JP2015189497A - Vial with plastic cap - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vial with a plastic cap which enables sufficient sterilization of a rubber stopper where a cap is fitted with a small cumulative quantity of an electron beam that does not cause the degradation of a pharmaceutical in a bottle, can keep a sterilized state of the rubber stopper after the sterilization, and can keep tight contact between the rubber stopper and a bottle mouth inner wall surface in the use.SOLUTION: A vial 1 with a plastic cap includes: a rubber stopper 20 having a protruding part 20b that protrudes from a surface of a flange 20a having a diameter that is larger than an inner diameter of a bottle mouth 10a and is inserted in the bottle mouth 10a; and a plastic cap 50 fitted to a side surface and the other surface of the flange 20a in a tightly contacting manner. In a covering part of the cap 50 for covering the other surface of the flange 20a, a part corresponding to a puncture allowing surface 21 which allows an injection needle to puncture and has a diameter smaller than the inner diameter of the bottle mouth 10a on the other surface of the flange 20a is formed as a removable part 40b, and the rubber stopper 20 fitted to the bottle mouth 10a is sterilized by electron beams in a state where the rubber stopper is covered with the cap 50.

Description

  The present invention relates to a vial with a plastic cap in which a plastic cap is attached to a rubber stopper attached to a mouth of a bottle filled with a medicine and sterilized with an electron beam.

  A vial is one in which a cap is attached to a rubber stopper attached to a bottle opening of a bottle filled with a medicine. The bottle mouth has an inner diameter smaller than that of the body which is the main body of the bottle. Further, the rubber stopper is provided with a flange-like ridge having a diameter larger than the inner diameter of the bottle mouth of the bottle and a protruding portion protruding from one surface of the flange-like ridge. In the rubber stopper, the injection needle is pierced into the inside of the bottle from the other surface of the flange-like ridge protruding from the bottle mouth with the protruding portion inserted into the bottle mouth. In this way, the side surface and the other surface of the flange-like ridge protruding from the bottle mouth are exposed surfaces. Conventionally, these exposed surfaces are covered with an aluminum cap attached to a flange-like flange of a rubber plug.

  When a vial with an aluminum cap attached to a flange-shaped bottle of rubber stopper is subjected to electron beam sterilization, the irradiated electron beam is attenuated due to the influence of the aluminum cap. The side surface and the other surface of the flange-shaped flange of the rubber stopper thus formed are likely to be insufficiently sterilized even with an accumulated amount of electron beams that are sufficiently sterilized in the bottle body.

  On the other hand, if the cumulative amount is increased by extending the electron beam irradiation time in order to sufficiently sterilize the side surface and the other surface of the flange-like ridge, the medicine in the bottle may be degraded due to decomposition or the like.

  In addition, the attachment of the rubber plug, the attachment of the cap to the rubber plug, etc. is performed in a clean room of Class A high cleanliness. However, when the aluminum cap is attached to the rubber plug, the rubber plug It is necessary to wind up the cap attached to. At that time, aluminum dust may be generated to reduce the cleanliness in the clean room.

  In addition, the aluminum cap has a circular fragile part that is partly cut so that it can be easily removed on the part corresponding to the pierceable surface through which the needle of the rubber stopper is pierced. Is formed. Therefore, even if the sterilization is sufficiently performed on the side surface and the other surface portion of the flange-like ridge, air containing fine particles such as dust and bacteria flows from the cuts forming the weakened portion of the cap, and the rubber plug May contaminate the pierceable surface. Therefore, even if a vial with an aluminum cap attached to a flanged collar of a rubber stopper is sterilized by electron beam, the sterility cannot be guaranteed. It is necessary to disinfect the passable surface with alcohol cotton for disinfection.

  Instead of a vial in which an aluminum cap is attached to the flange-like flange of the rubber stopper, a vial in which a plastic cap is attached to the rubber stopper is used. For example, the following Patent Documents 1 and 2 describe a plastic cap in which a cap outer frame is attached to an inner frame of a cap in which a slit that covers a flange-like flange of a rubber stopper attached to a bottle mouth is formed. Further, in Patent Document 3 below, a rubber stopper having a top surface and a leg portion formed with a flange and having a recess provided on the axis of the top surface, and a caulking member for fixing the rubber stopper to the mouth portion of the vial And a puncture needle that pierces the top surface, the skirt portion, and a rubber stopper provided through the top surface on the top surface axis, and from above the rubber stopper and the caulking member attached to the mouth of the vial. There is described a plastic drip vial cap comprising a cap-shaped liquid extraction nozzle that is slidably crowned and a cap that is removably crowned at a liquid outlet of the liquid extraction nozzle. Further, Patent Document 4 includes a cylindrical body in which a weakening line is formed in a part of a side wall in an axial direction, and a lid for closing an upper opening of the cylindrical body, and the cylindrical body is broken along the weakening line. In the vial cap that is a synthetic resin-made integral molded product, the cylindrical body has an engaging portion that engages with the flange portion of the vial mouth portion in the vicinity of the lower portion of the inner peripheral portion. In either one of the cylindrical body and the lid, a plastic vial cap having a rubber stopper pressing portion that presses a rubber stopper tightly fitted in the vial mouth portion is described.

