Method of manufacturing stopper with septum for medical container, stopper and polymer composition for septum

Abstract

To provide a method of manufacturing a stopper with a septum capable of preventing liquid from leaking for a long period of time.SOLUTION: A manufacturing method for a stopper to be used in a medical container, the stopper having a septum and a housing supporting the septum, comprises: creating the septum by a first molding process using a thermoplastic elastomer composition; creating the housing by a second molding process using a plastic composition, and allowing the septum to be pre-compressed in a radial direction perpendicular to a needle penetration direction of the septum by the second molding process; and subjecting the stopper to a steam sterilization. After the septum is subjected to the steam sterilization, the septum exhibits a residual pre-compression level of 12% to 30% in the radial direction compared to when the septum is uncompressed, and the residual pre-compression level is measured based on a thickness or average diameter of the septum.SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a non-provisional patent application that claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 538,687, filed September 15, 2023, and entitled "METHOD OF MANUFACTURING STOPPER WITH SEPTUM FOR MEDICAL CONTAINER, THE STOPPER AND POLYMER COMPOSITION FOR THE SEPTUM," which is incorporated herein by reference.

[0002] The present invention relates to a stopper with a septum for a medical container and a method for making said stopper, said septum being made from a polymer composition, in particular a polymer composition comprising a thermoplastic elastomer (TPE). [Background technology]

[0003] A medical infusion bag is a container that is typically used to package liquids such as blood or infusions. To prevent the filled liquid from leaking, a stopper is embedded in the opening of the container. Typically, the stopper structure includes a septum and a housing that supports the septum. During use, a needle can pierce the septum and release the liquid. Therefore, if the needle is removed or left inserted for a long time, a septum leak may occur.

[0004] To address this issue, Patent Document 1, CN1091023C, discloses a rubber stopper in which the diameter of at least one of the upper and lower surfaces of the rubber stopper shrinks by 1-10% when compressed by an external holder. Patent Document 2, TW570824B, discloses a needle stopper having a puncture section made of a thermoplastic elastomer, which is heat-treated at 80-120°C to relieve internal stress. Although these prior art documents claim to prevent septum leakage, in reality, various problems still need to be improved. Summary of the Invention [Problem to be solved by the invention]

[0005] Effects of permanent compression and thermal stress (tension)

[0006] The inventors of the present application have found that when a needle is inserted into a septum for a long period of time, a slit is likely to occur at the insertion site due to compression deformation, resulting in unavoidable leakage, especially when the IV bag contains high liquid pressure. Furthermore, when the surface tension of the liquid is low, leakage can occur even at low liquid pressure. Furthermore, in the process of first molding the plastic housing by injection molding and then molding the TPE septum by injection molding, the large thermal contraction of the septum material during the cooling process (from about 200°C to room temperature) generates internal tension. The coefficient of thermal expansion (CTE) of low-elasticity elastomers is about 200-250×10 -6 / ℃, and the thermal expansion coefficient of PP is about 60~100×10 -6 / °C. This internal tension can be partially released during steam sterilization, but is never completely released. This tension exacerbates the slit created by the insertion of the needle.

[0007] The inventors of the present application also noticed that in the stopper assembly disclosed in Patent Document 1, which uses a rubber stopper as a septum, a synthetic resin film must be added between the rubber stopper and the outer holder to bond them together due to the incompatibility between the rubber and the outer holder. In Patent Document 2, a thermoplastic elastomer is used in the puncture part (septum), but since residual stress in the puncture part easily causes liquid leakage, Patent Document 2 requires that the puncture part be heat-treated to remove the stress. The methods of Patent Documents 1 and 2 increase the complexity of the septum manufacturing process. On the other hand, the inventors of the present application found that when a thermoplastic elastomer septum is given a shrinkage as described in Patent Document 1, the diameter shrinkage rate is already as high as 8%, and still cannot meet the expected leakage prevention effect, and further unexpectedly found that the shrinkage rate of the thermoplastic elastomer septum continues to decrease slowly when the storage time is extended or when the septum is stored under an unfavorable environment. [Means for solving the problem]

[0008] The present invention provides mechanical pre-compression of the septum to overcome the effects of the permanent compression deformation and thermal stress mentioned above. The septum is made of a thermoplastic elastomer, and does not require an additional synthetic resin film between the septum and the support housing. Furthermore, after steam sterilization, the stopper of the present invention maintains a residual pre-compression level of 12%-30%, preferably 12%-25%, more preferably 12%-20% in the radial direction. This high level of residual pre-compression allows the septum to retain sufficient internal compression stress for a long period of time. When the internal compression stress gradually decreases due to changes in the external environment, the septum of the present invention with its high internal compression stress prevents this stress from quickly decreasing below the critical value. Thus, the septum of the present invention can effectively prevent liquid leakage for a long period of time, which is advantageous for storage and other multi-purpose applications. Furthermore, the septum of the present invention does not become excessively stiff due to the high residual pre-compression level, and maintains good puncture performance.

