Medical rubber composition, medical rubber parts, and prefillable syringe

Abstract

To provide a medical rubber composition having excellent elution properties and gas permeability.SOLUTION: A medical rubber composition disclosed herein contains (a) butyl rubber, (b) diene rubber, and silica with a BET specific surface area of 130 m2 / g or more, the content of (a) butyl rubber being more than 30 pts.mass to less than 55 pts.mass in 100 pts.mass of a rubber component comprising (a) butyl rubber and (b) diene rubber.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to a medical rubber composition, a medical rubber part using the same, and a prefilled syringe, and more particularly to a technique for improving the gas permeability of a medical rubber part.

Background Art

[0002] In recent years, from the viewpoints of preventing medical errors, improving convenience during use, and enhancing hygiene, the use of prefilled syringes in which a syringe barrel is prefilled with a medicinal solution has been on the rise. A nozzle cap is attached to the tip of the nozzle side of the syringe barrel of the prefilled syringe to ensure liquid tightness, air tightness, sterility, etc.

[0003] Prefilled syringes include a syringe with a needle in which a needle is embedded in the nozzle of the syringe barrel in advance, and a syringe without a needle in which the nozzle cap is removed during use and an injection needle is set. The nozzle cap has a puncture part for a syringe with a needle, and there are a needle shield type that covers the nozzle with the needle punctured several millimeters into the puncture part and a type that covers the nozzle of a syringe without a needle (see Patent Documents 1 to 3, etc.).

[0004] The prefilled syringe is sterilized by ethylene oxide gas (EOG), steam sterilization, radiation sterilization by gamma rays, etc. with the nozzle cap covering the nozzle of the syringe barrel before filling with the medicinal solution, then the syringe barrel is aseptically filled with the medicinal solution, a sterilized gasket is plugged, and then packaged and shipped as a product.

[0005] In gas sterilization using EOG or steam, it is required to allow gas such as EOG or steam to permeate inside through the rubber forming the nozzle cap, so that, for example, in the case of a syringe with a needle, the entire needle including the tip punctured in the puncture part and the nozzle can be sterilized.

[0006] After EOG sterilization, it is required that residues such as ethylene oxide used for sterilization and its secondary products such as ethylene glycol and ethylene chlorohydrin can be quickly removed by degassing aeration. Also, after steam sterilization, it is required that adsorbed moisture can be quickly removed by drying.

[0007] Patent Document 4 discloses a rubber stopper for pharmaceutical containers, which is obtained by vulcanizing a butyl halide rubber compounded with 5 to 25 parts by weight of ultra-high molecular weight polyethylene fine powder per 100 parts by weight of the butyl halide rubber in the absence of a zinc compound using at least one kind of 2-substituted-4,6-dithiol-s-triazine derivative or an organic peroxide.

[0008] Patent Document 5 discloses a nozzle cap for a prefilled syringe, which is composed of a rubber composition containing a rubber component in which a diene rubber and a non-diene rubber are blended so that the proportion of the diene rubber in 100 parts by mass of the total amount of the two rubbers is 20 parts by mass or more and 70 parts by mass or less.

[0009] In addition, for medical rubber stoppers that seal the openings of syringes, etc., many items such as non-elution, high cleanliness, chemical resistance, needle puncture resistance, self-sealing property, and high slidability are essential. The quality characteristics required for medical rubber stoppers should conform to the rubber stopper test for infusions in the 17th revised Japanese Pharmacopoeia due to their applications.

[0010] Medical rubber parts are manufactured by producing an unvulcanized rubber sheet from a medical rubber composition and pressing and molding this unvulcanized rubber sheet. After pressing, the molded sheet is demolded from the mold and punched to produce medical rubber parts. When the strength of the molded product (molded sheet) is low, the molded sheet may break when demolding it from the mold. There is a problem that vulcanized rubber fragments remain in the mold, resulting in a decrease in productivity. Also, the broken molded sheet cannot be punched. In addition, when a medical rubber composition with poor moldability is used, weld lines occur in the molded product. Molded products with weld lines give a poor impression as medical rubber parts.

Prior Art Documents

Patent Documents

[0011]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0012] The present disclosure has been made in view of the above circumstances, and an object thereof is to provide a medical rubber composition having gas permeability suitable for gas sterilization while maintaining non-elution characteristics. Further, an object of the present disclosure is to provide a medical rubber composition having good moldability and high molding strength.

Means for Solving the Problems

[0013] The medical rubber composition of the present disclosure contains (a) butyl rubber, (b) diene rubber, and silica having a BET specific surface area of 130 m 2 / g or more, and the content of (a) butyl rubber is more than 30 parts by mass and less than 55 parts by mass in 100 parts by mass of a rubber component composed of (a) butyl rubber and (b) diene rubber.

Effects of the Invention

[0014] By using the medical rubber composition of the present disclosure, a medical rubber composition having gas permeability excellent for gas sterilization while maintaining non-elution characteristics and a medical rubber part using the same can be obtained. By using the medical rubber composition of the present disclosure, a medical rubber part having high moldability and high strength of the molded article can be obtained. By using the medical rubber composition of the present disclosure, a nozzle cap having excellent gas sterilization property for gas sterilization while maintaining non-elution characteristics and a prefillable syringe using the same can be obtained.

Brief Description of Drawings

[0015]

Figure 1

Figure 2

Mode for Carrying Out the Invention

[0016] The medical rubber composition of the present disclosure contains (a) butyl rubber, (b) diene rubber, and silica having a BET specific surface area of 130 m 2 / g or more, and the content of (a) butyl rubber is more than 30 parts by mass and less than 55 parts by mass in 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber.