JP-A-7-187216 JP-A-8-34466 JP-A-8-192865 JP 2007-8517 A

  The plastic caps described in Patent Documents 1 and 2 have a complicated structure, and external air may flow from a slit formed in the cap inner frame, which may contaminate a sterilized rubber stopper. Further, the plastic drip vial cap described in Patent Document 3 requires the use of a rubber stopper provided with a depression on the top surface axis, and the protrusion on one surface of the flange-shaped bottle is a bottle bottle. A rubber plug inserted into the mouth cannot be used. Further, when the vial equipped with the plastic vial cap of Patent Document 4 is used, since the entire cap is removed from the rubber stopper, the pressing force for pressing the rubber stopper into the bottle mouth is released. There is a possibility that the adhesiveness with the inner wall surface of the mouth is lowered.

  The present invention has been made in order to solve the above-mentioned problems, and even if the cumulative amount of a small amount of electron beams does not cause decomposition of the medicine in the bottle, the rubber stopper with the cap attached thereto is sufficiently provided. To provide a vial with a plastic cap that can be sterilized and can be preserved by maintaining the sterilized state of the rubber stopper even after sterilization, and can maintain the adhesion between the rubber stopper and the inner wall surface of the bottle mouth during use. Objective.

  The vial with a plastic cap of the present invention made to achieve the above object has a bottle opening at one end, a bottle filled with a medicine, a rubber stopper inserted into the bottle opening, and a cover for the rubber. It consists of a plastic cap and is sterilized by electron beam.

  The vial with a plastic cap includes the bottle; a flange-like ridge having one surface, another surface, and a side surface, and having a diameter larger than the inner diameter of the bottle mouth, and a protruding portion protruding from the one surface of the flange-shaped ridge The rubber stopper in which the projection is inserted into the bottle mouth and the injection needle is inserted into the inside of the bottle from the other surface of the flange-shaped bottle; A plastic cap provided on the flange-like flange of the stopper so as to cover the side surface and the other surface in close contact with an inner wall surface and provided with a covering portion for covering the other surface; In the covering portion, a portion corresponding to a pierceable surface having a diameter smaller than the inner diameter of the bottle mouth, through which the injection needle is pierced to the other surface of the rubber stopper, is formed as a removable portion. In addition, the cap is attached to the rubber stopper attached to the bottle mouth. There preferably those electron beam sterilization while being deposited.

  In the vial with a plastic cap, a belt-shaped step portion is provided around the inner peripheral edge of the bottle mouth on the outer peripheral surface of the bottle mouth, and the ring covers the side surface of the flange-like bottle. A plurality of locking arms each formed with a claw portion that is suspended from the lower end side of the side surface covering portion and is engaged with the lower end side of the stepped portion at the tip portion, and the side surface covering portion It is preferable that it is formed from an other surface covering portion that is joined to the upper end surface and covers the other surface of the flange-like ridge.

  In the vial with a plastic cap, it is preferable that a fragile portion is formed on the other surface covering portion so as to surround the removable portion.

  The vial with plastic chap has the bottle, a flange surface having one surface, the other surface, and a side surface, and having a diameter larger than the inner diameter of the bottle mouth, and a protruding portion protruding from the one surface of the flange surface. The rubber stopper in which the injection needle is pierced from the other surface of the flange-like ridge into the inside of the bottle with the protrusion inserted into the bottle mouth, and the rubber in the attachment state A first film that covers the side surface of the flange-like ridge and the periphery of the other surface of the stopper, and a portion that covers the other surface of the flange-like ridge and covers the periphery of the other surface of the first film. It is preferable to include a plastic cap made of a second film removably joined and sterilized by electron beam in a state where the rubber stopper mounted on the bottle mouth is covered with the cap.

  In the vial with plastic chapp, the cumulative amount of electron beams received in the vial with plastic cap by the electron beam sterilization is preferably 15 to 40 kGy.

  In the vial with a plastic chap, it is preferable that the accumulated amount of the electron beam transmitted through the cap and received by the rubber stopper by the electron beam sterilization is 15 to 40 kGy.

  In the vial with a plastic chap, the drug is preferably a powder having a moisture content of 2.0% or less.

  It is preferable that the vial with the plastic chap is provided with the rubber stopper and the cap attached to the bottle mouth of the bottle filled with the medicine in the clean room.