[0009] Furthermore, in preferred embodiments, the thermoplastic elastomer septa of the present invention do not require heat treatment or other pretreatment to relieve stress prior to precompression.

[0010] The present invention provides a method for producing a pre-compressed elastomeric septum suitable for co-injection molding, insert molding, overmolding, or multi-shot injection molding processes, rather than first injection molding a plastic housing and then injection molding the elastomeric septum.

[0011] The method of the present invention includes (1) first, an overmolding process injecting a molded elastomeric septum (e.g., using a thermoplastic elastomer composition) or an insert molding process using a molded elastomeric septum as an insert member, and (2) a process of injection molding a plastic housing around the elastomeric septum in a radial direction. The injection temperature, injection pressure and holding pressure must be high enough to (i) cause a large radial compression of the elastomeric septum, and (ii) bond firmly to the elastomeric septum. In a preferred embodiment, the common lower mold for supporting the elastomeric septum is provided with a movable pin below the centerline of the elastomeric septum, forming a cavity for the elastomeric septum to expand. In a preferred embodiment, a plastic melt is used to compress the elastomeric septum radially inward, which causes the elastomeric septum to radially compress and expand axially (i.e., perpendicular to the radial direction) into the cavity. As a result, the elastomeric septum is radially compressed by the plastic housing, creating a built-in pre-compression. Effect of the Invention

[0012] In some embodiments, the invention provides at least one of the following features.

[0013] The present invention provides a stopper (e.g., a plug for an IV container) with an elastomeric septum (e.g., when using a thermoplastic elastomer composition) that has a high level of residual precompression in the radial direction (a direction substantially perpendicular to the needle insertion direction) that can quickly reseal to prevent leakage after needle withdrawal.

[0014] The present invention uses a co-injection molding process, an insert molding process, an overmolding process, or a multi-shot injection molding process to first mold an elastomeric septum (e.g., a thermoplastic elastomer composition) and then mold a plastic housing. In the molding step of the plastic housing, the present invention utilizes the pressure of the plastic melt of the plastic housing to radially inwardly compress the elastomeric septum (e.g., a thermoplastic elastomer composition) and deform the elastomeric septum into space in the axial direction (i.e., in a direction perpendicular to the radial direction), thereby generating a radial pre-compression.

[0015] The desired pre-compression level produced by co-injection molding process, insert molding process, overmolding process, or multi-shot injection molding process should be more than 12% to 40% or less. After steam sterilization at 110°C or 121°C for 30 minutes, the residual pre-compression level should be 12% to 30% or less, preferably 12% to 25% or less, and more preferably 12% to 20% or less. The pre-compression level and the residual pre-compression level of the septum are calculated based on the thickness or average diameter of the septum at the molding step.

[0016] The precompressed septum concept of the present invention may be applied to a variety of materials and compositions, particularly thermoplastic elastomer compositions. Thermoplastic elastomers include thermoplastic vulcanizates (TPVs), styrenic block copolymers (SBCs), thermoplastic polyurethane elastomers (TPUs), thermoplastic polyolefin elastomers (TPOs), thermoplastic polyester elastomers (TPE-Es), or thermoplastic polyamide elastomers (TPEAs). In a preferred embodiment, the styrenic block copolymer comprises one or any combination of styrene-ethylene-butylene-styrene block copolymers (SEBS), styrene-isoprene-styrene block copolymers (SIS), styrene-butadiene-styrene block copolymers (SBS), styrene-ethylene-propylene-styrene block copolymers (SEPS), styrene-(isoprene / butadiene)-styrene block copolymers (S-(I / B)-S), or styrene-[ethylene-(ethylene-propylene)]-styrene block copolymers (SEEPS). In a preferred embodiment, the thermoplastic elastomer is a thermoplastic vulcanizate (TPV) or a styrene block copolymer (SBC) and has a residual precompression level of 12% to 30%, preferably 12% to 25%, more preferably 12% to 20%. In a preferred embodiment, the thermoplastic elastomer composition has a Shore A hardness of Shore A30 to Shore A50, preferably Shore A35 to Shore A50, more preferably Shore A35 to Shore A45. In a preferred embodiment, the thermoplastic elastomer composition has a breaking elongation of 250% or more, more preferably more than 300%.

