JPH0645206B2 - Manufacturing method of plastic container stopper for pharmaceutical products - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of use] The present invention relates to a method for producing a stopper applied to the mouth of a plastic container for pharmaceuticals, and according to the present invention, the 11th revision Japanese Pharmacopoeia It is possible to efficiently provide a high quality, highly safe and highly practical stopper that complies with or complies with the standards of the infusion liquid plastic container test method and the infusion rubber plug test method.

[Prior Art] Although glass containers are widely used at present as liquid medicine containers and the like, due to the drawbacks such as damage during transportation and large transportation weight, a plastic container that is hard to break and is lightweight has been used. The container body and its stopper are being actively researched.

Of these, many studies have already been reported on the sealing method and the drug collecting method for the stopper. For example, a plug body obtained by injection-molding a rubber material in a mold, and then injection-molding a plastic to completely seal the rubber, its manufacturing method (Japanese Patent Publication Nos. 61-30583 and 61-49980), and a partition wall. (Japanese Patent Application Laid-Open No. 61-23
No. 2851). Further, the shape of the plastic diaphragm on the liquid contact surface has been devised so that the fitting with the rubber stopper has been improved (Japanese Utility Model Publication No. Sho 58-41964), the rubber stopper has an H-shaped cross section, and the partition wall and the rubber. A stopper having a void on its lower surface (Japanese Utility Model Laid-Open No. 59-169835), others such as Japanese Utility Model Laid-Open Nos. 56-116042, 57-74049 and 57.
-93337, 60-163933, 61-240
56, there are stoppers and the like described in each publication.

In all of these conventional techniques, a rubber stopper is used as a self-sealing member at the time of drug collection or after a needle is inserted, and the stopper body and the liquid contact portion are made of plastic.

FIG. 5 is a cross-sectional view showing the basic structure of a conventionally used stopper, which includes a leg portion 51 and a diaphragm 52 welded to the mouth of the container.
And a rubber stopper 1 and an outer stopper 54. The inner plug 53 and the outer plug 54 are separately manufactured by injection molding of plastic, and the rubber plug 1 is separately manufactured by cross-linking molding, and these are manufactured in combination.
The inner plug 53 acts as a welded portion with the container mouth, and the diaphragm 52
Thus, the hermeticity of the container is ensured, and it has a function of supporting the rubber stopper 1 and separates the chemical liquid from the rubber stopper.

Further, in place of the relatively thick diaphragm of the type shown in FIG. 5, a rubber stopper covered with a plastic thin film is pushed into a plastic inner wax, and a thermoplastic resin is injected to the outer periphery of the inner wax and the rubber stopper. Body (Actually 55-59640, 57
-45932 publications) are also known.

[Problems to be Solved by the Invention] As the most important requirements for pharmaceutical containers,
The quality retention of the drug solution during the storage period after manufacturing until use, the ease of operation when using the drug solution, the safety, the price, and the like are included.

The glass vials that are in widespread use today have been well studied in their long history and have solved the above requirements. On the other hand, the plastic container is a technology that has been recently developed and is in the process of improvement, so the basic requirement, that is, the sealing property during the storage period, has been solved, but the operability and safety during use are not The reality is that it has not been resolved yet.

In the conventional product whose basic structure is shown in FIG. 5, first of all, when the needle pierces the stopper during drug solution collection or mixed injection operation,
Due to its considerable thickness and hardness, the plastic diaphragm between the drug solution and the rubber stopper is crushed and drops into the drug solution in the container, which causes the contamination of fine particles and coarse particles. Diaphragm 52 of inner plug 53 manufactured by injection molding
It must be said that it is extremely difficult to reduce the thickness to, for example, about 300 μm or less at the current technical level.

The second problem is that the plastic diaphragm 52 and the rubber stopper 1
Is not fused (or welded) and has a space 55,
For example, the chemical solution may enter through the holes of the diaphragm 52 that are formed during the piercing and come into contact with the rubber stopper 1. There is no problem as long as the quality of the rubber stopper 1 passes the infusion rubber stopper test of the 11th revised pharmacopoeia, but unfortunately most of them are unsuitable, and the deposit from the rubber stopper 1 is the chemical liquid. There is a risk of polluting. In addition, since the space 55 is present, it is very difficult to clean or sterilize the site, which may lead to contamination of the chemical liquid derived from fine particles or bacteria. It is only necessary to have the space 55, but it is very difficult to bond the cross-linked molded rubber plug 1 to the plastic diaphragm 52 without using an adhesive.

