JPH0822936B2 - Rubber stopper - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a rubber stopper such as a syringe, a reagent and a container for chemicals, which is particularly used for pharmaceutical products.

(Prior Art) A rubber stopper for a drug container must have characteristics specified by law unlike ordinary rubber stoppers.
Moreover, in recent years, the reliability requirements for pharmaceutical containers have become much more severe.

As one method, various rubber plugs laminated with a fluororesin have been proposed and put into practical use.

In general, fluororesins are extremely inert and have excellent chemical resistance, so fluororesin-laminated rubber stoppers prevent elution of rubber compounding ingredients into pharmaceutical products, Since there is no elution component, the drug in the container will not be contaminated.

However, as described above, since the fluororesin is inactive and lacks adhesiveness and compatibility with rubber, conventionally, in order to produce a fluororesin laminated rubber stopper, the fluororesin film is previously subjected to arc discharge treatment and corona discharge treatment. Adhesion with rubber is improved by applying an adhesive treatment. However, even by these treatments, there is a problem that the effect of adhering the stretched portion at the time of shaping is insufficient, and the required properties have not yet been satisfied. On the other hand, in rubber stoppers used for syringes, drug stoppers, etc., it is necessary to reduce the components that elute into the medicines used as much as possible.

The generation of eluate from the rubber plug is mainly due to sulfur and the vulcanization accelerator, but if the cause of increasing this eluate is a reinforcing agent, etc., it is possible to reduce this, but sulfur and In the case of a vulcanization accelerator, if it is reduced, the degree of cross-linking will decrease, and the compounding ingredients in the rubber stopper will easily elute. A peroxide crosslinking method has been proposed to solve these problems.

Japanese Unexamined Patent Publication (Kokai) No. 58-39436 discloses a rubber stopper obtained by peroxide-crosslinking a blended product of nitrile rubber and halogenated butyl rubber.

Although the rubber stopper obtained by the method certainly has less eluate due to chemicals, the material becomes brittle due to peroxide crosslinking, and cracks may occur when pierced with an injection needle, or the stopper operation may be difficult. Repeatedly, there were problems such as chipping of rubber pieces on the surface, and it is still at an unsatisfactory level.

(Problems to be Solved by the Invention) As a result of earnestly studying to obtain a rubber plug which is excellent in adhesiveness with a fluororesin film, has little elution with respect to chemicals, and is unlikely to crack did.

Means for Solving the Problems That is, the present invention is composed of isoprene or isoprene and butadiene and / or styrene, and has an isoprene content of at least 50 mol% and a 1.4-bonded isoprene unit content of 20 to 85 mol%. Provided is a rubber plug whose main component is a crosslinked product obtained by peroxide-crosslinking an isoprene (co) polymer.

(Means for Solving Problems) The isoprene (co) polymer of the present invention needs to have an isoprene content of at least 50 mol% or more. If it is less than 50 mol%, the adhesiveness to the fluororesin film will be poor, and if it is peroxide-crosslinked, cracks are likely to occur, which is not preferable.

The isoprene (co) polymer of the present invention can be synthesized by various methods. 1.4 (Co) polymers with high bond are catalyst systems using rare earth metal compounds (for example, JP-A-58-57410, 58-5390).
8, 58-61107), or a catalyst system using a transition metal (for example, Japanese Patent Publication No. 45-13589).

The isoprene (co) polymer having a relatively high vinyl bond is usually obtained by using an anionic polymerization catalyst. (For example,
57-87406, 58-122945, 59-206423, 59-64645, 58-
210943, 57-100145, 58-215435, 60-252642) In the isoprene (co) polymer of the present invention, if the 1.4-bond isoprene unit content is less than 20%, the adhesiveness with the fluororesin film is poor. Moreover, when peroxide-crosslinked, cracking is likely to occur, which is not preferable.

1.4 If the content of bound isoprene units exceeds 85%,
When the rubber is peroxide-crosslinked, the rubber tends to soften significantly and the amount eluted into the chemical increases, which is not preferable. The microstructure of the isoprene (co) polymer obtained in the present invention is ¹³
Determined by C-NMR.

A preferred embodiment of the isoprene (co) polymer of the present invention is a high 1.4 type butadiene isoprene copolymer,
1.4 type styrene-isoprene copolymer, high vinyl type butadiene-isoprene copolymer with 15 to 80% of 1.2 bonds + 3.4 bonds in isoprene part, high vinyl type isoprene polymer, high vinyl tile styrene-isoprene copolymer Examples thereof include polymers and high vinyl type styrene-butadiene-isoprene copolymers.

A filler such as carbon black, silica, clay or calcium carbonate is added to the isoprene (co) polymer of the present invention and compounded and kneaded, and compounded and molded using a vulcanization accelerator, sulfur and an organic peroxide as a crosslinking agent. A rubber plug can be produced by crosslinking. The compounding amount of the filler is preferably 10 to 200 parts by weight with respect to 100 parts by weight of the rubber component, and the compounding amount of the crosslinking agent is preferably 0.1 to 5 parts by weight. Further, silica and clay are preferable as the filler.