[0017] The plastic composition used for the housing preferably comprises any rigid plastic having a modulus of elasticity greater than 3,000 psi. In a preferred embodiment, the plastic composition has a modulus of elasticity greater than 10,000 psi, more preferably greater than 50,000 psi, and has a Tg (glass transition temperature) greater than -90°C or a Tm (melting point) greater than 121°C. Specific examples of the main components of the plastic composition include polyolefins, polycarbonates, polycarbonate alloys, PP / SEBS alloys, high modulus thermoplastic polyurethane elastomers (TPUs), and high modulus thermoplastic polyester elastomers (TPE-Es).

[0018] The present invention provides a stopper produced by the above method.

[0019] The present invention also includes other aspects and various embodiments for solving other problems. These and other aspects are detailed in the Examples. [Brief description of the drawings]

[0020] DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS The invention will now be described in more detail with reference to exemplary specific embodiments shown in the accompanying drawings, in which:

[0021] [Figure 1A] FIG. 1A is a schematic diagram of a first molding process in one embodiment of the present invention; [Figure 1B] FIG. 1B is a schematic diagram of a first molding process in one embodiment of the present invention; [Figure 1C] FIG. 1C is a schematic diagram of a first molding process in one embodiment of the present invention; [Figure 2A] FIG. 2A is a schematic diagram of a second molding process of an embodiment of the present invention; [Figure 2B] FIG. 2B is a schematic diagram of a second molding process of an embodiment of the present invention; [Figure 2C] FIG. 2C is a schematic diagram of a second molding process of an embodiment of the present invention; [Diagram 3] FIG. 3 is a schematic diagram of a stopper with a septum and a housing according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] In order to fully understand the present invention and the claims of this application, the following preferred embodiments of the present invention are presented. In order to avoid obscuring the present invention, the following description omits known components, related materials, and processing techniques related thereto. The relevant processing techniques can be found in the following documents: T / CNPPA3016-2021: Technical Guide for Co-Infusion Closures for Intravenous Containers (CN); ISO15759:2005 Medical Infusion Devices-Plastic Caps with Inserted Elastomer Liners for Containers Produced by Blow-Fill-Seal (BFS) Method.

[0023] Septum Material-Thermoplastic Elastomer Composition

[0024] The septum of the present invention may be manufactured from various thermoplastic elastomer compositions as described above. The thermoplastic elastomer compositions include one or any combination of thermoplastic vulcanizates (TPVs), styrenic block copolymers (SBCs), thermoplastic polyurethane elastomers (TPUs), thermoplastic olefin elastomers (TPOs), thermoplastic polyester elastomers (TPE-Es), or thermoplastic polyamide elastomers (TPE-As). Among them, thermoplastic vulcanizates (TPVs) refer to a blend of rubber and plastics that has been subjected to a dynamic vulcanization process. Specific examples include TPVs such as Santoprene and Geolast, with Celanese's Santoprene 8281-35MED and Santoprene 8281-45MED being preferred choices. Examples of styrene block copolymers (SBC) include SEBS (styrene-ethylene-butylene-styrene block copolymer), SIS (styrene-isoprene-styrene block copolymer), SBS (styrene-butadiene-styrene block copolymer), SEPS (styrene-ethylene-propylene-styrene), and SEEPS (styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer). Thermoplastic polyurethanes (TPU) are copolymers of polyester or polyether and diisocyanate. Thermoplastic polyolefin elastomers (TPO) are mainly composed of polypropylene or polyethylene combined with ethylene-propylene-diene monomer rubber, examples of which include Vistamaxx, Versaflex HC, and COHERE TPO. Thermoplastic polyester elastomers (TPE-E) are copolymers of polyester and polyether, examples of which include Hytrel and Arnitel TPE-E. Thermoplastic polyesteramides (TPEA) are composed of polyesters and polyamides, examples include Vestamid® Care and Arnitel® VT.

[0025] In a preferred embodiment, hydrogenated styrene block copolymers are preferred. Compared with rubber materials and other thermoplastic elastomers, hydrogenated styrene block copolymers have inherently superior elasticity, processability and weatherability, and do not require the addition of vulcanizing or crosslinking agents. This can reduce the risk of contaminating the contents when used in medical packaging.

