JPH0464938B2 - - Google Patents

Description

[Detailed description of the invention]

[Field of Industrial Application] The present invention relates to a laminated rubber stopper, and more specifically, the present invention relates to a laminate rubber stopper, and more specifically, a stopper body that includes a lid having excellent chemical resistance, airtightness, non-adsorption properties, and improved flexibility, at least at the container mouth insertion portion. It has improved fitability by laminating a base resin film and is particularly suitable as a rubber stopper for pharmaceuticals and medical devices. Regarding laminate rubber stoppers. The laminated rubber stopper of the present invention can be used as a container for pharmaceutical products, which can pass the standard tests of various compendial documents required in the pharmaceutical field, and can also meet test items related to foreign matter and fine particles, which are problematic from a pharmaceutical standpoint. This rubber stopper is suitable for preserving and preserving the purity of formulations for long periods of time. For example, in Japan, the manufacture of pharmaceuticals requires approval from the Ministry of Health and Welfare according to the Pharmaceutical Affairs Law, and the containers and equipment used for these are regulated by the above law. Therefore, the laminate rubber stoppers used as medicine stoppers are subject to the Japanese Pharmacopoeia (10th revision), the Test Method for Rubber Stoppers for Infusions, and the Test Method for Plastic Containers for Infusions.
In principle, products are required to have quality that complies with the above test methods, and in addition to the above test methods, they are also required to have hygienic properties as specified in the Ministry of Health and Welfare notification. Regarding medical equipment, Ministry of Health and Welfare Notification No. 98
(Packaging of Containers), Ministry of Health and Welfare Notification No. 442 (Standards for Disposable Syringes), Ministry of Health and Welfare Notification No. 301 (Standards for Disposable Infusion Sets), etc.
Each must meet predetermined criteria. [Prior Art] Glass has been used as a container material for pharmaceuticals since ancient times, and plastic has also been used in recent years. The material used to seal the mouth of such containers is heat resistant, compressive strain resistant, flexible, chemically inert, and permeable to gases such as oxygen, nitrogen, carbon dioxide, and water vapor. things are selected. Jii. Kay. Melnikova recommends copolymer rubber of isoprene and isobutylene (hereinafter referred to as IIR) as such a material. On the other hand, new technologies include mixing polyethylene fine powder with rubber, co-crosslinking chlorinated butyl rubber with nitrile rubber, using styrene-butadiene-styrene block copolymers, and adding silicone or fluorine compounds after molding rubber plugs. Coatings with compounds or lamination of rubber plugs with films of polypropylene, polyethylene, nylon, or fluorine resin have been proposed (Utility Model Act 1973-
No. 27753, No. 45-17831, No. 49-21346, No. 54
−29207, Special Publication No. 52-1355, No. 54-9119,
(Refer to each publication No. 57-53184). However, although coating with silicone and fluorine-based compounds reduces the stickiness of the rubber surface, when viewed as a pharmaceutical rubber stopper, it causes problems in terms of chemical properties, physical properties, and especially fine particles. There is. Regarding these properties, the above-mentioned laminate rubber stopper is excellent. However, when we looked deeper into laminated rubber stoppers, we found that conventional fluororesin films such as polytetrafluoroethylene (PTFE) have poor moldability and mechanical strength.
Lamination requires a lot of man-hours and has the disadvantage of poor adhesion between the rubber and resin film. In order to solve these drawbacks, there is a technique of laminating at the same time as rubber vulcanization by using a fluorine-based copolymer (see Japanese Patent Laid-Open No. 59-5046). This production technology is excellent as a method for producing rubber stoppers, and as fluorine-based copolymers, tetrafluoroethylene-ethylene alternating copolymer, followed by tetrafluoroethylene-hexafluoropropylene copolymer, are cited as desirable. There is.
However, conventionally known tetrafluoroethylene-ethylene alternating copolymers have relatively high tensile elongation and tensile strength near the molding temperature, and are reasonably satisfactory in laminate molding processability, but when molding laminated rubber plugs, In addition, the resulting laminated rubber stopper has a hard resin film, which impairs the elasticity and compressive strain resistance of the rubber. This may cause problems such as air leaks during the vacuum formulation process. Furthermore, the sealing performance was also unsatisfactory. In addition, tetrafluoroethylene-hexafluoropropylene copolymer has slightly inferior mechanical properties near the molding temperature compared to tetrafluoroethylene-ethylene copolymer, resulting in poor lamination formability and poor adhesion between rubber and film. It has serious drawbacks such as poor performance. Standards for pharmaceutical rubber stoppers are stipulated in the Japanese Pharmacopoeia (10th revision) mentioned above, as well as British Standards 3263 (1960) and West German Industrial Standards (DIN). However, with these contents, conditions suitable for long-term retention and storage of recent high-performance pharmaceuticals cannot be sufficiently achieved. Furthermore, as pharmaceutical formulation technology has progressed, rubber stoppers have come to play an important role.
