seal 50 and universal seal housing 44 is the same as previously described; therefore, it will not be described again in connection with the trocar arrangement of FIG. 3 .
Referring now to FIGS. 6 and 7 in combination, FIG. 6 shows the universal seal 50 as it comes out of the mold in which the elastomeric material forming the universal seal 50 is cast. When the universal seal 50 is put in the universal seal housing 44 , it will be pushed down as is illustrated in FIG. 7 . The inner ring 62 pushes down as is pictorially illustrated in FIGS. 2 and 5 .
Referring now to FIG. 8 , a modified universal seal 94 is shown which can still fit in the universal seal housing 44 . The modified universal seal 94 has an outer ring 96 which is secured in position between the bottom 42 and top 48 of the universal seal housing 44 . An inner ring 98 is connected by an air bladder 100 with outer ring 96 . Extending inward from inner ring 98 is upper membrane 102 and lower membrane 104 , both of which have a center opening 106 .
The inner ring 98 will be in rubbing contact with the bottom 42 and top 48 of the universal seal housing 44 . The modified universal seal 94 will flex generally in the same way as the universal seal 50 described in the preferred embodiment with the inner ring 98 flexing as the medical instrument inserted therethrough may move from side to side. Also, the modified universal seal 94 will accommodate varying sizes of medical instruments being inserted.
Referring to FIG. 9 , a further modification of the universal seal is shown and is referred to generally by reference numeral 108 . The modified universal seal 108 still has an outer ring 110 that is securely clamped into position by a universal seal housing 44 . However, in the modified version shown in FIG. 9 , the inner ring has been replaced entirely by an annular air bladder 112 . The outer portion of the annular air bladder 112 is formed integral with the outer ring 110 . Extending inward from the annular air bladder 112 to a central opening 114 is the center membrane 116 . Again, as described with the prior embodiments, the annular air bladder 112 will allow for side to side movement of the medical instruments being inserted through the central opening 114 . The annular air bladder 112 will continue to urge the medical instruments, if it moves in a side to side manner, back toward the center of the cannula passage. | A universal seal is shown with orbital movement of a center opening for use in endoscopic surgery A two part seal housing encloses the universal seal in an annulus surrounding an insertion port. The outer periphery of the universal seal is clamped between the two parts at the outer edge of the annulus. An inner ring of the universal seal is free to move from side-to-side inside the annulus while maintaining rubbing contact with the upper and lower surfaces of the annuluses for vertical support. The seal housing and universal seal are mounted on a proximal end of a cannula which allows access therethrough for the endoscopic surgery. The center opening of the universal seal is in general alignment with the insertion port of the seal housing, but the center opening and inner ring may move from side to side when medical instruments are inserted through the insertion port, the center opening, and the cannula and moved from side to side. | 0 |
FIELD OF THE INVENTION
This invention relates primarily to the development of fungal strains which express proteins at levels substantially higher than the parental strains.
BACKGROUND AND PRIOR ART
For some 20 years, desired foreign proteins have been produced in microorganisms. However, having introduced the necessary coding sequence and obtained expression, much still remains to be done in order to optimise the process for commercial production One area of interest concerns strain improvement, that is to say finding or making strains of the host microorganism which enable the protein to be made in higher yields or better purity, for example.
To increase the yield, once a good expression system (eg transcription promoter) has been devised, one might envisage trying to increase the copy number of the coding sequence (although this will have the desired effect only if DNA transcription was the limiting factor), or to increase the stability of the mnRNA or to decrease the degradation of the protein. Thus, as an example of the latter approach, yeast strains (eg pep4-3) which are deficient in certain proteases have been used for producing desired foreign proteins. In another approach, the number of 2 μm-based plasmids in the yeast Saccharomyces cerevisiae has been increased by introducing a FLP gene into the genome under the control of a regulated promoter, eg GAL. Upon switching to a growth medium containing galactose as the sole carbon source, plasmid copy number rises (11), but the plasmid copy number increase is uncontrolled since the GAL promoter is not repressed by REP1/REP2. This leads to reduced growth rate and thence clonal selection of cir o derivatives of the original cir + strain (11,20).
We have mutated yeast strains by application of mutagens in order to generate mutants randomly and thereby hopefully find mutant strains which produce heterologous proteins in better yield (16,21). We have now characterised such a randomly-produced mutant which maintained a higher number of copies of the plasmid expressing the desired protein and have found that the mutation occurred in one of the genes encoding ubiquitin-conjugating enzymes, namely UBC4. The UBC4-encoded enzyme (and the closely related UBC5-encoded) enzyme are involved in degrading aberrant and short lived proteins and there was no reason to have supposed that the deletion of either of them would have enabled an increased yield of a normal, desired, protein to have been obtained.
Several genes encoding ubiquitin conjugating enzymes (UBC) have been implicated in the bulk protein degradation and in the stress response of yeast. UBC1, UBC4 and UBC5 act together to mediate important functions for cell growth and cell viability (2,3). Yeast strains with a mutation in a single gene are viable and have similar growth rates to the parental strains, but ubc4/ubc5 double mutants have reduced growth rates and are sensitive to amino acid analogues, while a triple mutant is inviable, indicating that their activities overlap. The UBC4 and UBC5 genes are closely related and the two coding DNA sequences share 77% identical residues, while the predicted amino acid sequences of the two proteins show 92% identical residues (3). Because of the near identity of the Ubc4 and Ubc5 proteins (hereafter abbreviated to Ubc4p and Ubc5p) it has been suggested that UBC4 could complement for the loss of function of the ubc5 mutant and vice versa (3). This would explain why the dramatic reduction in growth rate was only observed in ubc4/ubc5 double mutants. Pulse chase experiments have indicated that Ubc4p and Ubc5p are responsible for the degradation of short-lived and abnormal proteins, but that the turnover of these proteins was only reduced in strains with the ubc4/ubc5 double mutation. It was not reduced in strains with single ubc4 or ubc5 mutations (3). This reference, therefore, suggested that the use of single ubc4 and ubc5 mutant fungal strains would not be beneficial.
Structurally, all known UBC genes encode a conserved domain (known as the UBC domain) of approximately 16kDa containing the conserved conjugating cysteine (1,22). Transfer of activated ubiquitin results in the covalent attachment of the C-terminus of ubiquitin via a thioester bond to the cysteine residue. UBC genes have been divided into different classes (reviewed in 22). Class I UBC genes are composed almost exclusively of the conserved UBC domain, class II and class III UBC genes have C-terminal or N-terminal extension, respectively, while class IV UBC genes have both C- and N-terminal extensions (22).
The fungal genome is composed of chromosomes, extrachromosomal copies of chromosomal genes, eg nucleosomes, and occasionally stable extrachromosomal elements. These extrachromosomal elements have developed a benignly parasitic relationship with their host, where they successfully balance the theft of cellular resource for the replication and segregation of the element, while not compromising the fitness of the host. General reviews of fligal extrachromosomal elements are covered by references 5 and 6, while the DNA plasmids of the yeasts Saccharomyces species are covered by references 7 and 8 and Kluyveromyces species are covered by reference 9.
The 2 μm plasmids of Saccharomyces species are extrachromosomal DNA species which have evolved mechanisms to ensure their long term autonomous survival without any associated phenotype. The 2 μm plasmid resides in the nucleus and is packaged into chromatin. The plasmid origin of replication acts as an autonomously replicating sequence, while other sequences ensure the maintenance of a controlled high copy number and allow the plasmid to partition uniformly into the daughter cells at mitosis. The plasmid is not required for normal mitotic growth and does not provide the host with any selective advantage since Saccharomyces species devoid of 2 μm plasmid, denoted as cir o , grow only slightly faster than their 2 μm plasmid containing, or cir + , parents.
The 2 μm plasmid is a double stranded circular plasmid of approximately 6,318 bp, comprising two unique regions of 2,774 and 2,346 bp separated by a pair of exact inverted repeats, each 599 bp long (10). In vivo the monomeric plasmid exists as an equal mixture of the two inversion isomers (A and B) that form following site specific recombination between the two inverted repeats. The 2 μm plasmid has four open reading frames known as FLP (also known as A), REP1 (also known as B), REP2 (also known as C) and RAF (also known as D). The plasmid also contains a region, located between RAF and the origin of replication, called STB or REP3, which is composed of a series of imperfect 62 bp repeat elements This element is required in cis, along with the trans acting elements, REP1 and REP2, to enable efficient partitioning of the plasmid between the mother and the daughter cell.
The 2 μm plasmid copy number is also indirectly under the control of chromosomal genes, since it is known that 2 μm plasmid copy number does vary between different Saccharomyces cerevisiae strains and because the chromosomal recessive mutation, known as nib1, results in clonal lethality due to uncontrolled amplification of 2 μm plasmid copy number (39). Yeast strains carrying the nib1 mutation resemble engineered yeast strains where FLP gene expression is galactose induced. The involvement of proteins of the fungal ATP-dependent ubiquitin protein degradation pathway in the regulation of fungal plasmid copy number is not described in the art. Nor is it disclosed that genes of the fungal ATP-dependent ubiquitin protein degradation pathway can be manipulated to control fungal plasmid copy number.
Although the 2 μm plasmid is a very common genetic component of Saccharomyces cerevisiae, other yeast strains are known to contain identifiable DNA plasmids, notably the pSR1 and pSB3 plasmids (6,251 bp and 6,615 bp) of Zygosaccharomyces rouxii, the pSB1 and pSB2 plasmids (6,550 bp and 5,415 bp) of Zygosaccharomyces baijii, the pSM1 plasmid (5,416) of Zygosaccharomyces fermentati and the pKD1 plasmid (4,757 bp) of Kluyveromyces drosophilarum (9). The most striking feature of all these plasmids is their resemblance to the Saccharomyces cerevisiae 2 μm plasmid. Each plasmid is circular, double stranded DNA and is composed of two approximately equally sized halves separated by inverted repeat sequences. Each plasmid contains a single Autonomously Replicating Sequence (ARS) close to one of the inverted repeat sequences and three or four open reading frames, one of which encodes a recombinase which catalyses recombination between the inverted repeats.
A Saccharomyces cerevisiae plasmid is considered to be “2 μm-based” if it contains at least one of the 2 μm plasmid elements (ARS, inverted repeat sequences or 2 μm open reading frames), especially the ARS.
SUMMARY OF THE INVENTION
One aspect of the present invention provides a process of producing a fungal cell derived product, comprising (i) providing a fungal cell having a plasmid, the plasmid comprising a functional coding sequence for a protein, and the fungal cell having a modified level of Ubc4p or Ubc5p (hereinafter, generically known as Ubcp activity), and (ii) culturing the cell to produce the fungal cell derived product.
Preferably the fungal cell derived product is a desired protein encoded by the said coding sequence, and the said modified level of Ubcp activity is lower than normal for the cell. This can be tested in vivo by assaying for the rate of abnormal protein turnover (3). The level of Ubcp (Ubc4p and/or Ubc5p) activity may be reduced to at most 50%, 40%, 30%, 20%, 10% or 1% of the wild-type level. Preferably, the cell has a minimal Ubc4p or Ubc5p activity. The cell should not, however, have a low level of both Ubc4p and Ubc5p, since its growth rate will generally be too low to be useful.
The reduction in Ubcp activity can be achieved in any one of a variety of ways. Firstly the cell can produce a compound which interferes with the binding of the UBC-encoded product to its receptor. Hence, a construct may be provided in the cell to express a polypeptide which competes for the binding of Ubc4p or Ubc5p to its target. This will facilitate a reduction in the effective Ubc4p or Ubc5p activity. This may be done by over-expressing the UBC domain encoded by UBC4 or UBC5 described above. It will be important to ensure that the over-expressed UBC domain encoded by UBC4 or UBC5 does not have any intrinsic Ubc4p or Ubc5p activity of its own, since this might actually contribute to the overall Ubc4p or Ubc5p activity. This may be achieved, by site directed mutagenesis, by removing or replacing (for example with an alanine) the cysteine which acts as the acceptor site for the ubiquitin within the UBC domain of UBC4 (or 5) or other conserved amino acids within the UBC domain. Over expression of the inactive UBC domain of UBC4 (or 5) may be achieved from its own endogenous promoter, or from any other convenient promoter. The construct may be integrated into the chromosome or episomal.
Alternatively, in order to achieve a reduced level of Ubcp activity, the endogenous UBC gene may be modified such that substantially no protein is produced therefrom or such that any protein produced therefrom has a reduced level of Ubc4p or Ubc5p activity. Thus, for example, the UBC gene may be deleted (either in a regulatory region or in the coding region or both) such that no polypeptide is produced or a mutant (defective) polypeptide product is produced. (By “regulatory region”, we include parts of the genome acting on the UBC gene indirectly, for example a gene producing a UBC gene activator.) Deletion of all or part of the UBC open reading frame (14) is preferred, as this will reduce or abolish Ubcp activity and generate a non-reverting mutant fungal strain. Alternatively, the activity can be reduced or abolished by classical mutagenesis procedures, whereby the DNA sequence of the UBC gene is mutated in such a way as to produce point mutations or deletions which modify and/or disrupt the normal amino acid sequence of the Ubcp. If a mutant Ubcp polypeptide is produced, it may be unstable (ie be subject to increased protein turnover relative to the native protein); or unable to conjugate ubiquitin, or unable to deliver bound ubiquitin to its substrate.
For example, the UBC gene may be modified such that the ubiquitin-accepting cysteine in any protein produced therefrom is absent or of reduced ubiquitin-accepting activity, for example due to alterations in the amino acid residues surrounding or otherwise interacting with the cysteine, as noted above in the context of producing competitive (but inactive) polypeptide. Alternatively, the UBC gene may be modified such that the capacity of any mutant protein produced therefrom is unable to interact with or has reduced affinity for the E1 ubiquitin donor (product of the UBA1 or UBA2 genes). Alternatively, the UBC gene may be modified such that the capacity of any mutant protein produced therefrom to interact with the final ubiquitin acceptor and/or the Ubiquitin ligase (E3) enzyme is absent or reduced. Specifically, mutations (deletion, insertions or substitutions) within the first 21 amino acids of the primary sequence and the first α helix (residues 3-13) of Ubc4p and Ubc5p (29) are preferred as the latter have been implicated in binding of Ubc2p, a related protein, to the ubiquitin protein ligase Ubr1p (33). Especially preferred are mutations affecting the glutamic acid at position 10 (Glu-10) within the primary sequence of Ubc4p and Ubc5p, particularly replacement by lysine (Glu10Lys) or arginine (Glu10Arg).
Alternatively a different promoter may be used to control expression of the UBC gene; such a promoter may be regulatable. For example, it may be inducible, as are promoters of the galactose utilisation pathway, or derepressed by the removal of an inhibitor, as are promoters of the acid phosphatase group.
Site directed mutagenesis or other known techniques can be employed to create single or multiple mutations, such as replacements, insertions, deletions, and transpositions, as described in reference 23. Suitable mutations include chain termination mutations (clearly stop codons introduced near the 3′ end might have insufficient effect on the gene product to be of benefit; the person skilled in the art will readily be able to create a mutation in, say, the 5′ three quarters of the coding sequence), point mutations that alter the reading frame, small to large deletions of coding sequence, mutations in the promoter or terminator that affect gene expression and mutations that de-stabilize the mRNA. Specific mutations can be introduced by an extension of the gene disruption technique known as gene transplacement (24).
Generally one uses a selectable marker to disrupt a gene sequence, but this need not be the case, particularly if one can detect the disruption event phenotypically. In many instances the insertion of the intervening sequence will be such that a stop codon is present in frame with the UBC sequence and the inserted coding sequence is not translated. Alternatively the inserted sequence may be in a different reading frame to UBC.
A third principal way to achieve a reduction of Ubcp activity is for the cell to produce UBC antisense mRNA. This may be achieved in conventional ways, by including in the cell an expression construct for an appropriate sequence. UBC antisense mRNA may be produced from a constitutive or regulated promoter system (eg promoters of the galactose catabolic pathway), thereby facilitating a reduction in translatable UBC mRNA. Use of the regulated UBC antisense mRNA also allows for control of the ubiquitin-dependent protein degradation pathway by the addition or removal of the activator.
Fungal cells useful in the methods of the invention include the genera Pichia, Saccharomyces, Zygosaccharomyces, Kluyveromyces, Candida, Torulopsis, Hansenula (now reclassified as Pichia), Schizosaccharomyces, Citeromyces, Pachysolen, Debaromyces, Aspergillus, Metschunikowia, Rhodoporidum, Leucosporidum, Botryoascus, Endomycopis, Trichoderma, Cephalosporium, Humicola, Mucor, Neurospora and the like. Preferred genera are Pichia, Saccharomyces, Zygosaccharomyces and Kluyveromyces. Examples of Saccharomyces sp. are Saccharomyces cerevisiae, Saccharomyces italicus, Saccharomyces diastaticus and Zygosaccharomyces rouxii. Examples of Kluyveromyces sp. are Kluyveromyces fragilis and Kluyveromyces lactis. Examples of Hansenula sp. are Hansenula polymorpha (now Pichia angusta ), Hansenula anomala (now Pichia anomala ) and Pichia capsulata. An example of a Pichia sp. is Pichia pastoris. Examples of Aspergillus sp. are Aspergillus niger and Aspergillus nidulans. Yarrowia lipolytica is an example of a suitable Yarrowiva species.
Preferred are yeast strains, and of these Saccharomyces cerevisiae is the particularly preferred host. The yeast strains used can be any haploid or diploid strain of Saccharomyces cerevisiae, but in the case of diploid strains it is preferred that the activity of the Ubcp enzyme from both copies of the UBC gene is reduced or abolished.
A number of species have been shown to have homologues of Saccharomyces cerevisiae UBC4 and UBC5 genes. UBC4 and UBC5 homologues have been described in Homo sapiens (34) , Drosophila melanogaster (35), Caenorhabditis elegans (36), Arabidopsis thaliana (37), Schizosaccharomyces pombe and Candida albicans (38). The Drosophila melanogaster and Caenorhabditis elegans homologues, UbcD1 and ubc-2, respectively, have also been shown to have Ubcp activity. It can be seen that a homologue need not be termed UBC4 or UBC5; equally, a gene which is called UBC4 or UBC5 need not be a homologue.
Of the known UBC4/UBC5 homologues in the literature, the similarity of the various proteins can be calculated by aligning the primary amino acid sequences. A suitable program is the Megalign Program, Lasergene, DNASTAR Inc, 1228 South Park Street, Madison, Wis. 53715, USA. Using such a program the calculated percentage similarity ranges from 75.7% to 97.3. These values are very high and reflect the highly conserved nature of the Ubc proteins. The highly conserved cysteine residue in the active site occurs at position 193 in the consensus sequence.
Of the other Ubc proteins, the calculated percentage similarity between them and to Saccharomyces cerevisiae Ubc4p and Ubc5p ranged from 24.2% to 63.5%. Proteins homologous to the Saccharomyces cerevisiae Ubc4p and Ubc5p can therefore be defined as any Class I (as defined by Jentsch, 1992, reference 22) ubiquitin conjugating enzyme, which possesses 66.7% or greater primary amino acid sequence similarity to Saccharomyces cerevisiae Ubc4p or Ubc5p, as defined by the Megalign program. A gene is deemed to be homologous to S. cerevisiae UBC4 or UBC5 if it encodes such an enzyme.
A number of species have also been shown to possess Ubcp activity. As stated previously ubc4/ubc5 double mutants of Saccharomyces cerevisiae have increased doubling time, reduced resistance to amino acid analogues and reduced resistance to heat shock. It is known that the Drosophila UBC1 protein, encoded by the UbcD1 gene, which is 79.6% and 80.3% similar to Saccharomyces cerevisiae Ubc4p and Ubc5p respectively, can reverse the phenotypes of a yeast with no Ubc4p or Ubc5p activity when placed downstream of the UBC4 promoter (35). Similarly it is also known that the Caenorhabditis protein ubc-2, encoded by the ubc-2 gene, which is 78.2% and 78.9% similar to Saccharomyces cerevisiae Ubc4p and Ubc5p respectively, has the same properties (36). This is therefore a functional test of whether a protein from an unknown source has Ubc4p or Ubc5p activity. It can also be seen that, for the examples of doubling time and survival rate after 24 hrs at 38° C., the single ubc4 or ubc5 mutant strains described by Seufert and Jentsch (3,36) have similar characteristics to the wild-type strain. The Ubcp activity of an unknown Ubc protein, or a mutant form of a known Ubc protein, relative to the natural Saccharomyces cerevisiae Ubc4p or Ubc5p, can be determined by its relative ability to return the doubling time or survival rate after 24 hrs at 38° C. (as described in references 3 or 36), of a double ubc4/ubc5 mutant strain to normal for a wild type or single ubc4 or ubc5 mutant Saccharomyces cerevisiae strain once the unknown or mutant Ubc protein has been integrated into the Saccharomyces cerevisiae genome under the control of the endogenous UBC4 or UBC5 promoter, preferably as a single copy integration at the endogenous UBC4 or UBC5 locus by procedures already described in the literature (36).
In a preferred aspect of the invention, the level of Ubc4p or Ubc5p activity is reduced. This has been found to increase the copy number of an expression plasmid in the cell, and to cause an increased level of expression of a desired protein expressed from the plasmid. Conversely, increasing the level of Ubc4p or Ubc5p activity will reduce the level of expression of the protein, which may be desirable in some circumstances, for, example where the plasmid-encoded protein inhibits production of the desired protein.
The term “desired protein” is used herein in the normal sense to mean any protein (or other polypeptide) which is desired in a given process at a higher level than the one at which the fungal cell would, without human intervention, produce it. The desired protein may be endogenous to the species in question, for example it may be an enzyme which is normally produced by the host cell. Usually, however, the protein is heterologous to the host cell. The protein may perform its required task in the host cell or host cell culture without being extracted. Usually, however, the protein is extracted from the cell culture and purified to some extent for use elsewhere. The protein may be a viral, microbial, fungal, plant or animal protein, for example a mammalian protein. Preferably, it is a human protein, for example albumin, immnunoglobulin or a fragment thereof (such as an Fab fragment or single chain antibody), (haemo-)globin, blood clotting factors (such as factors II, VII, VIII, IX), interferons, interleukins, α I -antitrypsin, insulin, calcitonin, cell surface receptors, fibronectin, pro-urokinase, (pre-pro)chymosin, antigens for vaccines, t-PA, tumour necrosis factor, erythropoietin, G-CSF, GM-CSF growth hormone, plateletderived endothelial cell growth factor, and enzymes generally, such as glucose oxidase and superoxide dismutase. The protein is, of course, not Ubc4p or Ubc5p itself, nor a fusion of either Ubc4p or Ubc5p in which the Ubc4p or Ubc5p performs its natural function.
The desired protein, if it is to be purified from the fungal cell culture, may be obtained by any technique suited to that protein. For example, albumin may be purified from a Saccharoznyces, Kluveromyces or Pichia cell culture according to the techniques disclosed in WO96/37515, EP-625 202 or EP-464 590, respectively.
Our work has principally involved human albumin, although there is no reason to suppose that the process of the invention is applicable only to this protein, especially since the invention has also been shown to be advantageous in the expression of human haemoglobin.
The term “human albumin” is used herein to denote material which is indistinguishable from human serum albumin or which is a variant or fragment thereof. By “variant” we include insertions, deletions and substitutions, either conservative or non-conservative, where such changes do not substantially alter the oncotic, useful ligand-binding or immunogenic properties or albumin. For example we include naturally-occurring polymorphic variants of human albumin or human albumin analogues disclosed in EP-A-322 094. Generally, variants or fragments of human albumin will have at least 50% (preferably at least 80%, 90% or 95%) of human serum albumin's ligand binding activity (for example bilirubin-binding) and at least 50% (preferably at least 80%, 90% or 95%) of human serum albumin's oncotic activity, weight for weight.
The desired protein coding region is preferably contained within a hybrid plasmid comprising a promoter sequence, a DNA coding sequence which is under the transcriptional control of the promoter, a leader sequence directing the secretion of the protein and a DNA sequence containing a eukaryotic transcription termination signal, which plasmid is then maintained as an extrachromosomal DNA sequence or is integrated into one or more chromosomes of the host organism.
Suitable promoters for the expression of the protein include those associated with the phosphoglycerate kinase (PGK1) gene, galactokinase (GAL1) and uridine diphosphoglucose 4-epimerase (GAL10) genes, iso-1-cytochrome c (CYC1), acid phosphatase (PHO5), alcohol dehydrogenase genes (ADH1and ADH2) and MFα-1. The preferred promoters are the glycerol-3-phosphate dehydrogenase (GPD1), described in EP 424 117, and the protease B (PRB1) promoter, described in EP-431 880 B1.
Suitable transcription termination sequences can be the 3′ flanking equence of the eukaryotic gene which contains proper signals for transcription termination and polyadenylation in the fungal host, or those of the gene naturally linked to the expression control sequence, or those associated with the phosphoglycerate kinase (PGK1) or the iso-1-cytochrome c (CYC1) gene. The preferred transcription termination sequence is from the alcohol dehydrogenase gene (ADH1).
Suitable secretory leader sequences are, for example, the natural human serum albumin leader sequence, the leader sequence from the Saccharomyces cerevisiae MFα-1 leader sequence, the Kluyveromyces lactis killer toxin leader, a fusion between the natural human serum albumin leader and the Saccharomyces cerevisiae MFα-1 leader sequence, or a fusion between the Kluyveromyces lactis killer toxin leader and the Saccharomyces cerevisiae MFα-1 leader sequence, or conservatively modified variations of these sequences, as described in WO 90/01063.
Hybrid plasmids may also be used which, apart from the expression control sequence, the heterologous gene sequence and the transcription termination sequence, contain additional sequences which are non-essential or less important for the function of the promoter, ie for the expression of the desired polypeptide, but which perform important functions in, for example, the propagation of the cells transformed with the said hybrid plasmids. The additional DNA sequences may be derived from prokaryotic and/or eukaryotic cells and may include chromosomal and/or extra-chromosomal DNA sequences. For example, the additional DNA sequences may stem from (or consist of) plasmid DNA, such as bacterial, yeast or higher eukaryotic chromosomal DNA. Preferred hybrid plasmids contain additional DNA sequences derived from bacterial plasmids, especially Escherichia coli plasmid pBR322 or related plasmids, bacteriophage, yeast 2 μm plasmid, and/or yeast chromosomal DNA.
In the preferred hybrid plasmids for the expression of the heterologous polypeptide, the additional DNA sequences carry a yeast replication origin and a selective genetic marker for yeast. Hybrid plasmids containing a yeast replication origin, eg an autonomously replicating segment (ARS), are extrachromosomally maintained with the yeast cells after transformation and are autonomously replicated upon mitosis. Hybrid plasmids containing sequences homologous to the yeast 2 μm plasmid DNA can be as well. These hybrid plasmids may be integrated by recombination into yeast 2 μm plasmids already present within the cell or may replicate autonomously. The integration vectors of EP-A-251 744 or the “disintegration” vectors of EP-A-286 424 may be used.
Advantageously, the additional DNA sequences which are present in the hybrid plasmids also include a replication origin and a selective marker for the bacterial host, especially Escherichia coli, and a selectable marker for the final fungal host. There are useful features which are associated with the presence of an Escherichia coli replication origin and an Esclerichia coli marker in a yeast hybrid plasmid. Firstly, large amounts of hybrid plasmid DNA can be obtained by growth and amplification in Escherichia coli and, secondly, the construction of hybrid plasmids is conveniently done in Escherichia coli making use of the whole repertoire of cloning technology based on Escherichia coli. Escherichia coli plasmids, such as pBR322 and the like, contain both Escherichia coli replication original and Escherichia coli genetic markers conferring resistance to antibiotics, for example tetracycline and ampicillin, and are advantageously employed as part of the yeast hybrid vectors. The selective fungal marker may be any gene which facilitates the selection of transformants due to the phenotypic expression of the marker. Suitable markers are particularly those expressing antibiotic resistance or, as in the case of auxotrophic yeast mutants, genes which complement host lesions. Corresponding genes confer, for example, resistance to the antibiotic cycloheximide or provide for prototrophy in an auxotrophic yeast mutant, for example the URA1, URA3, LEU2, HIS3, HIS4, TRP5, TRP1 and LYS2 genes.
It has been demonstrated that ftingal cells of the genera Pichia, Saccharomyces, Kluyveromyces, Yarrowia and Hansenula can be transformed by enzymatic digestion of the cell walls to give spheroplasts; the spheroplasts are then mixed with the transforming DNA and incubated in the presence of calcium ions and polyethylene glycol, then transformed spheroplasts are regenerated in regeneration medium. The regeneration medium is prepared in such a way as to allow regeneration and selection of the transformed cells at the same time.
Since the yeast genes coding for enzymes of nucleic acid or amino acid biosynthetic pathways are generally used as selection markers, the regeneration is preferably performed in yeast minimal medium. Methods for the transformation of Saccharomyces cerevisiae are taught generally in EP 251 744, EP 258 067, WO 90/01063 and by Hinnen et al (4), all of which are incorporated herein by reference.
Hence, in its broadest aspect, the invention provides the use of a means to vary UBC4 or UBC5 function in a fungal cell to control the copy number of a plasmid in that cell.
Preferred non-limiting embodiments of the invention will now be described by way of example and with reference to the accompanying drawings, in which:
FIG. 1 is a plasmid map of pDB2277;
FIG. 2 is photograph of a rocket immunoelectrophoresis gel showing the increased rHA productivity of ubc5 disrupted yeast. Strains were as follows: Sample 1, DS569 ura3 [pAYE329/YCplac33]; Samples 2-17, DS569 ura3 [pAYE329/pDB2276] transformants 1-16; Samples 18-33, DS1101 ura3 [pAYE329/pDB2276] transformants 1-16; Samples 34-38 HSA standards 100, 75, 50, 30, and 20 μg/mL HSA;
FIG. 3 is the genomic DNA sequence of the yeast Saccharomyces cerevisiae gene UBC4; the 2.066 kb sequence extends from the PstI site 0.95 kb upstream of the start of the UBC4 open reading frame to the PstI site 0.58 kb downstream of the translation stop codon;
FIG. 4 is a plasmid map of pAYE399;
FIG. 5 is a plasmid map of pAYE400;
FIG. 6 is a plasmid map of pUBT1;
FIG. 7 is a plasmid map of pUBT2;
FIG. 8 is a plasmid map of pHbD2-1;
FIG. 9 is a plasmid map of pAYE792;
FIG. 10 is a plasmid map of pBST+;
FIG. 11 is a plasmid map of pDB2258;
FIG. 12 is a plasmid map of pDB2259;
FIG. 13 is a plasmid map of pDB2260;
FIG. 14 is a plasmid map of pDB2261;
FIG. 15 is the genomic DNA sequence of the Saccharomyces cerevisiae UBCS gene; the 1.2 kb sequence extends from the BglII site 0.55 kb upstream of the start of the UBC5 open reading frame to the BclI site 0.12 kb downstream of the translation stop codon;
FIG. 16 is a plasmid map of pDB2262;
FIG. 17 is a plasmid map of pDB2264;
FIG. 18 is a plasmid map of pDB2275; and
FIG. 19 is a plasmid map of pDB2276.
DETAILED DESCRIPTION OF THE INVENTION
All standard recombinant DNA procedures are as described in reference 13 unless otherwise stated.
EXAMPLE 1
Disruption of the Saccharomyces cerevisiae UBC4 Gene
The Saccharomyces cerevisiae UBC4 gene is located on chromosome II The DNA sequence of the UBC4 gene is shown in FIG. 3 .
The UBC4 gene was mutated by the process of gene disruption (14) which deleted the entire UBC4 open reading frame, thereby preventing production of active Ubc4 protein. This was achieved by first amplifying by PCR a suitable marker gene (URA3) with mutagenic single stranded DNA primers which modified the 5′ and 3′ ends of the URA3 gene so as to include DNA sequences identical to regions 5′ and 3′ to the UBC4 open reading frame and then transforming a ura3 auxotrophic yeast strain to uracil protoerophy.
Two single stranded oligonucleotide primers (UBC4URA1 and UBC4URA2) suitable for PCR amplification of the 5′ and 3′ ends of the URA3 gene, incorporating UBC4 sequences at the extremes, were synthesised using an ABI 380B DNA Synthesiser.
UBC4URA1
5′TTTCATCGTC CAATCCCATA TAAATCTTGC
(SEQ ID NO:1)
TTCTCTTTTT CAGCTGAGTA AGCTTTTCAA
TTC ATCTTTT-3′
UBC4URA2
5′-TCTTATTTTT CATCTTAATA AATAATCCAG
(SEQ ID NO:2)
AGAATAAATC TATCCTGAAA AGCTTTTTCT
TTCCAATTTT-3′
PCR reactions were performed to amplify the URA3 gene from the plasmid YEp24 (15). Conditions were as follows: 1 μg/mL plasmid YEp24 DNA, 2 μM of each primer, denature at 94° C. for 30 seconds, anneal to 45° C. for 40 seconds, extend at 72° C. for 120 seconds for 20 cycles, followed by a 72° C. soak for 600 seconds, followed by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. Alternative conditions were, 2 ng/mL plasmid YEp24 DNA, 0.1 μM of each primer, denature at 94° C. for 30 seconds, anneal to 55° C. for 40 seconds, extend at 72° C. for 120 seconds for 30 cycles, followed by a 72° C. soak for 600 seconds, followed by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The product, 5′-UBC4-URA3-UBC4-3′, was analysed by gel electrophoresis and was found to be of the expected size, approximately 1.2 kb. The amplified PCR products were purified using a Promega Wizard PCR DNA purification kit according to the manufacturer's instructions.