[0026] In a preferred embodiment, the thermoplastic elastomer composition used to manufacture the medical container septum of the present invention comprises: (a) 100 parts by weight of a block copolymer of formula ABA, where A is a vinyl aromatic block; B is a hydrogenated conjugated diene block with a hydrogenation rate of more than 90%, (b) 50-250 parts by weight of a plasticizer, and (c) 5-100 parts by weight of a polyolefin homopolymer. Block A is derived from selected monomers including styrene, methylstyrene and all its isomers, ethylstyrene and all its isomers, cyclohexylstyrene, vinyl biphenyl, 1-vinyl-5-hexylnaphthalene, vinyl naphthalene, vinyl anthracene, and any combination thereof. Block B is derived from 1,3-butadiene, 2,3-dimethyl-1,3-butadiene, 3-butyl-1,3-octadiene, isoprene, 1-methylbutadiene, 2-phenyl-1,3-butadiene, and any combination thereof. In a preferred example, the A block is a styrene block, and the B block is a 1,3-butadiene block or an isoprene block, or a coblock of butadiene and isoprene. Specific examples of block copolymers include SEBS (styrene-ethylene-butylene-styrene block copolymer), which is a hydrogenated copolymer of SBS (styrene-butadiene-styrene block copolymer); SEPS (styrene-ethylene-propylene-styrene block copolymer), which is a hydrogenated copolymer of SIS (styrene-isoprene-styrene block copolymer); and SEEPS (styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer), which is a hydrogenated copolymer of S-(I / B)-S ([styrene-(isoprene / butadiene)]-styrene block copolymer). The block copolymer may be of a single type or a combination of multiple types. In a preferred embodiment, the block copolymer includes a first block copolymer and a second block copolymer. In one embodiment, the difference between the first block copolymer and the second block copolymer is that the weight average molecular weight of the first block copolymer is greater than the weight average molecular weight of the second block copolymer.More preferably, the ratio of the first block copolymer to the second block copolymer (first block copolymer:second block copolymer) is 1:4 to 1:1. For example, in a more preferred embodiment, the block copolymer includes SEBS (first block copolymer) having a weight average molecular weight of about 440,000 and SEBS (second block copolymer) having a weight average molecular weight of about 250,000, and the ratio of the first block copolymer to the second block copolymer is in the range of 1:4 to 1:1.

[0027] In a preferred embodiment, the thermoplastic elastomer composition used to manufacture the septum of the medical container further comprises (d) more than 0 parts by weight and not more than 150 parts by weight of a filler, and (e) more than 0 parts by weight and not more than 50 parts by weight of polyphenylene ether (PPE, also known as polyphenylene oxide or PPO, with PPO being more commonly used industrially). In a preferred embodiment, the melt flow index (MFI) of the thermoplastic elastomer composition is 2 g / 10 min to 60 g / 10 min (at 230° C. and 5 kg). In another embodiment, the weight average molecular weight (Mw) of the block copolymer is 200,000 to 500,000, preferably 200,000 to 450,000, more preferably 220,000 to 450,000, and the weight average molecular weight (Mw) of the block A is 5,000 to 100,000, preferably 10,000 to 80,000, more preferably 20,000 to 60,000. In another embodiment, the bound vinyl aromatic content of the block copolymer is 20% to 50% by weight, preferably 25% to 45% by weight, more preferably 30% to 40% by weight of the block copolymer. The vinyl bond content of the block copolymer is 32% to 42% by weight, preferably 32% to 40% by weight, more preferably 35% to 40% by weight of the block B of the block copolymer. In another embodiment, the plasticizer is white oil. In another embodiment, the plasticizer is polyisobutylene. In another example, the polyolefin homopolymer is polypropylene.In another example, the filler is kaolin, silica, mica, calcium silicate, or calcium carbonate.

