Thermoplastic elastomer composition for closed system transfer device

Abstract

A membrane for a closed system transfer device comprising 40-50% styrenic block copolymer, 0-10% polypropylene, and 45-60% mineral oil by weight. This membrane can be utilized in any element of a closed system transfer device or system, such as syringe adapters, patient connectors, vial adapters, IV bag spikes, etc. This membrane can also be used in cases where the cannula of the syringe adapter pierces the membrane and remains in the pierced position for an extended period of time, such as an hour or more.

Description

[Technical field]

[0001] Field of the Disclosure FIELD OF THE DISCLOSURE The present disclosure relates generally to thermoplastic elastomer compositions for closed system transfer devices. [Background technology]

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application Serial No. 63 / 227,570, filed July 30, 2021, the disclosure of which is incorporated herein by reference in its entirety.

[0003] 2. Description of Related Art Healthcare workers who reconstitute, transport, and administer hazardous drugs, such as cancer drugs, are at risk for exposure to these drugs, which can pose a hazard in the healthcare environment. Unintentional exposure to chemotherapy can affect the nervous system, damage the reproductive system, and increase the risk of developing blood cancers in the future. Some drugs must be dissolved or diluted before administration, which requires the transfer of a solvent from one container to a sealed vial containing the powdered or liquid drug using a needle. Drugs can be inadvertently released into the atmosphere in gas form or by aerosolization when the needle is removed from the vial or while the needle is in the vial if there is a pressure difference between the interior of the vial and the surrounding atmosphere. To reduce the risk of exposure of healthcare workers to toxic drugs, the transfer of these drugs is done using closed transfer devices or systems. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] US Patent Application Publication No. 2015 / 0297454 Summary of the Invention [Problem to be solved by the invention]

[0005] A closed transfer device or system may utilize a membrane to ensure the safe transfer of fluid between components. For example, a syringe adapter may include a membrane that contacts the membrane of a mating component, such as a patient connector, an IV bag spike, or a vial adapter. The membrane may be formed from a thermosetting isoprene rubber and is pierced by the needle of the syringe adapter. Thus, the membrane must meet sealing and leakage requirements while limiting membrane fragmentation, which can result in small material particles as the needle penetrates the membrane and pose a risk to the patient. A lubricant, such as silicone oil, can be applied to the needle surface and membrane to minimize membrane fragmentation. However, the use of lubricants on the needle and membrane surfaces can affect the leak performance, fragmentation, and flow rate through the syringe adapter. [Means for solving the problem]

[0006] The above and other features and advantages of the present disclosure, as well as the manner in which they are accomplished, will become more apparent, and the disclosure itself will be better understood, by reference to the following description of embodiments of the disclosure taken in conjunction with the accompanying drawings, in which: [Brief description of the drawings]

[0007] [Figure 1] FIG. 1 is a front view of a patient connector according to one aspect or embodiment of the present application. [Diagram 2] 2 is a cross-sectional view of the patient connector of FIG. 1. FIG. [Diagram 3] FIG. 3 is a cross-sectional view of the patient connector of FIG. 1 showing the patient connector being inserted into the syringe adapter. [Figure 4] FIG. 4 is a cross-sectional view of the patient connector of FIG. 1 showing the patient connector inserted into the syringe adapter. [Diagram 5] FIG. 5 is a graph showing the final membrane fragmentation scores and average test results. [Figure 6]FIG. 6 is a graph showing the number of counted particles and the average value of the membrane fragmentation individual value plot in category 2 (50 um≦x≦100 um) and category 3 (x>100 um). [Figure 7] FIG. 7 is a graph showing a scatter plot of the average final fragmentation score versus percent oil. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set forth herein illustrate exemplary embodiments of the present disclosure, and such exemplifications should not be construed as limiting the scope of the present disclosure in any way. Detailed Description

[0009] The following description is provided to enable a person skilled in the art to make and use the described embodiments contemplated for practicing the invention. However, various modifications, equivalents, variations, and alternatives will remain readily apparent to those skilled in the art. All such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the present invention.

[0010] In the following description, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and derivatives thereof, refer to the invention as oriented in the figures of the drawings. It should be understood, however, that the invention may assume various alternative modifications unless expressly specified to the contrary. It should also be understood that the specific devices illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting.

[0011] Unless otherwise indicated, all ranges or ratios disclosed herein should be understood to encompass the starting and ending values, as well as any subranges or subratios subsumed therein. For example, a stated range or ratio of "1 to 10" should be considered to include any subrange or subratio between (and including) the minimum value of 1 and the maximum value of 10, i.e., any subrange or subratio beginning with a minimum value of 1 or greater and ending with a maximum value of 10 or less.

[0012] The terms "first," "second," and the like are not intended to refer to a particular order or chronology, but rather to different conditions, characteristics, or elements.