The Saccharomyces cerevisiae strain DS569 cir 0 (16) was transformed to leucine prototrophy with the recombinant human albumin (rHA) secretion plasmid pAYE329 (19). The promoter sequence in this plasmid corresponds to that of the Saccharomyces cerevisiae NAD-linked glycerol-3-phosphate dehydrogenase (GPD1) gene, rather than the FAD-linked glycerol-3-phosphate dehydrogenase (GUT2) gene as originally described (19).
The ura3 auxotrophic derivative of the Saccharomyces cerevisiae strain DS569 [pAYE329] was created by mutating the URA3 gene by the process of gene disruption (14) which deleted part of the URA3 coding sequence, thereby preventing the production of active Ura3 protein. The plasmid YEp24 (15) was digested to completion with HindIII and the products resolved by gel electrophoresis. The 1.17 kb HindIII URA3 gene fragment was isolated and ligated into the unique HindIII site of pACYC184 (17) to create plasmid pAYE399, FIG. 4 . Plasmid pAYE339 was digested to completion with PstI and partially digested with NcoI, the products were resolved by gel electrophoresis and the 5.41 kb NcoI-PstI DNA fragment lacking the central part of the URA3 gene was isolated, blunt-end filled with the Klenow fragment of DNA Polymerase and religated. The resultant plasmid pAYE400, FIG. 5, possesses a deletion within the URA3 open reading frame and an NcoI site at the deletion site. The deletion derivative of URA3 gene (ΔURA3) was isolated as a 0.94 kb HindIII fragment from plasmid pAYE400. A ura3 auxotrophic mutant of DS569 [pAYE329] was created by transforming DS569 [pAYE329] with the ΔURA3 0.94 kb HindIII fragment and selecting for Ura − yeast by resistance to 5-fluoro-orotic acid (18). Colonies able to grow on this medium were purified, tested to verify that they were unable to grow in the absence of uracil supplementation and that the defect could be complemented by introduction of the URA3 gene by transformation.
One such strain, DS569 ura3 [pAYE329], was transformed to uracil prototrophy with the 5′-UBC4-URA3-UBC4-3′ PCR product. A Southern blot of digested genomic DNA of a number transformants was probed with the UBC4 gene as a 2.07 kb PstI DNA fragment and confirmed the disruption of the UBC4 gene. The new strain was designated UB05 [pAYE329].
These methods are equally applicable to the disruption of UBC4 in any haploid Saccharomyces cerevisiae strain. If the desired host already carries a ura3 auxotrophic mutation, then disruption of UBC4 can be performed with the 5′-UBC4-URA3-UBC4-3′ PCR product described above. If the desired haploid host does not carry a ura3 auxotrophic mutation, then disruption of UBC4 can be performed once the strain has been made ura3 by transformation with the ΔURA3 0.94 kb HindIII fragment from pAYE400 and selecting for Ura − yeast by resistance to 5-fluoro-orotic acid as described above In the case of a diploid host it is necessary to disrupt both UBC4 genes. This can be achieved by disrupting the UBC4 gene in each of the two parental haploid strains first before diploidisation.
EXAMPLE 2
Disruption of the Saccharomyces cerevisiae UBC4 Gene Enhanced the Production of Recombinant Human Albumin
The rHA productivity of the yeast strain DS569 [pAYE329] (which does not have a UBC4 disruption) and two independent isolates of UB05 [pAYE329], called UB05-1 [pAYE329] and UB05-6 [pAYE329] (both of which do have a UBC4 disruption) was assessed in 10 mL shake flask culture. Yeast were inoculated into YNB (Difco) minimal medium, buffered with sodium phosphate/citrate pH 6.0 and containing 2% w/v glucose, and incubated at 30° C., 200 rpm for 3 days. The rHA productivity was estimated by rocket immunoelectrophoresis against HSA standards (25-150 μg/mL). The rHA productivity of DS569 [pAYE329] under these conditions was calculated to be 45 mg/L, while the rHA productivity of the two UB05 [pAYE3291 isolates measured under identical conditions was calculated to be 77 and 75 mg/L, respectively.
EXAMPLE 3
Disruption of the Saccharomyces cerevisiae UBC4 Gene Increases Hybrid 2 μm Plasmid Copy Number
The plasmid copy number of the hybrid 2 μm plasmid of the yeast strains DS569 [pAYE329] and two independent isolates of UB05 [pAYE329], called UB05-1 [pAYE329] and UB05-6 [pAYE329], was assessed in 100 mL shake flask culture. Yeast were inoculated into YNB minimal medium, buffered with sodium phosphate/citrate pH 6.0 and containing 2% w/v glucose, and incubated at 30° C., 200 rpm for sufficient time, usually 1 to 2 days, to allow the culture density to exceed 5 AU/mL, equivalent to mid-logarithmic growth phase. Total genomic DNA was extracted by glass disruption of the yeast cells, followed by solvent extraction, dialysis and ethanol precipitation. The total genomic DNA was digested to completion with HindIII and the products analysed by gel electrophoresis. The ethidium bromide staining of the plasmid specific DNA bands increased relative to the ethidium bromide staining of the ribosomal DNA (rDNA) bands. indicating that the plasmid copy number of the hybrid 2 μm plasmid had increased. Quantitation of the hybrid 2 μm plasmid copy number relative to the copy number of the rDNA was performed by Southern blot analysis with a joint rDNA/HSA cDNA probe. This showed that the plasmid copy number of the hybrid 2 μm plasmid pAYE329 increased from 48.9±9.2 copies per haploid genome in DS569 [pAYE329] to 83.1±12.5 and 116.8±29.0 copies per haploid genome in UB05-1 [pAYE329] and UB05-6 [pAYE329], respectively.
EXAMPLE 4
Antisense UBC4 mRNA Expression.
One way to disrupt expression of the UBC4 gene is to arrange for expression of an antisense polynucleotide.
The antisense transcript can be expressed from a copy, or copies, of the antisense expression cassette which have been integrated into the chromosome(s), or it can be expressed from a low plasmid copy number vector, eg a centromeric vector like YCp50 (25) or YCplac1111, YCplac33, YCplac22 (26) or plasmids p413 through to p416 containing the GAL1, GALL or GALS promoters (27). The antisense transcript can also be expressed from a high plasmid copy number vector like pJDB207 (12), YEp13 or YEp24 (15). All of these expression plasmids or integrating cassettes require a yeast selectable marker eg URA3, HIS3 or TRP1 to facilitate selection during transformation of yeast containing the appropriate auxotrophic marker(s).
The promoter used to drive the expression of the antisense UBC4 or anti-sense UBC5, may be the native promoter, or a related promoter. This has the advantage of promoting expression of the antisense transcript at the same time as the appearance of the sense transcript. In an especially preferred embodiment, the antisense expression cassette is provided on a high plasmid copy number plasmid to ensure an excess of the antisense transcript over the sense transcript Alternative promoters include strong constitutive promoters such as the glycolytic promoters, eg PGK1, PYK1, TDH2/TDH3 and ENO1/ENO2. Use of strong regulated promoters will have the advantage that plasmid copy number can be regulated at the will of the operator. Examples of such promoters are the GAL1, GALL and GALS promoters (Mumberg et al, 27). These galactose-induced promoters have been incorporated into both high and low plasmid copy number vectors, separated from the CYC1 terminator by a multiple cloning site. The example described below utilises a plasmid called p426 GAL1 (Mumberg et al, 27). The antisense UBC4 transcript can be effective in inactivating UBC4 sense transcript only if the host fungal strain contains a proficient UBC4 gene. However, expression of a UBC4 antisense transcript in a ubc4 fungal strain may be beneficial in mopping up other UBC4-like transcripts, so this is an option as well.
Two single stranded oligonucleotide primers (UBC43 and UBC44) suitable for PCR amplification of the UBC4 open reading frame were synthesised using an ABI 380B DNA Synthesiser.
UBC43
5′-ATAAACAAGC TTCCAAAAAA ACATGATTTC ACT
(SEQ ID NO.:3)
GACTATA GAGTACATAC-3′
UBC44
5′-GTAAGGACTT AAGCTTTATA CAGCGTATTT CT
(SEQ ID NO.:4)
TTGTCCAT TCTCTGGCTG TAGC-3′
PCR reactions were performed to amplify the UBC4 gene from genomic DNA prepared from the yeast strain S288C. Conditions were as follows: 5 μg/mL S288C genomic DNA, 2 μM of each primer, denature at 94° C. for 30 seconds, anneal to 45° C. for 40 seconds, extend at 72° C. for 120 seconds for 35 cycles, followed by a 72° C. soak for 600 seconds, followed by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer, Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The product, 5′-(HindIII)-UBC4-(HindIII)-3′; was analysed by gel electrophoresis and was found to be of the expected size, approximately 0.58 kb. The amplified PCR products were purified using a Promega Wizard PCR DNA purification kit according to the manufacturer's instructions. Use of these two primers, UBC43 and UBC44, introduced HindIII sites 5′ and 3′ to the UBC4 open reading frame.
The purified PCR product, 5′-(HindIII)-UBC4-(HindIII)-3′, was digested to completion with HindIII, and ligated into the unique HindIII site situated between the GAL1 promoter and the CYC1 terminator of plasmid p426GAL1 (Mumberg et al, 27) generating two plasmids pUBT1 and pUBT2 (FIGS. 6 and 7 ). Plasmid pUBT1 contained the UBC4 open reading frame so orientated as to produce an antisense UBC4 transcript from the GAL1 promoter, while plasmid pUBT2 contained the UBC4 open reading frame so orientated as to produce a sense UBC4 transcript from the GAL1 promoter.
Yeast strains deficient in uracil biosynthesis due to the presence of a non-functional ura3 gene, such as DS569 ura3 [pAYE329] (Example 1), were transformed to uracil prototrophy with plasmid pUBT1. UBC4 antisense transcript production was induced by switching from a yeast growth medium containing glucose as the sole carbon source to a medium containing galactose as the sole carbon source. Conversely, UBC4 anti-sense transcript production was repressed by switching from a yeast growth medium containing galactose as the sole carbon source to a medium containing glucose as the sole carbon source.
EXAMPLE 5
Sense UBC4 mRNA Expression from the GAL1 Promoter
Plasmid pUBT2 (FIG. 7) allows for the over-expression of the UBC4 transcript. In a ubc4 deficient fungal strain transformed with plasmid pUBT2, when the carbon source is switched from glucose to galactose, UBC4 mRNA expression will be increased and will force plasmid copy number down. This is yet another way to facilitate control over plasmid copy number by switching between repressing and activating carbon sources. Again this can be done in either a ubc4 or UBC4 background.
Yeast strains deficient in uracil biosynthesis due to the presence of a non-functional ura3 gene, such as DS569 ura3 [pAYE329] (16) or a ura3 derivative of UB05 [pAYE329] (Example 1), were transformed to uracil prototrophy with plasmid pUBT2. UBC4 sense transcript production was induced by switching from a yeast growth medium containing glucose as the sole carbon source to a medium containing galactose as the sole carbon source. Conversely, UBC4 sense transcript production from pUBT2 was repressed by switching from yeast growth medium containing galactose as the sole carbon source to a medium containing glucose as the sole carbon source.
EXAMPLE 6
Disruption of the Saccharomyces cerevisiae UBC4 Genes Enhances the Production of other Recombinant Human Proteins
Elimination of the ubc4 gene will increase the expression of other heterologous proteins. This was exemplified by analysing the expression level of recombinant human haemoglobin in DS569 and DS1101 (described later in Example 7) which possesses a mutation within the UBC4 open reading frame. The human haemoglobin expression plasmid, called pHbD2-1 (FIG. 8 ), was based on the whole 2 μm disintegration vector pSAC35 (16). Transcription of the human α-globin chain was directed by the GPD1 promoter (19) and terminated by the PGKI terminator. Transcription of the human β-globin chain was directed from the PRB1 promoter and terminated by the ADH1 terminator (16).
The rHb productivity of the yeast strains DS569 and DS1101 transformed to leucine prototrophy with pHbD2-1 was assessed in 10 mL shake flask culture. Yeast were inoculated into YNB minimal medium, buffered with sodium phosphate/citrate pH 6.0 and containing 2% (w/v) glucose, and incubated at 30° C., 200 rpm for 3 days. The rHb productivity in yeast soluble cell extracts was quantitated by a spectrophotometric assay from the height of the Soret peak in a second derivative spectrum, by comparison with standard HbA of known concentration (28). Total soluble protein concentration was quantitated by Coomassie Protein Assay Reagent, according to the Manufacturer's Instructions (Pierce). The expression level of soluble rHb in DS569 [pHbD2-1] was calculated to be equivalent to 0.4% (w/v) total soluble protein. The expression level of soluble rHb increased to 0.8% (w/v) in the strain DS1101 [pHbD2-1] carrying the ubc4 deletion.
EXAMPLE 7
Mutation of the Saccharomyces cerevisiae UBC4 Gene
As described above, the original mutation was produced by random chemical mutagenesis. The starting strain for this process was DS569 [pAYE329] (16). DS569 [pAYE329] was subjected to chemical mutagenesis by N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and potential rHA over-expressing mutant strains selected by a plate screening procedure described in EP431880. One such mutant strain was called DS1101 [pAYE329]. Analysis of the rHA productivity of DS569 [pAYE329] and DS1101 [pAYE329] was performed in 10 mL shake flask culture as described in Example 2. The rHA productivity was estimated by rocket immunoelectrophoresis against HSA standards (25-150 μg/mL). The rHA productivity of DS569 [pAYE329] under these conditions was calculated to be approximately 45 mg/L, while the rHA productivity of DS1101 [pAYE329], measured under identical conditions, was calculated to be 78 mg/L.
The plasmid copy number of the hybrid 2 μm plasmid of the yeast strains DS569 [pAYE329] and DS1101 [pAYE329] was assessed in 100 mL shake flask culture, as described in Example 3. Quantitation of the hybrid 2 μm plasmid copy number relative to the copy number of the rDNA was performed by Southern blot analysis with a joint rDNA/HSA cDNA probe. This showed that the plasmid copy number of the hybrid 2 μm plasmid pAYE329 increased from 48.9±9.2 copies per haploid genome in DS569 [pAYE329] to 70.5±15.9 copies per haploid genome in DS1101 [pAYE329].
To enable the identification of the nature of the original mutation which was responsible for the increased plasmid copy number and rHA productivity observed in DS1101 [pAYE329] a partial Sau3A genomic DNA library was prepared from DS569 high molecular weight genomic DNA in the centromeric vector YCp50 (30). A new yeast strain DS1101 ura3 [pAYE329] was prepared from DS1101 [pAYE329] by the method described in Example 1. DS1101 ura3 [pAYE329] was transformed to uracil prototrophy with DNA from the DS569 YCp50 genomic library. The transformants were assayed for reduced rHA expression by an anti-HSA antibody dependant plate screening procedure described in EP431880. One isolate, DS1101 ura3 [pAYE329/pAYE792], was identified which had reduced rHA productivity when assessed in 10 mL in shake flask culture. Yeast were inoculated into YNB (Difco) minimal medium, buffered with sodium phosphate/citrate pH 6.0 and containing 2% w/v glucose, and incubated at 30° C., 200 rpm for 3 days. The rHA productivity was estimated by rocket immunoelectrophoresis against HSA standards and was shown to be reduced compared to the DS1101 ura3 [pAYE329/YCp50] control, but similar to the DS569 ura3 [pAYE329/YCp50] control. The plasmid copy number of the hybrid 2 μm plasmid of the yeast strains DS569 ura3 [pAYE329/YCp50], DS569 ura3 [pAYE329/pAYE792], DS1101 ura3 (pAYE329/YCp50] and DS1101 ura3 [pAYE329/pAYE792] was assessed in 100 mL shake flask culture, as described in Example 3. Quantitation of the hybrid 2 μm plasmid copy number relative to the copy number of the rDNA was performed by Southern blot analysis with a joint rDNA/HSA cDNA probe. This showed that the plasmid copy number of the hybrid 2 μm plasmid pAYE329 reduced from 59.4±6.0 copies per haploid genome in DS1101 ura3 [pAYE329/YCp50] to 38.3±1.3 copies per haploid genome in DS1101 ura3 [pAYE329/pAYE792], but remained unchanged in DS569 ura3 [pAYE329/YCp50] and in DS569 ura3 [pAYE329/pAYE792] at 33.0±5.3 and 27.5±4.5 copies per haploid genome, respectively.
The pAYE792 centromeric plasmid DNA was isolated from strain DS1101 ura3 [pAYE329/pAYE792] (31) into E.coli and DNA sequenced (FIG. 9 ). This revealed that the plasmid pAYE792 contained a contiguous 9.05 kb genomic insert from chromosome II of Saccharomyces cerevisiae (32) spanning the region incorporating the UBC4, TEC1 and MIS1 genes. Subsequent subcloning of the three individual genes showed that the UBC4 gene was responsible for the reduced rHA productivity and reduced plasmid copy number associated with pAYE792 in the strain DS1101 ura3 [pAYE329/pAYE792].
In order to establish the nature of the mutation introduced into DS1101 by the NTG mutagenesis of DS569 the UBC4 gene from DS1101 was isolated by PCR. Two single stranded oligonucleotide primers (UBC4A and UBC4B) suitable for the PCR amplification of the 2.1 kb UBC4 genomic. PstI fragment (FIG. 3) were prepared using an ABI 380B DNA Synthesiser.
(SEQ ID NO.: 5)
UBC4A
5′-ACTCCTGCAG TTATTCTTCT GCC-3′
(SEQ ID NO.: 6)
UBC4B
5′-GTGTACAATA AGCTGCAGTA CTC-3′
PCR reactions were performed to amplify the UBC4 gene from high molecular weight genornic DNA prepared from DS1101 according to reference 30. Conditions were as follows: 50 ng/mL to 0.5 ng/nL DS110 genomic DNA, 2 μM of each primer, denature at 94° C. for 30 seconds, anneal to 50° C. for 40 seconds, extend at 72° C. for 120 seconds for 40 cycles, followed by a 72° C. soak for 600 seconds, followed by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The amplified 2.1 kb DNA product was purified by TAE agarose gel electrophoresis by Geneclean III DNA extraction kit (Bio101 Inc., 1070 Joshua Way, Vista, Calif. 92083, USA) and digested to completion with PstI. The plasmid pBST+ (FIG. 10) was prepared from the phagemid pBS+(Stratagene, 1101 North Torrey Pines Road, La Jolla, Calif. 92037, USA) by digesting pBS+ with EcoRI and HindIII. The isolated linearised vector was ligated with a double stranded oligonucleotide linker with the sequence:
5′-
AGCTCCTAGGCCCGGGCGGCCGCAAGCTTGTCGACGCTAGCTGCAGAAGG
3′-GGATCCGGGCCCGCCGGCGTTCGAACAGCTGCGATCGACGTCTTCC
ATCCAGATCTCGAGGCGCCATCGAT-3′ (SEQ ID NO.:7)
TAGGTCTAGAGCTCCGCGGTAGCTATTAA-5′ (SEQ ID NO.:8)
Plasmid pBST+ was linearised with PstI and ligated with the PstI digested PCR amplified 2.1 kb UBC4 DNA product to generate four separate plasmid isolates, called pDB2258, pDB2259, pDB2260 and pDB2261 (FIGS. 11 - 14 ). The PstI inserts of all four plasmids (DS1101 derived) and the UBC4 gene isolated from pAYE792 (DS569 derived) were DNA sequenced. The DNA sequence analysis revealed a mutation within the DS1101 UBC4 gene. This mutation, a G to an A substitution, was located in the tenth codon and had the DNA sequence:
DS569 UBC4 gene:
ATG TCT TCT TCT AAA CGT ATT GCT AAA GAA CTA
(SEQ ID NO.:9)
Met Ser Ser Ser Lys Arg Ile Ala Lys Glu Leu
(SEQ ID NO.:10)
DS1101 UBC4 gene:
ATG TCT TCT TCT AAA CGT ATT GCT AAA AAA CTA
(SEQ ID NO.:11)
Met Ser Ser Ser Lys Arg Ile Ala Lys Lys Leu
(SEQ ID NO.:12)
The mutation was such that it would change the tenth amino acid from a glutamic acid to a lysine, denoted as Glu10Lys.
This mutant form, or indeed any mutant form, of the UBC4 gene can be introduced into any strain in which the UBC4 gene has already been disrupted by URA3, as already described in Example 1, by procedures sunilar to those already described in the literature for the replacement of the endogenous Saccharomyces cerevisiae UBC4 gene by the Caenorhabditis elegans ubc-2 gene (36). The yeast strain UB05 (Example 1) was transformed to ura3 (Ura−) with the 2.1 kb PstI fragment from either of the plasmids pDB2258, pDB2259, pDB2260 or pDB2261 (FIGS. 11-14) and selecting for Ura − yeast by resistance to 5-fluoro-orotic acid (18). Colonies able to grow on this medium were purified, tested to verify that they were unable to grow in the absence of uracil supplementation and that the defect could be complemented by introduction of the URA3 gene by transformation. Removal of the URA3 gene from the UBC4 locus in UB05 and its replacement by the Glu10Lys mutant form of the UBC4 gene was confirmed by Southern Blot.
EXAMPLE 8
Disruption of the Saccharomyces cerevisiae UBC5 Gene
The Saccharomyces cerevisiae UBC5 gene is located on chromosome IV. The DNA sequence of the UBC5 gene is shown in FIG. 15 .
The UBC5 gene was mutated by the process of gene disruption (14) which deleted the entire UBC5 open reading frame, thereby preventing production of active Ubc5 protein. This was achieved by first amplifying by PCR a suitable marker gene (URA3) with mutagenic single stranded DNA primers which modified the 5′ and 3′ ends of the URA3 gene so as to include DNA sequences identical to regions 5′ and 3′ to the UBC5 open reading frame and then transforming a ura3 auxotrophic yeast strain to uracil prototrophy.
Two single stranded oligonucleotide primers (UBC5URA1 and UBC5URA2) suitable for PCR amplification of the 5′ and 3′ ends of the URA3 gene, incorporatincg UBC5 sequences at the extremes, were synthesised using an ABI 380B DNA Synthesiser.
UBC5URA1 5′-AGGACTGCTT ATTGACTACC ATCTTGAAAA GTCATTTTCT GCTCACCACC AGCTTTTCAA TTCATCTTTT-3′ (SEQ ID NO.:13)
UBC5URA2 5′-TTGATGTGTG CGCTGAGGAA GGTAAGTCTA CACAATTTAT CCGTTAGCCC AGCTTTTTCT TTCCAATTTT-3′ (SEQ ID NO.: 14)
PCR reactions were performed to amplify the URA3 gene from the plasimid YEp24 (15). Conditions were as follows: 1 μg/mL plasmid YEp24 DNA, 2 μM of each primer, denature at 94° C. for 30 seconds, anneal to 45° C. for 40 seconds, extend at 72° C. for 120 seconds for 20 cycles, followed by a 72° C. soak for 600 seconds, following by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. Alternative conditions were, 2 ng/mL plasmid YEp24 DNA, 0.1 μM of each primer, denature at 94° C. for 30 seconds, anneal to 55° C. for 40 seconds, extend at 72° C. for 120 seconds for 30 cycles, followed by a 72° C. soak for 600 seconds, followed by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The product, 5′-UBC5-URA3-UBC5-3′, was analysed by gel electrophoresis and was found to be of the expected size, approximately 1.2 kb. The amplified PCR product was purified using a Promega Wizard PCR DNA purification kit according to the manufacturer's instructions.
DS569 ura3 [pAYE329] was transformed to uracil prototrophy with the 5′-UBC5-URA3-UBC5-3′ PCR product. A Southern blot of digested genomic DNA of a number of transformants was probed with the UBC5 gene as a 0.5 kb MluI-Asp718 DNA fragment and confirmed the disruption of the UBC5 gene. The new strain was designated UB1 [pAYE329].
In an alternative method to disrupt the UBC5 gene portions corresponding to the 5′ and 3′ ends of the UBC5 gene were cloned by PCR. Two pairs of single stranded oligonucleotide primers suitable for PCR amplification of the 5′ end of the UBC5 gene (DS101 and DS102) and the 3′ end of the UBC5 gene (DS103 and DS104), were synthesised using an ABI 380B DNA Synthesiser.
DS101
5′-TGACGCGGCC GCTCTAGATG TATTGCTAGT
(SEQ ID NO.:15)
GCTAGTACGG TG-3′
DS102
5′-TGACGTCGAC AAGCTTGGAA AATAAAACTC
(SEQ ID NO.:16)
CAACCATC-3′
DS103
5′-TGACAAGCTT GTGTAGACTT ACCTTCCTCA
(SEQ ID NO.:17)
GCGC-3′
DS104
5′TGACGCTAGC ACGCGTCTGA CTTCTAATCA
(SEQ ID NO.:18)
GAAGATTATG GG-3′
PCR reactions were performed to amplify the 5′ end of the UBC5 gene. Conditions were as follows: 1000-10 ng/mL S288C genomic DNA, 2 μM DS101 primer, 2 μM DS102 primer, denature at 94° C. for 30 seconds, anneal to 37° C. for 30 seconds, extend at 72° C. for 60 seconds for 30 cycles, followed by a 72° C. soak for 600 seconds, following by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The product, 5′-UBC5, was analysed by gel electrophoresis and was found to be of the expected size, 229 bp. The amplified PCR product was purified using a Promega Wizard PCR DNA purification kit according to the manufacturer's instructions.
PCR reactions were performed to amplify the 3′ end of the UBC5 gene. Conditions were as follows: 1000‥10 ng/mL S288C genomic DNA, 2 μM DS103 primer, 2 μM DS104 primer, denature at 94° C. for 30 seconds, anneal to 37° C. for 30 seconds, extend at 72° C. for 60 seconds for 30 cycles, followed by a 72° C. soak for 600 seconds, following by a 4° C. soak, using a Perkin-Elmer-Cetus Thermal Cycler and a Perkin-Elmer-Cetus PCR kit employing AmpliTaq Thermal Stable DNA Polymerase, total reaction volume 50 μL, according to the manufacturer's instructions. The product, 3′-UBC5, was analysed by gel electrophoresis and was found to be of the expected size, 327 bp.
The 5′-UBC5 DNA fragment was digested to completion with NotI and SalI, phenol/chloroform extracted and cloned into NotI/SalI linearised and phosphatased pBST+ to generate plasmid pDB2262 (FIG. 16 ). The 3′-UBC5 DNA fragment was digested to completion with NheI and HindIII, phenol/chloroform extracted and cloned into NheI/HindIII linearised and phophatased pBST+ to generate plasmid pDB2264 (FIG. 17 ). The DNA inserts of pDB2262 and pDB2264 were sequenced to confirm their identity. Plasmid pDB2264 was digested to completion with HindIII/NheI and the 327 bp fragment corresponding to the 3′ end of UBC5 isolated and cloned into pDB2262, linearised with HindIII/NheI and phophatased. The resultant plasmid called pDB2275 contained the 5′ and 3′ ends of the UBC5 gene, separated by a unique HindIII site (FIG. 18) The entire genomic URA3 gene isolated as a 1.2 kb HindIII fragment was cloned into linearised pDB2275 with HindIII and phosphatased, generating plasmids pDB2276 (FIG. 19) and pDB2277 (FIG. 1) which only differed from each other by the orientation of the URA3 marker gene.
DS569 ura3 [pAYE329] was transformed to uracil prototrophy with the 5′-UBC5-URA3-UBC5-3′ disrupting fragment isolated from either pDB2276 or pDB2277 as 1.7 kb MluI-XbaI fragments. The rHA productivity of these yeast transformants was assessed in 10 mL shake flask culture. Yeast were inoculated into YNB (Difco) minimal medium, buffered with sodium phosphate/citrate pH 6.0 and containing 2% w/v glucose, and incubated at 30° C., 200 rpm for 3 days. The rHA productivity was estimated by rocket immunoelectrophoresis against HSA standards (25-150 μg/mL). The rHA productivity of DS569 [pAYE329] under these conditions was calculated to be approximately 40 mg/L, while the rHA productivity of some of the pDB2276 or pDB2277 transformants measured at the same time was increased to a level greater than that of DS569 [pAYE329], calculated to be approximately 60 mg/L (FIG. 2 ).
REFERENCES
1. Varshavsky, A. (1992) Cell 69, 725-735.
2. McGarth, J. P., et al (1991) EMBO J. 10, 227-236.
3. Seufert, W. and Jentsch, S. (1990) EMBO J. 9, 543-550.
4. Hinnen, A., et al (1978) P.N.A.S. ( USA ) 75, 1929.
5. Esser, K., et al (1986) “Plasmids of eukaryotes” Springer-Verlag K G, Heidelberg, Germany.
6. Wickner, R. B., et al (1986) “Extrachromosomal elements in lower eukaryotes” Plenum Publishing Corp., New York.
7. Murray, J. A. H. (1987) Molecular Microbiology 1, 14.
8. Futcher, A. B. (1988) Yeast 4, 2740.
9. Volkert, F. C., et al (1989) Microbiological Reviews 53, 299-317.
10. Hartley, J. L. and Donelson, J. E. (1980) Nature (Lond) 286, 860-
11. Murray, J. A. H., et al (1987) EMBO J. 6, 4205-4212.
12. Beggs, J. D. (1981) “Molecular Genetics in Yeast” Alfred Benz on Symposium 16, 383-395.
13. Maniatis, T., et al (1982) and Sambrook et al (1989) “Molecular Cloning: A Laboratory Manual” Cold Spring Harbor Laboratory, Cold Spring, N.Y.
14. Rothstein, R. J. (1983) Methods Enzymol. 101, 203-211.
15. Botstein, D., et at (1979) Gene 8, 17-24.
16. Sleep, D., et al (1991) Bio/Technology 9, 183-187.
17. Chang, A. C. Y. and Cohen, S. N (1978) J. Bacteriol. 134, 1141-1156.
18. Boeke, J. D., et al (1987) Methods Enzymol. 154, 164-175.
19. Sleep, D., et at (1991) Gene 101, 89-96.
20. Rose, A. B. and Broach, J. R. (1990) Methods Enzymol. 185, 234-279.
21. EP-A-0 431 880.
22. Jentsch, D. (1992) Annu. Rev. Genet. 26, 179-207.
23. Botstein and Shortle (1985) “Strategies and Applications of In Vitro Mutagenesis” Science 229, 193-210.
24. Winston, F. et al (1983) Methods Enzymol. 101, 211-228.
25. Rose, M., et al (1987) Gene 60, 237-243.
26. Gietz, R. and Sugino, A. (1988) Gene 74, 527-534.
27. Mumberg D., et al (1994) Nuc. Acids Res. 22, 5767-5768.
28. Ogden, J. E. et al (1994) Meth. Enz. 231, 374-390.
29. Cook, W. et al (1993) Biochemistry 32, 13809-13817.
30. Rose, M. D. et al (1987) Gene 60, 237-243.
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33. Worthylake, et al (1998) J. Biol. Chem 273, 6271-6276.
