Medical rubber products

Abstract

To provide a sterilization method of medical rubber products that can maintain non-elusion characteristics even after gamma-ray sterilization and is less in troubles in a producing process of medical products.SOLUTION: A medical rubber product of the present invention is a medical rubber product formed of an elastic body and sterilised by irradiating gamma rays or electron beams (beta rays), and when a surface portion of the elastic body is measured by an ATR method using FT-IR, and when an area of an infrared absorption peak around a wave number 1650 cm-1 in an obtained infrared absorption spectrum is As and an area of the infrared absorption peak around a wave number 1470 cm-1 is Bs, Ss=(As / Bs)×100≤6.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to medical rubber products, and more particularly to sterilized medical rubber products.

Background Art

[0002] For medical rubber stoppers that seal openings such as syringes and vials, many items such as non-elution property, high cleanliness, chemical resistance, needle puncture resistance, self-sealing property, and high slidability are essential. The quality characteristics required for medical rubber stoppers should comply with the infusion rubber stopper test of the 17th revised Japanese Pharmacopoeia for their intended use.

[0003] For example, Patent Document 1 discloses a rubber stopper for a pharmaceutical container, which is obtained by vulcanizing a butyl rubber halide compounded with 5 to 25 parts by weight of ultra-high molecular weight polyethylene fine powder per 100 parts by weight of butyl rubber halide 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.

[0004] There is an increasing demand for ready-to-use (RTU) medical rubber products (such as syringe gaskets and vial stoppers) to be delivered in a state with sterilization guaranteed. As sterilization guarantee methods, there are autoclaving, ethylene oxide gas (EOG) sterilization, and gamma-ray sterilization. Gamma-ray sterilization has the advantage that medical rubber products can be sterilized while being packaged, so they can be delivered without opening the package. EOG sterilization has environmental problems and tends to be switched to gamma-ray sterilization.

[0005] Gamma sterilization ensures sterilization based on the set absorbed dose and the measured value. When multiple medical rubber products are packed in a packaging bag and gamma sterilized, there may be a bias in the medical rubber products inside the packaging bag. Therefore, even if the packaging bag is irradiated with gamma rays at a predetermined irradiation dose, variations in the absorbed dose of gamma rays occur inside the packaging bag, resulting in products with a lower absorbed dose of gamma rays and those with a higher absorbed dose of gamma rays. However, it is necessary to ensure the minimum absorbed dose capable of sterilizing each medical rubber product, and the packaging bag needs to be irradiated with gamma rays at a dose equal to or higher than the minimum absorbed dose. Therefore, there are medical rubber products in the packaging bag that absorb excessive gamma rays during gamma sterilization.

[0006] Patent Document 2 discloses a rubber composition mainly composed of an isobutylene copolymer with a density of 0.95 or less, which is used for a medical rubber stopper or a rubber composition for a medical rubber product that is easy to be radiation-treated, or a crosslinked product thereof.

[0007] Patent Document 3 discloses a method for packaging an elastomeric part (1) such as a stopper for a pharmaceutical container, including a step of packing the part (1) in a primary bag (10) made of a material that substantially does not allow air to pass through, and a step of applying an atmosphere of at least 80% nitrogen into the primary bag (10), and putting the primary bag (10) into a secondary bag (20), and evacuating the space between the primary bag (10) and the secondary bag (20).

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0009] When a medical rubber product is sterilized by irradiating it with gamma rays, cleavage and crosslinking of the polymer constituting the medical rubber product occur simultaneously. When excessive gamma rays are absorbed, cleavage of the polymer main chain constituting the medical rubber product is promoted, generating low molecular components. Therefore, the elution performance of the medical rubber product after gamma sterilization deteriorates. In addition, the cut low molecular components bleed out to the surface of the rubber product, and when medical rubber products adhere to each other, troubles such as clogging of the parts feeder used in the manufacturing process of medical supplies occur.

[0010] In preparation for absorbing excessive gamma rays, it is also conceivable to blend an antioxidant into the medical rubber product. However, the addition of an antioxidant raises concerns about a decrease in elution characteristics and an adverse effect on drugs.

[0011] The present invention has been made in view of the above circumstances, and an object thereof is to provide a sterilization method for a medical rubber product that maintains non-elution characteristics even after gamma sterilization.

Means for Solving the Problems

[0012] The medical rubber product of the present invention is a medical rubber product formed of an elastic body and sterilized by irradiating it with gamma rays or electron beams. When the surface portion of the elastic body is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), the wave number 1650 cm in the obtained infrared absorption spectrum -1 Let the area of the infrared absorption peak near be As, and the area of the infrared absorption peak near the wave number 1470 cm -1 be Bs. It is characterized in that Ss = (As / Bs) × 100 ≦ 6.

Effects of the Invention

[0013] According to the present invention, non-elution characteristics are maintained even after gamma sterilization, and a medical rubber product with few troubles in the manufacturing process of medical supplies can be provided.

