Sterilization method for medical rubber parts

Abstract

To provide a sterilization method for a medical rubber part that includes a body made from an elastic material with an inactive resin film stacked on at least a portion of the body surface, whereby the non-eluting characteristics of the medical rubber part can be maintained even after sterilization with gamma rays.SOLUTION: A sterilization method for a medical rubber part according to the present invention involves irradiating a packaged article with gamma rays. The packaged article contains a plurality of medical rubber parts, where each of the medical rubber parts includes a body made from an elastic material with an inactive resin film stacked on at least a portion of the body surface. The packaged article has an oxygen level of 5% or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for sterilizing medical rubber parts. [Background technology]

[0002] Medical rubber stoppers, which seal the openings of syringes, vials, etc., are required to have many properties, such as non-elution, high cleanliness, chemical resistance, needle-prick resistance, self-sealing properties, and high sliding properties. The quality characteristics required of medical rubber stoppers should conform to the rubber stopper test for infusions in the 17th revision of the Japanese Pharmacopoeia, given their intended use.

[0003] There is an increasing demand for ready-to-use (RTU) medical rubber products (such as syringe gaskets and vial stoppers) that are delivered in a sterilized state. Sterilization assurance methods include high-pressure steam sterilization, ethylene oxide gas (EOG) sterilization, and gamma ray sterilization. Gamma ray sterilization allows medical rubber products to be sterilized in their packaging, so it has the advantage of allowing them to be delivered without opening the packaging. Due to environmental concerns, there is a trend towards gamma ray sterilization over EOG sterilization.

[0004] Gamma ray sterilization guarantees sterilization by setting and measuring the absorbed dose. When multiple medical rubber parts are packed into a packaging bag and then gamma ray sterilized, uneven distribution of the medical rubber parts within the packaging bag may occur. Therefore, even if the packaging bag is irradiated with gamma rays at a specified exposure dose, variations in the absorbed dose of gamma rays may occur within the packaging bag, resulting in some with a low absorbed dose and others with a high absorbed dose. However, it is necessary to ensure a minimum absorbed dose that can sterilize each medical rubber part, and therefore the packaging bag must be irradiated with gamma rays that is equal to or greater than the minimum absorbed dose. As a result, some medical rubber parts within the packaging bag will absorb excessive gamma rays during gamma ray sterilization.

[0005] Patent Document 1 discloses a rubber composition or crosslinked product thereof that is used for medical rubber stoppers or medical rubber products, which has an isobutylene copolymer as the main component and a density of 0.95 or less and is easy to treat with radiation.

[0006] Patent Document 2 discloses a method for packaging an elastomer part (1) such as a stopper for a pharmaceutical container, which comprises the steps of packing the part (1) into a primary bag (10) made of a material that is substantially impermeable to air, and applying an atmosphere of at least 80% nitrogen to the primary bag (10), and is characterized in that the primary bag (10) is placed into a secondary bag (20), and a vacuum is created between the primary bag (10) and the secondary bag (20). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2002-301133 [Patent Document 2] Special Publication No. 2017-531604 Summary of the Invention [Problem to be solved by the invention]

[0008] When medical rubber parts are sterilized by gamma rays, the polymers that make up the medical rubber parts undergo scission and crosslinking simultaneously. Excessive gamma rays accelerate scission of the polymer backbone that makes up the medical rubber parts, resulting in the generation of low-molecular-weight components. This results in a deterioration in the non-elution performance of the medical rubber parts after gamma ray sterilization.

[0009] Some medical rubber parts have an inactive resin film laminated on at least a portion of the surface of a main body made of an elastic material to improve non-elution properties and / or sliding properties. However, when a medical rubber part having an inactive resin film laminated on at least a portion of the surface of a main body made of an elastic material is irradiated with gamma rays, the inactive resin film deteriorates. The deterioration of the inactive resin film reduces the non-elution properties of the medical rubber part. Therefore, medical rubber parts laminated with an inactive resin film have the problem of being unsuitable for sterilization by gamma rays.

[0010] The present invention has been made in view of the above circumstances, and aims to provide a method for sterilizing medical rubber parts, in which an inactive resin film is laminated on at least part of the surface of a main body made of an elastic material, and the non-elution properties are maintained even after gamma ray sterilization. [Means for solving the problem]

[0011] The method for sterilizing medical rubber parts of the present invention is characterized by irradiating a package of medical rubber parts containing multiple medical rubber parts, each having an inactive resin film laminated on at least part of the surface of a main body made of an elastic body, with gamma rays, and the package has an oxygen concentration of 5% or less. [Effects of the Invention]

[0012] The present invention provides a method for sterilizing medical rubber parts that maintains the non-elution properties even when the medical rubber part, which has an elastic body with an inactive resin film laminated on at least a portion of its surface, is sterilized by gamma radiation. Furthermore, since the inactive resin film is not deteriorated after gamma ray sterilization, the medical rubber part has excellent sliding properties and sealing properties against drug solutions. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 2 is an explanatory view schematically illustrating an example of a packaging form for the medical rubber part of the present invention. [Figure 2]FIG. 4 is an explanatory view schematically showing another example of packaging of the medical rubber part of the present invention. [Figure 3] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 4] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 5] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 6] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 7] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 8] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. [Figure 9] FIG. 1 is an explanatory view schematically illustrating an example of a medical rubber part of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0014] The method for sterilizing medical rubber parts of the present invention is characterized by irradiating a package of medical rubber parts containing multiple medical rubber parts, each having an inactive resin film laminated on at least part of the surface of a main body made of an elastic body, with gamma rays, and the package has an oxygen concentration of 5% or less.

[0015] <Sterilization method> First, the sterilization method of the present invention will be described. Examples of gamma rays include gamma rays emitted from cobalt 60 and cesium 137, with gamma rays emitted from cobalt 60 being preferred.

[0016] The gamma ray absorbed dose of medical rubber parts is established through actual sterilization validation procedures. For typical medical devices, 15 kGy is often used as the minimum absorbed dose. The gamma ray exposure dose required to ensure that all medical rubber parts in a package receive an absorbed dose of 15 kGy or more varies depending on the number and arrangement of the medical rubber parts in the package, but is generally 1.4 to 2.0 times 15 kGy. Similarly, if the minimum absorbed dose is 20 kGy, the exposure dose should be 1.4 to 2.0 times 20 kGy, and if the minimum absorbed dose is 25 kGy, the exposure dose should be 1.4 to 2.0 times 25 kGy. The gamma ray absorbed dose can be confirmed by attaching a dosimeter to the irradiated object.

