Additive-modified thermoplastic elastomer composition

Abstract

A membrane modified with an ultra-high molecular weight siloxane polymer for use in closed system transfer device membranes.

Description

[Technical field]

[0001] Field of Disclosure The present disclosure relates generally to thermoplastic elastomeric compositions for use in membranes for medical devices. [Background technology]

[0002] This application claims priority to U.S. Provisional Application No. 63 / 230,979, filed August 9, 2021, entitled "Additive-Modified Thermoplastic Elastomer Compositions," the entire disclosure of which is incorporated herein by reference in its entirety.

[0003] 2. Description of Related Art Healthcare workers reconstitute, transport, and administer hazardous drugs, such as cancer drugs, which can put health care workers at risk for exposure and pose hazards 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 during the withdrawal of the needle from the vial and while the needle is inside the vial if there is a pressure difference between the inside of the vial and the surrounding atmosphere. To reduce the risk of exposure to toxic drugs for health care workers, the transfer of these drugs is performed using closed transfer devices or systems.

[0004] A closed transfer device or system can utilize a membrane to ensure the safe transfer of fluids between components. For example, a syringe adapter can include a membrane that contacts the membrane of a mating component such as a patient connector, IV bag spike, or vial adapter. Elastomers are commonly used to form fluid-tight seals between parts that move relative to one another. In particular, elastomers are useful for forming fluid-tight seals against piercing needles. Thermoplastic elastomers (TPEs) are used throughout the medical industry because they are easily manufactured and exhibit unique properties that allow the performance of specific functions to be easily optimized. TPEs are similar to synthetic rubber elastomers (or called thermoset rubbers) in that they are stretchable, but do not rely on a permanent crosslinked structure for their stretch properties. This, in turn, allows the properties of TPEs to be optimized through formulation and compounding, while also providing benefits such as better recyclability and manufacturing efficiency.

[0005] Current closed transfer devices or systems may include a membrane formed from a thermosetting isoprene rubber that is pierced by the needle of a syringe adapter. The membrane of the closed transfer device is required to be resealable and have suitable detachment force, fragmentation, and membrane cohesion. Thus, the membrane is required to meet the requirements for seal and leakage while limiting membrane fragmentation, which can generate 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. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] US Patent Application Publication No. 2015 / 0297454 Summary of the Invention [Problem to be solved by the invention]

[0007] 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]

[0008] Summary of the Invention According to one embodiment of the present invention, the ultra-high molecular weight siloxane film contains 0.5% to 2.5% of a lubricant additive material.

[0009] According to another embodiment of the present invention, the ultra-high molecular weight siloxane film includes 0.5% to 2% of a lubricant additive material.

[0010] According to another embodiment of the present invention, the ultra-high molecular weight siloxane film includes 0.5% to 1% of a lubricant additive material.

[0011] According to another embodiment of the present invention, the ultra-high molecular weight siloxane film includes 1% to 2.5% of a lubricant additive material.

[0012] According to another embodiment of the present invention, the ultra-high molecular weight siloxane film includes 1% to 2% of a lubricant additive material.

[0013] According to another embodiment of the present invention, the ultra-high molecular weight siloxane film includes a second lubricant additive material.

[0014] According to another embodiment of the present invention, the lubricant additive material is Dow Corning MB50-002 and / or Silaplast ES7722-DS.

[0015] According to another embodiment, the ultra-high molecular weight siloxane film contains two lubricity additives at concentration levels of 0.5% to 3%.

[0016] According to another embodiment, the ultrahigh molecular weight siloxane film is used in a medical device. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is an illustration of the setup of Compression Set B (CSB) according to conventional testing procedures. [Diagram 2] FIG. 2 is an illustration of a SEM image of a top surface of a sample in accordance with one embodiment of the present invention. [Diagram 3] FIG. 3 is a graphical representation of a leakage plot of an injector membrane and a connector membrane in accordance with an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] 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.

[0019] 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 are not to be construed as limiting the scope of the present disclosure in any way.

[0020] Detailed Description 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.

[0021] 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 respective 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.

[0022] 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.

[0023] The terms "first", "second", etc. do not imply a particular order or chronology but rather refer to different conditions, characteristics, or elements.

[0024] 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.

[0025] One potential solution to the problems identified above is to apply lubricants or low surface energy polymers such as fluororesins or silicone emulsions directly to the membrane surface by spray coating or dipping techniques to reduce friction between the needle and membrane. Due to inherent limitations in polymer migration, this method is not applicable to thick membranes and is not suitable for multi-penetration applications. Another solution is to use thermoplastic elastomers.