  The vial with a plastic cap according to the present invention is an electron beam cap irradiated when an electron beam sterilization is carried out by attaching a plastic cap to a flanged bottle of a rubber stopper attached to a bottle mouth. The inner wall of the cap, the side surface of the rubber stopper, and the other surface are sufficiently sterilized, even if the amount of electron beam accumulated is small, and there is almost no attenuation and the medicine filled in the bottle does not decompose. it can. In addition, the inner wall surface of the cap covers the side surface and the other surface of the rubber stopper in close contact with each other. Even if the vial sterilized by electron beam is stored or transported in a non-sterile atmosphere, the side surface of the rubber stopper And the other side can prevent contamination by the inflow of outside air. When such a vial with a plastic cap of the present invention is used, by removing a part of the cap covering the other surface of the rubber stopper, the piercable surface on the other surface of the sterilized rubber stopper is exposed. The piercable surface is maintained in a sterilized state, and the injection needle can be pierced without being sterilized with alcohol cotton for disinfection. In addition, at that time, the rubber stopper is pressed into the bottle mouth by the remaining part of the cap from which the removable part has been removed, and the adhesion between the rubber stopper and the inner wall of the bottle mouth can be maintained.

It is a disassembled perspective view of the vial with a plastic cap to which this invention is applied. It is a fragmentary sectional perspective view of a rubber plug among the members shown in FIG. It is a partial cross-sectional perspective view of the other surface coating | coated part which comprises a cap among the members shown in FIG. It is a perspective view of a vial with a plastic cap to which the present invention is applied showing a state in which a ring-shaped side surface covering portion is attached to a rubber stopper attached to a bottle mouth of a bottle. It is a perspective view of a vial with a plastic cap to which the present invention is applied, showing a state where a cap is attached to a rubber stopper attached to a bottle mouth of the bottle. It is a perspective view which shows the manufacturing method of another vial with a plastic cap to which this invention is applied.

  Hereinafter, embodiments of the present invention will be described in detail, but the scope of the present invention is not limited to these embodiments.

  FIG. 1 is an exploded perspective view for explaining an example of the vial with a plastic cap of the present invention. A vial 1 with a plastic cap shown in FIG. 1 includes a glass bottle 10, a rubber stopper 20, and a plastic cap 50. The cap 50 includes a ring-shaped member 30 and a flat plate member 40. The bottle 10 is made of transparent glass, and a bottle mouth 10a having an inner diameter smaller than the inner diameter of the body portion 10c as a main body is opened at one end. On the outer peripheral surface of the bottle mouth 10a, a belt-like stepped portion 10b is provided along the inner peripheral edge of the bottle mouth 10a. The bottle 10 is filled with a powdery drug 12 dried by a drying means such as freeze drying.

  The water content of the drug 12 is preferably 2.0% or less. Thereby, deterioration by the decomposition | disassembly etc. which the powdery chemical | medical agent 12 originates in electron beam sterilization can be prevented. In addition, when the drug contains sugar or carbohydrate, a very small amount of water can be retained in order to prevent dust explosion when the powder is transported or filled. It is 5-2.0%, More preferably, it is 0.6-1.8%. It is possible to prevent the powdery medicine 12 from being degraded due to decomposition by electron beam sterilization or the like, and dust explosion during electron beam sterilization. When handling in an environment with a reduced oxygen concentration, for example, an inert gas environment such as nitrogen or argon, a moisture content of less than 0.5% is acceptable. A drug that is a powder having a moisture content of 0% to 2.0% can be used.

  Further, by using the glass bottle 10, a conventional vial assembly line can be used, and it is possible to avoid the drug 12 irradiated with the electron beam from adhering to the inner wall of the bottle 10.

  As shown in FIG. 1, the rubber stopper 20 attached to the bottle mouth 10a of the bottle 10 includes a flange-like ridge 20a and a protruding portion 20b protruding on one surface thereof. The outer diameter of the flange-like ridge 20a is substantially equal to the outer diameter including the step portion 10b of the bottle mouth 10a. Further, the protrusion 20b has an outer diameter that is substantially equal to the inner diameter of the bottle mouth 10a, and as shown in FIG. 2, a recess 20c that opens to the tip surface is formed. The recess 20c is formed in a mortar shape whose inner diameter gradually increases in the tip surface direction, and the thickness of the protruding portion 20b gradually decreases in the tip surface direction. When attaching such a rubber stopper 20 to the bottle mouth 10a, the tip of the protrusion 20b is easily deformed, and the protrusion 20b to the bottle mouth 10a can be easily inserted. A range indicated by a two-dot chain line on the other surface corresponding to the recess 20c of the rubber stopper 20 is a pierceable surface 21 through which the injection needle can be pierced. The mounting of the rubber stopper 20 to the bottle mouth 10a is completed when the peripheral edge of one surface of the flange-shaped flange 20a comes into contact with the end face of the bottle mouth 10a. By attaching the rubber stopper 20 to the bottle mouth 10a, the medicine 12 filled in the bottle 10 is sealed.