Brief Description of the Drawings

[0014]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Mode for Carrying Out the Invention

[0015] The medical rubber product of the present invention is a medical rubber product formed of an elastomer and sterilized by irradiation with gamma rays or electron beams, and when the surface portion of the elastomer is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), the area of the infrared absorption peak near the wave number 1650 cm -1 is designated as As, and when the area of the infrared absorption peak near the wave number 1470 cm -1 is designated as Bs, it is characterized in that Ss = (As / Bs) × 100 ≦ 6.

[0016] The medical rubber product of the present invention is a medical rubber product sterilized by irradiation with gamma rays or electron beams. By measuring the surface portion of the elastomer constituting the medical rubber product by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), an infrared absorption spectrum (vertical axis: absorbance, horizontal axis: wave number) can be obtained.

[0017] The surface portion of the medical rubber product is cut out with a razor from the surface of the rubber product to a thickness (for example, 0.5 mm to 2.0 mm) that can be placed on the measuring device to prepare a measurement sample. The measurement sample is placed on the measuring device, and light is irradiated to a region with an outer diameter of 1 mm on the surface portion for measurement.

[0018] In the infrared absorption spectrum, an infrared absorption peak A having an absorption peak of absorbance appears in the vicinity of a wave number of 1650 cm -1 . This infrared absorption peak corresponds to a carbonyl group (C=O stretching vibration) group (ketone, aldehyde, carboxylic acid, ester, etc.) attributed to the oxide of the polymer constituting the elastomer. Note that the vicinity of a wave number of 1650 cm -1 means preferably a wave number region of 1650 cm -1 ±100 cm -1 , and more preferably means a wave number region of 1650 cm -1 ±50 cm -1 .

[0019] In the infrared absorption spectrum, an infrared absorption peak B having an absorption peak of absorbance appears in the vicinity of a wave number of 1470 cm -1 . The infrared absorption peak B is attributed to the scissoring vibration (in-plane bending vibration) of -CH2- in the polymer main chain constituting the elastomer. Note that the vicinity of a wave number of 1470 cm -1 means preferably a wave number region of 1470 cm -1 ±50 cm -1 , and more preferably means a wave number region of 1470 cm -1 ±20 cm -1 .

[0020] When the surface part of the elastomer constituting the medical rubber product of the present invention has an area of the infrared absorption peak A as As and an area of the infrared absorption peak B as Bs, it is preferable that the Ss value calculated by Ss = (As / Bs) × 100 is 6 or less, preferably 5.5 or less, and more preferably 5.0 or less. If the Ss value is 6 or less, the deterioration of the polymer constituting the elastomer of the medical rubber product is suppressed, and the non-elution characteristics are excellent. Further, since the surface part of the elastomer is oxidized during the manufacturing process of the medical rubber product, the Ss generally exceeds 3.0, and more generally exceeds 3.5.

[0021] The medical rubber product is cut out from the central part, and the exposed interior is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR) to obtain an infrared absorption spectrum (vertical axis: absorbance, horizontal axis: wavenumber).

[0022] Specifically, it is cut vertically so as to pass through the center in the plan view of the medical rubber product. From the central part of the obtained cross-section, a measurement sample is cut out with scissors to a thickness (for example, 0.5 mm to 2.0 mm) that can be placed on the measuring device. The measurement sample is placed on the measuring device, and light is irradiated onto a region with an outer diameter of 1 mm on the surface part (the central part of the cross-section) for measurement.

[0023] In the infrared absorption spectrum, an infrared absorption peak A having an absorption peak of absorbance appears in the vicinity of a wavenumber of 1650 cm -1 . This infrared absorption peak is attributed to the oxide of the polymer constituting the elastomer. The vicinity of the wavenumber of 1650 cm -1 means preferably a wavenumber range of 1650 cm -1 ±100 cm -1 , and more preferably means a wavenumber range of 1650 cm -1 ±50 cm -1 .

[0024] In the infrared absorption spectrum, an infrared absorption peak B having an absorption peak of absorbance appears in the vicinity of a wavenumber of 1470 cm -1 . The infrared absorption peak B is attributed to the scissoring vibration (in-plane deformation vibration) of -CH2- in the polymer main chain of the elastomer. The vicinity of the wavenumber of 1470 cm -1 means preferably a wavenumber range of 1470 cm -1 ±50 cm -1 , and more preferably means a wavenumber range of 1470 cm -1 ±20 cm -1 .

[0025] Inside the elastomer constituting the medical rubber product of the present invention, when the area of the infrared absorption peak A is Ai, the area of the infrared absorption peak B is Bi, and Si = (Ai / Bi) × 100, it is preferable that P = (Ss / Si) × 100 is 150 or less, preferably 140 or less, and more preferably 130 or less. The P (= Ss / Si) is an index indicating the degree of deterioration between the inside and the surface part of the medical rubber product. If the P is 150 or less, the deterioration of the surface part is small, and the non-elution property and non-tackiness are good. The lower limit of the P is not particularly limited.

