Self-healing thermoplastic elastomer composition

Abstract

The self-healing membrane comprises a material having a molecular weight greater than 35 kDa, at least 50% by weight mineral oil, at least 40% styrenic block copolymer, and 0-10% polypropylene. The membrane may be utilized in any component of a closed system transfer device or system, such as a syringe adapter, patient connector, vial adapter, IV bag spike, etc. The membrane may also be utilized in other medical device components, more specifically, medical device components where the membrane is punctured by a needle.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 227,585, filed July 30, 2021, the entire disclosure of which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to self-healing thermoplastic elastomeric compositions. [Background technology]

[0003] Description of Related Art Healthcare providers who reconstitute, transport, and administer hazardous medications, such as cancer treatments, put the provider at risk of exposure to these medications and potentially pose a hazard to the healthcare environment. Unintentional exposure to chemotherapy can affect the nervous system, impair the reproductive system, and increase the risk of developing blood cancers in the future. Some medications must be dissolved or diluted before they are administered, which involves transferring a solvent from one container, by needle, to a sealed vial containing the medication in powder or liquid form. The drug can be inadvertently released into the atmosphere in gas form or by aerosolization during withdrawal of the needle from the vial and while the needle is in the vial if a pressure differential exists between the interior of the vial and the surrounding atmosphere. To reduce the risk of healthcare providers being exposed to toxic drugs, the transfer of these drugs is accomplished utilizing a closed system transfer device or system.

[0004] A closed system 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 penetrated by the needle of the syringe adapter. Thus, the membrane must meet the sealing and leakage requirements while limiting membrane fragmentation, which can generate small material particles as the needle penetrates the membrane, posing 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.

[0005] 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 the embodiments of the disclosure taken in conjunction with the accompanying drawings. [Brief description of the drawings]

[0006] [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] 3 is a cross-sectional view of the patient connector of FIG. 1 showing the patient connector inserted into the syringe adapter. [Figure 4] 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 diagram of the styrene-ethylenebutylene-styrene structure correlating with elasticity and processability of thermoplastic elastomers. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] Corresponding reference characters indicate corresponding parts throughout the several views. The illustrations presented herein illustrate exemplary aspects of the present disclosure, and such illustrations are not to be construed as limiting the scope of the present disclosure in any way.

[0008] 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 be readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the present invention.

[0009] For purposes of explanation hereinafter, the terms "top", "bottom", "right", "left", "vertical", "horizontal", "top", "bottom", "transverse", "vertical", and their derivatives refer to the invention as oriented in the drawings. It will be understood, however, that the invention may be subject to 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. As such, specific dimensions and other physical characteristics relating to aspects disclosed herein are not to be considered as limiting.

[0010] Unless otherwise indicated, all ranges or ratios disclosed herein should be understood to encompass the starting and ending values, and any and all subranges or subratios contained therein. For example, a specified range or ratio of "1 to 10" should be considered to include any and all subranges or subratios between (and including) the minimum value of 1 and the maximum value of 10, i.e., all subranges or subratios begin with a minimum value of 1 or greater and end with a maximum value of 10 or less.

[0011] The terms "first," "second," and the like are not intended to refer to any particular order or chronology, but rather to different conditions, properties, or elements.

[0012] 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 combination of any two or more of A, B, or C. For example, "at least one of A, B, and C" includes one or more A alone, or one or more B alone, or one or more C alone, or one or more A and one or more B, or one or more A and one or more C, or one or more B and one or more C, or all of A, B, and C.

[0013] In one aspect or embodiment of the present application, the self-healing membrane 10 includes a material having a molecular weight greater than 35 kDa, at least 50% by weight mineral oil, at least 40% styrenic block copolymer, and 0-10% polypropylene. The membrane 10 may be utilized 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, etc. The membrane 10 may be utilized with a syringe adapter as shown and described in U.S. Patent Application Publication No. 2015 / 0297454, which is incorporated herein by reference in its entirety. The membrane 10 may also be utilized in other medical device components, more specifically, medical device components in which the membrane 10 is punctured by a needle.