  Silicone rubber or butyl bromide rubber can be used as the rubber forming the rubber plug 20. However, silicone rubber is less deteriorated by electron beam irradiation than butyl bromide rubber, but it is inferior to butyl bromide in water vapor permeability and needle penetration test. It is preferable to use it as a stopper. On the other hand, butyl bromide rubber is superior in water vapor permeability and needle penetration test compared to silicone rubber, but since deterioration due to electron beam irradiation is larger than that of silicone rubber, even if the cumulative amount of electron beam is small. It is preferable to use it for a rubber stopper when it is good.

  A plastic cap 50 is attached to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a, and the inner surface of the cap 50 is covered with the other surface and side surface of the flange-shaped flange 20a. . The cap 50 is formed by the ring-shaped member 30 and the flat plate member 40. The ring-shaped member 30 includes a ring-shaped side surface covering portion 30a and a locking arm 30b for locking the side surface covering portion 30a to the stepped portion 10b of the bottle 10 (see FIG. 1). The locking arm 30b protrudes inward of the side surface covering portion 30a to the lower end side of the stepped portion 10b at the tip end portion of the plurality of arms 31a hanging from the lower end side of the side surface covering portion 30a and each arm 31a. It is comprised from the nail | claw part 31b inserted.

  Further, the flat plate member 40 has an outer surface whose outer diameter is substantially the same as the outer diameter of the ring-shaped side surface covering portion 30a, and which is a covering portion that covers the other surface of the flange-shaped flange 20a, It consists of a removable portion 40b surrounded by an annular fragile portion 40c formed at the center. A rod 40d is erected at the center of the removable portion 40b. As shown in FIG. 3, the weak part 40c is a thin part thinner than the other part of the other surface covering part 40a. The annular fragile portion 40c can be broken by applying a force to tilt the rod body 40d in one direction, and the removable portion 40b can be removed.

  The cap 50 is integrated by joining the peripheral edge portion of the other surface covering portion 40a of the flat plate member 40 to the end surface of the side surface covering portion 30a of the ring-shaped member 30 (see FIG. 5). The cap 50 is attached to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a, and the other surface and side surfaces of the flange-shaped flange 20a are covered. The flat plate member 40 of the cap 50 is a covering portion that covers the other surface of the flange-shaped flange 20a. FIG. 4 shows a state where the flat plate member 40 is removed. As shown in FIG. 4, the ring-shaped member 30 includes a ring-shaped side surface covering portion 30 a that covers the side surface of the flange-shaped flange 20 a of the rubber plug 20 and a plurality of arms 31 a that are suspended from the side surface covering portion 30 a. The claw portion 30c at the tip is inserted and locked to the lower end side of the step portion 10b of the bottle 10. The end surface of the side surface covering portion 30 a attached to the bottle mouth 10 a is flush with the other surface of the rubber stopper 20. The other surface covering portion 40a of the flat plate member 40 having the peripheral edge joined to the end surface of the side surface covering portion 30a is in close contact with the other surface of the rubber plug 20 and is airtightly covered. In addition, it is preferable that joining of the end surface of the side surface covering portion 30a and the peripheral edge portion of the other surface covering portion 40a is ultrasonic bonding.

  In order to attach the cap 50 to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a, first, as shown in FIG. 4, the ring-shaped side surface covering portion 30a is attached to the flange-shaped flange 20a of the rubber stopper 20. After adhering to the side surface, the claw portion 31b at each tip of the plurality of arms 31a suspended from the side surface covering portion 30a is inserted into the lower end side of the stepped portion 10b of the bottle 10 to lock the side surface covering portion 30a. Next, the cap 50 can be attached to the flange-shaped flange 20a by joining the end surface of the side surface covering portion 30a and the peripheral edge portion of the other surface covering portion 40a by ultrasonic bonding or the like. Moreover, you may adhere | attach the cap 50 which joined the end surface of the side surface coating part 30a and the peripheral part of the other surface coating part 40a in advance on the flange-shaped collar 20a.

  The plastic forming the cap 50 is preferably a plastic that is not easily deteriorated by the irradiated electron beam. Examples of such plastics include polystyrene, acrylonitrile butadiene styrene copolymer, polyethylene, polyamide, polyethylene terephthalate, silicone resin, polyurethane, polyimide, styrene acrylonitrile copolymer, epoxy resin, polysulfone, and phenol resin. Vinyl chloride and polypropylene tend to be deteriorated by the irradiated electron beam.

  Moreover, filling of the chemical | medical agent 12 to the bottle 10, attachment of the rubber stopper 20 to the bottle mouth 10a, and adhesion to the rubber stopper 20 of the ring-shaped member 30 and the flat plate member 40 are performed in a clean room, and thereby each member. It is preferable because particles such as dust adhering to the surface and bacteria can be reduced. In particular, in a clean room, it is preferable that the fine particles having a particle size of 0.5 μm or more have a class A atmosphere of 100 or less per cubic foot because the amount of fine particles adhering to each member can be further reduced.