[0026] [Medical rubber product] The medical rubber product of the present invention is formed from an elastomer. The elastomer is not particularly limited as long as it contains a polymer having a methylene chain (-CH2-) in the main chain, and is preferably an elastomer composed of a rubber component.

[0027] The elastomer is preferably a cured product of a medical rubber composition containing (a) a base polymer containing halogenated butyl rubber and (c) a triazine derivative as a crosslinking agent, and more preferably a cured product of a medical rubber composition containing (a) a base polymer containing halogenated butyl rubber, (b) polyethylene, and (c) a triazine derivative as a crosslinking agent. Hereinafter, the raw materials contained in the medical rubber composition of the present invention will be described.

[0028] First, the (a) base polymer containing halogenated butyl rubber will be described. Examples of the halogenated butyl rubber include chlorinated butyl rubber, brominated butyl rubber, and brominated copolymers of isobutylene and p-methylstyrene rubber (brominated isobutylene paramethylene styrene copolymer rubber).

[0029] As the halogenated butyl rubber, chlorinated butyl rubber or brominated butyl rubber is preferred. The chlorinated butyl rubber or brominated butyl rubber is obtained, for example, 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. Note that butyl rubber is a copolymer obtained by polymerizing isobutylene and a small amount of isoprene.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] The above-mentioned (a) base polymer may contain a rubber component other than halogenated butyl rubber. Examples of other rubber components include nitrile rubbers such as butyl rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, natural rubber, chloroprene rubber, acrylonitrile-butadiene rubber, etc., 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, phosphazene rubber, or 1,2-polybutadiene, etc. These may be used alone or in combination of two or more.

[0034] When using other rubber components, the content of 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. Also, a preferred embodiment is that the (a) base polymer consists only of halogenated butyl rubber.

[0035] The medical rubber composition of the present invention preferably contains (b) polyethylene. Polyethylene is more likely to absorb gamma rays than the (a) base polymer and has the effect of preventing the chain breakage of the (a) base polymer by gamma ray irradiation. Also, polyethylene with a low degree of crystallinity has branches and is considered to undergo crosslinking without the main chain being broken even by gamma ray irradiation. As a result, it is considered that the elution performance of the medical rubber composition is improved.

[0036] From such a perspective, examples of the (b) polyethylene used in the present invention include high-density polyethylene (HDPE) or low-density polyethylene (LDPE). High-density polyethylene (HDPE) and low-density polyethylene (LDPE) may be used alone or in combination.

[0037] When high-density polyethylene (HDPE) and low-density polyethylene (LDPE) are used in combination, the mass ratio of high-density polyethylene (HDPE) to low-density polyethylene (LDPE) (HDPE / LDPE) is preferably 0.3 or more, more preferably 0.5 or more, even more preferably 1.0 or more, preferably 5.0 or less, more preferably 4.0 or less, and even more preferably 3.0 or less. If the mass ratio of high-density polyethylene (HDPE) to low-density polyethylene (LDPE) (HDPE / LDPE) is within the above range, the radical absorption effect during gamma-ray irradiation and the appropriate hardness of the rubber can be ensured.

[0038] (b) The polyethylene preferably contains polyethylene having a crystallinity of 70% or less.

[0039] The crystallinity of high-density polyethylene (HDPE) is preferably 60% to 80%, more preferably 60% to 75%, and even more preferably 60% to 70%. The crystallinity of low-density polyethylene (LDPE) is preferably 30% to 50%, more preferably 30% to 45%, and even more preferably 30% to 40%. If the crystallinity of the polyethylene is within the above range, the radicals generated by gamma-ray irradiation can be effectively absorbed, preventing the cleavage of the polymer main chain.

[0040] (b) The crystallinity of the polyethylene is determined by the following formula. Crystallinity (%) = (measured heat of fusion (J / g) / heat of fusion of a perfect crystal (J / g)) × 100 The heat of fusion of a perfect crystal (J / g) is 293 J / g (literature value), which is the heat of fusion of polyethylene at 100% crystallinity. The method for measuring the heat of fusion of polyethylene will be described later.

[0041] (b) As the polyethylene, low-density polyethylene is preferred. The density (g / cm 3 ) of high-density polyethylene is preferably 0.930 to 0.960, and more preferably 0.930 to 0.950. The density (g / cm 3) is not particularly limited, but is preferably 0.910 to 0.925, more preferably 0.910 to 0.920.

[0042] (b) As the polyethylene, a fine powder form is preferably used. The volume average particle diameter of the fine powder polyethylene is preferably 10 μm or more, more preferably 15 μm or more, further preferably 20 μm or more, preferably 200 μm or less, more preferably 160 μm or less, and further preferably 120 μm or less. When the particle diameter of the fine powder polyethylene is within the above range, it is easier to uniformly mix and disperse in the polymer.

[0043] (b) The blending amount of the polyethylene is preferably 3 parts by mass or more, more preferably 5 parts by mass or more, further preferably 10 parts by mass or more, preferably 30 parts by mass or less, more preferably 25 parts by mass or less, and further preferably 20 parts by mass or less with respect to 100 parts by mass of the (a) base polymer. If the blending amount of the (b) polyethylene is within the above range, radicals generated during gamma-ray irradiation can be effectively absorbed, and cleavage of the polymer main chain can be prevented.