[0017] First, (a) the above-mentioned butyl rubber will be described. As the butyl rubber, for example, a copolymer obtained by polymerizing isobutylene and a small amount of isoprene is preferable.

[0018] The butyl rubber is preferably a halogenated butyl rubber. Examples of the halogenated butyl rubber include chlorinated butyl rubber, brominated butyl rubber, and brominated copolymers of isobutylene and p-methylstyrene. As the halogenated butyl rubber, chlorinated butyl rubber or brominated butyl rubber is preferred. The chlorinated butyl rubber or brominated butyl rubber is obtained by adding or substituting chlorine or bromine to the isoprene structural part in butyl rubber, specifically, to the double bond and / or the carbon atom adjacent to the double bond.

[0019] The halogen content in the halogenated butyl rubber is preferably 0.5% by mass or more, preferably 1% by mass or more, more preferably 1.5% by mass or more, preferably 5% by mass or less, more preferably 4% by mass or less, and even more preferably 3% by mass or less.

[0020] Specific examples of the chlorinated butyl rubber include, for example, CHLOROBUTYL 1066 manufactured by Japan Butyl Co., Ltd. [Stabilizer: NS, Halogen content rate: 1.26%, Mooney viscosity: 38 ML 1+8 (125 °C), Specific gravity: 0.92]; at least one such as LANXESS X_BUTYL CB1240 manufactured by LANXESS Corporation.

[0021] Specific examples of the brominated butyl rubber include, for example, BROMOBUTYL 2255 manufactured by Japan Butyl Co., Ltd. [Stabilizer: NS, Halogen content rate: 2.0%, Mooney viscosity: 46 ML 1+8 (125 °C), Specific gravity: 0.93]; at least one such as LANXESS X_BUTYL BBX2 manufactured by LANXESS Corporation.

[0022] The medical rubber composition of the present disclosure contains (b) a diene rubber as a rubber component. The diene rubber is a rubber obtained by polymerizing a diene monomer and is a rubber having a double bond in the main chain. In the present disclosure, (a) butyl rubber, which is a copolymer obtained by polymerizing isobutylene and a small amount of isoprene, is treated as not belonging to the diene rubber although it copolymerizes a small amount of isoprene.

[0023] Examples of the diene rubber include natural rubber (NR), isoprene rubber (IR), polybutadiene (BR), styrene-butadiene rubber (SBR), chloroprene rubber (CR), and acrylonitrile-butadiene rubber (NBR). These may be used alone or in combination of two or more.

[0024] In the present disclosure, as the diene rubber, it is preferable to use a diene rubber containing (b) polybutadiene. The content of polybutadiene in the diene rubber is preferably 50% by mass or more, more preferably 70% by mass or more, and even more preferably 90% by mass or more. Also, a preferred embodiment is that the diene rubber consists only of polybutadiene.

[0025] The content of (a) butyl rubber in the medical rubber composition of the present disclosure is preferably more than 30 parts by mass, more preferably 31 parts by mass or more, even more preferably 33 parts by mass or more, preferably less than 55 parts by mass, more preferably 54 parts by mass or less, and even more preferably 52 parts by mass or less per 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber. If the content of (a) butyl rubber is within the above range, the gas permeability can be increased while maintaining excellent non-elution characteristics. As a result, for example, the time of the gas sterilization process of the prefillable syringe before filling with the chemical solution can be shortened.

[0026] The medical rubber composition of the present disclosure preferably contains (c) a crosslinking agent, and more preferably contains (c1) a peroxide-based crosslinking agent. The (c1) peroxide-based crosslinking agent is mainly compounded to crosslink (b) the diene rubber.

[0027] (c1) Specifically, examples of the peroxide-based crosslinking agent include dialkyl peroxide, peroxy ester, peroxy ketal, hydroperoxide, etc. Examples of the dialkyl peroxide include di(2-t-butylperoxyisopropyl)benzene, dicumyl peroxide, 2,5-dimethyl-2,5-di(t-butylperoxy)hexane, t-butylcumyl peroxide, di-t-hexyl peroxide, di-t-butyl peroxide, 2,5-dimethyl-2,5-di(t-butylperoxy)hexyne-3, etc. Examples of the peroxy ester include t-butyl peroxymaleate, t-butyl peroxy-3,3,5-trimethylcyclohexanoate, t-butyl peroxylaurate, t-butyl peroxyisopropyl monocarbonate, t-hexyl peroxybenzoate, 2,5-dimethyl-2,5-di(benzoylperoxy)hexane, t-butyl peroxyacetate, t-butyl peroxybenzoate, etc. Examples of the peroxy ketal include 1,1-di(t-hexylperoxy)-3,3,5-trimethylcyclohexane, 1,1-di(t-hexylperoxy)cyclohexane, 1,1-di(t-butylperoxy)-2-methylcyclohexane, 1,1-di(t-butylperoxy)cyclohexane, 2,2-di(t-butylperoxy)butane, n-butyl-4,4-di(t-butylperoxy)valerate, 2,2-di(4,4-di(t-butylperoxy)cyclohexyl)propane, etc. Examples of the hydroperoxide include p-menthane hydroperoxide, diisopropylbenzene hydroperoxide, etc. These organic peroxides may be used alone or in combination of two or more.

[0028] In the medical rubber composition of the present disclosure, the content of (c1) the peroxide crosslinking agent is preferably 0.05 parts by mass or more, more preferably 0.1 parts by mass or more, still more preferably 0.15 parts by mass or more, preferably 7 parts by mass or less, more preferably 5 parts by mass or less, and still more preferably 2 parts by mass or less, based on 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber. If the content of (c1) the peroxide crosslinking agent is within the above range, softening of the butyl rubber component can be suppressed and non-elution property can be maintained.

