VISCOELASTIC MEMORY FLOW CONTROL VALVE FOR SINGLE-USE SYRINGE

Abstract: Solid disks of polyethylene oxide are radiation crosslinked to instill viscoelastic memory. The disks are then pierced with a needle, heated, cooled and the needle removed to form disks containing a flow orifice in each, which upon contact with water will revert to solid disks. A disk with a flow orifice made as just described when used as a memory flow control valve in a conventional injection device will produce a syringe with a single-use, auto-destruct capability. When the disk (1b) is inserted in a retainer (10) in the flow channel (12) of the injection device, a drug/vaccine can be drawn into the syringe and then expelled for a preselected time less than ten minutes before the water in the drug/vaccine causes the flow orifice in the disk to close, the disk then reverting to its solid shape due to its viscoelastic memory.

Description: Description Viscoelastic Memory Flow Control Valve For Single-Use Syringe Technical Field The invention relates generally to hydrophilic polymers with viscoelastic memory and to the use of such polymers, particularly polyethylene oxide (PEO) , to produce single-use, a to-destruct (self-annulling) injection devices. Such injection devices, through the polymer of the invention, are rendered inoperative after a single injection without requiring any positive action on the part of the user. The risk of the transmission of disease through the use of unsterile syringes and needles is of high concern to health care personnel. Childhood immunization requires some five injections, the safety of which must be assured if an immunization program is to achieve and maintain universal acceptance. The inadvertent transmission of disease during immunization is eliminated if one sterile syringe and one sterile needle are used for each injection. Consequently, it has become a priority among health care organizations to develop disposable injection devices that are inexpensive, cannot be used more than once, and can be introduced with little or no vaccinator retraining. Background Art A single-use, self-annulling injection syringe has been disclosed and claimed in U.S. Patent No. 4,781,683 ('683) which is incorporated herein by reference. The syringe of the '683 patent achieves single-use goals by the action of an insert pressed within the barrel of a conventional syringe with attached needle (cannula) . The insert, in one embodiment, is composed of a crosslinked, hydrophilic polymer plug which swells upon contact with the water in the drug/vaccine being injected and thereby blocks the flow channel in the syringe. Therefore, the '683 patent provides for an inexpensive, single- use, and easy-to-use syringe. Potential problems remain, however. The insert of the •683 patent can take up to 30 minutes to render the syringe inoperative which may be sufficient time to permit substantial reuse of the syringe. Further, if the hydrophilic plug is dehydrated, it might shrink to its original size rendering the syringe operative again. Finally, to enhance manufacturability, a different design for the plug/insert than those disclosed in the '683 patent is desirable. Disclosure of Invention The possible problems described above are avoided, to a great extent, through the practice of the invention. Illustratively, a hydrophilic polymer, e.g., polyethylene oxide, in the form of a solid disk is radiation crosslinked to instill viscoelastic memory. The solid disk of PEO is then pierced with a needle to form a hole or flow orifice in the center. The disk is then heated and cooled before the needle is removed. Thus, a viscoelastic memory means and, more particularly, a flow control valve (memory valve) is created which when used in an injection device produces a single-use, auto-destruct action as described below. The disk-shaped memory valve with flow orifice in the center is press-fit into the cavity of a cup-shaped retainer where it is retained by a flange on the retainer's inside rim. A hole in the bottom of the retainer is aligned with the flow orifice in the memory valve. The memory valve-retainer unit is then pressed into an otherwise conventional injection device with the aligned hole and flow orifice being aligned with the flow channel created by the syringe barrel and the cannula (injection needle) . In use, the injection device is similar to a conventional syringe in appearance; in the filling, aspiration, and injection steps; and in the thumb force needed to make the injection. However, in a preselected time interval (depending on the memory valve's material properties and flow orifice size) after a water-based drug/vaccine first contacts and activates the memory valve, i.e., after fluid is first drawn into the injection device, the viscoelastic memory in the memory valve closes the flow orifice. By reverting to a solid, the disk-shaped memory valve renders the injection device inoperable. Two design features prevent tampering or removal of the memory valve. First, the memory valve-retainer unit is locked into the syringe barrel by a ridge molded into the barrel. Second, as is well known in the art, removal of the plunger from the syringe barrel is prevented by a flange on the plunger and by one or more indentations (produced by "hot fingers") pressed into the syringe barrel during the final step of assembly. For a more complete appreciation of the invention, attention is invited to the following detailed description of a preferred embodiment of the invention taken with the figures of the drawings. The scope of the