55-59640, 56-47654, 57
In the plug body described in each of the above-cited patents, the above first problem is solved by covering the top and bottom of the rubber plug with a plastic thin film to eliminate the diaphragm. However, since it is difficult to bond the rubber and the plastic as described above, the upper and lower plastic thin films are integrated with the plastic on the outer peripheral portion of the plug body, and the rubber plug itself is not bonded or tightly bonded to the plastic. In other words, the second problem remains unsolved, and in the case where the top and bottom surfaces of the rubber stopper are provided with an uneven portion, the plastic thin film shape must be adapted to this, and in addition to difficulty, More likely to create space.

Therefore, the present inventors have decided to eliminate the plastic diaphragm,
Or, in addition to making it extremely thin, overcoming the above-mentioned problems by solving the problem that the plastic plug portion and the rubber plug laminated with the plastic film are fused without an adhesive. , The purpose of the present invention is to provide a stopper for a plastic container for pharmaceuticals, which secures the sealing property during storage, the ease of needle sticking during use, and the safety, and to proceed with the research, and is shown in Fig. 1 (F). As described above, the rubber plug 1 is tightly bonded to the plastic cap body and the laminate film 2 of the fusible plastic film. The laminate film 2 and the plastic shell 5 (the plastic part of the cap body in the present invention are The structure in which the inner wall 53 of the conventional structure shown in FIG. 5 in which the diaphragm 52 is removed and the inner wall of the main body of the plug, which is composed of the outer plug 54, are fused together has the above-mentioned object. Together with the manufacturing method Kangaetsuki and may be made, already filed as Japanese Patent Application No. Sho 63-48742.

The object of the present invention is the same as the object of the invention of Japanese Patent Application No. 63-48742 mentioned above. Among the manufacturing methods proposed in Japanese Patent Application No. 63-48742, the injection molding method is further improved to improve the safety. Another object of the present invention is to provide a method capable of more efficiently producing the plastic container stopper for pharmaceutical products at a lower cost.

[Means and Actions for Solving the Problems] In order to realize the structure shown in FIG.
The outer shell support is divided into two stages, the outer tubular part 3 and the inner tubular part 4, and formed by injection molding, and the laminated rubber plugs (1, 2) are fitted between the first and second stages of injection molding. By means of welding the outer shell 5 and the laminate film 2 at the time of the second injection molding, the assembly process of the laminated rubber plugs (1, 2) and the plastic outer shell can be omitted, and the contamination resulting from this step can be eliminated. It was found that the method is suitable as a method for producing a stopper body for medicines, since it is free from the risk of the above and does not contaminate not only when the stopper body is used but also in the manufacturing process.

That is, according to the present invention, a rubber plug having at least a part of its surface laminated with a plastic film is fitted into a plastic outer shell forming a column body to form a top surface, and the outer shell and the laminated rubber plug are formed. In the method for manufacturing a stopper for a plastic container for pharmaceuticals, in which the above is welded, the outer shell is formed by injection molding by dividing it into two stages of an outer tubular part and an inner tubular part, and by the first step injection molding. A laminated rubber stopper is fitted into the formed outer tubular portion, the inner tubular portion is formed by the subsequent second-stage injection molding to integrate the outer shell portion, and at the same time, the outer shell portion and the laminate film are welded together. A method for producing a stopper for a plastic container for pharmaceuticals.

In a particularly preferred embodiment of the present invention, first, a first lower mold is combined with a first upper mold to form a first space having an outer cylindrical portion shape, and plastic is injection-molded in the first space to form the outer cylindrical portion. After forming, a laminate rubber plug is fitted into the outer cylindrical portion in a state of being put in the molding lower mold, and subsequently, a second upper mold matching the inner surface side shape of the inner cylindrical part is combined,
A method of forming the inner tubular portion by injecting a plastic that can be welded to the laminate film into the second space of the inner tubular portion thus formed can be mentioned. Since the lower molding die is a common die, efficient production is possible.