[0029] The medical rubber composition of the present disclosure can contain a crosslinking agent other than (c1) the peroxide crosslinking agent as long as the effects of the present disclosure are not impaired. Examples of the crosslinking agent other than (c1) the peroxide crosslinking agent include (c2) triazine derivatives, (c3) sulfur, (c4) metal oxides, (c5) resin crosslinking agents, etc., and these can be used alone or in combination of two or more.

[0030] The medical rubber composition of the present disclosure preferably contains a (c2) triazine derivative. The triazine derivative acts as a crosslinking agent for (a) butyl rubber. Examples of the triazine derivative include compounds represented by the general formula (1). [Chemical formula] [In the formula, R is -SH, -OR 1 , -SR 2 , -NHR 3 or -NR 4 R 5 (R 1 , R 2 , R 3 , R 4 and R 5 represent an alkyl group, an alkenyl group, an aryl group, an aralkyl group, an alkylaryl group or a cycloalkyl group. R 4 and R 5 may be the same or different. ). M 1and M 2 is H, Na, Li, K, 1 / 2Mg, 1 / 2Ba, 1 / 2Ca, an aliphatic primary amine, secondary amine or tertiary amine, a quaternary ammonium salt or a phosphonium salt. M 1 and M 2 may be the same or different.]

[0031] In the general formula (1), examples of the alkyl group include alkyl groups having 1 to 12 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, tert-pentyl group, n-hexyl group, 1,1-dimethylpropyl group, octyl group, isooctyl group, 2-ethylhexyl group, decyl group, or dodecyl group. Examples of the alkenyl group include alkenyl groups having 1 to 12 carbon atoms such as vinyl group, allyl group, 1-propenyl group, isopropenyl group, 2-butenyl group, 1,3-butadienyl group, or 2-pentenyl group. Examples of the aryl group include monocyclic or condensed polycyclic aromatic hydrocarbon groups, and aryl groups having 6 to 14 carbon atoms such as phenyl group, naphthyl group, anthryl group, phenanthryl group or acenaphthylenyl group. Examples of the aralkyl group include aralkyl groups having 7 to 19 carbon atoms such as benzyl group, phenethyl group, diphenylmethyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 2,2-diphenylethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylpentyl group, 2-biphenylylmethyl group, 3-biphenylylmethyl group or 4-biphenylylmethyl group. Examples of the alkylaryl group include alkylaryl groups having 7 to 19 carbon atoms such as tolyl group, xylyl group or octylphenyl group. Examples of the cycloalkyl group include cycloalkyl groups having 3 to 9 carbon atoms such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group or cyclononyl group.

[0032] Specific examples of the triazine derivative represented by the general formula (1) include, for example, 2,4,6-trimercapto-s-triazine, 2-methylamino-4,6-dimercapto-s-triazine, 2-(n-butylamino)-4,6-dimercapto-s-triazine, 2-octylamino-4,6-dimercapto-s-triazine, 2-propylamino-4,6-dimercapto-s-triazine, 2-diallylamino-4,6-dimercapto-s-triazine, 2-dimethylamino-4,6-dimercapto-s-triazine, 2-dibutylamino-4,6-dimercapto-s-triazine, 2-di(iso-butylamino)-4,6-dimercapto-s-triazine, 2-dipropylamino-4,6-dimercapto-s-triazine, 2-di(2-ethylhexyl)amino-4,6-dimercapto-s-triazine, 2-dioleylamino-4,6-dimercapto-s-triazine, 2-laurylamino-4,6-dimercapto-s-triazine or 2-anilino-4,6-dimercapto-s-triazine, or sodium salts or disodium salts thereof.

[0033] Among these, 2,4,6-trimercapto-s-triazine, 2-dialkylamino-4,6-dimercapto-s-triazine, and 2-anilino-4,6-dimercapto-s-triazine are preferred, and 2-dibutylamino-4,6-dimercapto-s-triazine is particularly preferred because of its easy availability.

[0034] In addition, examples of the triazine derivative include one or more of 6-[bis(2-ethylhexyl)amino]-1,3,5-triazine-2,4-dithiol, 6-diisobutylamino-1,3,5-triazine-2,4-dithiol, 6-dibutylamino-1,3,5-triazine-2,4-dithiol, 6-dibutylamino-1,3,5-triazine-2,4-dithiol·monosodium, 6-anilino-1,3,5-triazine-2,4-dithiol, 1,3,5-triazine-2,4,6-trithiol, etc.

[0035] In the present disclosure, as the triazine derivative, one type may be used alone, or two or more types may be used in combination.

[0036] In the present disclosure, it is preferable to use (c1) a peroxide-based crosslinking agent and (c2) a triazine derivative in combination. In this case, the mass ratio of (c1) peroxide-based crosslinking agent / (c2) triazine derivative is preferably 0.05 or more, more preferably 0.1 or more, further preferably 0.15 or more, preferably 0.5 or less, more preferably 0.25 or less, and further preferably 0.2 or less. By setting (c1) peroxide-based crosslinking agent / (c2) triazine derivative within the above range, it is possible to achieve both low elution property and the crosslinking degree required for the blend polymer.

[0037] Examples of (c3) sulfur used as a crosslinking agent include powdered sulfur, fine sulfur, precipitated sulfur, colloidal sulfur, sulfur chloride, and the like.

[0038] Examples of (c4) metal oxide used as a crosslinking agent include magnesium oxide, calcium oxide, zinc oxide, copper oxide, and the like.

