Medical rubber product packaging and sterilization method thereof

Abstract

To provide a novel package in which a medical rubber product is accommodated, and which can hold oxygen in the package at a prescribed concentration or less, and enables visual confirmation of an oxygen concentration in the package so as to easily assure quality by sterilization processing.SOLUTION: The present invention relates to a package in which a medical rubber product is sealed. The package is made of an oxygen-impermeable packaging material, and has a first space portion in which the medical rubber product is accommodated, and a second space portion in which an oxygen detecting agent whose color tone changes according to an oxygen concentration is accommodated. The first space portion and the second space portion are partitioned by an oxygen-permeable partition.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to the sterilization of medical rubber products, and more particularly to a package for medical rubber products and a method for sterilization thereof. [Background technology]

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

[0003] There is an increasing demand for ready-to-use (RTU) medical 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 radiation sterilization.

[0004] When medical rubber products are sterilized with EOG, there is a concern that EOG residue may remain, so work is required to remove the EOG. When medical rubber products are sterilized with high-pressure steam, time is required for the steam to dry. Gamma ray sterilization, a type of radiation sterilization, can sterilize medical rubber products while they are still packaged, which has the advantage that they can be delivered without opening the packaging. For this reason, there is a trend to switch to gamma ray sterilization for medical rubber products.

[0005] Technologies relating to radiation sterilization are disclosed in, for example, Patent Documents 1 and 2.

[0006] Patent Document 1 discloses a method for sterilizing a plastic-containing article by irradiation with radiation or an electron beam, which comprises sealing the plastic-containing article together with an oxygen scavenger in a substantially non-breathable bag or container, and irradiating the article with radiation or an electron beam after deoxidization.

[0007] Patent Document 2 discloses a packaging material for radiation sterilization treatment comprising a laminate having an odor adsorption layer, characterized in that the odor adsorption layer is made of a resin composition containing an odor adsorbent comprising an inorganic porous body and a chemical adsorbent supported on the inorganic porous body. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Publication No. 8-89561 [Patent Document 2] JP 2014-233408 A Summary of the Invention [Problem to be solved by the invention]

[0009] When medical rubber products are sterilized by irradiating them with gamma rays, the polymers that make up the medical rubber products are simultaneously cleaved and crosslinked. Excessive gamma radiation absorbed promotes the cleavage of the polymer main chains that make up the medical rubber products, producing low molecular weight components. This leads to a deterioration in the elution performance of the medical rubber products after gamma ray sterilization. In addition, the cleaved low molecular weight components bleed out onto the surface of the rubber products, causing the medical rubber products to adhere to each other, which can cause problems with clogging the parts feeders used in the manufacturing process of medical supplies.

[0010] One option is to incorporate an antioxidant into medical rubber products in order to protect against excessive gamma radiation absorption. However, there are concerns that the addition of an antioxidant may result in a decrease in elution characteristics and adverse effects on pharmaceuticals.

[0011] In view of the above problems, the applicant of the present application has found that a medical rubber product with maintained non-elution performance can be obtained by reducing the oxygen concentration of a package containing the medical rubber product and performing gamma ray sterilization, and has filed patent applications (Patent Application Nos. 2021-208609 and 2022-169472). However, it is difficult to check for each package whether the oxygen concentration in the package before sterilization and before shipment is below a predetermined concentration, which creates quality assurance problems.

[0012] The present invention has been made in consideration of the above circumstances, and an object of the present invention is to make it possible to visually check the oxygen concentration in a package, thereby facilitating quality assurance through sterilization treatment. [Means for solving the problem]

[0013] The packaging body of the present invention is a packaging body in which a medical rubber product is sealed, the packaging body being made of an oxygen-impermeable packaging material and having a first space portion in which the medical rubber product is contained and a second space portion in which an oxygen detector whose color tone changes depending on the oxygen concentration is contained, the first space portion and the second space portion being separated by an oxygen-permeable partition.

[0014] The packaging body of the present invention is a secondary packaging body containing a primary packaging body in which a medical rubber product is sealed, the primary packaging body being made of an oxygen-impermeable packaging material and having a first space portion in which the medical rubber product is contained, a second space portion in which an oxygen detector whose color tone changes depending on the oxygen concentration is contained, and a third space portion in which an oxygen scavenger and / or an oxygen detector whose color tone changes depending on the oxygen concentration is contained, the first space portion and the second space portion being partitioned by an oxygen-permeable partition, and the first space portion and the third space portion being partitioned by an oxygen-impermeable partition, The primary packaging body is characterized in that an air hole is formed which communicates the third space with the internal space of the secondary packaging body.

[0015] The present invention includes a method for sterilizing the package of the present invention. Effect of the Invention

[0016] According to the present invention, the oxygen concentration in the package can be visually confirmed, making it easy to ensure quality through sterilization treatment. [Brief description of the drawings]

[0017] [Figure 1] FIG. 2 is an explanatory diagram showing a schematic diagram of an example of a packaging form for the medical rubber product of the present invention. [Diagram 2] FIG. 4 is an explanatory diagram showing a schematic diagram of another example of a packaging embodiment of the medical rubber product of the present invention. [Diagram 3] FIG. 1 is an explanatory diagram showing a schematic diagram of another example of a packaging embodiment of the medical rubber product of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] <Package> The packaging body of the present invention is a packaging body in which a medical rubber product is sealed, the packaging body being made of an oxygen-impermeable packaging material and having a first space portion in which the medical rubber product is contained and a second space portion in which an oxygen detector whose color tone changes depending on the oxygen concentration is contained, the first space portion and the second space portion being separated by an oxygen-permeable partition.

[0019] The package of the present invention is a package in which film-like packaging materials are stacked on top of each other and the edges are sealed to form a storage section within the package. Examples of the package form include a four-sided sealed type and a three-sided sealed type.

[0020] A four-sided sealed package is made by stacking two sheets of film-like packaging material of the same shape and size, with peripheral seals provided on the three surrounding sides. The remaining side is an opening through which the contents are filled and contained, and then the opening is sealed again to seal the package.

[0021] A three-sided sealed package is made by folding a sheet of film-like packaging material in half along a fold line, with the areas partitioned by the fold line forming the front and back films, and providing peripheral seals on two sides. The remaining side is the opening through which the contents are filled and contained, and then the opening is sealed to hermetically seal the package.

[0022] The shape of the package of the present invention in plan view is not particularly limited, but is preferably an approximately rectangular shape, more preferably a rectangular shape. The length of one side of the approximately rectangular shape is preferably 17 cm or more, more preferably 20 cm or more, and is preferably 75 cm or less, more preferably 52 cm or less.

[0023] The packaging body of the present invention has a first space in which a medical rubber product is contained, and a second space in which an oxygen detector that changes color depending on the oxygen concentration is contained. The first space and the second space are separated by an oxygen-permeable partition.

[0024] The package of the present invention has a vertical direction and a width direction perpendicular to the vertical direction. The upper side of the package is the side where the opening for inserting the medical rubber product, the oxygen absorber and / or the oxygen detector, etc. is provided, and is the side that is sealed after these contents are placed in the package.

[0025] The package of the present invention preferably has at least an upper edge seal portion and a side edge seal portion, and may have an upper edge seal portion, a side edge seal portion, and a lower edge seal portion. The seal portion of the peripheral edge of the package is preferably formed by thermal welding (heat sealing).

[0026] The peripheral seal of the package is preferably provided linearly along the periphery of the package, and more preferably linearly. The seal width of the peripheral seal of the package is preferably 0.05 mm or more, more preferably 0.1 mm or more, even more preferably 0.5 mm or more, preferably 5.0 mm or less, more preferably 3.0 mm or less, and even more preferably 1.0 mm or less. By making the width of the peripheral seal of the package 0.05 mm or more, the airtightness of the package is increased. By making the width of the peripheral seal of the package 5.0 mm or less, the storage space inside the package can be increased.