[0044] The medical rubber composition of the present invention preferably contains a triazine derivative as the (c) crosslinking agent.

[0045] The triazine derivative acts as a crosslinking agent for the halogenated butyl rubber. Examples of the triazine derivative include compounds represented by the general formula (1).

Chemical formula

[0046] In 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 examples thereof include 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.

[0047] 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.

[0048] 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.

[0049] Examples of the triazine derivative also include one or more of, for example, 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.

[0050] In the present invention, as the triazine derivative, one type may be used alone, or two or more types may be used in combination.

[0051] In the medical rubber composition of the present invention, the content of (c) the triazine derivative is preferably 0.1 part by mass or more, more preferably 0.3 part by mass or more, still more preferably 0.5 part by mass or more, preferably 2.0 parts by mass or less, more preferably 1.4 parts by mass or less, and still more preferably 1.2 parts by mass or less with respect to 100 parts by mass of the (a) base polymer component. If the content of (c) the triazine derivative is within the above range, it is possible to obtain a rubber having good rubber physical properties (hardness, tensile strength, C set), elution performance, and processability (less scorching).

[0052] The medical rubber composition of the present invention preferably does not contain a vulcanization accelerator. This is because the vulcanization accelerator may remain in the final rubber product and elute 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).

[0053] The medical rubber composition of the present invention 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 products. 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 magnesium oxide can also function as an acid acceptor.

[0054] Examples of hydrotalcite include, for example, 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 based hydrotalcites such as Mg-Al based hydrotalcite such as CO3·1.7H2O can be mentioned.

[0055] Specific examples of hydrotalcite include, for example, DHT-4A (registered trademark)-2 manufactured by Kyowa Chemical Industry Co., Ltd.

[0056] In the medical rubber composition of the present invention, 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 part 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 base polymer component (a). If the total content of the acid acceptor (hydrotalcite and MgO) is within the above range, generation of rust on a mold or the like can be suppressed, and the problem that the raw material itself becomes a white spot foreign matter can be reduced.

[0057] The medical rubber composition of the present invention 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 (meth)acrylate-based compound having two or more functional groups, even 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".

[0058] 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.

[0059] The medical rubber composition of the present invention may contain (d) a filler. (d) Examples of the filler include inorganic fillers such as silica, clay, and talc. As the filler, clay or talc is more preferable. The filler functions to adjust the rubber hardness of the medical rubber product and also functions to reduce the production cost of the medical rubber product as a bulking agent.

[0060] 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.

[0061] Specific examples of the talc include, for example, Hytron 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.

[0062] The medical rubber composition of the present invention may further contain a coloring agent such as titanium oxide and carbon black, a processing aid, polyethylene glycol as a crosslinking activator, a plasticizer (for example, paraffin oil), etc. in appropriate proportions.

[0063] The medical rubber composition of the present invention is obtained by kneading (a) a base polymer containing a halogenated butyl rubber, (b) polyethylene, (c) a triazine derivative as a crosslinking agent, and other compounding materials added as necessary. The kneading can be carried out 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.

[0064] By press-molding a ribbon-shaped, sheet-shaped, or pellet-shaped kneaded product, a medical rubber product of 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.

[0065] 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, dried, and packaged to produce a medical rubber product.

[0066] The JIS-A hardness of the elastomer constituting the medical rubber product of the present invention is preferably 30 or higher, more preferably 35 or higher, further preferably 40 or higher, preferably 70 or lower, more preferably 65 or lower, and further preferably 60 or lower. If the JIS-A hardness of the elastomer is within the above range, the product performances such as the sealing performance and the needle puncture resistance required for the rubber stopper can be compatible.

[0067] The compression set of the elastomer constituting the medical rubber product of the present invention, measured under the conditions of 70 °C, 22 hours, and 25% in accordance with JIS K6262, is preferably 20% or less, more preferably 15% or less, and further preferably 10% or less. If the compression set of the elastomer is within the above range, the sealing performance required for the rubber stopper and the needle hole is quickly blocked and no liquid leakage occurs when the needle is withdrawn after the needle puncture.

[0068] [Sterilization method] The medical rubber product of the present invention is preferably sterilized by radiation irradiation, and more preferably sterilized by gamma-ray or electron-beam irradiation. The sterilization method preferably irradiates radiation to a package of medical rubber products in which a plurality of medical rubber products are accommodated.

[0069] Examples of the radiation used for sterilization treatment include α-rays (helium nuclei), β-rays (electron beams), and γ-rays (gamma rays). Since the dose rate of β-rays (electron beams) is extremely high (tens of thousands of times that of γ-rays), the sterilization treatment time is short, but due to being a particle beam, the penetration power is small. On the other hand, γ-rays have a large penetration power, but the dose rate is small compared to electron beams, so the treatment time becomes long. In the present invention, from the viewpoint of sterilizing a package of medical rubber products containing a plurality of medical rubber products, it is preferable to perform sterilization treatment using γ-rays.