[0013] As used herein, "at least one" is synonymous with "one or more." For example, the phrase "at least one of A, B, and C" means any one of A, B, or C, or any two or more of A, B, or C in combination. For example, "at least one of A, B, and C" includes one or more of A alone, one or more of B alone, one or more of C alone, one or more of A and one or more of B, one or more of A and one or more of C, one or more of B and one or more of C, or one or more of all of A, B, and C.

[0014] In one aspect or embodiment of the present application, the membrane 10 for a closed system transfer device comprises a material having 40-50% by weight styrenic block copolymer, 0-10% by weight polypropylene, and 45-60% by weight mineral oil. The membrane 10 can be used in any component of a closed system transfer device or system, such as a syringe adapter, a patient connector, a vial adapter, an IV bag spike, and the like. The membrane 10 can be utilized with a syringe adapter as shown and described in U.S. Patent Application Publication No. 2015 / 0297454, the entirety of which is incorporated herein by reference.

[0015] With reference to Figures 1-4, the membrane 10 is shown connected to a patient connector 16 that is utilized to connect one component of a closed system transfer device or system to a patient's venous line. For example, the patient connector 16 may be connected to a syringe adapter 18 to facilitate the transfer of fluid from one container, such as a syringe barrel, to another container or line, such as an intravenous line, an IV bag, or other component. The membrane 10 is configured to prevent leakage through the membrane 10 when the membrane 10 is punctured by a cannula 20. During use, the cannula 20 of the syringe adapter 18 may puncture the membrane 10 and be quickly withdrawn from the membrane, such as in 10 seconds or less. The membrane 10 may also be utilized in a scenario where the cannula 20 of the syringe adapter 18 punctures the membrane 10 and remains in the punctured position for an extended period of time, such as an hour or more. Membrane 10 is configured to prevent leakage through it, such as through an opening caused by cannula 20 puncturing membrane 10 or through an interface between cannula 20 and membrane 10. Top 24 of membrane 10 is configured to mate with membranes of other components, as described below. Membrane 10 may include a flange 28, among other features and structures.

[0016] 1 and 2, the patient connector 16 includes a body 40 having a first end 42 and a second end 44, the body 40 defining a passageway 46, a line connection 48 disposed at the second end 44 of the body 40, and a membrane 10 disposed at the first end 42 of the body 40. The line connection 48 may be a luer lock connection, although other suitable connections may be utilized. The membrane 10 is received by an opening 50 defined by the body 40 of the patient connector 16. The opening 50 of the patient connector 16 is wider than the passageway 46. The body 40 of the patient connector 16 includes a locking extension 52 at the first end 42 of the body 40, the locking extension 52 extending radially inwardly and configured to secure the membrane 10 to the body 40 of the patient connector 16. The patient connector 16 also includes a locking arrangement 54 configured to secure the patient connector 16 to the syringe adapter 18.

[0017] In a further aspect or embodiment, a system 58 for closed transfer of fluids includes a patient connector 16 and a syringe adapter 18, although the system 58 may also include other components of a closed transfer device or system. The syringe adapter 18 includes a housing 60 having a syringe adapter membrane 62 received within the housing 60 and a cannula 20. The syringe adapter membrane 62 is movable from a first position within the housing 60 of the syringe adapter 18 to a second position within the housing 60 when the patient connector 16 is disposed within the housing 60 of the syringe adapter 18, as shown in FIG. 4. The membrane 10 of the patient connector 16 is configured to mate with the syringe adapter membrane 62. The cannula 20 is configured to pierce the membrane 10 of the patient connector 16 and the syringe adapter member 62 when the patient connector 16 is disposed within the housing 60 of the syringe adapter 18. The syringe adapter membrane 62 is received by a collet 64, although other suitable arrangements may be utilized. The syringe adapter 18 includes a luer connector 66 configured to be secured to a syringe barrel. The operation of the syringe adapter 18 is described in U.S. Patent Application Publication No. 2015 / 0297454. Thus, the membrane 10 and the syringe adapter member 62 must maintain a seal to form a closed system while minimizing fragmentation of material during puncture of the membranes 10, 62 by the cannula 20.

[0018] One potential solution to meet the membrane fragmentation and sealing requirements is to apply a lubricant or other low surface energy polymer, such as a fluororesin or silicone emulsion, directly to the surface of the membrane 10 by spray coating or dipping techniques to reduce friction between the needle and the membrane. Due to the inherent mobility limitations of the polymer, this method is not applicable to thick membranes and is not compatible with multi-penetration applications and complex manufacturing processes. Another solution is to use thermoplastic elastomers (TPEs). TPEs are similar to synthetic rubber elastomers in that they are stretchable, but do not rely on permanent crosslinking for their stretchability. Therefore, the properties of TPEs can be optimized through formulation and compounding, and they also offer benefits such as better recyclability and manufacturing efficiency. Additionally, the advantage of switching from isoprene rubber to TPEs is that TPEs are easier to tailor in composition to the desired material properties, resulting in fewer trade-offs in product requirements.