[0027] The partition between the first space and the second space is preferably provided so as to extend from the upper edge seal portion of the package to one of the side edge seal portions. The shape of the partition between the first space and the second space is not particularly limited, but is preferably linear, and more preferably curved or bent. The upper edge seal portion of the first space and the upper edge seal portion of the second space are preferably adjacent to each other in the width direction to form the upper edge seal portion of the package. The side edge seal portion of the first space and the side edge seal portion of the second space are preferably adjacent to each other in the up-down direction to form one of the side edge seal portions.

[0028] The second space is defined by the upper edge seal portion, the side edge seal portion, and a partition, and forms a space for accommodating an oxygen detector that changes color depending on the oxygen concentration.

[0029] The first space is defined by the upper edge seal, the side edge seal, the lower edge of the packaging body, and a partition, and forms a space for housing the medical rubber product.

[0030] It is preferable that the partition between the first space and the second space has an air hole through which the medical rubber product and the oxygen detector cannot pass, and that the air hole allows oxygen to pass between the first space and the second space.

[0031] The partition between the first space and the second space is preferably provided with an air hole by discontinuously heat-sealing an oxygen-impermeable packaging material. The first space and the second space communicate with each other through the air hole. The width of the seal portion forming the partition between the first space and the second space is preferably 0.3 mm or more, more preferably 0.5 mm or more, and even more preferably 1.0 mm or more, and is preferably 3.0 mm or less, more preferably 2.5 mm or less, and even more preferably 2.0 mm or less.

[0032] The number of vent holes provided in the partition between the first space and the second space is not particularly limited, but is preferably 1 or more, more preferably 3 or more, and preferably 10 or less, and preferably 5 or less. The width of one vent hole is preferably 1 mm or more, preferably 3.0 mm or more, and preferably 15 mm or less, and preferably 10 mm or less. By setting the number and width of the vent holes as described above, the ventilation of the first space and the second space is improved. In addition, by keeping the width of the vent hole within the above range, the oxygen detector that changes color depending on the oxygen concentration contained in the second space can be prevented from moving to the first space.

[0033] In an embodiment in which an oxygen detector is contained in the second space, the first space and the second space are in communication with each other, so that the oxygen detector detects the oxygen concentration in the first space. The oxygen detector changes color depending on the oxygen concentration, so that the oxygen concentration in the first space of the package can be visually recognized.

[0034] The second space may contain an oxygen scavenger together with the oxygen detector, and in this embodiment, the oxygen concentration in the first space and the second space can be reduced by the oxygen scavenger. For example, in a package in which the internal space is filled with an inert gas and sealed, it is possible to remove oxygen remaining in the internal space or oxygen that has permeated from the outside of the package into the first space.

[0035] The package of the present invention preferably further has a third space portion for accommodating an oxygen scavenger and / or an oxygen detector.

[0036] Unlike the partition between the first space and the second space, the partition between the first space and the third space is preferably provided without an air hole and is oxygen impermeable. The partition between the first space and the third space is preferably a sealed part formed by continuously heat-sealing an oxygen-impermeable packaging material.

[0037] The partition between the first space and the third space is provided so as to span from the upper edge seal portion to one of the side edge seal portions. The shape of the partition between the first space and the third space is not particularly limited, but is preferably linear, and more preferably curved or broken.

[0038] The third space is defined by the upper edge seal portion, the side edge seal portion, and a partition, and forms a space for accommodating an oxygen absorber and / or an oxygen detector that changes color depending on the oxygen concentration.

[0039] The width of the seal portion forming the partition between the first space and the third space is preferably 0.3 mm or more, more preferably 0.5 mm or more, even more preferably 1.0 mm or more, preferably 3.0 mm or less, more preferably 2.5 mm or less, and even more preferably 2.0 mm or less. By making the width of the seal portion of the partition 0.3 mm or more, the airtightness of the third space is increased. By making the width of the seal portion of the partition 3.0 mm or less, the storage space of the third space can be increased.

[0040] The upper edge seal portion of the first space is located between the upper edge seal portion of the second space and the upper edge seal portion of the third space. The upper edge seal portion of the first space, the upper edge seal portion of the second space, and the upper edge seal portion of the third space are adjacent in the width direction to form the upper edge seal portion of the package. The side edge seal portion of the third space and the side edge seal portion of the first space are adjacent in the vertical direction to form one of the side edge seal portions.

[0041] The third space may be provided with a vent hole communicating with the outside of the package. The vent hole is preferably provided with a size that prevents the oxygen absorber and / or the oxygen detector that changes color depending on the oxygen concentration from leaking out. The vent hole is preferably provided in the side edge seal portion of the third space.

[0042] Examples of embodiments in which the packaging body of the present invention has a second spatial portion and a third spatial portion include a first embodiment in which an oxygen detector is accommodated in the second spatial portion and an oxygen absorber is accommodated in the third spatial portion; a second embodiment in which an oxygen detector is accommodated in the second spatial portion and an oxygen absorber and an oxygen detector are accommodated in the third spatial portion; a third embodiment in which an oxygen detector and an oxygen absorber are accommodated in the second spatial portion and an oxygen absorber is accommodated in the third spatial portion; and a fourth embodiment in which an oxygen detector and an oxygen absorber are accommodated in the second spatial portion and an oxygen absorber and an oxygen detector are accommodated in the third spatial portion.

[0043] The oxygen concentration in the internal space of the package of the present invention is preferably 1.0% by volume or less, more preferably 0.5% by volume or less, and even more preferably 0.1% by volume or less. If the oxygen concentration in the package is 1.0% by volume or less, deterioration of the rubber caused by gamma ray irradiation is suppressed, and the non-elution characteristics of the medical rubber product after gamma ray sterilization treatment are improved.

[0044] The internal space of the package of the present invention is preferably filled with an inert gas. By filling the package with an inert gas, the oxygen concentration in the package is reduced. Therefore, the amount of oxygen absorber used can be reduced, or a desired oxygen concentration can be achieved without using an oxygen absorber. Even when an oxygen absorber is used, the amount of decrease in the internal pressure of the package can be reduced by the oxygen absorber's absorption of oxygen, and adhesion between products caused by the decrease in internal pressure can be prevented. Examples of the inert gas include rare gases such as helium, neon, and argon, and nitrogen gas. The internal space of the package of the present invention is preferably filled with nitrogen.

[0045] <Secondary packaging> The present invention provides a secondary packaging body containing a primary packaging body in which a medical rubber product is sealed, the primary packaging body being made of an oxygen-impermeable packaging material and having a first space portion in which the medical rubber product is contained, a second space portion in which an oxygen detector whose color tone changes depending on the oxygen concentration is contained, and a third space portion in which an oxygen scavenger and / or an oxygen detector whose color tone changes depending on the oxygen concentration is contained, the first space portion and the second space portion being partitioned by an oxygen-permeable partition, and the first space portion and the third space portion being partitioned by an oxygen-impermeable partition, The primary packaging body The present invention includes a packaging body characterized in that an air hole is formed that communicates the third space with the internal space of the secondary packaging body.

[0046] Details of the primary package contained in the secondary package of the present invention are as described above and will not be described here.

[0047] The secondary packaging body is not particularly limited as long as it is made of an oxygen-impermeable packaging material. The secondary package may be formed from the same packaging material as that constituting the primary package, or may be formed from a different packaging material.

[0048] The secondary packaging body is preferably obtained by making a bag from a film-like packaging material. The secondary packaging body is a body in which film-like packaging materials are stacked on top of each other, and the edges are sealed to form a storage section inside. Examples of the form of the packaging body include a four-sided sealed type and a three-sided sealed type.

[0049] The shape of the secondary packaging body in a plan view is not particularly limited, but is preferably an approximately rectangular shape, more preferably a rectangular shape. In addition, from the viewpoint of storing a plurality of primary packaging bodies, the length of one side of the approximately rectangular shape of the secondary packaging body is preferably 30 cm or more, more preferably 50 cm or more, preferably 100 cm or less, more preferably 85 cm or less.

[0050] Examples of embodiments in which the primary packaging contained in the secondary packaging of the present invention has a second spatial portion and a third spatial portion include a first embodiment in which an oxygen detector is contained in the second spatial portion and an oxygen absorber is contained in the third spatial portion; a second embodiment in which an oxygen detector is contained in the second spatial portion and an oxygen absorber and an oxygen detector are contained in the third spatial portion; a third embodiment in which an oxygen detector and an oxygen absorber are contained in the second spatial portion and an oxygen absorber is contained in the third spatial portion; and a fourth embodiment in which an oxygen detector and an oxygen absorber are contained in the second spatial portion and an oxygen absorber and an oxygen detector are contained in the third spatial portion.

