JPH0550386B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for manufacturing a rubber stopper for a vial for preparing and enclosing a pharmaceutical for injection.

[Conventional technology]

Conventionally, rubber stoppers for vials contain vulcanization accelerators and other compounding agents, so pharmaceutical products using such rubber stoppers are free from these substances during the manufacturing process and storage. This has become a problem as it may increase the amount of fine particles in the product.

To solve this problem, we used fluorine-based resin laminate on the entire leg of the vial as a rubber stopper.
A method has been proposed in which a rubber stopper is used to prevent impurities from leaching into the drug solution by avoiding direct contact between the rubber of the rubber stopper leg and the drug solution. (Jitsukai 58-
Publication No. 29939, Japanese Patent Publication No. 1983-9119, Japanese Patent Publication No. 1983
−5046 Publication, Special Publication No. 52-1355, Actual Publication No. 1977-
No. 27753, Jitko No. 45-17831, Jitko No. 49-21346
Publication No. ) As a method for manufacturing such a rubber stopper, the present applicant proposed a method for manufacturing a laminated rubber stopper by two-step molding as shown in FIG. 3 (Japanese Patent Publication No. 57-53184).

That is, a resin film 4 and an unvulcanized rubber sheet 5 are placed in a lower mold 2 having a molding recess 3 for a bottle mouth insertion portion, and the resin film 4 has a shape larger than the outer diameter of the finished product and is resistant to the medicine or medicinal drug to be packaged. The polymer is sequentially polymerized and heated and pressurized with the lower mold and the upper mold 1 to form an element whose lower surface is covered with a resin layer and whose upper surface is a rubber surface. The finished product is cut to at most 2/3 width or less to form a blank plug (first stage), and then an unvulcanized rubber sheet 11 is polymerized on the top surface of the blank plug loaded in the lower mold. death,
A laminated rubber stopper formed by heating and pressurizing and molding a finished product (second stage) with an upper mold having an enlarged head molding recess 12 having the same diameter as the outer diameter of the upper end contact surface of the finished product. This is a manufacturing method.

[Problem that the invention seeks to solve]

However, recently, in order to improve the quality of pharmaceuticals such as cephalosporin, it has become necessary to maintain the airtightness of the vial for a longer period of time than before. Therefore, the inventors of the present invention have studied this point and have met this requirement by forming a portion that is not laminated coated, that is, a bare rubber surface, on the peripheral edge 2 of the leg base of the laminated rubber stopper A as shown in FIG. (Utility Application No. 59-116191)

The manufacture of such a rubber stopper is carried out by the above-mentioned method of manufacturing the known laminated rubber stopper of the present inventors.
This can be achieved by cutting the upper end contacting surface of the bottle opening of the base body in the first step to at most 2/3 of the width of the finished product or less.

[Means for solving problems]

As a result of various studies on the cutting operation in the production of the above-mentioned known laminated rubber stoppers, the present invention has been developed by making the depth of the outer recess of the lower mold in the second stage deeper than that of the lower mold in the first stage. Next, a rubber plate that is not laminated is brought into contact with the upper part of the leg of the molded product, thereby making the base of the leg bare rubber. By employing this means, products can be mass-produced more efficiently than in the above-mentioned known method disclosed in Japanese Patent Publication No. 57-53184. Furthermore, in the present invention, when the top of the first molded product is trapezoidal, the leg base and the top surface formed on the top can be firmly bonded and integrated with the first molded product.