34. Jensen, J. P. et al (1995) J. Biol. Chem. 270, 30408-30414.
35. Treier, M. et al (1992) EMBO. J. 11, 367-372.
36. Zhen, M. et al (1993) 13, 1371-1377.
37. Girod, P-A. et ac (1993) Plant J. 3, 545-552.
38. Damagnez, V. et al (1995) Gene 155, 137-138.
39. Holm, C. (1982) Cell 29, 585-594.
20
70 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR primer”
NO
NO
1
TTTCATCGTC CAATCCCATA TAAATCTTGC TTCTCTTTTT CAGCTGAGTA AGCTTTTCAA 60
TTCATCTTTT 70
70 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR primer”
NO
NO
2
TCTTATTTTT CATCTTAATA AATAATCCAG AGAATAAATC TATCCTGAAA AGCTTTTTCT 60
TTCCAATTTT 70
50 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR primer”
NO
NO
3
ATAAACAAGC TTCCAAAAAA ACATGATTTC ACTGACTATA GAGTACATAC 50
54 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
4
GTAAGGACTT AAGCTTTATA CAGCGTATTT CTTTGTCCAT TCTCTGGCTG TAGC 54
23 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
5
ACTCCTGCAG TTATTCTTCT GCC 23
23 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
6
GTGTACAATA AGCTGCAGTA CTC 23
75 base pairs
nucleic acid
double
linear
other nucleic acid
/desc = “OLIGONUCLEOTIDE LINKER”
NO
NO
7
AGCTCCTAGG CCCGGGCGGC CGCAAGCTTG TCGACGCTAG CTGCAGAAGG ATCCAGATCT 60
CGAGGCGCCA TCGAT 75
75 base pairs
nucleic acid
double
linear
other nucleic acid
/desc = “OLIGONUCLEOTIDE LINKER”
NO
NO
8
AATTATCGAT GGCGCCTCGA GATCTGGATC CTTCTGCAGC TAGCGTCGAC AAGCTTGCGG 60
CCGCCCGGGC CTAGG 75
33 base pairs
nucleic acid
double
linear
DNA (genomic)
NO
NO
9
ATGTCTTCTT CTAAACGTAT TGCTAAAGAA CTA 33
11 amino acids
amino acid
<Unknown>
linear
protein
NO
NO
10
Met Ser Ser Ser Lys Arg Ile Ala Lys Glu Leu
1 5 10
33 base pairs
nucleic acid
double
linear
DNA (genomic)
NO
NO
11
ATGTCTTCTT CTAAACGTAT TGCTAAAAAA CTA 33
11 amino acids
amino acid
<Unknown>
linear
protein
NO
NO
12
Met Ser Ser Ser Lys Arg Ile Ala Lys Lys Leu
1 5 10
70 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
13
AGGACTGCTT ATTGACTACC ATCTTGAAAA GTCATTTTCT GCTCACCACC AGCTTTTCAA 60
TTCATCTTTT 70
70 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
14
TTGATGTGTG CGCTGAGGAA GGTAAGTCTA CACAATTTAT CCGTTAGCCC AGCTTTTTCT 60
TTCCAATTTT 70
42 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
15
TGACGCGGCC GCTCTAGATG TATTGCTAGT GCTAGTACGG TG 42
38 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
16
TGACGTCGAC AAGCTTGGAA AATAAAACTC CAACCATC 38
34 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
17
TGACAAGCTT GTGTAGACTT ACCTTCCTCA GCGC 34
42 base pairs
nucleic acid
single
linear
other nucleic acid
/desc = “PCR PRIMER”
NO
NO
18
TGACGCTAGC ACGCGTCTGA CTTCTAATCA GAAGATTATG GG 42
2072 base pairs
nucleic acid
double
linear
DNA (genomic)
NO
NO
19
CTGCAGTACT CTTTTGATTC TGTAGGAAAC CAGCGAAGAA CGTACTCTTG CCTGAAGAGA 60
AGTTTTTTTT ATTTATTTAT ATTTTGTTCT GGAAGCTCTT TACAGAATGG AGTAGGAAAA 120
TATATAGAGA GGAAAAGCGA AATCGTTACG AGAATAAATA ATCAAGAAAA GAAACTTGAA 180
CTTGGCTTTT CCAAAACAAC AGAAGTAGCG TTAATTTACT TTCACCGTAA AATTCAACTC 240
TTTAAATATA GTCCACTTAG TAAATTCTTG CCAATTTGCA TGATAAATTC GAACCCATTC 300
CTCAAAATAA AGGGTCCTCA TACATTCCAT GGAAAGAAAG TTTTCTTGAA CATTAAGAAT 360
AAAAAGGCAA AAAAGAAAAA AAAAAGCACA GCTACTGTTT TAGTCAACAT TCCTTTCTCA 420
CTGGAATGCA CAAGGTGTCA TTCCTGAACA AGGGTAACTG CACTATTCAT ATGTCCACCT 480
TATGACTTCA TAAAAAGTTT GACAATAAGT AGTCTTACGT GATAAGAAAT GATGTAACAT 540
AAGGCTAATG TCCTTATTCC AAAGTATCTC ATTTATACAA TAAACAAAAC TGATCTTACC 600
GCCTATCCTC CTCTCCGCAC TAATCAATTG TTATAGTTTT TCTCGAAGCG AGGATCAAAT 660
GGCCGAGCAA CAGGAAAAGG AGTACCGGCG GTCACATGGT CTGCGAGATT TTTCCCGCTG 720
CGGAAAAACC TGGCAACAGC TCACCTTGAA AGGCCTTGGC CTGTATTTTT CTTTTTTCTT 780
CATCCTTCTT TCTTTTTCTT TATTCTTATT TTTCATCTTA ATAAATAATC CAGAGAATAA 840
ATCTATCCTG AAAAAAAATA AAGTAAAGAA GCCAGGAAAA TCACTATCGC CACAAGTAAA 900
TAAATTTCAC TGACTATAGA GTACATACAT AAACAAGCAT CCAAAAAAAC ATGTCTTCTT 960
CTAAACGTAT TGCTAAAGAA CTAAGTGATC TAGAAAGGTA TGTCTAAAGT TATGGCCACG 1020
TTTCAAATGC GTGCTTTTTT TTTAAAACTT ATGCTCTTAT TTACTAACAA AATCAACATG 1080
CTATTGAACT AGAGATCCAC CTACTTCATG TTCAGCCGGT CCAGTCGGCG ATGATCTATA 1140
TCACTGGCAA GCATCCATCA TGGGACCTGC CGATTCCCCA TATGCCGGCG GTGTTTTCTT 1200
CTTGTCTATC CATTTCCCAA CCGACTACCC ATTCAAGCCA CCAAAGATCT CCTTCACAAC 1260
CAAGATATAT CATCCAAATA TCAATGCCAA TGGTAACATC TGTCTGGACA TCCTAAAGGA 1320
TCAATGGTCT CCAGCTCTAA CTCTATCGAA GGTCCTATTA TCCATCTGTT CTTTGTTAAC 1380
AGACGCTAAT CCTGACGATC CTTTAGTACC AGAAATCGCT CATATCTACA AGACTGACAG 1440
ACCCAAGTAC GAAGCTACAG CCAGAGAATG GACAAAGAAA TACGCTGTAT AAACAGAAGT 1500
CCTTACTCAG CTGAAAAAGA GAAGCAAGAT TTATATGGGA TTGGACGATG AAAAGAATAT 1560
TAGATACAAT GTATTTAAGA AAGAATACAA TAAAATATAT GTATATTCTA TCTCTAATAA 1620
CATAGATTTA CTGATATAAG ATATAAGACT ATTGTTGGCA ACAGTACAGG GGAACCTTTT 1680
TTTTTTTTTC CAAACAACTC GAATCGTAAA CCTTAATTTA ATTTATTCAG GGGAGATTCA 1740
TGAACATTTT TTTCCTCGAA CAGTATGGAG AATTTTTGCT TAGTTACATG CACGCAAGCG 1800
CGGGTATACC CGCATATATT TCAGTTGTGG TTCATAATTT GACCTAACTT GTCGAGGGAG 1860
CGTCAACGTT AACCGTACCT TTTTCATTTC TAGTCTATCT GTAGGTTAAT TACTATTGTC 1920
ATTAACATCA TTTCTGGGGT GAAGCCTATT TAAATTTTTG AAGTTCAACG CATAGCTAGT 1980
ATATGTAATC AACGATCAAT GACTGGTTCT CTGTTTGGCA AAAATTCTGA GGAGCATTAC 2040
ACTGTACTAA GGAGGCAGAA GAATAACTGC AG 2072
1206 base pairs
nucleic acid
double
linear
DNA (genomic)
NO
NO
20
AGATCTGCTA TTGCATGTGG TGAAAGTTAT ACCAACATTT TTGCTTATAT GAAATCATCT 60
GCAACAACCA ATTGGATAAG GATAGATTTC TCAAATATAT TAAATTATGT CTTGGTTTAC 120
TTACACAGAA AGTCCCAAAG TACAGATGAA TTATACTAGG GTTGTGTTCA TTGTTCCATG 180
AGAGGCTGTA CTTTTTGCCT ACTTATTTTG GTACTCATTC ATTAGGCTCA TAAACCGATT 240
TTTCTTATAT TGTGCGTAAT TCAATTAGAT ATCTAGATGT ATTGCTAGTG CTAGTACGGT 300
GTAAACTCTC GTAGCAAGCG TTTTGAAGCA TGGCTGTGGT GGAGGTAGTT GCCACTGCGA 360
GCGGGTAATA AAGCGGCTGC CGCCTTACTC ATTTGTACCA AAGATAGCCG ACCCAAAATT 420
ATAAAAAATA ATTGTATCCC GGATTTTAAT AGATGGTTGG AGTTTTATTT TCCAAGGTCA 480
GGACTGCTTA TTGACTACCA TCTTGAAAAG TCATTTTCTG CTCACCACCC TCAACTAAAC 540
TAAAAATGTC TTCCTCCAAG CGTATTGCCA AGGAATTAAG TGATTTAGGG AGGTATGTTA 600
AAAATAAAAT AATGATTTTT CTTGATCTGT AAAGAAAAAG GATTACTAAC ATGAGTTTCT 660
TTTTTGAACT TTTTTCCGAA GAGATCCTCC TGCTTCATGT TCAGCAGGAC CTGTAGGGGA 720
TGACCTGTAT CATTGGCAAG CCTCTATTAT GGGTCCTTCA GACTCACCCT ACGCTGGTGG 780
CGTTTTCTTT TTGTCTATTC ACTTTCCAAC TGATTATCCA TTCAAGCCAC CGAAGGTAAA 840
CTTTACGACC AAAATTTATC ATCCGAATAT TAATTCGAGT GGTAATATCT GCCTTGATAT 900
TTTAAAGGAC CAGTGGTCAC CGGCGCTAAC CCTTTCAAAA GTTTTGTTGT CTATTTGCTC 960
TCTTTTAACA GATGCTAATC CCGACGATCC TTTGGTCCCT GAAATTGCTC AAATCTACAA 1020
GACAGATAAG GCTAAGTATG AAGCCACCGC TAAGGAGTGG ACTAAAAAAT ATGCTGTTTG 1080
ATTAATTTGG GCTAACGGAT AAATTGTGTA GACTTACCTT CCTCAGCGCA CACATCAATA 1140
TATTATATAT TCTTTACGTA TACAAACACG CAAATTCTTA TAGGTATAGC GATATTAGTT 1200
TGATCA 1206 | The use of a means to vary Ubc4p or Ubc5p activity in a fungal cell to control the copy number of a plasmid in the cell. The level of Ubc4p or Ubc5p activity may be reduced/abolished (for example by gene deletion, mutagenesis to provide a less active protein, production of antisense mRNA or production of competitive peptides) to raise the copy number and increase yield of a protein encoded by the plasmid. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a means for securely adjoining a blood collection needle and a needle holder. More particularly, this invention relates to a friction coating or material in cooperation with a needle assembly and a needle holder to prevent the needle assembly from prematurely disengaging from the needle holder.
2. Description of Related Art
Blood collection needle assemblies are typically used in conjunction with conventional needle holders in order to facilitate the collection of blood into a tube or several tubes. However, there is no means for preventing the needle from prematurely disengaging from the needle holder.
Therefore, a need exists to provide a means for preventing premature disengagement of a needle from a needle holder.
SUMMARY OF THE INVENTION
The present invention is a friction coating or material located on the hub of a needle. More particularly, the friction coating or material is located on the flange of the hub adjacent the threaded connection used to engage the needle assembly with a needle holder.
Preferably, the needle assembly of the present invention comprises a cannula and a hub. Preferably, the cannula is a conventional double ended needle. The hub comprises a threaded end, a ribbed end and a flange separating the threaded and ribbed ends. The flange comprises a threaded end surface and a ribbed end surface. The needle is connected to the hub whereby the needle comprises a non-patient end and an intravenous end.
Most preferably, the friction coating or material is located on the threaded end surface of the flange of the hub adjacent the threaded end. The friction coating or material may be located on only a portion or portions of the flange surface or on the entire flange surface.
Preferably, the friction coating is a solid elastomeric material, or another material with similar properties. Preferably, the friction coating is a thermoset adhesive and most preferably a UV curable acrylic thermoset adhesive such as for example, acrylated urethane. Preferably the thermoset adhesive cures rapidly to form flexible, transparent bonds when exposed to ultraviolet and/or visible light of sufficient irradiance. Preferably, the friction coating is a good adhesion coating between thermoplastics such as those used in medical devices.
A commercially available adhesive that may be used in the present invention is Loctite Product 3341 distributed by the Loctite Corporation of Rocky Hill, Conn.
Alternatively, the friction material may be a spring washer structure located on the entire surface area of the flange. The friction material may be metal or plastic.
A notable advantage of the present invention is that the friction coating or material is that it prevents a blood collection needle from "spinning-out" of its associated holder.
The "spinning-out" effect may be caused when a safety device is associated with the collection needle and the safety device is rotated or when an evacuated tube is inserted into the needle holder.
Another notable feature of the friction coating or material of the present invention is that it does not interfere with the normal and conventional methods of using blood collection devices.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a needle assembly with a friction coating material on a portion of the flange surface.
FIG. 2 is a perspective view of a needle assembly with a friction coating on a substantial portion of the surface of the flange.
FIG. 3 is a top plan view of the needle assembly of FIG. 1 taken along line 3--3 thereof.
FIG. 4 is a top plan view of the needle assembly of FIG. 2 taken along line 4--4 thereof.
FIG. 5 is a perspective view of the needle assembly of FIG. 1 with a needle holder.
FIG. 6 is a perspective view of an alternative embodiment of a needle assembly with a safety device and a friction coating on the surface of the flange.
FIG. 7 is a perspective view of the needle assembly of FIG. 6 with a needle holder.
DETAILED DESCRIPTION
While this invention is satisfied by embodiments in many different forms, there is shown in the drawings and will herein be described in detail, the preferred embodiments of the invention, with the understanding that the present disclosure is to be considered as exemplary of the principles of the invention and is not intended to limit the invention to the embodiments illustrated. Various other modifications will be apparent to and readily made by those skilled in the art without departing from the scope and spirit of the invention. The scope of the invention will be measured by the appended claims and their equivalents.
Referring to the drawings in which like reference characters refer to like parts throughout the several views thereof, FIGS. 1 through 4 illustrate a needle assembly with the friction coating of the present invention. Needle assembly 20 includes a needle, a hub, and a friction coating.
As shown in FIGS. 1 and 2, the needle includes a non-patient end 42, an intravenous end 44 and a passageway extending between the non-patient end and the intravenous end. An elastomeric sleeve 48 covers the non-patient end.
As shown in FIGS. 1 and 2, hub includes a threaded end 64, a ribbed end 66 and a passageway extending between the threaded end and the ribbed end. Threaded end 64 and ribbed end 66 are separated by flange 68. Flange 68 includes a threaded end surface 70 a ribbed end surface 72. Non-patient end 42 of the needle extends from threaded end 64 and intravenous end 44 of the needle extends from ribbed end 66. Preferably, threaded end 64 comprises male threads 80 for mounting the hub on a conventional needle holder and ribbed end 66 comprises male ribs 82. As more particularly shown in FIGS. 3 and 4, friction coating 90 is located on threaded end surface 70 of flange 68.
The needle assembly is assembled together whereby the needle is connected to the hub and sealed with adhesive at the ends of the hub. Friction coating 90 is added to the threaded end surface 70 of flange 68. It is within the purview of the invention that the friction coating or friction material may cover a portion, portions or the entire threaded end surface of the flange as shown in FIGS. 3 and 4.
In use, a needle holder is screwed onto the hub of the needle assembly, as shown in FIG. 5, whereby the friction coating forms a removably secure adhesion between the threaded hub of the needle assembly and the needle holder during use. The friction coating allows the needle assembly to be removed from the needle holder in conjunction with a convention disposal container.
FIG. 6 is a further embodiment of the invention that includes many components which are substantially identical to the components of FIGS. 1-4. Accordingly, similar components performing similar functions will be numbered identically to those components of FIGS. 1-4, except that a suffix "a" will be used to identify those similar components in FIG. 6.
Alternatively, the needle assembly of the present invention may be used in conjunction with a safety shield assembly, as illustrated in FIG. 6.
A safety shield assembly comprising a shield 100 and a collar 110 are connected to needle assembly 20a. As shown in FIG. 6, friction coating 90a is located on threaded end surface 70a of flange 68a. In use, the needle holder is screwed onto the hub of the needle whereby the friction coating forms a removably secure adhesion between the needle assembly and the needle holder.
In use, as exemplified in FIG. 7, a needle holder is screwed onto the hub of the needle assembly with the safety shield whereby the friction coating forms a removably secure adhesion between the threaded hub of the needle assembly and the needle holder during use. The friction coating allows the needle assembly to be removed from the needle holder in conjunction with a convention disposal container. | The present invention is a needle assembly comprising a friction coating or material to prevent the needle assembly from prematurely disengaging from a needle holder. Preferably, the friction coating is UV curable acrylic or a spring washer. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a system for pleasurable use by people of all ages with youthful minds in operating remotely controlled vehicles simultaneously in a somewhat confined area. In the system of this invention, the vehicles can be remotely controlled to perform competitive or cooperative tasks. The system includes control pads for operation by the users, vehicles remotely controlled in accordance with the operation of the control pads and a central station for coordinating the operation of the control pads and the vehicles. In addition to the inventive aspects of the system, each of the control pads, the central station and the vehicles includes features of an inventive nature. The system of this invention also includes stationary plants (e.g. power plants and elevators) which are controlled by the operation of the control pads. The invention additionally relates to methods including methods for controlling the operation of the vehicles on a remotely controlled basis.
More specifically, this invention relates to remotely controlled vehicles having inventive features such as toy self-loading dump trucks, trailers, forklifts and bulldozers that can be operated to mimic the operation of similar full-size vehicles by employing highly-maneuverable skid steering, having automatic tow hitch actuation mechanisms and having motorized accessories for scooping up transportable elements, transferring the transportable elements to a hopper, automatically activating the hopper to dump the transportable elements, for gripping, lifting and translating transportable elements, and for pushing transportable elements along a surface.
2. Description of the Related Art
Various types of toy systems exist, and have existed for some time, in which vehicles are moved on a remotely controlled basis. Examples of a vehicle in such a system are an automobile, airplane, truck, water vehicle or construction vehicle. In most such systems, however, the functions and activities that the vehicle is capable of are limited to merely maneuvering a vehicle about on the ground, in the air or in the water. Other types of toy systems involve the use of blocks for building structures. These blocks often include structure for providing an interlocking relationship between abutting blocks. In this way, elaborate structures can be created by users with creative minds. However, such structures are generally built by hand manipulation of the blocks or hand manipulation of a mechanism of toy vehicle for handling the blocks.
Experience has proven that there is a desirability, and even a need, for play systems in which vehicles are remotely operated to perform functions other than merely being steered or maneuvered through a path of travel. For example, there exists a desire for a play system in which the remotely controlled vehicles have the capability of transporting elements such as building blocks maneuverable into position to build a toy or other structure. It is desirable that such systems employ a plurality of vehicles remotely controlled by switches in hand-held control pads so that users can compete against one another in performing various tasks such as moving building blocks or marbles.
Co-pending application Ser. No. 08/580,753 filed by John J. Crane on Dec. 29, 1995, for a "Remote Control System for Operating Toys" and assigned of record to the assignee of record of this application discloses and claims a play system for use by people of all ages with youthful minds. It provides for a simultaneous control by each player of an individual one of a plurality of remotely controlled vehicles. This control is provided by the operation by each such player of switches in a hand-held unit or pad, the operation of each switch in such hand-held unit or pad providing a control of a different function in the individual one of the remotely controlled vehicles. Each of the remotely controlled vehicles in the system disclosed an claimed in application Ser. No. 08/580,753 can be operated in a competitive relationship with others of the remotely controlled vehicles or in a co-operative relationship with others of the remotely controlled vehicles. The vehicles can be constructed to pick up and transport elements such as blocks or marbles and to deposit such elements at displaced positions.
When manually closed in one embodiment of the system disclosed and claimed in application Ser. No. 08/580,753, switches in pads control the selection of toy vehicles and the operation of motors for moving the vehicles forwardly, rearwardly, to the left and to the right and moving upwardly and downwardly (and rightwardly and leftwardly) a receptacle for holding transportable elements (e.g. marbles) or blocks.
When sequentially and cyclically interrogated by a central station, each pad in the system disclosed and claimed in application Ser. No. 08/580,753 sends through wires to the central station signals indicating the switch closures in such pad. Such station produces first binary signals addressing the vehicle selected by such pad and second binary signals identifying the motor control operations in such vehicle. Thereafter the switches identifying in such pad the control operations in such selected vehicle can be closed without closing the switches identifying such vehicle.
The first and second signals for each vehicle in the system disclosed and claimed in application Ser. No. 08/580,753 are transmitted by wireless by the central station to all of the vehicles at a common carrier frequency modulated by the first and second binary signals. The vehicle identified by the transmitted address demodulates the modulating signal and operates its motors in accordance with such demodulation. When the station fails to receive signals from a pad for a particular period of time, the vehicle selected by such pad becomes available for selection by another pad and such pad can select that vehicle or another vehicle.
A cable may couple two (2) central stations (one as a master and the other as a slave) in the system disclosed and claimed in application Ser. No. 08/580,753 so as to increase the number of pads controlling the vehicles. Stationary accessories (e.g. elevator) connected by wires to the central station become operative when selected by the pads.
Co-pending application Ser. No. 08/763,678 filed by William M. Barton, Jr., Peter C. DeAngelis and Paul Eichen on Dec. 11, 1996 for a "System For And Method Of Selectively Providing The Operation Of Toy Vehicles" and assigned of record to the assignee of record of this application discloses and claims a system wherein a key in a vehicle socket closes contacts to reset a vehicle microcontroller to a neutral state. Ribs disposed in a particular pattern in the key operate switches in a particular pattern in the vehicle to provide an address for the vehicle with the vehicle inactive but powered. When the vehicle receives such individual address from an individual one of the pads in a plurality within a first particular time period thereafter, the vehicle is operated by commands from such pad. Such individual pad operates such vehicle as long as such vehicle receives commands from such individual pad within the first particular period after the previous command from such individual pad. During this period, the vehicle has a first illumination to indicate that it is being operated.
When the individual pad of the system disclosed and claimed in application Ser. No. 08/763,678 fails to provide commands to such vehicle within such first particular time period, the vehicle becomes inactive but powered and provides a second illumination. While inactive but powered, the vehicle can be addressed and subsequently commanded by any pad including the individual pad, which thereafter commands the vehicle. The vehicle becomes de-activated and not illuminated if (a) the vehicle is not selected by any of the pads during a second particular time period after becoming inactivated but powered or, alternatively, (b) all of the vehicles become inactivated but powered and none is selected during the second particular period. The vehicle becomes de-activated and not illuminated. The key can thereafter be actuated to operate the vehicle to the inactive but powered state.
Co-pending application Ser. No. 08/696,263, filed by Peter C. DeAngelis on Aug. 13, 1996 for a "System And Method Of Controlling The Operation Of Toys" and assigned of record to the assignee of record of this application discloses and claims a system wherein individual ones of pads remotely control the operation of selective ones of vehicles. In each pad, (a) at least a first control provides for the selection of one of the vehicles, (b) second controls provide for the movement of the selected vehicle and (c) third controls provide for the operation of working members (e.g. pivotable bins) in the selected vehicle. Each pad provides a carrier signal, preferably common with the carrier signals from the other pads. Each pad modulates the carrier signal in accordance with the operation of the pad controls. The first control in each pad provides an address distinctive to the selected one of the vehicles and modulates the carrier signal in accordance with such address.
Each pad of the system disclosed and claimed in application Ser. No. 08/696,263 sends the modulated carrier signals to the vehicles in a pseudo random pattern, different for each pad, with respect to time. Each vehicle demodulates the carrier signals to recover the address distinctive to such vehicle. Each vehicle then provides a movement of such vehicle and an operation of the working members in such vehicle in accordance with the modulations provided in the carrier signal by the operation of the second and third controls in the pads selecting such vehicle. Each vehicle is controlled by an individual one of the pads for the time period that such pad sends control signals to such vehicle within a particular period of time from the last transmission of such control signals to such vehicle. Thereafter such vehicle can be selected by such pad or by another pad.
What has been needed, and heretofore unavailable, is a toy system including vehicles remotely operated to accomplish tasks such as lifting, scooping, dumping, leveling, pushing and hauling suitably sized materials and towing of trailers carrying such material, or other vehicles, in combination to create a miniature community or industrial environment, thus providing a person having a youthful mind with the opportunity to employ a remotely-controlled system of vehicles and mechanisms to accomplish these tasks and others within a reduced-scale, industrial environment in cooperation or competition with other individuals in a pleasurable manner.
SUMMARY OF THE INVENTION
The toy vehicle disclosed herein comprises a wheeled, highly-maneuverable, motor driven, skid steering, fork lift vehicle with a gripping lifter having the capability to releasably tow other vehicles and which is compatible with a sophisticated remote-control system. Either single or dual motors are employed to drive the wheels and skid steering while only a single additional motor is employed to drive the lifter and hitching mechanisms. Another motor is shown in the disclosed embodiment for driving the gripping mechanism.
The toy fork lift vehicle is for use as part of a toy system for use by people of all ages with youthful minds. The system provides for a simultaneous control by each player of an individual one of a plurality of remotely controlled vehicles, including the forklift vehicle. This control is provided by the operation by each such player of switches in a hand-held unit or control pad, the operation of each switch in such hand-held unit providing a control of a different function in the individual one of the remotely controlled vehicles.
Each of the remotely controlled vehicles in the system of this invention can be operated in a competitive relationship with others of the remotely controlled vehicles or in a cooperative relationship with others of the remotely controlled vehicles. The vehicles can be constructed to pick up and transport elements such as blocks or marbles or other transportable elements and to deposit such elements at displaced positions. Moreover, the vehicles are constructed having a particular ration of wheel track to wheel base to improve the maneuverability and stability of the vehicle while utilizing skid steering to steer the vehicle.
When manually closed in one embodiment of the invention, switches in control pads control the selection of toy vehicles and the operation of motors for moving the vehicles forwardly, rearwardly to the left and to the right and moving upwardly and downwardly (and rightwardly and leftwardly) a receptacle for holding, lifting and transporting transportable elements (e.g. marbles).
When sequentially and cyclically interrogated by a central station, each control pad sends through wires to the station signals indicating the switch closures in such control pad. Such station produces first binary signals addressing the vehicle selected by such control pad and second binary signals identifying the motor control operations in such vehicle. Thereafter the switches identifying in such control pad the motor control operations in such selected vehicle can be closed without closing the switches identifying such vehicle.
The first and second signals for each vehicle are transmitted by wireless to all of the vehicles at a common carrier frequency modulated by the first and second binary signals. The vehicle identified by the transmitted address demodulates the modulating signals and operates its motors in accordance with such demodulation. When the station fails to receive signals from a control pad for a particular period of time, the vehicle selected by such control pad becomes available for selection by another control pad and such control pad can select that vehicle or another vehicle.
A cable may couple two (2) central stations (one as a master and the other as a slave) to increase the number of control pads controlling by the vehicles. Stationary accessories (e.g. elevator) connected by wires to the central station become operative when selected by the control pads.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings, where like reference numerals indicate like or similar components, elements and features across the several figures:
FIG. 1 is a schematic diagram of a system constituting one embodiment of the remote-control system invention;
FIG. 2 is a schematic diagram, primarily in block form, of a control pad control system incorporated in the system shown in FIG. 1;
FIG. 3 is a schematic diagram, primarily in block form, of the different features included in a central station included in the system shown in FIG. 1;
FIG. 4 is a schematic diagram, primarily in block form, of the different features in a vehicle included in the system shown in FIG. 1;
FIG. 5A is a side view of an embodiment of a toy fork lift vehicle having a gripper assembly;
FIG. 5B is a front view of the toy fork lift vehicle depicted in FIG. 5A illustrating the details of the gripper assembly;
FIG. 6 is a front view of the motor and gear assembly of the gripper assembly of the toy fork lift vehicle of FIG. 5A;
FIG. 7 is an isometric, elevational view showing an embodiment of the motor and gear mechanism for raising and lowering the gripper assembly and for opening and closing the hitch pin of the vehicle shown in FIG. 5A;
FIG. 8 is an elevational view of a loading dock accessory illustrating an environment in which the toy vehicle shown in FIG. 5A operates; and
FIG. 9 is a side view of another embodiment of an accessory illustrating the play environment showing a toy bulldozer ascending a series of ramps before crossing a bridge.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The drawings will now be described in more detail, wherein like referenced numerals refer to like or corresponding elements among the several drawings. Moreover, reference may be made to United States patent applications Ser. No. 08/580,753, Ser. No. 08/763,678 and Ser. No. 08/696,263, which are hereby incorporated in their entirety.
In one embodiment of the invention, a system generally indicated at 10 in FIG. 1 is provided for controlling the selection and operation of a plurality of toy vehicles. Illustrative examples of toy vehicles constitute a dump truck, generally indicated at 12, a fork lift, generally indicated at 14, a skip loader, generally indicated at 16 and another form of skip loader, generally indicated at 17. The toy vehicles such as the dump truck vehicle 12, the fork lift 14 and the skip loaders 16 and 17 are simplified small scale replicas of corresponding full-size commercial units. For example, the dump truck vehicle 12 may include a working or transport member such as a pivotable tip up bin or container 18; the fork lift 14 may include a working or transport member such as a pivotable platform 20; the skip loader 16 may include a working or transport member such as a pivotable bucket 22 disposed at the front end of the skip loader; and the skip loader 17 may include a working or transport member such as a pivotable bin or container 23 disposed at the rear end of the skip loader. The working or transport members such as the pivotable bin or container 18, the pivotable platform 20 and the pivotable bins or containers 22 and 23 are constructed to carry storable and/or transportable eletnents such as blocks 24 or marbles 26 shown schematically in FIG. 1.
Each of the toy vehicles 12, 14, 16 and 17 may also have a trailer hitch 19 mounted on the front or rear of the vehicle for hooking a hitch member of another vehicle, such as a trailer (not shown) to the hitch 19 of the vehicles 12, 14, 16 and 17. The trailer hitch 19 may be remotely controlled in similar fashion to the working or transport member of the toy vehicle. Alternatively, the trailer hitch may be mechanically interconnected with the working or transport member such that remote control of the working or transport member also controls the trailer hitch 19.
Each of the dump truck 12, the fork lift 14 and the skip loaders 16 and 17 may include a plurality of motors. For example, the dump truck 12 includes a pair of reversible motors 28 and 30 (FIG. 4) to move the dump truck vehicle forwardly or rearwardly and to pivot the vehicle to the right or to the left. The motor 28 drives the movement of the front and rear wheels on the left side of the dump truck 12, and the motor 30 drives the front and rear wheels on the right side of the dump truck 12.
When the motors 28 and 30 are simultaneously operated in one direction, the dump truck 12 moves forwardly. The dump truck 12 moves rearwardly when the motors 28 and 30 are moved in the opposite direction. The dump truck 12 turns toward the left when the motor 30 is operated without simultaneous operation of the motor 28. The dump truck 12 turns toward the right when the motor 28 is operated without a simultaneous operation of the motor 30.
The dump truck 12 spins to the right when the motor 30 operates to move the vehicle forwardly at the same time that the motor 28 operates to move the vehicle rearwardly. The dump truck 12 spins to the left when the motors 28, 30 are operated in directions opposite to the operations of the motors in spinning the vehicle to the right.
Another reversible motor 32 in the dump truck 12 operates in one direction to pivot the bin 18 about its rearward hinge 13 upwardly and in the other direction to pivot the bin downwardly. In another embodiment, continued rotation of the motor 32 to pivot the bin 18 in an upwardly direction may cause the trailer hitch 19 to open. When the motor 32 is operated in the other direction, the trailer hitch 19 closes and the bin 18 pivots downwardly. An additional motor 33 may operated in one direction to turn the bin 18 to the left and in the other direction to turn the bin 18 to the right.
The construction of the motors 28, 30, 32 and 33 and the disposition of the motors and controls in the dump truck 12 to operate the dump truck are considered to be well known in the art. The fork lift 14 and the skip loaders 16 and 17 may include motors to those described above for the dump truck 12.
The system 10 may also include remotely-controlled, motorized stationary plants or accessories. For example, it may include a remotely-controlled motorized pumping station, generally indicated at 34 (FIG. 1), and driven by a pumping motor responsive to a control (not shown), for pumping elements such as the marbles 26 from a hopper 34a through a conduit 36. The system may also include a remotely-controlled motorized conveyor, generally indicated at 38, and driven by a conveyor motor responsive to a control (not shown), for moving the elements such as the marbles 26 from a hopper 38a upwardly on a ramp 40. When the marbles 26 reach the top of the ramp 40, the elements such as the marbles 26 may fall into the bin 18 in the dump truck vehicle 12 or into the bin 22 in the skip loader 16 or 17. For the purposes of this application, the construction of the pumping station 34 and the conveyor 38 may be considered to be within the purview of a person of ordinary skill in the art. Accessories or stationary plants 34 and 38 may be connected to the central station 64 either directly or through a junction box such as miniature building 35 as shown in FIG. 1.
The system 10 may also include a plurality of hand held control pads, generally indicated at 42a, 42b, 42c and 42d (FIG. 1). Each of such control pads may have a substantially identical construction. Each of the control pads may include a plurality of actuatable buttons. For example, each of the control pads may include 4-way cruciform buttons 44 configured with four wings disposed over respective control buttons 44 arranged to drive individual ones of a plurality of switches 46, 48, 50, and 52 (FIG. 2).
One wing of the button 44 may be depressed to engage the button associated with the switch 46 to close the circuit in one direction through the motor 28 (FIG. 4) moving the selected one of the vehicle 12 forwardly. Similarly, the opposite wing of button 44 may be depressed, to close the switch 48 to close the circuit in the opposite direction through motor 28 (FIG. 4) moving the vehicle 12 rearwardly. The selective depression of the left and right segments of the button 44 closes the respective switches 52 and 50, in turn, respectively closing the circuit in one direction then the opposite direction through the respective motors 28 and 30 respectively turning the selected vehicle 12 toward the left and the right about its vertical axis.
It will be appreciated that the buttons 44 may be tilted in one diagonal direction or the other by simultaneously pressing two neighboring wings of buttons 44 to simultaneously close respective neighboring pairs of switches 46 (forward) & 50 (right) to obtain a simultaneous movement of the vehicle 12 forwardly and to the right. However, a simultaneous actuation of the top and bottom wings of the button 44 will not have any effect since such actuations represent contradictory commands. This is also true of a simultaneous actuation of the left and right wings of the button 44.
Each of the control pads 42a, 44b, 42c and 42d includes a button 56 (FIG. 1) connected to switch 57 (FIG. 2). Successive depressions of the button 56 within a particular period of time cause different ones of the stationary accessories or plants such as pumping station 34 and conveyer 38. For example, a first depression of the button 56 in one of the control pads 42a, 42b, 42c and 42d may cause the pumping station 34 to be energized and a second depression of the button 56 within the particular period of time in such control pad may cause the conveyor 38 to be energized. When other stationary accessories are included in the system 10, each may be individually energized by depressing the button 56 a selective number of times within the particular period of time. When the button 56 is depressed twice within the particular period of time, the energizing of the pumping station 34 is released and the conveyor 38 is energized. This energizing of a selective one of the stationary accessories occurs at the end of the particular period of time.
A vehicle selection button 58 is provided in each of the control pads 42a, 42b, 42c and 42d to select one of the vehicles 12, 14, 16 and 17. The individual one of the vehicles 12, 14, 16 and 17 selected at any instant by each of the control pads 42a, 42b, 42c and 42d is dependent upon the number of times that the button is depressed in that control pad within a particular period of time. For example, one (1) depression of the button 58 may cause the dump truck vehicle 12 to be selected and two (2) sequential selections of the button 58 within the particular period of time may cause the fork lift 14 to be selected.
