JP2001340425A - Medical rubber stopper - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent invasion of air and water in a medical container through a medical rubber stopper. SOLUTION: The medical rubber stopper 10 is applied to an opening of the medical container and has a penetration part through which a needle of an injector can be penetrated. A nylon film layer 6 with a thickness from 20 to 200 μm is provided on a top face of the medical rubber stopper 10.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical rubber stopper applied to the mouth of a pharmaceutical container, and more particularly, to sealing or closing an opening of a medical container, for example, a vial for storing a lyophilized preparation. Medical rubber stopper.

[0002]

2. Description of the Related Art Medical rubber stoppers applied to the mouth of pharmaceutical containers are required to have high quality and physical properties. For example, the quality characteristics required of a medical rubber stopper that seals or closes the opening of a vial storing antibiotics and other preparations conform to the 13th edition of the Japanese Pharmacopoeia Rubber Infusion Rubber Plug Test. Should. Furthermore, medical rubber stoppers that seal the opening of vials include gas permeation resistance, non-elution properties, high cleanliness, chemical resistance, needle stick resistance, self-sealing properties, high sliding properties, etc. Item is required.

[0003] In the case of a medical rubber stopper for sealing or closing the opening of the vial, the method of use is as follows. That is, the vial is filled with a predetermined amount of the chemical solution,
After inserting a rubber stopper for medical use into the vial opening in a half stopper shape, a large number of the rubber stoppers were aligned on each shelf in the freeze-drying cabinet, and freeze-vacuum dried under predetermined conditions (temperature, degree of vacuum, time). Thereafter, the medical rubber stopper is dried at a predetermined temperature for a predetermined period of time, and the medical rubber stopper is pressed by a pressing plate of a freeze-drying shelf, and the medical rubber stopper is completely fitted into the mouth of the vial and plugged.

[0004] The preparation for freeze-vacuum drying is required to prevent contact with air and moisture, and to prevent invasion of air or the like from the outside during sealed storage or to maintain the airtightness inside the vial. Polybutadiene rubber, polyisoprene rubber, butyl rubber, and the like are generally used as materials for medical rubber stoppers. Then, when administering the infusion to the patient, an injection needle for injecting a drug solution is punctured into the puncture portion of the medical rubber stopper and used.

[0005] In recent years, as part of the cost reduction accompanying the reduction of the drug price of pharmaceuticals, it is urgent to improve the productivity, and as a method of this, the speed of pharmaceutical manufacturing machines is increasing. Therefore, it has become necessary to improve mechanical transportability, slidability, high operability, and the like in the required characteristics of the medical rubber stopper.

[0006] Butyl rubber is a material having a low degree of unsaturation and a low cross-linking density, so that it has poor elasticity and a strong adhesiveness on the rubber surface. Therefore, when butyl rubber is used as the material of the medical rubber stopper, the rubber stopper of butyl rubber is
After the freeze-vacuum drying is completed, when the rubber stopper is pressed by the pressing plate on the shelf of the freeze-drying cabinet and plugged, the rubber stopper top surface adheres to the pressing plate, and the rubber stopper adheres to the pressing plate when the pressing plate is raised. When the vial is lifted with and falls after a few seconds,
As a result, the vials in the vicinity are turned over, which hinders removal of the vials from the freeze-drying cabinet and transportation to the next step.

Therefore, in order to improve the adhesiveness, which is a basic property of rubber, a medical rubber stopper whose top surface is coated with silicone has been used. By coating the top surface of the medical rubber stopper with silicone, it is possible to give the top surface a slidability, and it is possible to improve the mechanical transportability of the medical rubber stopper during pharmaceutical preparation. Was. In addition, by coating the top surface of the medical rubber stopper with silicone, it was possible to reduce the adhesion between the top surface of the rubber stopper and the pressing plate of the freeze-drying cabinet.

However, there is a problem that a trace amount of silicone coated on the top surface migrates to a pharmaceutical preparation machine, or migrates to a rubber stopper foot (a portion that enters the vial) to cause fine particles. became. In addition, when the injection needle is pierced into the rubber stopper of the vial to aspirate the drug solution when the injection is used, a needle puncture fragment may be generated depending on the thickness of the needle, the finished state and the shape, etc. Sex became a problem.

[0009] Therefore, a medical rubber stopper having a top surface portion laminated with a fluororesin film has been proposed. By laminating the top surface with a fluororesin film, it was possible to improve the slidability and mechanical transportability of the top surface and reduce the generation of fine particles. In general, it is a well-known fact that the relationship between the occurrence of a needle stick fragment and a rubber stopper is such that the higher the surface smoothness of the rubber stopper, the lower the occurrence of fragments. When the top surface was laminated with a fluororesin film, the surface lubricity of the top surface could be relatively improved, so that it was possible to prevent the occurrence of needle stick fragments from the needle when puncturing the injection needle. . Furthermore, by not only laminating the top surface with a fluororesin film but also laminating the medical rubber stopper on the chemical contact portion with the fluororesin film, it was possible to further reduce the occurrence of needle stick fragments. .

[0010]

However, even if a fluororesin film is laminated on the top surface of the medical rubber stopper, it is difficult to sufficiently prevent air and moisture from entering the medical container. . In particular, the air permeability of the fluororesin film does not show a sufficiently low value among the air permeability of the resin film. In recent years, pharmaceuticals whose quality is degraded by contact with a minute amount of air have been developed. Even if a medical rubber stopper whose top surface is laminated with a fluororesin film is used, if oxygen in the air enters the medical container through the medical rubber stopper, the drug will undergo an oxidation reaction with oxygen. This is a very problematic quality fluctuation.

The present invention has been made to solve the above-mentioned problem, and secures mechanical transportability at the time of manufacturing a drug, prevents adhesion between a top surface of a rubber stopper and a pressing plate of a freeze-drying cabinet, and provides an injection. Prevents the generation of needle stick fragments when the needle is punctured, and also sufficiently prevents air and moisture from entering the inside of the medical container through the medical rubber stopper. An object is to provide a medical rubber stopper that can be used even when required.

[0012]

According to a first aspect of the present invention, there is provided a medical rubber stopper which is applied to a mouth of a medical container and which is capable of puncturing a needle of a syringe. A medical rubber stopper having a nylon film layer having a thickness of 20 to 200 μm on a top surface of the medical rubber stopper.

[0013] Since there is a puncture portion that allows the injection needle of the syringe to be pierced, the injection needle of the syringe can be pierced into a rubber stopper of a medical container for inhaling a drug solution when an injection is used.