[0014] As shown in FIGS. 1-4, the membrane 10 is shown in association with a patient connector 16 that is utilized to connect one component of a closed system transfer device or system to a patient 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, IV bag, or other component. The membrane 10 is configured to prevent leakage through the membrane 10 when the membrane 10 is pierced by a cannula 20. In use, the cannula 20 of the syringe adapter 18 may pierce the membrane 10 and be withdrawn from the membrane quickly, e.g., in 10 seconds or less. The membrane 10 may also be utilized in scenarios where the cannula 20 of the syringe adapter 18 pierces the membrane 10 and remains in the pierced position for an extended period of time, e.g., an hour or more. Membrane 10 is configured to prevent leakage through membrane 10, for example, through an opening caused by cannula 20 puncturing membrane 10 or through an interface between cannula 20 and membrane 10. Top surface 24 of membrane 10 is configured to engage a corresponding membrane of another component, as described below. Membrane 10 may include a flange 28 as well as other features and structures.

[0015] 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 the 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 securing extension 52 at the first end 42 of the body 40, the securing 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.

[0016] 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 system transfer device or system. The syringe adapter 18 includes a housing 60 having a syringe adapter membrane 62 received therein 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 engage 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.

[0017] Thermoplastic elastomers (TPEs) offer similar properties to traditional rubber materials such as thermoset rubber and silicone rubber. TPEs are crosslinked by physical interactions of polymer chains rather than through covalent bonds, making them recyclable and easier to process compared to thermoset rubber and silicone. Extruded TPE articles are widely used as key components in medical device applications such as septa, stoppers, resealable membranes, and tubing, which generally require high elasticity, flexibility, and good stability.

[0018] The elasticity of TPEs results from styrenic block copolymers (SBCs) that form a phase separation between glassy and rubbery domains. Examples of SBCs include SBS block copolymers (styrene-butadiene-styrene), SIS block copolymers (styrene-isoprene-styrene), and SI / BS block copolymers (styrene-isoprene / butadiene-styrene), as well as hydrogenated SBCs such as SEBS (styrene-ethylenebutylene-styrene), SEPS (styrene-ethylene / propylene-3-methylbutene-styrene), SEEPS (styrene-ethylene-ethylene / propylene-styrene), and SIPS (styrene-isoprene-styrene-block copolymer). A typical TPE is formulated by blending SBCs, polyolefins such as PP and PE, plasticizers, fillers, stabilizers, and other additives. To obtain satisfactory elasticity for different TPE applications, both molecular weight and SBC structure affect the elasticity or resilience of the resulting TPE. Generally, higher molecular weight (Mw) SBC provides better elasticity due to longer and tighter polymer chain entanglement. However, the longer SBC chains with higher Mw (Mw>35kDa) are likely to be processed at much higher temperature / shear extrusion conditions or require sufficient time to reach a molten state for extrusion, so the proper selection of the appropriate SBC with the appropriate Mw is important to balance the elasticity and manufacturability of the TPE. Generally, there are two types of SBC: linear and radial structures. Most commercial grades of SBC are manufactured in linear structures by conventional anionic living polymerization, which provides superior performance in elastomer applications. The radial structure of SBC exhibits smaller molecular volume and similar Mw range, which allows easier melt processing and leads to more homogeneous TPE formulations after compounding. As shown in Figure 5, the resulting TPE with radial SEBS also provides great elasticity while exhibiting excellent processability.

[0019] Unlike isoprene rubber, the properties of TPEs can be optimized by compounding and compounding while also offering benefits such as better recyclability and manufacturing efficiency. Additionally, the benefit of switching from isoprene rubber to TPEs means fewer trade-offs in product requirements as TPEs are more easily tunable in composition for desired material properties. According to one aspect or embodiment of the present application, a material composition is provided that includes a blend of radially structured SEBS, PP copolymer, and mineral oil with self-sealing capabilities that enhance the leakage performance of needle-penetrable elastomeric articles. The TPE material of the present application meets the desired hardness and has a room temperature compression set of less than about 10%. Molded articles made from such TPE compounds are resealable and have demonstrated excellent leakage and fragmentation performance in needle-penetrable elastomeric articles, including closed system transfer device products. Although described in connection with membrane 10, the materials described below may be utilized for syringe adapter member 62 or any other membrane utilized in closed system transfer devices.