[0028] Housing-Plastic Composition

[0029] The housing of the present invention can be made from a variety of plastic compositions as described above. The preferred choices are materials that can be manufactured with high impact resistance and chemical durability. The plastic composition is comprised of one or any combination of polyolefins, polycarbonates, polycarbonate alloys, polypropylene / styrene-ethylene-butylene-styrene block copolymer alloys (PP / SEBS alloys), highly elastic thermoplastic polyurethane elastomers, or highly elastic thermoplastic polyester elastomers. Specific examples of polyolefins include polypropylene (PP) and high density polyethylene (HDPE). Specific examples of polycarbonates (PC) include Makrolon, LEXAN, and Panlite. Polycarbonate alloys are materials made by blending polycarbonate with other polymers (ABS, PBT, PET, etc.). Specific examples include Makrolon PC+ABS, PC+PBT, Lexan PC+ABS, PC+PET, etc. PP / SEBS alloys are blends of polypropylene and hydrogenated styrene block copolymers, examples of which are Kraton Polymers, SABIC, and LyondellBasell's PP / SEBS alloys. Examples of high modulus thermoplastic polyurethane elastomers (TPUs) include Elastollan, Irogran, and Desmopan high modulus TPUs. Examples of high modulus thermoplastic elastomers (TPE-Es) include Kraton TPE-E series and Tritan TPE-E. It is worth noting that when using TPU as the thermoplastic elastomer composition, PC is the preferred paired plastic composition for material compatibility.

[0030] Manufacturing process for stoppers for medical containers

[0031] The present invention provides a manufacturing method for a stopper for use in a medical container, the stopper having a septum and a housing supporting the septum, the manufacturing method comprising: Step (1): First, a septum is prepared by a first molding process using a thermoplastic elastomer composition; Step (2): Next, a housing is made using a plastic composition by a second molding process, where the septum is precompressed in a radial direction perpendicular to a needle penetration direction of the septum by the second molding process; Step (3): subjecting the stopper to steam sterilization; wherein after the septum undergoes steam sterilization, the septum exhibits a residual pre-compression level in a radial direction of 12% to 30% compared to when the septum is uncompressed, the residual pre-compression level being measured based on a thickness or average diameter of the septum.

[0032] Step (1): First molding process

[0033] Step (1): A septum is prepared by a first molding process using a thermoplastic elastomer composition. In detail, first, a suitable thermoplastic elastomer composition is prepared by melt-kneading various components of the composition in an extruder according to a formulation, and pellets for injection molding are produced to produce a septum. Referring to FIG. 1A, FIG. 1B and FIG. 1C, the first molding process includes providing a first upper mold 1a and a common lower mold 2a. The first upper mold 1a has a channel 1aF through which the molten thermoplastic elastomer composition flows and enters the first cavity 1a1 to form a septum 3b. The second cavity 1a2 is for accommodating a part of the common lower mold 2a. The common lower mold 2a has a movable pin 4 that can move up and down, a channel 2aF defined by the inner wall of the common lower mold 2a for the movement of the movable pin 4, and a support stand P. When the first upper mold 1a is assembled with the common lower mold 2a as shown in FIG. 1B, the molten thermoplastic elastomer composition, under the temperature and pressure suitable for injection molding, enters the first cavity 1a1 as the mold is closed, resulting in the formation of the septum 3b. It is worth noting that the movable pin 4 does not need to perform any telescopic action during the first molding process, but only serves to support and hold the septum 3b. FIG. 1C shows a schematic diagram after the injection molding of the septum 3b is completed and the first upper mold 1a is separated from the common lower mold 2a. It is important that the septum 3b remains on the common lower mold 2a at this point, so that the septum 3b can remain in the position where it was completed in the first molding process before the second molding process.