The medical rubber stopper according to the present invention has a nylon film layer provided on the top surface. Nylon films are highly capable of preventing the passage of air and moisture. In particular, the air permeability of a nylon film has a considerably lower value than the air permeability of other resin components. Therefore, by providing the nylon film layer on the top surface, it is possible to prevent oxygen existing in the air from entering the inside of the medical container. Since oxygen can be prevented from entering the inside of the medicine container, the medicine can be prevented from the oxidation reaction, and the medicine can be stably stored for a long period of time. The gas permeability coefficient P (10 ⁻¹¹ m ³ · m / m ² · s · MPa) of oxygen is 7.22 at a measurement temperature of 20 ° C. for Teflon (registered trademark), and is measured for polyethylene. It is 4.2 at a temperature of 30 ° C., for example, in the case of nylon 6, it is 0.0011 at a measurement temperature of 30 ° C. The gas permeability coefficient P (10 ⁻¹¹ m ³ · m / m ² · s · MPa) of carbon dioxide is 17.5 at a measurement temperature of 20 ° C. for Teflon, and 30 ° C. for polyethylene. For example, in the case of nylon 6, it is 0.0046 at a measurement temperature of 30 ° C. Teflon means polytetrafluoroethylene, and is a trademark of duPont.

The thickness of the nylon film layer is 20 to 2
00 μm. The thickness of the nylon film layer is 20
When it is smaller than μm, the thickness is insufficient from the viewpoint of preventing the transmission of air and moisture. Further, when the thickness of the nylon film layer is smaller than 20 μm, it is difficult to handle in the step of forming the nylon film on the top surface of the medical rubber stopper because the thickness is thin. Further, the thickness of the nylon film layer is 20 μm.
If it is smaller than this, the durability of the nylon film is insufficient, and the nylon film may be broken in the step of forming the nylon film layer on the top surface of the medical rubber stopper.

On the other hand, when the thickness of the nylon film layer is 2
In the case where the thickness is larger than 00 μm, the thickness from the viewpoint of preventing the transmission of air and moisture is sufficient,
There is a possibility that puncture resistance when puncturing the injection needle of the syringe into the puncture part may be increased. If the puncture resistance of the injection needle increases, there is a problem in the usability as a medical rubber stopper. In addition, when the injection needle is punctured in the resin film, and then the injection needle is pulled out, the puncture hole which is a hole generated when the injection needle is punctured is usually caused by the elastic force of the resin used for the resin film. The hole diameter gradually decreases and finally the puncture hole closes. However, if the thickness of the nylon film layer is 2
When it is larger than 00 μm, the puncture hole generated when the injection needle is punctured becomes difficult to close even after the injection needle is pulled out. Therefore, after pulling out the injection needle,
The drug inside the medical container may come into contact with air. Therefore, the thickness of the nylon film layer provided on the top surface of the medical rubber stopper is 20 to 200 μm.

According to a second aspect of the present invention, there is provided a medical rubber stopper according to the first aspect, wherein the nylon film layer comprises nylon 6, nylon 66,
Medical rubber that is a nylon film layer formed of a nylon resin containing at least one of nylon 610, nylon 621, nylon 11, nylon 12, copolymer nylon, monomer casting nylon, nylon MXD, and nylon 46 It is a stopper.

Nylon 6, Nylon 66, Nylon 61
0, nylon 621, nylon 11, nylon 12, copolymer nylon, monomer casting nylon, nylon MXD, and nylon 46, wherein the nylon film layer is formed of a nylon resin containing at least one of the components. In particular, it is possible to sufficiently prevent air from entering the medical container through the medical rubber stopper, and use the medical rubber stopper without any problem even when the medicine inside the medical container requires a sufficiently dry state. can do.

The medical rubber stopper according to the present invention, as described in claim 3, is the invention according to claim 1 or 2, wherein the nylon film layer contains a filler. A medical rubber stopper.

By blending a filler into the nylon film layer formed on the top surface of the medical rubber stopper, the performance is further improved, and it is suitable for use in the field, and has extremely excellent quality and hygiene. It becomes possible to obtain a medical rubber stopper.

As the filler, an organic filler or an inorganic filler can be used. One of the advantages of using an inorganic filler as the filler is that the thermal conductivity at the time of crosslinking of a rubber material used for a medical rubber stopper can be improved, and crosslinking can be performed uniformly. It shows the effect of preventing deformation of medical rubber stoppers as a product.

The filler may be added in an amount of 5 to 20 parts by weight based on 100 parts by weight of the nylon resin. If the blending amount of the filler exceeds 20 parts by weight, fine particles of the filler are generated from the surface of the medical rubber stopper, which is not preferable. If the amount is less than 5 parts by weight, the effect of adding the filler is hardly exhibited.

According to a fourth aspect of the present invention, there is provided a medical rubber stopper according to any one of the first to third aspects, wherein the nylon film layer is formed of polyvinylidene chloride (vinylidene chloride). A medical rubber stopper coated with PVDC).

A nylon film layer provided on the top surface of a medical rubber stopper is coated with polyvinylidene chloride (PVDC) to form a polyvinylidene chloride-coated nylon film layer, and the polyvinylidene chloride-coated nylon film layer is used for medical treatment. When the rubber stopper is provided on the top surface of the rubber stopper, it becomes possible to further improve the moisture permeability resistance and the air permeability resistance of the medical rubber stopper.

There are two types of polyvinylidene chloride (PVDC), a vinylidene chloride / vinyl chloride copolymer and a vinylidene chloride / acrylic acid ester copolymer. It is possible to improve the minute permeability and the air permeability resistance.

[0026]

FIG. 1 is a schematic sectional view of one embodiment of a medical rubber stopper 10 according to the present invention. Medical rubber stopper 10
Comprises a top plate 1 and a plug leg 2. Top board 1
The medical device has a puncturing portion 3 that allows the injection needle of a syringe to be punctured, and a flange portion 1b that is in contact with the upper edge surface 4a of the container opening of the medical container 4. The stopper leg 2 protrudes from the lower surface of the top plate 1 and is fitted into the mouth of the medical container. The plug leg 2 has a substantially cylindrical shape,
A notch 7 is provided. A nylon film layer 6 is provided on the top surface of the top plate 1 of the medical rubber stopper 10. The thickness of the nylon film layer is 20 to 200 μm
Set within the range. By providing the nylon film layer 6 on the top surface of the medical rubber stopper 10, mechanical transportability during the production of pharmaceuticals can be ensured, and the adhesion between the top surface of the rubber stopper and the pressing plate of the freeze-drying cabinet is prevented. did it. Further, by providing the nylon film layer 6 on the top surface of the medical rubber stopper 10, the degree of surface smoothness of the top surface can be increased, and the generation of needle stick fragments at the time of puncturing the injection needle could be prevented.