[0070] Examples of γ-rays include γ-rays emitted from, for example, cobalt 60 and cesium 137, and γ-rays emitted from cobalt 60 are preferable.

[0071] Gamma-ray irradiation is established based on the absorbed dose of γ-rays of medical rubber products in the actual sterilization validation procedure. In many ordinary medical devices, 15 kGy is often used as the minimum absorbed dose. The irradiation dose of γ-rays to ensure that the absorbed dose of γ-rays of all medical rubber products in the package is 15 kGy or more will vary depending on the number and packaging method of the medical rubber products in the package, but generally, it is irradiated with a dose in the range of 1.4 times or more and 2.0 times or less of 15 kGy. Similarly, when 20 kGy is the minimum absorbed dose, it is irradiated with a dose in the range of 1.4 times or more and 2.0 times or less of 20 kGy, and when 25 kGy is the minimum absorbed dose, it is irradiated with a dose in the range of 1.4 times or more and 2.0 times or less of 25 kGy. The absorbed dose of γ-rays can be confirmed by attaching a dosimeter to the irradiated object.

[0072] The package containing medical rubber products before γ-ray irradiation preferably has an oxygen concentration of 5% or less, more preferably 3% or less, and even more preferably 1% or less. This is because by setting the oxygen concentration in the package to 5% or less, deterioration of the medical rubber products due to γ-ray irradiation can be suppressed.

[0073] As methods for reducing the oxygen concentration in the package to 5% or less, there can be mentioned a method of replacing the air in the package with an inert gas and a method of accommodating an oxygen scavenger in the package.

[0074] Examples of the inert gas include noble gases such as helium, neon, and argon, or nitrogen gas.

[0075] Examples of the oxygen scavenger include iron-based oxygen scavenger Agentless (commercially available products).

[0076] The package for accommodating medical rubber products is not particularly limited as long as it can be irradiated with gamma rays. Examples of the package include shapes such as bags and boxes. Examples of the packaging bag include a packaging bag formed of a thermoplastic resin film such as polyethylene, polyamide, or polyester, or aluminum. The packaging bag is preferably one that can be sealed. The packaging box is not particularly limited, and examples include cardboard boxes and corrugated boxes.

[0077] Examples of the package include a breathable package and an airtight (gas-sealed) package, and it is also preferable to use these in combination.

[0078] Gamma ray irradiation of medical rubber products may be performed, for example, on a package (such as a cardboard box) that contains a plurality of primary packages (such as packaging bags) each containing a plurality of medical rubber products.

[0079] FIG. 1 is an explanatory diagram schematically showing an example of a packaging mode for gamma irradiation. In the mode shown in FIG. 1, a primary package 3 containing a plurality of medical rubber products 1 is further housed in a secondary antistatic package 5 and a tertiary antistatic package 7. As the primary package 3, those having air permeability are preferable, and the secondary antistatic package 5 and the tertiary antistatic package 7 are preferably those capable of sealing gas. The secondary antistatic package 5 and the tertiary antistatic package 7 are preferably sealed by heat seals 9 respectively. When using an oxygen scavenger 11, it is preferable to arrange the oxygen scavenger 11 between the primary package 3 and the secondary package 5 so that the oxygen scavenger 11 does not directly contact the medical rubber product 1. By arranging the oxygen scavenger 11 in the secondary package 5, the oxygen concentration in the secondary package 5 and the primary package 3 can be made 5% or less. A plurality of the tertiary antistatic packages 7 can be housed in a quaternary package (for example, a cardboard box) for gamma irradiation.

[0080] FIG. 2 is an explanatory diagram schematically showing another example of a packaging mode for gamma irradiation. In the mode shown in FIG. 2, a primary package 3 containing a plurality of medical rubber products 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 by heat seals 9 respectively. As the primary package 3, those having air permeability are preferable, and the secondary antistatic package 5 and the tertiary antistatic package 7 are preferably those capable of sealing gas. The secondary package 5 containing the primary package 3 is filled with an inert gas. By filling with an inert gas, the oxygen concentration in the secondary package 5 and the primary package 3 can be made 5% or less. A plurality of the tertiary antistatic packages 7 can be housed in a quaternary package (for example, a cardboard box) for gamma irradiation.

[0081] In addition, at the time of gamma irradiation, the package containing a plurality of medical rubber products is preferably irradiated with gamma rays in a state of being housed in a storage container made of, for example, an aluminum alloy.

[0082] The sterilized medical rubber product of the present invention preferably has a viable cell count (cfu: colony forming unit: the number of colonies that appear when cultured) of 0 in the bioburden measurement test.

[0083] Examples of the medical rubber product of the present invention include rubber stoppers and seal members for containers for various drugs (such as vials) for liquid preparations, powder preparations, freeze-dried preparations, etc., rubber stoppers for vacuum blood collection tubes, plunger stoppers for prefilled syringes, or sliding or seal parts such as nozzle caps.