[Structure, operation, and embodiments of the invention]

The present invention consists of (i) a leg first mold 2 having a W-shaped concave portion 3 whose outer shape conforms to the shape of the leg;
and a top first mold 1 having a trapezoidal recess 4 or having a flat plate shape, vulcanization is performed by applying pressure and heating, and a fluorine-based resin laminate is applied to the entire outer peripheral surface of the leg, Step a of obtaining a primary molded product 7 having a flat or trapezoidal portion on which no laminate is applied on the upper part;
(ii) Steps b and c of removing the burr portion 8; (iii) The primary molded product 7 thus obtained is shaped so that it conforms to the shape of the leg and the depth of the outer recess is the same as that of the leg. The unvulcanized compounded rubber plate 13 is placed on the top of the second leg mold 10 having a W-shaped recess 11 deeper than that of the first mold 2. A second top mold 9 having a recess 12 that matches the shape of the top part is pressed and heated to vulcanize the mold to form the leg base and the top part, and also to form the leg base and the top part. Step d of integrating with the primary molded product, (iv) Steps e and f of removing the burr portion 15 of the molded product 14, except that the fluorine resin laminate is not applied to the outer peripheral base of the leg. This is a method for manufacturing a rubber stopper for a vial having a bare rubber surface 16 applied only to the entire surface of the leg.

In the present invention, by adopting the above configuration, the outer surface recess 11 of the second mold is configured deeper than the recess 3 of the first leg mold, and the laminate is placed on the upper part of the first molded product 7. Since the leg base 16 and the top part, which are not covered, are integrally formed, half-stopping is possible.
Full stoppering - Rubber stoppers that can maintain airtightness for a long time until they are wrapped with aluminum can be efficiently mass-produced. When the top of the primary molded product is trapezoidal, the leg bases and the top surface formed on the top can be firmly bonded and integrated with the primary molded product.

For the unvulcanized compounded rubber plate in the present invention, a compound of synthetic rubber or natural rubber such as butyl rubber, isoprene rubber, butadiene rubber, halogenated butyl rubber, ethylene propylene terpolymer, silicone rubber, etc. is used, and the fluorine-based rubber plate to be laminated is used. The resins include tetrafluoroethylene resin, trifluorochloroethylene resin, tetrafluoroethylene-hexafluoride propylene copolymer resin, vinylidene fluoride resin, fluorovinyl resin, tetrafluoroethylene-ethylene copolymer resin, or Ethylene trifluoride chloride-ethylene copolymer resin and the like are used. The thickness of the film is
0.002 to 0.5 mm is preferred.

Embodiments of the present invention will be described based on FIGS. 1 and 2. As shown in Figures a and a', the first leg mold 2 has a W-shaped recess 3 that matches the shape of the leg. The top P of the central part of the W-shaped recess is made higher than the height of the outer periphery of the recess (FIG. 1a) or approximately the same height (FIG. 2 a'). When the top is raised, the thickness of the rubber on the top becomes thinner,
Facilitates needle stick when using injectable drugs. The first mold 1 on the top surface has a trapezoidal recess 4 or a flat plate (Fig. 2 a'), and between both molds an unvulcanized compounded rubber plate laminated with a surface-treated fluorine-based resin film on one side is placed. Place, pressurize, and heat. Through this operation, vulcanization is performed, and a fluorocarbon resin laminate is applied to the entire outer peripheral surface of the leg as shown in Figures b and b', and a trapezoidal or flat part that is not laminated is formed on the upper part. A primary molded product 7 or 6 is obtained. The pressure and heating conditions in this process vary slightly depending on the material of the fluorocarbon resin laminate plate used, the type of compounded rubber, compounding agents, thickness, etc., but it is 150℃ to 175℃, 40 to 70Kg/cm ² in
Around 10 minutes is appropriate. For example, tetrafluoroethylene-ethylene copolymer resin film and butyl rubber
For 58% compound rubber, temperature 160-165℃, pressure approximately 50℃
Vulcanization is carried out at kg/cm ² for about 15 minutes.

Next, this is taken out from the mold and the peripheral burr 8 or 7 is removed by a punching operation to obtain a primary molded product as shown in Figures c and c'.