The properties required of the laminated rubber stopper are broadly classified into chemical properties and physical properties. Fluorine resin can be selected as a material with excellent chemical properties. However, in terms of physical properties, as mentioned above, conventional fluororesins have not been able to satisfy all of the requirements such as flexibility, moldability, and adhesiveness. [Object of the invention] The object of the present invention is, for example,
The aim is to solve the problems that occur when using the conventional fluororesin rubber stopper as a laminate material as described in the above publication, namely, to improve the laminate resin film to have even better molding processability and to improve chemical processing. To provide a laminate rubber stopper that satisfies all physical and physical properties. More specifically, regarding the improvement of the conventional tetrafluoroethylene-ethylene alternating copolymer as a laminated resin film, it has excellent moldability without impairing the chemical properties and suppresses the occurrence of defective products during the production of laminated rubber stoppers. It is an object of the present invention to provide a laminate rubber stopper that generates less fine particles from the stopper, has excellent flexibility, and has improved fit with a container opening. [Disclosure of the Invention] As a result of various studies, the present inventors have found that a copolymer with a specific composition range of tetrafluoroethylene and ethylene has improved flexibility and can be used to make a copolymer film into a rubber stopper. If the laminated rubber stopper is laminated, the fit between the container mouth and the laminated rubber stopper will be improved, and the sealing performance will be dramatically improved.Furthermore, the number of defective products in the manufacture of laminated rubber stoppers will be drastically reduced, and fine particles from the stopper will be reduced. They have discovered that the occurrence can be reduced and have completed the present invention. That is, the gist of the present invention is to provide a rubber stopper in which at least the container mouth insertion portion of the rubber stopper body is laminated with a fluorine resin film, and the resin film is composed of tetrafluoroethylene, ethylene, and the formula: CH ₂ =CX-Rf () [in the formula] , X represents hydrogen or fluorine, and Rf represents a fluoroalkyl group. A copolymer consisting of a copolymerizable fluorine-containing vinyl monomer represented by ], in which the molar ratio of tetrafluoroethylene to ethylene is 62:38 to 90:10, and the copolymerizable fluorine-containing vinyl monomer Monomer content is 0.1 relative to the total number of moles of tetrafluoroethylene and ethylene
A laminate rubber stopper characterized in that it is a film of a copolymer having a composition in the range of ~5 mol %. The conventionally known tetrafluoroethylene-ethylene copolymer is an alternating copolymer with a molar ratio of tetrafluoroethylene to ethylene of 40/
The ratio is 60 to 60/40, and in reality it is close to 50/50, but the copolymer used in the present invention has a significantly increased proportion of tetrafluoroethylene. By greatly increasing the content of tetrafluoroethylene in this way, flexibility that cannot be obtained with conventional tetrafluoroethylene-ethylene alternating copolymers can be obtained. The copolymerizable fluorine-containing vinyl monomer has the formula:
_CH2 =CFR'f, _CH2 =CH-Rf [wherein, Rf represents a fluoroalkyl group]. ], specifically CH ₂ = CFC ₃ F ₆ H, CH ₂ =
Examples include CFC ₅ F ₁₀ H, CH ₂ =CHC ₄ F ₉ and CH ₂ =CHC ₆ F ₁₃ . By using the monomer represented by the formula (), the elongation at break of the resin film at lamination temperature can be improved, and film breakage during lamination can be reduced. The content of the fluorine-containing vinyl monomer may be 0.1 to 5 mol% based on the total number of moles of tetrafluoroethylene and ethylene, and from the viewpoint of heat resistance etc.
~5 mol% is preferred. If the copolymer has a composition within this range, a laminated rubber stopper can be obtained that has excellent chemical and physical properties, and particularly satisfies all properties such as flexibility, processability, and adhesiveness. The production of such a copolymer used in the laminated rubber stopper of the present invention is described in detail in JP-A-60-248710, and polymerization methods include bulk, solution, suspension, emulsification, and gas phase polymerization. Legal etc. can be adopted. Industrially, suspension polymerization in an aqueous medium using a chlorofluoroalkane as a solvent and an organic peroxide as a polymerization initiator is preferred. As the chlorofluoroalkane, trichlorotrifluoroethane, dichlorotetrafluoroethane, dichlorodifluoromethane, chlorodifluoromethane, dichlorofluoromethane, etc. are advantageously employed.
The amount of solvent to be used is preferably 10 to 100% by weight based on water in terms of suspension dispersibility and economical efficiency. The organic peroxide used as a polymerization initiator has the formula:

[Formula] [In the formula, Y represents hydrogen, fluorine or chlorine, and m represents an integer of 2 to 8. ] Examples include peroxides represented by the following, and specific examples include jeeperfluoropropionyl peroxide, di(ω-hydroperfluorohexanoyl) peroxide, and di(ω-chloroperfluoropropionyl) peroxide. . Also,
formula: [In the formula, l represents an integer from 1 to 10. ] Peroxides represented by these, such as di(trichloroperfluorohexanoyl) peroxide, are also preferred. Furthermore, hydrocarbon-based organic peroxides such as diisobutyl peroxide and diisopropyl peroxydicarbonate are also suitable. The polymerization temperature is not particularly limited, but
Industrially, the temperature may be 0 to 100°C. In order to avoid a decrease in heat resistance due to the formation of ethylene-ethylene chains in the copolymer, low temperatures are generally preferred. The polymerization pressure may generally be 0 to 50 kg/cm ² G, and a relatively low pressure of 1 to 15 kg/cm ² G is desirable for polymerization operations, and is also preferred for safety. The polymerization pressure is appropriately determined depending on the type and amount of the solvent used, as well as other polymerization conditions such as vapor pressure and polymerization temperature. When producing the copolymer used in the present invention, common chain transfer agents such as isopentane, n-hexane, cyclohexane, methanol, ethanol, carbon tetrachloride, chloroform, methylene chloride, methyl chloride, etc. are used to control the molecular weight. be able to. To produce the resin film to be laminated to the rubber stopper of the present invention, for example, using a normal film extruder, the above copolymer is heated to 260 to 360°C by a T-die method.
It is sufficient to form a film at a temperature of . If necessary, the film thus obtained can be re-stretched to easily produce a film having a uniform thickness of 0.002 to 0.5 mm. The above-mentioned copolymer film can also be subjected to electrical discharge treatment (corona treatment, gas plasma treatment, etc.) in order to improve its adhesion to rubber. The shape of the rubber stopper in the present invention is not particularly limited, and even a rubber stopper with a complicated shape can be easily vulcanized and laminated with a film at the same time. The laminated rubber stopper of the present invention will now be explained with reference to the accompanying drawings. FIG. 1 shows a perspective view of a specific example of the laminate rubber stopper of the present invention. Since the laminate film portion is not clearly shown in FIG. 1, a cross section is shown in FIG. 2 or 3 to make the structure clearer. As shown in the cross-sectional view in Figure 2, the rubber stopper consists of a bare stopper part that is inserted into the bottle, or a foot part _A1 and a head part.
Consists of A ₂ . Each of these is made of rubber material. The laminated rubber stopper of the present invention is shown in Figures 2 and 3.
The laminated film indicated by the bold line in the figure is laminated on the surface of the rubber material, and it may be laminated except for the lower surface of the head around the base plug as shown in Figure 2, or it may be laminated around the base of the base plug as shown in Figure 3. A laminated structure including the lower surface of the head may also be used. In addition, in FIG. 3, A indicates a rubber material. Furthermore, in order to clarify the difference between the laminated rubber stopper of the present invention and a normal rubber stopper, Fig. 4 shows a cross-sectional view of a normal rubber stopper, but unlike the laminate rubber stopper shown in Figs. There is no laminate film, only a rubber stopper. According to the present invention, when a rubber stopper having the shape shown in FIG. 1 in a perspective view and in FIG. Since the film is stretched eight times, unless it can withstand these conditions, it will break during the vulcanization process, resulting in a defective product as a laminated rubber stopper. In the present invention, since the above-mentioned copolymer is used as an element of the resin film, the tensile strength at high temperature,