Example

[0084] Hereinafter, the present invention will be described in detail with reference to examples. However, the present invention is not limited by the following examples, and modifications and embodiments within the scope not departing from the gist of the present invention are all included in the scope of the present invention.

[0085] [Preparation of medical rubber composition] Among the components shown in Table 1, components other than the crosslinking component (triazine-based crosslinking agent) were blended and kneaded at a filling rate of 75% using a 10 L pressure-sealed kneader. After aging at room temperature, the crosslinking component was added and kneaded on an open roll to prepare a rubber composition.

[0086]

Table 1

[0087] [Manufacture of Medical Rubber Stoppers] The rubber composition was formed into a sheet shape, sandwiched between an upper mold and a lower mold, and subjected to vacuum press molding at 180 °C for 6 minutes. The rubber stoppers for vials of freeze-dried injections with a flange diameter of 19.0 mm, an overall height of 13.0 mm, a leg diameter of 7.20 mm, and a thickness of the flange puncture part of 2.5 mm were continuously formed on one sheet of the above-mentioned sheet. Next, a silicone-based lubricating coating agent was applied to both sides of the sheet, and then the rubber stoppers were manufactured through the steps of appearance inspection, punching, washing, sterilization, and drying. The manufactured rubber stoppers were used for eluate tests and adhesion tests. The sterilization treatment conditions by gamma rays are shown in Table 2.

[0088]

Table 2

[0089] [Evaluation Method] (1) Fourier Transform Infrared Spectrophotometer (FT-IR) Measurement From the top surface of the sterilized medical rubber stopper, a thickness (about 1.0 mm) that can be placed on the measuring device was cut out with a razor to prepare a measurement sample. The medical rubber stopper was cut longitudinally so as to pass through the center in a plan view, and from the center part of the obtained cross section, a thickness (for example, 0.5 mm to 2.0 mm) that can be placed on the measuring device was cut out with a razor to obtain a measurement sample. The measurement sample was placed on the measuring device, and light was irradiated on the outer diameter 1 mm region of the surface part for measurement.

[0090] The FT-IR measurement was performed using a Frontier GeATR unit MIRAcle manufactured by Perkin Elmer Co., Ltd. with a wavenumber resolution of 4 cm -1 and 16 accumulations.

[0091] Figure 3 is an FT-IR chart of the surface part of a medical rubber product subjected to sterilization treatment No. 1. Figure 4 is an FT-IR chart of the surface part of a medical rubber product subjected to sterilization treatment No. 7.

[0092] In the obtained infrared absorption spectrum, an infrared absorption peak A having an absorption peak of absorbance around a wavenumber of 1650 cm -1 and an infrared absorption peak B having an absorption peak of absorbance around a wavenumber of 1470 cm -1 appear. Regarding the infrared absorption peak A, a baseline was drawn between 1750 cm -1 and 1590 cm -1 , and its area (As) was calculated. Regarding the infrared absorption peak B, a baseline was drawn between 1510 cm -1 and 1408 cm -1 , and its area (Bs) was calculated. Similarly for the inside of the medical rubber stopper, the area (Ai) of the infrared absorption peak A and the area (Bi) of the infrared absorption peak B were calculated.

[0093] (2) Measurement of the heat of fusion of polyethylene The heat of fusion of polyethylene is obtained from the first heating test of differential scanning calorimetry (DSC: Differential Scanning Calorimetry). DSC measurement conditions: 20°C to 200°C, heating rate 10°C / min

[0094] (3) Eluate test Measurement sample: With the medical rubber stopper placed in a polyethylene bag (the packaging form shown in Figures 1 and 2), it was irradiated with gamma rays under the environment and absorbed dose inside the package described in Table 2 to obtain a rubber stopper after gamma ray irradiation. For the measurement sample, the "eluate test" described in the "7.03 Rubber Stopper Test Method for Infusions" of the 17th revised Japanese Pharmacopoeia was carried out. The compliance conditions were as follows. Properties of the test solution: Colorless and clear UV transmittance: With 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 If any item is not satisfied, it is evaluated as "non-conforming", and if all items are satisfied, it is evaluated as "conforming".

[0095] (4) TOC test For the eluate obtained by performing the eluate test in (3), the total organic carbon value TOC (NPOC: aeration treatment method under acidic conditions) was measured. Measurement and analysis apparatus: Shimadzu Total Organic Carbon Analyzer TOC-L CPH (Combustion oxidation method) Measurement and analysis conditions: Combustion tube temperature 680 °C, using a high-sensitivity catalyst, Carrier gas: High-purity air 150 mL / min, Injection volume 150 μL, Acid addition concentration 1%, Aeration treatment time 60 sec

[0096] The elution characteristics before and after gamma-ray irradiation were evaluated. With the TOC before gamma-ray irradiation set as 100%, the TOC after gamma-ray irradiation was evaluated using a relative index. The larger the number, the worse the elution performance compared to before gamma-ray irradiation. Evaluation criteria 〇: 125% or less (equivalent to before irradiation) △: More than 125% and 150% or less (slightly deteriorated compared to before irradiation) ×: More than 150% (significantly deteriorated compared to before irradiation)