[0051] The secondary packaging of the present invention may contain only one of the above-mentioned embodiments, or may contain primary packaging of any combination of the above-mentioned embodiments. The number of primary packaging contained in the secondary packaging is not particularly limited as long as it is 1 or more, and is preferably 2 or more, more preferably 10 or less, and more preferably 4 or less.

[0052] The internal space of the secondary packaging body of the present invention is preferably filled with an inert gas. By filling the secondary packaging with an inert gas, the oxygen concentration in the secondary packaging is reduced. Therefore, the amount of oxygen absorber used can be reduced. Examples of the inert gas include rare gases such as helium, neon, and argon, and nitrogen gas. The internal space of the packaging of the present invention is preferably filled with nitrogen.

[0053] The internal space of the secondary packaging body of the present invention may be filled with air as long as the oxygen concentration in the internal space of the primary packaging body is controlled to a predetermined value or less (preferably 1.0% by volume or less). This is because, if the oxygen concentration in the internal space of the primary packaging body is controlled to a predetermined value or less (preferably 1.0% by volume or less), the deterioration of the non-elution properties of the medical rubber product due to gamma ray sterilization can be suppressed. In addition, there is no need to fill the secondary packaging body with an inert gas, which improves production efficiency.

[0054] In an embodiment in which an oxygen detector is contained in the third space of the primary package, the third space and the internal space of the secondary package are in communication with each other, so that the oxygen detector detects the oxygen concentration in the internal space of the secondary package. The oxygen detector changes color depending on the oxygen concentration, so that the oxygen concentration in the internal space of the secondary package can be visually recognized.

[0055] In an embodiment in which an oxygen absorber is accommodated in the third space of the primary packaging body, the third space and the internal space of the secondary packaging body are in communication with each other, so that the oxygen absorber absorbs oxygen in the internal space of the secondary packaging body. In this embodiment, the oxygen absorber can reduce the oxygen concentration in the internal space of the secondary packaging body. For example, when the internal space of the secondary packaging body is filled with air and sealed, the oxygen absorber can reduce the oxygen concentration in the internal space of the secondary packaging body, thereby preventing oxygen from permeating from the internal space of the secondary packaging body to the first space of the primary packaging body. In addition, when the internal space of the secondary packaging body is filled with an inert gas and sealed, oxygen remaining in the internal space of the secondary packaging body can be removed, thereby reliably preventing oxygen from permeating from the internal space of the secondary packaging body to the first space of the primary packaging body.

[0056] It is also preferable that the secondary packaging body of the present invention is further housed in a packaging body (for example, a tertiary packaging body to a quintic packaging body, etc.). The tertiary packaging body to the quintic packaging body are not particularly limited as long as they can be irradiated with gamma rays. Examples of the tertiary packaging body to the quintic packaging body include shapes such as bags and boxes. Examples of the packaging bag include packaging bags formed from thermoplastic resin films such as polyethylene, polyamide, and polyester, or aluminum. It is preferable that the packaging bag be sealable. Examples of the packaging box include, but are not particularly limited to, paper boxes, cardboard boxes, etc.

[0057] <Materials that make up the packaging> The packaging body of the present invention is formed from an oxygen-impermeable packaging material. The oxygen-impermeable packaging material used in the present invention has an oxygen transmission concentration (ml / (m 2 ·24h·atm)) is 10000ml / (m2 ·24h·atm) or less, and 1000ml / (m 2 ·24h·atm) or less is more preferable, and 20ml / (m 2 ·24h·atm) or less. 2 ·24h·atm) or less, and 200ml / (m 2 ·24h·atm) or less is more preferable, and 20ml / (m 2 It is more preferable that the oxygen permeability is within the above range (eg, 24h atm) or less. By using a packaging material with an oxygen permeability within the above range, the oxygen concentration within the package can be controlled.

[0058] The oxygen-impermeable packaging material used in the present invention is preferably one that can be heat-sealed, because the packaging material can be easily made into a bag by heat-sealing. In addition, the packaging material is preferably a transparent or semi-transparent material so that the color change of the oxygen detector can be confirmed.

[0059] The oxygen-impermeable packaging material used in the present invention is preferably a laminated film, which preferably has, for example, a base layer, a barrier layer, a sealant layer, and the like.

[0060] The substrate layer may be a resin film. Examples of the resin component of the resin film include polyethylene, polypropylene, cyclic polyolefin, fluorine-based resin, polystyrene, acrylonitrile-styrene copolymer (AS resin), acrylonitrile-butadiene-styrene copolymer (ABS resin), polyvinyl chloride, fluorine-based resin, poly(meth)acrylic resin, polyester such as polycarbonate, polyethylene terephthalate (PET), and polyethylene naphthalate, polyamide such as various nylons, polyimide, polyamideimide, polyarylphthalate, silicone resin, polysulfone, polyphenylene sulfide, polyethersulfone, polyurethane, acetal resin, and cellulose resin.

[0061] As the substrate layer, for example, an unstretched nylon film, a stretched nylon film, a PET film, a linear low-density polyethylene film, or a low-density polyethylene film is preferable.

[0062] The substrate layer preferably contains a film using one or more resins selected from the above, and may be composed of one layer or two or more layers of the same or different compositions.

[0063] The substrate layer may be a single layer or a multilayer film formed by a film forming method such as an extrusion method, a cast molding method, a T-die method, a cutting method, an inflation method, etc. The thickness of the substrate layer can be appropriately determined by a person skilled in the art, but is preferably 6 μm or more, more preferably 9 μm or more, and is preferably 150 μm or less, and more preferably 130 μm or less.

[0064] The barrier layer is a layer for preventing the intrusion of water vapor and oxygen from the outside into the inside of the package.

[0065] The barrier layer may be, for example, a metal foil, a transparent gas barrier film, or the like. Examples of the metal foil include foils made of pure aluminum, aluminum alloys, or the like. Examples of the transparent gas barrier film include films having inorganic deposition films or organic coating films on resin films such as polyolefin, vinyl polymer, polyester, and polyamide. Examples of the inorganic deposition films include aluminum deposition films, silica deposition films, alumina deposition films, and silica-alumina binary deposition films. Examples of the organic coating films include polyvinylidene chloride coating films and polyvinylidene fluoride coating films.

[0066] The thickness of the barrier layer is, for example, preferably 5 μm or more, more preferably 7 μm or more, and preferably 30 μm or less, more preferably 10 μm or less in order to provide an appropriate strength to the package and ensure processability such as heat sealing.

[0067] The sealant layer is a layer that imparts heat-sealing properties to the packaging material. Polyolefin resins are generally used as the material for the sealant layer, among thermoplastic resins. Specifically, ethylene resins such as low-density polyethylene resin (LDPE), medium-density polyethylene resin (MDPE), linear low-density polyethylene resin (LLDPE), ethylene-vinyl acetate copolymer (EVA), ethylene-α-olefin copolymer, and ethylene-methacrylic acid resin copolymer, blend resins of polyethylene and polybutene, and polypropylene resins such as homopolypropylene resin (PP), propylene-ethylene random copolymer, propylene-ethylene block copolymer, and propylene-α-olefin copolymer can be used. Cycloolefin polymer (COP) or cycloolefin copolymer (COC) can also be used.

[0068] The packaging material used in the present invention may be laminated by providing an adhesive layer between each of the layers such as the base layer, barrier layer, sealant layer, etc. Examples of the adhesive layer include an EC (extrusion coat) layer, a layer made of an adhesive for dry lamination, an adhesive for non-solvent lamination, etc.

[0069] When the adhesive layer is laminated using an extrusion coat, the adhesive layer or adhesive composition can be formed by extrusion coating on the layer to be adhered, although there is no particular limitation. In the extrusion coating, the adhesive or adhesive composition is first heated and melted, and then extruded in a curtain shape by expanding and stretching in the required width direction using a T-die, and the melt is allowed to flow down onto the layer to be adhered, and is sandwiched between a rubber roll and a cooled metal roll, thereby simultaneously forming the adhesive layer and adhering and laminating it onto the layer to be adhered.

