Method for producing stopper having diaphragm for medical container, stopper, and polymer composition for diaphragm

Abstract

The present invention provides a method for manufacturing a stopper for a medical container, the stopper having a diaphragm and a housing supporting the diaphragm, the method comprising: first making a thermoplastic elastomer composition into the diaphragm using a first molding process; a plastic composition is made into the shell through a second molding process, and the diaphragm is pre-compressed in the radial direction perpendicular to the needling direction of the diaphragm through the second molding process; and performing vapor sterilization on the stopper, in which, after the diaphragm is subjected to the vapor sterilization, the diaphragm exhibits a residual pre-compression degree of 12% to 30% in the radial direction as compared to when the diaphragm is not compressed, the residual pre-compression degree being measured based on a thickness or an average diameter of the diaphragm.

Description

Technical Field

[0001] The present invention relates to a stopper with a septum for a medical container and a method for producing the stopper, wherein the septum is made of a polymer composition, in particular a polymer composition containing a thermoplastic elastomer (TPE). Background Art

[0002] Medical infusion bags are usually containers for packaging liquids (such as blood or intravenous fluids). In order to prevent the liquid filled therein from leaking, a stopper is embedded in the opening of the container. Generally, the structure of the stopper has a diaphragm and a shell supporting the diaphragm. When in use, the diaphragm can be pierced by a needle to discharge the liquid. Therefore, when the needle is pulled out or punctured for a long time, diaphragm leakage may occur.

[0003] To solve the above problems, patent document 1CN1091023C discloses a rubber stopper which is compressed by an external support member so that the diameter of at least one of the top and bottom surfaces of the rubber stopper shrinks by 1-10%. Patent document 2TW570824B discloses a puncture stopper having a stopper body and a puncture portion made of a thermoplastic elastomer, wherein the puncture portion is heat treated in hot air at 80-120°C to eliminate internal stress. Although the prior art including the above patent documents claims to have the effect of preventing diaphragm leakage, there are still various problems to be improved in practice. Summary of the invention

[0004] Problems to be solved by the invention

[0005] Compression set and thermal stress (tension) effects

[0006] The inventors of the present application have found that inserting the needle into the diaphragm for a long time can easily cause a narrow gap on the diaphragm at the insertion position due to compression deformation, which in turn causes inevitable leakage, especially when there is a large hydraulic pressure in the liquid in the intravenous bag. Moreover, if the surface tension of the liquid is low, leakage may also occur under lower hydraulic pressure. Moreover, for the process of injection molding the plastic shell first and then the TPE diaphragm, due to the high thermal shrinkage of the diaphragm material during the cooling process, built-in tension (~200°C to room temperature) will be generated in the diaphragm material. The CTE (coefficient of thermal expansion) of low modulus elastomers is about 200~250×10 -6 / ℃, the CTE (coefficient of thermal expansion) of PP is about 60~100×10 -6 Although the built-in tension in this diaphragm can be partially released during steam sterilization, it cannot be fully released. This tension can exacerbate the gap created by the spike insertion.

[0007] The inventors of the present application also noticed that in the plug assembly of Patent Document 1 using a rubber plug as a diaphragm, because the rubber material is incompatible with the outer support, it is necessary to additionally provide a synthetic resin film between the rubber plug and the outer support so that the rubber plug and the outer support can be melted and bonded to each other. Patent Document 2 uses thermoplastic elastomer to make the needle insertion part (diaphragm), but the residual stress of the needle insertion part is easy to cause leakage of the liquid medicine, so Patent Document 2 requires that the needle insertion part be heat treated first to remove the stress. The practices of Patent Documents 1 or 2 increase the complexity of such diaphragm processes. At the same time, the inventors of the present application also found that when the thermoplastic elastomer diaphragm is compressed as described in Patent Document 1, its diameter shrinkage rate is as high as 8% and still fails to achieve the expected leak-proof effect, and it is also unexpectedly found that as the storage time is prolonged or stored in an unfavorable environment, the shrinkage rate of the thermoplastic elastomer diaphragm will continue to slowly decrease.

[0008] Means of solving the problem

[0009] The present invention provides mechanical pre-compression of the diaphragm to overcome the above-mentioned compression permanent deformation and thermal stress effects. The diaphragm is made of a thermoplastic elastomer, and there is no need to additionally provide a synthetic resin film between the diaphragm and the supporting shell. At the same time, after the plug of the present invention is treated with steam sterilization, the diaphragm maintains a residual pre-compression degree of 12% to 30% in the radial direction, preferably 12% to 25%, and more preferably 12% to 20%. Such a high residual pre-compression degree can enable the diaphragm to maintain a sufficient amount of internal compressive stress for a long time. When the internal compressive stress gradually decreases due to changes in the external environment, the diaphragm of the present invention can prevent the internal compressive stress from rapidly dropping below the critical value due to the high internal compressive stress. Therefore, the diaphragm of the present invention can maintain the property of effectively preventing liquid leakage for a long time, which is conducive to storage and other multi-purpose uses. At the same time, the diaphragm of the present invention is not over-hardened due to its high residual pre-compression degree, and the diaphragm of the present invention can still maintain good puncture performance.