[0017] The packaging that houses the medical rubber part before gamma ray irradiation preferably has an oxygen concentration of 5% or less, more preferably less than 5%, even more preferably 3% or less, and particularly preferably 1% or less. By keeping the oxygen concentration in the packaging at 5% or less, deterioration of the medical rubber part due to gamma ray irradiation can be suppressed.

[0018] Methods for reducing the oxygen concentration in the package to 5% or less include replacing the air in the package with an inert gas and placing an oxygen absorber in the package.

[0019] Examples of the inert gas include rare gases such as helium, neon, and argon, and nitrogen gas.

[0020] The oxygen absorber may include an iron-based oxygen absorber, Ageless (commercially available product).

[0021] The packaging for housing the medical rubber part is not particularly limited as long as it can be irradiated with gamma rays. Examples of the packaging include bags and boxes. Examples of the packaging bag include bags made of thermoplastic resin films such as polyethylene, polyamide, and polyester, or aluminum. It is preferable that the packaging bag be airtight. Examples of the packaging box include, but are not particularly limited to, paper boxes, cardboard boxes, and the like.

[0022] The packaging material may be a breathable packaging material or a non-breathable (gas-tight) packaging material, and it is also preferable to use a combination of these.

[0023] Gamma ray irradiation of medical rubber parts may be performed, for example, on a primary package (e.g., a packaging bag) containing multiple medical rubber parts, which in turn may be contained in a package (e.g., a cardboard box) containing multiple medical rubber parts.

[0024] FIG. 1 is a schematic diagram illustrating an example of a packaging configuration for gamma ray irradiation. In the configuration shown in FIG. 1, a primary package 3 containing multiple medical rubber parts 1 is further housed in a secondary antistatic package 5 and a tertiary antistatic package 7. The primary package 3 is preferably breathable, and the secondary antistatic package 5 and the tertiary antistatic package 7 are preferably gas-tight. The secondary antistatic package 5 and the tertiary antistatic package 7 are preferably sealed with a heat seal 9. If an oxygen absorber 11 is used, it is preferable to place the oxygen absorber 11 between the primary package 3 and the secondary package 5 so that it does not come into direct contact with the medical rubber part 1. By placing the oxygen absorber 11 in the secondary package 5, the oxygen concentration in the secondary package 5 and the primary package 3 can be kept below 5%. Multiple tertiary antistatic packages 7 can be housed in a quaternary package (e.g., a cardboard box) and then irradiated with gamma rays.

[0025] FIG. 2 is an explanatory diagram schematically illustrating another example of a packaging embodiment for gamma ray irradiation. In the embodiment shown in FIG. 2, a primary package 3 containing multiple medical rubber parts 1 is further housed in a secondary antistatic package 5 and a tertiary antistatic package 7. The secondary antistatic package 5 and the tertiary antistatic package 7 are preferably sealed with a heat seal 9. The primary package 3 is preferably breathable, and the secondary antistatic package 5 and the tertiary antistatic package 7 are preferably gas-tight. The secondary package 5 containing the primary package 3 is filled with an inert gas. By filling the secondary package 5 and the primary package 3 with an inert gas, the oxygen concentration in the secondary package 5 and the primary package 3 can be kept below 5%. A plurality of the tertiary antistatic packages 7 can be housed in a quaternary package (e.g., a cardboard box) and then irradiated with gamma rays.

[0026] It is preferable that the gamma ray irradiation be performed on the package containing the medical rubber parts while it is housed in a container made of aluminum alloy, for example.

[0027] <Medical rubber parts> Next, a medical rubber part to which the present invention is applied will be described. The medical rubber part to which the present invention is applied has a main body made of an elastic body and an inactive resin film laminated on at least a part of the surface of the main body.

[0028] <Elastic body that makes up the main body of medical rubber parts> The elastic body is not particularly limited, but may be any body that has the property of being deformed when a force is applied and returning to its original shape when the force is removed.

[0029] From this viewpoint, the elastic body preferably has a compression set of 20% or less, more preferably 15% or less, and even more preferably 10% or less, measured after 22 hours at 70°C in accordance with the measurement method described in JIS K6262: 2013. The lower limit of the compression set of the elastic body is not particularly limited.

[0030] The rubber hardness of the elastic body is preferably 30 or more, more preferably 35 or more, and even more preferably 40 or more in terms of 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 - Determination of hardness - Part 3: Durometer hardness", and is preferably 70 or less, more preferably 65 or less, and even more preferably 60 or less.

[0031] Examples of materials that can be used to form the elastic body include rubber and thermoplastic elastomer.

[0032] Examples of the thermoplastic elastomer include polyurethane elastomers, polyester elastomers, polyamide elastomers, olefin elastomers, and styrene elastomers.

[0033] Examples of rubbers constituting the elastic body include butyl rubber, isoprene rubber, butadiene rubber, styrene butadiene rubber, natural rubber, nitrile rubbers such as chloroprene rubber and acrylonitrile butadiene rubber, hydrogenated nitrile rubber, norbornene rubber, ethylene propylene rubber, ethylene-propylene-diene rubber, acrylic rubber, ethylene acrylate rubber, fluororubber, chlorosulfonated polyethylene rubber, epichlorohydrin rubber, silicone rubber, urethane rubber, polysulfide rubber, phosphane rubber, and 1,2-polybutadiene. Of these, butyl rubbers are preferred as the rubber constituting the elastic body, and halogenated butyl rubber is more preferred.

[0034] The material constituting the elastic body may be used alone or in the form of a blend of multiple components.

[0035] The elastic body constituting the main body of the medical rubber part is preferably a cured product of a medical rubber composition containing (a) a base polymer containing a halogenated butyl rubber. The raw materials contained in the medical rubber composition are described below.

[0036] First, (a) the base polymer containing halogenated butyl rubber will be described. Examples of halogenated butyl rubber include chlorinated butyl rubber, brominated butyl rubber, and brominated copolymer rubber of isobutylene and p-methylstyrene (brominated isobutylene-paramethylene-styrene copolymer rubber).