[0039] Examples of (c5) resin crosslinking agents include alkylphenol formaldehyde resins such as alkylphenol formaldehyde resins, thermoreactive phenol resins, phenol dialcohol resins, bisphenol resins, and thermoreactive bromomethylalkylated phenol resins.

[0040] The medical rubber composition of the present disclosure preferably does not contain a vulcanization accelerator. This is because the vulcanization accelerator may remain in the final rubber product and dissolve into the chemical solution in the syringe or vial. Examples of the vulcanization accelerator include guanidine-based accelerators (e.g., diphenylguanidine), thiuram-based accelerators (e.g., tetramethylthiuram disulfide, tetramethylthiuram monosulfide), dithiocarbamate-based accelerators (e.g., zinc dimethyldithiocarbamate), thiazole-based accelerators (e.g., 2-mercaptobenzothiazole, dibenzothiazyl disulfide), and sulfenamide-based accelerators (N-cyclohexyl-2-benzothiazole sulfenamide, N-t-butyl-2-benzothiazole sulfenamide).

[0041] The medical rubber composition of the present disclosure may contain hydrotalcite. Hydrotalcite functions as a scorch inhibitor during the crosslinking of butyl rubber halide and also functions to prevent an increase in the compression set of medical rubber parts. Furthermore, hydrotalcite functions as an acid acceptor to absorb chlorine-based gases and bromine-based gases generated during the crosslinking of butyl rubber halide and prevent the occurrence of crosslinking inhibition and the like caused by these gases. Note that the magnesium oxide described above can also function as an acid acceptor.

[0042] Examples of hydrotalcite include Mg 4.5 Al 2 (OH) 13 CO 3 ·3.5H 2 O, Mg 4.5 Al 2 (OH) 13 CO 3 、Mg 4 Al 2 (OH) 12 CO 3 ·3.5H 2 O, Mg 6 Al 2 (OH) 16 CO 3 ·4H 2 O, Mg 5 Al 2 (OH) 14 CO3 ·4H 2 O, Mg 3 Al 2 (OH) 10 CO 3 ·1.7H 2 One or more of Mg-Al-based hydrotalcites such as 3 4H 2 O, Mg 3 Al 2 (OH) 10 CO 3 ·1.7H 2 O can be mentioned.

[0043] Specific examples of hydrotalcite include, for example, DHT-4A (registered trademark)-2 manufactured by Kyowa Chemical Industry Co., Ltd.

[0044] In the medical rubber composition, when hydrotalcite is used as an acid acceptor, it is preferably used in combination with MgO. In this case, it is preferable to consider the blending amount of hydrotalcite in terms of the total amount of the acid acceptor (hydrotalcite and MgO). The total content as the acid acceptor (hydrotalcite and MgO) is preferably 0.5 parts by mass or more, more preferably 1 part by mass or more, preferably 15 parts by mass or less, and more preferably 10 parts by mass or less with respect to 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber. If the total content of the acid acceptor (hydrotalcite and MgO) is within the above range, rust generation on molds and the like can be suppressed, and the problem that the raw material itself becomes white dot foreign matter can be reduced.

[0045] The medical rubber composition of the present disclosure may contain a co-crosslinking agent. The co-crosslinking agent is considered to act on the radicals of the (b) diene rubber formed by the peroxide-based crosslinking agent to form crosslinks.

[0046] The co-crosslinking agent is preferably a polyfunctional (meth)acrylate compound. The polyfunctional (meth)acrylate compound is more preferably a (meth)acrylate-based compound having two or more functional groups, still more preferably a (meth)acrylate-based compound having three or more functional groups, preferably an (meth)acrylate-based compound having eight or fewer functional groups, and preferably an (meth)acrylate-based compound having six or fewer functional groups. Examples of the (meth)acrylate compound having two or more functional groups include compounds having at least two acryloyl groups and / or methacryloyl groups. Note that "(meth)acrylate" means "acrylate" and / or "methacrylate".

[0047] Examples of the (meth)acrylate-based compound having two or more functional groups include di(meth)acrylate of polyethylene glycol, 1,4-butanediol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, 1,9-nonanediol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, trimethylolethane tri(meth)acrylate, pentaerythritol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, glycerin tri(meth)acrylate, dipentaerythritol tri(meth)acrylate, dipentaerythritol tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, dipentaerythritol hexa(meth)acrylate, tripentaerythritol tetra(meth)acrylate, tripentaerythritol penta(meth)acrylate, tripentaerythritol hexa(meth)acrylate, tripentaerythritol hepta(meth)acrylate, and the like. The co-crosslinking agent may be used alone or in combination of two or more.

[0048] The content of the co-crosslinking agent in the medical rubber composition of the present disclosure is preferably 0.1 part by mass or more, more preferably 0.4 part by mass or more, still more preferably 0.6 part by mass or more, preferably 10 parts by mass or less, more preferably 5 parts by mass or less, and still more preferably 3 parts by mass or less, based on 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber. If the content of the co-crosslinking agent is within the above range, softening of the butyl rubber component can be suppressed and non-elution properties can be maintained.

[0049] The medical rubber composition of the present disclosure preferably contains silica having a BET specific surface area of 130 m 2 / g or more as the (d) filler. By containing the silica, the strength of the obtained medical rubber product becomes good.

[0050] The BET specific surface area of the silica is preferably 130 m 2 / g or more, more preferably 140 m 2 / g or more, still more preferably 150 m 2 / g or more, particularly preferably 160 m 2 / g or more, and preferably 300 m 2 / g or less, more preferably 240 m 2 / g or less, and still more preferably 200 m 2 / g or less. If the specific surface area of the silica is within the above range, the strength of the obtained medical rubber product becomes good.

