INJECTION SET FOR EXTERNAL INFUSION SYSTEM

Abstract: An injection set for use with an external infusion source of fluid such as insulin, constructed using multiwall tubing (10). The interior (12) of the multiwall tubing (10) is made of a material which is completely insulin compatible, such as polyethylene, while the exterior (16) of the multiwall tubing (10) is made of a material which may be solvent bonded such as flexible polyvinyl chloride. The multiwall tubing (10) facilitates solvent bonding of an insert moulded needle assembly (20,22) and a connector (30) to the ends of the tubing (10) without the use of epoxy bonding and its attendant disadvantages.

Description: The present invention relates generally to injection devices for use with an external infusion system whereby insulin is subcutaneously delivered to a patient. The invention is particularly applicable to a disposable injection set for delivering insulin to a patient, using materials which will not result in any reaction of the insulin passing through the system, thereby avoiding the adverse results of such an insulin reaction. Generally, in order to dispense a fluid subcutaneously from an external source to a patient, the distal end of a hollow needle is inserted through the skin of the patient, thereby providing a passageway to the desired subcutaneous injection location under the skin of the patient. The proximal end of the hollow needle located externally of the skin of the patient is connected to one end of a tube, the other end of which is connected to the external source of the fluid to be injected, typically with a luer connector made of hard PVC (polyvinylchloride) and which may be easily connected by merely inserting the mating connectors together and twisting to lock them together. A preferred technique for connecting the tube to the needle involves the moulding of a hard PVC segment around the proximal end of the needle, and then using flexible PVC tubing which may be solvent bonded to the hard PVC segment moulded around the proximal end of the needle. Solvent bonding is preferred because of the relative ease of the solvent bonding operation, the strength and durability of the solvent bond, and the inexpensive cost of solvent bonding. Since such infusion sets are disposable, cost and acceptable shelf life are important criteria by which such an infusion set will be judged. The recent popularity of insulin infusion pumps as an alternative to multiple daily injections for insulin-dependent diabetics requires the use of such an injection set to deliver insulin from a small, portable insulin infusion pump to the subcutaneous injection location. It has been determined that there exists a substantial problem with the use of injection sets as described above in that flexible PVC is not completely insulin compatible. This is in contrast to hard PVC, which is perfectly safe for use with insulin. While the exact nature of the reaction exhibited by insulin in contact with flexible PVC has not been determined with certainty, it is believed that the insulin, which is pH sensitive, reacts with CO₂; the flow of CO₂ is not inhibited by flexible PVC. In addition, the large quantities of plasticiser used in flexible PVC may result in a leaching problem when used with insulin. Since flexible PVC is not a barrier for CO₂, the CO₂ which flows through the flexible PVC tubing will react with the insulin, causing the insulin to aggregate and to precipitate out of solution. This precipitation may well cause clotting and blockage in the tube or in the needle, thereby inhibiting the flow of insulin to the subcutaneous depot. Heat can also accelerate the clotting process of insulin in flexible PVC tubing without the pH change caused by CO₂. The reason for this has not been finally determined, but it may be due to zinc in the insulin forming zinc chloride. In any event, heat will further compound the situation faced by the delivery of insulin through flexible PVC tubing. The amount of insulin leaving the injection set can therefore vary considerably, with portions of the insulin becoming attached to the interior of the tube and eventually coating the interior of the tube even if blockage does not occur. Over time, the situation will improve somewhat assuming blockage of the tube per se does not occur, but the amount of insulin actually delivered to the patient will vary considerably even in the best circumstances. It may therefore be appreciated that the use of a flexible PVC tubing injection set to deliver insulin from an insulin infusion pump is neither desirable nor medically acceptable. It should be noted that other substances exhibit reactions when delivered through flexible PVC tubing. Lipids and proteins have adverse reactions with flexible PVC delivery systems, and nitroglycerin also reacts to some degree with a flexible PVC environment. One solution to the problem which has been discovered is the use of polyethylene tubing, which