Every time that the button 58 is actuated or depressed within the particular period of time, a switch 59 (in FIG. 2) is closed. The particular period of time for depressing the button 58 may have the same duration as, or a different time than, the particular period of time for depressing the button 56. An adder is included in the control pad 42 to count the number of depressions of the button 58 within the particular period of time. The count is converted into a plurality of binary signals indicating the count. The count is provided at the end of the particular period of time. Each individual count provides for a selection of a different one of the vehicles 12, 14, 16 and 17. The count representative of the selection of one of the vehicles 12, 14, 16 and 17 is maintained in a memory, which may be located either in the control pads 42a, 42b, 42c and 42d, or in the central station 64.
The control pads 42a, 42b, 42c and 42d include buttons 60a and 60b. When depressed, the buttons 60a and 60b respectively close switches 62a and 62b in FIG. 2. The closure of the switch 62a is instrumental in producing an operation of the motor 32 to lift the bin 18 in the dump truck 12 when the dump truck has been selected by the proper number of depressions of the button 58. In like manner, when the dump truck 12 has been selected by the proper number of depressions of the switch 58, closure of the switch 62b causes the bin 18 in the dump truck 12 to move downwardly as a result of the operation of the motor 32 in the reverse direction.
It will be appreciated that other controls may be included in each of the control pads 42a, 42b, 42c and 42d. For example, buttons 61a and 61b may be included in each of the control pads 42a, 42b, 42c and 42d (FIG. 1) which operate upon depression to close respective second accessory switches 63a and 63b (FIG. 2) to pivot the bin 18 to the right or left when the vehicle 12 has been selected. Such pivotal movements of bin 18 facilitate loading, transportation and unloading of transportable elements such as marbles 26 or blocks 24. It will be appreciated that different combinations of buttons may be actuated simultaneously to produce different combinations of motions. For example, a bin in a selected one of the vehicles may be moved at the same time that the selected one of the vehicles is moved.
A central station, generally indicated at 64 in FIG. 1, processes the signals from the individual ones of the control pads 42a, 42b, 42c and 42d and sends the processed signals to the vehicles 12, 14, 16 and 17 when the button 58 on an individual one of the control pads has been depressed to indicate that the information form the individual ones of the pads is to be sent to the vehicles. The transmission may be on a wireless basis from an antenna 68 (FIG. 1) in the central station to antennas 69 on the vehicles.
The transmission may be in packets of signals. This transmission causes the selected ones of the vehicles 12, 14, 16, 17 and 350 to perform individual ones of the functions directed by the depression of the different buttons on the individual ones of the control pads. When the commands from the individual ones of the control pads 42a, 42b, 42c and 42d are to pass to the stationary accessories 34 and 38 as a result of the depression of the buttons 56 on the individual ones of the pads, the central station process the commands and sends signals through cables 70 to the selected ones of the stationary accessories.
FIG. 2 shows the construction of the control pad 42a in additional detail. It will be appreciated that each of the control pads 42b, 42c and 42d may be constructed in a substantially identical manner to that shown in FIG. 2. As shown in FIG. 2, the control pad 42a includes the switches 46, 48, 50 and 52 and the switches 57, 59, 62a, 62b, 63a and 63b. Buses 74 are shown as directing signals from the switches 46, 48, 50, 52, 57, 59, 62a, 62b, 63a and 63b to a microcontroller, generally indicated at 76 in FIG. 2. Buses 78 are shown for directing signals from the microcontroller 76 to the switches.
The microcontroller 76 is shown as including a read only memory (ROM) 80 and a random access memory (RAM) 82. Such a microcontroller may be considered to be standard in the computing industry. However, the programming in the microcontroller and the information stored in the read only memory 80 and the random access memory 82 are individual to this invention.
The read only memory 80 stores permanent information and the random access memory stores volatile (or impermanent) information. For example, the read only memory 80 may store the sequence in which the different switches in the control pad 42a provide indications of whether or not they have been closed. The random access memory 82 may receive this sequence from the read only memory 80 and may store indications of whether or not the switches in the particular sequence have been closed for each individual one of the control pads 42a, 42b, 42c and 42d.
The control pad 42a in FIG. 2 receives the interrogating signals from the central station 64 through a line 84. These interrogating signals are not synchronized by clock signals on a line 86. Each of the interrogating signals intended for the control pad 42a may be identified by an address individual to such control pad. When the control pad 42a receives such interrogating signals, it sends to the central station 64 through lines 88 a sequence of signals indicating the status of the successive ones of the switches 46, 48, 50 and 52 and the switches 57, 59, 62a, 62b, 63a and 63b. These signals are synchronized by the clock signals on the line 86. It will be appreciated that the status of each of the switches 57 and 59 probably is the first to be provided in the sequence since these signals indicate the selection of the stationary accessories 34 and 38 and the selection of the vehicles 12, 14, 16 and 17.
As previously indicated, the control pad 42a selects one of the vehicles 12, 14, 16 and 17 in accordance with the number of closings of the switch 59. As the user of the control pad 42a provides successive actuations or depressions of the button 58, signals are introduced to a shift register 90 through a line 92 to indicate which one of the vehicles 12, 14, 16 and 17 would be selected if there were no further depressions of the button. Each one of the depressions of the button 58 causes the indication to be shifted to the right in the shift register 90. Such an indication is provided on an individual one of a plurality of light emitting diodes (LED), generally indicated at 93. The shifting of the indication in the shift register 90 may be synchronized with a clock signal on a line 95. Thus, the illuminated one of the light emitting diodes 93 at each instant indicates at that instant the individual one of the vehicles 12, 14, 16 and 17 that the control pad 42a has selected at such instant.
The central station 64 is shown in additional detail in FIG. 3. It includes a microcontroller, generally indicated at 94, having a read only memory (ROM) 96 and a random access memory (RAM) 98. As with the memories in the microcontroller 76 in the control pad 42a, the read only memory 96 stores permanent information and the random access memory 98 stores volatile (or impermanent) information. For example, the read only memory 96 sequentially selects successive ones of the control pads 42a, 42b, 42c and 42d to be interrogated on a cyclic basis. The read only memory 96 also stores a plurality of addresses each individual to a different one of the vehicles 12, 14, 16 and 17.
Since the read only memory 96 knows which one of the control pads 42a, 42b, 42c and 42d is being interrogated at each instant, it knows the individual one of the control pads responding at that instant to such interrogation. The read only memory 96 can provide this information to the microcontroller 94 when the microcontroller provides for the transmittal of information to the vehicles 12, 14, 16 and 17. Alternatively, the microcontroller 76 in the control pad 42a can provide an address indicating the control pad 42a when the microcontroller sends the binary signals relating to the status of the switches 46, 48, 50 and 52 and the switches 57, 59, 62a, 62b, 63a and 63b to the central station 64.
As an example of the information stored in the random access memory 98 in FIG. 3, the memory stores information relating to each pairing between an individual one of the control pads 42a, 42b, 42c and 42d and a selective one of the vehicles 12, 14, 16 and 17 in FIG. 1 and between each individual one of such control pads and a selective one of the stationary accessories 34 and 38. The random access memory 98 also stores the status of the operation of the switches 46, 48, 50 and 52 for each control pad and the operation of the switches 57, 59, 62a, 62b, 63a and 63b for each control pad.
When the central station 64 receives from the control pad 42a the signals indicating the closure (or the lack of closure) of the switches 46, 48, 50 and 52 and the switches 57, 59, 62a, 62b, 63a and 63b, the central station retrieves from the read only memory 96 the address of the individual one of the vehicles indicated by the closures of the switch 59 in the control pad. The central station may also retrieve the address of the control pad 42a from the read only memory 96.
The central station 64 then formulates in binary form a composite address identifying the control pad 42a and the selected one of the vehicles 12, 14, 16 and 17 and stores this composite address in the random access memory 98. The central station 64 then provides a packet or sequence of signals in binary form including the composite address and including the status of the opening and closing of each of the switches in the control pad 42a. This packet or sequence indicates in binary form the status of the closure each of the switches 46, 48, 50 and 52 and the switches 57, 59, 62a, 62b, 63a and 63b.
Each packet of information including the composite addresses and the switch closure information for the control pad 42a is introduced through a line 102 (FIG. 3) to a radio frequency transmitter 104 in the central station 64. The radio frequency transmitter 104 is enabled by a signal passing through a line 106 from the microcontroller 94.
When the radio frequency transmitter 104 receives the enabling signal on the line 106 and the address and data signals on the line 102, the antenna 68 (also shown in FIG. 1) transmits signals to all of the vehicles 12, 14, 16 and 17. However, only the individual one of the vehicles 12, 14, 16 and 17 with the address indicated in the packet of signals from the central station 64 will respond to such packet of signals.
The microcontroller 94 stores in the random access memory 98 the individual ones of the vehicles such as the vehicles 12, 14, 16 and 17 being energized at each instant by the individual ones of the control pads 42a, 42b, 42c and 42d. Because of this, the central station 64 is able to prevent the interrogated one of the control pads 42a, 42b, 42c and 42d from selecting one of the energized vehicles. Thus, for example, if the vehicle 14 is being energized by one of the control pads 42a, 42b, 42c and 42d at a particular instant, a first depression of the button 58 in the control pad being interrogated at that instant will cause the vehicle 12 to be initially selected and a second depression of the button by such control pad will cause the vehicle 14 to be skipped and the vehicle 16 to be selected.
Furthermore, in the example above where the control pad 42a has previously selected the vehicle 14, the microcontroller 94 in the central station 64 will cause the vehicle 14 to be released when the control pad 42a selects any of the vehicles 12, 350, 16 or 17. When the vehicle 14 becomes released, it becomes available immediately thereafter to be selected by any one of the control pads 42a, 42b, 42c and 42d. The release of the vehicle 14 by the control pad 42a and the coupling between the control pad 42a and a selected one of the vehicles 12, 14, 16, 17 and 350 are recorded in the random access memory 98 in the microcontroller 94.
The vehicles 12, 14, 16 and 17 are battery powered. As a result, the energy in the batteries in the vehicles 12, 14, 16 and 17 tends to become depleted as the batteries provide the energy for operating the vehicles. The batteries in the vehicles 12 and 14 are respectively indicated at 108 and 110 in FIG. 3. The batteries 108 and 110 are chargeable by the central station 64 because the central station may receive AC power from a wall socket via a transformer 65 and cable 65a (FIG. 1). The batteries are charged only for a particular period of time. This particular period of time is preset in the read only memory 96. When each battery is being charged for the particular period of time, a light 109 in a circuit with the battery becomes illuminated. The charging current to each of the batteries 108 and 110 may be limited by a resistor 111. The light 109 becomes extinguished when the battery has been charged. Charging capability is provided to system 10 by any of a number of possible configurations including locations in the junction box station 35 or as separate stationary plants or other types of accessories such as those depicted by 34 and 38 (FIG. 1) any of which may be placed conveniently throughout the system 10 as desired by the users.
Each central station 64 may have the capabilities of servicing only a limited number of control pads. For example, each central station 64 may have the capabilities of servicing only the four (4) control pads 42a, 42b, 42c and 42d. It may sometimes happen that the users of the system elect to service more than four (4) control pads. Under such circumstances, the microcontroller 94 in the central station 64 and a microcontroller, generally indicated at 94a, in a second central station corresponding to the central station 64 may be connected by cables 114a and 114b to an adaptor, generally indicated at 115.
One end of the cable 114b is constructed so as to be connected to a ground 117 in the adaptor 115. This ground operates upon the central station to which it is connected so that such central station is a slave to, or subservient to, the other central station. For example, the ground 117 in the adaptor 115 may be connected to the microcontroller 94a so that the central station including the microcontroller 94a is a slave to the central station 64. When this occurs, the microcontroller 94 in the central station 64 serves as the master for processing the information relating to the four (4) control pads and the four (4) vehicles in its system and the four (4) control pads and the four (4) vehicles in the other system.
The expanded system including the microcontrollers 94 and 94a may be adapted so that the address and data signals generated in the microcontroller 94a may be transmitted by the antenna 68 in the central station 64 when the central station 64 serves as the master station. The operation of the central station 64a may be clocked by the signals extending through a line 118 from the central station 64 to the adaptor 115 and through a corresponding line from the other central station to the adaptor.
The microcontroller 122 includes a read only memory (ROM) 124 and a random access memory (RAM) 126. As with the memories in the control pad 42a and the central station 64, the read only memory 124 may store permanent information and the random access memory 126 may store volatile (or impermanent) information. For example, the read only memory 124 may store information indicating the sequence of the successive bits of information in each packet for controlling the operation of the motors 28, 30, 32 and 33 in the vehicle 12. The random access memory 126 stores information indicating whether there is a binary 1 or a binary 0 at each successive bit in the packet.
The particular embodiment reflected by vehicle 12 includes a plurality of switches 128, 130 and 132. These switches are generally pre-set at the factory to indicate a particular Arabian number such as the number "5". However, the number can be modified by the user to indicate a different number if two central stations are connected together as discussed above and if both stations have vehicles identified by the numeral "5". The number can be modified by the user by changing the pattern of closure of the switches 128, 130 and 132. The pattern of closure of the switches 128, 130 and 132 controls the selection of an individual one of the vehicles such as the vehicles 12, 14, 16 and 17. Additional switches similar to the switches 128, 130 and 132 and configured to work in cooperation with such switches may be added to the vehicles to accommodate addressing of larger numbers of vehicles so that each may have its own unique address.
The pattern of closure of the switches 128, 130 and 132 in one of the vehicles can be changed when there is only a single central station. For example, the pattern of closure of the switches 128, 130 and 132 can be changed when there is only a single central station with a vehicle identified by the numeral "5" and when another user brings to the central station, from such other user's system, another vehicle identified by the numeral "5".
The vehicle 12 also includes a light such as a light emitting diode 134. This diode is illuminated when the vehicle 12 is selected by one of the control pads 42a, 42b, 42c and 42d. In this way, the other users can see that the vehicle 12 has been selected by one of the control pads 42a, 42b, 42c and 42d in case one of the users (other than the one who selected the vehicle 12) wishes to select such vehicle. It will be appreciated that each of the vehicles 12, 14, 16 and 17 may be generally different from the others so each vehicle may be able to perform functions different from the other vehicles. This is another way for each user to identify the individual one of the vehicles that the user has selected.
As previously described, the user of one of the control pads such as the control pad 42a selects the vehicle 12 by successively depressing the button 58 a particular number of times within a particular time period. This causes the central station 64 to produce an address identifying the vehicle 12. When this occurs, the central station 64 stores information in its random access memory 98 that the control pad 42a has selected the vehicle 12. Because of this, the user of the control pad 42a does not thereafter have to depress the button 58 during the time that the control pad 42a is directing commands through the station 64 to the vehicle 12. As long as the buttons on the control pad 42a are depressed within a particular period of time to command the vehicle 12 to perform individual functions, the microprocessor 94 in the central station 64 will direct the address of the vehicle 12 to be retrieved from the read only memory 96 and to be included in the packet of the signals transmitted by the central station to the vehicle 12.
The read only memory 96 in the microprocessor 94 at the central station 64 stores information indicating a particular period of time in which the vehicle 12 has to be addressed by the control pad 42a in order for the selective coupling between the control pad and the vehicle to be maintained. The random access memory 98 in the microcontroller 94 stores the period of time from the last time that the control pad 42a has issued a command through the central station 64 to the vehicle 12. When the period of time in the random access memory 98 equals the period of time in the read only memory 96, the microcontroller 94 will no longer direct commands from the control pad 42a to the vehicle 12 unless the user of the control pad 42a again depresses the button 58 the correct number of times within the particular period of time to select the vehicle 12.
The vehicle 12 also stores in the read only memory 124 indications of the particular period of time in which the vehicle 12 has to be addressed by the control pad 42a in order for the selective coupling between the vehicle and the control pad to be maintained. This period of time is the same as the period of time specified in the previous paragraph. The random access memory 126 in the microcontroller 122 stores the period of time from the last time that the control pad 42a has issued a command to the vehicle 12.
Once the particular button 58 of particular pad has been actuated to select and energize a vehicle, that vehicle remains operative and associated with such particular pad for a predetermined period of time as dictated by random access memory 126. When the period of time stored in the random access memory 126 of the microcontroller 122 in the vehicle equals the period of time in the read only memory 124, the microcontroller 122 issues a command to extinguish the light emitting diode 134. This indicates to the different users of the system, including the user previously controlling the operation of the vehicle 12 that the vehicle is available to be selected by any one of the users, including the user previously directing the operation of that vehicle.
When one of the vehicles such as the vehicle 12 is being moved in the forward direction, the random access memory 126 records the period of time during which such forward movement of the vehicle 12 is continuously occurring. This count is continuously compared in the microcontroller 122 with a fixed period of time recorded in the read only memory 124. When the period of time accumulated in the random access memory 126 becomes equal to the fixed period of time recorded in the read only memory 124, the microcontroller 122 provides a signal for increasing the speed of the movement of the vehicle 12 in the forward direction. Similar arrangements are provided for each of the vehicles 14, 16 and 17. This increased speed may illustratively be twice that of the original speed.
The system and method described above have certain important advantages. They provide for the operation of a plurality of vehicles by a plurality of users, either on a competitive or a cooperative basis. Furthermore, the vehicles can be operated on a flexible basis in that a vehicle can be initially selected for operation by one user and can then be selected for operation by another user after the one user has failed to operate the vehicle for a particular period of time. The vehicles being operated at each instant are also visible by the illumination of the lights 134. The apparatus and method of this invention are also advantageous in that the vehicles are operated by the central station 64 on a wireless basis without any physical or cable connection between the central station and the vehicles.
Furthermore, the central station 64 communicates with the vehicles in the plurality through a single carrier frequency. The system and method of this invention are also advantageous in that the vehicles can selectively perform a number of different functions including forwardly and rearwardly movement, as well as turns to the left and to the right, and manipulation of accessories such as containers, bins or platforms carried on the respective vehicles. Different movements can also be provided simultaneously on a coordinated basis. Vehicles may also be employed in a cooperative manner to work with stationary plants and accessories 34 and 38 for the movement and storage of materials such as blocks 24 and marbles 26.
Referring now to FIGS. 5A and 5B, a fork lift 350 incorporating several novel aspects of the present invention is shown. The fork lift 350 has four wheels 355 (only the wheels 355 on the left side are shown), a front and rear left pair of wheels driven by the motor 28 (FIG. 4), and a front and rear right pair of wheels driven by the motor 30 (FIG. 4). The front wheels are mounted on a front axle and the rear wheels are mounted a rear axle. Typically, the two axles are of equal length, although the axles could be of different lengths. The width of the wheels and axle, measured from the outside of the wheel on the left side of the fork lift 350 to the outside of the wheel on the right side of the fork lift 350 is commonly called the track of the vehicle.
The axles are mounted to a chassis 352 at selected, spaced apart locations on a bottom side of the chassis 352. The distance between the cross-sectional center of the front axle and the cross-sectional center of the rear axle is typically known in the art as the wheel base of the vehicle.
The fork lift 350 has a rotatable lifter arm shaft 361 and a leveling arm shaft 363 rotatably mounted in the chassis 352 and extending through the chassis 352 such that the ends of the lifter arm shaft 361 and the leveling arm shaft 363 extend beyond the sides of the chassis 352. A proximal end of an upper lifter arm 356 is mounted on the end of the leveling arm shaft 363 extending through the left side of the chassis 352. A distal end of the upper lifter arm 356 is mounted to a rotatable shaft 358 rotatably mounted in a left side of an upper portion of a gripper assembly 360. Similarly a proximal end of an upper lifter arm 356 is mounted on the end of the leveling arm shaft 363 extending through the right side of the chassis 352. A distal end of the upper lifter arm 356 is mounted to a rotatable shaft 358 rotatably mounted in a right side of the upper portion of the gripper assembly 360.
A proximal end of a lower lifter arm 357 is mounted on the end of the lifter arm shaft 361 extending through the left side of the chassis 352. A distal end of the lower lifter arm 357 is mounted to a rotatable shaft 359 rotatably mounted in the left side of a lower portion of the gripper assembly 360. Similarly a proximal end of a lower lifter arm 357 is mounted on the end of the lifter arm shaft 361 extending through the right side of the chassis 352. A distal end of the lower lifter arm 357 is mounted to a rotatable shaft 359 rotatably mounted in the right side of the lower portion of the gripper assembly 360. The structure formed by this arrangement of upper and lower lifter arms 356, 357 and shafts 358, 359, 361 and 363 form a parallel four bar assembly. When lifter arm shaft 361 is rotationally driven by a motor, as will be described more fully below, the rotation of lifter arm shaft 361 in one direction operates to lift the gripper assembly 360 in an upwardly direction. Rotation of the lifter arm shaft 361 in the opposite direct operates to lower the gripper assembly 360. The four bar assembly translates the rotation of lifter arm shaft 361 such that the gripper assembly 360 is lifted and lowered in a parallel manner, e.g., bins or other items gripped by the gripping assembly 360 are prevented from tipping during lifting or lowering. Use of this assembly is thus useful in preventing the contents of a bin from spilling while being lifted or lowered by the fork lift 350.
The fork lift 350 also has a counterweight 365 mounted to the chassis 352. The counterweight 365 assists in balancing the weight of a bin or object gripped by the gripper assembly 360 when the gripper assembly is controlled to lift the bin or object to prevent overbalancing or tipping of the fork lift 350. A hitch pin 432 is mounted on the rear of the chassis 352 of the fork lift 350. The hitch pin 432 may be used as an attachment point for a cable attached to an object or structure such that the fork lift 350 may be controlled to pull the object or structure. Alternatively, a trailer may be attached to the hitch pin 432.
The gripper assembly 360 comprises a body 368 on which is mounted a motor 367, a gear assembly 371 and a pair of gripper arms 389 and 391 mounted to a first gear rack 388 and a second gear rack 390 respectively (FIG. 5B). Referring now to FIG. 6, the motor 367 has a transistor drive 369, which is similar in design and function to the motor 32 and its respective transistor driver 120 described in FIG. 4. A worm gear 370 is mounted on a distal end of the shaft of motor 367. The worm gear 370 is meshed to cluster gear 372 mounted about shaft 374 which is secured to the body 368 of the gripper assembly 360. A spur gear 367 is also mounted on the shaft 374 such that spur gear 367 rotates in a coordinated fashion with cluster gear 372. A spur gear and clutch 380 is mounted on a distal end of a rotatable shaft 382, the proximal end of which is rotatably mounted to the body 368 of the gripper assembly 360. The spur gear 376 is meshed to the spur gear and clutch 380 mounted on axle 382. A pinion gear 384 is also mounted on shaft 382 such pinion gear 384 rotates in coordination with the rotation of the spur gear and clutch 380. The first gear rack 388 and the second gear rack 390 are slidably mounted to the body 368 of the gripper assembly 360 and are in opposing engagement with the pinion gear 384. Grips 389 and 391 are mounted on the outermost lateral ends of gears racks 388 and 390 respectively.
FIG. 7 depicts one embodiment of an arrangement of motor and gears that is capable of rotating the lifter arm shaft 361 to lift and lower the gripper assembly 360 and to actuate the hitch pin 432. A motor 405 having a transistor driver 407 is mounted on the chassis 352 of the fork lift 350 (not shown). The motor has a rotating shaft 406 that is driven by the motor in response to control signals from the transistor driver 407. A worm gear 408 is mounted on a distal end of the motor shaft 406. A spur gear 410 is mounted at a first end of a shaft 412 and a worm gear 414 is mounted on a second, opposite end of the shaft 412. The shaft 412 is rotatably mounted to the chassis 352, and positioned such that the teeth of spur gear 410 engage the teeth of the worm gear 408.
A generally "Z" shaped linkage plate 427 is slidably mounted on the chassis 352. At a first end of the linkage plate 427, there is an upturned portion 413. The upturned portion 413 has a generally flat face 416 and an upper end 418. The upper end 418 has a pair of generally hooked shaped tabs 418a and 418b extending towards a second end of the linkage plate 427. The hook shaped tabs 418a and 418b are formed to rotatably receive and retain one end of a rotating shaft 419. The other end of shaft 419 is rotatably mounted to the chassis 352.
A clutch gear 415 is mounted on the shaft 419, and meshes with the teeth of the worm gear 414. A spur gear 417 is also mounted on the shaft 419 such that spur gear 417 rotates in coordination with clutch gear 415 when shaft 419 rotates. A follower roller 424 is mounted on the shaft 419 between the hook shaped tabs 418a and 418b of the upper end 418 of the upturned portion 413 of the linkage plate 427. The follower roller 424 is mounted on the shaft 419 such that the roller 424 may rotate independent of the rotation of the shaft 419.
A spur gear 420 is mounted on the lifting arm shaft 361 and in operative engagement with the gear 417 mounted on shaft 419. A cam 422 is also mounted on the lifter arm shaft 361.
When the motor 405 is controlled to lift the gripper assembly 360, the motor shaft 406, and thus worm gear 408, may rotate in a clockwise direction. This clockwise rotation of worm gear 408 produces a counterclockwise rotation of spur gear 410, which is transmitted by shaft 412 to rotate worm gear 414 in a counterclockwise direction, which causes the clutch gear 415 to rotate in a clockwise direction. Since clutch gear 415 is fixedly mounted to shaft 419, gear 417, also fixedly mounted on shaft 419, also rotates in a clockwise direction. Clockwise rotating gear 417, in operative engagement with gear 420, causes gear 420 to rotate in a counterclockwise direction. This counterclockwise rotation of gear 420 causes the lifter arm shaft to also rotate in a counterclockwise direction, which in turn causes the right and left lower lift arms 357 to move upwards, lifting the gripper assembly 360. As will be apparent to one skilled in the art, controlling the motor 405 to rotate shaft 406 in the opposite, or in this case, counterclockwise direction, causes the lifter arm shaft 361 to rotate in a clockwise direction to lower the right and left lift arms 357.
It will be understood that the specific ratios of the teeth of the gears described previously may be altered as necessary to change the relative rotational speeds of the various shafts. For example, the ratios of the various gears may be altered to accommodate motors 405 having different speeds, or to provide greater or lesser mechanical advantage.
At a second end of the linkage plate 427 there is a tab 426 that engages a drive arm 430 of a lever 428 mounted on a shaft 429 that is rotatably mounted to the chassis 352. The follower arm 431 of the lever 428 engages a pin 433 formed on an upper end of the hitch pin 432. Although not shown, the hitch pin 432 is slidably mounted through an opening at the rear end of the chassis such that the hinge pin 432 may move upwardly and downwardly in response to upwards and downwards movement of the end of the follower arm 433 of the lever 428.
The cam 422 mounted on the lifter arm shaft 361 is slidablely engaged with the roller 424 that is mounted on shaft 419, which in turn is rotatably mounted to the hook shaped tabs 418a and 418b of the upturned portion 413 of the linkage plate 427. In the embodiment illustrated in FIG. 7, the roller 424, and thus the linkage plate 427, is biased in a rearward direction by a spring 425 disposed between the flat face 416 of the upturned portion 413 of the linkage plate 427 and the chassis 352. When the lifter arms 357 are in the lowered position, the cam 422 engages the roller 424 and pushes the roller 424, and thus the linkage plate 427 in a forwardly direction against the rearward bias due to the spring 425. When the linkage plate 427 is in such a forward position, the tab 426 is also in a forward position, allowing the follower arm 433 of the lever 428 and hinge pin 432 to drop down, closing the hitch.
As described above, when motor 405 is controlled to rotate the lifter arm shaft 361 to lift the gripper assembly 360, the lifter arm shaft 361 rotates in the counterclockwise direction. Such rotation also causes cam 422 to rotate upwardly in coordination with the rotation. When the cam 422 has rotated upwardly a sufficient amount, the roller 424 may become disengaged from the cam 422, allowing the linkage plate 427 to move in a rearwards direction in response to the rearward bias caused by the spring 425. The rearward movement of the linkage plate 427 also causes the tab 426 to move rearwards and engage the drive arm 430 of the lever 428. As the linkage plate 427 and tab 426 move progressively rearwards, tab 426 pushes on drive arm 430, causing the lever 428 to rotate about shaft 429 and move the end of the follower arm 431 in an upwards direction. As the end of the follower arm 431 moves upwards, it engages pin 433 and lifts the hitch pin 432 upwards, opening the hitch. Similarly, when the lifter arm shaft rotates in a clockwise direction to lower the lift arms 357, the cam 422 is rotated downwards and into engagement with the roller 424, pushing roller 424 and the linkage plate 427 forwards against the bias caused by the spring 425. The forward movement of the linkage plate 427 causes the tab 426 to move forwards, allowing the lever 428 to rotate in a counterclockwise direction about the shaft 429, lowering the end of follower arm 431 and the hitch pin 432, closing the hitch.
In operation, the motorized gripping mechanism 360 of FIG. 6 is actuated by inputs originating in pads 42 after receipt by radio frequency transmission from central station 64, demodulation by vehicle receiver 121 and after processing by vehicle microcontroller 122. The mechanism 360 is operated by a single motor 367 driving the gear train described above for sliding gear racks 388 and 390 together with a clamping force sufficient to enable frictional gripping to provide lifting and translation of transportable elements such as bins or other objects. The magnitude of available clamping force depends upon the selection of a clutch 380 appropriate for the available torque of motor 367, the strength of the materials from which gripper assembly 360 is fabricated and the strength of the materials from which the transportable elements are fabricated. By design, the clutch 380 decouples the motor 367 torque from the gripping assembly once a predetermined force has been attained during the gripping of transportable elements.
Referring now to FIGS. 8 and 9, one novel aspect of the construction of the vehicles 12, 14, 16 and 17 will now be described. FIG. 8 shows one embodiment of the fork lift 350 lifting and carrying a bin 302. The fork lift 350 is shown positioned on the raised deck of a miniature model of a loading dock, generally indicated at 300. Also shown in FIG. 8 is a trailer 304 that may be connected to the vehicles 12, 14, 16, 17 and 350 by connecting a tongue 306 of the trailer 304 to the hitch 19 of a selected one of the vehicles 12, 14, 16, 17 and 350. As is apparent from FIG. 8, the fork lift 350 is capable of grasping the bin 302 with its gripper assembly and upon receiving the appropriate signal from the central station 64 (FIG. 1), can be operated to lift the bin to an elevated position. The operator may then control the fork lift 350 to move forward on the deck of the loading dock 300 until the bin 302 is suspended over the trailer 304. The fork lift can then be controlled to lower the bin 302 onto the trailer 304, and release the gripper assembly 360.
As is illustrated by FIGS. 8 and 9, various model environments can be constructed to provide for intriguing and enjoyable play by persons of youthful minds. Such model environments, however, may constrain the design and function of the vehicles 12, 14, 16, 17 and 350 so that the vehicles may be easily operated within the environment. For example, the raised deck of the loading dock 300 in FIG. 8 is accessed by the fork lift 350 by ascending an inclined ramp 308. In operation, the vehicles 12, 14, 16, 17 and 350 should be capable of climbing the ramp 308 to reach the raised deck of the loading dock 300 without suffering a loss of vehicle stability caused by the inclined attitude achieved by the vehicle as it ascends the ramp 308.
Additionally, the various structural accessories used with the system 10 may also be relatively small to maximize the use of available space. Such small accessories, such as the loading dock 300, may require that the vehicles 12, 14, 16, 17 and 350 be capable of precise movements within the tight confines of such a structure. For example, after the fork lift 350 climbs the ramp 308, it must turn sharply to the left to gain access to the trailer 304. FIG. 9 depicts a further example of the operation of a vehicle 16 to climb a ramp 310, turn to the right on an intermediate deck 318, climb a second ramp 314, traverse a bridge 316, and then descend another ramp or series of ramps 318. Precise maneuverability of the fork lift 350 and the vehicle 16 avoids unnecessary jockeying of the vehicle backwards and forwards to accomplish the sharp turns required by the dimensions of the loading dock 300 (FIG. 8) and the intermediate deck 314 (FIG. 9).
In a preferred embodiment, the vehicles 12, 14, 16, 17 and 350 accomplish the movements required to traverse the structures described above by employing skid steering. Skid steering of the vehicles 12, 14, 16, 17 and 350 is accomplished by controlling, for example, motor 28 of the fork lift 350 to cause the wheels on the left side of the fork lift 350 to rotate to move the fork lift 350 in a forwardly direction. At the same instant, motor 30 of the fork lift 350 is not energized, thus the wheels 355 on the right side of the fork lift 350 do not rotate. Since only the wheels 355 on the left side of the fork lift 350 are controlled to move the vehicle forward, the fork lift 350 pivots to the right. Alternatively, motor 30 of the fork lift 350 may be controlled to rotate the wheels 355 on the right side of the fork lift 350 in the opposite direction to the wheels 355 driven by motor 28 on the left side of the fork lift 350. In this manner, the fork lift 350 may be controlled to pivot rapidly to the right around its axis. Similarly, to turn to the left, motor 30 may be controlled to move the fork lift 350 in a forwardly direction, while motor 28 is either not energized, resulting in the wheels 355 on the left side of the fork lift 350 remaining stationary, or motor 28 may be controlled to drive the wheels on the left side of the fork lift 350 in the direction opposite to the wheels on the right side of the fork lift 350. While the concept of employing skid steering to steer a vehicle is well known in the art, the present invention controls the ratio of wheelbase and track dimensions of the vehicles 12, 14, 16, 17 and 350 in combination with careful placement of counterweights to provide for optimal maneuverability and stability.