[0037] The halogenated butyl rubber is preferably chlorinated butyl rubber or brominated butyl rubber. The chlorinated butyl rubber or brominated butyl rubber is obtained by, for example, adding or substituting chlorine or bromine to the isoprene structure of butyl rubber, specifically to the double bond and / or the carbon atom adjacent to the double bond. Note that butyl rubber is a copolymer obtained by polymerizing isobutylene and a small amount of isoprene.

[0038] 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, and is preferably 5% by mass or less, more preferably 4% by mass or less, and even more preferably 3% by mass or less.

[0039] A specific example of the chlorinated butyl rubber is CHLOROBUTYL 1066 (stabilizer: NS, halogen content: 1.26%, Mooney viscosity: 38ML) manufactured by Japan Butyl Co., Ltd. 1+8 (125°C, specific gravity: 0.92); LANXESS X_BUTYL CB1240 manufactured by LANXESS.

[0040] A specific example of the brominated butyl rubber is BROMOBUTYL 2255 (stabilizer: NS, halogen content: 2.0%, Mooney viscosity: 46ML) manufactured by Nippon Butyl Co., Ltd. 1+8(125°C, specific gravity: 0.93); LANXESS X_BUTYL BBX2 manufactured by LANXESS.

[0041] The base polymer (a) may contain a rubber component other than halogenated butyl rubber. Examples of other rubber components include butyl rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, natural rubber, nitrile rubber such as chloroprene rubber or acrylonitrile-butadiene rubber, hydrogenated nitrile rubber, norbornene rubber, ethylene-propylene rubber, ethylene-propylene-diene rubber, acrylic rubber, ethylene-acrylate rubber, fluororubber, chlorosulfonated polyethylene rubber, epichlorohydrin rubber, silicone rubber, urethane rubber, polysulfide rubber, phosphane rubber, and 1,2-polybutadiene. These may be used alone or in combination of two or more.

[0042] When other rubber components are used, the content of the halogenated butyl rubber in the (a) base polymer is preferably 90% by mass or more, more preferably 95% by mass or more, and even more preferably 98% by mass or more. In a preferred embodiment, the (a) base polymer consists solely of the halogenated butyl rubber.

[0043] The medical rubber composition preferably contains a (b) crosslinking agent. The (b) crosslinking agent is blended to crosslink the halogenated butyl rubber component contained in the (a) base polymer. The (b) crosslinking agent is not particularly limited as long as it is capable of crosslinking the halogenated butyl rubber. Examples of the (b) crosslinking agent include sulfur, metal oxides, resin crosslinking agents, organic peroxides, and triazine derivatives, which may be used alone or in combination of two or more.

[0044] Examples of sulfur used as a crosslinking agent include powdered sulfur, finely divided sulfur, precipitated sulfur, colloidal sulfur, and sulfur chloride.

[0045] Examples of metal oxides used as crosslinking agents include magnesium oxide, calcium oxide, zinc oxide, and copper oxide.

[0046] Examples of the resin crosslinking agent include alkylphenol formaldehyde resins such as alkylphenol formaldehyde resin, heat-reactive phenol resin, phenol dialcohol resin, bisphenol resin, and heat-reactive bromomethyl alkylated phenol resin.

[0047] Specific examples of the organic peroxides include dialkyl peroxides, peroxyesters, peroxyketals, and hydroperoxides. Examples of dialkyl peroxides include di(2-t-butylperoxyisopropyl)benzene, dicumyl peroxide, 2,5-dimethyl-2,5-di(t-butylperoxy)hexane, t-butylcumyl peroxy, di-t-hexyl peroxy, di-t-butyl peroxy, and 2,5-dimethyl-2,5-di(t-butylperoxy)hexyne-3. Examples of peroxyesters include t-butyl peroxymaleate, t-butylperoxy-3,3,5-trimethylcyclohexanoate, t-butyl peroxylaurate, t-butylperoxyisopropyl monocarbonate, t-hexyl peroxybenzoate, 2,5-dimethyl-2,5-di(benzoylperoxy)hexane, t-butyl peroxyacetate, and t-butyl peroxybenzoate. Examples of peroxyketals 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, and 2,2-di(4,4-di(t-butylperoxy)cyclohexyl)propane. Examples of hydroperoxides include p-menthane hydroperoxide and diisopropylbenzene hydroperoxide. These organic peroxides may be used alone or in combination of two or more.

[0048] The medical rubber composition preferably contains a triazine derivative as the crosslinking agent (b).

[0049] The triazine derivatives include, for example, compounds represented by the general formula (1). [ka] [Wherein 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 represents an alkyl group, an alkenyl group, an aryl group, an aralkyl group, an alkylaryl group, or a cycloalkyl group. 4 and R 5 may be the same or different. 1 and M 2 is H, Na, Li, K, 1 / 2Mg, 1 / 2Ba, 1 / 2Ca, an aliphatic primary amine, a secondary amine, or a tertiary amine, a quaternary ammonium salt, or a phosphonium salt. 1 and M 2 may be the same or different.]

[0050] In general formula (1), examples of the alkyl group include alkyl groups having 1 to 12 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, tert-pentyl, n-hexyl, 1,1-dimethylpropyl, octyl, isooctyl, 2-ethylhexyl, decyl, and dodecyl. Examples of the alkenyl group include alkenyl groups having 1 to 12 carbon atoms, such as vinyl, allyl, 1-propenyl, isopropenyl, 2-butenyl, 1,3-butadienyl, and 2-pentenyl. Examples of the aryl group include monocyclic or fused polycyclic aromatic hydrocarbon groups, such as aryl groups having 6 to 14 carbon atoms, such as phenyl, naphthyl, anthryl, phenanthryl, and acenaphthylenyl. Examples of aralkyl groups include aralkyl groups having 7 to 19 carbon atoms, such as benzyl, phenethyl, diphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 2,2-diphenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 2-biphenylylmethyl, 3-biphenylylmethyl, and 4-biphenylylmethyl. Examples of alkylaryl groups include alkylaryl groups having 7 to 19 carbon atoms, such as tolyl, xyl, and octylphenyl. Examples of cycloalkyl groups include cycloalkyl groups having 3 to 9 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and cyclononyl.

[0051] Specific examples of the triazine derivative represented by general formula (1) include 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- Examples include 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, and 2-anilino-4,6-dimercapto-s-triazine, or sodium salts or disodium salts thereof.

[0052] 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 due to its easy availability.

[0053] Examples of triazine derivatives 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, and 1,3,5-triazine-2,4,6-trithiol.

[0054] In the medical rubber composition, one type of triazine derivative may be used alone, or two or more types may be used in combination.