  As shown in FIG. 5, a plastic cap 50 is attached to the rubber stopper 20 attached to the bottle mouth 10a, and the plastic cap vial 1 in which the side surface and the other surface of the flange-like collar of the rubber stopper 20 are covered is an electronic Wire sterilization is applied. In this electron beam sterilization, the accumulated amount of the electron beam received in the vial 1 with the plastic cap is 15 to 40 kGy, and in particular, the accumulated amount of the electron beam transmitted through the cap 50 and received in the rubber stopper 20 is 15 to 40 kGy. preferable. If the cumulative amount is less than 15 kGy, sterilization of the rubber plug 20 or the cap 50 tends to be insufficient, and if it exceeds 40 kGy, the rubber plug 20 tends to be deteriorated or the drug 12 tends to be decomposed. The cumulative amount of electron beam received in a plastic-attached vial or the like was calculated by measuring the absorbance of a cellulose triacetate film dosimeter affixed to a measurement location with a spectrophotometer and using a standard calibration curve.

  Thus, in the vial 1 with a plastic cap subjected to electron beam sterilization, the attenuation of the irradiated electron beam at the cap 50 can be reduced, and a small amount of electrons that do not cause decomposition of the drug 12 or deterioration of the rubber stopper 20 occur. Even with the accumulated amount of the wire, the side surface and the other surface of the flange-shaped flange 20a of the rubber plug 20 can be sufficiently sterilized. Furthermore, since the cap 50 is in close contact with the side surface and the other surface of the sterilized flange-shaped ridge 20a, and the inflow of outside air can be prevented, the sterilized vial 1 with a plastic cap is placed in a non-sterile atmosphere. Even if it is placed, the outside air containing fine particles, bacteria, etc. does not flow into the side surface and the other surface of the sterilized flanged ridge 20a, and the sterilized state can be maintained. For this reason, the vial 1 with a plastic cap in which the side surface and the other surface of the flange-shaped flange 20a of the rubber stopper 20 are sterilized can be stored and transported in a non-sterile atmosphere.

  Further, when the vial 1 with a plastic cap shown in FIG. 5 is used, by applying a force to tilt the rod body 40d erected on the other surface covering portion 40a of the flat plate member 40 constituting the cap 50 to one side. The fragile portion 40c is destroyed and the removable portion 40b is removed. The pierceable surface 21 on the other surface of the flange-like ridge 20a exposed by removing the removable portion 40b is maintained in a sterilized state, and the injection needle is inserted without being disinfected with alcohol cotton for disinfection. I can pass. Further, the cap 50 from which the removable portion 40b has been removed still presses the rubber stopper 20 into the bottle opening 10a with the remaining portion of the other surface covering section 40a, so that the rubber stopper 20 and the bottle opening 10a can be kept in close contact. .

  The vial 1 with a plastic cap shown in FIGS. 1 to 5 is formed of a ring-shaped member 30 and a flat plate member 40 formed into a predetermined shape as a cap 50. However, as shown in FIG. It may be formed. The cap 50 shown in FIG. 6 includes a side surface of the flange-shaped bottle 20a of the rubber stopper 20 attached to the bottle opening 10a of the bottle 10 filled with the drug 12, a step portion 10b of the bottle 10, and the other surface of the flange-shaped bottle 20a. Shrinkable shrink film 32 as a first film covering the peripheral edge of the film, and the peripheral edge of shrink film 32 covering the entire other surface of flange-shaped flange 20 and covering the peripheral edge of the other surface of flange-shaped flange 20a And a tamper film 42 as a second film bonded to the substrate. The tamper film 42 is a covering portion that covers the other surface of the flange-shaped flange 20a. The joint portion between the peripheral portion of the shrink film 32 and the tamper film 42 covering the peripheral portion of the other surface of the flange-like ridge 20a is a fragile portion that can be peeled off by pulling the tamper film 42 with a finger.

  To form the cap 50 shown in FIG. 6, as shown in FIG. 6A, the side surface of the flange-like ridge 20 a of the rubber stopper 20 attached to the bottle mouth 10 a of the bottle 10 filled with the drug 12 and the bottle 10. The shrink film 32 is wound around the step portion 10b. The shrink film 32 is heated and contracted as shown in FIG. 6B to adhere to the side surface of the flange-shaped ridge 20a and the step portion 10b of the bottle 10. The contracted shrink film 32 also covers the peripheral edge portion of the other surface of the flange-shaped flange 20a. Further, a tamper film 42 that covers the entire other surface of the flange-shaped rod 20a is placed on the other surface of the flange-shaped rod 20a. The peripheral portion of the tamper film 42 and the portion of the shrink film 32 that covers the peripheral portion of the other surface of the flange-like flange 20a are joined by heat sealing or the like. By this joining, a cap 50 including the shrink film 32 and the tamper film 42 shown in FIG. 6C is formed.