Providing sufficient maneuverability while maintaining vehicle stability on an incline is particularly important for enjoyable operation of the fork lift 350. As a bin 302 is raised by the gripper assembly 360 of the fork lift 350, the additional weight of the bin 302 and any contents of the bin, such as marbles 26 or blocks 24 (FIG. 1) may adversely affect the stability of the fork lift 350 when it is controlled by a user to move forwards or backwards, or to turn to the right or left. Accordingly, the details of the embodiment of the present invention illustrating the improved maneuverability and stability of the vehicles 12, 14, 16, 17 and 350 is described with reference to the fork lift 350. It will be understood, however, that the principles are equally applicable to each of the vehicles 12, 14, 16 and 17.
It has been determined during testing that maneuverability and stability of the fork lift 350, and thus the vehicles 12, 14, 16 and 17, is optimized when the ratio of the track to the wheelbase of the fork lift 350 is approximately equal to 1.5. For example, a fork lift 350 having a track equal to 85 millimeters and a wheelbase equal to 55 millimeters has been found to have excellent maneuverability in the tight confines of representative model structures such as the loading dock 300 in FIG. 8, while also providing for stable operation of the fork lift 350 while ascending or descending inclined ramps as illustrated in FIGS. 8 and 9.
While several forms of the invention have been illustrated and described, it will also be apparent that various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited, except by the appended claims. | A remotely-controllable motorized toy vehicle having a highly-maneuverable skid steering system driven by single or dual motors, having a separately motorized lift device pivotally secured to the chassis of the vehicle operative to lift and transport transportable elements, and also having an automatic tow hitch mechanism. The lift and hitching mechanism is coupled to a motorized lift gear train which provides for the sequential actuation of the lift for lifting and transport of the transportable elements and acutation of the hitch mechanism for hitching and unhitching towed vehicles. The vehicle is constructed with a particular wheel track to wheel base ratio providing improved skid steering as well as enhanced manueverability and stability. The mechanisms and gear trains have proper ratios and dimensions providing for the proper sequence of hitch actuation during upward and downward movement of the lift device whereby the hitch is operative only upon extended upward operation of the lift. The remote central control device or station being capable of controlling a plurality of vehicles with control inputs from a plurality of operators. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to lactam derivatives, methods for their production, and methods for their use.
2. Description of Related Art
The preparation of various reaction products of ε-caprolactam, formaldehyde, and hydroxyl-containing compounds is known: for example, N-[(isopentyloxy)methyl]caprolactam from V. A. Chauzov et al., Journal of General Chemistry of the USSR, 59 (1989) p. 425; and N-[(2,6-di-tert-butylphenoxy)methyl]caprolactam from DE-A 26 16 374. The preparation of N,N-linked bislactam compounds is described in DE-A 35 06 473; the preparation of N-methylolcaprolactam in DE-A 37 00 451.
Melamine resins made from melamine and formaldehyde are general knowledge and are described, for example, in “Kunststoff-Handbuch”, 2nd edition, 1988, vol. 10, pp. 41 to 49. Melamine-formaldehyde precondensates whose methylol groups are unetherified or etherified in part with alcohols such as methanol are generally prepared in an aqueous medium and also commercialized in aqueous form. They are used preferably for impregnating paper webs, especially decorative paper webs, which are subsequently employed to produce laminates, decoratively coated chipboard panels or compression-formed laminates. For this purpose, the paper webs are impregnated to a defined resin content in the aqueous impregnating-resin solutions, to which a curing agent may have been added, and are dried to a defined residual moisture content at temperatures from 120 to 200° C. The fabric or paper webs treated in this way are pressed onto woodbase materials or a stack of resinated papers employing pressures of from 0.8 to 12 MPa (from 8 to 120 bar) and temperatures of from 100 to 180 C.
In this way, decorative laminates and coated woodbase materials are obtained which are employed primarily in interior furnishing, for producing furniture or as a floor covering, to cite but a few of the possible applications.
Melamine resins are prepared by condensing formaldehyde with melamine, the condensation being continued only to a point at which the reaction products are still soluble and meltable. When this point is reached, the condensation is terminated by cooling and by establishing a weakly alkaline pH. This gives products which have not been fully condensed, these products also being termed melamine resin precondensates and being used in the form of their aqueous solutions, for example, as impregnating resins. It is also now possible to replace up to 20% of the melamine by one or more other amino resin formers, examples being guanamines (e.g., acetoguanamine, benzoguanamine and caprinoguan-amine), dicyandiamide, urea and thiourea, and also cyclic ureas (e.g. ethylene- and propyleneurea).
When the fabric or paper webs which have been impregnated with impregnating resin and dried are pressed into laminates, curing takes place as a result of thorough crosslinking of the condensate. When coating woodbase materials in particular it is important that the melamine resins employed are elasticized with modifiers in order to prevent subsequent cracking of the coated surface. The impregnating resin can be etherified in part with lower alcohols or modified with modifiers such as polyhydric alcohols, carboxamides, glycols, sulfonamides and sugars, and can also be catalyzed with acidic inorganic or organic salts.
In the art, diethylene glycol and ε-caprolactam are frequently employed as modifiers. They give the cured films the necessary elasticity coupled with good surface properties, such as low soiling tendency, low sensitivity to steam and boiling water, low yellowing propensity, high scratch resistance, low propensity to cracking, and good postforming properties.
A disadvantage of these modifiers is their relatively high volatility. When papers impregnated with resins modified in this way are dried, some of the modifiers present are given off into the air. This problem is exacerbated when the dryer temperatures are raised owing to higher machine speeds. In accordance with the art, customary drying temperatures are from 140 to 200° C. In order to avoid these emissions, it is therefore necessary with prior art resins to make considerable investment in filter units and/or post-combustion units, in general.
This problem applies in particular to ε-caprolactam, for which a MAC level of 5 mg/m 3 has been laid down.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide modifiers for impregnating resins and resins modified therewith which when used in the coating of woodbase materials result in minimal amounts of organic compounds being emitted. In addition, the coatings produced with these resins should be elastic and should not tend to crack.
It is also an object of the invention to provide methods of making and using such modifiers.
In accordance with these and other objectives, there has been provided in accordance with the present invention an N-alkoxymethyllactam of the formula VI
where X is —(OCH 2 -CR 1 H) m —OR 2 , and R 1 and R 2 in each case independently of one another are hydrogen or a linear or branched alkyl radical having 1 to 6 carbon atoms,
l is 3to 12and m is 1 to 20,
or where X is —O—(CH 2 ) n —OR 3 , and R 3 is hydrogen or a linear or branched alkyl radical having 1 to 6 carbon atoms and n is 2 to 8, obtained by reacting a lactam of the formula I
where 1 is as defined above, with formaldehyde and hydroxyl-containing compounds selected from diols and/or diol monoethers of formula II
H(—O—CH 2 -CR 1 H) m —OR 2 (II),
where R 1 , R 2 and m are as defined above, and diols and/or diol monoethers of formula III
HO—(CH 2 ) n —OR 3 (III)
where R 3 and n are as defined above, wherein the reaction comprises reacting from 1 to 4 mol of formaldehyde and from 0.5 to 6 mol of the hydroxy containing compound one another per mole of the lactam of the formula I.
In accordance with these and other objectives, there has also been provided a is a mixture comprising one or more N-alkoxymethyllactams of the formula VI
and one or more N-methylollactams of the formula IV
and one or more N, N′-methylenebislactams of the formula V
in which X is —(OCH 2 —CR 1 H) m —OR 2 or —O—(CH 2 ) n —OR 3 , R 1 , R 2 and R 3 independently of one another are hydrogen or a linear or branched alkyl radical having 1 to 6 carbon atoms and l is an integer from 3 to 12, m is 1 to 20, and n is 2 to 8.
In accordance with these and other objectives, there has been provided a melamine impregnating resin formulation comprising or prepared from an N-alkoxymethyllactam of the formula VI as modifier in a proportion by mass of from 1 to 20%, based on the mass of the solid melamine resin.
In accordance with these and other objectives, there has been provided a melamine impregnating resin formulation comprising or prepared from and a mixture as discussed above as modifier in a proportion by mass of from 1 to 20%, based on the mass of the solid melamine resin.
Further objects, features, and advantages of the invention will become apparent from the detailed description that follows.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
It has now been found that the disadvantages of the use of prior art modifiers can be avoided if the modifier employed comprises reaction products of lactams of the formula I
in which l is from 3 to 12, preferably 3, 4, 5 or 11 and, with particular preference, is 5 (caprolactam) and 11 (laurolactam) with formaldehyde and diols and/or diol monoethers of the formula II
H(OCH 2 —CR 1 H) m —OR 2 (II)
in which R 1 and R 2 are hydrogen or a linear or branched alkyl radical having 1 to 6, preferably 1 to 4 and, with particular preference, 1 or 2 carbon atoms and m is from 1 to 20, preferably from 2 to 4
or with diols and/or diol monoethers of the formula III
HO—(CH 2 ) n —OR 3 (III)
in which R 3 is hydrogen or a linear or branched alkyl radical having 1 to 6, preferably 1 to 4 and, with particular preference, 1 or 2 carbon atoms and n is from 2 to 8, preferably from 2 to 4.
It is also useful in accordance with the invention to employ mixtures of different lactams; similarly, mixtures of the diols or diol monoethers of the formulae II and III, respectively, can also be employed.
The N-alkoxymethyllactams may be prepared as desired. In one process the molar ratio of the precursors (starting materials) is chosen so that from 1 to 4 mol of formaldehyde and from 0.5 to 6 mol of the diol and/or of the diol monoether of the formula II and/or from 0.5 to 6 mol of the diol and/or of the diol monoether of the formula HII are reacted with one another per mole of the lactam of the formula I. If the diol and/or the diol monoether of the formula II and/or of the formula III is employed in excess for reaction with the lactam of the formula I, then it is additionally effective as a solvent.
The reaction between the lactam of the formula I, formaldehyde and the diol and/or diol monoether of the formula II and/or of the formula III generally takes place at temperatures between 50 and 200° C., preferably between 80 and 140° C., in the presence of known water-eliminating catalysts, preferably of an acidic catalyst. Any desired catalysts can be used. Examples of suitable acidic catalysts include inorganic acids or strong organic acids, such as sulfamic acid, phosphoric acid, hydrochloric acid, nitric acid, sulfuric acid, formic acid, oxalic acid, benzenesulfonic acid, or toluenesulfonic acid, and also acidic salts, such as alkali metal hydrogen sulfates.
It is also useful to carry out the reaction between the lactam of the formula I, formaldehyde and the diol and/or diol monoether of the formula II and/or of the formula III in two stages: in the first stage initially in the presence of alkaline inorganic or organic compounds, such as alkali metal hydroxides, alkali metal carbonates or alkaline earth metal carbonates, and also amines, the lactam I and formaldehyde are reacted with one another at temperatures between 50 and 200° C., preferably between 80 and 120° C., in the abovementioned molar ratio. In this stage, the lactam of the formula I is methylolated. Subsequent condensation then takes place in the second stage in the presence of known water-eliminating catalysts, preferably of an acidic catalyst. Suitable acidic catalysts are the abovementioned inorganic and strong organic acids.
In order to bring the reaction to completion it is useful, during the reaction or thereafter, to distill off the water of the reaction, at atmospheric or reduced pressure. In this context, the condensation reaction can also be conducted in the presence of water-immiscible solvents, preferably inert aromatic hydrocarbons, which are able to form an azeotrope with water. The use of inert aromatic hydrocarbons as solvents for the reaction is particularly advantageous when formaldehyde is employed in the form of aqueous formaldehyde solutions, since in that case the removal of the entrained water is promoted by azeotropic distillation. The water can in this case be removed substantially or completely from the product mixture by azeotropic distillation, with the solvent possibly being recycled in a known manner following phase separation from the water.
The formaldehyde can be employed in the form of an aqueous solution, preferably a solution with a concentration of more than 30%, or in the form of a solution of formaldehyde gas in the diol or diol monoether of the formula II or III employed in the reaction, or else in a low-boiling alcohol. Preferably, however, the formaldehyde is supplied to the reaction in the form of paraformaldehyde. Where aqueous solutions of formaldehyde or solutions in low-boiling alcohols are employed, it should be ensured that the water or lower alcohol introduced with the formaldehyde solution is able to distill off from the reaction mixture, which is promoted in particular, in the presence of water, by adding an organic solvent which forms an azeotropic mixture with the water. Where paraformaldehyde is employed as the formaldehyde source, the distillative removal of the water of the reaction can be omitted.
The reaction products obtainable by the process of the invention are mixtures of different lactam derivatives. In the course of the reaction, the lactam in the formula I reacts with the formaldehyde to form N-methylollactams of the formula IV,
N,N′-methylenebislactams of the formula V
and, with the formaldehyde and the diol and/or diol monoether of the formula II and/or with the diol of the formula III employed, to give novel condensation products of the formula VI
in which X is —(OCH 2 —CR 1 H) m —OR 2
and R 1 , R 2 , l and m are as defined above or
in which X is —O—(CH 2 ) n —OR 3
and R 3 , l and n are as defined above.
The lactam derivatives of the formula VI obtainable by the process of the invention have not been described previously; they are likewise provided by the present invention.
The mixtures obtainable in accordance with the process of the invention can include any desired proportions of components, and generally include proportions by mass of from 5 to 50%, preferably from 10 to 45%, of N-alkoxymethyllactams of the formula VI, from 30 to 80%, preferably from 35 to 75%, of N,N′-methylenebislactams of the formula V and from 0 to 5%, preferably less than 2%, of unreacted lactams of the formula I; the remainder to 100% (i. e. from 0 to 65%, preferably from 5 to 60%) is N-methylol-lactam of the formula IV.
Any desired lactams of formula (I) and components of formula (II) and (III) can be used. Examples of lactams of formula (I) which can be used in the present invention include 2-pyrrolidone (γ-butyrolactam), 2-piperidone (δ-valerolactam), ε-caprolactam and laurolactam, each individually or in a mixture. ε-Caprolactam is particularly preferred.
As diols of formula (II) or (III) it is useful to employ ethylene glycol, 1,2- and 1,3-propylene glycol, 1,4-butanediol and also the oligomeric oxyethylene and oxypropylene glycols with degrees of polymerization of from 2 to 20, preferably from 2 to 4. It is also useful to use mixed oligomers with oxyethylene and oxypropylene units. Preference is given to oligooxyethylene and oligooxypropylene glycols having degrees of polymerization from 2 to 4, especially diethylene glycol.
The diol monoethers which can be employed in accordance with the invention include monoetherified diols selected from those set out above. In this case, the alkyl group has 1 to 6, preferably 1 to 4 and, with particular preference, 1 or 2 carbon atoms; specific mention is made of the monomethyl and monoethyl ethers of ethylene glycol and diethylene glycol. The diols and diol monoethers can each be used individually or in a mixture.
Very particular preference is given to modifiers which can be obtained by reacting ε-caprolactam, formaldehyde and diethylene glycol.
The crude mixtures prepared in accordance with the invention, which are preferably used as they are, can be added as modifiers for melamine resins (impregnating resins) in any phase of melamine resin production.
Alternatively, it is useful to separate the N-alkoxymethyllactams VI by a fractional precipitation, for example, and to employ them alone as modifiers.
Any desired amount of the modifier can be added to the melamine. Particularly useful melamine impregnating resin formulations are obtained if the modifiers of the invention are added to melamine resins in a molar ratio of melamine to formaldehyde of from 1 mol:1.4 mol to 1 mol:1.8 mol. The lactam derivatives of the invention, or the product mixtures, are added to the resins to be modified in an amount such that the ratio m L /m MR of the mass m L of the lactam derivative (or of the product mixture) to the mass m MR of the melamine resin solid is from 1 to 20%, preferably from 2 to 10%, addition being possible before, during or after the condensation of the resin. In addition to the lactam derivatives of the invention it is also possible to add other modifiers as well, such as butanediol, ε-caprolactam, diethylene glycol, phenoxy-ethanol or sugars, in proportions by mass of in total of from 2 to 20%, preferably from 5 to 15%, based on the mass of the solids of the modified resin.
The resulting resins modified in accordance with the invention (melamine impregnating resin formulations) have a highly uniform quality, good stability on storage and are outstandingly suitable for impregnating decorative paper which can be processed conventionally on all common types of machines both by the short-cycle process for producing upgraded chipboard panels and by the CPL (continuously pressed laminates) process or HPL (high pressure laminates) process for producing laminates. The resulting surfaces are highly resistant both chemically and mechanically, exhibit high elasticity, are free from cracks, and display a high and uniform gloss.
In particular, when the melamine impregnating resin formulations of the invention are used, compared with prior art resins, there are markedly lower emissions when the resinated papers are dried.
The production of decoratively coated woodbase panels using the melamine impregnating resin formulations of the invention takes place by impregnating the paper or fabric web with a melamine resin modified in accordance with the invention and then subjecting said web to conventional further processing (cf. e.g. Ullmanns Enzyklopädie der techn. Chemie, 4th edition, volume 7 (1974), p. 417 f., hereby incorporated by reference in its entirety).
In the examples which follow, as in the text which precedes them, all figures with the unit “%” are proportions by mass unless indicated otherwise. Parts are always by mass. Concentrations in % are proportions by mass of the dissolved substance in the solution, unless stated otherwise. The examples are for illustrative purposes only and do not limit the scope of the invention.
The following measurement methods are employed for characterization:
nonvolatiles content
A sample of mass m P = 2 g is dried at 120° C. in
a drying oven for one hour in a glass (G) or
aluminum (Al) weighing boat. The mass of the
dry residue is m T ; m T,G when using glass boats
and m T,A1 when using aluminum boats.
The parameter stated is the mass proportion of
the dry residue W T,G = m T,G /m P (=NVC (glass))
or W T,Al = m T,Al /m P (=NVC (alu)).
water dilutability
deionized water is added slowly at 20° C. to one
part of resin having the mass m R and the volume
V R , until there is distinct turbidity. The amount
of water required for this is t parts with the mass
m W or the volume V W . The parameter stated is
the volume ratio ψ WR = V W /V R (t parts by
volume of water, 1 part by volume of resin) in
cm 3 /cm 3 , or the mass ratio ζ WR = m W /m R
(t parts by mass of water, 1 part by mass of resin)
in g/g.
Flow time:
The flow time of a liquid from a flow cup in
accordance with DIN 53211 having a 4 mm
diameter exit aperture
EXAMPLES
A. Preparing the Modifiers
Example 1
A 4 l three-necked flask with KPG stirrer, reflux condenser and internal thermometer was charged with 1486 g (14.0 mol) of diethylene glycol, 1584 g (14.0 mol) of ε-caprolactam, 924 g of 91% paraformaldehyde (Granuform®, Degussa, 28.0 mol) and 13.3 g of p-toluenesulfonic acid.H 2 O (0.070 mol) and this initial charge was heated with stirring to 100° C. over 90 minutes. The reaction mixture was stirred at 100° C. for 30 minutes, during which time it became a solution. The condensation was terminated by cooling the solution to 30° C. and adjusting the pH to 8 with about 11 g of 50% strength sodium hydroxide solution. The finished modifier is of infinite miscibility with water and has the following characteristics:
nonvolatiles content (alu)
w T,Al =
77%
pH (20° C.)
8.3
Concentration of free formaldehyde
7.6%
(DIN 16 746 A)
Brookfield viscosity
158 mPa.s
(23° C., LV 2, 60 min −1 )
According to quantitative 13 C-NMR(H 2 O+10% DMSO), the mixture contains the following species:
ε-Caprolactam
24.1; 30.1; 31.3; 37.0; 43.7; 182.9 ppm.
N,N′-Methylenebis-
24.2; 28.9; 30.5; 37.6; 49.7; 58.8; 180.9 ppm.
caprolactam
N-(7-Hydroxy-2,5-
24.3; 29.3; 30.6; 37.9; 50.1; 62.0; 68.6; 71.1;
dioxaheptyl)-caprolactam
73.2; 78.3; 181.1 ppm.
Diethylene glycol
61.9; 73.3 ppm.
Of the ε-caprolactam employed for the reaction, 1% was present as free ε-caprolactam, 42% as N,N′-methylenebiscaprolactam and 24% as N-(7-hydroxy-2,5-dioxaheptyl)caprolactam in the mixture. 33% could not be allocated to any one defined compound.
Of the diethylene glycol employed for the reaction, 24% was present as N-(7-hydroxy-2,5-dioxaheptyl)caprolactam and 49% as free diethylene glycol. 27% could not be allocated to any one defined compound.
Example 2
A 4 l three-necked flask with KPG stirrer, reflux condenser and internal thermometer was charged with 2122 g (20 mol) of diethylene glycol, 2263 g (20 mol) of ε-caprolactam, 1320 g of 91% paraformaldehyde (Granuform®, Degussa, 40 mol) and 171 g of p-toluenesulfonic acid H 2 O (0.90 mol) and this initial charge was heated with stirring to 100° C. over 30 minutes. The reaction mixture was stirred at 100° C. for 10 minutes, during which time it became a solution. The condensation was terminated by cooling the solution to 30° C. and adjusting the pH to 8 with about 105 g of 50% strength sodium hydroxide solution.
Of the ε-caprolactam employed for the reaction, according to 13 C-NMR, 1% was present as free ε-caprolactam, 50% as N,N′-methylenebiscaprolactam and 23% as N-(7-hydroxy-2,5-dioxaheptyl)caprolactam in the mixture. 26% could not be allocated to any one defined compound.
Example 3
A 0.5 l three-necked flask with KPG stirrer, reflux condenser and internal thermometer was charged with 212 g (2.0 mol) of diethylene glycol, 226 g (2.0 mol) of ε-caprolactam, 66 g of 91% paraformaldehyde (Granuform® Degussa, 2.0 mol) and 0.80 g (10 mmol) of 50% strength sodium hydroxide solution and this initial charge was stirred at 100° C. for 30 minutes. Then 19 g (0.10 mol) of p-toluenesulfonic acid.H 2 O were added and stirring was continued at 100° C. for 10 minutes. The condensation was terminated by cooling the solution to 3° C. and adjusting the pH to 8 with about 9 g (0.11 mol) of 50% strength sodium hydroxide solution.
Of the ε-caprolactam employed for the reaction, according to 13 C-NMR, 5% was present as free ε-caprolactam, 65% as N,N′-methylenebiscaprolactam and 22% as N-(7-hydroxy-2,5-dioxaheptyl)caprolactam in the mixture; 8% could not be allocated to any one defined compound. 47% of the diethylene glycol employed was in free form.
Example 4
The procedure is as for Example 3. Following addition of the p-toluenesulfonic acid, the reaction mixture was heated to an internal temperature of 140° C. over a period of 2 hours, during which time a total of 23 g of water were removed by distillation. The condensation was terminated by cooling to 30° C. and adjusting the pH to 9 with about 9 g (0.11 mol) of 50% strength sodium hydroxide solution.
Of the ε-caprolactam employed for the reaction, according to 13 C-NMR, 6% was present as free ε-caprolactam, 70% as N,N′-methylenebiscaprolactam and 24% as N-(7-hydroxy-2,5-dioxaheptyl)caprolactam in the mixture. 52% of the diethylene glycol employed was in free form.
Example 5
Modifiers were prepared in analogy to Example 1 using 1,4-butanediol and, respectively, polyethylene glycol 200 (PEG 200). The batches were stirred at 100° C. for 30 minutes, cooled and neutralized with an amount of sodium hydroxide solution equivalent to the amount of acid. The amounts employed and characteristics of the resulting modifiers are given in the table below:
Characteristics
Ex-
NVC
pH
Flow
ample
Composition
(glass)
(1:1)
time
5A
339.5 g (3.0 mol)
ε-caprolactam
89%
8.3
29 s
270.4 g (3.0 mol)
1,4-butanediol
99.0 g (3.0 mol)
91% paraform-
aldehyde
2.85 g (0.015 mol)
p-toluenesulfonic
acid.H 2 O
5B
339.5 g (3.0 mol)
ε-caprolactam
83%
6.7
28 s
270.4 g (3.0 mol)
1,4-butanediol
198.0 g (6.0 mol)
91% paraform-
aldehyde
2.85 g (0.015 mol)
p-toluenesulfonic
acid.H 2 O
5C
282.9 g (2.5 mol)
ε-caprolactam
92%
5.8
30 s
500.0 g (2.5 mol)
polyethylene
glycol 200
82.5 g (2.5 mol)
91% paraform-
aldehyde
2.38 g (0.013 mol)
p-toluenesulfonic
acid.H 2 O
5D
282.9 g (2.5 mol)
ε-caprolactam
90%
5.4
37 s
500.0 g (2.5 mol)
polyethylene
glycol 200
165.0 g (5.0 mol)
91% paraform-
aldehyde
2.38 g (0.013 mol)
p-toluenesulfonic
acid.H 2 O
pH (1:1): pH of the sample diluted with deionized water in a ratio of 1:1 by mass.
B. Preparing the Impregnating Resins
Example 6
A 1 liter three-necked flask with KPG stirrer, reflux condenser and internal thermometer was charged with 219.3 g of deionized water, 88 g of the modifier from Example 1 and 395 g (5.1 mol) of 39% formaldehyde. Then 0.4 g (5 mmol) of 50% strength sodium hydroxide solution and, subsequently, 454 g (3.6 Mol) of melamine were added. The pH (23° C.) of the reaction mixture was 9.9. The reaction mixture was heated to reflux temperature (about 103° C.) and stirred at reflux for 10 minutes, then cooled to 85° C. and condensed to a water dilutability ψ WR =2 (1 part by volume of resin to 2 parts by volume of deionized water). The condensation was terminated by cooling to 30° C. The resin obtained had a content by mass w T,Al of nonvolatiles of 59%.
Example 7
A 50 l reactor with stirrer, reflux condenser and internal thermometer was charged with 9.3 kg of deionized water, 40 kg of the modifier from Example 2 and 17.1 kg (223 mol) of 39% formaldehyde. Then 17.4 g (0.22 mol) of 50% strength sodium hydroxide solution and, subsequently, 19.6 kg (156 mol) of melamine were added. The pH (23° C.) of the reaction mixture was 9.6. The reaction mixture was heated to reflux temperature (about 103° C.) and stirred at reflux for 10 minutes, then cooled to 85° C. and condensed to a water dilutability of 1 part by volume of resin to 1.9 parts by volume of deionized water. The condensation was terminated by cooling to 30° C. The resin obtained had the following characteristics:
NVC (glass)
w T,G = 60.6%
Density (20° C.)
ρ = 1247 kg/m 3
pH
9.7
Discharge time
18.0 s
Water dilutability
ζ WR = 1.6 g/g
Storage life
about 4 weeks
Example 8
Impregnating resins were prepared in accordance with Example 6 using the modifiers from Example 5. The composition of the reaction mixtures and the characteristics of the resins are given in the table below:
Characteristics
Dis-
Exam-
NVC
charge
ple
Composition
(alu)
ζ WR
pH
time
8A
184.0 g
deionized water
59%
1.7
9.2
15 s
72.4 g
modifier from
g/g
Example 5A
2.24 ml
2 N sodium
hydroxide soln.
369.8 g
39.1% strength
aqueous
formaldehyde
403.5 g
melamine
8B
197.3 g
deionized water
59%
1.4
9.2
17 s
82.5 g
modifier from
g/g
Example 5B
2.24 ml
2 N sodium
hydroxide soln.
346.4 g
39.1% strength
aqueous
formaldehyde
403.5 g
melamine
8C
179.4 g
Deionized water
60%
1.6
9.1
16 s
68.7 g
Modifier from
g/g
Example 5C
2.24 ml
2 N sodium
hydroxide soln.
378.0 g
39.1 strength
aqueous
formaldehyde
403.5 g
melamine
8D
188.1 g
deionized water
60%
1.6
9.2
17 s
75.3 g
modifier from
g/g
Example 5D
2.24 ml
2 N sodium
hydroxide soln.
362.9 g
39.1 strength
aqueous
formaldehyde
403.5 g
melamine
Comparative Example 1
A 50 l reactor with stirrer, reflux condenser and internal thermometer was charged with 8.3 kg of deionized water, 1.5 kg of ε-caprolactam, 1.4 kg of diethylene glycol and 19.1 kg (249 mol) of 39% formaldehyde. Then 17.4 g (0.22 mol) of 50% strength sodium hydroxide solution and, subsequently, 19.6 kg (156 mol) of melamine were added. The pH (23° C.) of the reaction mixture was 9.7. The reaction mixture was heated to reflux temperature (about 103° C.) and stirred at reflux for 10 minutes, then cooled to 85° C. and condensed to a water dilutability ψ WR =1.9 (1 part by volume of resin to 1.9 parts by volume of deionized water). The condensation was terminated by cooling to 30° C.
The resin obtained had the following characteristics:
(NVC (glass), 2 g, 1 h 120° C.)
w T,G = 60.7%
Density (20° C.)
ρ = 1245 kg/m 3
pH
9.6
Discharge time
17.5 s
Water dilutability
ζ WR = 1.5 g/g
Storage life
about 5 weeks
Comparative Example 2
A 1 l three-necked flask with KPG stirrer, reflux condenser and internal thermometer was charged with 145 g of deionized water and 444 g (5.77 mol) of 39% formaldehyde. Then 2.5 ml of 2 N (5 mmol) sodium hydroxide solution and, subsequently, 454 g (3.6 mol) of melamine were added. The pH (23° C.) of the reaction mixture was 9.4.
The reaction mixture was heated to reflux temperature (about 103° C.) and stirred at reflux for 10 minutes, then cooled to 85° C. and condensed to a water dilutability ψ WR =1.9 (1 part by volume of resin to 1.9 parts by volume of deionized water). The condensation was terminated by cooling to 30° C. The resin obtained had the following characteristics:
NVC (Alu)
w T,Al = 58.8%
pH
9.4
water dilutability
ζ WR = 1.3 g/g
storage life
4 days
Comparative Example 3
In relation to the resins of Example 8, the corresponding resins modified with the simple modifiers 1,4-butanediol or polyethylene glycol 200 (molar mass about 200 g/mol) and ε-caprolactam, for purposes of comparison. The procedure is as for Comparative Example 1; the composition of the reaction mixtures, and the characteristics, are given in the table below:
Characteristics
Compa-
Dis-
rative
NVC
charge
Example
Composition
(alu)
ζ WR
pH
time
3A
171.1 g
deionized water
60%
1.9 g/g
9.3
16 s
Com-
34.5 g
ε-caprolactam
parison
27.4 g
1,4-butanediol
with
2.24 ml
2 N sodium
Example
hydroxide soln.
8A and B
393.2 g
39.1% strength
aqueous
formaldehyde
403.5 g
melamine
3B
171.1 g
deionized water
60%
1.6 g/g
9.2
16 s
Com-
22.4 g
ε-caprolactam
parison
39.6 g
polyethylene
with
glycol 200
Example
2.24 ml
2 N sodium
8C and D
hydroxide soln.
393.2 g
39.1% strength
aqueous
formaldehyde
403.5 g
melamine
C. Investigating the Emissions Behavior
Investigation 1
The smoking behavior of films impregnated with the resins from Example 7 and Comparative Example 1 was assessed qualitatively. The overall composition of the two resins (melamine, formaldehyde, εcaprolactam and diethylene glycol) is the same. The resins were adjusted with an acidic amine salt (p-toluenesulfonic acid/morpholine) to a turbidity time (T time) of from 5 to 5½ minutes at 100° C. These liquid impregnating formulations were used to impregnate decorative paper which was then dried in a drying cabinet at 180° C. The smoking behavior was monitored at intervals of a minute. The results are set out in the table below:
T time
100° C.
Smoking behavior at 180° C. after
Resin
min
1 min
2 min
3 min
4 min
Example 7
5½
nothing
nothing
nothing
slight
found
found
found
smoking
Comparative
5
nothing
nothing
slight
distinct
Example 1
found
found
smoking
smoking
Investigation 2
The emissions of ε-caprolactam (capro) and diethylene glycol (DEG) from the resins from Example 7, Comparative Example 1 and Comparative Example 2 were investigated by means of GC analysis. For this purpose, the resin solutions were injected directly at a block temperature of 120° C. or 160° C. respectively. The results obtained are set out in the tables below:
GC analysis at 120° C. (volatile fractions based on resin solution):
GC analysis at 120° C. (volatile fractions based on resin solution):
Resin
Modification
Capro
DEG
Capro + DEG
Example 7
in accordance with
0.8%
0.6%
1.4%
the invention with
modifier from Ex. 2
Comp.
Caprolactam and
2.5%
2.3%
4.8%
Example 1
diethylene glycol
Comp.
unmodified
<0.1%
<0.1%
<0.1%
Example 2
GC analysis at 160° C. (volatile fractions based on resin solution):
Resin
Modification
Capro
DEG
Capro + DEG
Example 7
in accordance with
0.4%
1.9%
1.3%
the invention with
modifier from Ex. 2
Comp.
Caprolactam and
1.9%
2.6%
4.5%
Example 1
diethylene glycol
Comp.
unmodified
<0.1%
<0.1%
Example 2
By using the impregnating resin of the invention from Example 7, comprising the modifier of the invention from Example 2, it is possible to reduce markedly the emissions of ε-caprolactam and diethylene glycol in comparison to the impregnating resin from Comparative Example 1 which is modified with the simple modifiers ε-caprolactam and diethylene glycol.
Investigation 3
The smoking behavior of films impregnated with the resins from Example 8 and Comparative Example 3 was assessed qualitatively. The overall composition of the resins (melamine, formaldehyde, εcaprolactam and 1,4-butanediol from Example 8A, 8B and Comparative Example 3A, and the overall composition of the resins (melamine, formaldehyde, ε-caprolactam and polyethylene glycol 200) from Example 8C, 8D and Comparative Example 3B, is the same in each case. The resins were adjusted with an acidic amine salt p-toluenesulfonic acid/morpholine) to a turbidity time (T time) of from 5 to 5½ minutes at 100° C. These liquid impregnating formulations were used to impregnate decorative paper which was then dried in a drying cabinet at 180° C. The smoking behavior was monitored at intervals of a minute. The results are set out in the table below:
Smoking behavior at 180° C. after:
Resin
1 min
2 min
3 min
4 min
Example 8A
nothing
nothing
Slight
distinct
found
found
Example 8B
nothing
nothing
Slight
distinct
found
found
Comparative
nothing
slight
Distinct
severe
Example 3A
found
Example 8C
nothing
nothing
Nothing
distinct
found
found
found
Example 8D
nothing
nothing
nothing
distinct
found
found
found
Comparative
nothing
nothing
distinct
severe
Example 3B
found
found
By using the impregnating resins of the invention from Example 8 it is possible to achieve a marked reduction in smoking relative to the prior art (Comparative Example 3).