[0097] (4) Microbiological limit test The microbiological limit test method applied the combined use of the ultrasonic recovery method and the medium immersion method. Operation procedure a: Each sample was transferred to a test tube of φ18 mm × 180 mm in which 10 mL of PTS recovery solution (1% peptone, 0.1% Tween 80, 0.85% saline) had been dispensed. b: Ultrasonic treatment was carried out for 15 minutes. c: Each recovered solution was suction filtered through a Milliflex membrane filter (MF). d: The filtered Milliflex membrane filter (MF) was attached to an SCDA (Solid Soybean - Casein - Digest Agar Medium) plate medium. e: The sample after ultrasonic treatment was transferred to a deep - type petri dish and immersed in an SCDA medium containing 0.002% triphenyltetrazolium chloride. f: Cured at 30 °C to 35 °C for 7 days. g: After curing for 7 days, the medium was observed, and the total viable count of the ultrasonic recovery method and the viable count of the medium immersion method was taken as the viable count (cfu). The viable count (cfu) is the average value of 5 samples for each sample.

[0098] (5) Adhesion test Using the Shimadzu desktop testing machine EZ - SX, the following was done. As shown in Figure 5, the sample 13 was fixed to the lower fixing jig 15, the upper metal probe 17 was pressed onto the sample 13, and after reaching the set pressure, it was held for 10 seconds. Then, the metal probe 17 was raised upward, and the peak value of the adhesive force generated between the metal probe 17 and the sample 13 was taken as the tack value. The measurement was carried out 5 times for each sample, and among the obtained results, the average value of 3 measurement values excluding the maximum value and the minimum value was calculated. Taking the adhesive force of the sample before gamma - ray irradiation as 100, the adhesive force of the sample after gamma - ray irradiation was indexed. The smaller the index, the lower the adhesiveness and the better it is. Measurement conditions: Pressing speed: 0.5 mm / s Pressing load: 1000 g - weight Pressing holding time: 10 seconds Pulling - up speed: 10 mm / s Final pulling - up distance: 3 mm Probe diameter: 10 mm Evaluation criteria: 〇: 120% or less (equivalent to before irradiation) △: More than 120% and 150% or less (slightly deteriorated compared to before irradiation) ×: More than 150% (significantly deteriorated compared to before irradiation)

[0099] The results of the eluate test, TOC test, and adhesion test are shown together in Table 2.

[0100] Regarding the suitability of READY TO USE, the judgment was made as follows. When the eluate test result is compliant, the TOC test result is an evaluation result of Δ or higher, and the adhesion test result is Δ or higher, and the viable cell count (cfu) is zero, it is determined that it is compliant with READY TO USE. If any one of the evaluation results is not satisfied, it is regarded as non-compliant.

[0101] From the results in Table 2, a medical rubber product formed of an elastomer and sterilized by irradiation with gamma rays or electron beams (beta rays), when the surface part of the elastomer is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), the area of the infrared absorption peak at a wavenumber of 1650 cm -1 nearby is designated as As, and the area of the infrared absorption peak at a wavenumber of 1470 cm -1 nearby is designated as Bs, a medical rubber product for which Ss = (As / Bs) × 100 ≤ 6 maintains non-elution characteristics and has few troubles in the manufacturing process of medical supplies.

Industrial Applicability

[0102] According to the present invention, it is possible to provide a medical rubber product that maintains non-elution characteristics even after gamma sterilization and has few troubles in the manufacturing process of medical supplies.

Explanation of Signs

[0103] 1: Medical rubber product, 3: Primary package, 5: Secondary package, 7: Tertiary package, 9: Heat seal, 11: Oxygen absorber, 13: Sample, 15: Fixing jig, 17: Metal probe

[0104] A preferred embodiment (1) of the present invention is a medical rubber product formed of an elastomer and sterilized by irradiation with gamma rays or electron beams (beta rays), wherein when the surface portion of the elastomer is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), the area of the infrared absorption peak near the wavenumber 1650 cm -1 is designated as As, and the area of the infrared absorption peak near the wavenumber 1470 cm -1 is designated as Bs, and a medical rubber product characterized in that Ss = (As / Bs) × 100 ≤ 6.

[0105] A preferred embodiment (2) of the present invention is when the interior is cut out from the central portion of the medical rubber product and the exposed internal infrared absorption spectrum is measured, the interior has an area of the infrared absorption peak near the wavenumber 1650 cm -1 designated as Ai, and the peak area near the wavenumber 1470 cm -1 designated as Bi, and when Si = (Ai / Bi) × 100, a medical rubber product according to embodiment (1), wherein P = (Ss / Si) × 100 ≤ 150.

[0106] A preferred embodiment (3) of the present invention is a medical rubber product according to embodiment (1) or (2), wherein the elastomer is a cured product of a rubber composition containing (a) a base polymer containing a halogenated butyl rubber and (c) a triazine derivative as a crosslinking agent.