[0010] In addition, in a preferred embodiment, the thermoplastic elastomer diaphragm of the present invention does not need to be heat-treated or otherwise pre-treated to remove stress before being pre-compressed.

[0011] The present invention provides a method suitable for producing the pre-compression of the elastomeric diaphragm by a co-injection molding process, an insert-molding process, an over-molding process or a multi-shot injection molding process. The present invention does not use a process of first injection molding the plastic housing and then injection molding the elastomeric diaphragm.

[0012] The method of the present invention comprises: (1) an overmolding process of first injection molding an elastomeric diaphragm (e.g., a thermoplastic elastomer composition), or an insert injection molding process with a molded elastomeric diaphragm as an insert; and (2) injection molding a plastic shell radially surrounding the elastomeric diaphragm. At this time, the injection temperature, injection pressure, and holding pressure need to be high enough to produce (i) significant radial compression of the elastomeric diaphragm and (ii) sufficient adhesion to the elastomeric diaphragm. In a preferred embodiment, a common lower mold for supporting the elastomeric diaphragm has a movable telescopic part below the center line of the elastomeric diaphragm to form a cavity for the elastomeric diaphragm to expand into. In a preferred embodiment, the present invention uses a plastic melt to extrude the elastomeric diaphragm radially inward, and the elastomeric diaphragm will be compressed in the radial direction and expand into the cavity in the axial direction (i.e., perpendicular to the radial direction). Therefore, the elastomeric diaphragm will be squeezed by the plastic shell in the radial direction to produce built-in pre-compression.

[0013] In certain embodiments, the invention provides at least one of the following features.

[0014] The present invention provides a stopper (e.g., an IV container stopper) having an elastomeric diaphragm (e.g., a thermoplastic elastomer composition) with a high degree of residual pre-compression in the radial direction (roughly perpendicular to the direction of nail / needle puncture) that can be immediately resealed to prevent liquid leakage after the needle is pulled out or removed.

[0015] The present invention adopts a co-injection molding process, an insert injection molding process, an over-injection molding process or a multi-injection molding process, wherein an elastomeric membrane (e.g., a thermoplastic elastomer composition) is molded first, and then a plastic housing is molded. In the step of molding the plastic housing, the present invention utilizes the pressure of the plastic melt of the plastic housing to extrude the elastomeric membrane (e.g., a thermoplastic elastomer composition) radially inward, so as to extrude the elastomeric membrane to deform in the space in the axial direction (i.e., in the direction perpendicular to the radial direction), thereby generating radial pre-compression.

[0016] The desired pre-compression degree produced by the co-injection molding process, the insert injection molding process, the over-injection molding process or the multi-injection molding process is greater than 12% to 40%. After steam sterilization at 110° C. or 121° C. for 30 minutes, the residual pre-compression degree is still between 12% and 30%, preferably between 12% and 25%, and more preferably between 12% and 20%. The pre-compression degree and the residual pre-compression degree of the diaphragm are calculated based on the thickness or average diameter of the diaphragm in the diaphragm molding step.

[0017] The aforementioned pre-compressed diaphragm concept of the present invention can be used for a variety of materials and compositions, in particular 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 copolymers include one or a combination of the following: 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), styrene-[ethylene-(ethylene-propylene)]-styrene block copolymers (SEEPS). In a preferred embodiment, the thermoplastic elastomer is a thermoplastic vulcanizate (TPV) or a styrenic block copolymer (SBC), and the residual pre-compression degree is between 12% and 30%, preferably between 12% and 25%, and more preferably between 12% and 20%. In a preferred embodiment, the Shore A hardness of the thermoplastic elastomer composition is Shore A30 to Shore A50, preferably Shore A35 to Shore A50, and more preferably Shore A35 to Shore A45. In a preferred embodiment, the elongation at break of the thermoplastic elastomer composition is greater than or equal to 250%, and more preferably greater than 300%.

[0018] The plastic composition for the housing preferably includes any rigid plastic with an elastic modulus greater than 3,000 psi. In a preferred embodiment, the plastic composition preferably has an elastic modulus greater than 10,000 psi, or preferably greater than 50,000 psi, and a glass transition temperature (glass transition temperature, Tg) greater than -90 ° C or a melting point (melting temperature, Tm) greater than 121 ° C. The main components of the plastic composition specifically include polyolefins, polycarbonates, polycarbonate alloys, PP / SEBS alloys, high modulus thermoplastic polyurethane elastomers (TPU), high modulus thermoplastic polyester elastomers (TPE-E), etc.