[0055] The content of the (b) crosslinking agent in the medical rubber composition is preferably 0.1 parts by mass or more, more preferably 0.3 parts by mass or more, and even more preferably 0.5 parts by mass or more, and is preferably 2.0 parts by mass or less, more preferably 1.4 parts by mass or less, and even more preferably 1.2 parts by mass or less, per 100 parts by mass of the (a) base polymer component. This is because, when the content of the (b) crosslinking agent is within the above range, a rubber having good rubber properties (hardness, tensile strength, Cset), elution performance, and processability (less discoloration) can be obtained.

[0056] The medical rubber composition preferably does not contain a vulcanization accelerator. This is because the vulcanization accelerator may remain in the final rubber product and leach into the medicinal solution in the syringe or vial. Examples of the vulcanization accelerator include guanidine-based accelerators (e.g., diphenyl guanidine), 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, Nt-butyl-2-benzothiazole sulfenamide).

[0057] The medical rubber composition may contain hydrotalcite. Hydrotalcite functions as a scorch inhibitor during crosslinking of halogenated butyl rubber and also functions to prevent the compression set of medical rubber parts from increasing. Furthermore, hydrotalcite functions as an acid acceptor, absorbing chlorine-based gases and bromine-based gases generated during crosslinking of halogenated butyl rubber and preventing crosslinking inhibition caused by these gases. The aforementioned magnesium oxide can also function as an acid acceptor.

[0058] Examples of hydrotalcite include Mg 4.5 Al2(OH) 13 CO3·3.5H2O, Mg 4.5 Al2(OH) 13 CO3, Mg4Al2(OH) 12 CO3·3.5H2O, Mg6Al2(OH) 16 CO3·4H2O, Mg5Al2(OH) 14 CO3·4H2O, Mg3Al2(OH) 10 One or more of Mg-Al hydrotalcites such as CO3·1.7H2O can be used.

[0059] A specific example of hydrotalcite is DHT-4A (registered trademark)-2 manufactured by Kyowa Chemical Industry Co., Ltd.

[0060] When hydrotalcite is used as an acid acceptor in the medical rubber composition, it is preferably used in combination with MgO. In this case, the blending amount of hydrotalcite is preferably considered to be the total amount of acid acceptors (hydrotalcite and MgO). The total content of the acid acceptors (hydrotalcite and MgO) is preferably 0.5 parts by mass or more, more preferably 1 part by mass or more, and preferably 15 parts by mass or less, and more preferably 10 parts by mass or less, per 100 parts by mass of the (a) base polymer component. This is because, if the total content of the acid acceptors (hydrotalcite and MgO) is within the above range, rust formation on molds and the like can be suppressed, and problems such as the raw materials themselves becoming white spots can be reduced.

[0061] The medical rubber composition may contain a co-crosslinking agent. The co-crosslinking agent is preferably a polyfunctional (meth)acrylate compound. The polyfunctional (meth)acrylate compound is more preferably a difunctional or higher (meth)acrylate compound, even more preferably a trifunctional or higher (meth)acrylate compound, preferably an octafunctional or lower (meth)acrylate compound, and preferably a hexafunctional or lower (meth)acrylate compound. Examples of difunctional or higher (meth)acrylate compounds include compounds having at least two acryloyl groups and / or methacryloyl groups. Note that "(meth)acrylate" means "acrylate" and / or "methacrylate".

[0062] Examples of the difunctional or higher functional (meth)acrylate compounds include polyethylene glycol di(meth)acrylate, 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, and glycerin tri(meth)acrylate. (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, etc. The co-crosslinking agent may be used alone or in combination of two or more thereof.

[0063] The medical rubber composition may contain a filler. Examples of the filler include inorganic fillers such as silica, clay, and talc. Clay or talc is more preferred as the filler. The filler functions to adjust the rubber hardness of the medical rubber part and also functions as an extender to reduce the production cost of the medical rubber part.

[0064] Examples of the clay include calcined clay and kaolin clay. Specific examples of the clay include SILLITIN (registered trademark) Z manufactured by HOFFMANN MINERAL, SATINTONE (registered trademark) W manufactured by ENGELHARD, NN kaolin clay manufactured by Tsuchiya Kaolin Kogyo Co., Ltd., and PoleStar 200R manufactured by Imerys Specialties Japan.

[0065] Specific examples of the talc include Hitron A manufactured by Takehara Chemical Industry Co., Ltd., MICRO ACE (registered trademark) K-1 manufactured by Nippon Talc Co., Ltd., and Mistron (registered trademark) Vapor manufactured by Imerys Specialties Japan.

[0066] The medical rubber composition may further contain colorants such as titanium oxide and carbon black, processing aids, polyethylene glycol as a crosslinking activator, plasticizers (for example, paraffin oil), etc. in appropriate proportions.

[0067] <Inactive resin film> The medical rubber part to which the present invention is applied has an inactive resin film laminated on at least a portion of the surface of a main body made of an elastic body. The inactive resin film prevents components of the elastic body from leaching into the pharmaceutical product. The inactive resin film also provides the medical rubber part with, for example, sliding properties and the ability to seal against pharmaceutical solutions.

[0068] The inactive resin film may be laminated on at least a part of the surface of the main body of the medical rubber part made of an elastic body, and is preferably laminated in an appropriate manner depending on the shape of the medical rubber part.

[0069] The resin constituting the inactive resin film is not particularly limited, but at least one fluororesin or olefin resin selected from the group consisting of tetrafluoroethylene-ethylene copolymer (ETFE), polytetrafluoroethylene (PTFE), and polychlorotetrafluoroethylene (PCTFE) is preferred in terms of providing good chemical resistance.

[0070] Tetrafluoroethylene-ethylene copolymer (ETFE) is a copolymer of ethylene and tetrafluoroethylene in a molar ratio of 30 / 70 to 70 / 30. Modified ETFE can also be obtained by copolymerizing other components for the purpose of modification. These other components include fluorine-containing olefins and hydrocarbon olefins. Specifically, these include α-olefins such as propylene and butene; fluorine-containing olefins such as hexafluoropropylene, vinylidene fluoride, perfluorobutylethylene, and trifluorochloroethylene; vinyl ethers such as ethylene vinyl ether, perfluoromethyl vinyl ether, and perfluoropropyl vinyl ether; and fluorine-containing acrylates. These components are copolymerized at approximately 2 to 10 mol% to modify ETFE.