invention, however, is limited only through the claims appended thereto. Brief Description of Drawings FIG. 1, consisting of FIGs. la and lb, illustrates a top view and a cross sectional view, taken along line lb—lb of the top view, of the disk-shaped memory flow control valve of the invention with flow orifice. FIG. 2 is a cross sectional view of the retainer of the invention. FIG. 3 is a cross sectional view of the memory valve- retainer unit of the invention shown in an injection device. FIG. 4, consisting of FIGs. 4a, 4b and 4c, illustrates the feature of the invention preventing removal of the plunger from the syringe barrel with FIG. 4c being a cross sectional view of the plunger of FIG. 4b taken along line 4c—4c. Best Mode for Carrying Out the Invention Viscoelastic memory or "shape-memory" is developed within the molecular structure of a polymer by virtue of exposure to high energy radiation (i.e., gamma rays or electron-beam) as discussed below and in U.S. Patent Nos. 3,429,794 and 4,596,728, which are incorporated herein by reference. When polymers are exposed to radiation, two general types of reactions occur, scissions and crosslinking. Scission refers to degradation of the polymeric main chain structure without secondary reaction. Crosslinks form when a main chain molecule is broken and the resulting free radical reacts with a nearby molecule to form an interchain covalent carbon-carbon bond. When crosslinking dominates over scissions the reaction leads to a three dimensional network structure. The crosslink structure is unaffected by heat while the portions of the polymer not incorporated in the crosslinks, the amorphous regions, melt when raised above the crystalline melt temperature. At temperatures below the crystalline melt temperature the irradiated polymer has the properties of a conventional plastic material, however, above its melt point the material acts as an elastomer (rubber-like) . When subject to a force in the elastomeric state, the material deforms temporarily to a second configuration, but returns to its original shape or first configuration upon removal of the force. If the polymer is cooled in the elastically distorted state or second configuration, the amorphous regions recrystallize and the material remains in a deformed state. If the deformed material is exposed to one of the normal solvents of the unirradiated material (or is reheated above the crystalline melt temperature) , the material again becomes elastomeric and relaxes to release the internal stress thus returning to its original shape or first configuration. This is the basic principle behind the manufacture and use of the viscoelastic memory means and flow control valve (memory valve) made therefrom which is used to produce a single-use, auto-destruct injection device. The preferred material for use in the viscoelastic memory means and flow control valve of the invention is the hydrophilic polymer, polyethylene oxide (PEO) , a thermoplastic with the following repeating unit: (CH 2 -CH 2 -0) n . The factor n, which is the number of repeating units combined to form the overall molecular structure, is called the degree of polymerization. For use in a single-use, auto-destruct injection device, PEO with a degree of polymerization of more than approximately 4,500 or, equivalently, a molecular weight of more than approximately 2 x 10 5 (The repeating unit has a molecular weight of 44; consequently, e.g., 44 x 4,500 2 x 10 5 .) is satisfactory with PEO at the higher molecular weights being preferred in terms of memory valve strength, tolerance to heat and humidity, and workability. Also, PEO with higher molecular weight needs less irradiation, which is costly, but, on the other hand, such PEO is more difficult to mold. Special care should be taken in the polymerization of the selected PEO to insure very low-order (ppm) contamination with any potential toxic residuals. The viscoelastic memory means and flow control valve fabrication process begins by forming PEO into a first configuration of solid disks. This is done using conventional thermoplastic injection molding or extrusion techniques and/or stamping disks from sheets of PEO. Crosslinks are then formed in the solid disk inserts by exposure to radiation. (The PEO may also be irradiated prior to the disks being formed.) In the actual processing, disks are placed in a chamber in which air has been purged and replaced with an inert gas. An inert gas environment is necessary because the free radicals created by the irradiation can react with the oxygen in air and degrade the material. The chamber in which the inserts are placed is kept cool during the irradiation with a cooling water jacket. Cooling is necessary since the irradiation generates heat which could melt the PEO if not properly cooled. The disks are exposed to cobalt-60 gamma rays to a total dose of more than approximately 5 Mrads. The crosslinking may also be accomplished using electron-beam irradiation. The irradiation forms crosslinks which instill the disk memory valves with the preferred shape or first configuration as a solid. The irradiation dosage and molecular weight used will be a function of the intended insert disk application, timing, and cost, e.g. , the greater the dosage the greater the crosslinks formed and the higher the cost; the higher the molecular weight the less dosage is needed; and the faster the closure time required the greater the number of crosslinks required. Following the crosslinking step, the individual disks are pierced by and stacked on a sharp needle. Preferably, the disk