JPH07323072A - Laminated rubber plug for medicine - Google Patents

Abstract

PURPOSE:To shorten a process of closing containers by laminating a surface contacting medicines with a synthetic resin body nonpolluting the medicines and arranging a skirt part in which a top rubber covering the upper rim of a container mouth part extends to the external side of the container to improve sealing property, hygienic performance, needling property and the like. CONSTITUTION:A surface contacting a drug 3 of a rubber plug 1 is covered with a synthetic resin film 7 nonpolluting a medicine, a top part 5 and a skirt part 6 are made of rubber to wrap a port 9 of a container firmly together to the external wall surface of the container from the top surface part and a flange 10 at the port of the container is rolled and tightened with a jaw part 8 formed at the final end of the skirt part. The synthetic resin body herein used is preferably one or more selected from among ultrahigh-molecular weight polyethylene, polypropylene, polycarbonate, a polyester, polymethylpentene, a fluororesin, an olefin based thermoplastic elastomer or a polymer consisting of a cyclic olefin compound or a cross-linked polycyclic hydrocarbon compound as a polymer component.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a laminated rubber stopper for pharmaceuticals suitable for use as a sealing member for a pharmaceutical container and a syringe / container. Glass products have been used as medicine containers for a long time, but recently they are light and fragile, convenient to transport and handle, and easy to incinerate after use. Many instruments are used, and there is a demand for something that is even easier to operate. The present invention relates to a novel laminated rubber stopper for pharmaceuticals which is used in a container that can meet such demands.

[0002]

2. Description of the Related Art For rubber stoppers for pharmaceuticals, maintaining the quality of the pharmaceuticals together with the main body of the pharmaceuticals is the most important requirement, and the next important requirement is hygienic and easy to use the pharmaceuticals. It is required that the drug can be used or administered. Therefore, the rubber stopper used for this purpose is required to hermetically retain the drug in the container, guarantee the quality without contaminating the retained drug, and be suitable for needle stick at the time of administration. There is. At present, for drug containers and vials, a rubber stopper is capped on the container mouth, and the outer ring thereof is wound with an aluminum cap, or a synthetic resin cap is wound on the rubber stopper. That is, a two-step operation of capping a rubber plug and tightening a cap is used.

[0003]

It is well known that a substance exhibiting rubber elasticity is the most suitable as a sealing material used for containers and is most often used in reality. Substances that exhibit rubber elasticity even in pharmaceutical containers and vials,
That is, a rubber vulcanizate and / or a rubber stopper made of a thermoplastic elastomer is stoppered, and the rubber stopper and the container opening are tightly closed by sealing with an aluminum cap to preserve the contents and guarantee the quality, as well as air leakage. Is preventing. The rubber stopper is also used for the purpose of safely administering a prescribed amount of the drug in the container (medicine-prepared drug, tablet, injectable drug, etc. in a form ready for immediate use) to the human body. The requirement of being suitable is also required, and physical properties, chemical properties, and operability are very important. An object of the present invention is to provide an economical laminated rubber stopper for pharmaceuticals, which has good sealing property, hygiene property, needle stick property, and the like, and in which the container sealing step can be performed more easily than before.

[0004]

Means for Solving the Problems As a means for solving the above problems, the present invention provides a rubber stopper applied to a container mouth, in which a surface contacting a drug is laminated with a synthetic resin body which does not contaminate the drug. A laminated rubber stopper for pharmaceuticals is characterized in that the top rubber covering the upper edge of the container mouth has a skirt portion extending from the container mouth to the outer surface of the container. As a particularly preferred embodiment of the present invention, the inner surface of the skirt portion is engaged with a protrusion or recess at the edge of the container, and further, the skirt portion has a jaw portion projecting inward at the end, The jaw portion is formed by engaging with a protrusion at the rim of the container, and further has a leg portion into which the rubber stopper is fitted in the container, and the surface of the leg portion contacting the medicine is the medicine. A synthetic resin body that does not contaminate is laminated and has a protrusion of a rubber element surface at its base, and the edge portion of the container is compressed by the protrusion element surface and the rubber element surface on the inner surface side of the skirt to seal the container opening portion. In addition, the rubber stopper is fixed to the mouth of the container. In the present invention, the outer peripheral surface of the rubber stopper is made of a film of a synthetic resin body which is the same as or different from the synthetic resin body of the surface in contact with the drug.
It is also a particularly preferred embodiment that it is laminated and coated with at least one layer. Particularly preferred as the synthetic resin body in the present invention are ultra-high molecular weight polyethylene, polypropylene, polycarbonate, polyester, polymethylpentene, fluorine resin, olefin thermoplastic elastomer, cyclic olefin compound or crosslinked polycyclic hydrocarbon. One or more compounds selected from compounds containing a compound as a polymer component are mentioned. It is particularly preferable that the rubber stopper of the present invention has a liquid leakage pressure of 3 kgf / cm ² or more when applied to the mouth of a container.