tends not to allow a reaction with insulin. Polyethylene is a barrier to CO₂, and the major problem of CO₂ passing through the tubing is thereby eliminated. Additionally, the problem of the insulin clotting due to heat is also substantially reduced. However, polyethylene is not solvent bondable as is flexible PVC, and a substantial problem in manufacturing injection sets using polyethylene has arisen. The preferred method to date has been to use an epoxy material to "pot" the polyethylene tubing to the needle, without using a hard PVC segment moulded onto the needle. Although the hard PVC segment could be used, since polyethylene is not susceptible to solvent bonding it would be necessary to use an epoxy to bond the polyethylene tubing to the hard PVC segment, resulting in a higher cost injection set. Several problems have arisen with the use of epoxy bonded polyethylene infusion sets, all of which are due to the relative disadvantage of the epoxy bonding process compared to the solvent bonding process. First of all, an epoxy bond is simply not as strong as a solvent bond. Secondly, epoxy bonds have substantial ageing problems, which limit the shelf life of the injection set. Since the epoxy bond loses its mechanical bonding properties over time, the injection set will become less sturdy, with the potential for the tubing coming loose from the needle increasing substantially over time. Thirdly, batch control of epoxy used in epoxy bonding is time consuming and cumbersome. Finally, epoxy bonding or "potting" is a more expensive process than solvent bonding, resulting in a product having an economic disadvantage relative to a product made by solvent bonding. It is thereby apparent that there exists a substantial need for an injection set for delivery of insulin, which uses polyethylene tubing to inhibit reactions and subsequent degradation of the insulin. It is a primary objective of the injection set to be susceptible to manufacture by solvent bonding, thereby resulting in a superior mechanical bond having great strength and excellent shelf life. It is also desirable that the improved injection set be economical to manufacture, resulting in an inexpensive disposable product which may be easily marketed. Finally, it is desirable that the injection set should be able to achieve the aforementioned advantages and solve the previously mentioned disadvantages without substantial disadvantage. US-A-4349022 discloses a standard injection set comprising a needle, a length of tubing mechanically connected to the needle and a connector mechanically connected to the other end of the tubing for attachment to a liquid source. US-A-4464l76 discloses a catheter tube having an inner layer of polyethylene and an outer layer of polyvinylchloride. According to the present invention, there is provided an injection set comprising length of flexible tubing (10), a hollow needle (22), and a connector (30), the needle (22) having a holder (20) at or near its proximal end and having a free distal end, one end of the tubing (10) being mechanically connected to the proximal end of the needle (22) and being in fluid communication with the needle (22), and the other end of the tubing (10) being in fluid connection with the connector (30), characterised in that the one end of the tubing (10) is solvent-bonded to the holder (20), the other end of the tubing (10) is solvent-bonded to the connector (30), and the flexible tubing (10) is of multilayer construction comprising an inner layer (12) of a first material which is compatible with insulin and an outer layer (16) of a second material which is solvent-bondable to the material of the holder (20) and the connector (30). More specifically, there may be provided an injection set for use with an external infusion system to deliver a desired fluid to a subcutaneous injection location under the skin of a patient, comprising: a segment of flexible tubing having a first end and a second end, said tubing being open on said first and second ends and having a passage therethrough communicating with said first and second ends, said tubing being of multiwall construction and having an inner annular layer defining said passage, said inner annular layer being made of a first material which is compatible with said desired fluid, said tubing also having an outer annular layer which is flexible and solvent bondable; a connector for facilitating fluid communication with said first end of said tubing, said connector being mechanically connected to said first end of said tubing to supply said desired fluid from said external infusion system to said passage in said tubing; and a needle having a proximal end and a distal end, said needle for insertion by the distal end thereof into said subcutaneous injection location under the skin of said patient, the proximal end of said needle being mechanically attached to said second end of said tubing in a manner whereby said proximal end