The improved elongation reduces the incidence of defective products of the laminated rubber stoppers, making it possible to economically supply them to the pharmaceutical industry. The rubber compound material constituting the rubber stopper body of the present invention can be manufactured substantially according to conventional techniques. Namely, IIR, isoprene rubber (IR), butadiene rubber (BR), styrene-butadiene rubber (SBR), ethylene-propylene rubber (EPM), ethylene-propylene-diene rubber (EPDM), chlorosulfonated polyethylene (CSM), ethylene -Vinyl acetate copolymer (EVA), styrene-isoprene rubber (SIR), thermoplastic elastomer, natural rubber, etc., along with vulcanizing agents, vulcanization accelerators, vulcanization activators, processing aids, fillers, and reinforcing agents. It is formulated with the following ingredients to maintain the physical properties and heat resistance of a rubber stopper. [Example] Next, production examples, examples, and comparative examples of the resin used for the laminate film of the laminate rubber stopper of the present invention will be shown to specifically explain the usefulness of the present invention. The present invention is not limited in any way. (1) Resin film First, production examples of resins used in the following Examples and Comparative Examples will be shown. The composition of the copolymer obtained in the production example was calculated by dividing the difference between the total amount charged during copolymerization and the amount recovered after copolymerization by the amount of copolymer obtained. , and the composition of other monomers is determined from the content of the modified monomer and the elemental analysis values. Furthermore, the physical properties of the copolymer were measured as follows. Flow value Using a Koka type flow tester, measure the volume (ml/sec) of copolymer flowing out per unit time from a nozzle with a diameter of 2 mm and a length of 8 mm at 300℃ and under a load of 7 kg, and calculate this as the flow value. shall be. Melting point Using a Perkin-Elmer type DSC device, 20
The melting peak when the temperature is increased at a rate of °C/min is recorded, and the temperature corresponding to the maximum value is taken as the melting point. Production Example (Production of Resin) A glass-lined autoclave with an internal volume of 4 was charged with 1.2 liters of deoxygenated water, evacuated, and 1 kg of dichlorotetrafluoroethane was charged, and the temperature inside the tank was maintained at 15°C. To this, CH ₂ = CFC ₃ F ₆ H23.5g
Add 1.5 ml of cyclohexane and stir.
A mixed gas of tetrafluoroethylene/ethylene (molar ratio 97.4/2.6) was injected to a pressure of 6 kg/cm ² G. Next, 2.1 g of di(ω-hydroperfluorohexanoyl) peroxide was charged to initiate polymerization. As the pressure decreases as the polymerization progresses,
Tetrafluoroethylene/ethylene/CH ₂ =
CFC ₃ F ₆ H mixed gas (molar ratio 63.3:34.0:2.7) was further pressurized to maintain the polymerization pressure at 6 Kg/cm ² G. 2
0.6 g of each of the above peroxides was charged twice every hour, and polymerization was carried out for 27.7 hours. The contents were collected to obtain 311 g of white powder. Polymer composition, tetrafluoroethylene: ethylene: CH ₂ = CFC ₃ F ₆ H =
63.3:34.0:2.7 (molar ratio) [tetrafluoroethylene/ethylene = 65.1/34.9 (molar ratio), CH ₂ =
CFC ₃ F ₆ H2.7 (molar ratio)]. Melting point 225℃. flow value
0.4x10 ^-2 ml/sec. Comparative resin production example: Pour 1.2 liters of deoxygenated water into a glass-lined autoclave with an internal volume of 3, create a vacuum, then add 1 kg of dichlorotetrafluoroethane and bring the temperature inside the tank to 15.
It was kept at ℃. To this, 9.5 g of CH ₂ =CFC ₃ F ₆ H and 25 ml of n-pentane were charged, and while stirring, a mixed gas of tetrafluoroethylene/ethylene (molar ratio 83.2:
16.8) was press-fitted to 6 kg/cm ² G. Next, 1.93 g of di(ω-hydroperfluorohexanoyl) peroxide was charged to initiate polymerization. As the pressure decreases as the polymerization progresses, additionally pressurize the tetrafluoroethylene/ethylene/CH ₂ = CFC ₃ F ₆ H mixed gas (molar ratio 52.0:45.9:2.1) to maintain the polymerization pressure at 6 Kg/cm ² G. Ta. 1.16 g of each of the above peroxides was charged every 2 hours, and polymerization was carried out for 5.5 hours. The contents were collected to obtain 89.8 g of polymer powder. Composition, tetrafluoroethylene: ethylene:
_CH2 = _{CFC3F6H52.0 :45.9:2.1 (molar ratio) [tetrafluoroethylene/ethylene=53.1/46.9 (molar ratio), CH2=CFC3F6H2.1 ( molar ratio} )]. Melting point 268.5
℃. The flow value was 0.74×10 ⁻² ml/sec. Table 1 shows the physical properties of the copolymers and films obtained in resin production examples and comparative resin production examples. In addition, "TFE" in the table represents "tetrafluoroethylene." The physical values of the copolymer were measured as follows. Tensile Test A copolymer film (100 μn) punched into a JIS No. 3 dumbbell was pulled at a pulling rate of 200 mm/min at temperatures of 25°C and 180°C, and the elongation and strength at break were measured. Durometer hardness Measured using a copolymer sheet (2 mm) at a temperature of 25°C according to ASTM D2240. Flexural Modulus Measured using a copolymer sheet (1 mm) at a temperature of 25°C according to ASTM D747.