[0005]

According to the present invention, in the conventionally used rubber stopper for vials, by extending the top rubber surface of the rubber stopper and providing the skirt portion which wraps from the container rim to the outer wall surface of the container integrally with the top surface, The skirt portion of the rubber stopper can tightly seal the edge portion of the container without using a conventional cap. Hereinafter, the laminated rubber stopper for pharmaceuticals of the present invention may also be referred to as a "skirted rubber stopper". In the rubber stopper of the present invention, the skirt portion closely adheres to the outer wall portion of the container opening, prevents the rubber stopper from separating, can seal without leaking the medicine, and has a firm protective effect similar to the conventional aluminum cap tightening. Have. Since the contact surface with the drug is coated with a synthetic resin that does not contaminate the drug, rubber does not affect the drug content. In addition, in manufacturing, only one step of filling a rubber stopper after filling the contents is required, which is very economical. As a method of manufacturing a rubber stopper with a skirt, the portion in contact with the drug (medicine) is formed by laminating a resin film on rubber or by molding only a synthetic resin body, and then the portion having the top surface and the skirt portion. Is molded with only rubber or with a resin film laminated on rubber, and at the same time, it is molded and vulcanized so as to be integrated with the above-mentioned drug contact portion. A method for producing such a rubber plug having a complicated shape and a designed portion coated with a resin is according to the method already proposed by the present inventors in JP-B-57-53184 and JP-A-61-272134. It can be easily molded by using a mold having a skirt mold.

Hereinafter, the rubber stopper with a skirt of the present invention will be specifically described with reference to the drawings. In FIG. 1, a glass container 2 is filled with a drug (medicine) 3, and a rubber stopper 1 with a skirt is inserted into a container port 9
It is sectional drawing which shows the state plugged in. The surface of the rubber stopper that comes into contact with the medicine 3 is covered with a synthetic resin film (abbreviated as resin film) 7, and the top surface portion 5 and the skirt portion 6 are made of rubber and are integrated from the top surface portion to the outer wall surface of the container. Jaw 8 tightly wrapped around the container mouth 9 and provided at the end of the skirt
Then, the flange 10 of the container mouth is wound and tightened.

FIG. 2 is a sectional view showing another embodiment of the rubber stopper with a skirt of the present invention. In FIG. 2, the plug body is made of rubber 4 and rubber 11. The synthetic resin film 7 is firmly adhered to the surface of the rubber 11 forming the leg portion which is in contact with the medicine. Further, the portion of the top surface side rubber 4 which is in contact with the inner wall surface of the container opening is provided with the annular projection 12 while keeping the rubber surface. The protrusion 12 and the skirt portion 6, and the skirt portion jaw portion 8
Since the two are integrally connected, the wall surface of the container mouth can be strongly pressed from inside and outside to be brought into close contact. Further, in this example, the outer periphery of the rubber 4 on the top surface is also laminated and coated with the synthetic resin film 13. However, the synthetic resin film 13 is of the same type as the synthetic resin film 7 coated on the portion in contact with the drug. However, different types may be used. Further, in this example, the rubber 4 is thinner in the center than the outer peripheral wall thickness. The thick outer peripheral wall improves the sealing performance, and the thin central portion facilitates needle stick and prevents the rubber pieces from dropping.