of said needle is in fluid communication with said passage in said tubing. Preferably, the inner layer of the tubing is made of polyethylene and the outer layer of the tubing is made of flexible polyvinyl chloride. Preferably, the tubing has an intermediate layer between the inner layer and the outer layer. Preferably, the intermediate layer is made of a material which has good adhesion qualities to both the first and second materials, such as ethylene-vinyl acetate. Preferably, the segment is insert moulded onto the needle near its proximal end, the segment having a cylindrical cavity into which the proximal end of the needle extends, the cylindrical cavity having an opening through which the one end of the tubing is inserted whereby the proximal end of the needle is in fluid communication with the tubing, the inner surface of the cylindrical cavity being solvent bonded to the outer layer of the tubing. The segment is preferably made of hard polyvinyl chloride. Preferably, the solvent used in the solvent bonding is a 100% reagent solvent such as cyclohexanone. Preferably, the inner layer of the tubing is so arranged and configured as to overlap and to seal a portion of the proximal end of the needle. Preferably, the connector includes an internal flange having an aperture the tubing being mounted in the connector in an abutting relationship with the flange, and the aperture in the flange being aligned with the centre of the inner layer of the tubing and being in fluid communication with the tubing. The connector may be a female luer connector. The disadvantages and limitations of the background art discussed above may thus be overcome by the present invention. Multiwall tubing such as coextruded or triextruded tubing having polyethylene as the inner layer and flexible PVC as the outer layer can be used advantageously to construct an injection set. The needle can be made by using insert moulding technology, with a hard PVC segment moulded around the proximal end of the needle. One end of the tubing can be inserted into the hard PVC segment with the inner polyethylene tubing layer around the proximal end of the needle, and the outer flexible PVC layer solvent bonded to the hard PVC segment. The other end of the tubing can be solvent bonded to a hard PVC connector, typically a luer connector. In a preferred coextruded tubing, an outer layer of flexible PVC tubing is extruded over an inner layer of polyethylene. A triextruded tubing, which can be used in a more preferred embodiment, has a middle layer which bonds to both flexible PVC and polyethylene, and the bond achieved between the layers is better than the bond between flexible PVC and polyethylene in the coextruded tubing. According to another aspect of the present invention, there is provided a method of making an injection set, which comprises insert moulding a segment of hard polyvinyl chloride around the proximal end of a hollow needle; inserting one end of a length of flexible tubing into a cavity in the segment, the tubing being in fluid communication with the needle; and connecting the other end of the tubing to a hard polyvinyl chloride connector, the needle also being in fluid communication with the interior of the connector; characterised in that the flexible tubing is of multilayer construction comprising an inner annular layer of polyethylene and an outer annular layer of flexible polyvinyl chloride, and by the steps of solvent bonding the outer layer both to the interior of the cavity and to the connector. According to a preferred embodiment of the present invention, there may be provided an injection set comprising: a length of multiwall tubing having an inner annular layer of polyethylene and an outer annular layer of flexible PVC, said tubing having a passage therethrough; a hollow needle having a distal end and a proximal end; a segment of hard PVC mounted around the proximal end of said hollow needle, said segment having a cavity therein into which one end of said tubing is inserted, the outer layer of said tubing being solvent bonded to the interior of said cavity with said passage being in fluid communication with said proximal end of said needle; and a hard PVC connector solvent bonded to the other end of said tubing, said passage also being in fluid communication with the interior of said connector. According to a more specifically preferred embodiment of the present invention, there may be provided an injection set for use with an external drug infusion pump to deliver insulin supplied by said pump to a subcutaneous injection location under the skin of a patient, comprising: a segment of said triextruded flexible tubing having a first end and a second end, said tubing being open on said first and second ends, said tubing having an inner annular layer defining a passage therethrough between said first and second ends, said inner annular layer being made of a polyethylene, said tubing having an intermediate