[0019] The present invention provides a plug, which is manufactured by the aforementioned manufacturing method.

[0020] The present invention also includes other aspects and various embodiments to solve other problems. The above-mentioned aspects and other aspects are combined and disclosed in detail in the embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The invention will be explained in more detail below based on exemplary embodiments shown in the accompanying drawings, in which:

[0022] Figure 1A , Figure 1B and Figure 1C is a schematic diagram of a first molding process in one embodiment of the present invention;

[0023] Figure 2A , Figure 2B and Figure 2C is a schematic diagram of a second molding process in one embodiment of the present invention;

[0024] Figure 3 Schematic diagram of a plug having a diaphragm and a housing in one embodiment of the present invention.

[0025]

Explanation of symbols

[0026] 1a The first upper mold 2a Shared lower mold

[0027] 1aF flow channel 3a flow channel outlet

[0028] 1a1 First space 1a2 Second space

[0029] 4 telescopic parts 2aF pipe

[0030] P support platform 3b diaphragm

[0031] 1b Second upper mold 1b1 Third space

[0032] 3bs sidewall 2at top

[0033] 2as side wall 5a upper cavity

[0034] 5b lower cavity 6 housing

[0035] 8a expansion zone 8b expansion zone

[0036] 7. Plug Z acupuncture direction

[0037] X radial 9 needling surface perpendicular to the needling direction

[0038] 10 Liquid junction 6a Flow channel

[0039] 6a1 flow channel DETAILED DESCRIPTION

[0040] In order to make the present invention and the scope of the patent application claimed for protection be fully understood, the preferred embodiments of the present invention will be demonstrated below. To avoid obscuring the content of the present invention, the following description omits known components, related materials, and related processing technologies. For related processing technologies, please refer to the following documents T / CNPPA3016-2021: Technical guide for co-injection closure for intravenous container (CN) (Technical guide for co-injection closure for intravenous container (CN)); ISO15759:2005 Medical infusion equipment-Plastics caps withinserted elastomeric liner for containers manufactured by the blow-fill-seal (BFS) process (Medical infusion equipment-Plastic caps with inserted elastomeric liner for containers manufactured by the blow-fill-seal (BFS) process).

[0041] Diaphragm material - thermoplastic elastomer composition

[0042] The diaphragm of the present invention can be made of various thermoplastic elastomer compositions as described above. Thermoplastic elastomer compositions include one or a combination of the following: thermoplastic vulcanizates (TPV), styrene block copolymers (SBC), thermoplastic polyurethane elastomers (TPU), thermoplastic polyolefin elastomers (TPO), thermoplastic polyester elastomers (TPE-E) or thermoplastic polyamide elastomers (TPEA). Wherein, thermoplastic vulcanizates (TPV, Thermoplastic Vulcanizates) refer to a blend composed of rubber and plastic and subjected to dynamic vulcanization treatment, and specific examples are TPVs such as Santoprene and Geolast, preferably Santoprene 8281-35MED or Santoprene 8281-45MED of Celanese Corporation. Specific examples of styrene block copolymers (SBC) are, for example, SEBS (styrene-ethylene-butylene-styrene block copolymer), SIS (styrene-isoprene-styrene block copolymer), SBS (styrene-butadiene-styrene block copolymer), SEPS (styrene-ethylene-propylene-styrene block copolymer), S-(I / B)-S (styrene-(isoprene / butadiene)-styrene block copolymer), SEEPS (styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer), etc. Thermoplastic polyurethane elastomers (TPU, Thermoplastic Polyurethanes) are copolymers of polyester or polyether and diisocyanate, and specific examples are, for example, TPU from Estane and Texin, preferably TPU from BASF. Soft 35A 12P or B CF 45A 12P. Thermoplastic polyolefin elastomers (TPO) are mainly composed of polypropylene or polyethylene and ethylene-propylene-diene monomer rubber. Specific examples include Vistamaxx, Versaflex HC, and COHERE TPO. Thermoplastic polyester elastomers (TPE-E) are copolymers of polyester and polyether. Specific examples include Hytrel and Arnitel TPE-E. Thermoplastic polyamide elastomers (TPEA) are composed of polyester and polyamide. Specific examples include Care, VT.

[0043] In a preferred embodiment, hydrogenated styrene block copolymers are preferred. Compared with rubber materials or other thermoplastic elastomers, hydrogenated styrene block copolymers have good elasticity, processability, and weather resistance, and do not require the addition of additional vulcanizers and crosslinking agents. When used as medical packaging, the risk of contamination of the contents can be reduced.