should have flat opposite faces. The needle is then placed in a low temperature oven and the PEO is brought above its crystalline melt temperature for several minutes. Elevating the temperature brings the crosslinked PEO into its elastic state while each memory valve is distorted into the shape of a disk with a flow orifice through its center by virtue of the needle. The needle, stacked with inserts, is removed from the oven and allowed to cool naturally to room temperature. Cooling recrystallizes the amorphous regions of the PEO, locking the memory valve into the desired shape or second configuration of a disk with a flow orifice through its center as shown in Figs, la and lb. The memory valves are then removed from the needle. A retainer 10 (Fig. 2) is used to incorporate the viscoelastic memory valve into the barrel of a standard injection device to produce the desired single-use, auto- destruct syringe and to protect the memory valve from any tampering or attempt at removal. As shown in Fig. 2, the retainer 10 is cup-shaped with a cavity for receiving the memory valve and with a hole centered in the bottom of the cup. The memory valve 16 (see Fig. 3) is press-fit into the retainer 10 with the flow orifice in the disk (memory valve) being aligned with the hole in the retainer 10; a flange 11 protruding from the inside rim of the retainer 10 keeps the memory valve in the cavity. This operation reduces the memory valve and retainer to a single unit (memory valve-retainer unit) . In the next step of assembly, a memory valve-retainer unit is inserted in the flow channel of an injection device. A detailed drawing of the memory valve-retainer unit and its positional relationship within the syringe barrel 12 is shown in Fig. 3. (Note, as disclosed in U.S. Patent No. 4,781,683, the memory valve retainer unit can also be placed in the interior flow channel of a coupling member which is connected to an injection needle. The coupling member/memory valve- retainer unit/injection needle combination can then be attached to the tip of a syringe barrel.) The unit is placed into the plunger end of the syringe barrel 12 and is pressed forward the full length of the barrel. The outside diameter of the retainer 10 is sized to the same diameter as the syringe barrel diameter to ensure a tight frictional fit. It is the friction between the retainer 10 and syringe barrel 12 and/or a small ridge 14 molded into the inside of the barrel 12 that ensures that the memory valve 16- retainer 10 unit cannot be removed once it is installed. The follow-on steps of injection device manufacture (needle attachment, siliconization, and plunger insert) are the same as those for a traditional disposable plastic injection device. As an added measure to inhibit tampering with the memory valve, the plunger 18 (FIGs. 4a, 4b, and 4c) cannot be removed from the syringe barrel 12. This is accomplished as the last step in assembly of the injection device by a technique known in the art as shown in FIG. 4a by pressing at least one, and preferably two or more, indentations (produced by "hot fingers") 20 in the syringe barrel 12. A flange 22 molded on the plunger 18 shaft near the rubber piston end (see FIGs. 4b and 4c) contacts the indentations when the shaft is fully extended preventing removal of the plunger from the barrel. Following printing and blister packaging, sterilization of the completed single-use, auto-destruct injection device is done using either the electron-beam or ETO (ethylene oxide) gas process. Either process is the same as that used in the case of a conventional syringe although, for the ETO sterilization, the processing levels of heat and humidity must be controlled within certain limits to ensure that the viscoelastic memory is not triggered to close the flow orifice. Cobalt-60 irradiation can be used for sterilization of the injection device of the invention but this process can effect the crosslink network and alter the timing of the viscoelastic memory valve. In operation, the flow orifice in the memory valve allows fluid to be drawn into and expelled from the injection device but, after a short period of time, the orifice closes by action of its viscoelastic memory to prevent any further fluid flow. The flow orifice closing response is a result of exposing the memory valve to water (a common base for most drugs/vaccines) which softens the crystalline structure. The softening enables the tension stored within the crosslink network to return the memory valve to its original solid shape or first con iguration. The initial diameter of the orifice is preferably at least twice as large as the internal lumen of the injection needle 17 (see Fig. 3) and, consequently, there is no restriction in the flow or thumb force needed to expel vaccine for the first time use. The flow orifice begins to close upon the initial filling of the syringe with a water-based drug but does not reach the final stage of being fully closed until a preselected time interval (less than 30 minutes and, preferably^ between one and ten minutes depending on the initial flow orifice diameter) . In the final stage of closing there is increased flow resistance until the point when fluid can neither be expelled from nor drawn into the syringe. This produces the novel single-use, auto-destruct feature of the invention. Drying the memory valve will not cause the flow orifice to return since a solid disk is the shape instilled during the radiation crosslinking step. This ensures that the single-use, auto-destruct feature is permanent and cannot be reversed by drying.