annular layer around said inner layer, said intermediate layer being made of EVA, said tubing also having an outer annular layer, said outer layer being made of flexible PVC, a female luer connector for connection with said first end of said tubing, said connector being made of hard PVC, said connector being solvent bonded to said outer layer of said tubing to supply said desired fluid from said external infusion system to said passage in said tubing; a needle for insertion by the distal end thereof into said subcutaneous injection location under the skin of said patient; and a hard PVC segment which is insert moulded onto said needle near the proximal end thereof, said segment having a cylindrical cavity therein in which said proximal end of said needle is located, said cylindrical cavity having an opening therein, said tubing being inserted into said cylindrical cavity in a manner whereby the proximal end of said needle is in fluid communication with said passage in said tubing, the inner portion of said cylindrical cavity of said segment being solvent bonded to said outer layer of said tubing. When the inner layer of the multiwall tubing is polyethylene, the injection set of the present invention is particularly suitable for use with insulin and other fluids exhibiting a reaction when delivered through flexible PVC tubing. When the outer layer of the multiwall tubing if flexible PVC, solvent bonding may be used in the construction of the injection set, thereby resulting in a product having excellent strength and shelf life characteristics while being of economical manufacture. It may therefore be appreciated that the present invention results in a product having substantial advantages over the background art, while presenting no apparent disadvantages. The tubing and connectors may be similar in any respect to those described in relation to the injection set of the invention. The present invention can be carried into practice in various ways and some embodiments will now be described by way of example with reference to the accompanying drawings in which: Figure 1 is a plan view of an injection set in accordance with the present invention; Figure 2 is a sectional view of the needle end of the injection set of Figure 1, illustrating the connection of triextruded tubing to a hard PVC segment insert moulded onto the proximal end of a needle; Figure 3 is a sectional view of the female connector end of the injection set shown in Figure 1, illustrating the connection of triextruded tubing to a hard PVC female luer connector; Figure 4 is a cross sectional view of the triextruded tubing used in the preferred embodiment; and Figure 5 is a plan view of an extension piece in accordance with the present invention. A first embodiment is illustrated in Figures 1 to 3, and is constructed using multiwall tubing having polyethylene as an annular inner layer and flexible PVC as an annular outer layer. Multiwall tubing is generally manufactured by co-extrusion, i.e. by extruding the inner or innermost tubing first, and successively extruding one or more additional annular layers around the previously extruded layer or layers. The present invention requires a multi-layer tubing, having therefore at least two layers. The inner layer is preferably polyethylene and the outer layer is preferably flexible PVC. Practice has shown that coextruded tubing has a propensity to separate somewhat under certain conditions, and this separation may allow backwashing of insulin to occur into the space between the inner and outer layers of tubing. Such a phenomenon would result in a shortage of insulin in the supply stream to the patient, and the difficulty in fabrication of a stable coextruded tubing of the desired inner and outer materials makes the coextruded tubing less desirable from both reliability and performance standpoints. Therefore, in the preferred embodiment of the present invention a triextruded multiwall tubing is used. A segment of triextruded multiwall tubing 10 is shown in Figure 1, in section in Figures 2 and 3, and in cross section is Figure 4. The triextruded tubing 10 has as its innermost layer an annular polyethylene tubing layer 12, which would be extruded first. In the preferred embodiment, the polyethylene tubing 12 has an inner diameter of 0.01 to 0.025 inches (0.254 to 0.635mm), and a thickness of 0.005 to 0.012 inches (0.127 to 0.305mm) preferably, 0.007 to 0.009 inches (0.178 to 0.229mm). An intermediate layer 14 is extruded around the inner tubing layer 12, which intermediate layer 14 is made of a material which will have good adhesion qualities to both polyethylene and to flexible PVC. In the preferred embodiment, the intermediate layer is a member of the polyethylene family having superior adhesion characteristics to both polyethylene and to flexible PVC, such as EVA (ethylene-vinyl acetate). The intermediate layer 14 is relatively thin, being of the order of 0.0005 to 0.005 inches (0.013 