[0026] In one aspect or embodiment of the present invention, a very small amount of a lubricant, such as an ultra-high molecular weight siloxane polymer, is compounded into a thermoplastic elastomer formulation for use in medical device membranes. The resulting material enhances the inherent lubricity of the siloxane polymer. Furthermore, such high molecular weight and pre-compounded olefin-based masterbatches aid in uniform blending and reduce the tendency for migration to surfaces. Parts molded with this new compound improve fragmentation and reduce membrane tack and adhesion while causing minimal scarring to leak performance. This additive can also be utilized in other TPE-related applications.

[0027] The membrane can 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 can 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 can also be utilized in other medical device components, more specifically, medical device components where the membrane is pierced by a needle.

[0028] 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 more recyclable and easier to process than thermoset rubber and silicones. Extruded and molded 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.

[0029] The various formulations are shown in Table 1. Compounding extrusion was used to produce all the formulations in Table 1 with the two lubricant additives at various concentration levels ranging from 0.5% to 3%. The resulting resins were molded into standard ASTM sheets and samples were prepared for tensile, tear, compression set, and wear testing. The resulting materials were evaluated to understand how the additive concentration of the TPE affects the mechanical properties of the material, which potentially impacts the product performance later.

[0030] [Table 1]

[0031] One lubricity additive, Dow Corning MB50-002, was identified as being compoundable with TPE formulations at various loadings ranging from 0.5% to 2% as shown in Table 2. The resulting lubricity additive modified TPEs were processed by injection molding and the molded parts were assembled for product testing. The assembled closed system delivery medical devices were then tested for product performance including leakage, fragmentation, attachment force, and peel force.

[0032] [Table 2]

[0033] All extrusion compounds using siloxane fillers were then characterized using mechanical methods. Tensile tests were performed on samples prepared from the molding materials according to ASTM D412. Five tensile tests were performed on each sample and the tensile strength was calculated from the data and reported in Table 3. MB50 was found to consistently improve tensile strength by up to 25% while the Silaplast additive maintained the same performance.

[0034] [Table 3]

[0035] Tear strength was performed using ASTM D624 tear strength samples prepared from the molding materials. Four samples were run for each material and tear strength was calculated from the test results and is shown in Table 3. Both MB50 and Silaplast improved tear strength at silicone additive loadings of 5 phr or less.

[0036] Abrasion testing was performed to understand the notch depth after exposure to repeated surface abrasion. Briefly, a 50g weight was used to cyclically scrape the surfaces of all manufactured formulations for a total of 1120 cycles, with the scraper tip being cleaned with isopropyl alcohol and Kimwipes after every 280 cycles. The materials were allowed to rest for 24 hours before being placed on a profilometer to measure the abrasion depth. Table 3 provides an overview of the abrasion depth obtained from the software. It is clearly shown that increasing the MB50 load reduces the notch depth by more than 25%. This improvement in properties correlates with the improved fragmentation and adhesion performance of the new film formulation.

[0037] Compression set (CSB) was measured according to ASTM D395 using a CSB setup as shown in Figure 1. The polymer sample was placed between metal plates with a metal spacer of known thickness. After placing the material in the setup and clamping the device, the material was allowed to rest for a set time, after which the device was disassembled and the material was allowed to rest for a short time before measurements were taken. Twelve 10 mm wide disks were cut from the molded sheet and stacked four of each to create samples with thicknesses of 6.5 to 7.5 mm. After measuring the thickness of the sample, a 4.8 mm thick metal washer was placed in the setup and compressed to 4.8 mm and left at room temperature for 22 hours. It was then compressed to 4.8 mm and left at room temperature for 22 hours. After releasing these, they were left at rest for 30 minutes and the new thickness was measured. The average CSB of all samples and its standard deviation were calculated using equation (1).

[0038] Formula 1:

[0039]

number

[0040] T 初期 is the initial thickness of the four laminated disks, T 最終 is the thickness after 22 hours of compression and 30 minutes of rest, T スペーサー is the thickness of the washer used as a spacer (4.8 mm). The calculation results are shown in Table 4.

[0041] [Table 4]

[0042] For the base formulations, M3 and S2 shown in Table 4, 10 mm flat disks of material were used for testing. For Mediprene and other MB50 containing Mediprene formulations, molded connector membranes were used for testing shown in Table 5.