[0051] The compounding amount of the silica is preferably 2 parts by mass or more, more preferably 3 parts by mass or more, preferably less than 10 parts by mass, more preferably 9 parts by mass or less, and still more preferably 7 parts by mass or less, based on 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber. If the content of the silica is 2 parts by mass or more, the strength of the obtained medical rubber product becomes good. Further, if the content of the silica is less than 10 parts by mass, the occurrence of patterns (welds) during molding is suppressed on the surface of the obtained medical rubber product.

[0052] In the medical rubber composition of the present disclosure, fillers other than silica may be blended. (d) Examples of the filler include inorganic fillers such as clay and talc, olefin resins, styrene elastomers, or resin powders of ultra-high molecular weight polyethylene (UHMWPE). Among these, as the filler, inorganic fillers are preferred, and clay or talc is more preferred. The filler functions to adjust the rubber hardness of medical rubber parts and also functions to reduce the production cost of medical rubber parts as a bulking agent.

[0053] Examples of the clay include calcined clay and kaolin clay. Specific examples of the clay include, for example, SILLITIN (registered trademark) Z manufactured by HOFFMANN MINERAL, SATINTONE (registered trademark) W manufactured by ENGELHARD, NN kaolin clay manufactured by Tsuchiya Kaolin Industry Co., Ltd., PoleStar200R manufactured by Imerys Specialties Japan Co., Ltd., and the like.

[0054] Specific examples of the talc include, for example, HITRON A manufactured by Takehara Chemical Industry Co., Ltd., MICRO ACE (registered trademark) K-1 manufactured by Nippon Talc Co., Ltd., Mistron (registered trademark) Vapor manufactured by Imerys Specialties Japan Co., Ltd., and the like.

[0055] The content of the filler other than silica is preferably set appropriately according to the rubber hardness and the like of the target medical rubber part. The content of the filler other than silica is, for example, preferably 10 parts by mass or more, more preferably 15 parts by mass or more, still more preferably 20 parts by mass or more, preferably 40 parts by mass or less, more preferably 35 parts by mass or less, and still more preferably 30 parts by mass or less with respect to 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber.

[0056] The medical rubber composition of the present disclosure may further contain a colorant such as titanium oxide or carbon black, stearic acid, a lubricant of low-density polyethylene (LDPE), a processing aid, polyethylene glycol as a crosslinking activator, a plasticizer (e.g., paraffin oil), etc. in appropriate proportions.

[0057] For the medical rubber composition of the present disclosure, the content rate (mass %) of the inorganic filler is preferably 10% or more, more preferably 15% or more, still more preferably 20% or more, preferably 45% or less, more preferably 40% or less, and still more preferably 35% or less. If the content rate of the inorganic filler is within the above range, moldability and kneading processability can be achieved simultaneously, and the impurity concentration can also be suppressed. The inorganic filler includes, for example, silica, kaolin, magnesium oxide, etc., but does not include carbon black.

[0058] The present disclosure includes a medical rubber part formed by molding the medical rubber composition of the present disclosure. Examples of the medical rubber part of the present disclosure include a rubber stopper and a sealing member for containers for various drugs such as liquid preparations, powder preparations, and freeze-dried preparations, a rubber stopper for a vacuum blood collection tube, a plunger stopper for a prefilled syringe, or a sliding or sealing part such as a nozzle cap.

[0059] The medical rubber composition of the present disclosure is obtained by kneading (a) butyl rubber, (b) diene rubber, silica, and other compounding materials added as necessary. The kneading can be performed using, for example, an open roll, a closed kneader, etc. The kneaded product is preferably formed into a ribbon shape, a sheet shape, a pellet shape, etc., and more preferably formed into a sheet shape.

[0060] By press-molding a ribbon-shaped, sheet-shaped, or pellet-shaped kneaded product, a medical rubber part with a desired shape can be obtained. During pressing, the crosslinking reaction of the medical rubber composition proceeds. The molding temperature is preferably, for example, 130°C or higher, more preferably 140°C or higher, preferably 200°C or lower, and more preferably 190°C or lower. The molding time is preferably 2 minutes or longer, more preferably 3 minutes or longer, preferably 60 minutes or shorter, and more preferably 30 minutes or shorter. The molding pressure is preferably 0.1 MPa or higher, more preferably 0.2 MPa or higher, preferably 10 MPa or lower, and more preferably 8 MPa or lower.

[0061] From the molded product after press molding, unnecessary parts are cut off and removed to obtain a predetermined shape. The obtained molded product is washed, sterilized, dried, and packaged to produce a medical rubber part.

[0062] Also, a resin film may be laminated and integrated with the medical rubber part in the same manner as in the prior art. Examples of the resin film include films of inert resins such as polytetrafluoroethylene (PTFE), tetrafluoroethylene-ethylene copolymer (ETFE), modified products thereof, and ultra-high molecular weight polyethylene (UHMWPE).

[0063] The resin film may be integrated with the medical rubber part formed after press molding, for example, by press molding in a state of being stacked on a rubber composition in a sheet shape.

[0064] The medical rubber part of the present disclosure is preferably represented by the durometer type A hardness (Shore A hardness) measured in accordance with the measurement method described in Japanese Industrial Standard JIS K6253-3:2012 "Vulcanized Rubber and Thermoplastic Rubber - Method for Measuring Hardness - Part 3: Durometer Hardness" and is preferably 35 or higher and preferably 70 or lower.

[0065] Sliding or sealing parts such as plunger stoppers and nozzle caps for prefillable syringes preferably have a Shore A hardness of 40 or more and preferably 70 or less. In the case of a nozzle cap of the needle shield type for a syringe with a needle, in order to make it easier to pierce the needle into the piercing part and more reliably prevent the needle from bending, the Type A durometer hardness of the nozzle cap is particularly preferably 55 or less.