[0044] In a preferred embodiment, the thermoplastic elastomer composition for manufacturing a medical container diaphragm of the present invention comprises: (a) 100 parts by weight of a block copolymer having the formula ABA, wherein A is a vinyl aromatic block; B is a hydrogenated conjugated diene block having a hydrogenation degree of 90% or more; (b) 50 to 250 parts by weight of a softener, and (c) 5 to 100 parts by weight of a polyolefin homopolymer. Block A is derived from styrene, methyl styrene and all isomers thereof, ethyl styrene and all isomers thereof, cyclohexyl styrene, 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 embodiment, block A is a styrene block, and block B is a 1,3-butadiene block or an isoprene block or a butadiene and isoprene co-block. Specific examples of block copolymers are, for example, SEBS (styrene-ethylene-butylene-styrene block copolymer), i.e., a hydrogenated copolymer of SBS (styrene-butadiene-styrene block copolymer), SEPS (styrene-ethylene-propylene-styrene block copolymer), i.e., a hydrogenated copolymer of SIS (styrene-isoprene-styrene block copolymer), SEEPS (styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer), i.e., a hydrogenated copolymer of S-(I / B)-S (styrene-(isoprene / butadiene)-styrene), etc. The above block copolymers may be one or more combinations. In a preferred embodiment, the block copolymer comprises 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, and preferably the content ratio of the first block copolymer to the second block copolymer is 1:4 to 1:1. For example, in a preferred embodiment, the block copolymer comprises SEBS with a weight average molecular weight of about 440,000 as the first block copolymer and SEBS with a weight average molecular weight of about 250,000 as the second block copolymer, and the content ratio of the first block copolymer to the second block copolymer is 1:4 to 1:1.

[0045] In a preferred embodiment, the thermoplastic elastomer composition for manufacturing a medical container diaphragm of the present invention further comprises: (d) a filler greater than 0 and equal to or less than 150 parts by weight; and (e) a polyphenylene ether (PPE; also known as Polyphenylene Oxide, PPO, where PPO is more commonly used in industry) greater than 0 and equal to or less than 50 parts by weight. In a preferred embodiment, the melt flow index (MFI) of the thermoplastic elastomer composition is 2 g / 10 min to 60 g / 10 min (230° C., 5 kg). In another example, the block copolymer has a weight average molecular weight (Mw) of 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 block A is 5,000 to 100,000, preferably 10,000 to 80,000, more preferably 20,000 to 60,000. In another example, the bound vinyl aromatic content of the block copolymer is 20% to 50%, preferably 25% to 45%, more preferably 30% to 40%, based on the weight of the block copolymer; the vinyl bond content of the block copolymer is 32% to 42%, preferably 32% to 40%, more preferably 35% to 40% of the weight of block B of the block copolymer. In another example, the softener is white oil. In another example, the softener is polyisobutylene. In another example, the polyolefin homopolymer is polypropylene.In another example, the filler is kaolin, silica, mica, calcium silicate or calcium carbonate.

[0046] Shell-plastic combination

[0047] The shell of the present invention can be made of various plastic compositions as described above. Preferably, it is a material that can be made into high-strength impact resistance and chemical resistance. The plastic composition includes one of the following or a combination thereof: polyolefin, polycarbonate, polycarbonate alloy, polypropylene / styrene-ethylene-butylene-styrene block copolymer alloy (PP / SEBS alloy), high modulus thermoplastic polyurethane elastomer, high modulus thermoplastic polyester elastomer. Specific examples of polyolefin are polypropylene (PP, Polypropylene) and high-density polyethylene (HDPE, High-Density Polyethylene). Specific examples of polycarbonate (PC, Polycarbonate) are Makrolon, LEXAN, and Panlite PC. Polycarbonate alloy is a material blended with polycarbonate and other polymers (such as ABS, PBT or PET, etc.), and specific examples are Makrolon PC+ABS, PC+PBT, Lexan PC+ABS and PC+PET, etc. PP / SEBS alloy is a material mixture composed of polypropylene and hydrogenated styrene block copolymer, and specific examples are PP / SEBS alloys of Kraton Polymers, SABIC, and LyondellBasell. Specific examples of high modulus thermoplastic polyurethane elastomers (TPU) are high modulus TPUs of Elastollan, Irogran, and Desmopan. Specific examples of high modulus thermoplastic polyester elastomers (TPE-E) are Kraton TPE-E series and Tritan TPE-E. It is worth noting that if the thermoplastic elastomer composition uses TPU, then considering the material compatibility, PC is preferably used as the plastic composition matched therewith.