Nylon 6, Nylon 66, Nylon 61
0, nylon 621, nylon 11, nylon 12, copolymerized nylon, monomer-casting nylon, nylon MXD, and nylon 46, and the nylon film layer can be formed of a nylon resin. .

Nylon 6 is made by ring opening polymerization of epsilon caprolactam. As a polymerization vessel used for ring-opening polymerization, a double cylinder made of stainless steel can be used.
When the polymerization temperature is 260 ° C., the water content is 10 to 20% from the top.
When the lactam liquid of the above is allowed to flow down, it is possible to continuously polymerize. It takes 15 hours to polymerize pure lactam, but the reaction time can be shortened by adding 5-6% aminocaproic acid and using it as a catalyst. 1/200 as a viscosity stabilizer
It is also possible to add molar acetic acid.

Nylon 66 is produced by polycondensation of hexaethylenediamine and adipic acid. It is possible to polymerize by adding an equivalent amount of adipate to an aqueous solution of hexamethylenediamine to obtain an aqueous solution of a nylon salt, filtering and measuring, concentrating the water to 30 to 40% in an evaporator, and then transferring the solution to a polymerization tank. is there. For example, 0.35 part of hexamethylene diammonium acetic acid was added as a viscosity stabilizer to 578 parts of a nylon salt, and placed in an autoclave together with 24.7 parts of distilled water.
After heating at 7.6 atm for 2.5 hours,
It is possible to obtain nylon 66 by raising the temperature to ℃ and conducting a polymerization reaction at normal pressure for 1.5 hours.

[0030] Nylon 610 is produced by polycondensation of hexamethylene diamine and sebacic acid. Nylon 610 has a lower melting point (about 250 ° C.) and less moisture absorption because the methylene chain of the acid composition is longer than nylon 66. Therefore, it has the feature that the decrease in strength under high humidity is small.

The copolymer nylon is composed of caprolactam and AH
It is produced by copolymerization with a salt. The physical properties of the copolymerized nylon vary depending on the composition ratio of caprolactam and AH salt. For example, AH salt 60%, caprolactam 40%
Is soluble in alcohol and is generally used as an adhesive film.

The monomer-casting nylon can be obtained by melting epsilon caprolactam, which is a monomer, adding a basic catalyst, and then directly column-molding the mixture under atmospheric pressure into a mold, and simultaneously performing polymerization molding. .

Nylon MXD6 is a crystalline thermoplastic polymer obtained from meta-xylenediamine and adipic acid, and has slightly different properties from nylon 6 and nylon 66. In general, it has been found that composite materials reinforced with glass fibers, inorganic fillers and the like have many excellent properties.

Nylon 46 was developed by DSM in the Netherlands, and its trade name is stannyl, and can be obtained from the polymerization reaction of 1,4-aminobutane and adipic acid. Acrylonitrile reacts with hydrogen cyanide to produce succinic nitrile, which is hydrogenated to produce 1,4-diaminobutane (DAB). Next, a salt is formed from 1,4-diaminobutane (DAB) and adipic acid, which is converted into a low molecular weight prepolymer in water under moderate pressure, and the prepolymer is recovered as a solid. In the next step it is heated to about 250 ° C. under an atmosphere of nitrogen and steam. In this way, it is possible to obtain nylon 46.

Nylon 612 can be obtained by polycondensation of caprolactam and lauryl lactam.
Nylon 11 is produced by polycondensation of 11-aminoundecanoic acid. Its properties are similar to nylon 12 except that it is slightly more hygroscopic than nylon 12 and has a slightly higher melting point. Nylon 12 can be obtained by obtaining aminododecanoic acid from cyclohexanone as a raw material via peroxyamine and cyanoundecanoic acid, and polymerizing this. Alternatively, laurin lactam can be obtained from butadiene as a raw material through several steps including a photosynthesis method, and purified and polymerized to obtain laurin lactam.

The nylon film layer 6 can contain a filler. As the filler, an organic filler or an inorganic filler can be used.

As the inorganic filler, aluminum,
Metal powders such as copper, iron, lead, nickel, and silver, silica, diatomaceous earth, alumina, oxides such as titanium oxide, calcium oxide, magnesium oxide, zinc oxide, iron oxide, beryllium oxide, aluminum hydroxide, and hydroxide Hydroxides such as magnesium, calcium hydroxide, aluminate hydrate,
Talc, clay, mica, asbestos, bentonite,
Use silicates such as zeolite, calcium silicate and montmorillonite, carbonates such as calcium carbonate, magnesium carbonate and hydrotalcite, and sulfates such as calcium sulfate sulfate, calcium sulfite, barium sulfate and calcium sulfite. In addition, molybdenum disulfide, potassium titanate, silicon carbide and the like can be used as the inorganic filler.

Further, as the organic filler, linter,
Linen, sisal wood flour, silk, leather flour, collagen fiber,
Viscose, acetate, vinylon, Teflon powder and the like can be used.

It is not desirable to mix a large amount of heavy metal such as lead as a filler. This is because in the field of use of the medical rubber stopper according to the present invention, excessive presence of heavy metals may not be preferable. In addition, by taking into account the compounding of the filler in this manner, a medical rubber stopper having high sanitary properties and passing various official standards can be obtained.

The nylon film layer 6 provided on the top surface of the medical rubber stopper 10 is coated with polyvinylidene chloride (PVD).
It is possible to coat C). As a method for coating polyvinylidene chloride (PVDC) on a nylon film layer, polyvinylidene chloride (PVDC) is used.
It is possible to adopt a method of preparing the film C) and laminating the polyvinylidene chloride film to the nylon film layer. Incidentally, polyvinylidene chloride resin can be produced as a copolymer with vinyl chloride, acrylate, acrylonitrile, vinyl acetate, etc., the production method is a suspension polymerization, peroxide by emulsion polymerization method It is possible to carry out by the radical polymerization method used. Further, the polyvinylidene chloride film is generally transparent, has excellent chemical resistance and water resistance, and has a property of being impermeable to gas and moisture.

As a laminating method, for example, wet lamination, dry lamination,
Extrusion lamination or the like can be employed.

Wet lamination refers to a method of performing lamination using a solution type adhesive. An organic solution type adhesive (urethane or the like), an aqueous emulsion (acrylic emulsion or the like), or the like can be used. After coating on one film, the solvent is evaporated by heating, or laminated as it is.