[0034] Step (2): The second molding process

[0035] In step (2), a housing is formed from the plastic composition by a second molding process. This second molding process pre-compresses the septum in a radial direction perpendicular to the needle-piercing direction of the septum. The second molding process includes clamping the septum between the second upper mold 1b and the aforementioned common lower mold 2a. The common lower mold 2a was used in the first and second molding processes. Specifically, first, commercially available plastic materials or self-prepared plastic compositions are melt-kneaded with all components in an extruder according to the formulation, and pellets are produced for injection molding to produce the housing. Referring to Figures 2A, 2B, and 2C, the second molding process includes providing a second upper mold 1b, the aforementioned common lower mold 2a, and a septum 3b produced from the first molding process. The second upper mold 1b has at least two channels 6a for the molten plastic composition to flow and enter the third cavity 1b1 through the outlet 6a1 to form a housing. As described above, the common lower mold 2a includes a movable pin 4 and a support P. As shown in the figure, the housing has an outline defined by the third space 1b1, the side wall 3bs of the septum 3b, a part of the top 2at of the common lower mold 2a that does not support the septum 3b, the side wall 2as, and the support P. In particular, the second upper mold 1b has a recessed space that defines an upper cavity 5a corresponding to the top of the septum 3b. As shown in FIG. 2B, when the second upper mold 1b is combined with the common lower mold 2a (i.e., when the septum 3b is clamped between the second upper mold 1b and the common lower mold 2a), the upper cavity 5a is located directly above the top of the septum 3b. At this time, the movable pin 4 moves downward to form a further space that defines the lower cavity 5b. The upper cavity 5a and the lower cavity 5b are aligned along the needle piercing direction Z of the septum 3b. The molten plastic composition then enters the cavity (third cavity 1b1) that is formed after the mold is closed under a temperature and pressure suitable for injection molding, thereby forming the housing 6. Figure 2B shows the molten plastic composition injected radially (the X direction shown in the figure is an example of a direction perpendicular to the needle piercing direction) around the septum 3b.The connection between the housing 6 and the side surface 3bs of the septum 3b is formed by pressing the septum 3b with a hot-molten plastic composition, and the housing 6 and the septum 3b are firmly joined to form the stopper. As shown in FIG. 2C, the radial pressure exerted by the molten plastic composition causes the septum 3b to be radially compressed and expand into the upper cavity 5a and the lower cavity 5b, forming expansion regions 8a and 8b. FIG. 3 is a schematic diagram of a stopper 7 including the septum 3b and the housing 6 after being removed from the mold following the first and second molding processes. The figure shows a needle piercing direction Z and a radial direction X perpendicular to the needle piercing direction Z, and indicates the needle piercing surface as 9 and the liquid contact surface as 10. As shown in FIG. 3, the stopper 7 includes a septum 3b and a housing 6 supporting the septum 3b. The septum 3b is made of a thermoplastic elastomer composition, and the housing 6 is made of a plastic composition. The housing 6 is firmly bonded to the side wall 3bs of the septum 3b, and the bond between the housing 6 and the septum 3b can be achieved without the housing 6 contacting the needle piercing surface 9 and the liquid contact surface 10 of the septum 3b. The present invention is not limited thereto. The case where the edge portion of the needle piercing surface 9 or the liquid contact surface 10 near the side wall 3bs of the septum 3b contacts the housing 6 is also within the scope of the present invention. As described above, the needle piercing surface 9 expands slightly upward and the liquid contact surface 10 expands slightly downward as the molten plastic composition radially presses the septum 3b. In particular, the present invention is not limited by the attached drawings. For example, the shapes of the upper cavity 5a and the lower cavity 5b or the shape of the movable pin 4 in the attached drawings are merely one of the preferred embodiments of the present invention. Other suitable dies having different shapes of the upper cavity or the lower cavity but similar functions, or suitable movable pins having different shapes but similar functions are within the scope of the present invention.

[0036] Step (3): Sterilize the stopper with steam

[0037] In accordance with ISO 15759, the stopper is steam sterilized at 121° C. for 30 minutes. If the septum retains a residual precompression level of 12% to 30% in the radial direction after steam sterilization, it may pass the ISO 15759 high pressure bubble leakage test. In a preferred embodiment, the stopper may also pass the ISO 15759 liquid leakage and load test or the average puncture force test. In a more preferred embodiment, the stopper passes all three tests of ISO 15759: the high pressure bubble leakage test, the liquid leakage and load test, and the average puncture force test.

[0038] The precompression level and the residual precompression level may be measured based on the thickness or average diameter of the septum. In particular, the following measurement is made before the septum undergoes steam sterilization and is called the "precompression level": the increase in thickness or decrease in average diameter of the septum due to compression of the plastic composition of the housing during housing molding divided by the initial thickness or average diameter of the septum before the housing molding step (i.e., when the septum has not yet been compressed). After the septum is steam sterilized, the precompression level of the septum may change. Thus, the compression level measured after the septum is steam sterilized is the "residual precompression level". In particular, the following measurement is made after the septum undergoes steam sterilization and is called the "residual precompression level": the increase in thickness or decrease in average diameter of the septum due to compression of the plastic composition of the housing during housing molding divided by the initial thickness or average diameter of the septum before the housing molding step (i.e., when the septum has not yet been compressed). The precompression level or residual precompression level can be measured with a caliper or alternatively by a side view x-ray scan of the completed medical IV stopper.