[0048] Molding process for stoppers of medical containers

[0049] The present invention provides a method for manufacturing a plug for a medical container, wherein the plug has a diaphragm and a shell supporting the diaphragm, and the manufacturing method comprises: step (1) using a first molding process to first form a thermoplastic elastomer composition into a diaphragm; step (2) using a second molding process to form a shell into a plastic composition, and the second molding process pre-compresses the diaphragm in a radial direction perpendicular to the needle puncture direction of the diaphragm; step (3) steam sterilizing the plug, wherein after the diaphragm undergoes steam sterilization, the diaphragm exhibits a residual pre-compression degree of 12% to 30% in the radial direction compared to when it is not compressed, and the residual pre-compression degree is measured based on the thickness or average diameter of the diaphragm.

[0050] Step (1) First Molding Process

[0051] Step (1) uses a first molding process to make a thermoplastic elastomer composition into a diaphragm. Specifically, first prepare a suitable thermoplastic elastomer composition, that is, melt and knead the various components of the thermoplastic elastomer composition in an extruder according to the formula to prepare pellets of each sample for injection molding to manufacture the diaphragm. Figure 1A , Figure 1B and Figure 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 flow channel 1aF for the molten thermoplastic elastomer composition to pass through and flow from the flow channel port 3a into the first space 1a1 to be molded into a diaphragm 3b. The second space 1a2 is used to accommodate a part of the common lower mold 2a. The common lower mold 2a has a telescopic member 4 that can be telescopically moved up and down, a channel 2aF for the telescopic member 4 to move is defined by the inner wall of the common lower mold 2a, and a support platform P. When the first upper mold 1a is combined with the common lower mold 2a as shown in FIG. Figure 1B As shown, the molten thermoplastic elastomer composition enters the first space 1a1 after the mold is closed at an appropriate temperature and pressure for injection molding, thereby obtaining the diaphragm 3b. It is worth noting that the telescopic member 4 does not need to be telescopically actuated at this time, and it only plays the function of supporting and maintaining the diaphragm 3b in the first molding process. Figure 1C After the injection molding of the diaphragm 3b is completed, the first upper mold 1a leaves the common lower mold 2a. It is worth noting that the diaphragm 3b is still kept on the common lower mold 2a at this time, so that the diaphragm 3b can remain in the position where the first molding process is completed and then enter the second molding process.

[0052] Step (2) Second Molding Process

[0053] Step (2) uses a second molding process to make the plastic composition into a shell, and the second molding process pre-compresses the diaphragm in a radial direction perpendicular to the needle-piercing direction of the diaphragm. The second molding process includes sandwiching the diaphragm between a second upper mold 1b and the aforementioned common lower mold 2a, and the lower mold used in the first molding process and the second molding process is the same as the common lower mold 2a. Specifically, first prepare a commercially available plastic material, or prepare a suitable plastic composition by yourself, that is, place the various components of the plastic composition in an extruder according to the formula, melt and knead to prepare pellets of each sample, which are used for injection molding to manufacture the shell. Reference Figure 2A , Figure 2B and Figure 2C, the second molding process includes providing a second upper mold 1b, the aforementioned common lower mold 2a, and the diaphragm 3b completed in the first molding process. The second upper mold 1b has at least two runners 6a for the molten plastic composition to pass through and flow from the runner opening 6a1 into the third space 1b1 to be molded into a shell. As mentioned above, the common lower mold 2a has a telescopic part 4 that can be telescopically moved up and down and a support platform P. As shown in the figure, the appearance of the shell is defined by the third space 1b1, the side wall 3bs of the diaphragm 3b, the top 2at and side wall 2as of the portion of the common lower mold 2a that does not support the diaphragm 3b, and the support platform P. It is worth noting that the second upper mold 1b has a recessed space that defines an upper cavity 5a to correspond to the top of the diaphragm 3b. When the second upper mold 1b and the common lower mold 2a are molded as shown Figure 2B When the diaphragm 3b is shown (i.e., the diaphragm 3b is sandwiched between the second upper mold 1b and the common lower mold 2a), the upper cavity 5a is just above the top of the diaphragm 3b. At this time, the telescopic member 4 moves downward to form an additional space, defining the lower cavity 5b. The upper cavity 5a and the lower cavity 5b are arranged along the needle puncture direction Z of the diaphragm 3b. At this time, the molten plastic composition enters the cavity formed after the mold is closed, that is, the third space 1b1, under appropriate temperature and pressure, to perform injection molding, thereby obtaining the housing 6. Figure 2B The molten plastic composition injection molded in the radial direction (the X direction in the figure is a schematic illustration perpendicular to the needle puncture direction) surrounds the diaphragm 3b. The shell 6 and the side 3bs of the diaphragm 3b are tightly adhered together by the hot molten plastic composition to form a plug. The radial pressure generated by the molten plastic composition compresses the diaphragm 3b in the radial direction and causes the diaphragm 3b to expand and extend into the upper cavity 5a and the lower cavity 5b, thereby forming expansion areas 8a and 8b, as shown in FIG. Figure 2C shown. Figure 3 Schematic diagram of a plug 7 having a diaphragm 3b and a housing 6 taken out of a mold after the aforementioned first molding process and second molding process. The figure shows the puncture direction Z of the diaphragm 3b and the radial direction X perpendicular to the puncture direction Z, wherein the puncture surface is 9 and the liquid junction surface is 10. Figure 3The plug 7 shown has a diaphragm 3b and a shell 6 supporting the diaphragm 3b, the diaphragm 3b is made of a thermoplastic elastomer composition, the shell 6 is made of a plastic composition, the shell 6 is tightly connected to the diaphragm 3b from the side 3bs of the diaphragm 3b, and the shell 6 can complete the adhesion of the shell 6 to the diaphragm 3b without contacting the needle-punched surface 9 and the liquid junction surface 10 of the diaphragm 3b. The present invention is not limited to this. It is still within the scope of the present invention to make the edge portion of the needle-punched surface 9 close to the side 3bs of the diaphragm 3b or the edge portion of the liquid junction surface 10 close to the side 3bs of the diaphragm 3b contact with the shell 6. As mentioned above, the melt of the plastic composition extrude the diaphragm 3b in the radial direction, forming the needle-punched surface 9 to expand slightly upward and the liquid junction surface 10 to expand slightly downward. It is worth noting that the present invention is not limited to the accompanying drawings. For example, the shape of the upper cavity 5a and the lower cavity 5b or the shape of the telescopic member 4 in the accompanying drawings are only one of the preferred embodiments of the present invention. Other suitable molds with upper or lower cavities having the same function but different shapes, or suitable telescopic parts with different shapes and the same function, all belong to the scope of the present invention.