Further, in the present invention, by forming the outer cylindrical portion and the top surface upper surface pull-top portion integrated with the cylindrical portion by injection molding of plastic, a pull-top portion 7 as shown in FIG. 2 (C) is provided. A stopper can be manufactured.

In the stopper of the present invention, the material of the outer shell may be any plastic material that can be used as a pharmaceutical container, for example, polyethylene, polypropylene, polyester, ethylene vinyl acetate resin or a resin containing a mixture thereof as a main component. And those having excellent hygiene that can withstand high-pressure steam sterilization are preferable.

As the rubber plug material, for example, natural rubber, isoprene rubber (IR), butadiene rubber (BR), styrene-butadiene rubber (SBR), isoprene-isobutylene rubber (IIR, BIIR, CIIR), etc., alone or in two or three kinds. The complex and the like can be mentioned, but a high quality one suitable for use as a drug container part is selected. In particular, when the rubber material surface is in direct contact with the chemical solution, it is necessary to use a high-quality rubber that passes various standards without any fear of contamination.

The material of the laminate film is a plastic that can be fused with the plastic of the outer shell, and it is naturally preferable that it is thinner than the conventional plastic diaphragm, and the thickness of the laminate film is 3
It is particularly preferable that it is in the range of 0 μm to 150 μm. If it is less than 30 μm, it is too thin, which is inconvenient.
If it exceeds 0 μm, a problem of crushing at the time of needle stick occurs. As such a laminate film material, a plastic of the same system as the outer shell is preferable from the viewpoint of adhesiveness, and for example, a plastic film containing polyethylene, polypropylene, polyester, ethylene vinyl acetate resin or a mixture thereof as a main component is selected. You can

[Examples] Hereinafter, the manufacturing method of the present invention will be specifically described based on Examples with reference to the drawings.

I. Laminated rubber plug (top surface) manufacturing process First, a laminated rubber plug is obtained by simultaneously performing cross-linking molding of the rubber plug and forming a laminated film.

As shown in FIG. 3 (A), the laminated film material 2'has been dug in at least a part of its surface in the middle of the upper and lower molds 8 and 9 having a rubber plug-shaped dug. A crosslinked rubber sheet 1'is arranged. Whether the laminated film is formed on both sides or one side can be arbitrarily selected at this stage. Next, as shown in FIG. 3B, heating and pressurization are performed to simultaneously perform cross-linking molding on the rubber plug 1 and formation of the laminate film 2 on the surface. General conditions at this time are, for example, a temperature at pressurization of 140 to 170 ° C. and a pressure of 50 to 100 kg / c.
m ² , time 7-14 minutes. This is the same figure
Since laminated rubber plugs (1, 2) continuous in a sheet shape as shown in (C) can be obtained, only the dug portion is punched out by the upper blade 15 and the lower blade 16 as shown in FIG. And remove the laminated rubber stoppers (1, 2) shown in Fig. (E).
To get This is washed by a known technique to clean the surface of the rubber stopper.

II. Assembly process by injection molding A molding lower die (common lower die) 10 having a digging corresponding to the outer surface shape of the outer shell portion and a convex first upper die 11 corresponding to the inner surface shape of the outer tubular portion of the outer shell portion are combined. The mold is clamped [FIG. 1 (A)], and the resin for the outer tubular portion is injected into the first space 12 formed by the common lower mold 10 and the first upper mold 11. The general conditions at this time are, for example, an injection temperature of 200 ° C for polypropylene, 180 ° C for polyethylene, and an injection pressure of 200.
Examples include kg / cm ² . After completion of molding, the mold is opened and only the first upper mold 11 is removed [(B) in the same figure]. The laminated rubber plugs (1, 2) prepared in step I are fitted into the molded outer tubular portion 3 in the common lower mold 10 [FIG. (C)]. Next, the convex second upper mold 13 corresponding to the inner surface shape of the inner tubular portion is combined and the mold is clamped [FIG. (D)], and the first lower mold 13 formed by the common lower mold 10 and the second upper mold 13 is joined. The resin for the inner tubular portion is injection-molded into the space 2 [(E)] At the time of this injection molding, the outer tubular portion 3, the inner tubular portion 4 and the rubber plug laminate film 2 are formed.
Are welded and integrated to obtain the plug body of the present invention [FIG. (F)]. Reference numeral 6 indicates a laminate welded portion.