D. Performance Testing
Investigation 4
The impregnating resins from Example 7 and Comparative Example 1 were subjected to performance testing for use in the short-cycle process. For this purpose, the resin solutions were adjusted with an acidic amine salt (p-toluenesulfonic acid/morpholine) to a turbidity time of about 5 minutes. The decorative papers (PWA, A-60 S, 80 g/m 2 ) impregnated with these resin solutions were dried in a drying cabinet and then pressed onto chipboard panels (60 s, 160° C. at the paper, 3 MPa [=30 bar], press plate HS-18). The results of the test are given in the table below:
Testing the coated chipboard panel
Melamine film
Temper-
Resid-
ing acc.
Resin
ual
Kiton
to DIN
con-
mois-
test
Over-
68765,
Resin
tent
ture
Surface
2h
curing
4.6
Example 7
60%
6.0%
nothing
2-3
nothing
nothing
found
found
found
Comparative
58%
6.1%
nothing
2
nothing
nothing
Example 1
found
found
found
Kiton Test
Testing of surfaces treated with MF resin
Solution I
1000 ml of H 2 O
20 ml of H 2 SO 4
20 ml of 2% strength aqueous solution of ®Lissamine Red B
(manufacturer: ICI)
A “glass eye” (dome) filled with solution I is applied to the sample and allowed to act at room temperature for 2 hours. Thereafter, the test site is cleaned thoroughly with water and assessed using a 6-point color scale.
The stages of coloring range from
stage 1: no staining=overcuring, to
stage 6: dark violet staining=complete undercuring.
In the case of treated chipboard panels, the aim should be to achieve cures of stage 2 or 2-3 (good, good-moderate).
There are no differences in terms of short-cycle performance between the resin of the invention from Example 7 and the prior art resin from Comparative Example 1.
Investigation 5
The impregnating resins from Example 7 and Comparative Example 1 were subjected to performance testing for use in the CPL process. For this purpose, the resin solutions were adjusted with an acidic amine salt (p-toluenesulfonic acid/morpholine) to a turbidity time of about 5 minutes. The decorative papers (PWA, A-60 S, 80 g/m 2 , resin add on about 60%, residual moisture about 6%) or core ply papers (sodium kraft, 135 g/m 2 , resin add on about 50%, residual moisture about 6.7%) impregnated with these resin solutions were dried in a drying cabinet and then pressed to give laminates consisting of one decorative film ply and 3 core plys (35 s, 175° C., 3.5 MPa [=35 bar], press plate HS-18). The results of the test are given in the table below:
Testing of the laminates
Kiton
Steam
Boil
Boil
test
test*
test #
test #
Post-
Resin
Surface
2h
60 min
2h
6h
forming +
Example 7
nothing
3
nothing
nothing
nothing
nothing
found
found
found
found
found
Comp. Ex. 1
nothing
2
nothing
nothing
nothing
nothing
found
found
found
found
found
*in accordance with DIN-EN 438, section 24
# in accordance with DIN-EN 438, section 7
+ in accordance with DIN-EN 438, section 20
There are no differences in terms of laminate production performance between the resin of the invention from Example 7 and the prior art resin from Comparative Example 1.
German Application 197 44 942.5 filed Oct. 10, 1997 (the priority document of the present application) is hereby incorporated by reference in its entirety.
Although only a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention. | N-Alkoxymethylactams are obtained by reacting lactams with formaldehyde and hydroxyl-containing compounds selected from diol monoethers. The substituted lactams are useful as an additive to melamne impregnating resings. | 2 |
TECHNICAL FIELD
The present invention relates generally to floating devices, and more particularly to an ensemble of singular construction comprising a table and a plurality of seating means attached thereto that is sufficiently buoyant to float when disposed in a body of water.
BACKGROUND
Swimming pools and other bodies of water have been used for recreational purposes since the earliest of times. In order to enhance the bathing experience, various and sundry water toys such as floating basketball hoops, balls and other items have been devised.
One class of recreational item commonly used in association with swimming pools is a floating chair and floating rafts. Typically, such devices accommodate a single user, who sits in the chair or raft and relaxes, usually in the sun, while in contact with the water in the pool to take advantage of its cooling effect for providing refreshment. Often, such devices include accessory features such as cup holders, so that a person residing within such a floating chair may enjoy their favorite beverage in order to enhance the pleasure of the experience.
Some have found a floating but stable table structure, such as a table to be a desirable item for use in a swimming pool. The device described in U.S. Pat. No. 6,171,160 provides a table of sufficient sturdiness such that even when floating it will support a drink without spillage, owing to its primary feature of a stabilizing weight which is suspended beneath the table when in use.
Another device useful in enhancing the experience of bathing is described in U.S. Pat. No. 19,593 which teaches a plurality of life-preserving mattress tied together by belt-and-buckle strapping to form a raft. U.S. Pat. No. 4,894,033 teaches a structure including several inflatable rafts connected together by “T” and ring or loop interconnector devices. A floating chair made up of individual rigid sections but having flexible straps permanently interconnecting the sections is provided by U.S. Pat. No. 5,176,554. U.S. Pat. No. 5,411,425 teaches a floating structure having utility as a watercraft float which includes a pair of floating pillows interconnected by a seat, with connections being made only at the four corners of the pillows and seat. U.S. Pat. No. 3,694,837 teaches a floating body for bathing purposes that comprises a hollow cylindrical body having a partition wall that divides the interior of the body into an outer annular section and an inner central section. The inner central section has in its lower portion at least one opening through which water may enter into the section and that the upper portion of the inner central section has an opening to the atmosphere and a manually operable control valve for controlling the inner central section upper opening in order to vary the draught of the floating body. U.S. Pat. No. 4,724,773 provides a pedestal table in which the pedestal is to be releasably secured to the floor area of a smooth-surfaced hot tub, spa or pool, with the central support shaft of the table extending vertically through the water to the hot tub, spa or pool to support a table above the surface of the water. The pedestal table comprises: a) a generally cylindrical collar having a first and second ends, with at least the second end having an open passage therethrough; b) a peripheral flange extending from the collar adjacent to the first end of the collar; c) at least three elastomeric suction cups attached to the peripheral flange such that the suction cups are equally spaced about the peripheral flange and extend from the side of the flange facing away from the cylindrical collar, wherein the suction cups can be engaged with the floor area of the hot tub, spa or pool to releasably secure the collar to the floor area; d) an elongate, cylindrical column having sufficient length to extend from the floor area to the surface of the water, wherein the column has first and second ends, with the first end being received in sliding, the removable engagement within the second open end of the collar such that the column extends vertically upward from the collar; e) a cover for the cylindrical collar, wherein the cover has the shape of a truncated cone in which the cone covers the peripheral flange, the suction cups and the cylindrical collar, with the column extending through the truncated top of the cover; f) a planar tabletop member, and g) a means for attaching the planar top member to the second end of the column. U.S. Pat. No. 5,465,677 provides a float post apparatus comprising an elongated post having first and second opposite ends, a tether having first and second ends, tether mounting means attached to the post adjacent the second end, the first end of the tether having attachment means to attach the tether to the tether mounting means and the second end of the tether having attachment means to attach the tether to a person, the first end of the post adapted to be anchored at the bottom of a body of water, a mounting stand having a post receiving seat adapted to receive the first end of the float post, the mounting stand having a neck portion and having the post receiving seat formed in the neck portion, an aperture formed through the neck portion and a corresponding aperture formed through the post adjacent the first end of the post and being in alignment with the aperture in the neck when the post is received in the post receiving seat, and a locking member received in the apertures to lock the post to the mounting stand and a storage locker mounted on the second end of the post. U.S. Pat. No. 5,823,121 discloses a self-adjusting portable table for use in a spa having a floor and being filled with water to create a water surface, the self-adjusting portable table comprising: a) a base member, wherein the base member is adapted for positioning on the floor of the spa; b) a planar table top member having a substantially planar top surface, wherein the table top member is adapted to float on the water surface of the spa; and c) a self-adjusting vertical support member interconnecting the base member and the planar table top member, wherein the self-adjusting vertical support member is adapted for supporting the planar table top member in a generally horizontal position on the water surface of the spa; wherein the self-adjusting vertical support member comprises: an engaging member, wherein the engaging member is removably coupled to the base member, and a sleeve member, wherein the sleeve member is secured to the planar table top member, wherein the engaging member and the sleeve member are slidably telescopically coupled together such that the sleeve member slides freely over the engaging member, whereby the planar table top member is vertically self-adjustable towards and away from the base member corresponding to changes in a distance between the floor of the spa and the water surface of the spa U.S. Pat. No. 6,171,160 teaches a floating devices connection and/or storage system, comprising: a) a floating device having a peripheral edge; b) a predetermined number of connection devices arrayed about the floating device peripheral edge, each the connection device being hermaphroditic in construction; c) a means for assuring secure interconnection of a selected connection device with another, similar connection device; and d) a means for storing the floating device, comprising a plurality of suspension means on a vertical surface interconnected with the connection devices, and spacing means for separating the floating device from the vertical surface, thus assuring air flow about substantially the entire floating device and thus reducing the possibility of mildew and/or mold formation on the floating device during storage.
However, of all of the devices of the prior art, none thus far have provided a device which comprises a floating table around which two or more persons may sit while bathing in a body of water such as a swimming pool. Further, none have provided a floating table having a plurality of seating means associated with it, which are an integral part of the construct of such a floating table. Further, none have provided a floating table having a plurality of seating means as part of a unitary construction which is further provided with means for providing equalizing balancing means to provide a level tabletop surface even in cases where persons of significantly different weight are seated about such a table. The present invention provides such a table having a plurality of seating means disposed about it in a single unitary construction having ballasting means for compensating for the differences in weight of persons disposed about such a floating table, in addition to other advantageous features which will be recognized from a thorough reading of this specification and its appended claims.
SUMMARY OF THE INVENTION
The present invention provides an ensemble comprising a table and a plurality of seating means connectively attached thereto that is sufficiently buoyant as a whole to float when disposed in a body of water. An ensemble according to one form of the invention comprises a substantially planar framework which itself includes: a first linear frame member having a first end portion and a second end portion and having a hollow interior portion; a second linear frame member having a first end portion and a second end portion and having a hollow interior portion; a third linear frame member having a first end portion and a second end portion and having a hollow interior portion; and a fourth linear frame member having a first end portion and a second end portion and having a hollow interior portion. The first end portion of each of the first, second, third, and fourth linear frame members are connected to one another such that the hollow interior portions of each of the frame members are in fluid contact with one another. Each of the first, second, third, and fourth linear frame members are radially disposed about a common centerpoint. There is a first hollow structural conduit having a hollow interior portion, a first end portion, and a second end portion. The first end portion of the first hollow structural conduit is connected to the first linear frame member at a point between the first end portion and the second end portion of the first linear frame member. The second end portion of the first hollow structural conduit is connected to the second linear frame member at a point between the first end portion and the second end portion of the second linear frame member. There is a second hollow structural conduit having a hollow interior portion, a first end portion, and a second end portion, and the first end portion of the second hollow structural conduit is connected to the second linear frame member at a point between the first end portion and the second end portion of the second linear frame member. The second end portion of the second hollow structural conduit is connected to the third linear frame member at a point between the first end portion and the second end portion of the third linear frame member. There is a third hollow structural conduit having a hollow interior portion, a first end portion, and a second end portion. The first end portion of the third hollow structural conduit is connected to the third linear frame member at a point between the first end portion and the second end portion of the third linear frame member. The second end portion of the third hollow structural conduit is connected to the fourth linear frame member at a point between the first end portion and the second end portion of the fourth linear frame member. There is a fourth hollow structural conduit having a hollow interior portion, a first end portion, and a second end portion. The first end portion of the fourth hollow structural conduit is connected to the fourth linear frame member at a point between the first end portion and the second end portion of the fourth linear frame member. The second end portion of the fourth hollow structural conduit is connected to the first linear frame member at a point between the first end portion and the second end portion of the first linear frame member. The hollow interior portion of each of the hollow structural conduits are in fluid contact with the hollow interior portions of the linear frame members. The framework includes an opening between the space enclosed by the interior portions of the hollow structural conduits and the linear frame members and the space external to the interior portions of the hollow structural conduits and the linear frame members sufficient to admit water when the framework is submerged in a body of water. The second end portion of each of the first, second, third, and fourth linear frame members are curved upwardly from the plane of the planar framework. There is a seating means disposed at the second end portion of each of the first, second, third, and fourth linear frame members. There is a vertical support beam having a first end portion and a second end portion. The first end of the vertical support beam is connected to the planar framework at the common centerpoint about which the first, second, third, and fourth linear frame members are radially disposed. There is a buoyant tabletop having a planar top surface disposed at the second end portion of the vertical support beam.
In a more general sense, the invention comprises a substantially planar framework comprising hollow structural members each having an interior volume, wherein the interior volume at least two of the structural members of the framework are in fluid contact with one another. The framework includes an opening to render the interior volume to be in fluid contact with the external surroundings, such that water is admitted into the interior volume upon submersion of the framework into a body of water. There is a buoyant tabletop portion centrally disposed above the plane of the planar framework, and a plurality of seating means connected to the framework. The seating means are disposed so that the tabletop portion is centrally located with respect to the seating means.
BRIEF DESCRIPTION OF THE DRAWINGS
In the annexed drawings:
FIG. 1 is a perspective view of a floating table and seat ensemble according to one preferred form of the invention;
FIG. 2 is a side perspective view of a floating table and seat ensemble according to one preferred form of the invention;
FIG. 3 is an overhead view of the framework portion of a table and seat ensemble according to one preferred form of the invention;
FIG. 4 is a is an overhead view of the framework portion of a table and seat ensemble according to one preferred form of the invention, including the seating means;
FIG. 5 is a see-through view of the framework portion of a table and seat ensemble according to one preferred form of the invention;
FIG. 6 is a side perspective view of a floating table and seat ensemble according to one preferred form of the invention;
FIG. 7 a is a side view of a buoyant tabletop portion of an ensemble according to one preferred form of the invention;
FIG. 7 b is an overhead view of a buoyant tabletop portion of an ensemble according to one preferred form of the invention;
FIG. 8 a is a side view of a buoyant tabletop portion of an ensemble according to one alternate form of the invention;
FIG. 8 b is an overhead view of a buoyant tabletop portion of an ensemble according to one alternate form of the invention; and
FIG. 9 is an overhead view of a buoyant tabletop portion of an ensemble according to one alternate form of the invention.
DETAILED DESCRIPTION
Referring to the drawings and initially to FIG. 1 there is shown a perspective view of a floating table and seat ensemble 69 according to one preferred form of the invention. In this FIG. 1 are shown the first linear frame member 14 a , second linear frame member 14 b , third linear frame member 14 c , and fourth linear frame member 14 d arranged wherein the first end portion of each of the aforesaid linear frame members are connected to one another at a common center point of intersection from which each of the linear frame members may be said to be disposed about radially.
There is also shown in FIG. 1 the first hollow structural conduit 16 a , second hollow structural conduit 16 b , third hollow structural conduit 16 c , and fourth hollow structural conduit 16 d.
In this FIG. 1, the first hollow structural conduit 16 a has its first end portion connected to the first linear frame member 14 a at a point between the first end portion and the second end portion of the first linear frame member 14 a , and the second end portion of the first hollow structural conduit 16 a is connected to the second linear frame member 14 b at a point between the first end portion and the second end portion of the second linear frame member 14 b . Additionally, the second hollow structural conduit 16 b has its first end portion connected to the second linear frame member 14 b at a point between the first end portion and the second end portion of the second linear frame member 14 b , and the second end portion of the second hollow structural conduit 16 b is connected to the third linear frame member 14 c at a point between the first end portion and the second end portion of the third linear frame member 14 c . The third hollow structural conduit 16 c has its first end portion connected to the third linear frame member 14 c at a point between the first end portion and the second end portion of the second linear frame member 14 c , and the second end portion of the third hollow structural conduit 16 c is connected to the fourth linear frame member 14 d at a point between the first end portion and the second end portion of the fourth linear frame member 14 d . The fourth hollow structural conduit 16 d has its first end portion connected to the fourth linear frame member 14 d at a point between the first end portion and the second end portion of the fourth linear frame member 14 d , and the second end portion of the fourth hollow structural conduit 16 d is connected to the first linear frame member 14 a at a point between the first end portion and the second end portion of the first linear frame member 14 a.
FIG. 1 also shows the vertical support beam 12 with its first end portion attached to the center of the planar framework defined by the plurality of hollow structural conduits and linear frame members, extending upwardly from the plane of the planar framework, and having a the buoyant tabletop 10 with its planar top surface disposed on the second end portion of the vertical support beam 12 .
There are a plurality of seating means 21 disposed at the second end portion of each of the first, second, third, and fourth linear frame members. From FIG. 1, it is apparent according to one preferred form of the invention that the second end portion of each of the linear frame members are curved upwardly from the plane of the planar framework which is comprised of the linear frame members and the hollow structural conduits, and that it is at the curved end at which the seating means are connectively attached. Such seating means provides a location for people to sit while using and enjoying the benefits of an ensemble 69 according to the invention.
FIG. 2 shows a side perspective view of a floating table and seat ensemble 69 according to one preferred form of the invention, showing the respective positions of the second linear frame member 14 b , fourth linear frame member 14 d , second hollow structural conduit 16 b , and third hollow structural conduit 16 c . Disposed on the ends of the linear frame members which curve upwardly from the plane of the framework comprised of the linear frame members and the hollow structural conduits are flanges at 27 which in one form of the invention serve as a convenient connection means for the seating means 21 . The flange at 27 may be simply a plate of metal attached to the second end portion of the linear frame member, to which a seating means may be conveniently attached to the ensemble 69 as a whole using conventional fastening means, as the attachment of seating means to metal plates is well known in the art. The seating means 21 may be a flat piece of wood, metal, or plastic, or may comprise a cushioned seat, filled with foam or other soft materials, as are known in the art. The size of the seating means is not critical, and the main requirement is that it should be of sufficient area to accommodate the seating size requirements of most people. There is also shown the vertical support 12 having its first end portion connected to the planar framework at the common centerpoint about which the first, second, third, and fourth linear frame members are radially disposed. The vertical support 12 extends upwardly from the plane of the planar framework which is comprised of the linear frame members and the hollow structural conduits. There is a buoyant tabletop 10 having a planar top surface disposed at the second end portion of the vertical support beam. For added strength, braces 86 are connectively attached to the vertical support 12 and each of the hollow structural conduits.
In FIG. 3 is shown an overhead view of the framework portion of a table and seat ensemble 69 according to one form of the invention. In this figure are shown the various linear frame members 14 a , 14 b , 14 c , 14 d , and the various hollow structural conduits 16 a , 16 b , 16 c , and 16 d , as well as the intersection point 20 of the first end portions of the linear frame members and the mounting points 27 for the flanges where the seating means are preferably mounted. The first hollow structural conduit 16 a and the first and second linear frame members 14 a and 14 b define the outer perimeter of a first planar footspace, 99 a within the same plane as the planar framework. Further, the second hollow structural conduit 16 b and the second and third linear frame members 14 b and 14 c define the outer perimeter of a second planar footspace 99 b . Further the third hollow structural conduit 16 c and the third and fourth linear frame members 14 c and 14 d define the outer perimeter of a third planar footspace 99 c . Further, the fourth hollow structural conduit 16 d and the fourth and first linear frame members 14 d and 14 a define the outer perimeter of a fourth planar footspace 99 d . These footspaces are the locations where a person sitting on the ensemble 69 of the invention may rest their feet, by virtue of each of the planar footspaces each including a floor portion means 34 connected to the hollow structural conduit and linear frame members which define the respective footspaces. According to one preferred form of the invention, the floor portion means is non-metallic. Preferably, the floor portion means is made from a woven polymer, such as woven nylon, PVC, or polyolefin and is attached to the framework by conventional means such as adhesives or being woven to tied to one or more holes in the framework elements.
In FIG. 4 is shown a is an overhead view of the framework portion of a table and seat ensemble 69 according to one preferred form of the invention, including the seating means 21 mounted at 27 . There is also shown the first, second, third, and fourth linear frame members 14 a , 14 b , 14 c , 14 d , with their first end portions intersecting at 20 . Also shown are the first, second, third, and fourth hollow structural conduits 16 a , 16 b , 16 c , and 16 d.
In FIG. 5 is shown a is a see-through overhead view of the framework portion of a table and seat ensemble 69 according to one preferred form of the invention, including the seating means 21 mounted at 27 . There is also shown the first, second, third, and fourth linear frame members 14 a , 14 b , 14 c , 14 d , with their first end portions intersecting at 20 . Also shown are the first, second, third, and fourth hollow structural conduits 16 a , 16 b , 16 c , and 16 d . In this figure, the arrows indicate the possible motion of water within the interior spaces of the linear frame members and hollow structural conduits, which water is admitted into such interior spaces by virtue of the presence of an opening between the space enclosed by the interior portions of the hollow structural conduits and the linear frame members, and the space external them. Preferably, the hole is disposed beneath the intersection point 20 , at location shown as 25 in FIG. 6 . According to one preferred form of the invention, there are openings 23 disposed at or near the seating means mounting point 27 of each of the linear frame members, to facilitate the entry of water into the cavernous interior spaces of the linear frame members and hollow structural conduits, for in the absence of such openings air would otherwise be entrained in the space where the second end portions of the linear frame members curve upwardly and would preclude the flow of water therein. By enabling admittance of water into the device as provided by such a construct, advantageous buoyancy of the ensemble 69 of the invention as a whole is provided.
FIG. 6 shows a see-through side perspective view of a floating table and seat ensemble 69 according to one preferred form of the invention, showing the respective positions of the second linear frame member 14 b , fourth linear frame member 14 d , second hollow structural conduit 16 b , and third hollow structural conduit 16 c . Disposed on the ends of the linear frame members which curve upwardly from the plane of the framework comprised of the linear frame members and the hollow structural conduits are flanges at 27 which in one form of the invention serve as a convenient connection means for the seating means 21 . There is also shown the vertical support 12 having its first end portion connected to the planar framework at the common centerpoint about which the first, second, third, and fourth linear frame members are radially disposed. The vertical support 12 extends upwardly from the plane of the planar framework which is comprised of the linear frame members and the hollow structural conduits. There is a buoyant tabletop 10 having a planar top surface disposed at the second end portion of the vertical support beam. For added strength, braces 86 are connectively attached to the vertical support 12 and each of the hollow structural conduits. In FIG. 6 is also shown the flow of water through the various structural elements of the ensemble 69 including the linear frame members, the hollow structural conduits, and the vertical support 12 . When an ensemble 69 according to the invention is placed in a body of water, water is admitted into the interior volume defined by these structural elements through the hole at 25 which is located on the underside of the framework as a whole, at the intersection point 20 of the first end portions of the linear frame members. According to one form of the invention, the vertical support 12 has an opening at its second end. According to another form of the invention, the vertical support 12 includes a hole 77 disposed along its length, for the purpose of facilitating entry of water into the space within the vertical support 12 . Also shown in FIG. 6 is the vertical support guide 31 , which may be a bore, sleeve, or channel which is contoured identically to the second end portion of the vertical support 12 , but is of a slightly larger inner dimension to accommodate the insertion of the second end portion of the vertical support 12 therein to provide an interference fit between the vertical support and the tabletop 10 . In one form of the invention, the vertical support 12 is square in cross section, and the vertical support guide 31 is a square shaped tube of slightly larger dimension than the vertical support 12 . In another form of the invention, the vertical support 12 is round in cross section, and the vertical support guide 31 is a round tube of slightly larger dimension than the vertical support 12 . The vertical support guide may be an integral part of the tabletop portion 10 , or it may be a separate article of manufacture attached to the tabletop portion by any conventional means, such as welding or conventional fasteners such as screws, nuts and bolts, or rivets, etc.
FIG. 7 a shows a side view of a buoyant tabletop portion 10 of an ensemble 69 according to one preferred form of the invention. In this figure is seen the vertical support guide 31 centrally disposed within the tabletop portion.
FIG. 7 b shows an overhead view of a buoyant tabletop portion 10 of an ensemble 69 according to one preferred form of the invention. In this figure is seen the vertical support guide 31 centrally disposed within the tabletop portion.
FIG. 8 a shows a side view of a buoyant tabletop portion 10 of an ensemble 69 according to one preferred form of the invention. In this figure is seen the vertical support guide 31 centrally disposed within the tabletop portion. Also shown are cutout portions 88 , useful for containing a beverage container such as a glass or soda pop can. Such cutout portions 88 are holes or voids.
FIG. 8 b shows an overhead view of a buoyant tabletop portion 10 of an ensemble 69 according to one preferred form of the invention. In this figure is seen the vertical support guide 31 centrally disposed within the tabletop portion. Also shown are cutout portions 88 , useful for containing a beverage container such as a glass or soda pop can.
FIG. 9 shows an overhead view of a buoyant tabletop portion 10 of an ensemble 69 according to one preferred form of the invention. In this figure is seen the vertical support guide 31 centrally disposed within the tabletop portion. Also shown are cutout portions 88 , useful for containing a beverage container such as a glass or soda pop can.
The main structural elements of the present invention include the linear frame members 14 a , 14 b , 14 c , 14 d , the hollow structural conduits 16 a , 16 b , 16 c , 16 d , and the vertical support 12 . According to one preferred form of the invention, these elements each contain a hollow interior space. This is readily provided for by selecting the materials from which they are fabricated from a tubular stock. In the simplest case, the aforesaid structural elements are made from tubing, such as metal pipes, or PVC tubing. PVC plastic is particularly preferred because of its relatively low weight, inertness, and strength. However, metallic tubing may be selected as the material from which these structural elements are comprised, such as aluminum, galvanized steel, or stainless steel tubing. These structural elements are connected to one another using conventional means, such as by welding when they are comprised of a metallic material which can be welded. In the case when PVC or other polymeric material comprises the structural elements, means known in the art for joining polymeric materials are suitable for connecting the structural elements, including solvent welding, adhesives, etc. In addition, conventional fasteners such as adhesives, brackets, nuts and bolts, screws, rivets, etc. may be employed to fasten the various structural elements to one another to provide an ensemble 69 according to the invention. In one preferred form of the invention, the linear frame members and hollow structural conduits are made from square metallic tubing having a cross section measurement, and the ends of the hollow structural conduits are fitted over holes in the side walls of the linear frame members in a sealing fashion, such as by a weld bead around the perimeter of the joint. The holes in the side walls of the linear frame members are of a lesser dimension than the cross section measurement of the square metallic tubing employed. In addition, although the hollow structural elements in FIG. 1 et al. all collectively define a square by virtue of each of the hollow structural elements comprising a portion that has an angle of about 90° along their length between their first end portion and their second end portion, the present invention contemplates other shapes for these hollow structural elements, including the case where the hollow structural elements are arcuate in shape and thus collectively define a circle when viewed as a whole.
The tabletop portion 10 preferably comprises a hollow box that in one preferred form of the invention is shaped substantially in the form of a rectangular solid as shown in the various figures. The purpose of the tabletop portion 10 is to provide buoyancy to the ensemble 69 of the invention as a whole. The tabletop portion 10 provides buoyancy by virtue of its being filled with air, which provides a buoyancy effect by displacing water with the air contained within the tabletop portion 10 when the ensemble 69 of the invention is placed into a body of water. By allowing water to be admitted into the structural elements of the ensemble 69 and by having the buoyancy provided by the centrally-located tabletop, an especially stable structure is provided upon which people may sit and enjoy a truly unique recreational experience of sitting at a table in the water.
Thus, the tabletop portion excludes water from its interior in order to provide a buoyancy to the ensemble 69 as a whole. In one preferred form, the tabletop is comprised of a floor portion, four wall portions, and a flat top portion. In one preferred form of the invention, the floor portion is provided with a square hole in its center. A section of square tubing functions as vertical support guide 31 and is placed through the hole and welded or attached using conventional means described elsewhere herein, either on the inside, outside, or both surfaces where the square tubing meets the floor portion. In such fashion, the tabletop may be lowered onto the second end portion of the vertical support 12 , for the case when the cross section of the vertical support 12 is square and of slightly smaller diameter than the vertical support guide 31 . Analogous arrangements are functionally-equivalent possibilities for cases when the tubing is circular in cross section, or has other cross-sectional geometries. In addition, the vertical support guide 31 may include a stop ( 50 in FIG. 8 a ) to limit the travel of the vertical support 12 in the bore defined by the vertical support guide 31 . According to one preferred form of the invention, the second end portion of the vertical support 12 is placed into the vertical support guide 31 and is welded in position. According to an alternate form of the invention, the second end portion of the vertical support 12 is placed into the vertical support guide 31 and is removably held in position by the use of conventional brackets and fasteners coupling the vertical support guide 31 to the vertical support 12 . One convenient means includes the use of a lynch pin disposed through a bore which is common to both the vertical support 12 and the vertical support guide 31 and which bore is disposed perpendicular to the length dimension of the vertical support 12 . By such provision, the tabletop portion is readily detachable from the remaining portions of the ensemble 69 .
The tabletop portion 10 may also, in an alternate form of the invention, be filled with a foamed material, such as expanded polystyrene. In any event, the tabletop portion is sufficiently buoyant to provide a degree of buoyancy to the ensemble 69 as a whole to float while said ensemble is disposed in a body of water and a total human mass in the range of 200 to 1000 lbs is disposed on the plurality of seating means present. According to a preferred form of the invention, the tabletop portion measures 3 feet wide by 3 feet long by 2 feet high for a total displacement of about 18 cubic feet which provides a maximum buoyancy of about 1100 pounds, which is more than adequate to support the device and four adult people.
The invention includes means for attaching weights to the framework, in order to adjust the degree of levelness of the tabletop for the various possible cases of persons having different weights seated on an ensemble according to the invention. Such means may be simple hooks where weights may be attached at various locations on the framework or other parts of the present invention, or may be a protruding flange such as at 66 in FIG. 2 where a weight may be placed. The present invention also contemplates the use of air entrained within a plastic or other membrane or enclosure, to be used to level the table top by affixing such contained air to any desired location of the framework or other elements of the invention.
Consideration must be given to the fact that although this invention has been described and disclosed in relation to certain preferred embodiments, obvious equivalent modifications and alterations thereof will become apparent to one of ordinary skill in this art upon reading and understanding this specification and the claims appended hereto. Accordingly, the presently disclosed invention is intended to cover all such modifications and alterations, and is limited only by the scope of the claims which follow. | Provided herein is a buoyant ensemble comprising a plurality of chairs having a table centrally located among the chairs. An ensemble according to the invention is especially well-suited to be placed into a recreational body of water, such as a lake or swimming pool, to provide a location at which a small group of people may congregate to relax or take advantage of having a tabletop present in the water around which they may sit and relax or play board games such as chess, checkers, backgammon, dominoes, etc. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part and claims priority from U.S. Provisional Patent Application No. 60/319,474 filed Aug. 15, 2002 and U.S. Provisional Patent Application No. 60/319,803 filed Dec. 19, 2002, both entitled “Early detection of pathogens in blood.” The specifications of both provisional applications are incorporated herein by reference.
FEDERAL RESEARCH STATEMENT
The present invention was made with the support of the U.S. Army Soldier and Biological Chemical Command under Grant No. DAAD13-01-C-0043. The Government has certain rights to this invention. Research and validation of the present invention was conducted at the Center for Biological Defense at the University of South Florida. The mission of the Center is to identify and develop new and innovative methods for recognizing and combating terrorism, and to promote the establishment of a bioterrorism preparedness program.
BACKGROUND OF INVENTION
Field of Invention
This invention relates to a method of detecting blood infections at an early stage of infection and more particularly to a method of detecting pathogens at low concentrations in circulation from a volume of blood.
The threat of bioterrorism (BT) and biological warfare presents challenges for the clinical setting that are best met with rapid and sensitive technologies to detect BT agents. Peripheral blood samples could contribute to early and specific clinical and epidemiological management of a biological attack if detection could take place when the concentration of the infecting organism is still very low. The worried well and recently infected patients would benefit, both psychologically and physically, from early pharmacological intervention.
Infection with Bacillus anthracis or Yersinia pestis often present initially as a nonspecific febrile or flu-like illness. The mediastinitis associated with inhalational anthrax ultimately results in bacilli entering the blood once the efferent lymphatics become laden with organisms. When bacteremia (the presence of bacteria in the blood) and sepsis (the invasion of bodily tissue by pathogenic bacteria) have initiated, the number of bacilli may increase quickly, doubling every 48 minutes, most often resulting in death of the patient.
It has been reported that microbiological studies on patient blood samples are useful for diagnosing pneumonic plague. The potential for Yersinia pestis bacilli to be present in peripheral circulating blood suggests that a PCR assay would make a useful diagnostic tool. Testing for pneumonic plague or inhalational anthrax would be effective when healthy patients present with “flu-like” symptoms (malaise, fever, cough, chest pain and shortness of breath) that may accompany other nonspecific symptoms. However, in order to maximize the probability of successful, detection of the infecting organism must take place early in the disease process, when the concentration of circulating bacteria is very low.
Extraction of pathogen DNA from whole blood typically requires between 200 μl to 500 μl of patient sample for each preparation event. Detection of early bacteremia is improved by using an entire 6 ml tube of patient blood for a single sample preparation event. Prior art literature describes a single tube blood culture system exploiting the selective lysis of blood elements, followed by centrifugation to pellet bacteria for plating on solid media. The technique has been examined thoroughly in conjunction with microbiological testing.