[0070] When a dry lamination adhesive is used as the adhesive layer, the adhesive dispersed or dissolved in a solvent is applied onto one film and dried, and the other film is then laminated on top of it. The adhesive is then cured by aging at 30°C to 120°C for several hours to several days, and the films are then laminated.

[0071] When using a non-solvent laminating adhesive, the adhesive adheres without dispersing or dissolving in the solvent. The adhesive itself is applied onto a film and dried, and then another film is placed on top of it to laminate. The adhesive is then aged at 30°C to 120°C for several hours to several days to harden the adhesive and laminate the films.

[0072] These adhesives may be heat-curable, ultraviolet-curable, electron beam-curable, etc. Examples of such adhesives include polyvinyl acetate adhesives such as polyvinyl acetate and vinyl acetate-ethylene copolymers, polyacrylic acid adhesives made of copolymers of polyacrylic acid and polystyrene, polyester, polyvinyl acetate, etc., cyanoacrylate adhesives, and ethylene adhesives made of copolymers of monomers such as vinyl acetate, ethyl acrylate, acrylic acid, and methacrylic acid. Examples of suitable adhesives include ethylene copolymer-based adhesives, cellulose-based adhesives, polyurethane-based adhesives, polyester-based adhesives, polyamide-based adhesives, polyimide-based adhesives, polyolefin-based adhesives, amino resin-based adhesives made of urea resin or melamine resin, phenol resin-based adhesives, epoxy-based adhesives, reactive (meth)acrylic-based adhesives, elastomer-based adhesives made of chloroprene rubber, nitrile rubber, styrene-butadiene rubber, etc., silicone-based adhesives, and inorganic adhesives made of alkali metal silicates, low-melting point glass, etc.

[0073] The adhesive may be in any form, such as an aqueous type, a solution type, an emulsion type, or a dispersion type, and may be in any form, such as a film / sheet type, a powder type, or a solid type. Furthermore, the adhesive mechanism may be in any form, such as a chemical reaction type, a solvent evaporation type, a thermal melting type, or a thermal pressure type.

[0074] The adhesive layer is formed by applying the adhesive by, for example, roll coating, gravure roll coating, kiss coating, etc., and the coating amount is 0.1 g / m 2 ~10g / m 2 By setting the coating amount of the adhesive in the above range, good adhesion can be obtained.

[0075] The thickness of the oxygen-impermeable packaging material used in the present invention is not particularly limited, but is preferably 10 μm or more, more preferably 20 μm or more, even more preferably 40 μm or more, and is preferably 300 μm or less, more preferably 200 μm or less, and even more preferably 150 μm or less, because if the thickness of the packaging material is within the above range, the strength of the packaging material and the workability of the bagging operation are not impaired.

[0076] <Oxygen detector> The oxygen detector used in the present invention changes color in response to the oxygen concentration. This is because the oxygen concentration in the package can be visually confirmed by changing the color of the oxygen detector in response to the oxygen concentration.

[0077] The oxygen detector used in the present invention is preferably capable of detecting an oxygen concentration of 1.0% by volume or less in the package, more preferably 0.5% by volume or less, and even more preferably 0.1% by volume or less. The lower the detectable concentration, the easier it is to guarantee the quality of medical rubber products after sterilization.

[0078] An example of an oxygen detector is one formed by applying an ink composition for an oxygen indicator, which contains a redox dye, a reducing agent, a binder made of a resin having both hydrophilic and hydrophobic groups, and a solvent, to a support.

[0079] In addition to methylene blue, redox dyes that can be used include new methylene blue, neutral red, indigo carmine, safranine T, phenosafranine, Capri blue, Nile blue, diphenylamine, xylene cyanol, nitrodiphenylamine, ferroin, and N-phenylanthranilic acid.

[0080] As reducing agents, in addition to ascorbic acid, erythorbic acid and its salts, ascorbate salts, reducing sugars such as D-arabinose, D-erythrose, D-galactose, D-xylose, D-glucose, D-mannose, D-fructose, and D-lactose, and metal salts such as stannous salts and ferrous salts can be used.

[0081] The concentration of oxygen in the surrounding atmosphere can be detected not only by the change in hue of the redox dye, but also by the change in hue due to mixing with other color dyes. For this purpose, a colorant can be added to the ink composition for oxygen indicators.

[0082] Examples of colorants to be added include red colorants such as Food Red No. 2 (amaranth), Food Red No. 3 (erythrosine), Food Red No. 40 (Allura Red AC), Food Red No. 102 (New Coccine), Food Red No. 104 (Phloxine), Food Red No. 106 (Acid Red), and natural cochineal pigments; yellow colorants such as Food Yellow No. 4 (tartrazine), Food Yellow No. 5 (Sunset Yellow FCF), and natural safflower yellow; and blue colorants such as Food Blue No. 1 (Brilliant Blue FCF) and Food Blue No. 2 (indigo carmine).

[0083] The binder is used to fix the redox dye, the reducing agent, and the colorant on the support, and is preferably a resin having both a hydrophilic group and a hydrophobic group, specifically, polyvinyl acetal resin, methyl cellulose, ethyl cellulose, polyester resin with a hydrophilic group, etc., and polyvinyl acetal resin is particularly preferred.

[0084] The solvent is preferably one that can uniformly and stably dissolve or disperse the redox dye, reducing agent, colorant, and especially the binder, etc. Specifically, aromatic hydrocarbons, aliphatic hydrocarbons, esters, alcohols, water, etc. are used.

[0085] The support is preferably one that does not react with the ink composition for oxygen indicators and does not inhibit the coloring of the redox dye. Specifically, paper, synthetic paper, nonwoven fabric, synthetic resin film, etc. are used.

[0086] A specific example of the oxygen detector is Ageless Eye (registered trademark) (manufactured by Mitsubishi Gas Chemical Co., Ltd.) The Ageless Eye is blue when the oxygen concentration is 0.5% by volume or more, and pink when the oxygen concentration is 0.10% by volume or less.

[0087] <Oxygen absorber> The oxygen scavenger used in the present invention is not particularly limited as long as it has oxygen absorbing properties. As the oxygen scavenger, known oxygen scavenger can be used, for example, sulfite, hydrogen sulfite, dithionite, hydroquinone, catechol, resorcin, pyrogallol, gallic acid, Rongalite, ascorbic acid and / or its salt, isoascorbic acid and / or its salt, sorbose, glucose, lignin, dibutylhydroxytoluene, butylhydroxyanisole, ferrous salt, iron powder or other metal powder as the oxygen absorbing main agent, and can be appropriately selected according to the purpose.

[0088] In addition, the metal powder-based deoxidizer may contain one or more oxidation catalysts, such as sodium chloride, potassium chloride, magnesium chloride, calcium chloride, aluminum chloride, ferrous chloride, ferric chloride, sodium bromide, potassium bromide, magnesium bromide, calcium bromide, iron bromide, nickel bromide, sodium iodide, potassium iodide, magnesium iodide, calcium iodide, and iron iodide.

[0089] The oxygen scavenger may contain moisture or may contain a moisture donor, and may also contain deodorants, deodorants, and other fillers, as required. The shape of the oxygen scavenger is not particularly limited, and may be, for example, any of powder, granules, blocks, sheets, and the like, or may be a sheet or film-like oxygen scavenger in which various oxygen absorbing compositions are dispersed in a thermoplastic resin.

[0090] A specific example of the oxygen scavenger used in the present invention is Ageless (registered trademark) (manufactured by Mitsubishi Gas Chemical Company, Inc.).

[0091] <Manufacturing method of packaging body> The package of the present invention can be obtained by making a bag from the packaging material. Specifically, the bag is made as follows.

[0092] One sheet of packaging material is folded so that the sealant layers (heat-sealed surfaces) of the packaging material face each other, or two sheets of packaging material are overlapped and the periphery is heat-sealed. At this time, the upper edge side of the periphery is not heat-sealed, and a bag body with an opening for storing medical rubber products, etc. is produced.