Dry lamination is a method of laminating a plastic film or the like via an adhesive.
It refers to a method of applying an adhesive solution, drying the solvent, and then bonding. As the adhesive, a polyurethane-based or isocyanate-based adhesive can be used, and a solvent such as toluene, ethyl acetate, or hexane can be used.

Extrusion lamination refers to a method of laminating a thin-film polymer on a substrate using an extruder. A plastic film or the like is used as a base material, and a laminated material and a thickness are selected according to purposes such as waterproofing and surface modification. Generally, a long web is unwound with a rewinding machine, a T-die is attached to the end of the extruder, and the molten polymer is placed in a film on a substrate, and then cooled from a cooling roll, a nip roll, and a backup roll. In a laminating section, lamination is performed by roll pressing.

The nylon film layer 6 is covered with a medical rubber stopper 10.
As a method of providing on the top surface of the nylon film,
It is possible to adopt a method of laminating on the top surface of the medical rubber stopper. As a method of laminating the nylon film on the top surface of the medical rubber stopper, as described above, wet lamination, dry lamination,
Extrusion lamination or the like can be employed.

The nylon film to be laminated on the top surface of the medical rubber stopper 10 is desirably biaxially stretched. Biaxial stretching can be specifically performed by the following method. That is, an unstretched sheet of a nylon film is prepared, and the unstretched sheet is first stretched in the first axial direction. Stretching can be performed in one step or two or more steps. Next, the uniaxially oriented film is once cooled below the glass transition point in the second axis direction, that is, in a direction orthogonal to the first axis direction, or is stretched by preheating without cooling, and the film is biaxially oriented. Get. In addition,
Performing the stretching in the first axial direction in two or more stages is preferable because good thickness uniformity can be achieved. Further, a method in which the film is stretched in the transverse direction and then stretched again in the longitudinal direction is also possible. The film thus obtained is heat-treated. At this time, re-stretching may be performed in the longitudinal direction, the lateral direction, or both directions during or after the heat treatment step. Thus, a nylon film is produced.

FIG. 2 shows a state in which the opening 4 b of the container 4 filled with the medicine is sealed with the medical rubber stopper 10.
In this embodiment, a vial for storing a lyophilized preparation is used as the container 4. When the liquid medicine contained in the container 4 is an injection liquid, the injection needle of the syringe is pierced into the puncture portion 3 of the top plate 1 and the injection liquid is sucked into the syringe without opening the medical rubber stopper 10. I have to. in this way,
The reason why the medical rubber stopper 10 is not opened is to prevent foreign substances from being mixed in the liquid medicine for injection in the container 4 and avoiding them.

On the top plate 1, a metal or resin cap 5 capable of covering the opening 4b of the container 4 and the medical rubber stopper 10 is provided. Medical rubber stopper 10
Is sealed with the cap 5 including the opening 4b in order to prevent the fungus from adhering to the puncture part 3 at the place where the injection needle of the syringe is stabbed and the fungus from the injection needle into the liquid medicine for injection. is there. As the type of the cap 5, a flip-off cap, a pull-top cap, a clean cap, or the like can be used. When a large amount of a drug solution for injection is used as in a hospital, it is preferable to use a clean cap that can be opened with one hand and that is easy to operate.

The material of the cap 5 is ASTM-D
According to the measuring method according to 2117, a thermoplastic resin or a thermoplastic resin composition having a melting point of 100 to 500 ° C. can be used. The reason is that it can be easily molded by injection molding. Specifically, for example, polyacetal (P
OM), polyamide (PA), polyarylate (PA
R), polyether / ether ketone, ethylene / propylene copolymer, polypropylene (PP), polyethylene terephthalate (PET), liquid crystal polyester (LC
P), polyphenylene ether (PPE) or modified polyphenylene ether, polycarbonate (PC), polymethylpentene (PMP), polyurethane (PU),
Polyethylene (PE), polybutylene phthalate, polysulfone (PS), polyethersulfone (PE
S), a synthetic resin comprising at least one selected from ultrahigh molecular weight polyethylene, a copolymer containing a cyclic olefin compound or a crosslinked polycyclic hydrocarbon as a polymer component, or a composition thereof. Further, when a thermoplastic resin in which an organic reinforcing agent or an inorganic reinforcing agent is blended with the thermoplastic elastomer constituting the plug is used, the cap 5 has very high hardness and high strength.

FIG. 3 shows that the medical drug solution filled in the container 4 is subjected to concentration drying or freeze vacuum drying (hereinafter referred to as concentration or freeze vacuum drying) in a sterilized state using a medical rubber stopper 10. FIG. 4 is a schematic cross-sectional view showing a state in which the device is in a position.

The distal end of the plug leg 2 to the middle position of the plug leg 2 is fitted into the opening 4b of the container 4 to hold the medical rubber plug 10 in a half-plugged state. At this time, since the deepest portion 7a of the notch 7 is designed to be located above the upper edge of the opening 4b, the notch 7 forms an air passage communicating between the inside and the outside of the container, and the vapor from the raw chemical solution is formed. Is exhausted from inside the container 4 to the outside.

The freeze-drying in a freeze-drying chamber is usually performed by
After freezing the drug solution at a temperature of -30 to -45 ° C, the degree of vacuum is 1 to
Maintain at 0.03 Torr and a temperature of −20 ° C. to + 30 ° C., and perform primary drying within a range of 12 to 36 hours. Furthermore, the temperature is kept at + 20 ° C. to + 40 ° C. and secondary drying is performed within a range of 1 to 6 hours, thereby completing the freeze-vacuum drying of the preparation.

After the medicine is completely dried, the medical rubber stopper 10 is immediately pressed in the direction of a white arrow by a stopper or the like in the concentrator / dryer tank or the tank with a freeze vacuum dryer. The whole 10 is inserted into the opening 4b. The pressing plate and the top surface of the rubber plug come into direct contact and are plugged. Therefore, the medical rubber stopper 10 can be completely sealed, sealed and fixed by a simple operation, that is, one action immediately after drying in a concentration / dryer tank or a tank with a freeze vacuum dryer under a sterile environment. Medical rubber stopper 10
Is performed by a stainless steel pressing plate on a freeze-drying cabinet. The plugging conditions at this time are generally a pressing force of 1 to 5 kg per vial, a pressing time of 1 to 10 minutes, and a pressing frequency of about 1 to 2 times.