[0066] On the other hand, in the case of a nozzle cap for a syringe without a needle, in order to further improve the sealing performance when storing the nozzle cap on the nozzle or more reliably prevent the nozzle cap from loosening and falling off the nozzle, the Type A durometer hardness of the nozzle cap is particularly preferably 40 or more.

[0067] The rubber hardness of medical rubber parts can be adjusted by changing the blending ratio of each raw material.

[0068] The medical rubber part formed by molding the medical rubber composition of the present disclosure has a gas permeability per 1 mm thickness of the sample (cc·cm / cm 2 ·sec·cmHg) measured by Method B (isobaric method) specified in Japanese Industrial Standard JIS K7126-1987 "Test Method for Gas Permeability of Plastic Films and Sheets" is preferably 2×10 -9 or more, more preferably 4×10 -9 or more, still more preferably 8×10 -9 or more, preferably 8×10 -8 or less, more preferably 4×10 -8 or less, and still more preferably 2×10 -8 or less. To adjust the gas permeability within the above range, it can be adjusted by changing the blending ratio of each raw material. The gas permeability is preferably measured using, for example, O 2 .

[0069] If the gas permeability is within the above range, good gas permeability can be ensured. During EOG sterilization, EOG can be quickly permeated into the inside of the nozzle cap, and the nozzle and the needle can be sterilized in a short time. Also, during degassing aeration, residues such as ethylene oxide, ethylene glycol, and ethylene chlorohydrin can be quickly reduced, shortening the sterilization time and improving the productivity of prefillable syringes. Also, if the gas permeability is too high, the permeation of general gases during normal storage except during sterilization will increase too much, deteriorating the sealing performance.

[0070] Also, during degassing aeration, the internal pressure generated inside the nozzle cap can be quickly released, preventing the nozzle cap from loosening and falling off the nozzle.

[0071] The rubber part formed by molding the medical rubber composition of the present disclosure can be suitably used as the nozzle cap of a prefillable syringe. Also, the present disclosure includes a prefillable syringe having the nozzle cap of the present disclosure. In the present disclosure, a prefillable syringe means a syringe used for a prefilled syringe and means a syringe before filling with a chemical solution. The prefillable syringe of the present disclosure is preferably gas-sterilized with the nozzle cap attached to the syringe.

[0072] Note that the nozzle cap may be called by names such as a needle cap, a needle shield, a rubber cap, a tip cap, a blander tip, a syringe sealing plug, etc. depending on the attachment form and the like.

[0073] Examples of the gas sterilization include steam sterilization and ethylene oxide gas (EOG) sterilization treatment.

[0074] EOG sterilization treatment is a method of sterilizing equipment in an atmosphere of ethylene oxide gas. The concentration of ethylene oxide gas is preferably 400 mg / l to 1100 mg / l, more preferably 450 mg / l to 900 mg / l, and even more preferably 500 mg / l to 700 mg / l. If the concentration of ethylene oxide gas becomes too high, the residual concentration of EOG gas tends to be high after sterilization. Also, the EOG sterilization temperature is preferably from 35°C to 70°C, and the sterilization humidity (relative humidity) is preferably 40%RH or more.

[0075] Figure 1(a) is a cross-sectional view showing an example of an embodiment of the nozzle cap of the present disclosure and the nozzle of a syringe barrel covering it, and Figure 1(b) is a cross-sectional view showing the state where the nozzle cap of Figure 1(a) is covering the nozzle.

[0076] The nozzle cap 9 is for covering the nozzle 12 of the syringe barrel 11 of the needleless syringe 10. The nozzle cap 9 is integrally formed of the above-described medical rubber composition. The nozzle cap 9 includes a cylindrical portion 13 having an inner diameter D3 slightly smaller than the outer diameter D4 of the nozzle 12.

[0077] One end side (the upper end side in the figure) of the cylindrical portion 13 is closed, and an opening 14 for inserting the nozzle 12 into the cylindrical portion 13 to cover the nozzle 12 with the nozzle cap 9 is provided on the other end side (the lower end side in the figure).

[0078] Figure 2(a) is a cross-sectional view showing another example of an embodiment of the nozzle cap of the present disclosure and the nozzle of a syringe barrel covering it, and Figure 2(b) is a cross-sectional view showing the state where the nozzle cap of Figure 2(a) is covering the nozzle.

[0079] The nozzle cap 1 is for a syringe 5 with a needle in which a needle 4 is embedded in the nozzle 3 of the syringe barrel 2 in advance. The nozzle cap 1 is entirely integrally formed of a medical rubber composition. The nozzle cap 1 includes a cylindrical portion 6 having an inner diameter D1 slightly smaller than the outer diameter D2 of the nozzle 3, and a needle puncturing portion 7 connected to one end side (the upper end side in the figure) of the cylindrical portion 6.

[0080] The puncturing part 7 is formed in a columnar shape having an outer surface continuous with the cylindrical part 6. On the other end side (the lower end side in the figure) of the cylindrical part 6, an opening 8 is provided for inserting the nozzle 3 into the cylindrical part 6 and covering the nozzle 3 with the nozzle cap 1.

[0081] The axial dimension L1 of the cylindrical part 6 from the one end where the puncturing part 7 is integrally formed and closed to the other end on the opening 8 side is set such that L1 < L2 with respect to the dimension L2 from the other end on the opening 8 side to the tip of the needle 4 in a state where the nozzle cap 1 covers the nozzle 3. Thereby, the tip part of the needle 4 can be punctured into the puncturing part 7 by about 5 mm and sealed to ensure liquid tightness, air tightness, sterility, etc.