[0093] The dividing line that forms the partition between the first space and the second space is heat sealed. The partition between the first space and the second space is discontinuously heat sealed according to the desired shape of the partition to form an air hole. The parts that are not heat sealed form the air hole. The heat sealing that forms the partition between the first space and the second space may be performed simultaneously with the process of heat sealing the peripheral edge of the package.

[0094] When the third space is formed in the package, the partition between the first space and the third space is formed by successively heat-sealing the first space and the third space according to the desired partition shape so that the first space and the third space do not communicate with each other. The heat-sealing to form the partition between the first space and the third space may be performed simultaneously with the process of heat-sealing the periphery of the package.

[0095] The conditions for heat sealing can be appropriately changed depending on the packaging material used, but for example, it is preferable to adopt the following conditions. Temperature: 130°C to 160°C is preferable, and 140°C to 150°C is more preferable. Time: 1 to 10 seconds is preferable, and 2 to 5 seconds is more preferable.

[0096] Next, a medical rubber product is contained in the first space of the bag, and an oxygen detector that changes color depending on the oxygen concentration is contained in the second space of the bag.

[0097] When the third space is formed in the package, an oxygen scavenger and / or an oxygen detector that changes color depending on the oxygen concentration is accommodated in the third space of the bag.

[0098] The bag containing the medical rubber product is set in a heat sealer, and the inside of the bag is replaced with an inert atmosphere. Specifically, the oxygen inside the bag is sucked out and the bag is filled with an inert gas. Examples of the inert gas include rare gases such as helium, neon, and argon, and nitrogen gas.

[0099] The upper edge of the pouch is then heat sealed to seal the opening of the pouch, thereby obtaining the package of the present invention in which the medical product is sealed.

[0100] In the present invention, the heat sealing method may be any known method such as bar sealing, rotary roll sealing, belt sealing, impulse sealing, high frequency sealing, ultrasonic sealing, etc.

[0101] [Medical rubber products] Examples of medical rubber products to be packaged in the present invention include rubber stoppers and sealing members for containers (e.g., vials) for various drugs such as liquid drugs, powder preparations, and freeze-dried preparations, rubber stoppers for vacuum blood collection tubes, plunger stoppers for prefilled syringes, and sliding or sealing parts such as nozzle caps.

[0102] The medical rubber product is preferably formed from a medical rubber composition containing (a) a rubber component. As the (a) rubber component, butyl rubber is preferable in terms of chemical resistance and gas permeability resistance, and halogenated butyl rubber is more preferable. Examples of halogenated butyl rubber include chlorinated butyl rubber, brominated butyl rubber, and brominated copolymer of isobutylene and p-methylstyrene. As the halogenated butyl rubber, chlorinated butyl rubber or brominated butyl rubber is preferable. The chlorinated butyl rubber or brominated butyl rubber is, for example, a butyl rubber obtained by adding or substituting chlorine or bromine to the isoprene structure portion of the butyl rubber, specifically, 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.

[0103] (a) The rubber component may contain a rubber component other than butyl rubber. Examples of the other rubber components include isoprene rubber, butadiene rubber, styrene butadiene rubber, natural rubber, chloroprene rubber, nitrile rubber such as 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, phosphanzene rubber, and 1,2-polybutadiene rubber. These may be used alone or in combination of two or more.

[0104] When other rubber components are used, the content of the butyl rubber in the (a) rubber component 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) rubber component is composed only of a halogenated butyl rubber.

[0105] The medical rubber composition preferably contains a crosslinking agent (b). The crosslinking agent (b) is blended to crosslink the rubber component (a). The crosslinking agent (c) is not particularly limited as long as it is a crosslinking agent capable of crosslinking rubber. Examples of the crosslinking agent (c) include sulfur, metal oxides, resin crosslinking agents, organic peroxides, and triazine derivatives, which may be used alone or in combination of two or more.

[0106] The content of the (b) crosslinking agent in the medical rubber composition is preferably 0.2 parts by mass or more, more preferably 0.4 parts by mass or more, and even more preferably 0.6 parts by mass or more, and is preferably 20 parts by mass or less, more preferably 15 parts by mass or less, and even more preferably 10 parts by mass or less, relative to 100 parts by mass of the (a) rubber component. This is because, if the content of the (b) crosslinking agent is within the above range, a rubber having good rubber properties (hardness, tensile strength, Cset) and good processability (less fading) can be obtained.

[0107] 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 dissolve into the drug solution in the vial. Examples of the vulcanization accelerator include guanidine-based accelerators (e.g., diphenyl guanidine), thiuram-based accelerators (e.g., tetramethyl thiuram disulfide, tetramethyl thiuram 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).

[0108] The medical rubber composition may contain (c) hydrotalcite. (c) Hydrotalcite functions as a scorch inhibitor during crosslinking of halogenated butyl rubber and also functions to prevent the compression set of medical rubber products 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.

[0109] Hydrotalcite is, 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 Examples of the hydrotalcite include Mg-Al hydrotalcite such as CO3·1.7H2O.

[0110] The medical rubber composition may further contain a filler (d). Examples of the filler (d) include inorganic fillers such as clay and talc, olefin resins, styrene elastomers, and ultra-high molecular weight polyethylene (UHMWPE) resin powders. Among these, inorganic fillers are preferred, and clay or talc are more preferred. The filler functions to adjust the rubber hardness of the medical rubber product, and also functions as an extender to reduce the production cost of the medical rubber product.

[0111] The content of the (d) filler in the medical rubber composition is preferably set appropriately depending on the rubber hardness of the intended medical rubber product, etc. The content of the (d) filler in the medical rubber composition is, for example, preferably 5 parts by mass or more, more preferably 10 parts by mass or more, and even more preferably 20 parts by mass or more, and preferably 200 parts by mass or less, more preferably 150 parts by mass or less, and even more preferably 100 parts by mass or less, per 100 parts by mass of the (a) rubber component.

[0112] The medical rubber composition may further contain colorants such as titanium oxide and carbon black, stearic acid, a low-density polyethylene (LDPE) lubricant, a processing aid, polyethylene glycol as a crosslinking activator, a plasticizer (e.g., paraffin oil), etc. in appropriate proportions.

[0113] [Sterilization method] The package in which the medical rubber product of the present invention is sealed is preferably sterilized by irradiation with radiation, more preferably by irradiation with gamma rays or electron beams. The sterilization method preferably involves irradiating the package in which the medical rubber product is packaged with a plurality of medical rubber products.

[0114] Examples of radiation used in sterilization include α-rays (helium nuclei), β-rays (electron beams) and γ-rays (gamma rays). β-rays (electron beams) have an extremely high dose rate (tens of thousands of times that of γ-rays), so the sterilization time is short, but since they are particle beams, they have low penetrating power. On the other hand, gamma rays have high penetrating power, but their dose rate is smaller than that of electron beams, so the treatment time is long. In the present invention, from the viewpoint of sterilizing a package of medical rubber products that contains multiple medical rubber products, it is preferable to use gamma rays for sterilization.

[0115] Examples of gamma rays include gamma rays emitted from cobalt 60 and cesium 137, with gamma rays emitted from cobalt 60 being preferred.

[0116] In gamma irradiation, the gamma ray absorbed dose of medical rubber products is established in the actual sterilization validation procedure. In many cases, 15 kGy is used as the minimum absorbed dose for ordinary medical devices. The gamma ray exposure dose required to ensure that the gamma ray absorbed dose of all medical rubber products in the package is 15 kGy or more varies depending on the number of medical rubber products in the package and how they are placed, but generally, the dose is 1.4 to 2.0 times 15 kGy. Similarly, if the minimum absorbed dose is 20 kGy, the dose is 1.4 to 2.0 times 20 kGy, and if the minimum absorbed dose is 25 kGy, the dose is 1.4 to 2.0 times 25 kGy. The gamma ray absorbed dose can be confirmed by attaching a dosimeter to the irradiated object.