[0019] In one aspect or embodiment, membrane 10 is provided with a high loading of mineral oil in the range of 40-63%. The resulting TPE material, through proper selection and appropriate loading of styrenic block copolymer (SBC) and polypropylene (PP), improves on the inherent lubricity from the mineral oil while maintaining other important mechanical properties including hardness, tensile, tear, compression set, etc. Although described in the context of membrane 10, the materials described below may be utilized in syringe adapter member 62, or other membranes utilized in closed system transfer devices.

[0020] The TPE materials were evaluated through both material characterization and product performance evaluation. For example, Table 1 lists six TPE material compositions having hardness ranging from 25 to 38 Shore A for evaluation in membrane applications in closed system transfer devices such as applications in membrane 10 or syringe adapter member 62. Material properties including tensile, tear, compression set, and tan δ were evaluated by standard methods and are summarized in Table 2.

[0021] [Table 1]

[0022] [Table 2]

[0023] After material characterization, all six TPEs were molded into membrane components and assembled into final products to evaluate their performance, including leakage and fragmentation. As shown in Table 3, TPE-3-5 passed all requirements, while other TPEs outside this composition range failed to meet all the critical requirements for closed system transfer equipment applications. Considering all product test results, it was concluded that a soft TPE with an ideal composition containing 45% to 60% mineral oil and 40% to 50% SBC and PP, more specifically, 40% to 50% SBC and 0% to 10% PP without fillers, was most suitable for closed system transfer equipment membrane applications.

[0024] [Table 3]

[0025] As shown in Figure 5, the higher oil concentration of the new TPE formulation also improved the fragmentation performance of the product, in this case, all six TPEs passed fragmentation without the application of silicone lubricant on the needle and membrane pocket. TPE-6, with the highest oil loading of 63%, showed the best fragmentation performance among all the candidates. Figure 6 also shows that TPE-6 performed best in category 3 for particle counts above 100um, while TPE-1, with the lowest oil % of 40%, generated the highest particle count in the same category. Further analysis in Figure 7 showed a linear relationship between the oil % of the TPE and the fragmentation score (average value), and a similar relationship was observed between the oil % of the TPE and the particle counts (average value) in fragmentation category 3 (Figure 6). Thus, fragmentation performance is strongly correlated with the oil % of the TPE.

[0026] However, as shown in Table 3, too much oil in a TPE formulation such as TPE-6 will result in low mechanical strength such as hardness, tensile, tear, compression set, and tan δ, which will impair the sealing ability of the TPE membrane. Too little oil in a TPE formulation such as TPE-1 and TPE-2 will result in high hardness and low elasticity of the TPE material, which will impair the sealing ability of the TPE membrane and the needle penetration force to the components of the closed system transfer device. The new TPE composition contains 45% to 60% mineral oil by weight, 40% to 50% SBC and PP by weight, more specifically, 40% to 50% SBC without filler and 0% to 10% PP by weight, which is optimal for closed system transfer device membrane applications.

[0027] The newly formulated thermoplastic elastomer as a sealing component of closed system transfer devices offers unique properties for sealing applications including: 1) unique composition of 45-60% oil, 40-50% SBC, 0-10% PP provides well-balanced mechanical properties including hardness (Shore A 32.5±6), tensile (>4Mpa), tear (>15kNm), 96hr compression set (<17%), tan δ (<0.07) to meet all requirements including leakage and fragmentation for needle-penetrable sealing part applications; 2) increased mineral oil loading significantly reduces the occurrence of fragmentation for needle-penetrable septum applications, improving safety and efficacy of closed system transfer device products with better fragmentation performance; and 3) elimination of the use of silicone oil on the needle surface and within the membrane pocket, preventing drug-silicone oil interaction and potentially increasing flow rate of drug delivery systems.

[0028] Although the present disclosure has been described as having an exemplary design, the present disclosure can be further modified within the spirit and scope of the present disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the present disclosure using the general principles of the present disclosure. Moreover, this application is intended to cover such departures from the present disclosure as are within the known or customary practice in the art to which the present disclosure pertains and fall within the limits of the appended claims. To the extent possible, one or more features of any aspect or embodiment described above can be combined with one or more features of any other aspect or embodiment.

Claims

1. A membrane for a closed system transfer device comprising a material consisting of 40-50% by weight styrene-based block copolymer, 0-10% by weight polypropylene, and 45-60% by weight mineral oil.

2. The membrane of claim 1, wherein the material has a Shore A hardness of 26.5 to 38.

5.

3. The membrane of claim 1 , wherein the material has a tensile strength greater than 4 Mpa.

4. 10. The membrane of claim 1, wherein the material has a tear resistance of greater than 15 kNm.

5. 10. The film of claim 1, wherein the material has a 96 hour compression set of less than 17%.

6. 10. The membrane of claim 1 , wherein the material has a tan δ of less than 0.

07.

7. The membrane of claim 1 , wherein the outer surface of the material is free of silicone oil.

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