  The joint portion between the shrink film 32 and the tamper film 42 is a fragile portion that can be peeled off by pulling the tamper film 42 with a finger. The temperature and time of heat sealing for bonding the shrink film 32 and the tamper film 42 are adjusted, and the bonding force is adjusted. The tamper film 42 used here guarantees that the cap 50 is not broken, and may be used as a label on which characters, figures, and the like are printed. In addition, the plastic which forms the shrink film 32 and the tamper film 42 should just be a thing which is hard to deteriorate with the irradiated electron beam, and can use the plastic mentioned above.

  The bottle 10 described so far is made of glass, but may be made of plastic. Moreover, as the chemical | medical agent 12, although the powdery thing was filled in the bottle 10, it may be a liquid thing.

  Examples of the present invention will be described in detail below, but the scope of the present invention is not limited to these examples.

(Example 1)
A 20 ml glass bottle 10 is filled with 0.5 g of glucose (moisture content 0.6%) manufactured by Sanei Saccharification Co., Ltd. as a drug 12, and the bottle mouth 10a is made of butyl bromide rubber (manufactured by Asahi Rubber Co., Ltd.). A rubber stopper 20 was attached. A polyethylene ring-shaped member 30 shown in FIG. 1 was attached to the flange-shaped flange 20a of the rubber plug 20. As shown in FIG. 3, the ring-shaped member 30 is configured so that each claw portion 31 b of the plurality of locking arms 30 b suspended from the ring-shaped side surface covering portion 30 a that covers the side surface of the flange-shaped flange 20 a It was inserted into the lower end side of the portion 10b and locked. At that time, the end surface of the side surface covering portion 30 a attached to the bottle mouth 10 a was made to be flush with the other surface of the rubber stopper 20. Further, the peripheral edge portion of the other surface covering portion 40a made of polyethylene is ultrasonically bonded to the end surface of the side surface covering portion 30a of the ring-shaped member 30, and the ring-shaped member 30 and the flat plate member 40 are integrated to form a cap. 50 was formed. The side surface and the other surface of the flange-shaped flange 20a of the rubber plug 20 are covered with the cap 50 in close contact.

  A cap 50 made of polyethylene was attached to obtain a vial 1 with a plastic cap shown in FIG. This vial 1 with a plastic cap was sterilized with an electron beam. In this electron beam sterilization, the electron beam irradiation time was adjusted so that the cumulative amount of electron beam received in the vial 1 with a plastic cap was 40 kGy. The cumulative amount of electron beam received in a plastic-equipped vial or the like is obtained by measuring the absorbance of a cellulose triacetate film dosimeter (FTR-125 manufactured by Fuji Film Co., Ltd.) affixed to a measurement location using a spectrophotometer (Hitachi High Corporation). Hitachi double beam spectrophotometer U-2900) manufactured by Technologies and calculated using a standard calibration curve.

  Degradation degree of glucose in vial 1 with plastic cap sterilized by electron beam sterilization is shown as an indicator of the amount of 5-hydroxymethylfurfural (5HMF) in the purity test (in Japanese pharmacopoeia general test method) The absorbance at a wavelength of 284 nm was measured. First, by applying a force to tilt the rod 40d of the vial 1 with plastic cap subjected to electron beam sterilization to one side, the fragile portion 40c is destroyed and the removable portion 40b is removed, and the other surface of the flange-like ridge 20a is removed. The pierceable surface 21 was exposed. The exposed pierceable surface 21 was maintained in a sterilized state. For this reason, the injection needle was pierced toward the inner space of the bottle 10 without sterilizing the pierceable surface 21 with alcohol cotton for disinfection. 20 ml of water was injected into the bottle 10 through the pierced injection needle, and glucose was used as a glucose solution. This glucose solution was extracted with another injection needle, and the absorbance at a wavelength of 284 nm was measured according to the purity test of the glucose injection solution of the Japanese Pharmacopoeia. As a result, the absorbance at a wavelength of 284 nm, which is an index of the amount of 5HMFs, was 0.52, which satisfied the Japanese Pharmacopoeia glucose test purity test standard of 0.80 or less.

  Further, in a clean room where the number of dust particles having a particle size of 0.5 μm or more when sucking 1 cubic foot is not more than 100 in a clean room, 20 bottles 10 are filled with glucose, and the rubber plug 20 When each operation of attaching and attaching the cap 50 was performed three times, the number of dusts was 250, 380, and 276.

(Comparative Example 1)
Example 1 is different from Example 1 except that a plastic cap 50 attached to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a of the bottle 10 is replaced with an aluminum cap. Similarly, electron beam sterilization was performed. In the cap made of aluminum, a fragile portion having a circular cut is formed in a portion corresponding to the pierceable surface through which the needle of the rubber stopper is pierced so that it can be easily removed. In this electron beam sterilization, when the irradiation time of the electron beam was adjusted so that the accumulated amount of the electron beam received in the vial was 40 kGy, the accumulated amount of the electron beam received in the barrel of the bottle 10 was 43 to 60.7 kGy. However, the cumulative amount of electron beam received by the rubber plug 20 covered with the cap made of aluminum was 12.7 kGy. Therefore, the irradiation time of the electron beam was adjusted so that the cumulative amount of the electron beam received in the vial was 60 kGy so that the cumulative amount of the electron beam received in the rubber stopper 20 covered with the cap was 25 kGy.