[0117] The method for sterilizing medical rubber products of the present invention preferably comprises irradiating a package containing an oxygen detector in a second space of the package, the oxygen concentration of which is lower than a predetermined value as detected by the oxygen detector, with gamma rays. The package containing the medical rubber products before gamma ray irradiation preferably has oxygen in it below a predetermined concentration. The oxygen concentration in the package is preferably 5% by volume or less, more preferably 3% by volume or less, and even more preferably 1% by volume or less. This is because by keeping the oxygen concentration in the package at 5% by volume or less, deterioration of the medical rubber products due to gamma ray irradiation can be suppressed.

[0118] Methods for reducing the oxygen concentration in the package to 5% by volume or less include replacing the air in the package with an inert gas and placing an oxygen scavenger in the package.

[0119] The inert gas may be a rare gas such as helium, neon, or argon, or nitrogen gas.

[0120] The packaging body (primary packaging body, secondary packaging body) that contains the medical rubber product of the present invention may be further contained in a packaging body and irradiated with gamma rays. Examples of the packaging body include a bag, a box, and the like. Examples of the packaging bag include a packaging bag formed from a thermoplastic resin film such as polyethylene, polyamide, or polyester, or aluminum. It is preferable that the packaging bag be sealable. Examples of the packaging box include, but are not limited to, a paper box, a cardboard box, and the like.

[0121] The packaging material may be a gas-permeable packaging material or a gas-non-permeable (gas-tight) packaging material, and it is also preferable to use a combination of these.

[0122] In addition, when irradiating with gamma rays, it is preferable to irradiate the package containing the multiple medical rubber products with gamma rays while it is stored in a storage container made of, for example, an aluminum alloy.

[0123] The sterilized medical rubber product of the present invention preferably has a viable cell count (cfu: colony forming unit: number of colonies that appear when cultured) of 0 in a bioburden measurement test.

[0124] The present invention will be further described below with reference to the drawings, but the present invention is not limited to the embodiments shown in the drawings. Fig. 1 is a plan view illustrating one embodiment of the package of the present invention. The package 1 has a vertical direction A and a width direction B perpendicular to the vertical direction.

[0125] The package 1 is generally rectangular in plan view. The package 1 is a four-sided sealed type, and is made by laminating two sheets of oxygen-impermeable packaging material, the edges of which are heat sealed. The package 1 has an upper edge seal portion 13, a side edge seal portion 15, and a lower edge seal portion 17.

[0126] The packaging body 1 has a first space 5 in which the medical rubber product 3 is housed, and a second space 9 in which an oxygen detector 8 whose color changes depending on the oxygen concentration is housed. The first space 5 and the second space 9 are separated by an oxygen-permeable partition 11.

[0127] The second space 9 is defined by an upper edge seal portion 13a, a side edge seal portion 15a, and a partition 11, and forms a space for accommodating an oxygen detector 8 whose color tone changes depending on the oxygen concentration.

[0128] The first space 5 is defined by the upper edge seal portion 13b, the side edge seal portions 15, 15b, the lower edge seal portion 17 and the partition 11, and forms a space for housing a medical rubber product.

[0129] The partition 11 between the first space 5 and the second space 9 is provided in a curved shape so as to extend from the upper edge seal portion 13 to one side edge seal portion 15 .

[0130] An upper edge seal portion 13b of the first space and an upper edge seal portion 13a of the second space 9 are adjacent in the width direction to form an upper edge seal portion 13 of the package 1. A side edge seal portion 15a of the second space and a side edge seal portion 15b of the first space are adjacent in the vertical direction to form one side edge seal portion 15 of the package.

[0131] A plurality of 10.0 mm-wide ventilation holes 12 are provided in the partition 11 between the first space 5 and the second space 9 by discontinuously heat-sealing an oxygen-impermeable packaging material. The first space 5 and the second space 9 communicate with each other through the ventilation holes 12.

[0132] In an embodiment in which the oxygen detector 8 is contained in the second space 9, the first space 5 and the second space 9 are in communication with each other, so that the oxygen detector 8 detects the oxygen concentration in the first space 5. The oxygen detector changes color depending on the oxygen concentration, so that the oxygen concentration in the first space 5 of the package 1 can be visually recognized.

[0133] In an embodiment in which the second space 9 contains an oxygen absorber 7 in addition to the oxygen detector 8, the first space 5 and the second space 9 are connected, so that the oxygen concentration in the first space 5 and the second space 9 can be reduced by the oxygen absorber 7.

[0134] The internal space of the package 1 is filled with nitrogen.

[0135] The three-side sealed package has the same structure as the package in FIG. 1 except that it does not have the bottom edge seal portion 17, and therefore a description thereof will be omitted.

[0136] 2 is a plan view illustrating another embodiment of the package of the present invention. The package 1 has a first space 5 for accommodating a medical rubber product 3, a second space 9 for accommodating an oxygen detector 8 whose color changes depending on the oxygen concentration, and a third space 19 for accommodating an oxygen scavenger 7.

[0137] The first space 5 and the second space 9 are separated by an oxygen-permeable partition 11 .

[0138] The second space 9 is defined by an upper edge seal portion 13a, a side edge seal portion 15a, and a partition 11, and forms a space for accommodating an oxygen detector 8 whose color tone changes depending on the oxygen concentration.

[0139] The partition 11 between the first space 5 and the second space 9 is provided in a curved shape so as to extend from the upper edge seal portion 13 to one side edge seal portion 15 .

[0140] A plurality of 10 mm-wide ventilation holes 12 are provided in the partition 11 between the first space 5 and the second space 9 by discontinuously heat-sealing an oxygen-impermeable packaging material. The first space 5 and the second space 9 communicate with each other through the ventilation holes 12.

[0141] An oxygen detector 8 is contained in the second space 9. Because the first space 5 and the second space 9 are in communication with each other, the oxygen detector 8 detects the oxygen concentration in the first space 5. Because the color tone of the oxygen detector 8 changes depending on the oxygen concentration, the oxygen concentration in the first space 5 of the package 1 can be visually recognized.

[0142] The first space 5 and the third space 19 are partitioned by a partition 21. The partition 21 between the first space 5 and the third space 19 is different from the partition 11 between the first space 5 and the second space 9 in that it does not have any ventilation holes and is provided so as to be oxygen impermeable. The partition 21 is preferably formed by continuously heat-sealing an oxygen-impermeable packaging material.

[0143] The third space 19 is defined by the upper edge seal portion 13c, the side edge seal portion 15c, and a partition 21, and forms a space for accommodating an oxygen absorber and / or an oxygen detector whose color changes depending on the oxygen concentration.

[0144] The first space 5 is defined by the upper edge seal portion 13b, the side edge seal portions 15b, 15b, the lower edge seal portion 17, and the partitions 11, 21, and forms a space for housing a medical rubber product.

[0145] A partition 21 between the first space 5 and the third space 19 is provided in a curved shape so as to extend from the upper edge seal portion 13 to one of the side edge seal portions 15 .

[0146] The upper edge seal portion 13b of the first space 5 is located between the upper edge seal portion 13a of the second space 9 and the upper edge seal portion 13c of the third space 19. The upper edge seal portion 13b of the first space 5, the upper edge seal portion 13a of the second space 9, and the upper edge seal portion 13c of the third space 19 are adjacent to each other in the width direction to form the upper edge seal portion 13 of the package 1. The side edge seal portion 15a of the second space 9 and the side edge seal portion 15b of the first space 5 are adjacent to each other in the vertical direction to form one side edge seal portion 15. The side edge seal portion 15c of the third space 19 and the side edge seal portion 15b of the first space 5 are adjacent to each other in the vertical direction to form the other side edge seal portion 15.

[0147] An air vent 23 is provided in the side edge seal portion 15c of the third space portion 19. The air vent 23 is preferably provided in a size that prevents the oxygen scavenger and / or the oxygen detector that changes color depending on the oxygen concentration from spilling out.

[0148] FIG. 3 is an explanatory diagram illustrating an embodiment in which a plurality of packages 1 in the embodiment of FIG. 2 are housed as primary packages in a secondary package 2. In FIG.