[0107] A preferred embodiment (4) of the present invention is a medical rubber product according to embodiment (3), wherein the halogenated butyl rubber is at least one selected from the group consisting of chlorinated butyl rubber, brominated butyl rubber, and brominated isobutylene paramethylstyrene copolymer rubber.

[0108] A preferred embodiment (5) of the present invention is a medical rubber product according to embodiment (3) or (4), wherein the rubber composition further contains (b) polyethylene.

[0109] A preferred embodiment (6) of the present invention is the medical rubber product according to embodiment (5), wherein (b) the polyethylene contains polyethylene with a crystallinity of 70% or less.

[0110] A preferred embodiment (7) of the present invention is the medical rubber product according to embodiment (5) or (6), wherein (b) the content of the polyethylene is 3 parts by mass or more and 30 parts by mass or less with respect to 100 parts by mass of the base polymer.

[0111] A preferred embodiment (8) of the present invention is the medical rubber product according to any one of embodiments (1) to (7), wherein the elastomer has a JIS-A hardness of 30 to 70 degrees and a compression set of 20% or less measured under the conditions of 70 °C, 22 hours, and 25% in accordance with JIS K6262.

[0112] A preferred embodiment (9) of the present invention is the medical rubber product according to any one of embodiments (1) to (8), wherein the medical rubber product 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. An elastomer formed of a cured rubber composition containing (a) a base polymer containing a halogenated butyl rubber, (b) polyethylene, and (c) a triazine derivative as a crosslinking agent, and sterilized by irradiation with gamma rays or electron beams (beta rays), wherein when the surface portion of the elastomer is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), the area of the infrared absorption peak at a wave number of 1650 cm －１ nearby is defined as As, and the area of the infrared absorption peak at a wave number of 1470 cm －１ nearby is defined as Bs, a medical rubber product characterized in that Ss = (As / Bs) × 100 ≦ 6.

2. When the internal infrared absorption spectrum is measured by cutting out from the central part of the medical rubber product, the internal part has an infrared absorption peak area near a wave number of 1650 cm －１ Let the area of the infrared absorption peak near the wave number be Ai, and the peak area near the wave number of 1470 cm －１ be Bi, and when Si = (Ai / Bi) × 100, the medical rubber product according to claim 1, wherein P = (Ss / Si) × 100 ≤ 150.

3. The halogenated butyl rubber is at least one selected from the group consisting of chlorinated butyl rubber, brominated butyl rubber, and brominated isobutylene para-methylstyrene copolymer rubber. The medical rubber product according to claim 1.

4. (b) The polyethylene contains polyethylene with a crystallinity of 70% or less. The medical rubber product according to claim 1.

5. (b) The content of the polyethylene is 3 parts by mass or more and 30 parts by mass or less with respect to 100 parts by mass of the base polymer (a). The medical rubber product according to claim 1.

6. The elastomer has a JIS-A hardness of 30 to 70 degrees, and the compression set measured under the conditions of 70 ° C., 22 hours, and 25% in accordance with JIS K6262 is 20% or less. The medical rubber product according to claim 1.

7. The medical rubber product 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. The medical rubber product according to any one of claims 1 to 6.

8. A method for determining ready-to-use of a medical rubber product formed of an elastomer and sterilized by irradiation with gamma rays or electron beams (beta rays), wherein the surface portion of the elastomer is measured by the total reflection measurement method (ATR method) using a Fourier transform infrared spectrophotometer (FT-IR), and when the area of the infrared absorption peak near the wave number 1650 cm-1 in the obtained infrared absorption spectrum is As and the area of the infrared absorption peak near the wave number 1470 cm-1 is Bs, Ss = (As / Bs) × 100 ≦ 6. A method for determining ready-to-use of a medical rubber product, characterized in that it is determined that the medical rubber product is suitable for ready-to-use.

9. Further, when the internal infrared absorption spectrum is measured by cutting out from the center portion of the medical rubber product, and the area of the infrared absorption peak near the wave number 1650 cm-1 in the interior is Ai and the peak area near the wave number 1470 cm-1 is Bi, and Si = (Ai / Bi) × 100, P = (Ss / Si) × 100 ≦ 150. The method for determining ready-to-use according to claim 8, wherein it is determined that the medical rubber product is suitable for ready-to-use.

10. The method for determining the ready-to-use of the medical rubber product according to claim 8, wherein the elastomer is a cured product of a rubber composition containing (a) a base polymer containing a halogenated butyl rubber, (b) polyethylene, and (c) a triazine derivative as a crosslinking agent.

11. The method for determining the ready-to-use of the medical rubber product according to claim 10, wherein the halogenated butyl rubber is at least one selected from the group consisting of chlorinated butyl rubber, brominated butyl rubber, and brominated isobutylene para-methylstyrene copolymer rubber.

12. The method for determining the ready-to-use of the medical rubber product according to claim 10, wherein the content of (b) the polyethylene is 3 parts by mass or more and 30 parts by mass or less with respect to 100 parts by mass of the (a) base polymer.

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