[0020] All TPE formulations were compounded on a Thermo Fisher 16mm twin screw extruder equipped with a customized strand die. The extruded polymer strands were cooled in a water bath and then chopped into pellets. DOE mixtures were designed with four different grades of SEBS, including three linear structure SEBS of low, medium and high molecular weight, and one radial structure SEBS of high molecular weight. In Table 1, eight formulations were made with 100 phr of SEBS each, as well as PP and oil with various phr. Both antioxidants and slip agents were also added to all eight formulations for material stability and processability purposes. Hardness was well controlled in the range of 25 Shore A to 35 Shore A, which is suitable for closed system transfer device applications, for example. Compression set at 22 hours and 96 hours was also tested. It is shown that COE-TPE 25, 27 and 28 performed best in compression set, which indicated the greater elastic properties provided by the higher molecular weight SEBS. All three TPEs, along with three off-the-shelf TPE references shown in Table 2, were compression molded into sheets for additional material characterization.

[0021] [Table 1]

[0022] In Table 2, COE-TPE 25, 27 and 28 are shown to have superior elastic property results from both compression set and DMA tan delta tests compared to the reference TPE, which generally correlates to the resealability of molded TPE parts after extended periods or multiple needle pierces. A simple and quick test was designed to evaluate the long-term resealability of TPEs in the form of disks. Disks were punched from molded TPE sheets and then crimped into vials containing dye solution. A needle was used to pierce the TPE disks nine times at the same location. For the tenth pierce, the needle was left in the disk for 96 hours. After the needle was withdrawn, the vials were inverted and placed on white paper for a few minutes to check for leakage from the pierced holes. The pierce score was determined by measuring the dab area on the paper, with the lowest value being the best performance. COE-TPE 25, 27 and 28 were leak-free after 96 hours of pierce testing. It has been clearly shown that both linear and radial structures of high Mw SEBS (Mw>35 kDa) result in better TPE compression set and DMA tan delta as well as penetration performance compared to reference TPEs likely made from low or medium Mw linear structure SEBS.

[0023] In addition, COE-TPEs 25, 27 and 28 also exhibited much lower adhesion levels versus the reference TPE from separation force tests between two identical TPE molded parts, providing advantages for the manufacturing assembly process. All six TPEs exhibited comparable and acceptable tensile strength, elongation at break and tear strength.

[0024] [Table 2]

[0025] All six TPEs, including three reference and three proprietary compounded TPEs, have been molded into parts and assembled into closed system transfer devices for product evaluation on short-term leakage, long-term leakage, fragmentation, and adhesion. As shown in Table 3, the use of appropriate SBCs (Mw>35kDa) with both linear and radial structures in appropriate compositions (>40% SEBS) significantly improves the short-term and long-term leakage of sealing articles without compromising their fragmentation and adhesion performance.

[0026] [Table 3]

[0027] The self-healing thermoplastic elastomers according to one aspect or embodiment of the present application provide the following properties: 1) significantly improved resealing properties of needle-penetrable elastomeric articles after prolonged compression due to the unique SEBS polymer structure (high Mw linear or radial, >35 kDa) and corresponding composition including 50% oil, >40% SBC, and <10% PP; 2) hardness (Shore A) that meets all requirements including leakage and fragmentation for closed system delivery device applications. 29±5), providing well-balanced mechanical properties including tensile (>3Mpa), tear (>12kNm), 96-hour compression set (<16%), and tan delta (<0.065), and potentially can be fine-tuned to other hardnesses for other needle-penetrable sealing applications, e.g., catheter septa, connectors, etc; 3) eliminating the use of silicone oil on the needle surface and sealing component surfaces, preventing drug interaction with silicone oil, potentially increasing the flow rate of the drug delivery system without compromising the fragmentation performance of needle-penetrable septa, thus improving the safety and efficacy of the drug delivery device.

[0028] Although the present disclosure has been described as having an exemplary structure, the present disclosure may 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 its general principles. Moreover, this application is intended to cover such departures from the present disclosure as come within the known or customary practice in the art to which the disclosure pertains and fall within the scope of the appended claims. To the extent possible, one or more features of any aspect or embodiment described above may be combined with one or more features of any other aspect or embodiment.

Claims

1. A self-healing membrane comprising a material having a molecular weight greater than 35 kDa, at least 50% by weight mineral oil, at least 40% styrene block copolymer, and 0-10% polypropylene.

2. The membrane of claim 1 , wherein the material contains at least one of a linear structure or a radial structure.

3. The membrane of claim 1, wherein the material has a Shore A hardness of 24-34.

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

5. 10. The membrane of claim 1, wherein the material has a tear resistance of greater than 12 kNm.

6. 10. The membrane of claim 1, wherein the material has a 96 hour permanent set of less than 16%.

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

065.

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

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