[0149] The secondary package 2 of the present invention is substantially rectangular in plan view. The secondary package 2 is a four-sided sealed type, and is made by laminating two sheets of oxygen-impermeable packaging material, the edges of which are heat sealed. The secondary package 2 has an upper edge seal portion 23, a side edge seal portion 25, and a lower edge seal portion 27. The peripheral seal portion of the secondary package 2 is provided in a straight line along the periphery of the secondary package.

[0150] An oxygen absorber 7 is contained in the third space 19 of the primary package 1. By providing an air hole 23 in the side edge seal portion 15c of the third space 19 of the primary package 1, when the primary package 1 is contained in the secondary package 2, the oxygen concentration in the internal space of the secondary package 2, which is outside the primary package 1, can be reduced.

[0151] 3 shows an embodiment in which the oxygen detector 8 is contained in the second space 9 of the primary package 1 and the oxygen absorber 7 is contained in the third space 19, but the oxygen detector 8 may be contained in the third space 19. In this embodiment, the oxygen detector 8 contained in the third space 19 of the primary package 1 can detect the oxygen concentration in the internal space of the secondary package 2. EXAMPLES

[0152] 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.

[0153] [Production of packaging for medical rubber products] Example 1 The packaging material was an Asahi Kasei film measuring 20 cm long and 17 cm wide (product name: Suntech LD, oxygen permeability: 7900 ml / (m 2 A bag was made by folding the bag and heat sealing the side edges to create an open-topped bag. At the same time as heat sealing the side edges, a partition between the first and second spaces, and a partition between the first and third spaces were also formed by heat sealing. A 10 mm-wide ventilation hole was formed in the partition between the first and second spaces by discontinuous heat sealing. The partition between the first and third spaces was heat sealed continuously to create an oxygen-impermeable partition without a ventilation hole.

[0154] The first space contained a rubber stopper for a vial as a medical rubber product, the second space contained Ageless Eye manufactured by Mitsubishi Gas Chemical Co., Ltd. as an oxygen detector, and the third space contained Ageless manufactured by Mitsubishi Gas Chemical Co., Ltd. as an oxygen scavenger. As the rubber stopper for the vial, a rubber stopper for a vial for a freeze-dried injection with a flange diameter of 19.0 mm, total height of 13.0 mm, leg diameter of 7.20 mm, and thickness of the flange puncture part of 2.5 mm was used.

[0155] The bag containing the medical rubber product, oxygen detector, and oxygen absorber was set in the heat sealer. The oxygen in the bag was sucked out and filled with nitrogen, and the top edge of the bag was heat sealed to seal the bag, creating a primary package. The bag was filled with nitrogen by inserting a degassing pipe and a nitrogen filling pipe into the bag, and the cycle of degassing and then filling with nitrogen was repeated three times.

[0156] The side edge seal of the third space of the primary package was cut to create an air hole that communicated the third space with the outside.

[0157] The secondary packaging material was a laminated film made by Kurilon Kasei Co., Ltd., measuring 50 cm long and 40 cm wide (product name: NJK, oxygen permeability: 49 ml / (m 2A 24-hour storage tank (2400 m2) was used. This packaging material was folded and overlapped so that the sealant layers faced each other, and the side edges were heat sealed to create a bag with an open top edge. One primary package was placed in the bag with the open top edge and set in a heat sealer. The top edge of the bag was heat sealed. Note that the primary package was placed in the bag without replacing the air inside with nitrogen, so air was present outside the primary package in the secondary package immediately after placement.

[0158] The resulting secondary packaging was sterilized by irradiating it with gamma rays so that the absorbed dose of gamma rays for the medical rubber product was 25 kGy.

[0159] (Evaluation Results of Example 1) The primary package of Example 1 has a second space and a third space, an oxygen detector is contained in the second space, and an oxygen absorber is contained in the third space. Oxygen in the air inside the secondary package is absorbed by the oxygen absorber in the third space. It was confirmed that the color of the oxygen detector in the second space of the primary package before the gamma ray sterilization process was pink, and the oxygen concentration inside the primary package was 0.1% by volume or less.

[0160] After gamma ray sterilization, the medical rubber products were removed from the primary packaging and subjected to an extractables test, with the results being good. Example 2 In the above-mentioned Example 1, instead of filling the secondary packaging with air, a degassing pipe and a nitrogen filling pipe were inserted into the bag for the secondary packaging, and the cycle of degassing and then filling with nitrogen was repeated three times. After that, the obtained secondary packaging was irradiated with gamma rays to sterilize the medical rubber product so that the gamma ray absorption dose of the medical rubber product was 25 kGy. In Example 2, too, it was confirmed that the color tone of the oxygen detector in the second space of the primary packaging before the gamma ray sterilization treatment was pink, and the oxygen concentration in the primary packaging was 0.1% by volume or less. After the gamma ray sterilization treatment, the medical rubber product was taken out of the primary packaging, and the result of the elution test was good.

[0161] Example 3 The packaging material was an Asahi Kasei film measuring 20 cm long and 17 cm wide (product name: Suntech LD, oxygen permeability: 7900 ml / (m 2 A bag was made with a 10 mm wide vent hole by folding the bag and heat sealing the side edges. At the same time as heat sealing the side edges, a partition between the first and second spaces was also formed by heat sealing. A 10 mm wide vent hole was formed in the partition between the first and second spaces by discontinuously heat sealing the partition.

[0162] The first space contained a rubber stopper for a vial as a medical rubber product, and the second space contained Ageless Eye, manufactured by Mitsubishi Gas Chemical Co., Ltd., as an oxygen detector. As the rubber stopper for the vial, a rubber stopper for a vial for a freeze-dried injection with a flange diameter of 19.0 mm, total height of 13.0 mm, leg diameter of 7.20 mm, and thickness of the flange puncture part of 2.5 mm was used.

[0163] The bag containing the medical rubber product and oxygen detector was set in the heat sealer. The oxygen in the bag was sucked out and filled with nitrogen, and the top edge of the bag was heat sealed to seal the bag, creating a primary package. The bag was filled with nitrogen by inserting a degassing pipe and a nitrogen filling pipe into the bag, and the cycle of degassing and then filling with nitrogen was repeated three times.

[0164] The secondary packaging material was a laminated film made by Kurilon Kasei Co., Ltd., measuring 50 cm long and 40 cm wide (product name: NJK, oxygen permeability: 49 ml / (m 2 A 100-milliliter (24h·atm) pressure was used. This packaging material was folded and overlapped so that the sealant layers faced each other, and the side edges were heat sealed to create a bag with an open top edge. One primary package was placed in the bag with an open top edge and set in a heat sealer. The oxygen inside the bag was sucked out and nitrogen was filled in, and the top edge of the bag was heat sealed to seal it. The bag was filled with nitrogen by inserting a degassing pipe and a nitrogen filling pipe into the bag, and the cycle of degassing and then filling with nitrogen was repeated three times.

[0165] The resulting secondary packaging was sterilized by irradiating it with gamma rays so that the absorbed dose of gamma rays for the medical rubber product was 25 kGy.

[0166] (Evaluation Results of Example 3) The primary package of Example 3 has a second space, and an oxygen detector is contained in the second space. The color tone of the oxygen detector in the second space before gamma ray sterilization is pink, and it was confirmed that the oxygen concentration in the primary package is 0.1% by volume or less.

[0167] After gamma ray treatment, the medical rubber products were removed from the primary packaging and subjected to an elution test, with the results being good. [Industrial Applicability]

[0168] According to the present invention, the oxygen concentration in the package can be visually confirmed, making it easier to ensure quality through sterilization treatment.

[0169] A preferred embodiment (1) of the present invention is a package in which a medical rubber product is sealed, the package being made of an oxygen-impermeable packaging material, A first space portion in which a medical rubber product is accommodated; The package has a second space portion containing an oxygen detector whose color changes depending on the oxygen concentration, and the first space portion and the second space portion are separated by an oxygen-permeable partition.

[0170] A preferred embodiment (2) of the present invention is the packaging body of embodiment (1), wherein the partition has an air hole through which the medical rubber product and the oxygen detector cannot pass, and the first space and the second space are configured to be oxygen permeable by the air hole.

[0171] A preferred embodiment (3) of the present invention is the package of embodiment (1) or (2), in which the partition between the first space and the second space is formed so as to have an air hole by discontinuously heat-sealing the packaging material.