[0054] Step (3) Steam sterilizing the stopper

[0055] According to ISO15759, the stopper is steam sterilized at 121°C for 30 minutes, wherein after the stopper is steam sterilized, if the diaphragm still maintains a residual pre-compression degree of 12% to 30% in the radial direction, it can at least pass the high-pressure bubble leakage test of ISO15759. In a preferred embodiment, it can also pass the liquid leakage and hanging weight test or the average puncture force test of ISO15759. In a more preferred embodiment, the high-pressure bubble leakage test, the liquid leakage and hanging weight test and the average puncture force test of ISO15759 can all be passed.

[0056] The degree of pre-compression and the degree of residual pre-compression can be measured based on the thickness or average diameter of the diaphragm. Specifically, the following measurement is performed before the diaphragm undergoes steam sterilization: the increase in diaphragm thickness or the decrease in average diameter due to radial extrusion of the plastic composition of the shell during shell molding is divided by the initial thickness or average diameter of the diaphragm before the shell molding step (i.e., when the diaphragm is not compressed), which is called the "degree of pre-compression". After the diaphragm undergoes steam sterilization, the "degree of pre-compression" of the diaphragm may change. Therefore, the degree of compression measured after the diaphragm undergoes steam sterilization is the "residual degree of pre-compression". Specifically, the following measurement is performed after the diaphragm undergoes steam sterilization: the increase in diaphragm thickness or the decrease in average diameter due to radial extrusion of the plastic composition of the shell during shell molding is divided by the initial thickness or average diameter of the diaphragm before the shell molding step (i.e., when the diaphragm is not compressed), which is called the "residual degree of pre-compression". The degree of pre-compression or residual pre-compression can be measured using a vernier caliper, or alternatively, by taking a side-view X-ray scan of the finished medical IV closure.

[0057] Example 1

[0058] An injection molding machine (trade name: 320C) manufactured by ARBURG, Germany, was used to take an appropriate amount of SEBS-A thermoplastic elastomer composition (composition and properties are shown in Table 1) to perform the first molding process in the above step (1). After obtaining the diaphragm, the initial average diameter of the diaphragm was measured with a vernier caliper. The average diameter of the diaphragm (measured at the needle-punched surface or liquid junction surface, because the diaphragm in this example is cylindrical, the needle-punched surface and the liquid junction surface are the same size) is about 14.0 mm, and the thickness of the diaphragm is about 3.0 mm. Then, an appropriate amount of plastic composition PP K4520 (manufactured by Taiwan Chemical Fiber Co., Ltd., elastic modulus of about 12,097 psi) was taken to perform the second molding process in the above step (2). In this way, a plug having a diaphragm and a shell can be obtained. After the plug is steam sterilized at 121°C for 30 minutes according to ISO15759, the average diameter of the diaphragm after extrusion is measured with a vernier caliper to calculate the residual pre-compression degree. At the same time, various related performance tests are performed on the plug.