[0039] Example 1

[0040] A first molding process in step (1) was carried out using an injection molding machine (model: 320C) manufactured by ARBURG, Germany, with an appropriate amount of SEBS-A thermoplastic elastomer composition (components and properties shown in Table 1) to obtain a septum. The initial average diameter of the septum was measured with a caliper, and the average diameter (measure the needle piercing surface or the liquid contacting surface, since the septum in this embodiment is cylindrical and the needle piercing surface is the same size as the liquid contacting surface) was about 14.0 mm, and the thickness was about 3.0 mm. Then, a second molding process described in step (2) was carried out using an appropriate amount of plastic composition PP K4520 (manufactured by Taiwan Chemical Fiber Co., Ltd., elastic modulus is about 12,097 psi). As a result, a stopper with both a septum and a housing was obtained. After steam sterilization of the stopper at 121°C for 30 minutes according to ISO15759, the average diameter of the compressed septum was measured with a caliper, and the residual precompression level was calculated. We also conducted various performance tests on the stopper.

[0041] The molding conditions of the first molding process are as follows: injection molding temperature: 180° C.; injection pressure: 600 bar; injection speed: 35 mm / sec; holding time: 2.0 seconds; upper and lower mold temperatures: 40° C. The molding conditions of the second molding process are as follows: injection molding temperature: 240° C.; injection pressure: 250-1500 bar (varies depending on the embodiment); injection speed: 75 mm / sec; holding time: 2.5 seconds; upper and lower mold temperatures: 50° C.

[0042] Examples 2 to 6 and Comparative Examples 1 to 6 are generally similar to Example 1, except that the composition of the thermoplastic elastomer or the injection pressure during the second molding process is different. Table 1 shows the specific components and properties of the thermoplastic elastomer compositions used in each Example and Comparative Example. Furthermore, all components of the thermoplastic elastomer compositions used in the Examples and Comparative Examples are commercially available. Tables 2 to 5 show the injection pressure, residual precompression level, and related performance test results in each Example and Comparative Example.

[0043] [Table 1]

[0044] [Table 2]

[0045] [Table 3]

[0046] [Table 4]

[0047] [Table 5]

[0048] In Tables 2 to 5, 19 / 20 represents the total number of samples (20), the number of passing samples (19), n represents the number of samples, Y represents passing, N represents failing, and 46.86 (40) represents the average value of 40 samples being 46.86. For the average pin penetration test, if it is less than 75N, it meets the standard.

[0049] According to the experimental data in Tables 2-5, the residual precompression levels of the thermoplastic elastomer compositions of the comparative examples are 5.78%-8.3%, none of which meets the basic criteria of the high-pressure bubble leakage test. The residual precompression levels of Examples 1-6 are 12% or more, which meet all the criteria required for the high-pressure bubble leakage test, the liquid leakage and load resistance test, and the average needle puncture force test. It is noteworthy that even under the same injection conditions and after steam sterilization, different thermoplastic elastomer compositions have different residual precompression levels. Furthermore, it can be directly demonstrated from Examples 1-6 that for the same elastomeric septum material, increasing the residual precompression level will significantly change the average needle puncture force, and it is estimated that Examples 5-6 still have the potential to continue increasing the residual precompression level upward (e.g., 20-30%) until the average needle puncture force approaches the upper limit specified by the ISO15759 standard.

[0050] Analysis method

[0051] Steam sterilization: Steam sterilization at 121°C for 30 minutes in accordance with ISO15759.

[0052] Melt flow index: Tested according to ASTM D1238.

[0053] High pressure bubble leakage test: Based on ISO15759 resealability test.

[0054] Leakage and load resistance tests: Based on ISO15759 static spike retention capacity and penetration leakage resistance tests.

[0055] Pin penetration test: Based on ISO15759 pin penetration test.

[0056] Weight average molecular weight of block copolymer: determined by gel permeation chromatography as known in the art.

[0057] Vinyl aromatic content of the block copolymer: determined using nuclear magnetic resonance spectrometers known in the art.

[0058] Vinyl content of block copolymers: determined using nuclear magnetic resonance spectrometers known in the art.

[0059] Weight average molecular weight of the vinyl aromatic block of the block copolymer: determined using gel permeation chromatography, a method known in the art.

[0060] Hardness: Per specification provided at time of purchase. If not available, test per ASTM D 2240.

[0061] Breaking elongation: Tested at 23°C in accordance with product specification information or ASTM D412 standard.

[0062] The above description is the preferred embodiment of the present invention, and does not limit the scope of this patent application. Any equivalent changes or modifications made without departing from the spirit of the present invention shall be included in the scope of the following claims.