[0071] As the modified ETFE, ETFE having a functional group that imparts adhesiveness can be suitably used, and examples of the functional group include a carboxyl group, a carboxyl anhydride group, an epoxy group, a hydroxyl group, an isocyanate group, an ester group, an amide group, an aldehyde group, an amino group, a cyano group, a carbon-carbon double bond, a sulfonic acid group, an ether group, etc. In addition, an example of a commercially available modified ETFE product is Fluon AH-2000 manufactured by Asahi Glass Co., Ltd.

[0072] Examples of olefin-based resins include polyethylene-based resins such as polyethylene, ethylene-propylene copolymer, ethylene-propylene-non-conjugated diene copolymer, ethylene-butene copolymer, ethylene-hexene copolymer, ethylene-octene copolymer, ethylene-vinyl acetate copolymer, ethylene-vinyl alcohol copolymer, ethylene-ethyl acrylate copolymer, and chlorinated polyethylene; polypropylene-based resins such as polypropylene, propylene-ethylene random copolymer, propylene-ethylene block copolymer, and chlorinated polypropylene; polybutene, polyisobutylene, polymethylpentene, and copolymers of cyclic olefins; and polyethylene (particularly ultra-high molecular weight polyethylene (UHMWPE)). The olefin-based resin may also contain fluorine.

[0073] The thickness of the inactive resin film may be adjusted appropriately according to the shape and size of the medical rubber part, but is preferably 10 μm or more, more preferably 20 μm or more, even more preferably 30 μm or more, and preferably 150 μm or less, more preferably 130 μm or less, and even more preferably 110 μm or less. If the thickness of the inactive resin film is within the above range, the film will not break during product molding, and wrinkles or lifting defects will not occur on the film surface of the product after molding, and both moldability and product properties can be achieved.

[0074] The arithmetic mean roughness Ra of the inactive resin film ranges from 0.01 to 0.03 μm for cast or extruded films to 0.10 μm for skived films, but by setting the surface roughness of the mold to 0.03 μm or less, medical rubber parts with excellent liquid adhesion and airtightness can be obtained. There is no particular lower limit for Ra of the inactive film itself.

[0075] The inactive resin film is preferably subjected to a treatment to enhance its adhesiveness to rubber, etc. Examples of treatments to enhance adhesiveness include chemical treatments, treatments to roughen the surface of the film, and combinations of these, and specific examples include sodium treatment, glow discharge treatment, plasma treatment (discharge treatment) under atmospheric pressure or in a vacuum, excimer laser treatment (discharge treatment), and ion beam treatment.

[0076] The medical rubber part to which the present invention is applied is obtained, for example, by press-molding a sheet made of an elastomer with the inactive resin film superimposed thereon to obtain a medical rubber part in which the main body made of an elastomer and the inactive resin film are integrated.

[0077] Specifically, (a) a base polymer containing halogenated butyl rubber, (b) a crosslinking agent, and other compounding materials added as needed are kneaded to obtain a medical rubber composition. Kneading can be carried out using, for example, an open roll or an internal kneader. The kneaded product is preferably formed into a ribbon, sheet, pellet, or other shape, and more preferably formed into a sheet.

[0078] An inactive resin film is laminated on the obtained rubber sheet and press-molded to obtain a medical rubber part in which the main body made of an elastic body and the inactive resin film are integrated.

[0079] The crosslinking reaction of the medical rubber composition proceeds during pressing. The molding temperature is, for example, preferably 130°C or higher, more preferably 140°C or higher, and preferably 200°C or lower, more preferably 190°C or lower. The molding time is preferably 2 minutes or longer, more preferably 3 minutes or longer, and preferably 60 minutes or shorter, more preferably 30 minutes or shorter. The molding pressure is preferably 0.1 MPa or higher, more preferably 0.2 MPa or higher, and preferably 10 MPa or lower, more preferably 8 MPa or lower.

[0080] After press molding, unnecessary parts are cut and removed to form the desired shape. The resulting molded product is then washed, dried, and packaged to produce medical rubber parts.

[0081] Examples of medical rubber parts to which the present invention can be applied include rubber stoppers and sealing members for containers for various drugs such as liquid drugs, powder preparations, and freeze-dried preparations, rubber stoppers for vacuum blood collection tubes, plunger stoppers for prefillable syringes, and sliding or sealing parts such as nozzle caps. Specific examples of medical rubber parts to which the present invention can be applied are described below.

[0082] <Plunger stopper> Figure 3 is an exploded view of a medical syringe that uses the medical rubber part of the present invention, a syringe known as a prefillable syringe 30. In Figure 3, half of the syringe barrel 31 and plunger stopper 33 are shown in cross section. The prefillable syringe 30 includes a cylindrical syringe barrel 31, a plunger 32 that is combined with the syringe barrel 31 and can move back and forth within the syringe barrel 31, and a plunger stopper 33 that is attached to the tip of the plunger 32. An inactive resin film is laminated on the surface of the plunger stopper 33 to improve sliding properties.

[0083] The plunger 32 is formed, for example, from a resin plate piece having a cross-shaped cross section, and is provided at its tip with a head portion 38 to which the plunger stopper 33 is attached. The head portion 38 is made of resin and formed integrally with the plunger 32, and is machined into a male thread shape. The plunger stopper 33 is a roughly cylindrical short-axis member, and its tip surface has, for example, an obtuse-angled chevron shape with the center of the axis protruding. A female thread-shaped mating recess 35 is formed axially from the rear end surface. The head portion 38 of the plunger 32 is screwed into the mating recess 35 of the plunger stopper 33, thereby attaching the plunger stopper 33 to the tip of the plunger 32.

[0084] FIG. 4 is a half-sectional front view of an example of a plunger stopper. Plunger stopper 40 includes a main body 41 made of an elastic body and an inactive resin film 42 laminated on the surface of the main body. Plunger stopper 40 has a short cylindrical shape and has multiple annular ribs 43, 44, and 45 on an outer peripheral surface 46 of the cylindrical shape. The annular ribs are in sliding contact with the inner peripheral surface of the syringe barrel. The multiple annular ribs are arranged in the axial direction from a leading end surface 47 to a rear end surface 48 of the plunger stopper. The number of annular ribs is not particularly limited as long as it is one or more, but is preferably two or more, more preferably three or more, and preferably six or less, more preferably five or less, and even more preferably four or less.