[0059] 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 mold temperature, lower mold temperature: 40°C. The molding conditions of the second molding process are as follows: injection molding temperature: 240°C; injection pressure: 250-1500 bar (varies according to different examples); injection speed: 75 mm / sec; holding time: 2.5 seconds; upper mold temperature, lower mold temperature: 50°C.

[0060] The operation methods of Examples 2 to 6 and Comparative Examples 1 to 6 are substantially the same as those of Example 1, except for the composition of the thermoplastic elastomer composition or the injection pressure of the second molding process. Table 1 shows the specific composition and physical properties of the thermoplastic elastomer composition used in each Example and Comparative Example. In addition, the components of all the thermoplastic elastomer compositions used as Examples and Comparative Examples of the present invention can be purchased from the market. Tables 2 to 5 show the injection pressure, residual pre-compression degree and related performance test results of the thermoplastic elastomer composition used in each Example and Comparative Example.

[0061] Table 1

[0062]

[0063]

[0064] Table 2: Injection pressure 1000 bar in the second molding process

[0065] Example 1 Example 2 Example 3 Thermoplastic elastomer composition SEBS-A SEBS-B TPV-45A Residual pre-compression degree 12.36％ 12.62％ 13.38％ Standard deviation of residual pre-compression degree (n) 0.31％(40) 0.37％(40) 0.60％(40) High pressure bubble leak test Y(20 / 20) Y(20 / 20) Y(20 / 20) Liquid leakage and hanging weight test Y(40 / 40) Y(40 / 40) Y(40 / 40) Average puncture force test (n) 46.86(40) 43.57(40) 40.12(40) Average puncture force standard deviation (n) 1.02(40) 1.78(40) 5.31(40)

[0066] Table 3: Injection pressure 1500 bar in the second molding process

[0067]

[0068] Table 4: Injection pressure 250 bar in the second molding process

[0069]

[0070]

[0071] Table 5: Injection pressure 500 bar in the second molding process

[0072] Comparative Example 4 Comparative Example 5 Comparative Example 6 Thermoplastic elastomer composition SEBS-B SEEPS-A TPV-45A Residual pre-compression degree 8.30％ 6.35％ 6.19％ Standard deviation of residual pre-compression degree (n) 0.36％(20) 0.47％(20) 1.70％(20) High pressure bubble leak test N(7 / 10) N(13 / 20) N(0 / 10) Liquid leakage and hanging weight test N(8 / 20) N(19 / 20) Y(20 / 20) Average puncture force test (n) 42.11(5) 38.65(20) 33.86(5) Average puncture force standard deviation (n) 0.72(5) 1.47(20) 0.45(5)

[0073] In Tables 2 to 5, the denominator of 19 / 20 represents the total number of samples (20), the numerator represents the number of samples that passed (19), and so on; n represents the number of samples; Y represents pass; N represents fail; 46.86 (40) represents the average value of 40 samples tested is 46.86, and so on. The average puncture force test meets the standard as long as it is less than 75N.

[0074] The experimental data in Tables 2 to 5 show that the residual pre-compression degree of the thermoplastic elastomer composition of the comparative example is between 5.78% and 8.3%, which cannot meet the most basic high-pressure bubble leakage test standard. The residual pre-compression degree of Examples 1-6 is above 12%, which can meet the standards required by the high-pressure bubble leakage test, liquid leakage and hanging weight test, and average puncture force test. It is worth noting that different thermoplastic elastomer compositions still show different residual pre-compression degrees even under the same injection conditions and after steam sterilization. In addition, it can be directly proved from Examples 1-6 that the elastomeric diaphragm of the same material will cause a significant change in the average puncture force when its residual pre-compression degree increases, and it can be estimated that Examples 5-6 still have the possibility of continuing to increase the residual pre-compression degree upward (such as 20-30%) until its average puncture force approaches the standard upper limit of the ISO15759 specification.

[0075] Analytical methods

[0076] Steam sterilization: According to ISO15759, steam sterilization at 121℃ for 30 minutes.

[0077] Melt flow index: tested according to ASTM D1238.

[0078] High pressure bubble leakage test: Resealability test based on ISO15759.

[0079] Liquid leakage and hanging weight test: Based on the static spike retention capability of the liner and leak resistance of the piercing area test of ISO15759.

[0080] Puncture force test: Based on the puncture force test of ISO15759.

[0081] The weight average molecular weight of the block copolymer is measured by colloid permeation chromatography, which is a measurement method well known to those skilled in the art.

[0082] The bonded vinyl aromatic content of the block copolymer is measured using a nuclear magnetic resonance analyzer, which is a measurement method well known to those skilled in the art.