FIG. 3 is a sectional view showing still another embodiment of the rubber stopper with a skirt of the present invention. In FIG. 3, the leg side portion of the stopper body is provided with an olefinic thermoplastic elastomer 15
It is formed by. After the elastomer is injection-molded, the rubber 4 on the top surface and the skirt and the resin film 13 on the outer circumference of the rubber are laminated, and simultaneously with the vulcanization of the rubber, lamination and coating are performed to manufacture. The top surface of the rubber stopper is formed so that the injection needle sticking position 14 is thin so that there is no needle sticking accident, and as shown in FIG.
As in the case of (1), since the rubber plug can be firmly plugged and closely attached to the container mouth by the projection 12, the skirt portion 6, and the jaw 8 which are the rubber blank surface, the rubber plug does not leak or separate.

FIG. 4 shows a syringe / container 20 in which a liquid medicine 17 is filled in an injection cylinder (hereinafter abbreviated as cylinder) 16 in advance. The tip 18 of the tube is sealed with a rubber stopper 19 with a skirt of the present invention,
The skirt portion 21 and the jaw fiber 22 are firmly fixed to the wall surface of the syringe tip opening portion. The syringe and container 20
Is a cartridge injector, and a double-ended needle 23 is attached to the tip of the cylinder 16 by a connector 24. When administering the drug solution 17, the needle tip 23 of the double-ended needle 23 is used.
After penetrating the top surface of the rubber stopper 19 with a skirt at a, the push rod 25 is connected to the piston 26 in the cylinder 16 and then press-fitted into the cylinder 16, whereby the chemical liquid 17 flows through the inner hole of the double-ended needle 23, and the needle tip It flows out from 23b.

A further embodiment of a rubber stopper with a skirt of the type shown in FIG. 4 is shown in FIGS.
Since the tip projection 25 of the cylinder is thick and large, the skirt portion 21 is designed correspondingly, and the projection 25 at the tip of the cylinder is wrapped around the jaw portion. The rubber stopper 22 has a structure that prevents the rubber stopper from coming off and leaks and can firmly adhere. 26 is 2
7 is a resin film laminated on the surface in contact with the chemical solution, 28 is a protrusion, and 29 is the bottom surface of the rubber stopper in contact with the tip surface of the cylinder.
The rubber stopper with a skirt shown in FIG. 5a has a flat leg having a short surface in contact with the chemical in the cylinder, and a resin film is laminated on the rubber at the contact surface with the tip of the cylinder and the chemical contact surface. . The rubber plug with a skirt shown in FIG. 5B is provided with two protrusions 28 on the surface in contact with the chemical liquid in the cylinder, and a recess 26 is provided between the protrusions 28 (center portion), and the protrusions 28 and the recess 26 correspond to each other. The top surface of the part has a thin rubber thickness. Adhesion of the rubber plug is improved between the protrusion 28, the skirt portion and the jaw portion, and the rubber thickness is particularly reduced in the central depressed portion to facilitate needle stick. The rubber plug with skirt shown in FIG. 5c is similar to FIG. 6 in that two protrusions 28 are provided on the surface in contact with the in-cylinder drug solution and a recess is provided in the center, but the drug solution contact surface is laminated with a resin film. Since it is a rubber element surface other than the coating, the tube tip surface and the rubber element surface are in contact with each other, so that the adhesion to the tube is enhanced. Figure 5
In the rubber plug with a skirt shown in d), one annular projection 30 is formed at the base of the projection 28. The portion that comes into contact with the chemical solution is laminated and covered with the resin film 27.
The portion of 0 that contacts the inner wall surface of the cylinder is left as it is as the rubber surface. Since this plug has a rubber surface from the outer peripheral wall to the inner wall of the cylinder and is wrapped with the jaw portion 22, the skirt portion and the annular protrusion 30 and tightened, the plug has a very high adhesion and a high fixing property.