Accordingly, what is needed in the art is: 1) a method of destroying and making soluble the spectrum of blood element components (erythrocytes, leukocytes, nuclear membranes, fibrin, and host nucleic acid) without damaging analyte particles (bacteria, virus, fungi, toxin, metabolic markers, disease state markers, or chemical agents) in order to expose and rapidly concentrate (via centrifugation, filtration, or capture) the analyte particles from large volumes of blood, 2) removal of the host DNA and the matrix associated biomass present in the large volume blood sample using a single step enzyme detergent cocktail that is amenable to automation and portable systems, and 3) an analyte particle concentration method that can be coupled to existing manual or automated processes for nucleic acid extraction, biosensor testing, or liquid chromatography separation and mass spectrometry analysis.
It is, therefore, to the effective resolution of the aforementioned problems and shortcomings of the prior art that the present invention is directed.
However, in view of the prior art in at the time the present invention was made, it was not obvious to those of ordinary skill in the pertinent art how the identified needs could be fulfilled.
SUMMARY OF INVENTION
Fibrin is an insoluble protein precipitated from blood that forms a network of fibers. In vivo, this process is central to blood clotting. Fibrin is created by the proteolytic cleavage of terminal peptides in fibrinogen. In the laboratory analysis of blood, an aggregate (pellet) of fibrin collects at the bottom of a tube when blood is centrifuged. Within the fibrin aggregate, pathogens are trapped. The analysis of these pathogens is highly desirable. However, like coins embedded in a slab of concrete, the captured pathogens are substantially hidden from analysis, trapped in the fibrin aggregate. For individuals potentially exposed to dangerous pathogens, time is of the essence and rapid identification of the captured pathogens is paramount.
Plasmin is a substance in blood capable of converting fibrin to fibrinogen monomers. Plasminogen is a precursor of plasmin in the blood. Streptokinase is an enzyme that activates plasminogen to form plasmin. The combination of plasminogen and streptokinase in the presence of the fibrin aggregate containing blood elements and bacteria (formally present in peripheral circulation) allows the conversion of the fibrin aggregate to a liquid state.
This conversion facilitates rapid and efficient pathogen analysis through blood culture, antibody based testing, or nucleic acid sequence based testing (Reverse Transcription PCR, PCR, NASBA, TMA or the like).
The addition of DNAse (a DNA nuclease) to the above-described reaction provides for the conversion of human DNA into short fragments. This conversion of human DNA into short fragments contributes to a more rapid and efficient protein hydrolysis process during DNA extraction. This conversion of human DNA into short fragments is done while the bacterial DNA is protected. The short fragment human DNA is carried less efficiently through the DNA extraction process and hence represents a smaller proportion of total DNA product. As a result, the reduced human DNA level presents less of an inhibitory component to the nucleic acid sequence based reactions.
The present invention is a method of extracting infectious pathogens from a volume of blood including the steps of creating a fibrin aggregate confining the pathogens and introducing a fibrin lysis reagent to expose the pathogens for analysis and DNAse to facilitate DNA extraction. The fibrin lysis reagents may be composed of DNAse, plasminogen and streptokinase frozen in coincident relation until the fibrin lysis reagent is needed whereby streptokinase enzymatically reacts with plasminogen to form plasmin upon thawing and introduction into the fibrin sample. Preferably, the plasminogen is suspended in an aqueous salt solution prior to freezing including NaCl and Na 3 PO 4 . The fibrin lysis reagent is preferably composed of DNAse and Phospholipase A 2 . The DNAse enzyme is used to facilitate the chemical and physical disruption of pelleted blood elements that result from the previously described protocol. Phospholipase A 2 is used to help human DNA digestion by destroying phospholipid bilayers and, hence, destruction of the nuclear membrane.
The present invention utilizes resuspension of the dried enzymes in a buffer solution using Potassium Phosphate as an aide to blood element solublization. It is imperative that the streptokinase and plasminogen are not mixed with the buffer solution until immediately prior to the addition of the blood sample. The Potassium Phosphate pH range is 7.8 to 8.0, differentiated from prior art claiming an effective pH range of 7.2 to 7.6. Prior art uses phosphate ion solutions with lower pH to act as a true buffer, however, the current method allows for optimal Phospholipase A 2 activity and Magnesium solubility. Magnesium is found in the buffer solution as the divalent cation driving the activity of Phospholipase A 2 in the presence of DNase. Prior art uses calcium as the classic divalent cation for driving Phospholipase A 2 activity, however, calcium is not compatible with the phosphate ions essential for blood element solublization.
An embodiment of the present invention includes concentrating and extracting particles such as prions, toxins, metabolic markers, cancerous matter, disease state markers, bacteria, virus, and fungi from a volume of blood by introducing an enzyme-detergent combination to expose pathogens in the blood sample and analyzing the blood sample for the particles now readily identifiable via the extraction. The enzyme-detergent may be a fibrin lysis reagent comprising plasminogen and streptokinase. The plasminogen and streptokinase may be frozen in coincident relation until the fibrin lysis reagent is needed. The streptokinase then reacts with the plasminogen to form plasmin upon thawing. The plasminogen may be suspended in an aqueous salt solution prior to freezing. Suitable salt solutions may include NaCl, NaPO 4 or the like. To enhance analysis, the particles may be replicated via polymerase chain reactions (PCR).
By introducing DNase, the process is facilitated by the conversion of DNA into short fragments thereby contributing to a more rapid and efficient protein hydrolysis process during DNA extraction and lowering the burden of inhibitory human DNA. Similarly, introduction of Endonuclease produces a similar advantage.
As an alternative to freezing, the enzyme-detergent may include dried streptokinase and dried plasminogen as the fibrin lysis reagents. The dried reagents may then be mixed and distributed into disposable test containers. This embodiment may be particularly useful for field-testing in locations where sophisticated laboratory equipment and controls are unavailable.
The plasminogen may be combined with Phospholipase A2. DNase, Endonuclease, Lipase, and combinations thereof. The dried enzyme-detergent combination may be suspended in pellets of trehalose buffer and packaged into tubes as a dry reagent. The dried reagents may then be resuspended in a buffer, added to a 1-10 ml volume of blood and incubated for 5-20 minutes at room temperature. More specifically, the dried reagent is comprised of 1,500-4,500 KU Phospholipase A2, 5,000-10,000 U Streptokinase, 2-10 U Plasminogen, 200-3,650 U DNase, 200-4,000 U Endonuclease, and 10,000-100,000 Lipase.
The solution may be centrifuged for approximately 20 minutes at 5,000-5,500×g at a temperature of 10-20° C., the supernatant decanted, and the pellet washed. The pellet may be washed three times with a 10-20 mM solution of Ecotine/20 mM HEPES ph 7.7 and/or a 10-20 mM solution of sucrose/20 mM HEPES ph 7.7. The resultant sample may then be applied to a commercially available nucleic acid extraction method.
Digesting the sample may include lysis and DNase inactivation or lysis and Endonuclease inactivation. 12.5-25 mg proteinase K, 1-105% SDS (sodium dodecyl sulfate), 10-200 mM aurintricarboxylic acid, and 10-20 mM sodium citrate buffer pH 7.8-8.4 may be utilized, the solution allowed to incubate at room temperature for 10 minutes. The sample may then be filtered with a 0.22-0.45 μm filter unit, washed with 10-200 mM Aurintricarboxylic Acid, digested with lysis and DNase inactivation and/or Endonuclease inactivation, and purified.
Digesting the sample may include the steps of combining 12.5-25 mg proteinease K, 1-1.5% SDS, 10-200 mM aurintricarboxylic acid, and 10-20 mM sodium citrate buffer, incubating at room temperature for 10 minutes, and eluting the lysate from the filter surface by addition of 3.5-4.2 M guanidine isothiocyanate pH 6.4.
The solutions may be applied directly to a biosensor device wherein, responsive to the presence of the pathogens in the blood sample, the patient develops pathogenic or native disease state markers that allow for the capture and detection of these markers by the biosensor device. Alternatively, the solution may be applied directly to a liquid chromatography mass spectrometry device whereby, responsive to the presence of the pathogens in the blood sample, the patient develops pathogenic or native disease state markers that allow for the detection of mass signatures associated with the structural components of the pathogens using the mass spectrometry device.
The buffer may contribute detergent and salts. This may be achieved by aiding blood element solublization by introducing 10-30 mM Potassium Phosphate at a pH range of 7.8 to 8.0, driving Phospholipase A 2 activity by adding 10-80 mM Magnesium Chloride as the divalent cation, adding 20-150 mM Sodium Chloride, and including 10-200 mM Aurintricarboxylic Acid during the DNase incubation process. The buffer may also include 1.0-1.2% TRITON X-100 (octylphenol ethoxylate). Additional steps may include combining 20-35 mM methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside and 0.05-0.1% Saponin; and storing the enzymes by using a trehalose buffer. Storing the enzymes is accomplished by using a trehalose buffer in combination with methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside. The trehalose storage buffer comprises 10 mM Potassium Phosphate, 0.01-0.04% TRITON X-100 (octylphenol ethoxylate), 1-5 mM Dithiothreitol, and 0.3-0.5 M Trehalose.
BRIEF DESCRIPTION OF DRAWINGS
For a fuller understanding of the nature and objects of the invention, reference should be made to the following detailed description, taken in connection with the accompanying drawings, in which:
FIG. 1 is a diagrammatic view of the method according to the invention according to the invention.
FIG. 2 is a diagrammatic view of the preparation of the fibrin lysis reagent according to Protocol 1 of the invention.
FIG. 3 is a table providing data on Bacillus anthracis blood protocol.
FIG. 4 is a table providing data on a comparison of two blood samples from different individuals.
FIG. 5 is a table providing data on an evaluation of the present method by a Department of Health laboratorian.
FIG. 6 is a table providing data on Yersinia pestis blood protocol.
FIG. 7 is a diagrammatic view of the setup of extraction reagents according to Protocol 1 of the invention.
FIGS. 8-9 are diagrammatic views of bacterial recovery and fibrin lysis according to Protocol 1 of the invention.
FIGS. 10-13 are diagrammatic views of bacterial lysis and nucleic acid extraction according to Protocol 1 of the invention.
FIG. 14 a is a diagrammatic view of the steps of extracting reagents according to Protocol 2 of the invention.
FIG. 14 b is a diagrammatic view of the steps of extracting reagents according to Protocol 2 of the invention.
FIG. 15 is a diagrammatic view of the steps of extracting reagents according to Protocol 3 of the invention.
FIG. 16 a is a diagrammatic view of the steps of extracting reagents according to Protocol 4 of the invention.
FIG. 16 b is a diagrammatic view of the steps of extracting reagents according to Protocol 4 of the invention.
FIG. 17 is a table providing data on noise band crossing points for blood samples spiked with B. anthracis and processed with plasminogen, streptokinase, phospholipase A 2 DNase I, and lipase with centrifugation or filtration.
FIG. 18 Sedimentation and solublization of tissue aggregates from 6 ml blood samples exposed to various detergent and enzyme treatments.
FIG. 19 Filtration characteristics of 6 ml blood samples exposed to various detergent and enzyme treatments.
DETAILED DESCRIPTION
In FIG. 1 , a blood draw 30 is performed on a patient. A solution of phosphate-buffered saline (PBS), pH 7.4 and 1.2% TRITON X-100 is added, the blood is vortexed and centrifuged 40 creating pellet 60 in a 15 ml tube 50 . Preferably, resins, metal hydroxides, and/or nano materials may be added with the PBS/TRITON X-100 solution to capture particles such as bacteria, virus, fungi, cancerous cells, prions, toxins and the like to contribute greater density to these particles. The increase in particle density allows lower speeds to run during centrifugation.
The supernatant is decanted leaving a fibrin aggregate. A fibrin lysis component 70 is added to tube 50 dissolving the fibrin aggregate and leaving pathogens 65 exposed for analysis. Pathogens 65 are vortexed, centrifuged, and subject to lysis to extract the pathogen DNA. The DNA is then replicated 90 and analyzed 100 for the identity of the suspected pathogen.
In an alternative embodiment of the invention, a device would be used to obviate the need for a centrifuge. The device will use flexible electrodes similar to a fish gill to collect particles (such as bacteria, virus, cancerous cells, prions, or toxins). The electrodes will also be used to collect resins and nano materials that have these particles attached to them. The device will resemble a bubble on a surface. An electrical potential will be used to accelerate pathogen capture. The device can be compressed to allow efficient removal of the contents. The device would preferably have the following properties: (1) a rigid base layer and flexible top layer; (2) flexible gills to be mounted on either the top or bottom layer; (3) Strepavidin and hyaluronic acid strands functionalized with bioactive peptides, antibodies, aptomers, molecular imprinted polymers, or metals that attract particles such as bacteria, virus, fungi, toxins, metabolic markers, disease state markers, or chemical agents are to be deposited on the flexible gill electrodes; (4) the flexible layer will have electrodes deposited on it; (5) counter electrodes for the gill electrodes will reside on the opposite side; (6) the average dead volume of the device is 300 micro liters it is preferred that there is to be no residual material in the device after squeezing out the material from the device; and (7) polyimide will form the flexible portion and the electrodes will be made of Pt, Au, or carbon. The device is preferably used as follows: (1) flow liquid into the device and apply voltage at this time; (2) add chemicals and heat the device; and (3) squeeze out the device to remove all contents. The device is used to prepare a sample for analysis of particles (such as bacteria, virus, cancerous cells, prions, or toxins) using spectrophotometric, mass spectroscopy, antibodies, culture, or nucleic acid (e. g. PCR, NASBA, TMA) based detection systems.
A filtering device may be used to filter out the particles from blood treated with the TRITON X-100/PBS/magnesium solutions with enzymes selected from the group of streptokinase, plasminogen, phospholipase A2, DNase, and lipase. A filtering device may also be used to filter out the particles from blood treated with a combination of methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside, Saponin, and PBS/magnesium plus enzymes selected from the group of streptokinase, plasminogen, phospholipase A2, DNase, and lipase. After washing away the enzyme and detergent treatment reagents and any residual broken down blood components, the particle is ready for analysis or further processing.
The preparation of the fibrin lysis reagent is shown as Protocol 1 in FIG. 2 wherein NaCl, MnCl Dithiothreitol (DTT), DNAse, and plasminogen are added to mixing tube 110 . Sodium phosphate is then added to mixing tube 110 and the solution is distributed into 1.5 ml reagent tubes 120 placed on ice. The reagent tubes 120 are frozen to −75° C. for approximately 20 minutes. Approximately 2,700 U of streptokinase 130 is added to the wall of reagent tubes 120 just above the frozen plasminogen solution.
FIGS. 3-6 provide PCR results derived from testing blood samples seeded with encapsulated vegetative avirulent Bacillus anthracis were grown according to CDC protocol # CDC.DFA.1.2, stored in 15% glycerol Trehalose storage buffer (TSB), and frozen at −75° C. Stocks of avirulent Yersinia pestis grown in TSB at 37° C., frozen in 15% glycerol TSB, and frozen at −75° C. Bacterial counts were tested at the time of harvest and retested at the time of sample spike.
Figures for average Bacillus anthracis CFU per six ml of human blood are derived from post-freezing testing given the large standard deviation encountered in side-by-side post freezing dilution events. No significant cellular death is recognized or expected. A 30% cellular death rate is the highest that is reasonably expected in the worst circumstances. A conservative approach would be to increase all calculated Bacillus anthracis CFU by 30%.
Figures for average Yersinia pestis CFU per six ml of blood are derived from pre-freezing testing. The low standard deviation of pre-freezing count replicates and concordance with post-freezing testing allows use of the pre-freezing bacteria count numbers. This is a conservative approach that can be utilized given the now predictable results that are derived from storing and diluting this organism.
The present invention reproducibly generates analyte DNA appropriate for PCR testing of Bacillus anthracis using patient blood samples that are up to 3 months old Sensitivity is 100% at <10 CFU/ml of human blood when using 6 ml of blood collected in a Becton Dickinson VACUTAINER (Tables 1 and 2). This protocol also allows detection of Yersinia pestis at 100% sensitivity at <10 CFU/ml for at least one of four oligo sets according to the more limited data gathered for this organism (Table 3). It should be noted that CDC does not consider samples positive for Y. pestis unless two oligo sets produce an acceptable PCR signal.
In accordance with Protocol 1, FIG. 7 shows a method of the setup of extraction reagents according to the invention. FIGS. 8-9 show a method of bacterial recovery and fibrin lysis according to the invention. FIGS. 10-13 show a method of bacterial lysis and nucleic acid extraction according to the invention.
In an alternative embodiment, as shown in FIGS. 14-16 b , the individual enzymes of streptokinase and plasminogen are made into dried powders, mixed, then distributed to disposable tubes. Alternatively, Phospholipase A 2 , plasminogen, DNase or Endonuclease, and lipase are suspended and dried in pellets of trehalose buffer. Phospholipase A 2 or any enzyme that will destroy nuclear membrane while keeping bacterial cell wall or viral coats in tact may also be used. Streptokinase is likewise suspended and dried in pellets of trehalose buffer. At least one pellet of the plasminogen and one pellet of the streptokinase are packaged into tubes as dried reagents.
The dried reagents previously described are then resuspended in a 10 ml buffer solution comprising 10-30 mM Potassium Phosphate, 10-80 mM Magnesium Chloride, 20-150 mM Sodium Chloride, 10-200 mM Aurintricarboxylic Acid and 1.0-1.2% TRITON X-100. Aurintricarboxylic Acid is evidenced to provide a level of protection to bacterial nucleic acid without impeding human DNA digestion. The use of Aurintricarboxylic Acid is not found in prior methods of human DNA digestion. Exclusion of TRITON X-100 is permitted upon addition of 20-35 mM methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside and 0.05-0.1% Saponin. The methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside is stored with the phospholipase A2, plasminogen, DNase I, and lipase in a Trehalose storage buffer. Substitution of the TRITON X-100 with the methyl 6-O-(N-heptylcarbamoyl)-α-D glucopyranoside and saponin solution allows for the efficient activity of Phospholipase A2, provides the action of breaking up protein aggregates without denaturation, and is more genial to bacterial walls than Triton-TRITON X-100. Use of Saponin and methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside in this combination is lacking in prior art. The Trehalose storage buffer comprises of 10 mM Potassium Phosphate pH 7.4, 0.01-0.04% Triton TRITON X-100 or methyl 6-O-(N-heptylcarbamoyl)-α-D-glucopyranoside, 1-5 mM Dithiothreitol, and 0.3-0.5 Trehalose. The buffer and enzyme mix are then immediately combined with a 10 ml blood sample, which may be scaled down to 1 ml. The sample is then incubated at room temperature for 5-10 minutes. The aforementioned components aide blood element solublization through minimizing certain particulates that would otherwise clog filters, impair biosensors or mass spectrometry devices, and impede nucleic acid extraction. Solublization occurs while human DNA is efficiently digested and as viral and/or bacterial DNA remain intact.
In accordance with Protocol 2 and 4, the enzyme combination is comprised of Streptokinase, Plasminogen, DNase or Endonuclease, Phospholipase A 2 , and Lipase. Alternatively, enzyme combinations comprising of Streptokinase, Plasminogen, DNase or Endonuclease, and Phospholipase A 2 may also be used but with less efficacy. In another alternative combination, Streptokinase, Plasminogen, DNase or Endonuclease may be used, as well as, DNase or Endonuclease, Phospholipase A 2 and Lipase but with even less efficacy. DNase or Endonuclease in combination with Phospholipase A 2 is yet another alternative. The efficacy of the three latter combinations was found to be equal.
In accordance with Protocol 3, the enzyme combination is comprised of Streptokinase, Plasminogen, DNase or Endonuclease, Phospholipase A 2 , and Lipase. Alternatively, enzyme combinations comprising of Streptokinase, Plasminogen, DNase or Endonuclease, and Phospholipase A 2 may also be used but with less efficacy. In another alternative combination, Streptokinase, Plasminogen, DNase or Endonuclease may be used with even less efficacy than the latter combination.
As shown in FIG. 14 with Protocol 2, the sample is centrifuged for a period of 20 minutes at 5,000-5,500×g at a temperature between 10-22° C. after incubation. The supernatant is then decanted and the pellet washed three times with a 10-20 mM solution of Ecotine/20 mM HEPES pH 7.7 and/or a 20-30 mM solution of Sucrose/20 mM HEPES pH 7.7.
Alternatively after incubation, the Protocol 2 sample is centrifuged in similar fashion and the supernatant decanted, followed by sample lysis and DNase or Endonuclease inactivation using 12.5-25 mg Proteinase K, 1-1.5% Sodium Dodecyl Sulfate (SDS), 10-200 mM Aurintricarboxylic Acid and 10-20 mM Sodium Citrate buffer pH 7.8-8.4. The sample is allowed to incubate at room temperature for 10 minutes. The digested sample may then be applied to any commercially available nucleic acid extraction method, shown in FIG. 14 b.
Yet in another alternative, referred to as Protocol 3 and depicted in FIG. 15 , the sample is filtered with a 0.22-0.45 μm filter unit and washed with 10-20 ml of 10-200 mM Aurintricarboxylic Acid, followed by sample lysis and DNase or Endonuclease inactivation. Sample lysis and DNase or Endonuclease inactivation is accomplished by using 12.5-25 mg Proteinase K, 1-1.5% SDS, 10-200 mM Aurintricarboxylic acid, and 10-20 mM Sodium Citrate buffer. The sample is then incubated at room temperature for 10 minutes. Addition of 3.5-4.2 M Guanidine Isothiocyanate pH 6.4 is necessary to elute the lysate from the filter surface. The nucleic acid extract may then be further purified using a commercially available method.
Another alternative, referred to as Protocol 4 and shown as FIG. 16 a , applies the sample directly to a biosensor device that will capture and detect bacteria, virus, fungi, toxins, prions, chemical agents, metabolic markers or native disease state markers developed by the patients own body in response to these pathogens and agents present in the blood sample.
In yet another Protocol 4 alternative shown in FIG. 16 b , the sample is applied directly to a liquid chromatography mass spectrometry device that will detect mass signatures of structural components that comprise bacteria, virus, toxins, prions, and chemical agents present in the blood sample or native disease state markers developed by the patients own body in response to these pathogens and agents present in the blood sample.
It will be seen that the objects set forth above, and those made apparent from the foregoing 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 matters contained in the foregoing 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 there between. | The present invention is a method of extracting infectious pathogens from a volume of blood including the steps of creating a fibrin aggregate confining the pathogens and introducing a fibrin lysis reagent to expose the pathogens for analysis. The fibrin lysis reagent is preferably composed of plasminogen and streptokinase frozen in coincident relation until the fibrin lysis reagent is needed whereby streptokinase enzymatically reacts with plasminogen to form plasmin upon thawing. The plasminogen is suspended in an aqueous salt solution prior to freezing including NaCl and Na 3 PO 4 . | 2 |
RELATED APPLICATION
This application is a continuation-in-part of U.S. patent application Ser. No. 07/965,896, filed Oct. 23, 1992, abandoned the entire disclosure of which is incorporated herein by reference.
TECHNICAL FIELD OF THE INVENTION
The invention relates in general to a composition and method for forming an insecticide, and more particularly to a composition and method for forming a Solenopsis saevissima v. richterii bait-insecticide.
BACKGROUND OF THE INVENTION
Solenopsis saevissima v. richterii, which are commonly known as fire ants, migrated into the United States from South America during the early 1900's. The rate at which the fire ants have been spreading has increased exponentially; and it has been calculated that in the U.S., fire ants infest with their ant hills (nests) up to 250 per hectare. The infestation into populated regions has caused incalculable problems which have, in the extreme, been fatal.
Prior art has attacked this infestation by using high concentrations of toxic chemicals, which kill a plethora of types of ants, insects, rodents and other species.
The amount of money spent on this problem is sizeable, and there is a noticeable quest for better, more effective pesticides. In fact, there is a wide variety of prior art pesticides that have been unsuccessful in combatting the problem.
For example, U.S. Pat. No. 4,874,611 by Wilson, et al. discloses a method of manufacture and composition of a core including an insect poison encapsulated in a shell material. The shell was resistant to water but could be penetrated by the insect. Because fire ants often have trouble penetrating the shell, this method is not very successful in causing the termination of large numbers of fire ants.
U.S. Pat. No. 3,962,461 by Brown, Jr., et al. discloses a toxic bait for insects, in which the bait contains suspended recrystallized Mirex in a sweet, aqueous solution. This substance is used to combat carpenter ants and is not specifically designed to attract fire ants. Fire ants, in fact, have not been greatly attracted to this bait, resulting in ineffective insecticide for fire ant application.
U.S. Pat. No. 4,460,606 and U.S. Pat. No. 4,540,711 by Bettarini, et al. disclose a method for fighting infestation by fire ants consisting of a bait comprising hydroquinone diether having at least one acetylenic and halogen-substituted chain and selected from 1- (5-chloro-pent-4-inyl)-oxy!-4 phenoxybenzene and 1,4-di-(5-chloro-4-pentinyloxy)-benzene. Like the Brown pesticide, the Bettarini disclosure has not been successful in reducing fire ant population significantly.
U.S. Pat. No. 3,220,921 by Greenbaum, et al. discloses a poison containing a bait --C 10 Cl 12 (C 5 Cl 6 dimer) composition. This composition eliminates fire ants population; however, this bait also attracted a plethora of other insects (i.e., bees, flies, beetles, etc.). Therefore, this bait has the disadvantages of attracting insects that should not be extinguished because it will upset the ecological balance and eliminates insects, such as honey bees, which are commercially desirable. Furthermore, although this bait attracts fire ants, it does not attract them to the degree necessary to rid large areas of fire ants. Lastly, there appear to be problems with the form of this composition (primarily solid), which makes it difficult to distribute in large quantities over a large geographical area.
U.S. Pat. No. 5,094,853, U.S. Pat. No. 5,104,658 and U.S. Pat. No. 5,116,618 by Hagarty disclose a killing composition containing an organophosphorous compound mixed with a corn sweetener. This composition by Hagarty is a pesticide in the form of an arthropodicidally-active foam matrix. Like the Greenbaum '921 patent composition, this insecticide was designed to control fire ants, as well as certain crustaceans, arachnids, a wide variety of crawling insects and certain myriapods. The problem with this composition, once again, is that it attacks more insects than simply fire ants. Therefore, it too appears to upset the ecological balance more than necessary and kill desirable insects. Furthermore, although this material does attract fire ants, it needs to be spread close to the fire ant hills to be an effective means of control.
None of these toxic compounds have a special affinity toward fire ants. None of these toxic compounds attract fire ants during cold weather. Unlike the present invention, the prior art toxic compositions are consumed by a variety of species and, thus, most cannot be used under circumstances where it is necessary for insects and other species to thrive. The present invention contains an agent which both attracts fire ants and detracts most other ants, insects, rodents and other species from ingesting the toxic compounds. Because most other insects and species will not consume the insecticide, less of the present invention needs to be spread to combat the fire ants. Furthermore, because fire ants appear to purposefully seek out the present invention (even in cold weather), the composition can be dispersed in small quantities throughout the area which needs to be controlled. Therefore, the present invention is more environmentally safe than the prior art.
Lastly, because the present invention can be produced as a liquid or gel and because of its specialized attraction to fire ants, this composition can be spread over a great area with little difficulty, which resultantly reduces the cost to eliminate the same number of fire ants as compared to prior art.
SUMMARY OF THE INVENTION
The present invention provides a method for forming fire ant bait that is normally in the form of a liquid or gel. This composition is comprised of an attracting agent, an enhancing agent, and a toxicant. The primary aspect of the present composition is to combat the infestation of fire ants. The attracting agent comprises a product formed from a liquid extracted from grapes ("grape extract"). One embodiment of the attracting agent comprises a grape jelly in a consistency to readily mix with other additives. The viscosity of the grape jelly can be reduced to the necessary consistency by, for example, heating or beating. Another embodiment of the attracting agent comprising grape juice thickened so that it has a consistency thick enough to keep the liquid from soaking into the ground soon after being spread. The viscosity of the grape juice may be increased by a standard thickening agent.
An enhancing agent is added to the attracting agent to create a composition that appears to be highly attractive to fire ants. The enhancing agent is a salt which reacts with the attracting agent and forms a compound that seems much more appealing to the fire ants than any other attracting agent previously disclosed. For the purposes of this invention, any edible salt may be used.
The addition of salt to the grape jelly and to the grape juice created unforeseen mixtures that each emit a distinct and foul smell. It was unanticipated that this composition would react in this manner and produce a material that seems to deter other types of ants, insects, rodents and mammals and attract the fire ant. Because this enhanced attracting agent emits such a particular odor, it is observed that a greater percent of the present invention enters the fire ant nests. This reduces the amount of composition that needs to be used, compared with other toxic substances, to kill the same number of fire ants.
An organophosphorous compound is added in small quantities to this mixture to make the composition toxic. For example, a suitable toxicant is acetylphosphoramidothiotic acid O,S-dimethyl ester, more commonly called "Acephate," and commercially available under the "Ortho" or "Orthene" brand names. (See also U.S. Pat. Nos. 3,716,600 and 3,845,172, both assigned to Chevron). The present composition is delayed acting, and, therefore, the fire ants will bring the toxic substances back to the ant hills before the insecticide begins to take effect.
The present composition can be in a liquid or gel form, although it can be prepared and then reduced to a solid form. The apparent mechanism of kill is that the fire ants actually ingest the toxic fluid instead of carrying toxic material back to the ant hill. Because literature indicates that fire ants feed from the juices of their dead, the toxic substance is transmitted rapidly throughout the ant community after the infected ants die. Furthermore, the liquid or gel composition appears to stay toxic for a longer period of time than the prior art. Interestingly, the liquid or gel composition maintains its toxicity even after traces of the toxicant can no longer be found in the composition. A major problem suspected with fire ants is that they repopulate old nests. With this apparent longer period of toxicity, the present composition will continue to kill new inhabitants of the nests. Thus, contrary to the majority of other toxic compositions, the composition rids both the present and future generations of fire ants.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, a bait-insecticide has been formed that can be used to control the infestation of fire ants. The invention in question comprises a composition of an attracting agent, an enhancing agent, and a toxicant.
The attracting agent comprises a grape extract that may be in the form of a grape jelly, a grape juice, or other similar sweet products. The composition comprising the flavored jelly preferably is at a concentration between approximately 95.0 weight percent and approximately 97.5 weight percent.
One possible embodiment of the attracting agent is grape jelly, preferably concord grape jelly (such as Concord® grape jelly). To mix with the other additives, the flavored jelly preferably has a consistency less than that found in the industry. The viscosity can be reduced by heating, beating, or otherwise thinning the jelly.
Another possible embodiment of the attracting agent comprises taking a liquid formed from grapes, preferably concord grapes. Optionally, the grape juice may be thickened so that it is capable of being spread without soaking into the ground soon thereafter. If the composition soaks into the ground it will pick up extra water, which can destroy the toxicity of the composition. Moreover, if the composition soaks into the ground, the composition will not be readily available to the fire ants and will not achieve its desired results. Because the composition can be used in ways other than spreading it on the ground (i.e. keeping the composition in a container and placing the container near the area to be treated), it is not critical that a thickening agent be added to the composition.
Thickening agents and methods to thicken liquid compositions are well known and need no detailed description here. The particular thickening agent and process to increase the viscosity of the attracting agent is not critical but merely must possess the property of increasing the viscosity to such an amount that after being spread it will not soon thereafter soak into the ground. To meet this property, the viscosity of the attracting agent may be increased to an amount greater than that of water (approximately 1 cp), and preferably greater than that of salad oil (approximately 30 cp).
An enhancing agent is added to the attracting agent. One possible embodiment of the enhancing agent is a salt at a concentration between approximately 2.4 weight percent and approximately 3.7 weight percent. This mixture forms a foul smelling gel that is distinct from the typical sweet odor of a flavored jelly or grape juice.
For purposes of the present invention, any edible salt, such as table salt, may be employed as the salt in the present invention. Examples of suitable edible salts include: organic acid salts, such as sodium citrate, sodium tartrate, sodium malate, sodium acetate, sodium lactate, and sodium succinate; phosphate salts such as sodium polyphosphate, sodium pyrophosphate, sodium metaphosphate, di- or tri-sodium phosphate, potassium polyphosphate, potassium pyrophosphate, potassium metaphosphate, and di or tri-potassium phosphate; carbonate salts such as sodium carbonate, sodium hydrogencarbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; sulfate salts such as potassium sulfate, sodium sulfate, calcium sulfate, and magnesium sulfate; glutamates, such as monosodium glutamate; sodium chloride; calcium chloride; and potassium chloride.
A toxicant is additionally added to this mixture. The toxicant comprises an organophosphorous compound at a concentration between approximately 0.04 weight percent and approximately 1.2 weight percent. For purposes of the present invention, suitable organophosphorous compounds include phosphates, phosphoronionates, and phosphorothionates. For example, a suitable, well-known organophosphorous compounds, useful as toxicants in the present invention includes acetylphosphoramidithiotic acid O,S-dimethyl ester, more commonly called "Acephate," and commonly available under the "Ortho" and Orthene" brand names (see also U.S. Pat. Nos. 3,716,600 and 3,845,172, both assigned to Chevron).