Claims: Claims 1. An improved viscoelastic memory means produced by the steps of: exposing the memory means to ionizing radiation sufficient to create intramolecular crosslinks within the memory means, heating the memory means, altering the shape of the memory means from a first configuration to a second configuration either before or after the heating step, and cooling the memory means while in the second configuration to reform the crystalline structure, wherein the improvement comprises: the memory means comprising a polyethylene oxide having a molecular structure characterized by a degree of polymerization of more than approximately 4,500 or, equivalently, a molecular weight of more than approximately 2 x 10 5 , and wherein the polyethylene oxide is exposed to cobalt-60 gamma rays to a total dose of more than approximately five megarads, whereby the polyethylene oxide will remain in the second configuration until exposed to water thereby causing the polyethylene oxide to revert from the second configuration to the first configuration in a preselected time interval less than 30 minutes. 2. The memory means as recited in claim 1, wherein the polyethylene oxide is exposed to electron beam radiation to a total dose of more than approximately five megarads. 3. The memory means as recited in claims 1 or 2, wherein the preselected time interval is from one to ten minutes. 4. A viscoelastic memory flow control valve for use in an auto-destruct injection device comprising the memory means as recited in claims 1 or 2. 5. The memory flow control valve as recited in claim 4, wherein the preselected time interval is from one to ten minutes. 6. The memory flow control valve as recited in claim 4, wherein the first configuration comprises a solid and the second configuration comprises a solid with a flow orifice. 7. The memory flow control valve as recited in claim 6, wherein the solid is a disk. 8. The memory flow control valve as recited in claim 7, wherein the flow orifice is at least twice as large as the internal lumen of the injection needle. 9. In an auto-destruct injection device having an internal flow channel and a viscoelastic memory flow control valve with a flow orifice, a device for retaining the memory flow control valve in the injection device comprising: a retainer with a cavity for receiving the memory flow control valve and a hole in the bottom of the retainer aligned with the flow orifice in the memory flow control valve; and a flange protruding from the inside rim of the retainer for keeping the memory flow control valve in the cavity; wherein the retaining device containing the memory flow control valve is inserted into the flow channel with the aligned hole and flow orifice aligned with the flow channel. 10. In an auto-destruct injection device having a variable volume chamber adapted to receive a drug containing water and an injection needle having an internal lumen, the injection needle connected to the variable volume chamber forming a flow channel between the variable volume chamber and the internal lumen of the injection needle, the improvement comprising: a viscoelastic memory flow control valve composed of a hydrophilic polymer, the memory flow control valve having a first configuration and a second configuration, the second configuration being positioned within the flow channel for reverting to the first configuration and blocking the flow channel after the second configuration is exposed to the drug containing water, thereby preventing reuse of the injection device. 11. The device as recited in claim 10, wherein the hydrophilic polymer is polyethylene oxide. 12. The device as recited in claim 11, wherein the polyethylene oxide has a molecular structure characterized by a degree of polymerization of more than approximately 4,500 or, equivalently, a molecular weight of more than approximately 2 x 10 5 . 13. The device as recited in claim 12, wherein the polyethylene oxide when exposed to the drug containing water will revert from the second configuration to the first configuration within a preselected time interval. 14. The device as recited in claim 13, wherein the preselected time interval is less than 30 minutes. 15. The device as recited in claim 13, wherein the preselected time interval is from one to ten minutes. 16. The device as recited in claim 13, wherein the first configuration comprises a solid and the second configuration comprises a solid with a flow orifice. 17. The device as recited in claim 16, wherein the solid comprises a disk. 18. The device as recited in claim 16, wherein the flow orifice is at least twice as large as the internal lumen of the injection needle. 