As shown in FIG. 2, the medical rubber stopper 10
Is fitted into the opening 4b, the lower surface of the flange 1b is in close contact with the upper edge surface 4a of the container opening of the medical container 4, and completely seals the opening 4b. The cap 5 is engaged and fixed to the outer periphery of the opening 4b, encloses the opening 4b and the medical rubber plug 10, and fixes them together. The vial in which the closure of the medical rubber stopper 10 has been completed is taken out of the freeze-drying cabinet, transported to the next step, and the cap 5 is wound around the rubber stopper, stoppered to obtain a preparation.

As the material of the container 4 of the present invention, those known in this field, such as glass and plastic, can be used.

A projection may be provided on the top surface of the medical rubber stopper 10 according to the present invention where the nylon film layer 6 is provided. Protrusions are provided to prevent adhesion of the rubber stopper to the rubber stopper during cleaning, sterilization and drying of the medical rubber stopper, and to prevent adhesion of the pressing plate to the rubber stopper. There is no particular limitation on the shape and position of the projections. For example, various projections such as a T-shaped projection and a semi-cylindrical projection can be provided. It is preferable that the cross-sectional shape of the projection be a line-contact shape when it comes into contact with the flat plate. If the shape is in line contact, the top forms a ridge. Further, as the shape of the projection, for example, a pentagonal shape can be adopted. Further, in the plan view, a projection having a rectangular shape, a square shape, an elliptical shape, or the like can be adopted.

A plurality of protrusions, for example, 3 to 15
When a rubber plug is fitted with a pressing plate, it is desirable that a predetermined load can be held. If the number of projections is less than three, the top surface of the rubber plug and the pressing plate are likely to be in close contact with each other. Become.

After freeze-drying the preparation in a vial, the medical rubber stopper 10 held in the vial opening 4b in the freeze-drying chamber in a half-stopped state is inserted into the vial opening by a pressing plate on the freeze-drying cabinet shelf. In order to prevent the top plate 1 from being in close contact with the pressing plate when the plug is completely inserted into the plug, it is preferable to provide the protrusions in an arc shape. Here, the pressing plate and the top surface of the rubber plug come into direct contact and are plugged.

FIG. 4 is a schematic sectional view of another specific example of the medical rubber stopper 10 according to the present invention. The medical rubber stopper 10 has a puncture part 3. A nylon film layer 6 is provided on the top surface of the medical rubber stopper 10. The medical rubber stopper 10 is mounted on a support 12. As a method of assembling, a medical rubber stopper 10 is attached to a support 12 which has been injection-molded in advance.
Or the medical rubber plug 10 having a predetermined shape and the outer support 12a are set in a mold to form the inner support 12
b is injection molded.

Before the nylon film 6 is provided on the top surface of the medical rubber plug 10, the surface of the top surface is subjected to corona discharge treatment, plasma discharge treatment, glow discharge treatment, or the like.
It is preferable to perform the treatment in advance by a known technique such as arc discharge treatment or sputter etching.

The rubber material constituting the medical rubber stopper 10 according to the present invention may be an epoxidized styrene-conjugated diene block copolymer, a carboxylated styrene-conjugated diene block copolymer or a hydroxyl group-containing styrene-conjugated diene block copolymer. A thermoplastic elastomer such as a block copolymer or a block copolymer obtained by hydrogenating these block copolymers (hereinafter referred to as a block copolymer elastomer) may be used alone or as a mixture of two or more kinds. However, in the case of a mixture of the epoxidized block copolymer elastomer and the carboxylated block copolymer elastomer, both of the functional groups react with each other and the adhesiveness to the film is lowered, so that it may not always be desirable.

Here, conjugated dienes include, for example, butadiene, isoprene, 1,3-pentadiene, 2,3-
One or more of dimethyl-1,3-butadiene and the like can be selected, and among them, butadiene, isoprene and a combination thereof are preferable.

Specific examples of the basic molecular chain skeleton of the block copolymer elastomer include styrene-isoprene-butadiene-styrene copolymer (SIBS structure),
Styrene-butadiene-styrene block copolymer (S
Styrene-ethylene-butylene-styrene block copolymer (SEBS structure), styrene-isoprene-styrene block copolymer (SIS structure) obtained by hydrogenating the double bond portion of butadiene, and isoprene double bond Examples thereof include a partially hydrogenated styrene-ethylene-propylene-styrene block copolymer (SEPS structure), styrene-ethylene-ethylene-propylene-styrene (SEEPS structure), and modified products thereof.

The above-mentioned SIBS structure, SBS structure,
SEBS structure, SIS structure, SEPS structure, SEEPS
The content of styrene in the structure is preferably in the range of 5 to 50% by weight, particularly 15 to 45% by weight in the copolymer. 5% by weight
If the amount is less than the above, the adhesion to the plastic film is poor, while if it is more than 50% by weight, the flexibility of the material is reduced,
It becomes difficult to pierce the injection needle, and it becomes difficult to obtain an excellent rubber stopper such as a decrease in self-sealing property.

In the present invention, the above-mentioned SIBS structure, SBS structure, SEBS structure, SIS structure, SEPS structure, SEE
A part of the molecular chain of the copolymer having the PS structure contains an epoxy group, a carboxyl group, or a hydroxyl group. For example, a styrene-butadiene-styrene block copolymer having a polybutadiene block containing an epoxy group (E
(SBS structure) is a block copolymer having a polystyrene at both ends as shown in the formula (1), and a polybutadiene having an epoxy group at an intermediate portion thereof. Further, the polybutadiene moiety of the formula (1) may be obtained by hydrogenating some or all of the double bonds. Further, a styrene-isoprene-styrene block copolymer having a polyisoprene block containing an epoxy group (ES
IS structure) is a block copolymer having polystyrene at both ends, the middle of which is polyisoprene containing an epoxy group, with some or all of the double bonds in the polyisoprene hydrogenated. It may be.

[0066]

Embedded image

In the formula (1), m, n, and o are all integers in the range of 1 to 10,000, and m, n, o
May be the same or different.

It is to be noted that the carboxy group or the hydroxyl group has at least one of the molecular chain terminal and the molecular chain inside of the block copolymer.

The content of the epoxy group, carboxyl group or hydroxyl group of the block copolymer having SBS structure, SIS structure or the like is preferably 0.05 to 10 mol%, particularly preferably 0.2 to 5 mol%. When the amount of the functional group such as the epoxy group is less than 0.05 mol%, the affinity with a plastic film such as a fluororesin decreases, and the adhesion and the adhesive strength cannot be improved. On the other hand, if it exceeds 10 mol%, the mixing and dispersion with the rubber component is deteriorated, and a rubber stopper having uniform physical properties cannot be obtained.