【table】

[Table] F- is the resin film according to the present invention obtained in the production example, and has improved tensile strength and elongation at high temperatures, hardness and bending compared to F- obtained in the comparative resin production example. It can be seen that the elastic modulus has been improved to become extremely flexible. Furthermore, in order to clarify the characteristics of the composition range of the resin used in the present invention, Table 2 shows the relationship between the tetrafluoroethylene/ethylene composition ratio, hardness, and flexural modulus.

[Table] The surface of the above film was heated to 1× pressure before forming the rubber plug.
Sputter etching treatment was performed at 10 ^-2 Torr, Rf voltage of 800 W, and winding speed of 0.3 m/min. (2) Rubber compound The rubber compound shown in Table 3 was used.

【table】

[Table] (3) Molding of laminated rubber stoppers The rubber compounds shown in Table 3 were compounded using a two-roll rubber roll or an internal mixer. The compounding operation is "Rubber Test Method" (edited by Japan Rubber Association)
This was carried out in accordance with the method described on pages 108-118, and a method was used in which the resin film was laminated simultaneously with the molding of the rubber plug. The procedure is to use the lower mold (number of rubber plugs 15 x 15 = 225
The above resin film and unvulcanized compounded rubber (corresponding to A ₁ in Fig. 2 and A in Fig. 3) are superimposed on top of the upper mold (in Fig. 2, a flat mold, In Figure 3, a mold with a depression for forming the head of the rubber stopper is placed, and the rubber is pressurized at a temperature of 150 ± 1°C to form and vulcanize the rubber stopper. (also called laminate). Next, it is cut to the specified size and completed. In addition, in the case of Fig. 2, the foot plug obtained above is further placed in the lower mold, and the unvulcanized compound rubber is placed on top of it.
A ₂ was placed, and then an upper mold having a depression for forming the head of the rubber stopper was placed, and pressure was applied at a temperature of 150±1°C to complete the rubber stopper. Cut the rubber stoppers into individual pieces. Then wash if necessary. Table 4 shows the vulcanization time and the breakage rate of the resin film during vulcanization.

[Table] As shown in Table 4, since the film according to the present invention has high breaking strength and breaking elongation at vulcanization temperature, the resin film has a low breakage rate during rubber stopper molding. Therefore, the quality assurance of the rubber stopper is high. (4) Product hygienic test Based on the hygienic test according to the "Rubber stopper test method for infusion" of the "Japanese Pharmacopoeia" (10th revision), 121±1
This example product passed all of the test item specifications for transmittance, foaming, PH change, zinc, potassium permanganate reducing substance, and evaporation residue for the liquid extracted with purified water at ℃ for 60 minutes. did. The British Standards (British Standards)