[0085] The plunger stopper 40 in FIG. 4 has, from the tip side, a first annular rib 43, a second annular rib 44, and a third annular rib 45. The radial compression rate of the first annular rib 43 at the tip is preferably 1% or more, more preferably 2% or more, even more preferably 3% or more, preferably 10% or less, more preferably 9% or less, and even more preferably 8% or less. The compression rate is calculated from the outer diameter D1 of the annular rib in an uncompressed state and the inner diameter R of the syringe barrel using the following formula: Compression rate (%) = 100 × (D1 - R) / D1

[0086] The linear length H1 (the axial length) of the sliding contact portion of the annular rib 43 at the tip is preferably 1% or more, more preferably 3% or more, and even more preferably 6% or more of the linear length Ho of the outer peripheral surface of the cylindrical shape (the axial length of the outer peripheral surface), and is preferably 25% or less, more preferably 20% or less, and even more preferably 15% or less.

[0087] The linear length H2 (axial length) of the sliding contact portion of the second annular rib 44 and the linear length H3 (axial length) of the sliding contact portion of the third annular rib 45 are each preferably 1% or more, more preferably 2% or more, and even more preferably 3% or more, of the linear length Ho (axial length of the outer peripheral surface) of the cylindrical outer peripheral surface, and are preferably 15% or less, more preferably 14% or less, and even more preferably 13% or less.

[0088] 4, the inactive resin film 42 is provided on almost the entire surface (tip surface 47 and outer peripheral surface 46) of the plunger stopper body, but the inactive resin film 42 may be provided on at least a part of the body 41 made of an elastic body. For example, the inactive resin film 42 may be laminated only on the mountain-shaped tip surface 47 that comes into contact with the medicinal solution when the plunger stopper is inserted into the syringe. The inactive resin film 42 is preferably a polytetrafluoroethylene film.

[0089] It is also preferable that the first annular rib 43 at the tip has one or more annular grooves formed by laser processing in the sliding contact portion thereof and extending in the circumferential direction.

[0090] The depth of the annular groove is preferably 2 μm or more, more preferably 3 μm or more, and even more preferably 5 μm or more, and is preferably 100 μm or less, more preferably 80 μm or less, and even more preferably 50 μm or less.

[0091] Furthermore, the width of the annular groove is preferably 10 μm or more, more preferably 20 μm or more, and even more preferably 30 μm or more, and is preferably 200 μm or less, more preferably 170 μm or less, and even more preferably 150 μm or less.

[0092] The plunger stopper may be called a stopper or a gasket.

[0093] <Rubber stopper> Fig. 5 is an explanatory diagram illustrating an example of a medical stopper to which the present invention is applied. More specifically, it is a rubber stopper for a vial. Fig. 5(a) is a plan view, and Fig. 5(b) is a cross-sectional view taken along line AA in Fig. 5(a).

[0094] The medical plug 50 has a top plate 53 and cylindrical leg portions 55 extending downward from the underside of the top plate 53. The top plate 53 and leg portions 55 are made of an elastic material. When a medical container is stoppered with the medical plug of the present invention, the leg portions 55 fit into the opening of the medical container. In Figure 5(b), the opposing inner surfaces of the cylindrical leg portions 55 are tapered so that the distance between the inner surfaces of the leg portions gradually decreases from the bottom to the top (towards the top surface).

[0095] The top plate 53 has a circular shape in a plan view. The top plate 53 has a puncture portion 53a that can be punctured with the needle of a syringe, and a flange portion 53b that comes into contact with the upper edge surface of the opening of the medical container when the medical container is capped.

[0096] A protrusion 57 is provided on the top surface of flange portion 53b to prevent it from coming into close contact with other rubber stoppers.

[0097] Puncture portion 53a is a region for inserting an injection needle to aspirate the medicinal liquid inside the container on top plate 53. Puncture portion 53a is circular in plan view and is located in the center of top plate 53. Puncture portion 53a is formed in a concave shape on the top surface.

[0098] 5, an inactive resin film 59 is laminated on the entire underside of the table top 53 and the entire surface of the legs 55. The inactive resin film 59 may be laminated on at least a portion of the underside of the table top 53 and the entire surface of the legs 55. A polytetrafluoroethylene film is preferred as the inactive resin film 59.

[0099] Figure 6 is an explanatory diagram showing another embodiment of a medical rubber stopper 50 to which the present invention is applied. Figure 6(a) is a plan view, and Figure 6(b) is a cross-sectional view taken along line BB in Figure 6(a). Descriptions of parts of the medical rubber stopper 50 in Figure 6 that are common in configuration to Figure 5 will be omitted.

[0100] The medical rubber stopper 50 of this embodiment has bifurcated legs 55 extending from the underside of the top plate 53. In Figure 6(b), the opposing inner surfaces of the bifurcated legs 55 are tapered so that the distance between the inner surfaces of the legs gradually decreases from bottom to top (towards the top surface). In the embodiment of Figure 6, the top plate 53 and legs 55 are made of an elastic body, and an inactive resin film 59 is laminated over the entire underside of the top plate 53 and the surface of the legs 55. The inactive resin film 59 may also be laminated over at least a portion of the underside of the top plate 53 and the surface of the legs 55.

[0101] A nylon film layer may be provided on the top surface of the top plate 53 of the medical rubber stopper 50 in Figures 5 and 6. By providing a nylon film layer on the top surface of the medical rubber stopper 50, mechanical transportability during pharmaceutical manufacturing can be ensured. In addition, by providing a nylon film layer on the top surface of the medical rubber stopper 50, the surface smoothness of the top surface can be increased, preventing the generation of needle fragments when punctured with an injection needle.

[0102] <Rubber stopper for vacuum blood collection tube> 7 is an explanatory diagram showing an example of a vacuum blood collection tube. A vacuum blood collection tube 90 consists of a bottomed tube 91 and a rubber stopper 93 that seals the opening of the bottomed tube 91. It is designed so that blood can be collected automatically by reducing the pressure inside the blood collection tube.