  About the vial equipped with the aluminum cap subjected to electron beam sterilization, the absorbance at a wavelength of 284 nm, which is an index of the amount of 5HMFs in glucose sealed in the bottle 10, was measured in the same manner as in Example 1. 1.2, which exceeded the standard of 0.8.

  In a non-working environment, an aluminum cap wrapping machine is installed in a clean room with a particle size of 0.5 μm or more when sucking 1 cubic foot and having a particle count of 100 or less, and 20 bottles 10 When the glucose filling, the rubber plug 20 attachment, and the aluminum cap attachment were performed three times, the number of dusts was 2490634, 2388421, and 2463283.

(Example 2)
The same procedure as in Example 1 was conducted except that 10 mg of rifampicin (manufactured by Sigma-Aldrich Japan Co., Ltd., moisture 0.7%) 10 mg produced in culture was filled in a 50 ml glass bottle 10 instead of the glucose of Example 1. Thus, a vial 1 with a plastic cap was obtained. This vial with a plastic cap was sterilized with an electron beam. In this electron beam sterilization, the electron beam irradiation time was adjusted so that the cumulative amount of electron beam received in the vial 1 with a plastic cap was 40 kGy. By applying a force to tilt the rod 40d of the vial 1 with plastic cap subjected to electron beam sterilization to one side, the fragile portion 40c is destroyed and the removable portion 40b is removed, and the stab on the other surface of the flange-like ridge 20a is removed. The passable surface 21 was exposed. The exposed pierceable surface 21 was maintained in a sterilized state. For this reason, the injection needle was pierced toward the inner space of the bottle 10 without sterilizing the pierceable surface 21 with alcohol cotton for disinfection. 50 ml of acetonitrile was injected into the bottle 10 via the pierced injection needle to obtain a rifampicin solution. When this rifampicin solution was extracted with another injection needle and quantified according to the rifampicin quantification method of the Japanese Pharmacopoeia, the content of rifampicin was 92%. The quantitative standard was rifampicin content of 90-110%, and this rifampicin solution was within the standard.

(Comparative Example 2)
Example 2 is different from Example 2 except that a plastic cap 50 attached to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a of the bottle 10 is replaced with an aluminum cap. Similarly, electron beam sterilization was performed. In this electron beam sterilization, the irradiation time of the electron beam is adjusted so that the accumulated amount of the electron beam received in the vial is 60 kGy so that the accumulated amount of the electron beam received in the rubber stopper 20 covered with the cap is 25 kGy. did. About the rifampicin sealed in the bottle 10 of the vial which performed electron beam sterilization, when content was measured like Example 2, it was 64% and it did not satisfy | fill the quantitative specification of 90-110%. .

(Example 3)
In a bottle 10 made of 20 ml of styrene acrylonitrile copolymer resin (manufactured by Mitsui Chemicals), 53 mg of glycyrrhetinic acid monoammonium glycyrrhetinate (manufactured by Maruzen Pharmaceutical Co., Ltd., moisture 1.6%) as a drug 12 and glycine ( 400 mg of Kyowa Hakko Bio Co., Ltd.) and 20 mg of L-cysteine hydrochloride (Kyowa Hakko Bio Co., Ltd.) were filled, and a rubber plug 20 made of butyl bromide rubber (manufactured by Asahi Rubber Co., Ltd.) was attached to the bottle mouth 10a. Further, a cap 50 made of acrylonitrile butadiene styrene resin (manufactured by Mitsui Chemicals, Inc.) as shown in FIG. 4 was attached to the flange-shaped flange 20a of the rubber stopper 20 to obtain a vial 1 with a plastic cap shown in FIG. . This vial 1 with a plastic cap was sterilized with an electron beam. In this electron beam sterilization, the electron beam irradiation time was adjusted so that the cumulative amount of electron beam received in the vial 1 with a plastic cap was 50 kGy.

  The residual amount of monoammonium glycyrrhetinate in the vial subjected to electron beam sterilization was measured. First, by applying a force to tilt the rod 40d of the vial subjected to electron beam sterilization to one side, the fragile portion 40c is destroyed and the removable portion 40b is removed, and the other surface of the flange-like ridge 20a can be pierced The surface 21 was exposed. The exposed pierceable surface 21 was maintained in a sterilized state. For this reason, the injection needle was pierced toward the inner space of the bottle 10 without sterilizing the pierceable surface 21 with alcohol cotton for disinfection. 20 ml of water was injected into the bottle 10 via the pierced injection needle, and the drug 12 was dissolved to obtain a solution. This solution was taken out via another injection needle, monoammonium glycyrrhetinate was quantified by high-speed chromatograph in the solution, and the residual amount of monoammonium glycyrrhetinate was calculated to be 94%. According to the vial with a plastic cap in which monoammonium glycyrrhetinate is sealed in the bottle 10 and subjected to electron beam sterilization, the monoammonium glycyrrhetinate can be stored in powder form.