It passed the syringe needle stick and underwater rubber drop tests for laminated rubber stoppers as specified in Standards) 3263 (1960). Furthermore, as a result of testing the amount of 10 μm fine particles listed in "Japanese Pharmacopoeia" 17 injection using a light-shielding automatic particle counter (manufactured by HIAC, USA), not a single fine particle was observed. (5) Moisture permeability test for rubber stoppers Test method Tubes for injections (JIS R3523-1978): TB ₃ (mouth inner diameter 12.5 ± 0.1 mm) is filled with powdered dry calcium chloride ± 0.05 g, and then The rubber stopper of the invention example or the rubber stopper of the comparative example was attached, and an aluminum cap was further tightened. After leaving the specimen in a test chamber at a temperature of 20 ± 1°C and a relative humidity of 95% (Na ₂ HPO ₄ 12H ₂ O), the weight increase was calculated based on the weight that had been left in phosphorus pentoxide for 4 hours. It was measured. Moisture permeability (%) = Test weight over time - Basis weight / Basis weight x
100 The results are shown in Table 5.

[Table] The rubber stopper laminated with the resin film of Example 1 has a better fit with the bottle mouth than the rubber stopper alone. On the other hand, the resin film of Comparative Example 2 was hard and had poor fit with the container mouth, resulting in an increase in weight due to calcium chloride absorption. In Example 2, the fit was slightly worse than in Example 1, and the moisture permeability was also higher, probably because the rubber stopper was laminated with a film up to the mouth of the container. However, this result shows that the fit is better than that of the rubber stopper laminated with a hard film, that is, Comparative Example 3. The fitting performance (sealing performance) of the rubber stopper laminated with a resin film according to the present invention is equivalent to or slightly better than that of the rubber stopper. (6) Other tests (a) Self-sealing test Pour 10.0 ml of water into an injection tube TB ₃ accurately.
A rubber stopper of the present invention is attached, and an aluminum cap is wrapped around it to prepare a sample. Measure the weight of the specimen in advance and call it A. The operation is to attach a hypodermic needle (22G, 1 1/4") to the syringe and pressurize 2.0ml of air into the specimen. Hold the specimen upside down and remove 2.0ml of water from the specimen. Next, remove the hypodermic needle. The remaining weight is B. The result was obtained as the average value of 20 test tubes. Amount of liquid leakage (mg) = A - (B + 2.0) (b) Vacuum retention test Injection tube bottle TB ₃ The laminated rubber stopper of the present invention is applied to a vacuum vial capping machine (internal vacuum level 20±
Adjust to 1Torr) and immediately tighten the aluminum cap. Store the specimen at room temperature for 20 minutes.
After being left at ±1°C for 28, 84, and 168 days, the degree of vacuum inside the specimen was measured using an electronic manometer (Toyoda Koki
Co., Ltd.). Table 6 shows the amount of leakage for the initial values. (c) Needleprick test (resistance value) A laminate rubber stopper of the present invention is attached to an injection tube TB ₃ , and an aluminum cap is further wrapped around the bottle to serve as a sample. Insert a hypodermic needle (21G RB) into this specimen.
(manufactured by TOP) measures the resistance value when it penetrates. The test machine used was Shimadzu Autograph DCS-100, and the speed was 200 mm/min. The results of these tests are shown in Table 6.