[0083] Vinyl bond content of the block copolymer: measured using a nuclear magnetic resonance analyzer, which is a measurement method well known to those skilled in the art.

[0084] The weight average molecular weight of the vinyl aromatic block of the block copolymer is measured by colloid permeation chromatography, which is a measurement method well known to those skilled in the art.

[0085] Hardness: Based on the product specification information at the time of purchase. If not available, test according to ASTM D2240 standard.

[0086] Elongation at break: Tested at 23°C according to product specifications or ASTM D412.

[0087] The above description is only a preferred embodiment of the present invention and is not intended to limit the scope of the patent application of the present invention;

[0088] Any other equivalent changes or modifications that do not depart from the spirit disclosed by the present invention should be included in the scope of the following patent applications.

Claims

1. A method for manufacturing a stopper for a medical container, the stopper having a diaphragm and a shell supporting the diaphragm, the manufacturing method comprising: Firstly, a thermoplastic elastomer composition is formed into the diaphragm by a first molding process; Then forming the plastic composition into the housing using a second molding process, the second molding process pre-compressing the diaphragm in a radial direction perpendicular to the needling direction of the diaphragm; The stopper is steam sterilized, wherein after the diaphragm is subjected to steam sterilization, the diaphragm exhibits a residual pre-compression degree of 12% to 30% in the radial direction compared to when the diaphragm is uncompressed, and the residual pre-compression degree is measured based on the thickness or average diameter of the diaphragm.

2. The manufacturing method according to claim 1, wherein: The thermoplastic elastomer composition includes one or a combination of the following: thermoplastic vulcanizate (TPV), styrenic block copolymer (SBC), thermoplastic polyurethane elastomer (TPU), thermoplastic polyolefin elastomer (TPO), thermoplastic polyester elastomer (TPE-E) or thermoplastic polyamide elastomer (TPEA).

3. The manufacturing method according to claim 1, wherein: The Shore A hardness of the thermoplastic elastomer composition is Shore A30 to Shore A50, and the elongation at break of the thermoplastic elastomer composition is greater than or equal to 250%.

4. The manufacturing method according to claim 1, wherein: The plastic composition comprises one of the following or a combination thereof: polyolefin, polycarbonate, polycarbonate alloy, polypropylene / styrene-ethylene-butylene-styrene block copolymer alloy (PP / SEBS alloy), high modulus thermoplastic polyurethane elastomer, and high modulus thermoplastic polyester elastomer.

5. The manufacturing method according to claim 1, wherein: The first molding process and the second molding process are implemented by the following methods: co-injection molding process, insert injection molding process, over-injection molding process or multi-injection molding process.

6. The manufacturing method according to claim 1, wherein: The second molding process includes extruding the diaphragm in the radial direction using a melt of the plastic composition, so that the diaphragm is compressed in the radial direction and expanded in a direction perpendicular to the radial direction.

7. The manufacturing method according to claim 1, wherein: The second molding process includes clamping the diaphragm between an upper mold and a common lower mold, wherein the upper mold has an upper cavity for accommodating the expansion of the diaphragm, and the common lower mold further includes a telescopic part, which can support and hold the diaphragm during the first molding process; during the second molding process, the telescopic part will move downward when the upper mold and the common lower mold are closed, forming a lower cavity for accommodating the expansion of the diaphragm.

8. The manufacturing method according to claim 1, wherein: The diaphragm is not subjected to any pre-treatment for stress relief before undergoing the pre-compression.

9. The manufacturing method according to claim 2, wherein: The styrene-based block copolymer includes one or a combination of the following: 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), and styrene-[ethylene-(ethylene-propylene)]-styrene block copolymer (SEEPS).

10. The manufacturing method according to claim 1, wherein: The thermoplastic elastomer composition comprises: (a) 100 parts by weight of a block copolymer having the formula ABA, wherein A is a vinyl aromatic block and B is a hydrogenated conjugated diene block having a hydrogenation degree of more than 90%; (b) 50 to 250 parts by weight of a softener, and (c) 5 to 100 parts by weight of a polyolefin homopolymer.

11. The manufacturing method according to claim 10, wherein: The block A is derived from a monomer selected from styrene, methylstyrene and all isomers thereof, ethylstyrene and all isomers thereof, cyclohexylstyrene, vinylbiphenyl, 1-vinyl-5-hexylnaphthalene, vinylnaphthalene, vinylanthracene and any combination thereof; the block B is derived from a monomer selected 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.

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

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

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

15. The manufacturing method according to claim 10, wherein: The bonded vinyl aromatic content of the block copolymer is 20% to 50% by weight of the block copolymer, and the vinyl bond content of the block copolymer is 32% to 42% by weight of the block B of the block copolymer.

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

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