Primary molded product 7 or 6 obtained in this way
As shown in FIGS. d and d', a W-shaped recess 11 or 10 that matches the shape of the leg and whose outer recess is deeper than that of the first leg mold 2 is used. The unvulcanized compounded rubber plate 13 or 11 is placed on top of the second mold 10 or 9, and pressurized between the second top mold and the second top mold, which has a recess that matches the shape of the top surface. The heating conditions for heating and vulcanization are preferably 160°C to 175°C for about 8 minutes. At this time, the primary molded product and the top rubber plate are firmly bonded together. At this time, if the top of the center of the primary molded product is made higher than the other surfaces, the thickness of the top surface will be thinner, and when used as a product in a vial, it will be easier to insert the syringe needle into this part than with conventional products. becomes easier. Next, this is taken out from the second mold, and peripheral burrs are removed to obtain a product as shown in Figures f and f'.

In the present invention, the outer shape of the leg of the product can be changed from a simple shape as shown in FIG. 1f to a tip end as shown in FIG. It may be modified as appropriate, such as by providing a step 2 or a protrusion 3 between the portion and the base.

〔Effect of the invention〕

The method for manufacturing a laminated rubber stopper according to the present invention includes:
It is possible to economically produce irregular shaped products suitable for pharmaceutical formulations. In other words, the base of the rubber stopper foot is made of bare rubber and has excellent fitting and sealing properties with the container opening, and the base of the foot is thick, the top surface of the rubber is thin, and the base of the foot is made of bare rubber. It is possible to efficiently manufacture irregularly shaped products such as those provided with protrusions.

To use the laminated rubber stopper for a vial manufactured by the method of the present invention, as shown in FIG. 5, the rubber stopper A is partially plugged into the mouth of a vial bottle B. This half-stoppered vial is placed in a freeze-drying chamber and freeze-dried.
All bottles are capped in the same storage (Fig. 6). As shown in FIG. 7, the outer periphery of the top surface and vial neck is wrapped with an aluminum cap C to obtain a product.

According to the method of the present invention, it is possible to efficiently mass-produce products that are free from foreign matter and maintain extremely good airtightness for a long period of time.

[Brief explanation of the drawing]

Figures 1 and 2 are process diagrams showing the method of manufacturing the rubber stopper for vials of the present invention, Figure 3 is a process diagram of the conventional method of manufacturing rubber stoppers for vials, and Figure 4 is a process diagram showing the method of manufacturing the rubber stopper for vials of the present invention. 5 is a longitudinal sectional view showing a partially capped state of the rubber stopper for a vial thus obtained, FIG. 6 is a longitudinal sectional view showing a fully capped state, and FIG. 7 is a longitudinal sectional view showing a fully capped state.
The figure is a longitudinal sectional view showing a state in which the winding is completed.

Claims (1)

[Claims] 1 (i) An unvulcanized compound rubber plate laminated with fluorocarbon resin on one side is molded into a first leg mold with a W-shaped recess whose outer shape matches the shape of the leg, and a truncated cone-shaped recess. Vulcanization is performed by hot pressing between the top mold and the first mold, which has a flat top surface, and a fluorine-based resin laminate is applied to the entire outer circumferential surface of the legs, and a trapezoidal part that is not laminated is applied to the upper part. or a step of obtaining a primary molded product having a flat portion, (ii) a step of removing the burr portion, (iii) a step of obtaining the primary molded product thus obtained,
The unvulcanized compounded rubber is placed in a second leg mold that has a W-shaped recess that matches the shape of the leg and whose outer recess is deeper than that of the first leg mold. The plate is placed, and this is used as the second leg mold, and is pressurized and heated to be vulcanized between the second top mold and the second top mold, which has a recess that matches the shape of the top, to form the leg base. A fluorine-based resin laminate is applied to the outer circumferential base of the leg, which comprises a step of forming a top surface portion and a top surface portion and integrating these with the primary molded product, and (vi) a step of removing burrs from the molded product. A manufacturing method for rubber stoppers for vials that are applied only to the entire surface of the legs.