[Table] The laminated rubber stopper of the present invention of Example 1 is superior to the conventional rubber stopper laminated with a film in the self-sealing property, vacuum retention test, and needle stick test. Among the contents, rubber is a material with excellent properties when it comes to vacuum retention and fitability with the container mouth, whereas conventional resin films do not fit well due to their bending elasticity and surface condition. Poor compatibility. However, it is understood from the above results that the resin film of the present invention is equivalent to or slightly superior to rubbers. In addition, the resistance value in the needle stick test was low overall. Resins with such low resistance values generally have poor self-sealing properties, but the resin film of the present invention also has excellent self-sealing properties. [Effects of the Invention] (1) Since the copolymer resin film of the laminate rubber stopper of the present invention is highly flexible, the laminate rubber stopper and the container opening have excellent fitting properties, and therefore have excellent sealing performance. It has extremely excellent properties. (2) The laminated rubber stopper of the present invention has excellent self-sealing properties. (3) The laminated rubber stopper of the present invention has a characteristic that resistance to needle penetration is greatly improved. (4) The copolymer resin film of the present invention has extremely excellent physical properties at high temperatures, ie, tensile strength and elongation, so it can be laminated into rubber plugs of complicated shapes at the same time as rubber vulcanization, and rubber The yield of plug production is approximately the same as that of non-laminated rubber production. (5) The laminated rubber stopper of the present invention is chemically inert and non-adsorbent, and conforms to Japanese Pharmacopoeia, British Standards 3263,
This is a new rubber stopper that passes other standard values and can hold and preserve high-grade pharmaceuticals for a long period of time.

[Brief explanation of drawings]

Fig. 1 is a perspective view of a laminated rubber stopper of the present invention, Fig. 2 is a cross-sectional view of a rubber stopper in which only the bare stopper part is laminated, and Fig. 3 is a rubber stopper laminated on the bare stopper part and the lower surface of the head. and FIG. 4 are cross-sectional views of the non-laminated rubber stopper. 1...Rubber stopper, 2...Laminated film.

Claims (1)

[Scope of Claims] 1. A rubber stopper in which at least the container mouth insertion portion of the rubber stopper body is laminated with a fluororesin film, wherein the fluororesin film contains tetrafluoroethylene, ethylene and the formula: CH ₂ =CX-Rf () [ In the formula, X represents hydrogen or fluorine, and Rf represents a fluoroalkyl group. ] A copolymer consisting of a copolymerizable fluorine-containing vinyl monomer represented by the formula, wherein the molar ratio of tetrafluoroethylene to ethylene is 62:38 to 90:10, and the copolymerizable fluorine-containing vinyl monomer A laminate rubber stopper characterized in that it is a copolymer film having a monomer content in a composition range of 0.1 to 5 mol % based on the total number of moles of tetrafluoroethylene and ethylene.