FIGS. 6A to 6C are cross-sectional views showing various embodiments of the rubber stopper 31 with a skirt of the present invention which is preferably used for a glass or plastic syringe in which the tip of the cylinder is thin and long and protrudes. . The tip of the cylinder is narrow and narrow, and in this type, the injection needle does not penetrate through the top surface of the rubber stopper when the drug solution is administered, so it is not necessary to thin the top rubber.
The rubber is laminated and covered with a synthetic resin film 27 to prevent the rubber from contaminating the chemical solution. In FIG. 6a, both the top surface portion and the skirt portion are formed of thick rubber, and an annular recess 33 is provided inside the skirt portion at a position corresponding to the protrusion of the cylinder so that the rubber stopper is firmly engaged with the cylinder. It is a rubber plug 31 with a skirt. FIG. 6b shows a rubber plug 31 with a skirt for a very long cylinder. In this example, the top surface of the cylinder and the contact portion with the chemical liquid are laminated and covered with a resin film. However, the surface of the skirt portion that contacts the outer circumference of the cylinder is a rubber bare surface, and the jaw portion is provided because this surface is very long. Can be tightly adhered and sealed without any liquid leakage. In FIG. 6c, a synthetic resin film 27 is laminated and covered from the chemical contact surface to the top surface of the cylinder and the skirt, and the skirt portion 21 has a skirt with an annular recess 33 corresponding to the protrusion of the cylinder. Rubber stopper 31
Is.

7A to 7C are cross-sectional views showing various embodiments of a rubber stopper with a skirt applicable to a wide-area type syringe with a thick barrel tip. In the case of this type, since the central portion of the rubber stopper is penetrated by the tip of the double-ended needle, it is required that the penetration is easy. Corresponding to this condition, a in FIG.
Keeps the rubber blank surface from the outer peripheral base of the long protrusion 28 that enters the inside of the tube 32 to the skirt to improve the sealing performance.
On the other hand, the surface in contact with the chemical liquid 17 is laminated and covered with a synthetic resin film 27. Further, the recesses between the protrusions 28 and the corresponding rubber plug center are thinned in order to facilitate the penetration of the needle tip 23a. Liquid leakage can be prevented by the internal pressure on the wall surface of the skirt, and the plug is not removed. 7b
Since the rubber stopper with a skirt comes into close contact with the annular projection 33 on the rubber blank surface that presses the inner wall surface of the cylinder and the cylinder wall surface of the skirt portion 21, the chemical solution 17 does not leak out. In this example, the rubber surface on the outer circumference of the plug is also laminated and covered with the synthetic resin film 34. 7c is a rubber plug similar to the above c, but by providing the annular unevenness 35 so that the inner surface of the skirt portion 21 engages with the unevenness at the tip of the plastic cylinder,
The stopper can be firmly fixed and adhered, and the drug can be sealed to prevent liquid leakage and stopper removal.

The various embodiments of the present invention described above are all capable of hermetically retaining the contents of the container, preventing liquid leakage, and particularly at about 130 ° C. in the high-pressure steam sterilization process.
It is a rubber stopper that does not leak even when heated. The present invention aims at a rubber stopper having a tightening force equivalent to the aluminum tightening force without an aluminum cap, and achieves this object by the structure of the skirt portion continuing to the top surface. A liquid leak test was performed at a pressure of 3 kgf / cm ² or more to determine whether the product passed or failed. This value is based on the fact that when a metal material is replaced with a plastic material, it is generally considered to have the same strength as the force per unit area of the plastic is 3 kgf / cm ² or more. Further, as a physical test of the rubber material of the rubber plug body, it is necessary that the tensile strength, hardness, compressive strain, heat resistance, aging resistance, etc. are within suitable ranges. Such physical properties depend on the type of rubber itself, the reinforcing agent, vulcanization accelerator, vulcanizing agent, processing aid, vulcanization conditions, etc. compounded in the rubber, but rubber compounding agents and physical properties are known. A rubber material suitable for the rubber plug with a skirt of the present invention could be obtained by appropriately applying the rubber technology of (1). In particular, the hardness of rubber is preferably 40 to 60 from the viewpoint of sealing property and liquid leakage resistance. If the hardness is higher than 60, rubber powder pieces may be generated when the needle is pierced. If the hardness is lower than 40, the purpose of tightening may not be achieved and the effect of firmly fixing the skirt jaw to the container rim may not be achieved. Conceivable.