[0172] A preferred embodiment (4) of the present invention is the package according to any one of embodiments (1) to (3), in which the upper edge seal portion of the first space and the upper edge seal portion of the second space are adjacent to each other.

[0173] A preferred embodiment (5) of the present invention is the package according to embodiment (4), wherein the upper edge seal portion of the first space and the upper edge seal portion of the second space are each sealed by heat welding.

[0174] A preferred embodiment (6) of the present invention is the package according to any one of embodiments (1) to (5), wherein the internal space of the package is filled with nitrogen.

[0175] A preferred embodiment (7) of the present invention is the package according to any one of the embodiments (1) to (6), in which an oxygen scavenger is accommodated in the second space together with the oxygen detector.

[0176] A preferred embodiment (8) of the present invention is a secondary package containing a primary package in which a medical rubber product is sealed, The primary packaging body is made of an oxygen-impermeable packaging material, A first space portion in which a medical rubber product is accommodated; A second space portion containing an oxygen detector that changes color depending on the oxygen concentration; and a third space portion in which an oxygen scavenger and / or an oxygen detector that changes color depending on the oxygen concentration is accommodated, The first space and the second space are separated by an oxygen-permeable partition, The first space and the third space are separated by an oxygen-impermeable partition, The primary packaging body The packaging body is characterized in that an air hole is formed that connects the third space portion with the internal space of the secondary packaging body.

[0177] A preferred embodiment (9) of the present invention is the packaging body of embodiment (8) in which the partition between the first space and the second space has an air hole through which the medical rubber product and the oxygen detector cannot pass, and the first space and the second space are configured to be oxygen permeable by the air hole.

[0178] A preferred embodiment (10) of the present invention is the package of embodiment (8) or (9), in which the partition between the first space and the second space is formed so as to have an air hole by discontinuously heat-sealing the packaging material.

[0179] A preferred embodiment (11) of the present invention is a package according to any one of embodiments (8) to (9), in which the upper edge seal portion of the first space portion is adjacent to the upper edge seal portion of the second space portion and the upper edge seal portion of the third space portion.

[0180] A preferred embodiment (12) of the present invention is the package according to any one of embodiments (8) to (11), wherein the upper edge seal portions of the first space, the second space and the third space are sealed by heat welding.

[0181] A preferred embodiment (13) of the present invention is The primary packaging body The internal space and Said secondary packaging The package according to any one of aspects (8) to (12), wherein the internal space of the package is filled with nitrogen.

[0182] A preferred embodiment (14) of the present invention is a method for sterilizing medical rubber products, which comprises irradiating a package according to any one of embodiments (1) to (7) with gamma rays.

[0183] A preferred embodiment (15) of the present invention is a method for sterilizing medical rubber products according to embodiment (14), in which an oxygen detector is contained in the second space, and the oxygen concentration detected by the oxygen detector is lower than a predetermined value, and gamma rays are irradiated to the package.

[0184] A preferred embodiment (16) of the present invention is a method for sterilizing medical rubber products, which comprises irradiating a package according to any one of embodiments (8) to (13) with gamma rays.

[0185] A preferred embodiment (17) of the present invention is a method for sterilizing medical rubber products according to embodiment (16), in which an oxygen detector is contained in the second space, and the oxygen concentration detected by the oxygen detector is lower than a predetermined value, and gamma rays are irradiated to the package. [Explanation of symbols]

[0186] 1: packaging body (primary packaging body), 2: secondary packaging body, 3: medical rubber product, 5: first space, 7: oxygen absorber, 8: oxygen detector, 9: second space, 11: partition, 13: upper edge seal, 15: side edge seal, 17: lower edge seal, 19: third space, 21: partition

Claims

1. A package in which a medical rubber product is sealed, the package being made of an oxygen-impermeable packaging material, a first space portion in which a medical rubber product is accommodated; and a second space portion containing an oxygen detector whose color tone changes according to the oxygen concentration, the first space portion and the second space portion being partitioned by an oxygen-permeable partition, The medical rubber products are rubber stoppers and sealing members for various drug containers, rubber stoppers for vacuum blood collection tubes, plunger stoppers for prefilled syringes, or nozzle caps, A package formed from a medical rubber composition containing a halogenated butyl rubber and not containing an antioxidant.

2. The packaging body described in claim 1, wherein the partition has an air vent through which the medical rubber product and the oxygen detector cannot pass, and the air vent allows oxygen to pass between the first space and the second space.

3. 3. The package according to claim 2, wherein the partition between the first space and the second space is formed by discontinuously heat-sealing the packaging material to have an air hole.

4. 2. The package according to claim 1, wherein an upper edge seal portion of the first space and an upper edge seal portion of the second space are adjacent to each other.

5. 5. The package according to claim 4, wherein the upper edge seal portion of the first space and the upper edge seal portion of the second space are each sealed by heat welding.

6. 2. The package according to claim 1, wherein the interior space of the package is filled with nitrogen.

7. 2. The package according to claim 1, wherein an oxygen absorber is accommodated in the second space together with the oxygen detector.

8. A secondary package containing a primary package in which a medical rubber product is sealed, The primary packaging body is made of an oxygen-impermeable packaging material, a first space portion in which a medical rubber product is accommodated; a second space portion containing an oxygen detector that changes color depending on the oxygen concentration; a third space portion in which an oxygen scavenger and / or an oxygen detector whose color tone changes depending on the oxygen concentration is accommodated; The first space and the second space are separated by an oxygen-permeable partition, The first space and the third space are separated by an oxygen-impermeable partition, A packaging body, characterized in that an air hole is formed in the primary packaging body, connecting the third space portion with the internal space of the secondary packaging body.

9. The packaging body described in claim 8, wherein the partition between the first space and the second space has an air hole through which the medical rubber product and the oxygen detector cannot pass, and the air hole allows oxygen to pass between the first space and the second space.

10. 10. The package according to claim 9, wherein the partition between the first space and the second space is formed by discontinuously heat-sealing the packaging material to have an air hole.

11. 9. The package of claim 8, wherein the top edge seal of the first space is adjacent to the top edge seal of the second space and the top edge seal of the third space.

12. 12. The package according to claim 11, wherein the upper edge seal portions of the first space, the second space and the third space are sealed by heat welding.

13. 9. The package according to claim 8, wherein the internal space of the primary package and the internal space of the secondary package are filled with nitrogen.

14. A method for sterilizing medical rubber products, comprising irradiating the package according to claim 1 with gamma rays.

15. A method for sterilizing medical rubber products as described in claim 14, wherein gamma rays are irradiated to a packaging body containing an oxygen detector in the second space portion, the oxygen concentration detected by the oxygen detector being lower than a predetermined value.

16. A method for sterilizing medical rubber products, comprising irradiating the package according to claim 8 with gamma rays.

17. A method for sterilizing medical rubber products as described in claim 16, wherein gamma rays are irradiated to a packaging body containing an oxygen detector in the second space portion, the oxygen concentration detected by the oxygen detector being lower than a predetermined value.

18. The package described in claim 1, wherein the medical rubber product contains (a) a rubber component and (b) a triazine derivative as a cross-linking agent, and (a) the rubber component is a cured product of a rubber composition consisting only of halogenated butyl rubber.

19. The packaging body of claim 18, wherein the rubber composition further contains polyethylene.

20. A method for sterilizing a medical rubber product as described in claim 15, wherein the medical rubber product contains (a) a rubber component and (b) a triazine derivative as a crosslinking agent, and (a) the rubber component is a cured product of a rubber composition consisting only of halogenated butyl rubber.

21. A method for sterilizing a medical rubber product as described in claim 20, wherein the rubber composition further contains polyethylene.

22. A method for sterilizing medical rubber products as described in claim 15, wherein the packaging body is contained in a secondary packaging body formed from an oxygen-impermeable packaging material, and the internal space of the secondary packaging body is filled with nitrogen.

23. A method for sterilizing medical rubber products as described in claim 20, wherein the packaging body is contained in a secondary packaging body formed from an oxygen-impermeable packaging material, and the internal space of the secondary packaging body is filled with nitrogen.

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