(Comparative Example 3)
Example 3 is the same as Example 2 except that a plastic cap 50 attached to the flange-shaped flange 20a of the rubber stopper 20 attached to the bottle mouth 10a of the bottle 10 is replaced with an aluminum cap. Similarly, electron beam sterilization was performed. In this electron beam sterilization, in order to sufficiently sterilize the rubber stopper 20 covered with the cap, the irradiation time of the electron beam was adjusted so that the accumulated amount of the electron beam received in the vial was 60 kGy. When the residual amount of monoammonium glycyrrhetinate sealed in the bottle 10 of the vial subjected to electron beam sterilization was measured and calculated in the same manner as in Example 3, it was reduced to 78%.

  The vial with a plastic cap of the present invention can be used for storage and transportation of drugs such as pharmaceuticals.

  1: vial with plastic cap, 10: bottle, 10a: bottle mouth, 10b: stepped portion, 10c: trunk, 12: drug, 20: rubber stopper, 20a: flange-like rod, 20b: protrusion, 20c: recess, 21: pierceable surface, 30: ring-shaped member, 30a: side covering portion, 30b: locking arm, 31a: arm, 31b: claw portion, 32: shrink film, 40: flat plate member, 40a: other surface covering portion 40b: Removable part, 40c: Fragile part, 40d: Rod, 42: Tamper film, 50: Cap

Claims (9)

  It has a bottle mouth at one end and is filled with a medicine, a rubber stopper inserted into the bottle mouth, and a plastic cap attached to the rubber, and is sterilized by electron beam Characteristic vial with plastic chaps. The bottle;
A flange-like ridge having one surface, another surface, and a side surface, and having a diameter larger than the inner diameter of the bottle mouth, and a protrusion protruding from the one surface of the flange-like mouth, the protrusion is provided on the bottle mouth In the inserted state, the rubber stopper through which the injection needle is inserted into the inside of the bottle from the other surface of the flange-shaped fold,
The flange-shaped flange of the rubber plug in the mounted state is attached so that the side wall and the other surface are in close contact with the inner wall surface, and is provided with a covering portion that covers the other surface. With a cap,
In the covering portion, a portion corresponding to a pierceable surface having a diameter smaller than the inner diameter of the bottle mouth, through which the injection needle is pierced to the other surface of the rubber stopper, is formed as a removable portion. ,
The vial with a plastic cap according to claim 1, wherein the vial is sterilized with an electron beam in a state where the cap is attached to the rubber stopper attached to the bottle mouth.   On the outer peripheral surface of the bottle mouth, a band-shaped stepped portion is provided along the inner peripheral edge of the bottle mouth, and the cap has a ring-shaped side surface covering portion that covers the side surface of the flange-shaped rod. A plurality of locking arms that are suspended from the lower end side of the side surface covering portion and formed with claw portions that are locked to the lower end side of the stepped portion at the front end portion, and are joined to the upper end surface of the side surface covering portion, The vial with a plastic cap according to claim 2, wherein the vial is formed from an other surface covering portion that covers the other surface of the flange-like ridge.   The vial with a plastic cap according to claim 2, wherein a fragile portion is formed on the other surface covering portion so as to surround the removable portion. The bottle;
A flange-like ridge having one surface, another surface, and a side surface, and having a diameter larger than the inner diameter of the bottle mouth, and a protrusion protruding from the one surface of the flange-like mouth, the protrusion is provided on the bottle mouth In the inserted state, the rubber stopper through which the injection needle is inserted into the inside of the bottle from the other surface of the flange-shaped fold,
A first film that covers the side surface of the flange-like ridge and the other surface of the flange-like ridge of the rubber plug in the mounted state; and the other surface of the first film that covers the other surface of the flange-like ridge A plastic cap comprising a second film removably joined to a portion covering the periphery of
The vial with a plastic cap according to claim 1, wherein the rubber stopper mounted on the bottle mouth is sterilized with an electron beam while being covered with the cap.   The vial with a plastic cap according to any one of claims 1 to 5, wherein a cumulative amount of the electron beam received in the vial with a plastic cap by the electron beam sterilization is 15 to 40 kGy.   The vial with a plastic cap according to any one of claims 1 to 6, wherein a cumulative amount of the electron beam transmitted through the cap and received by the rubber stopper by the electron beam sterilization is 15 to 40 kGy.   The vial with a plastic cap according to any one of claims 1 to 7, wherein the drug is a powder having a moisture content of 2.0% or less.   The said rubber stopper is mounted | worn in the said clean room, and the said cap was adhere | attached in the said bottle mouth of the said bottle with which the said chemical | medical agent was filled in the clean room. Vials with plastic caps.

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