Other examples of suitable organophosphorous compounds which have toxic effects toward fire ants, include, but are not limited to, phosphorothioic acid O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) ester, also known by "Chlorpyrifos", and commercially available under the "Dursban", "Lorsban", and "Pyrinex" brand names (see also U.S. Pat. No. 3,244,586 assigned to Dow Chemical); phosphorothioic acid O,O-diethyl O- 6-methyl-2-(1-methylethyl)-4-pyrimidinyl!ester, also known by "Dimpylate", and commercially available under the "Basudin", Diazinon", "Diazol", "Garden Tox", "Sarolex", and "Spectracide" brand names (see also U.S. Pat. No. 2,754,243 assigned to Geigy); phosphorothioic acid O,O-dimethyl O-(3-methyl-4-nitrophenyl) ester, also known by "Fenitrothion", and commercially available under the "Accothion", "Cyfen", Cyten", "Folithion", "MEP", "Metathion" and "Sumithion" brand names (see also Belgian Pat. No. 594,669 to Sumitomo as well as Belgian Pat. No. 596,091 to Bayer); phosphorothioic acid O,O-dimethyl O- 3-methyl-4-(methylthio)phenyl!ester, also known by "Fenthion", and commercially available under the "Baycid", "Baytex", "Entex", "Lebaycid", "Mercaptophos", "Queletox", "Spotton", "Talodex" and "Tiguvon" brand names (see also German Patent No. 1,116,656 as well as U.S. Pat. No. 3,042,703, both assigned to Bayer; see also Japanese Pat. No. 15,130, which issued in 1964 to Sumitomo); 4-ethoxy-7-phenyl-3,5-dioxa-6-aza-4-phosphaoct-6-ene-8-nitrile 4-sulfide, also known by "Phoxim", and commercially available under the "Baythion", "Sebacil" and "Volaton" brand names (see also U.S. Pat. No. 3,591,662 assigned to Bayer); and the O,O-dimethyl analog of O- 2-(diethylamino)-6-methyl-4-pyrimidinyl!phosphorothioic acid O,O-diethyl ester, also known by "Pirimiphos-methyl", and commercially available under the "Actellic", "Blex", and "Silo San" brand names. (See, e.g., entry numbers 25, 2167, 2968, 3910, 3927, 7251 and 7372, respectively, in "The Merck Index", 10th ed., published in 1983 by Merck & Co., Inc.).
One feature of the present invention is that the composition has been observed to be attractive to fire ants while repulsive to most other ants, insects, rodents and other species. This, in addition to the low toxicant concentration, makes the toxicant environmentally safer than other prior art. The present invention is environmentally safe because (1) only a small percentage of the composition contains a toxicant that has already been approved by the EPA; (2) the composition does not appear to interfere with the ecological balance because it is repulsive to other species; and (3) the composition does not need to be used in great quantities because it appears to be highly attractive to fire ants.
Besides fire ants, the composition has been shown to attract and kill other hostile ants, roaches, bumble bees and some crickets. The composition does not attract and kill native bees, docile ants, mammals, birds, or other animals. If the enhancing agent is left out of the composition, not only will the fire ants no longer be as attracted to the composition, the composition will now attract and kill native bees, docile ants, mammals, and birds. Furthermore, the foul smell created by the addition of the enhancing agent, detracts people from tasting the composition. Without the attracting agent, the composition is sweet smelling and could accidently be consumed by people.
Additionally, because the composition can be utilized as a liquid or gel, it has the capacity to be spread in numerous ways, which include both air and land dispersal. The invention will also be able to be applied in a variety of void spaces including cracks and crevices, beneath doors and around windows, and in pipes, drains, and other conduits.
An unforeseen result in this combination is that the toxicant, when combined with the flavored jelly or grape juice, will remain toxic for an extended period. For example, organophosphorous compounds, such as Orthene, cannot be spread on concord grapes because the concord grapes would retain the organophosphorous compound. Such grapes would not be fit for consumption and cannot be used to make wine.
Another unforeseen result is that, after 60 days the mixed toxicant is no longer perceptible in the composition; however, the composition maintains its toxicity and will continue to kill fire ants. The level of citric acid of the composition also noticeably increases after 60 days.
The present invention will hereunder be described in even greater detail by reference to the following Examples, which are given here for illustrative purposes only and are by no means intended to limit the scope of the present invention.
A large scale ant farm was built to determine the ants' migration and hibernation habits. It was determined that the ants would not probe the surface for food unless the ground temperature was 50° F. at a depth of four inches. As the temperature was physically changed, the fire ants moved their larvae into different chambers throughout the nest.
EXAMPLE 1
Two pounds of grape jelly were heated to enable one-half teaspoon of Orthene to be mixed evenly throughout. These components were well mixed and then allowed to cool. Capsules were filled with the jelly-Orthene composition and placed on a fire ant bed. The fire ants were unable to penetrate the capsules.
The capsules were then manually opened and the jelly-Orthene composition was spread on the ground. The fire ants began feeding on the composition and there were numerous dead fire ants within a 24-hour period.
EXAMPLE 2
A similar composition as in Example 1 was used except that the concentration of the Orthene was gradually increased. The process entailed placing a high concentration of jelly-Orthene out for a short period and watching the way the fire ants fed on the composition. The sample was then removed and a low Orthene concentration was substituted. After the fire ants returned to their normal feeding habits, a sample with a higher Orthene concentration than previously used was tested. From this procedure, it was discovered that the fire ants would avoid the jelly-Orthene composition when the composition contained greater than 12 weight percent of Orthene.
EXAMPLE 3
Two pounds of grape jelly were heated to easily mix two tablespoons of table salt into solution. This compound formed a foul smelling substance and did not emit the typical sweet smell normally associated with jelly. Moreover, the compound no longer had a sweet taste but, rather, had a very bad taste. This salted-jelly was placed on a fire ant mound, and, immediately, the fire ants attacked this food source.
EXAMPLE 4
Two pounds of grape jelly was heated to easily mix one tablespoon of salt in solution. The compound formed a foul smelling substance similar to Example 3. This compound was placed on a fire ant mound, and the fire ants attacked this food source. The compound's attraction to fire ants was apparent but was not as immediate as Example 3.
EXAMPLE 5
A composition as described in Example 3 was tested against ordinary grape jelly. A sample of grape jelly was placed on the fire ant mound and was ultimately covered with fire ants. A sample of salted-jelly was then placed on the same mound, and the fire ants immediately left the first sample (salt-free jelly) and consumed the salted-jelly.
EXAMPLE 6
A sample was prepared by heating two pounds of grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. One drop of the composition was placed in a vegetable garden in the middle of the rows every two to three feet. All fire ant mounds in the garden, as well as the fire ant mounds within 50 feet of the garden, were killed.
EXAMPLE 7
A few drops of the composition as described in Example 6 was placed on small pieces of cardboard and placed on fire ant trails located inside several houses. Within 12 hours the fire ants were no longer found within the houses, and typically a mound near each house was found soon thereafter with dead fire ants.
EXAMPLE 8
The purpose of this Example was to show that the composition does not attract ants other than aggressive ants. A sample was prepared by heating two pounds of grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. This composition was placed on three separate ant hills. The first ant hill was a Native Ant, Harvester, or Red Ant mound in which the ants were highly aggressive. The sample was placed on this first mound, and the ants immediately began to consume the composition. Within 24 hours, the first bed was covered with dead ants. There were no ants left on the first mound.
The second ant hill was a combination of ants with both aggressive and docile traits. The sample was placed on this mound, and the same proportion of aggressive ants immediately began to consume the composition. Within 24 hours, a portion of the ants were dead. A determination was made and it appeared that only the docile ants survived.
The last ant hill was a mound of docile ants. The sample was then placed on the mound and only a few ants began to consume the composition. Within 24 hours, only a negligible number of ants were dead.
EXAMPLE 9
The purpose of this Example was to show that the composition does not attract mammals. A sample was prepared by heating two pounds of grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. This composition was placed in dog food pans and placed within yards located on several different farms. Dogs, as well as other mammals, located on the yard would not eat the composition at all. The dog food pans containing the composition were also placed in yards that were remote from areas infested with fire ants. The composition was undisturbed by both ants and mammals.
EXAMPLE 10
The purpose of this Example was to show that the composition does not attract honey bees. Over a two year period, the composition of Example 9 was placed on the ground around a honey bee hive and around the entrance to the hive. Fire ants, which had infested the area, did not infest the hive. The honey bees went around the composition and did not eat it.
EXAMPLE 11
The purpose of this Example was to show that the composition does not attract birds. Killdeers nest on the ground and fire ants typically eat their eggs. Over a two year period, the composition of Example 9 was placed around the nests of killdeers located on a farm infested with fire ants. The killdeers did not consume the composition. Over the two year period, the number of killdeers on this farm increased at least 10-fold.
EXAMPLE 12
A sample was prepared by heating two pounds of grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. This composition was placed 400 feet from a large nest of fire ants. After three days there were no perceptible dead ants. The sample was then moved 10 feet closer, and the nest was watched for another three days. By this method, it was determined that the ants would travel 200 feet from their mound to reach the bait.
EXAMPLE 13
A sample was prepared by heating two pounds of grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. The composition was tested in cold weather, and the composition would kill 100 percent of the fire ant mounds located within 3 feet of the sample.
EXAMPLE 14
The composition was prepared by heating grape jelly and mixing it in a ratio of two pounds of grape jelly to two tablespoons of table salt to a half a tablespoon of Orthene. The composition was blown high into the air and let fall back to the ground. Approximately one quart of the composition was required per acre of land with a high density of fire ant mounds to ensure 100 percent kill of the mounds.
EXAMPLE 15
A sample was prepared by heating two pounds of concord grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. Once exposed to the elements, the sample remains active 30 to 60 days if there was not any heavy rain or heavy dew.
EXAMPLE 16
A sample was prepared by heating two pounds of concord grape jelly and mixing two tablespoons of table salt and a half a tablespoon of Orthene. The sample was kept in a container, and after 60 days the sample was tested for chemical composition. The level of citric acid in the composition had noticeably risen, and there was no perceptible trace of the Orthene in the composition. This composition was then placed near several fire ant mounds. The fire ant mounds were later found dead.
EXAMPLE 17
A sample was prepared by whipping eight fluid ounces of grape juice and one cup of flour into a thick mixture. The mixture was then further mixed with one-half a tablespoon of table salt and a quarter of a tablespoon of Orthene. This composition was then placed near several fire ant mounds. The fire ants at these mounds were later found dead.
While the preferred embodiments of the present invention and their advantages have been disclosed in the above detailed description, the invention is not limited thereto, but only by the spirit and scope of the appended claims. | A method for preparing and a product made thereby for a bait insecticide composition that is toxic toward fire ants (Solenopsis saevissima v. richterii). Such a composition is comprised of an attractant agent (concord grape extract) mixed with a toxicant (organophosphorous compound) and an enhancing agent (salt). This present invention has the ability to control fire ants while remaining environmentally safe by being inert with regard to most other ants and nearly all other types of insects, rodents and mammals. | 0 |
BACKGROUND OF THE INVENTION
[0001] Sensor devices that can monitor bioelectric data from a body are known. An example of such a device is described in U.S. Pat. No. 6,055,448. The apparatus described therein comprises an array of a plurality of N number of sensors where N is an integer, each sensor of which is capable of detecting an electrical signal associated with components of a heartbeat. In an associated known approach to monitoring the electrical signals detected by the sensors, executable instructions implemented by a processing device generate an indication of the quality of contact between each respective sensor of the array and the body of a patient, the heartbeat of whom the sensors are to monitor. Poor quality of contact between a sensor of the array and the body of the patient will produce a poor-quality signal, thereby preventing an optimal evaluation of the monitored heartbeat.
[0002] While this quality-of-contact evaluation functions to specifically indicate which one(s) of the sensor(s) is in poor contact with the patient, in the instance in which N is a comparatively high number, it is nonetheless difficult for a practitioner employing the sensor array to discern the specific position on the patient's body at which sensor contact quality is poor or otherwise insufficient.
SUMMARY OF THE INVENTION
[0003] In an embodiment, a system includes an array of N electrode elements configured to be attached to an external region of a patient, and a processing device coupled to the array. The processing device is configured to receive a set of bioelectric data signals from the array, determine from the set of data signals a set of elements of the array that are, according to a predetermined standard, insufficiently attached to the external region, and generate to a display device, in at least two dimensions, a representation of the external region and the spatial positioning of the insufficiently attached set of elements on the external region.
BRIEF DESCRIPTION OF THE DRAWING
[0004] Preferred and alternative embodiments of the present invention are described in detail below with reference to the following figures:
[0005] FIG. 1 is a high-level block diagram showing an ECG system 100 in accordance with an embodiment of the invention;
[0006] FIG. 2 is a schematic illustration of an arrangement of N electrodes in an array in accordance with an embodiment of the invention
[0007] FIG. 3 illustrates a graphical user interface according to an embodiment of the invention; and
[0008] FIG. 4 illustrates an exemplary respective connector-pin assignment for interfaces of the connector element 120 and console 130 of FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0009] Embodiments of the invention are operational with numerous general purpose or special purpose computing system environments or configurations. Examples of well known computing systems, environments, and/or configurations that may be suitable for use with the invention include, but are not limited to, personal computers, server computers, hand-held or laptop devices, multiprocessor systems, microprocessor-based systems, set top boxes, programmable consumer electronics, network PCs, minicomputers, mainframe computers, distributed computing environments that include any of the above systems or devices, and the like.
[0010] Embodiments of the invention may be described in the general context of computer-executable instructions, such as program modules, being executed by a computer and/or by computer-readable media on which such instructions or modules can be stored. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. The invention may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote computer storage media including memory storage devices.
[0011] Embodiments of the invention may include or be implemented in a variety of computer readable media. Computer readable media can be any available media that can be accessed by a computer and includes both volatile and nonvolatile media, removable and non-removable media. By way of example, and not limitation, computer readable media may comprise computer storage media and communication media. Computer storage media include volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can accessed by computer. Communication media typically embodies computer readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media. The term “modulated data signal” means a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, and not limitation, communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared and other wireless media. Combinations of the any of the above should also be included within the scope of computer readable media.
[0012] According to one or more embodiments, the combination of software or computer-executable instructions with a computer-readable medium results in the creation of a machine or apparatus. Similarly, the execution of software or computer-executable instructions by a processing device results in the creation of a machine or apparatus, which may be distinguishable from the processing device, itself, according to an embodiment.
[0013] Correspondingly, it is to be understood that a computer-readable medium is transformed by storing software or computer-executable instructions thereon. Likewise, a processing device is transformed in the course of executing software or computer-executable instructions. Additionally, it is to be understood that a first set of data input to a processing device during, or otherwise in association with, the execution of software or computer-executable instructions by the processing device is transformed into a second set of data as a consequence of such execution. This second data set may subsequently be stored, displayed, or otherwise communicated. Such transformation, alluded to in each of the above examples, may be a consequence of, or otherwise involve, the physical alteration of portions of a computer-readable medium. Such transformation, alluded to in each of the above examples, may also be a consequence of, or otherwise involve, the physical alteration of, for example, the states of registers and/or counters associated with a processing device during execution of software or computer-executable instructions by the processing device.
[0014] An embodiment of the invention enables a display device to display on a 3-D model of a torso the current status of electrode connectivity to assist a user in correcting poor-quality electrode contacts, as appropriate.
[0015] FIG. 1 is a high-level block diagram showing an ECG system 100 according to an embodiment. System 100 includes an N-lead electrode array 110 , a connector element 120 , and a signal-monitoring console 130 including, or otherwise coupled to, a processing device (processor) 140 .
[0016] According to an embodiment of the invention, the processor 140 employs a chip (not shown), such as a Texas Instruments® AD 1298 chip, 8 channel 24 bit ECG AFE, for ECG data acquisition. Alternatively, the chip may be a component of the connector element 120 . This chip provides a “lead-off” detection function using, for example, internal 10 MΩ pull-up resistors to detect whether one or more electrodes of the array 110 is in poor contact with the body of a patient (not shown). The indication of “lead-off” may be binary (i.e., ON or OFF).
[0017] FIG. 2 is a schematic illustration of the arrangement of the N electrodes in an embodiment of the array 110 . In the illustrated embodiment, the array 110 includes an anterior sub-array 210 (i.e., leads 1 - 61 ) configured to be positioned on the front of a patient's torso and a posterior sub-array 220 (i.e., leads 62 - 77 ) configured to be positioned on the back of a patient's torso. The connector element 120 may be configured to provide a common electrical interface to the console 130 for both the anterior and posterior sub-arrays 210 , 220 .
[0018] FIG. 3 illustrates a graphical user interface 300 according to an embodiment that may be employed by a user of the system 100 to perform a lead-contact-quality check. Once each lead of the array 110 has been attached to the patient, the user may, using a conventional pointer device, select a test-initiation button 310 to commence the contact-quality check.
[0019] Upon completion of the check, the interface 300 may display a first representation 320 of the front of the patient torso and the spatial positioning of sufficiently and insufficiently attached leads of the anterior sub-array 210 . The interface 300 may additionally display a second representation 330 of the back of the patient torso and the spatial positioning of sufficiently and insufficiently attached leads of the posterior sub-array 220 . The sufficiently attached leads may be illustrated in the interface 300 in a first format (e.g., “+” signs, as shown in FIG. 3 ) different from a second format (e.g., dots, as shown in FIG. 3 ) in which the insufficiently attached leads are illustrated. In this manner, the system 100 offers the user a more-intuitive “mapping” of the torso location of leads that require corrective attachment.
[0020] Each of the representations 320 , 330 may be rotated in three dimensions within the interface 300 , using a conventional input device, by the user to offer multiple views of the positioning of insufficiently attached leads relative to the patient's torso. Additionally, the interface 300 may include an indication, such as a meter 340 , of the quantity of the insufficiently attached leads.
[0021] It may be desirable to ensure compatibility between the connector element 120 and console 130 as a means of enabling, or disabling, electrical communication between the console and the array 110 . In an embodiment, this may be achieved by employing pull-up and/or pull-down combinations in the connector pins of the connector element 120 and console 130 as a means of implementing an “identification code.”
[0022] In such an embodiment, the array 110 is connected by pin connection to the connector element 120 . In turn, the connector element 120 may be connected to the console 130 with, for example, 20-wire cable. An exemplary respective connector-pin assignment for an interface 410 of the connector element 120 and an interface 420 of the console 130 is illustrated in FIG. 4 .
[0023] Table 1 illustrates an exemplary pin assignment table describing the connection between interfaces 410 and 420 .
[0000]
TABLE 1
Interface
Interface
Name
420
410
Status
GND (high imp)
1
2
5 V
2
4
SPI_CLK
3
14
GND (high imp)
4
12
5
6
SPI_START
7
11
SPI_DRDY
8
13
9
1
0
SPI_OUT
10
3
SPI_CS0
11
7
SPI_IN
12
5
PWDNB (3.3 V pull up)
13
6
1
14
15
16
RESETB (3.3 V pull up)
17
8
1
18
SPI_CS1
19
9
GND
20
10
[0024] In an embodiment, when the main power input, 5V, is applied to pin 2 of interface 420 of the console 130 , the pin status of pins 13 and 17 of interface 420 is high, as two pins may be pulled-up to 3.3V from interface 410 of the connector element 120 . By pulling-down pin 1 of interface 410 of the connector element 120 and pulling up pin 9 of interface 420 , an additional low line may be achieved. In this manner, the number of potential predetermined combinations that may be used as the above-referenced “ID code” is 2 3 =8. As such, in this example, by reading pins 9 , 13 and 17 of interface 420 , compatibility between the connector element 120 and console 130 can be ensured.
[0025] While the preferred embodiment of the invention has been illustrated and described, as noted above, many changes can be made without departing from the spirit and scope of the invention. Accordingly, the scope of the invention is not limited by the disclosure of the preferred embodiment. Instead, the invention should be determined entirely by reference to the claims that follow. | A system includes an array of N electrode elements configured to be attached to an external region of a patient, and a processing device coupled to the array. The processing device is configured to receive a set of bioelectric data signals from the array, determine from the set of data signals a set of elements of the array that are, according to a predetermined standard, insufficiently attached to the external region, and generate to a display device, in at least two dimensions, a representation of the external region and the spatial positioning of the insufficiently attached set of elements on the external region. | 0 |
This invention relates to improvements in opening packages containing materials in blisters of packages or cards and, more particularly, to a dispenser and method of opening blister packs containing medicinal materials, such as pills.
BACKGROUND OF THE INVENTION
Many different types of materials and products of small size are carried in blisters of blister packs. These packs are made up of cardboard cards having one or more blisters extending outwardly from holes in such a card so that each blister forms a pocket which is normally closed by a foil or other cover over the hole. Each blister is typically made from a transparent plastic material which can be severed by a knife or other cutting tool to gain access to the materials carried by the blister itself.
Among the various products which have been found to be suitably packaged in blister cards are medicinal materials, more specifically, one or more pills in each blister of a blister card. Also, small hardware stems, such as nuts and bolts, can be packaged in blisters of a blister card. Generally, these blister cards have a number of holes in them which are closed by blisters above a bottom layer of foil material which can be easily severed. Also, the blister for each hole extends upwardly from the upper surface thereof. The blisters are opened by hand by pressing inwardly on each blister one-by-one by the use of the thumbs.
The opening of the blisters of a blister card becomes an arduous and time consuming task when a nurse, for instance, must manually open the blister packs for a number of patients during the period when medication, such as a single pill, is to be given to the patients. Distributing a number of pills to a patient presents a problem because of the large number of patients in a hospital ward which must be given a relatively large number of pills, such as two or more, at each dosage time, over a given time period. Thus, a need exists for improved apparatus and a method for dispensing of materials, such as medicinal materials, in a way to facilitate the delivery of one or more medicinal items to a patient yet minimize the time required on the part of a nurse or other attendant to deliver and dispense the items to a number of patients. The present invention satisfies this need.
Disclosures of apparatus and methods of dispensing materials are found in the following U.S. patents:
______________________________________U.S. Pat. No. Name Issue Date______________________________________1,575,972 Cochran 03/09/19262,366,886 Van Tuyl 01/09/19453,279,651 Thompson 10/18/19664,690,279 Hochberg 09/01/19874,909,414 Heath 03/20/19904,975,015 Harding 12/04/19905,009,561 Lombardino 04/23/19915,038,968 Albetski 08/13/1991______________________________________
SUMMARY OF THE INVENTION
The present invention is directed to a dispenser and method for dispensing materials, particularly medicinal materials, such as one or more pills, from a blister pack of one or more blister cards. A single blister card having a plurality of blisters thereon can be used by itself or with other blister cards in a stack. More specifically, a stack of blister cards can be more readily accommodated with the dispenser and method of the present invention than if the blisters of the cards were manually and individually opened.
A stack of blister cards is placed in a support having a top plate provided with guide holes therethrough which are alignable with the blisters in the stack of blister cards. To dispense materials from the aligned blisters of stacked blister cards, a plunger or other force applying device is driven through a guide hole in the top plate and into the aligned holes having blisters therebelow. In this way, a plurality of blisters in a column can be quickly and cleanly opened by virtue of the fact that the plunger has a cutting edge on the end which engages the blisters. Thus, the blisters as well as the foils which close the tops of the holes having the blisters in the cards are severed and thereby opened. Thus, a plurality of medical pills can be liberated from the opened blisters and can easily gravitate to a collection region below the stack of blister cards.
Several embodiments of the mount for the blister card stack is disclosed. Moreover, the arrangement of the guide holes in the top plate and in the blister cards can be of any suitable configuration, such as rectangular or circular. The blister cards can be quickly and easily put in a stack and the stack can be held together as a unit below the normal position of the plunger. Thus, the stack will be located so as to permit rapid dispensing of pills from the blisters of a blister card. The dispensed pills are collected in a chute from whence they are given to a patient as a medicinal dose.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view, partially in schematic form, of the basic pill dispenser of the present invention, showing the guide holes in the top plate of the dispenser and the stacked pill-containing blister cards below the top plate for dispensing of pills from the blisters of the cards by the action of a plunger alignable with any one of the holes in the top plate;
FIG. 2 is an enlarged, fragmentary cross-sectional view of two of the stacked blister cards showing that the blisters each contain a pair of pills with the blisters being vertically stacked and closed with a foil which is pierced by the plunger;
FIG. 3 is a perspective view of a first embodiment of the support frame for a blister card, showing the side rails for anchoring a blister card against movement relative to the support frame;
FIG. 4 shows a fragmentary, perspective view of a blister card held in place by the support frame of FIG. 3;
FIG. 5 is a cross-sectional view taken along line 5--5 of FIG. 4;
FIG. 6 is a plan view, on an enlarged scale, of the blister card showing the holes for the blisters and the film for covering the holes from above;
FIG. 7 is a vertical section through the blister card, taken along line 7--7 of FIG. 6;
FIG. 8 is a cross-sectional view taken along line 8--8 of FIG. 6;
FIG. 9 is a bottom plan view of the support frame of the present invention;
FIG. 10 is a perspective view of a stack of five support frames without the blister cards coupled thereto, showing the frames being locked together in a stacked relationship;
FIGS. 11 and 11A are end elevational and top plan views of the assembly of cards shown in FIG. 1, the stack of blister cards being shown schematically in a block form beneath a plunger which can be adjustably mounted at any location alignable with a column of holes in the blister stack;
FIG. 12 is a top plan view of a circular blister card showing another embodiment of the way in which the pills can be dispensed from the blisters of such a card; and
FIG. 13 is a view similar to FIG. 12 but showing the foil layer on one half of the area of the blister card.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The basic dispenser and a first embodiment of the present invention is broadly denoted by the numeral 10 (FIG. 1) and includes a support 12 which can be a housing, a frame, or any other suitable structure for mounting a plurality of blister cards 14 in a vertically stacked relationship as shown in FIG. 1. The cards 14 are shown in cross-section in FIG. 2 and each card 14 has a series of holes 15 which are arranged in columns and rows with each hole 15 having a plastic sheet or blister 17 for forming a pocket to contain a single pill 19 while foil layer 21 covers the opening 15 so that the pills remain in respective pockets, out of contact with the atmosphere.
While the present invention will hereinafter be described with respect to the dispensing of medical pills, it is possible that any type of granular or particle-like materials could be dispensed from dispenser 10, such as granular, powdered, or liquid materials. In all likelihood, liquid materials will probably not be used, but it is possible in some cases to dispense liquids, if desired or deemed necessary.
Cards 14 are typically of plastic or cardboard material. Thus, they are generally stiff and do not bend; however, the films 21 and the plastic blisters 17 are severable by a plunger or other type of cutter 25 which may or may not have a cutter blade 27 (FIG. 2) on the lower end thereof. The plunger can move relative to housing 12 either manually or by an x-y transfer machine (not shown). The plunger 25 can also be electromechanical in nature so that, as it is remotely shifted by operation of an x-y machine, it can also be remotely controlled by means of a switch directing signals to the plunger by way of a cable (not shown). Thus, when the plunger 25 is vertically aligned as shown in FIG. 2, with a column of aligned blisters 17, the plunger will descend and cut the film and the aligned blisters 17 so that one or more pills in the blisters will be free to fall and will so fall into a hopper or collector 28 below the stack of cards 14 as shown in FIGS. 1 and 2. The pills can then be removed from the collector 28 and given to and ingested by the patient. The blisters can be scored in some suitable manner to facilitate the opening of the blisters to liberate the pills therein.
The support 12 typically has a pair of side walls 30 provided with projections 32 extending inwardly from the side walls. Side walls 30 present shelves for supporting the side margins of blister cards in vertically stacked, parallel relationship as shown in FIG. 1. When so positioned, the holes in the columns of blisters 17 when stacked, are aligned with holes 36 in a top plate 37 forming the top margin of support 12.
As shown in FIG. 1, there are, for instance, four columns of holes 36 extending from a top edge 37 to a bottom edge 40. There are also eight rows of holes 36 with each row having four holes in it. Thus, there are a total of thirty two holes in plate 37 and there are corresponding thirty two holes 15 in cards 14 below plate 37. As one example, instead of thirty two holes in top plate 37, there could be thirty two holes. Thus, as one example, a thirty two hole unit would be suitable for dispensing pills for one month, even though a month has twenty eight, twenty nine, thirty, or thirty one days.
A label 42 (FIG. 1) can be put on the outside of one of the side walls 30 to give the name of the patient for whom the pills are intended and other information needed to verify proper dosage. Moreover, special instructions as to the number of pills to be given per day or at each dosage period can also be included on the label 42.
In use, blister cards 14 are mounted on shelves 32 in vertically stacked relationship as shown in FIG. 1. The shelves 32 will have alignment guides 33 (FIG. 1) to position the cards precisely with respect to each other so that the holes 15 of the various cards 14 are vertically aligned as shown in FIG. 2. At the beginning of the month, the first column of holes 15 are opened by moving the plunger 25 downwardly in guided relationship to a hole 36 and in cutting relationship to foil strips 21 and the blisters 17 as shown in FIG. 2. The full line position of the plunger 25 in FIG. 2 is the position assumed by the plunger before the plunger is moved downwardly. The dashed lines in FIG. 2 represent the path of travel of the plunger as it passes through a hole 36 in guide plate 37 and through the corresponding openings 15 of the various cards 14 to liberate the pills 19 in the various blister packs so that the pills can fall into and be collected by collector 28 from which these pills can be given to the patient in the normal fashion.
The housing and the stacked cards remain together with each other for a particular patient for a particular month, for example. However, other arrangements of cards 14 can be provided, in which case the dosage for each column of holes 15 of the various blister cards 14 can be for specific patients who are to be medicated once a day on the pills dispensed for a particular column. Thus, with the five stacked cards 14 in FIG. 1, a total of thirty two patients can be provided with pills for one twenty four hour period, assuming all of the pills from a particular column will be ingested by a particular patient for that day. At the end of the day, the cards 14 can be dispensed with or thrown away. A new set of cards 14 would then be put into place for dispensing of pills therefrom.
Each blister 17 of hole 15 can be initially scored with a line of weakness extending in a direction parallel to the lower edge of plunger 25. The preferred position of each blister 17 is shown in FIG. 2 with the blisters being below the upper surface of the blister card 14. However, the card may be reversible so that each blister 17 is above the upper surface of the card and above the film 21. Another aspect of the present invention is the fact that a card 14 can be removed from the stack and replaced by another card having different medication. Thus, medication can be added or deleted at any time. Unused medications are fully retrievable at any time.
A preferred card mounting panel or support frame is denoted by the numeral 11 and is shown in FIGS. 3 and 4. Panel 11 has a pair of outer, relatively rigid strips 13 which are coupled by living hinges 13a (FIG. 6) to the main panel body of panel 11, whereby strips 13 can pivot or hinge about the pivot axis of each hinge 13a to thereby close the space between strip 13 and upper surface 41.
FIG. 3 shows the carrier panel 11 without the blister card 14a associated with panel 11; whereas FIG. 4 shows a blister card 14a which is secured by a side margin to carrier panel 11 by virtue of being clamped along the side margin 14b (FIG. 4) by the connection of buttons 38 with buttons 39 (FIG. 3). The buttons snap into place and can be separated by applying a manual force to the strip 13 near the vicinity of buttons 39.
A review of FIG. 5 shows the upper panel 14a in juxtaposition to panel 11. In this sense, the blister pack 17a extends partially through a hole 15a in bottom panel 11. The blister 17a contains a pill 21 and is covered by a film 21a. A plunger (not shown) is used to open the blister pack by severing the film 21a and the plastic of blister 17a.
FIG. 6 shows a plan view of blister card 14a. The opposed side margins 14c of the blister card 14a has semicircular recesses 14d (FIG. 6) which engage the buttons or pins 39 (FIG. 3) to position the holes in card 14a in vertical alignment with the corresponding holes 36 in carrier panel 11.
FIG. 8 shows the film 21a and the blister 17a. FIG. 9 is a view similar to FIG. 6 but showing the bottom of panel 11. A number of longitudinal support members 77 are secured to the underside of panel 11 in any suitable manner and the members run fore and aft. The purpose of the runners is to help in separating the adjacent carrier panels above and in the same stack in the manner shown in FIG. 10. FIG. 10 shows the carrier panels or support frames 11 stacked in place but without the blister cards 14 associated therewith.
Another embodiment of the dispenser of the present invention is denoted by the numeral 100 and includes a housing, frame or support 102 which receives a stack 104 of blister cards shown schematically as a single block in FIG. 11. The top plate 108 of dispenser 100 has a number of parallel beams or elongated members 112 which are secured in any suitable manner at the ends thereof to housing 102. The rails have holes 114 for mounting of thumb screws 116 of a plunger mechanism 119 having a plunger 121 which enters holes 123 in the upper plate 108 for severing the blister packs of the blister cards in the stack identified by block 104. A collection cup 127 receives the liberated medication and the medication can be removed from collector cup 127, if desired.
To change the position of the punch 119, the punch is removed by separating thumb screws 116 from holes 114 and beams 116, then the punch is moved to a new location and the thumb screws anchor the punch press anew for punching the columns of medication in any particular column whereby the medication is collected.
The foregoing description has been made with respect to a top plate of generally rectangular configuration with the holes of the top plate being in rows and columns. Another and preferred embodiment of a top plate is shown in FIG. 12 and is circular in design. It is mounted in some suitable manner so as to position one or more blister cards 14 below the holes 36 in the top plate. A suitable punch or plunger (not shown) can be moved relative to the top plate and into overlying relationship to one of the holes thereof. By actuating the plunger and causing it to move downwardly with respect to the top plate, the plunger will break the foil seal and a corresponding blister at each of a number of elevations below the top plate and the liberated medicinal materials from the blister will fall into a chute or collector from which the materials can be removed for ingestion by a patient. | A dispenser and method for dispensing materials from a blister pack of one or more blister cards. A single blister card having a plurality of blisters thereon can be used with other blister cards in a stack. To dispense materials from the aligned blisters of stacked blister cards, a plunger is driven through a guide hole in a top plate and into aligned blisters of a stack of blister cards. In this way, a plurality of blisters can be quickly and cleanly opened. Thus, a plurality of medical pills can be liberated from the blisters and can easily gravitate to a collection region below the stack of blister cards. Several embodiments of the mount for the blister card stack is disclosed. | 1 |
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