Styrene containing an epoxy group in the molecular chain
As a butadiene-styrene block copolymer (ESBS structure), for example, Epofriend A1010, ESBS A1010, ESBS from Daicel Chemical Industries, Ltd.
Products such as A1020 are commercially available.

A part of a polybutadiene block containing an epoxy group in the molecular chain is hydrogenated styrene-butadiene-styrene block copolymer from Daicel Chemical Industries, Ltd. as ESBS AT018 and ESBS.
Products such as AT019 are commercially available.

Further, a styrene-ethylene-propylene-styrene copolymer having a hydroxyl group added to a molecular chain terminal (SEP)
S structure), for example, HG-25 from Kuraray Co., Ltd.
Two products are commercially available.

Further, as a hydrogenated styrene-butadiene copolymer (SEBS structure) having a carboxyl group added to the molecular chain, for example, the product of Kraton GFG1901X is commercially available from Shell Japan.

Next, rubber materials constituting the medical rubber stopper 10 include isoprene rubber, butadiene rubber, and styrene rubber.
Butadiene rubber, butyl rubber, ethylene-propylene rubber, ethylene-propylene-butadiene rubber, acrylonitrile rubber, chloroprene rubber, and the like can be used alone or in combination of two or more.

The block copolymer elastomer is blended in an amount of 2 to 30 parts by weight, preferably 5 to 20 parts by weight, based on 100 parts by weight of the total of the rubber component and the block copolymer. If the amount is less than 2 parts by weight, no improvement in adhesion and adhesion to the plastic film is observed, while if it exceeds 30 parts by weight, the overall properties of the rubber stopper, such as needle sticking properties, resealability, coring, etc. Balance will be inferior.

A crosslinking agent can be used for the polymerization of the rubber material constituting the medical rubber stopper 10 according to the present invention. As the cross-linking agent, an aliphatic or alicyclic peroxide can be blended. Examples of the aliphatic or alicyclic peroxide include 3,3,5-trimethylhexanone peroxide, diisobutyryl peroxide, and 1,1-di (t
-Butylperoxy) 3,3,5-trimethylcyclohexane, 2,5-dimethyl2,5-di (t-butylperoxy) hexane, 2,5-dimethyl2,5-di (t-
(Butylperoxy) hexyne-3, n-butyl-4,4
-Bis (t-butylperoxy) valerate, di-se
c-butyl peroxydicarbonate and the like. Examples of the crosslinking assistant include triethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, 1,2-polybutadiene, vinyltrimethoxysilane, vinyltriacetoxysilane, and γ.
-Methacryloxypropyltrimethoxysilane, γ
-Glycidoxypropyl-tri-methoxysilane and the like can also be blended.

The rubber material constituting the medical rubber stopper 10 according to the present invention is, for example, isoprene rubber or isoprene rubber.
Isobutylene copolymer, halide of isoprene-isobutylene copolymer, copolymer rubber of isoprene-isobutylene with a third component, butadiene rubber, ethylene-propylene copolymer, ethylene-propylene-third component copolymer, natural It is possible to use a composition containing at least one selected from rubber, urethane rubber and thermoplastic elastomer as a main component. These rubber materials are elastic bodies having low compression strain and heat resistance. The rubber material of the present invention not only has high sealing properties at room temperature but also has high-pressure steam sterilization (temperature of 125 to 14).
(0 ° C.) or hot air sterilization (temperature: 170 to 180 ° C.), and can satisfy characteristics that can withstand fine deformation without severe deformation.

In order to conform to the standards according to the Japanese Pharmacopoeia 13th Edition Rubber Plug Test Method for Infusion,
Crosslinking is performed by selecting a crosslinking agent, an auxiliary agent, and the like.

The following can be used as such a crosslinking agent. That is, as a compound containing two or more acryloyl groups in one molecule, alkyl-modified dipentaerythritol tri (or penta)
Acrylate, ε-caprolactone-modified dipentaerythritol tri (or tetra) acrylate, caprolactone-modified neopentyl glycol hydroxypivalate diester diacrylate, diglycidylbisphenol A diacrylate, dipentaerythritol penta (or hexa) acrylate, trimethylolpropane triacrylate , Neopentyl glycol hydroxypivalate diacrylate, 1,4-butanediol diacrylate, 2-propenoic acid [2-
[1,1-dimethyl-2-[(1-oxo-2-propenyl) oxy] ethyl] -5-ethyl-1,3-dioxan-5-yl] methyl ester, 1,6-hexanediol diacrylate, Pentaerythritol triacrylate, dimethylolpropane diacrylate, triallyl (or iso) tricyanurate, triallyl triacrylate, tetramethylol methane tetraacrylate, neopentyl glycol diacrylate, di (or tetra) ethylene diacrylate, bis (4-
(Acryloxypolyethoxyphenyl) propane, 1,5
-Pentanediol diacrylate, tetramethylol methane triacrylate and the like can be used.

Compounds containing two or more methacryloyl groups in one molecule include, for example, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1,3-butylene glycol dimethacrylate, and trimethylol. Propane trimethacrylate allyl methacrylate, 1,6-hexanediol dimethacrylate, trimethylolethane trimethacrylate, dipropylene glycol dimethacrylate, 2,2-bis (4
-Methacryloxydiethoxyphenol) propane, neopentyl glycol dimethacrylate, diethylene glycol dimethacrylate, ethylene dimethacrylate,
Examples thereof include 1,3-butylene methacrylate and 1,4-butylene methacrylate.

Compounds containing two or more itaconoyl groups in one molecule include, for example, pentaerythritol ditriitacolate (a mixture of two or three itaconoyl groups), dipentaerythritol itacolate (itaconoyl) Radix 3, 4, 5, 6
A mixture of individual products).

In the present invention, a crosslinking accelerator, an inorganic filler such as calcined clay, silica, metal oxide, carbon black, oil, and the like can be appropriately blended in addition to the rubber material described above.

In the medical rubber stopper 10, a film of a synthetic resin that does not contaminate the medicine, such as a fluorine-based synthetic resin or polyethylene, is laminated on the surface of a portion that may come into contact with the medicine, such as the stopper leg 2. It is also possible to prevent the contamination of pharmaceuticals by the eluate of the drug.

The fluororesin film to be laminated is, for example, a copolymer of tetrafluoroethylene-ethylene copolymer (ETFE), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), or tetrafluoroethylene-perfluoroalkylvinyl ether. Polymer (PFA), chlorotrifluoroethylene-ethylene copolymer (ECTPE), polyvinyl fluoride (PVF), polyvinylidene fluoride (PVD)
F), polychlorotrifluoroethylene (PCTF
E), polytetrafluoroethylene (PTFE) and the like.