Claims

1. A manufacturing method for use in a stopper for a medical container, the stopper having a septum and a housing supporting the septum, the manufacturing method comprising: First, preparing the septum by a first molding process using a thermoplastic elastomer composition; then producing the housing by a second molding process using a plastic composition, the second molding process precompressing the septum in a radial direction perpendicular to a needle penetration direction of the septum; and subjecting the stopper to steam sterilization; 1. The method of claim 1 , wherein after the septum has undergone steam sterilization, the septum exhibits a residual pre-compression level in a radial direction of 12% to 30% compared to when the septum is uncompressed, the residual pre-compression level being measured based on a thickness or average diameter of the septum.

2. 2. The method of claim 1, wherein the thermoplastic elastomer composition comprises one or any combination of a thermoplastic vulcanizate (TPV), a styrenic block copolymer (SBC), a thermoplastic polyurethane elastomer (TPU), a thermoplastic olefin elastomer (TPO), a thermoplastic polyester elastomer (TPE-E), or a thermoplastic polyamide elastomer (TPEA).

3. The method according to claim 1, wherein the thermoplastic elastomer composition has a Shore A hardness of 30 to 50 and a breaking elongation of 250% or more.

4. 2. The method of claim 1, wherein the plastic composition comprises one or any combination of a polyolefin, a polycarbonate, a polycarbonate alloy, a polypropylene / styrene-ethylene-butylene-styrene block copolymer alloy (PP / SEBS alloy), a highly elastic thermoplastic polyurethane elastomer, or a highly elastic thermoplastic polyester elastomer.

5. The manufacturing method of claim 1 , wherein the first molding process and the second molding process are selected from one of a co-injection molding process, an insert molding process, an overmolding process, or a multi-shot injection molding process.

6. The method of claim 1 , wherein the second molding process includes extruding a melt of the plastic composition to radially compress the septum and expand the septum along a direction perpendicular to the radial direction.

7. 2. The manufacturing method of claim 1, wherein the second molding process includes placing the septum between an upper mold and a common lower mold, the upper mold having an upper cavity to accommodate an expansion of the septum, and the common lower mold further having a movable pin, the movable pin supporting and holding the septum during the first molding process; and, as the upper mold and the common lower mold are closed during the second molding process, the movable pin moves downward to form a lower cavity to accommodate an expansion of the septum.

8. The method of claim 1 , wherein the septum is not subjected to any stress relaxation pretreatment prior to the precompression.

9. 3. The method of claim 2, wherein the styrene block copolymer comprises one or any combination of styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-isoprene-styrene block copolymer (SIS), styrene-butadiene-styrene block copolymer (SBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-(isoprene / butadiene)-styrene block copolymer (S-(I / B)-S), or styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer (SEEPS).

10. 2. The process of claim 1, wherein the thermoplastic elastomer composition comprises: (a) 100 parts by weight of a block copolymer of the formula A-B-A, where A is a vinyl aromatic block and B is a hydrogenated conjugated diene block having a hydrogenation rate of greater than 90%, (b) 50 to 250 parts by weight of a plasticizer, and (c) 5 to 100 parts by weight of a polyolefin homopolymer.

11. 11. The process of claim 10, wherein block A is derived from one or any combination of styrene, methylstyrene and its isomers, ethylstyrene and its isomers, cyclohexylstyrene, vinyl biphenyl, 1-vinyl-5-hexylnaphthalene monomer, vinyl naphthalene, and vinyl anthracene, and block B is derived from one or any combination of 1,3-butadiene, 2,3-dimethyl-1,3-butadiene, 2,3-dimethyl-1,3-butadiene, 3-butyl-1,3-octadiene, isoprene, 1-methylbutadiene, and 2-phenyl-1,3-butadiene.

12. The method of claim 10, wherein the thermoplastic elastomer composition further comprises: (d) from greater than 0 parts by weight to less than 150 parts by weight of a filler; and (e) from greater than 0 parts by weight to less than 50 parts by weight of polyphenylene oxide.

13. The process according to claim 10, wherein the thermoplastic elastomer composition has a melt flow index (MFI) of 2 g / 10 min to 60 g / 10 min at 230° C. and 5 kg.

14. The method according to claim 10, wherein the weight average molecular weight of the block copolymer is 200,000 to 500,000, and the weight average molecular weight of the block A is 5,000 to 100,000.

15. 11. The method of claim 10, wherein the block copolymer has a bound vinyl aromatic content of 20% to 50% by weight of the block copolymer, and a vinyl bound content of the block B of the block copolymer of 32% to 42% by weight.

16. A stopper manufactured by the manufacturing method according to any one of claims 1 to 15.

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