19. The device as recited in claim 12, further comprising: a retainer with a cavity for receiving the memory flow control valve and a hole in the bottom of the retainer aligned with a flow orifice in the memory flow control valve; and a flange protruding from the inside rim of the retainer for keeping the memory flow control valve in the cavity; wherein the retainer containing the memory flow control valve is inserted into the flow channel with the aligned hole and flow orifice aligned with the flow channel. SUBSTITUTE SHEET 20. A method for making a viscoelastic memory flow control valve for use in an auto-destruct injection device comprising the steps of: exposing a solid disk of hydrophilic polymer to ionizing radiation sufficient to create intramolecular crosslinks within the hydrophilic polymer; forming a flow orifice in the disk of hydrophilic polymer; heating the disk of hydrophilic polymer containing the flow orifice either before or after the forming step; and cooling the disk of hydrophilic polymer containing the flow orifice to reform the crystalline structure; whereby the flow orifice formed in the disk of hydrophilic polymer will be retained until the hydrophilic polymer is exposed to a solvent of the hydrophilic polymer in an unirradiated state thereby causing the disk containing the flow orifice to revert to the solid disk. 21. The method as recited in claim 20, wherein the hydrophilic polymer when exposed to the solvent will revert from the disk containing the flow orifice to the solid disk in less than 30 minutes. 22. The method as recited in claim 21, wherein the solvent is water. 23. The method as recited in claims 20 or 22, wherein the hydrophilic polymer is polyethylene oxide. 24. The method as recited in claim 23, wherein the exposing step comprises exposing the polyethylene oxide to cobalt-60 gamma rays to a total dose of more than approximately five megarads. 25. The method as recited in claim 24, wherein the polyethylene oxide has a molecular structure characterized by a degree of polymerization of more than approximately 4,500 or, equivalently, a molecular weight of more than approximately 2 x 10 5 . 26. The method as recited in claim 23, wherein the exposing step comprises exposing the polyethylene oxide to electron beam radiation to a total dose of more than approximately five megarads. 27. The method as recited in claim 20, wherein the forming step comprises the step of piercing the center of the disk of hydrophilic polymer with a needle. 28. The method as recited in claim 27, wherein the cooling step is done while the disk of hydrophilic polymer is pierced by the needle. 29. The method as recited in claim 28, further comprising, after the cooling step, the step of removing the needle from the disk of hydrophilic polymer leaving a disk containing the flow orifice. 30. The method as recited in claim 20, wherein the hydrophilic polymer is exposed to ionizing radiation before the hydrophilic polymer is formed into a solid disk. 31. A method for retaining a viscoelastic memory flow control valve in an auto-destruct injection device with a flow channel, comprising the steps of: pressing the memory flow control valve into the cavity of a retainer, the retainer having a hole aligned with a flow orifice in the memory flow control valve; and inserting the combined memory flow control valve- retainer into the flow channel of the injection device with the aligned hole and flow orifice aligned with the flow channel. 32. In an auto-destruct injection needle device adapted to couple to the tip portion of a hollow syringe barrel and having a coupling member adapted to couple to the tip portion of an injection needle, the coupling member having an interior flow channel, and an injection needle having an internal lumen connected to one end of the coupling member so that the internal lumen is in fluid communication with the interior flow channel, the improvement comprising: a viscoelastic memory flow control valve composed of a hydrophilic polymer, the memory flow control valve having a first configuration and a second configuration, the second configuration being positioned within the interior flow channel for reverting to the first configuration and blocking the interior flow channel after the second configuration is exposed to the drug containing water, thereby preventing reuse of the injection device.

Inventors: ROBERTSON MICHAEL CHARLES, WOZNIAK JOHN JOSEPH, ROBERTSON, MICHAEL, CHARLES, WOZNIAK, JOHN, JOSEPH
Applicants: UNIV JOHNS HOPKINS, THE JOHNS HOPKINS UNIVERSITY
Application year: 1991
Main classification: B29K71
IPC codes: A61L31, A61M5, B29C61, B29K71, C08J7