to 0.127mm) and preferably 0.001 to 0.002 inches (0.025 to 0.051mm). An outer layer 16 is extruded over the intermediate layer 14 and the inner layer 12, and this outer layer 16 is a flexible PVC. The thickness of the outer layer 16 is between 0.005 and 0.015 inches (0.127 to 0.381mm), preferably, 0.010 to 0.012 inches (0.254 to 0.305mm). In the preferred embodiment, the completed triextruded tubing 10 will have an outside diameter of approximately 0.06 inches (1.524mm). It will be appreciated that the triextruded tubing 10 can have the best of both worlds, in that its inner layer is polyethylene and is therefore a desirable conduit for insulin, while its outer layer is flexible PVC, and is therefore able to be conveniently solvent bonded. Referring again to Figures 1 and 2, a hard PVC segment 20 is insert moulded around the area adjacent to the proximal or external end of a 27 Gauge pre-bent hollow needle 22. It is important to note that the proximal end of the needle 22 is located in a cylindrical cavity 24 in the hard PVC segment 20, which cavity 24 is open at the end of the hard PVC segment 20 opposite the end from which the internal or distal end of the needle 22 extends. Except for the fact that the proximal end of the needle 22 is within the cylindrical cavity 24 and not covered by the hard PVC segment 20, the configuration of the hard PVC segment 20 and the needle 22 is not unlike that known in the art. In fact, the technique of insert moulding a hard PVC segment on a needle is well known in the art. One end of the triextruded tubing 10 is inserted into the cylindrical cavity 24, which is sized to receive the outer diameter of the tubing 10. It will be appreciated that the outer flexible PVC layer 16 of the tubing 10 is adjacent the cylindrical cavity 24 of the hard PVC segment 20. The inner diameter of the inner polyethylene tubing layer 12 extends over the proximal end of the hollow needle 22 in sealing fashion to prevent the insulin from seeping out and into contact with the outer flexible PVC layer 16. The outer flexible PVC layer 16 is bonded to the portions of the cylindrical cavity 24 it contacts by solvent bonding in the preferred embodiment. A 100% reagent solvent such as cyclohexanone is used to form a strong, durable seal with excellent shelf life characteristics in an economical, highly repeatable operation. It may also be noted in Figure 1 that a flexible needle guard 26 is removably located over the needle 22 and a portion of the segment 20. Referring now to Figure 3, the other end of the triextruded tubing 10 is inserted into one end of a female luer connector 30 made of hard PVC. The female luer connector 30 has an aperture 32 through it which allows fluid communication between the connector 30 and the interior of the inner polyethylene tubing layer 12. The joint between the tubing 10 and the connector is sealed with solvent in a manner similar to that described above. The tubing 10 is inserted into the connector 30 so the butt end of the tubing 10 is sealed against a flange portion 34 of the connector 30, with the aperture 32 aligned with the centre of the inner tubing 12, thereby preventing insulin passing through the connector 30 and the tubing 10 from coming into contact with the flexible PVC outer layer 16. It will be appreciated that while Figures 1 to 3 illustrate a complete infusion set, the principals of construction of the present invention are equally applicable to a variety of similar devices, such as the extension illustrated in Figure 5. A female luer connector 30 is mounted on one end of the triextruded tubing 10, and a male luer connector 40 is mounted on the other end of the tubing 10. Similarly, although the present discussion pertains primarily to an insulin injection set, the teachings of the present invention are equally applicable to devices for use with other liquids which are sensitive to flexible PVC, such as lipids and proteins, as mentioned above. It will be understood that the present invention provides for transfer of insulin from an external infusion pump or the like to a subcutaneous infusion depot. Since the interior of the tubing of the injection set now uses polyethylene, the problems of blockage and clotting of insulin in the device are virtually eliminated. Neither CO₂ nor heat will have adverse effects mentioned previously on insulin supplied through the polyethylene inner tubing of the present invention. Additionally, since the outer surface of the tubing is flexible PVC, the assembly of the injection set may be made using solvent bonding. This makes the mechanical integrity of the injection set substantially better than injection sets assembled using epoxy bonding. The injection set of the present invention also has a superior shelf life, and the economical construction using solvent bonding gives it a highly desirable competitive advantage over similar devices for insulin use made using epoxy bonding of polyethylene.