[0103] FIG. 8 is an explanatory diagram illustrating an example of a medical stopper to which the present invention is applied. It is an explanatory diagram illustrating an example of a rubber stopper for a vacuum blood collection tube. FIG. 8(a) is a perspective view, and FIG. 8(b) is a cross-sectional view. The rubber stopper for a vacuum blood collection tube has a top plate 94 and a cylindrical leg portion 95 extending downward from the underside of the top plate 94. The top plate 94 and the leg portion 95 are made of an elastic material. The leg portion 95 fits into the opening of the vacuum blood collection tube when the vacuum blood collection tube is stoppered with the rubber stopper. A puncture portion 96, which is an area for inserting an injection needle, is provided in the center of the top plate 94. The puncture portion 96 is formed in a concave shape from the top surface. An inactive resin film 97 is laminated on the underside of the top plate 94 and the entire surface of the leg portion 95. Note that the inactive resin film 97 may be laminated on at least a portion of the underside of the top plate 94 and the surface of the leg portion 95.

[0104] <Nozzle cap> FIG. 9(a) is a cross-sectional view showing an example of a nozzle cap for a medical syringe and the nozzle of a syringe barrel to be fitted with the nozzle cap. FIG. 9(b) is a cross-sectional view showing the nozzle cap fitted over the nozzle. The nozzle cap 81 is integrally formed from a medical rubber composition. The nozzle cap 81 includes a cylindrical portion 86 having an inner diameter D8 slightly smaller than the outer diameter D9 of the nozzle 83, and a needle portion 87 connected to one end (the upper end in the figure) of the cylindrical portion 86. The needle portion 87 is formed in a columnar shape with an outer surface continuous with the cylindrical portion 86. The other end (the lower end in the figure) of the cylindrical portion 86 is provided with an opening 88 for inserting the nozzle 83 into the cylindrical portion 86 and fitting the nozzle cap 81 over the nozzle 83. An inactive resin film 84 is laminated on the inner surface of the nozzle cap 81 and on the surface of the lower end of the cylindrical portion 86. [Example]

[0105] The present invention will be described in detail below with reference to examples. However, the present invention is not limited to the following examples, and all modifications and embodiments that do not deviate from the spirit of the present invention are included within the scope of the present invention.

[0106] [Evaluation method] (1) Extractables test Measurement sample: As a medical rubber part, a plunger stopper was placed in a polyethylene bag (in the packaging form shown in Figures 1 and 2, in the environment inside the package described in Table 1) and irradiated with gamma rays so that the absorbed doses were 25 kGy and 50 kGy, to obtain a plunger stopper after gamma ray irradiation. The measurement samples were subjected to the "Elution Test" described in "7.03 Test Method for Rubber Stoppers for Infusion Solutions" in the 17th Edition of the Japanese Pharmacopoeia. The compliance conditions were as follows: Test liquid properties: clear and colorless UV transmittance: With a layer length of 10 mm, transmittance at wavelengths of 430 nm and 650 nm is 99.0% or more. Ultraviolet absorption spectrum: absorbance of 0.20 or less in the wavelength range of 220 nm to 350 nm 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 equal to or less than that of the standard solution. Potassium permanganate reducing agent: 2.0 mL / 100 mL or less (Pharmacopoeia standard) Evaporation residue: 2.0 mg or less If any item was not satisfied, it was rated as "non-compliant," and if all items were satisfied, it was rated as "compliant."

[0107] (2) TOC test The total organic carbon (TOC) value (NPOC: TOC after acidification and aeration treatment) of the eluate (1) was measured. Measurement and analysis equipment: Shimadzu Total Organic Carbon Analyzer TOC-VCSH (combustion oxidation method) Measurement and analysis conditions: combustion tube temperature 680 degrees, high-sensitivity catalyst used, Carrier gas: High-purity air 150 mL / min, Injection volume 200μL, Acid concentration 1.5%, Ventilation time: 90 seconds

[0108] The difference in TOC values ​​before and after gamma irradiation is shown. The smaller the difference, the less deterioration in elution performance there is. (Judgment criteria) 〇 (same as before irradiation): ΔTOC value 0.1 mg / L or less, △ (worse than before irradiation): ΔTOC value over 0.1 mg / L, 0.3 mg / L or less × (significantly worse than before irradiation): ΔTOC value over 0.3 mg / L

[0109] (3) Sliding properties The plunger stopper was inserted into a syringe barrel (1 mL COP resin syringe, inner diameter 6.35 mm), and the force required to push the plunger in at a speed of 100 mm / min was measured using a precision universal testing machine (AG-X 100 kN, manufactured by Shimadzu Corporation). The average value of the force required for sliding over a sliding distance of 10 mm to 15 mm was recorded as the sliding resistance (N). The difference in sliding resistance (N) before and after gamma ray irradiation (sliding resistance value after irradiation - sliding resistance value before irradiation) is shown. The smaller the difference, the less deterioration in sliding properties there was. (Judgment criteria) 〇: Δ sliding resistance value 2N or less △: Δ sliding resistance value over 2N, 5N or less ×: Δ sliding resistance value over 5N

[0110] (4) Chemical solution sealing (liquid leakage test) The plunger stopper was then attached to a syringe barrel (a 1 mL cycloolefin (COP) resin syringe, inner diameter 6.35 mm), after which the test solution was filled and the other end was capped. After storage at 40°C and leaving the syringes for one day and one week, the syringes were observed using a video microscope (Leica Microsystems DVM5000) at a 50x objective lens to check for leakage. Ten syringes were observed, and those in which the test solution had exceeded the first rib of the stopper were judged to have leaked, and the number of such cases was recorded. The test solution used was water to which 0.2 g / L of dye (methylene blue, Sigma-Aldrich Japan LLC) and 1.0 g / L of surfactant (polysorbate 80, NOF Corporation) had been added. (judgment criteria) 〇 (No leaks): 0 △ (slight leak): 1 bottle × (Leaking): 2 or more

[0111] (5) The suitability of READY TO USE was judged as follows: If the extractables test results are pass, the TOC test results are △ or higher, the sliding test results are △ or higher, and the liquid leakage test results are △ or higher, the product is deemed to be in compliance with READY TO USE. If any one of the evaluation results is not met, the product is deemed to be non-compliant.

[0112] [Production of medical rubber parts (plunger stoppers for syringes)] The components shown in Table 1, except for the crosslinking component, were blended and kneaded at a filling rate of 75% using a 10 L pressure-type closed kneader, and after aging at room temperature, the crosslinking component was added and kneaded using an open roll to prepare a rubber composition. The rubber composition was molded into a sheet.