The thickness of the fluororesin film used for lamination is preferably 0.01 to 0.2 mm,
If it is less than 1 mm, it may be damaged during processing and the product warranty may be insufficient. On the other hand, if it exceeds 0.2 mm, the rigidity is too strong and the self-sealing property and the needle sticking property are inappropriate.

Further, it is possible to provide a nylon film layer on the surface of the portion of the medical rubber stopper 10 which may come into contact with the medicine. The nylon film layer
Nylon 6, Nylon 66, Nylon 610, Nylon 621, Nylon 11, Nylon 12, Copolymer Nylon, Monomer Casting Nylon, Nylon MX
D and nylon 46 made of a nylon resin containing at least one of the components can be used. The thickness of the nylon film layer can be set to 20 to 200 μm. The nylon film layer can be coated with polyvinylidene chloride (PVDC).

The medical rubber stopper 10 having the structure shown in FIG. 1 is provided with various thicknesses of nylon film layers on the top surface thereof.
The air permeation index and the water permeation index were measured. Polyisoprene rubber was used as a rubber material for the medical rubber stopper 10. A medical rubber stopper not provided with the nylon film layer 6 on the top surface is Comparative Example 1, and a medical rubber stopper provided with the nylon film layer 6 having a thickness of 15 μm on the top surface is Comparative Example 2.
A medical rubber stopper having a nylon film layer 6 having a thickness of 50 μm provided on the top surface thereof is referred to as Example 1.
A medical rubber stopper provided with a 0 μm nylon film layer 6 was referred to as Example 2, and a medical rubber stopper provided with a 50 μm-thick ETFE film layer on a top surface was referred to as Comparative Example 3. Note that E
The TFE film is an ethylene / tetrafluoroethylene film.

The air permeation index is based on JIS K 7126.
It was determined by conducting an air permeability test according to Method A. JIS
The K7126 A method is a differential pressure method in which a test is performed using a gas permeability measuring device. The gas permeability measuring device includes a permeation cell for allowing gas to pass through the test piece, a pressure detector for detecting a pressure change caused by the permeated gas, a test gas supply device for supplying gas to the permeation cell, and a cell volume variable device. , A vacuum pump and the like.

The transmission cell has an upper part and a lower part.
When a test piece is attached to this, the transmission area becomes constant. The upper cell has an inlet for the test gas, and the lower cell is connected to a pressure detector. The specimen adhesion surface is
Smooth, flat ones were used to prevent leaks. The diameter of the transmission surface was 10 to 150 mm. The pressure detector used was capable of measuring a pressure change on the low pressure side with an accuracy of 5 Pa or less. For pressure detection, a vacuum gauge using mercury, other manometers, a diaphragm type electronic center, and the like can be used. When using a pressure detector using mercury, mercury can be used after being distilled up to three times,
It was constantly checked for dirt and, if necessary, replaced with a new one. The test gas supply device is a tank for storing the test gas, and supplies the gas to the high-pressure side cell from here. In order to measure the pressure in the tank, a pressure gauge having an accuracy of 100 Pa or less and having a capacity capable of preventing the pressure on the high pressure side from being reduced by permeation was used.
In addition, in order to extend the measurement range of the transmittance, it is also possible to use a cell capacity variable device such as an increasing tank or a cell adapter to adjust the volume on the low pressure side. The test gas used had a purity defined by Japanese Industrial Standards. As the vacuum pump, a vacuum pump capable of repelling the inside of the measurement system to a pressure of 10 Pa or less was used.

The operating method was as described below. That is, a filter paper having the same size as the transmission area is laid in the lower cell. Vacuum grease was applied thinly on the test piece mounting surface, and the test piece was mounted on the surface so as not to cause wrinkles and sagging.
A packing was set on the test piece and fixed with a uniform pressure so as not to cause air leakage. Activate the vacuum pump,
First, the low pressure side and then the high temperature side were evacuated. Care must be taken because the evacuation time varies depending on the type of test piece and the method of condition adjustment. Then, the exhaust on the low pressure side was stopped to maintain the vacuum. The pressure for baking the test gas to the high pressure side is introduced. At this time, the pressure Pu on the high pressure side is recorded. The pressure on the low pressure side starts to rise, and permeation is confirmed. A transmission curve is drawn, and measurement is continued until a linear portion indicating a steady state of transmission is confirmed. (D _p / d _t ) was determined from the slope of the linear portion of the transmission curve, and the gas permeability GTR was determined from Equation 1 shown below.

[0091]

(Equation 1)

GTR (mol / m ² · s · Pa)
Is the gas permeability, V _c (l) is the low pressure side volume, and T (K)
Is the test temperature, _Pu (Pa) is the differential pressure of the supplied gas, A
(M ² ) is the transmission area, and (d _p / d _t ) is the unit time (s)
Is the pressure change (Pa) on the low pressure side at
10 ³ (l · Pa / K · mol).

The gas permeability coefficient P (mol · m / m ²⁾
.S · Pa) can be calculated from Equation 2 shown below.

[0094]

(Equation 2)

Note that d (m) is the thickness of the test piece. The air permeation index is determined by comparing the gas permeability according to Comparative Example 1 with a reference value of 10.
The gas permeability according to Comparative Example 2, Comparative Example 3, Example 1, and Example 2 was determined as a relative ratio as 0. The air permeation index is shown in Table 1.

Next, the water permeation index is calculated according to JIS Z 0
It was determined by performing a moisture permeability test according to Method 208B. Moisture permeability refers to the amount of water vapor that passes through a unit area of a film material in a certain time, and in this standard, the temperature is 25 ° C or 40 ° C.
When the moisture-proof packaging material is used as a boundary surface, the air on one side is kept at a relative humidity of 90%, and the air on the other side is kept dry by a hygroscopic material, the mass of water vapor passing through this boundary in 24 hours (g) ) Is converted per 1 m ² of the material is referred to as the moisture permeability of the material.

The moisture permeable cup was used under the following conditions. That is, the moisture permeable area was set to 25 cm ² or more, and the moisture permeable area could be clearly defined. The moisture permeable area was calculated from the inner diameter of the ring. The material was impermeable to water vapor and did not corrode under the test conditions. In addition, it had sufficient rigidity to prevent deformation during operation. The periphery of the test piece was completely sealed.

The thermo-hygrostat was a device in which air maintained at a specified temperature and humidity could circulate on the test specimen at a speed of 0.5 to 2.5 m / s. The temperature and humidity conditions under which the test was performed were a temperature of 40 ± 0.5 ° C. and a relative humidity of 90 ± 2%.