Claims: An injection set comprising a length of flexible tubing (10), a hollow needle (22), and a connector (30), the needle (22) having a holder (20) at or near its proximal end and having a free distal end, one end of the tubing (10) being mechanically connected to the proximal end of the needle (22) and being in fluid communication with the needle (22), and the other end of the tubing (10) being in fluid connection with the connector (30), characterised in that the one end of the tubing (10) is solvent-bonded to the holder (20), the other end of the tubing (10) is solvent-bonded to the connector (30), and the flexible tubing (10) is of multilayer construction comprising an inner layer (12) of a first material which is compatible with insulin and an outer layer (16) of a second material which is solvent-bondable to the material of the holder (20) and the connector (30). An injection set as claimed in Claim 1 characterised in that the inner layer (12) of the tubing (10) is made of polyethylene and the outer layer (16) of the tubing (10) is made of flexible polyvinyl chloride. An injection set as claimed in Claim 1 or Claim 2 characterised in that the tubing (10) has an intermediate layer (14) between the inner layer (12) and the outer layer (16). An injection set as claimed in any preceding claim characterised in that the intermediate layer is made of a material which has good adhesion qualities to both the first and second materials. An injection set as claimed in Claim 4 characterised in that the intermediate layer is made of ethylene-vinyl acetate. An injection set as claimed in any preceding claim characterised in that the holder (20) is insert moulded onto the needle (22) near its proximal end and has a cylindrical cavity (24) into which the proximal end of the needle (22) extends, the cylindrical cavity (24) having an opening through which the one end of the tubing (10) is inserted whereby the proximal end of the needle (22) is in fluid communication with the tubing (10), the inner surface of the cylindrical cavity (24) being solvent bonded to the outer layer (16) of the tubing (10). An injection set as claimed in Claim 6 characterised in that the holder (20) is made of hard polyvinyl chloride. An injection set as claimed in Claims 6 or 7, characterised in that the inner layer (12) of the tubing (10) is so arranged and configured as to overlap and to seal a portion of the proximal end of the needle (22). An injection set as claimed in any preceding claim characterised in that the connector (30) includes an internal flange (34) having an aperture (32) the tubing (10) being mounted in the connector (30) in an abutting relationship with the flange (34), and the aperture (32) in the flange (34) being aligned with the centre of the inner layer (12) of the tubing (10) and being in fluid communication with the tubing (10). A method of making an injection set, which comprises insert moulding a holder (20) of hard polyvinyl chloride around the proximal end of a hollow needle (22); inserting one end of a length of flexible tubing (10) into a cavity (24) in the holder (20), the tubing (10) being in fluid communication with the needle (22); and connecting the other end of the tubing (10) to a hard polyvinyl chloride connector (30), the needle (22) also being in fluid communication with the interior of the connector (30); characterised in that the flexible tubing (10) is of multilayer construction comprising an inner annular layer (12) of polyethylene and an outer annular layer (16) of flexible polyvinyl chloride, and by the steps of solvent bonding the outer layer (16) both to the interior of the cavity (24) and to the connector (30).

Inventors: KONOPKA, APRIL A.
Applicants: PACESETTER INFUSION LTD.
Application year: 1987
Main classification: A61M5
IPC codes: A61M5, A61L31, A61M39