[0082] It is preferable to set the nozzle caps 1 and 9 to the region with the smallest thickness, that is, the thickness T2 of the cylindrical part 13 in the examples of FIGS. 1(a) and (b) and the thickness T1 of the cylindrical part 6 in the examples of FIGS. 2(a) and (b) to 1.0 ± 0.5 mm, respectively.

[0083] When the thicknesses T1 and T2 exceed this range, the permeation of gas or water vapor is suppressed, so that EOG sterilization, degassing aeration, or steam sterilization and subsequent drying may take a long time and the productivity of the prefillable syringe may decrease.

[0084] Also, during degassing aeration, or during steam sterilization or its drying, the internal pressure generated inside the nozzle caps 1 and 9 cannot be quickly released. Therefore, due to the increase in the internal pressure, the nozzle caps 1 and 9 may become loose and easily fall off from the nozzles 3 and 12. On the other hand, when the thicknesses T1 and T2 are less than the above range, the rigidity is insufficient, and it is likely to cause a capping defect when capping the nozzle caps 1 and 9 on the nozzles 3 and 12, which may reduce the productivity of the prefillable syringe.

[0085] On the other hand, when the thicknesses T1 and T2 are within the above ranges, good gas permeability is imparted to the nozzle caps 1 and 9, and particularly during EOG sterilization, EOG can rapidly permeate into the nozzle caps 1 and 9, enabling the nozzles 3 and 12 and the needle 4 to be sterilized in a short time. Moreover, during degassing aeration, residues such as ethylene oxide, ethylene glycol, and ethylene chlorohydrin can be rapidly removed, improving the productivity of the prefillable syringe.

[0086] Also, during degassing aeration, the internal pressure generated inside the nozzle caps 1 and 9 can be rapidly released, preventing the nozzle caps 1 and 9 from loosening and falling off from the nozzles 3 and 12.

[0087] Furthermore, by imparting appropriate rigidity to the nozzle caps 1 and 9, it is possible to reduce the occurrence of poor plugging when covering the nozzle caps 1 and 9 on the nozzles 3 and 12, improving the productivity of the prefillable syringe.

Example

[0088] Hereinafter, the present disclosure will be described in detail by way of examples. However, the present disclosure is not limited by the following examples, and any modifications and embodiments within the scope not departing from the spirit of the present disclosure are all included in the scope of the present disclosure.

[0089] [Preparation of Medical Rubber Composition] The materials shown in Table 1 were kneaded to prepare a medical rubber composition. The kneading was carried out at 20 °C for about 10 minutes using an open roll.

[0090]

Table 1

[0091] Details of the compounding materials used are as follows. Butyl rubber: HT-1066 (chlorinated butyl rubber) Diene rubber: polybutadiene rubber BR-1220 Silica: Nipsil (BET specific surface area 80m 2 / g~130m 2 / g, 130m 2 / g~190m 2 / g, 180m 2 / g~230m 2 / g) Magnesium Oxide: Kyowa Mag MF Talc: Mistron Fired Kaolin: Satinon PEG4000: Polyoxyethylene Glycol (average molecular weight 3100, freezing point 55°C) Carbon Black: Thermal MT Peroxide Crosslinking Agent: Perhexa 25B-40 Triazine Derivative: 6-Dibutylamino-1,3,5-triazine-2,4-dithiol

[0092] [Evaluation Method] (1) Gas Permeability Coefficient (cc·cm / cm 2 ·sec·cmHg) From the obtained medical rubber composition, a test piece for measuring the gas permeability coefficient was prepared, and the gas permeability coefficient was measured. The measurement was carried out by the differential pressure method using GTR-30XASR manufactured by GTR in accordance with JIS-K6275-1. Test Gas: O 2 Measurement Sample: The rubber composition formulated as described above was press-molded at 180°C for 6 minutes to prepare a slab with a thickness of 0.5 mm to 1.0 mm. [Relative Evaluation] In the table, O 2 When the permeability coefficient is 2.0×10 -9 (cc·cm / cm 2 ·sec·cmHg) or more, it is indicated as "〇", and when it is less than 2.0×10 -9 (cc·cm / cm 2 ·sec·cmHg), it is indicated as "×".

[0093] (2) Eluate Test Measurement Sample: The rubber composition formulated as described above was press-molded at 180°C for 6 minutes to prepare a 2 mm slab. It was punched out with a φ17 mm punch to obtain a test sample. For the manufactured samples, the "Eluate Test" described in the "7.03 Rubber Stopper Test Method for Infusions" of the 17th Revised Japanese Pharmaceutical Affairs Law was carried out. The compliance conditions were as follows. Appearance of the test solution: Colorless and clear UV transmittance: At a layer length of 10 mm, the transmittance at a wavelength of 430 nm and a wavelength of 650 nm is 99.0% or more Ultraviolet absorption spectrum: The absorbance at wavelengths from 220 nm to 350 nm is 0.20 or less pH: The difference between the test solution and the blank test solution is 1.0 or less Zinc: The absorbance of the sample solution is less than or equal to the absorbance of the standard solution Potassium permanganate reducing substances: 2.0 mL / 100 mL or less (Pharmacopoeia standard) Evaporation residue: 2.0 mg or less <Relative evaluation> In the table, when the concentration of potassium permanganate reducing substances is less than 0.5 mL / 100 mL, "○" is described, and when the concentration of potassium permanganate reducing substances is 0.5 mL / 100 mL or more, "×" is described.