2 (A) to (C) show another embodiment of the present invention, in which a lower mold 10 'having a dug-down for the top surface upper surface pull-up portion following the outer tubular portion is used. At the same time as the injection molding of the outer tubular portion 3, the pull top portion 7 is also molded on the upper surface of the top surface portion [FIG. 2 (A)]. The following molding procedure is the same as that described in the method of FIG. 1, and the portions having common reference numerals mean the same as in FIG. 1 [FIG. (B)]. As a result, the plug body of the present invention having the pull-top portion 7 as shown in FIG.

FIG. 4 is a view showing a state in which the stopper of the present invention is applied to the drug container 17 and is fused to the mouth of the container 17 by the legs of the outer shell 5.

[Effects of the Invention] As described above, according to the present invention, the chemical liquid is not contaminated by plastic fragments during use, and there is a problem in the quality of the rubber stopper, or the space between the rubber stopper and the plastic partition wall. If there is fine particle foreign matter or bacterial contamination in the space due to the presence of the drug, there is a possibility that the drug solution will be contaminated with the drug solution needle, but this can be prevented by adhesively laminating the rubber stopper with a plastic film. it can. Therefore, it is possible to inject the drug into the human body with high quality at the time of its production, so that it is very safe, and even if it is applied to a plastic container, its sealing property, easiness of needle stick, and safety are guaranteed. In addition, it is possible to realize a high-quality plastic container stopper for pharmaceuticals that is lightweight and hard to break easily and can be mass-produced.

Further, according to the present invention, if a material that can be welded to each other is selected as the plastic for the inner tubular portion of the outer tubular portion, the material, coloring, etc. can be changed, so that a product suitable for the application can be manufactured. There is an advantage.

Furthermore, in the manufacturing method of the present invention, since the inner tubular portion is injection-molded after inserting and fitting the laminated rubber stopper into the outer tubular portion, the risk of displacement of the laminated rubber stopper during injection is reduced, and the yield is also increased. It became good.

[Brief description of drawings]

1 (A) to (F) are sectional views showing an embodiment of the present invention in the order of steps, and FIGS. 2 (A) to (C) are sectional views showing another embodiment of the present invention in the order of steps, and FIG. Figures (A) to (E) are drawings for explaining the procedure for producing a laminated rubber stopper according to the present invention, FIG. 4 is a cross-sectional view showing an example in which a stopper is applied to a mouth part of a drug container, and FIG. FIG. In the figure, 1 is a rubber plug, 2 is a laminate film, 3 is an outer tubular portion, 4 is an inner tubular portion, 5 is an outer portion formed by the above 3, 4;
6 is a laminate welding part, 7 is a pull top part, 8 is an upper mold, 9 is a lower mold, 10 is a lower molding mold (common lower mold), 11 is a first upper mold, 12 is a first space, 13 is a first mold. 2 upper mold | type, 14 shows a 2nd space.

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Claims (3)

[Claims] 1. A rubber plug having at least a part of a surface laminated with a plastic film is fitted into a plastic outer shell forming a plug body to form a top surface, and the outer shell and the laminated rubber plug. In the method for manufacturing a stopper for a plastic container for pharmaceuticals, in which the above is welded, the outer shell is formed by injection molding by dividing it into two stages of an outer tubular part and an inner tubular part, and by the first step injection molding. A laminated rubber stopper is fitted into the formed outer tubular portion, and the inner tubular portion is formed by subsequent injection molding of the second step to integrate the outer portion and at the same time, the outer portion and the laminate film are welded. A method of manufacturing a stopper for a plastic container for pharmaceuticals. 2. A first lower mold is combined with a first upper mold to form a first space having an outer cylindrical portion shape, and plastic is injection-molded in the first space to form an outer cylindrical portion. A laminated rubber plug is fitted into the outer tubular portion that is placed in the lower molding die, and then a second upper die that matches the inner surface side shape of the inner tubular portion is combined, and the inner side formed by this The manufacturing method according to claim 1, wherein the inner tubular portion is formed by injection-molding a plastic that can be welded to the laminated film of the rubber stopper in the tubular portion-shaped second space. 3. The top cylindrical upper surface pull-top portion integrated with the outer tubular portion together with the outer tubular portion is formed by injection molding of plastic (1) or (2).
The manufacturing method described in.