Examples of the rubber base material used for the main body rubber plug in the present invention include natural rubber (NR), isoprene rubber (IR), butadiene rubber (BR), styrene-butadiene rubber (SBR), and isobutylene-isoprene copolymer rubber. (IIR), IIR halogenated rubber (BIIR,
CIIR), rubber obtained by polymerizing IIR with a third component (I
IRVR), acrylonitrile copolymer (NBR), NBR hydrogenated rubber and the like can be used. Examples of the compounding agent added to the rubber base material include organic peroxides, organic sulfur-donating vulcanizing agents, vulcanizing agents such as sulfur, vulcanization accelerators, vulcanization aids, reinforcing agents, processing aids, and the like. And these are compounded and vulcanized and molded. In the present invention, since the synthetic resin film that does not contaminate the drug is laminated and coated on the part that comes into contact with the drug, there is no particular limitation regarding the type and amount of the above-mentioned compounding agent, and the compounding means conventionally known. Compounding techniques can be applied. However, as described above, the rubber material of the present invention has a rubber hardness of 40 to 60.
(JIS) is preferable in terms of sealing property and liquid leakage resistance. The stopper of the rubber stopper of the present invention may be basically a conventional stoppering method. In the following examples, the rubber stopper gripping tool of the stopper is improved to correspond to the product of the present invention. The pressure was adjusted to an appropriate pressure and the stopper was attached.

[0015]

EXAMPLES The present invention will be described below in greater detail by giving Examples, but the present invention is not limited thereto. [Examples] The formulations shown in Table 1 below were prepared according to JIS K6384.
According to (1975), rubber compounding operation was performed using an open roll and an internal mixer. The cross-linking method is based on the method described in JP-B-57-53184, JP-A-61-272134, etc., and a mold having a skirt portion is used and heated at a temperature of 160 ° C. for 10 minutes. Then, the resin films shown in Table 2 were laminated and coated, and at the same time, crosslinked and molded. The following tests were performed on the obtained rubber stoppers with skirts. The test results are shown in Table 2. Water leak test: A rubber stopper with a skirt is plugged onto the tip of a glass syringe, 80% of the volume of the cylinder is filled with water, and air is sent by a compressor to pressurize the water. The leak condition was tested. Number of rubber pieces generated at the time of needle stick: Fill a glass bottle with water equivalent to about 80% of its capacity, cap a rubber stopper with a skirt, and use a syringe with 22G (0.70 x 32mm) as a test needle. Add 2 ml of water and put it in the rubber stopper and needle
Penetrate 0 times. At the 20th penetration, water in the syringe barrel was poured into the glass bottle, and then the needle was pulled out to count the number of rubber pieces in the bottle.

[0016]

[Table 1]

[0017]

[Table 2]

As shown in the results of Table 2, the rubber stopper with skirt of the present invention does not leak even if a water pressure of 5 kgf / cm ² or more is applied, and has the same performance as that of the conventional aluminum cap wound product. Have.

The rubber stopper with a skirt of the present invention prepared in Experiment 1 was subjected to a hygiene test in accordance with the 12th revised Japanese Pharmacopoeia. The test complies with the 49 plastic container test method for infusion, and the eluate test uses a rubber stopper in the container.
Put 10 pieces, add 200 ml of water, and heat this in a high-pressure steam sterilizer at 121 ° C for 60 minutes. Property, foaming, pH, chloride, sulfate, phosphate, ammonium salt, potassium camanganate reduction Conductive substances, evaporation residue, ultraviolet spectrum, acute toxicity test, skin reaction test, pyrogenic substance test, and hemolytic test were conducted. As a result, the rubber stopper with a skirt of the present invention passed and conformed to the regulations of the Japanese Pharmacopoeia in all the test items.

[0020]

EFFECTS OF THE INVENTION The laminated rubber stopper for pharmaceuticals of the present invention 1) seals the pharmaceutical in a container, maintains the quality for a long period of time, and prevents leakage of the chemical during heating such as high-pressure steam sterilization. 2) Since it is not necessary to tighten the aluminum cap on the rubber stopper as in the conventional case, the number of processes is reduced, the manufacturing time is shortened, the cost is reduced, and the incineration after use is facilitated. 3) Since there is no tightening of the aluminum cap, the generation of fine dust generated from aluminum is eliminated, and hygiene is further improved.