[0094] (3) Strength of the molded product 〈Tensile property test〉 The rubber composition formulated as described above was press-molded under the conditions of 180 °C × 6 minutes to form a sheet with a thickness of 2 mm. Each sheet was punched out to produce dumbbell-shaped No. 3 test pieces specified in Japanese Industrial Standard JIS K6251:2010 "Vulcanized Rubber and Thermoplastic Rubber - Method of Testing Tensile Properties". Then, under the environment of a temperature of 23 °C and a relative humidity of 55%, the tensile test described in the above standard was carried out to obtain the tensile strength TS (MPa), elongation at break Eb (%), and tensile stress at 100% elongation (100% modulus). The strength of the molded product was evaluated using the tensile strength TS (MPa).

[0095] (4) Moldability (occurrence of weld) A cap having the shape shown in Fig. 1(a) was produced by press molding under the conditions of 180 °C × 6 minutes, and then the surface of the side of the cap was visually inspected. When a weld (rubber flow pattern) could be confirmed, it was judged as ×, and when it could not be confirmed, it was judged as 〇.

[0096] The results of gas permeability, eluate test, molded product strength, and molding processability are shown together in Table 1.

[0097] It can be seen from Table 1 that the medical rubber parts formed from the medical rubber composition of the present disclosure are excellent in non-elution property and gas permeability.

[0098] The present disclosure (1) contains (a) butyl rubber, (b) diene rubber, and silica having a BET specific surface area of 130 m 2 / g or more, and the content of (a) butyl rubber is more than 30 parts by mass and less than 55 parts by mass in 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber.

[0099] The present disclosure (2) is the medical rubber composition according to the present disclosure (1), wherein the content of (a) butyl rubber is 31 parts by mass or more and 54 parts by mass or less in 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber.

[0100] The present disclosure (3) is the medical rubber composition according to the present disclosure (1) or (2), wherein (b) the diene rubber contains polybutadiene.

[0101] The present disclosure (4) is the medical rubber composition according to any one of the present disclosures (1) to (3), wherein the BET specific surface area of the silica is 160 m 2 / g or more and 240 m 2 / g or less.

[0102] The present disclosure (5) is the medical rubber composition according to any one of the present disclosures (1) to (4), which contains 2 parts by mass to less than 10 parts by mass of the silica with respect to 100 parts by mass of the rubber component.

[0103] The present disclosure (6) is the medical rubber composition according to any one of the present disclosures (1) to (5), which contains 3 parts by mass to 9 parts by mass of the silica with respect to 100 parts by mass of the rubber component.

[0104] The present disclosure (7) is further a medical rubber composition according to any one of the present disclosures (1) to (6) containing (c1) a peroxide-based crosslinking agent and (c2) a triazine derivative.

[0105] The present disclosure (8) is a medical rubber part formed by molding the medical rubber composition according to any one of the present disclosures (1) to (7).

[0106] The present disclosure (9) is a nozzle cap for a prefillable syringe formed by molding the medical rubber composition according to any one of the present disclosures (1) to (7).

[0107] The present disclosure (10) is a prefillable syringe characterized by having the nozzle cap described in the present disclosure (9).

[0108] The present disclosure (11) is the prefillable syringe according to the present disclosure (10), characterized in that the nozzle cap is gas sterilized in a state of being attached to the syringe.

Explanation of Signs

[0109] 1,9: nozzle cap, 2,11: syringe barrel, 3,12: nozzle, 4: needle, 5,10: syringe, 6,13: cylindrical part, 7: needle puncture part, 8,14: opening, D 1 ,D 3 : inner diameter, D 2 ,D 4 : outer diameter, L 1 ,L 2 : dimension, T 1 ,T 2 : thickness

Claims

1. (a) Butyl rubber, (b) a diene rubber, and silica having a BET specific surface area of 130 m ２ / g or more, which is a medical rubber composition containing (a) The content of butyl rubber is more than 30 parts by mass and less than 55 parts by mass in 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber, The medical rubber composition contains 3 parts by mass to 9 parts by mass of the silica with respect to 100 parts by mass of the rubber component, and the content rate of the inorganic filler is 10% by mass or more and 45% by mass or less. A medical rubber composition characterized by the above.

2. The medical rubber composition according to claim 1, wherein (a) the content of butyl rubber is 31 parts by mass or more and 54 parts by mass or less in 100 parts by mass of the rubber component composed of (a) butyl rubber and (b) diene rubber.

3. The medical rubber composition according to claim 1 or 2, wherein (b) the diene rubber contains polybutadiene.

4. The BET specific surface area of the silica is 160 m ２ / g or more and 240 m ２ / g or less, and the medical rubber composition according to any one of claims 1 to 3.

5. The medical rubber composition according to any one of claims 1 to 3, wherein the BET specific surface area of the silica is 130 m2 / g or more and 200 m2 / g or less.

6. The medical rubber composition according to any one of claims 1 to 5, wherein the inorganic filler contains clay or talc.

7. The medical rubber composition according to any one of claims 1 to 6, further containing (c1) a peroxide crosslinking agent and (c2) a triazine derivative.

8. The medical rubber composition according to claim 7, wherein the mass ratio ((c1) / (c2)) of (c1) the peroxide crosslinking agent and (c2) the triazine derivative is 0.05 or more and 0.25 or less.

9. The medical rubber composition according to any one of claims 1 to 8, wherein the (a) butyl rubber is halogenated butyl rubber.

10. A medical rubber part formed by molding the medical rubber composition according to any one of claims 1 to 9.

11. A nozzle cap for a prefillable syringe formed by molding the medical rubber composition according to any one of claims 1 to 9.

12. A prefillable syringe, characterized by having the nozzle cap according to claim 11.

13. The prefillable syringe according to claim 12, wherein the nozzle cap is gas sterilized in a state of being attached to the syringe.

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