[0113] [Table 1]

[0114] The details of the ingredients used are as follows: Butylated rubber: ExxonMobil HT-1066 (chlorine content: 1.26 wt%) Triazine derivative: Jisnet DB manufactured by Sankyo Kasei Co., Ltd. Talc: Mistron Vapor manufactured by Imerys Specialties Hydrotalcite: Alcamizer 1 manufactured by Kyowa Chemical Industry Co., Ltd. Magnesium oxide: Kyowa Chemical Industry Co., Ltd. Magsarat 150s Carbon black: Mitsubishi Chemical Diablack G Titanium oxide: Titanium Kogyo KR-380 Oil: Idemitsu Kosan PW380

[0115] An inert resin film with one side adhesive treatment was placed on the rubber sheet, placed on a molding die, and molded in a vacuum press at 175°C for 10 minutes to allow for vulcanization and adhesion. The plunger stopper was formed into a shape suitable for a 1 mL COP resin syringe (syringe barrel inner diameter 6.35 mm). The inert resin film was laminated over the entire tip surface and outer peripheral side surface of the gasket body made of crosslinked rubber (elastic body). The following inert resin film was used. Modified PTFE Skiving film: Nippon Valqua Industries Co., Ltd., product name "New Valflon", film thickness T = 70 μm, center line average roughness 0.11 μm

[0116] The dimensions of the resulting plunger stopper (see FIG. 4) are as follows: Number of annular ribs: 3 Ho: 7.0 mm First rib compression rate: 3.8% Second rib compression rate: 3.1% Third rib compression rate: 3.1% H1:1.0mm H2: 0.5mm H3: 0.5mm

[0117] One hundred of the resulting plunger stoppers were placed in a packaging bag and sterilized by irradiating them with gamma rays at the oxygen concentration and absorbed dose shown in Table 2. The stoppers after the sterilization treatment were subjected to an extractables test, TOC, and evaluation of liquid leakage, and the results are also shown in Table 2.

[0118] [Table 2]

[0119] The results in Table 2 show that the non-elution properties are maintained by sterilizing a medical rubber part package containing multiple medical rubber parts, each of which has an inert resin film laminated on at least part of the surface of a main body made of an elastic body, by irradiating the package with gamma rays at an oxygen concentration of 5% or less. Furthermore, because the inert resin film is not deteriorated, the medical rubber part obtained has excellent sliding properties and little liquid leakage. [Industrial Applicability]

[0120] According to the present invention, it is possible to provide a method for sterilizing medical rubber parts that maintains the non-elution property even after gamma ray sterilization and causes fewer problems in the manufacturing process of medical supplies. [Explanation of symbols]

[0121] 1: Medical rubber parts, 3: Primary packaging, 5: Secondary packaging, 7: Tertiary packaging, 9: Heat seal, 11: Oxygen absorber,

[0122] A preferred embodiment (1) of the present invention is a method for sterilizing medical rubber parts, characterized in that the method comprises irradiating a package containing a plurality of medical rubber parts, each having an elastic body with an inactive resin film laminated on at least a portion of the surface thereof, with gamma rays, the package having an oxygen concentration of 5% or less.

[0123] A preferred embodiment (2) of the present invention is the method for sterilizing medical rubber parts according to embodiment (1), in which the package having an oxygen concentration of 5% or less is irradiated with gamma rays.

[0124] A preferred embodiment (3) of the present invention is the method for sterilizing a medical rubber part according to embodiment (1) or (2), in which the package having an oxygen concentration of 3% or less is a package filled with nitrogen.

[0125] A preferred embodiment (4) of the present invention is the method for sterilizing medical rubber parts according to embodiment (1) or (2), in which the package having an oxygen concentration of 5% or less is a package containing an oxygen scavenger.

[0126] A preferred embodiment (5) of the present invention is the method for sterilizing a medical rubber part according to any one of the embodiments (1) to (4), in which gamma rays are irradiated so that the absorbed dose of gamma rays is 15 kGy or more.

[0127] A preferred embodiment (6) of the present invention is the method for sterilizing a medical rubber part according to any one of embodiments (1) to (5), wherein the elastic body is made of rubber or a thermoplastic elastomer, has a JIS-A hardness of 30 or more and 70 or less, and has a compression set of 20% or less.

[0128] A preferred embodiment (7) of the present invention is the method for sterilizing a medical rubber part according to any one of embodiments (1) to (6), in which the inactive resin is polytetrafluoroethylene (PTFE), a tetrafluoroethylene-ethylene copolymer, or ultra-high molecular weight polyethylene.

[0129] A preferred embodiment (8) of the present invention is the method for sterilizing a medical rubber part according to any one of the embodiments (1) to (7), wherein the inactive resin film has a thickness of 10 μm to 150 μm.

[0130] A preferred embodiment (9) of the present invention is the method for sterilizing a medical rubber part according to any one of embodiments (1) to (8), wherein the medical rubber part is a rubber stopper for a vial, a cap for a syringe, a plunger stopper, or a rubber stopper for a vacuum blood collection tube.

Claims

1. A method for sterilizing medical rubber parts, characterized in that the package contains multiple medical rubber parts, each having an inactive resin film laminated on at least a portion of the surface of a main body composed of an elastomer that is a cured product of a medical rubber composition containing a base polymer containing 90% by mass or more of halogenated butyl rubber, and the package has an oxygen concentration of 5% or less, and is irradiated with gamma rays.

2. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the package has an oxygen concentration of 3% or less and is irradiated with gamma rays.

3. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the package having an oxygen concentration of 5% or less is a package filled with nitrogen.

4. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the package having an oxygen concentration of 5% or less is a package containing an oxygen absorber.

5. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the gamma rays are irradiated so that the absorbed dose of the gamma rays is 15 kGy or more.

6. The method for sterilizing a medical rubber part according to claim 1, wherein the elastomer is made of rubber that is a cured product of a medical rubber composition containing a base polymer containing 90% by mass or more of halogenated butyl rubber, and has a JIS-A hardness of 30 or more and 70 or less, and a compression set of 20% or less.

7. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the inactive resin is polytetrafluoroethylene (PTFE), a tetrafluoroethylene-ethylene copolymer, or ultra-high molecular weight polyethylene.

8. 2. The method for sterilizing medical rubber parts according to claim 1, wherein the thickness of the inactive resin film is 10 μm to 150 μm.

9. 9. The method for sterilizing a medical rubber part according to claim 1, wherein the medical rubber part is a rubber stopper for a vial, a cap for a syringe, a plunger stopper, or a rubber stopper for a vacuum blood collection tube.

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