[0043] [Table 5]

[0044] Adding lubricant additive at levels above 5 phr (~2 wt%) increased the compression set for both MB50 and Silaplast, as shown in Table 3. When the loading of MB50 in the TPE formulation was reduced to below 2 wt%, the compression set remained in the same range, as shown in Table 5.

[0045] The coefficient of friction (COF) and contact angle were also measured for the material surface properties, as shown in Table 6. The addition of the lubricity additive significantly reduced both the static and kinetic coefficients of friction by approximately 50%. The contact angle results show that Silaplast ES7722-DS lowered the surface energy, while Dow Corning® MB 50-002 maintained nearly the same value. This improved property also correlates well with the improved tack, fragmentation, and adhesion performance of the new film formulation.

[0046] [Table 6]

[0047] To understand the distribution of silicone additive throughout the TPE samples, one of the TPE formulations (M3) was selected to measure the material composition distribution using SEM. The carbon, oxygen, and silicon of the top, bottom, and cross-section of the membrane were mapped in the EDS mode of the SEM, as shown in Figure 2. With continued reference to Figure 2, (a) reflects the SEM and EDS mapping of the top surface of the TPE with silicone additive, (b) reflects the SEM and EDS mapping of the bottom surface of the TPE with silicone additive, and (c) reflects the SEM and EDS mapping of the cross-section of the TPE with silicone additive.

[0048] As shown in Table 7, the silicon atomic % remained in the same order of magnitude between the two surfaces (top and bottom) and cross sections with values ​​ranging from 0.1% to 0.18%, indicating a uniform distribution of the lubricity additive in the film formulation of the present invention. This characteristic indicates improved lubricity of the film both inside and outside.

[0049] [Table 7]

[0050] The tack performance of the new formulation was measured by the membrane peel force, where two flat-surfaced membranes were pressed together and separated by an Instron to simulate the worst case in the storage / shipping / assembly process. As shown in Table 8, the addition of an ultra-high molecular weight siloxane polymer, such as Dow Corning® MB50-002, improved the tack performance of the new membrane formulation. This reduces the membrane scrape rate, improves manufacturing efficiency, and reduces the overall cost of the product.

[0051] [Table 8]

[0052] As shown in Table 9, in the absence of silicone oil on the needle surface and membrane pocket, the fragmentation performance of the new membrane met the pass requirements and was significantly improved by the addition of the ultra-high molecular weight siloxane polymer additive. The inherent lubricity of the new membrane formulation modified with the new additive significantly reduced the friction between the needle and membrane, reducing fragmentation along with the safety performance of the CSTD product.

[0053] [Table 9]

[0054] As shown in Table 10, without silicone oil on the needle surface and membrane pocket, the attachment performance of the novel membrane met the pass requirements and was significantly improved with the addition of ultra-high molecular weight siloxane polymer additive. The inherent lubricity of the novel membrane formulation modified with ultra-high molecular weight siloxane polymer significantly reduced the friction between the needle and membrane, resulting in reduced adhesion along with the safety performance of the closed system transfer device product.

[0055] [Table 10]

[0056] As shown in Figure 3, the new membrane formulation with <1% addition of ultra-high molecular weight siloxane polymer such as Dow Corning® MB50-002 improved the leak performance of the membrane without silicone oil on the needle surface and membrane pocket. With continued reference to Figure 3, note that N is the injection membrane and CS is the connector membrane. The inherent lubricity of the new membrane formulation modified with lubricant additive significantly reduced the friction between the needle and membrane, resulting in less coring and damage of the membrane during the needle penetration process and improved the sealing performance of the closed system transfer device product.

[0057] 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. An ultra-high molecular weight siloxane film containing 0.5% to 2.5% of a lubricant additive material.

2. 10. The film of claim 1, wherein the ultra-high molecular weight siloxane film comprises 0.5% to 2% of a lubricant additive material.

3. 10. The film of claim 1, wherein the ultra-high molecular weight siloxane film comprises 0.5% to 1% of a lubricant additive material.

4. 10. The film of claim 1, wherein the ultra-high molecular weight siloxane film comprises 1% to 2.5% of a lubricant additive material.

5. 10. The film of claim 1, wherein the ultra-high molecular weight siloxane film comprises 1% to 2% of a lubricant additive material.

6. The film of claim 1 further comprising a second lubricant additive material.

7. The membrane of any one of claims 1 to 6, wherein the lubricant additive material is Dow Corning MB50-002 and / or Silaplast ES7722-DS.

8. The film of any one of claims 1 to 3, comprising two lubricating oil additives at a concentration level of 0.5 to 3%.

9. 10. The membrane of claim 1 for use in a medical device.

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