[0021]

[Brief description of drawings]

FIG. 1 is a schematic cross-sectional view showing a state where a laminated rubber stopper for pharmaceuticals of the present invention is capped in a glass container.

FIG. 2 is a sectional view showing an embodiment of the laminated rubber stopper for pharmaceuticals of the present invention.

FIG. 3 is a cross-sectional view showing another embodiment of the laminated rubber stopper for pharmaceuticals of the present invention.

FIG. 4 is a schematic cross-sectional view showing a state in which the laminated rubber stopper for pharmaceuticals of the present invention is plugged on the barrel end of a syringe filled with a drug solution.

FIG. 5 is a schematic cross-sectional view showing various embodiments of the laminated rubber stopper for pharmaceuticals of the present invention which is stoppered at the tip of a cylinder.

FIG. 6 is a schematic cross-sectional view showing various embodiments of the laminated rubber stopper for pharmaceuticals of the present invention which is stoppered at the tip of a cylinder.

FIG. 7 is a schematic cross-sectional view showing various embodiments of the laminated rubber stopper for pharmaceuticals of the present invention which is stoppered at the tip of a cylinder.

[Explanation of symbols] 1 rubber stopper, 2 container, 3
Drug (medicine), 4 rubber, 5 top surface, 6 skirt part, 7 resin film, 8 jaw part, 9 container mouth, 10
Flange, 11 rubber, 12
Protrusion, 13 resin film, 14 needle stick position, 1
5 olefinic thermoplastic elastomer, 16 syringe, 17 chemical liquid, 18 tip,
19 Rubber cap with skirt, 20 Syringe / container, 2
1 skirt part, 22 jaw part, 23 double-ended needle, 24 connector, 25 protrusion,
26 hollow, 27 resin film, 28
Protrusion, 29 Bottom surface, 30
Annular protrusion, 31 rubber stopper with skirt, 32 plastic, 33 annular recess, 34 resin film,
35 unevenness.

Claims (7)

[Claims] 1. A rubber stopper applied to a container mouth,
The surface in contact with the drug is laminated with a synthetic resin body which does not contaminate the drug, and the top rubber covering the upper edge of the container mouth has a skirt portion extending from the container mouth to the container outer surface. A laminated rubber stopper for pharmaceuticals, which is characterized in that 2. The laminated rubber stopper for pharmaceuticals according to claim 1, wherein an inner surface of the skirt portion is engaged with a protrusion or a depression of a container edge portion. 3. The skirt portion has a jaw projecting inward at an end thereof, and the jaw is engaged with a projection of an edge portion of the container. 2. The laminated rubber stopper for pharmaceuticals according to 2. 4. The rubber stopper has a leg portion to be fitted into the container, and a surface of the leg portion in contact with a drug is laminated with a synthetic resin body which does not contaminate the drug, and a protrusion of a rubber raw surface is provided on the base thereof. And is configured to compress the container mouth edge portion by the protruding portion bare surface and the inner rubber side surface of the skirt portion to seal the container mouth portion and fix the rubber stopper to the container mouth portion. The laminated rubber stopper for pharmaceuticals according to any one of claims 1 to 3, wherein 5. The outer peripheral surface of the rubber stopper is also laminated and coated with one or more layers of a film of a synthetic resin body which is the same as or different from the synthetic resin body of the surface contacting the drug.
The laminated rubber stopper for pharmaceuticals according to claim 4. 6. The synthetic resin body comprises an ultrahigh molecular weight polyethylene, polypropylene, polycarbonate, polyester, polymethylpentene, a fluororesin, an olefin thermoplastic elastomer, a cyclic olefin compound or a crosslinked polycyclic hydrocarbon compound. The laminated rubber stopper for pharmaceuticals according to any one of claims 1 to 5, wherein the laminated rubber stopper is one or more selected from the combined components. 7. The laminated rubber stopper for pharmaceuticals according to claim 1, which has a liquid leakage pressure of 3 kgf / cm ² or more when applied to the mouth of the container.