[0099] For a chemical balance, the mass of the cup was 0.1 mg.
It was able to weigh up to. The hygroscopic material used was calcium chloride, and the particle size passed JIS Z 8801 nominal size of 2380 μm and remained at 590 μm.

[0100] A wax sealing agent satisfying the following conditions was used. That is, the test piece and the inner edge of the cup did not easily peel off, and the sealing operation was easy. In addition, at room temperature, it is not brittle, has no water supply or hygroscopicity, and has no fear of oxidation. The wax sealant was exposed under the above-mentioned temperature and humidity conditions, did not undergo softening deformation, and had a mass change of 1 mg or more in 24 hours when the exposed surface area was 50 cm ² . The test piece was a circular one having a diameter about 10 mm larger than the inner diameter of the cup to be used, and three or more test pieces were cut out from the same sample and used for the test.

The test operation was performed according to the following procedure. After the cup was cleanly dried, it was warmed to about 30-40 ° C. The dish containing the hygroscopic agent was placed in a cup and placed on a cup table which was kept horizontal. At this time, the surface of the desiccant was made as flat as possible so that the distance from the lower surface of the test piece was about 3 mm. Next, the test piece was placed at a position concentric with the cup. The guide was covered over the cup stand.
The ring was pushed in until the test piece adhered to the upper edge of the cup according to the guide, and the weight was placed on it. The guide was pulled up vertically and removed, taking care not to move the ring. While rotating the cup horizontally, the molten sealing agent was poured into the groove of the periphery of the cup, and the edge of the test piece was sealed. After the wax sealant was solidified, the weight and the cup base were removed, and the wax sealant adhering to portions other than the sealing portion was removed by cleaning with a cloth soaked with a suitable solvent to obtain a test specimen. The test specimen was placed in a thermo-hygrostat kept under the test conditions described above. After placing the specimen in a thermo-hygrostat for 16 hours or more, it was taken out, equilibrated to room temperature, and its mass was measured with a chemical balance. The test body was placed again in a thermo-hygrostat, the cup was taken out at appropriate time intervals, and the operation of weighing was repeated to measure the increase in mass of the cup. The mass increase per unit time was determined for each of the two successive weighings at this time, and the test was continued until the increase was constant within 5%.

The moisture permeability was calculated by the following equation (3).

[0103]

(Equation 3)

Note that s (cm ² ) is a moisture permeable area, and t (h)
Is the sum of the times of the last two weighing intervals in which the test was performed, and m (mg) is the sum of the increased masses of the last two weighing intervals in which the test was performed.

The moisture permeation index was determined using Comparative Example 2, Comparative Example 3, Example 1, and the moisture permeability according to Comparative Example 1 as a reference value of 100.
The moisture permeability according to Example 2 was determined as a relative ratio. The moisture permeability index is shown in Table 1.

Next, Example 1, Example 2, Comparative Example 1,
The rubber plug moldability of each of the medical rubber plugs 10 of Comparative Examples 2 and 3 was observed. Here, the rubber plug moldability refers to the finished state of the top surface of the medical rubber plug 10,
Good shape is indicated by a circle as a result of the finished state. On the other hand, when the nylon film of the nylon film layer 6 was torn or wrinkles occurred in the nylon film of the nylon film layer 6, it was indicated by x. The results of the rubber plug moldability are shown in Table 1.

[0107]

[Table 1]

The medical rubber stopper according to the present invention has a considerably low air permeation index, and can prevent air from passing through the medical rubber stopper and reaching the medicine in the medicine container.
As a result, it is possible to prevent the medicine in the medicine container from being brought into contact with oxygen in the air to cause a change in quality due to an oxidation reaction. Further, the medical rubber stopper according to the present invention has a considerably low water permeability index, and can prevent water from passing through the medical rubber stopper and reaching the medicine in the medicine container.
Further, the medical rubber stopper according to the present invention was able to provide a nylon film layer with good shape on the top surface.

On the other hand, in the medical rubber stopper according to Comparative Example 2, although the air permeability index could be suppressed to a predetermined value, it was difficult to provide a nylon film layer with good shape on the top surface. Further, the medical rubber stopper according to Comparative Example 1 did not show satisfactory values in both the air permeation index and the water permeation index. When compared with the medical rubber stopper according to Comparative Example 1, the medical rubber stopper according to Comparative Example 3 showed a low value in both the air permeation index and the moisture permeation index. It did not show satisfactory values in both of the transmission indices.

It should be understood that the embodiments disclosed herein are illustrative in all aspects and not restrictive. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

[0111]

EFFECT OF THE INVENTION The mechanical transportability during the production of pharmaceuticals is ensured,
Prevents the adhesion between the top surface of the rubber stopper and the pressing plate of the freeze-drying shelf, prevents the occurrence of needle stick fragments when puncturing the injection needle, and further allows air and moisture inside the medical container to pass through the medical rubber stopper. It was able to sufficiently prevent intrusion into. Thus, it offers unprecedented benefits in advanced hygiene products such as infusion devices, syringes, dialysis machines and drug containers.

[Brief description of the drawings]

FIG. 1 is a schematic sectional view illustrating a medical rubber stopper according to the present invention.

FIG. 2 is a schematic cross-sectional view showing a state where an opening of a medical container is sealed with a medical rubber stopper according to the present invention.

FIG. 3 is a schematic cross-sectional view showing a state in which a medical drug solution filled in a medical container is subjected to concentration drying or freeze vacuum drying in a sterilized state using a medical rubber stopper.

FIG. 4 is a schematic sectional view illustrating a medical rubber stopper according to the present invention.

[Explanation of symbols]

1 Top plate, 1b flange, 2 plug legs, 3 puncture,
4 container, 4b opening, 5 cap, 6 film, 7 notch, 10 medical rubber stopper.

Claims (4)

[Claims] 1. A medical rubber stopper which is applied to a mouth portion of a medical container and has a puncture portion which can puncture an injection needle of a syringe, wherein a thickness of the medical rubber stopper is 20 to 200 μm
A medical rubber stopper provided with a nylon film layer. 2. The nylon film layer comprises nylon 6, nylon 66, nylon 610, nylon 621,
2. A nylon film layer formed of a nylon resin containing at least one of nylon 11, nylon 12, copolymer nylon, monomer casting nylon, nylon MXD and nylon 46.
The medical rubber stopper according to the above. 3. The medical rubber stopper according to claim 1, wherein the nylon film layer contains a filler. 4. The medical rubber stopper according to claim 1, wherein the nylon film layer is coated with polyvinylidene chloride (PVDC).