As the rubber component of the rubber stopper of the present invention, in addition to the isoprene (co) polymer of the present invention, other diene rubber, natural rubber, polyisoprene rubber, polybutadiene rubber, styrene butadiene rubber, ethylene-propylene-diene rubber, butyl rubber- Halogenated butyl rubber can be blended and used. At that time, the isoprene (co) polymer of the present invention is preferably used in an amount of 50% by weight or more in the rubber component. It is preferable to laminate a fluororesin film on the rubber stopper of the present invention. At this time, the method for treating the fluororesin film is preferably performed according to the method described in JP-A-61-277445.

Such a laminated rubber stopper is produced by laminating the treated surface of a fluororesin sheet subjected to electric discharge treatment with an uncrosslinked isoprene (co) polymer sheet, pressurizing and heating in a mold to form a plug shape differently. It

Next, the present invention will be described with reference to examples, but the present invention is not limited to the examples.

(Example) (1) A film speed of 5 m / min at an output of 150 w / m ² at 110 KHz on one side of an ethylene tetrafluoroethylene copolymer (fluorine resin EPS20 manufactured by Daikin Industries, Ltd.) having a thickness of 50 μm. Was subjected to corona discharge treatment.

Next, the compounding formulation shown in Table 1 was kneaded with a 250 ^cc plastomill to prepare an unvulcanized compound sheet having a thickness of 8 mm.

This unvulcanized rubber sheet was laminated on the above fluororesin film and pressure-heated under the conditions of a pressure of 10 kg / cm ² , a temperature of 180 ° C. and a time of 10 minutes to laminate and adhere the sheet and the film. A test piece with a width of 10 mm was cut out from each sheet, and the adhesive strength by 180 ° peeling was evaluated at a tension rate of 200 mm / min under a temperature condition of 25 ° C. The results are shown in Table 3.

(2) On the other hand, a rubber stopper was manufactured by kneading with a 250 ^cc plastomill according to the compounding recipe shown in Table 2, and after molding, press-crosslinking with an organic peroxide. Table 3 shows the results of the tensile strength test, the crack generation test with an injection needle (1.5 mmφ), and the drug elution test.

It is clear from the results of Examples 1 to 4 in Table 3 that the desired effects of the present invention are exhibited.

(Note) * 1) 1.4-bond isoprene unit content in isoprene (co) polymer determined by ¹³ C-NMR.

* 2) BIR-I; obtained with neodymium octanoate / diethylaluminum chloride / triethylaluminum catalyst system. High cis 1.4 type butadiene-isoprene copolymer (butadiene / isoprene = 22/78 (molar ratio))
(Moonie viscosity = 55) * 3) BIR-II; Budadiene-isoprene copolymer (butadiene / isoprene = 38/62 (molar ratio)) obtained by the same catalyst system as BIR-I (Moonie viscosity = 51) * 4) BIR-III; Budadiene-isoprene copolymer (butadiene / isoprene = 85/15 (molar ratio)) obtained with the same catalyst system as BIR-I (Mooney viscosity = 48) * 5) BIR-IV Budadiene-isoprene copolymer obtained by the same catalyst system as BIR-I (butadiene / isoprene = 6/94 (molar ratio)) (Moonie viscosity = 50) * 6) HV-BIR-I; n-butyl High vinyl type butadiene-isoprene copolymer obtained with a lithium / tetrahydrofuran catalyst system (butadiene / isoprene = 12/88
(Molar ratio)) 1.2 bonds + 3.4 bonds = 55 mol% (Moonie viscosity = 49) * 7) HV-IR-I; n-butyllithium / tetrahydrofuran catalyst system, a high vinyl type isoprene polymer obtained with a catalyst system, 1.2 bond + 3.4 bond = 60 mol% (Moonie viscosity = 52) * 8) IR2200; high cis 1.4 type isoprene rubber JSR I
R2200 (Mooney viscosity = 80) * 9) Silica; using Nipsyl VN-3 * 10) MSA; N-oxydiethylene-2-benzothiazole sulfanamide * 11) Nippon Oil & Fats Perhexa 25B * 12) 1.5mmφ injection The occurrence of cracks when the needle was pierced into the rubber stopper 10 times, and the degree of adhesion of the rubber piece to the needle was evaluated on the III grade of good>acceptable> poor.

Good (No cracks, no rubber pieces attached) Yes (Some cracks occurred, some rubber pieces present) Poor (Significant cracks occurred, many rubber pieces) * 13) Evaluation by vulcanized sheet (JISK6301) (Effect) The rubber stopper mainly composed of a cross-linked product obtained by peroxide-crosslinking the specific isoprene (co) polymer of (1) has little elution with respect to chemicals, has good adhesiveness with the fluororesin film, and is injected. It has excellent resistance to cracking by a needle and is suitable for use as a rubber stopper for chemicals.

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Claims (1)

[Claims] 1. An isoprene (co) polymer composed of isoprene or isoprene and butadiene and / or styrene, having an isoprene content of at least 50 mol% and a content of 1.4-bonded isoprene units of 20 to 85 mol%. A rubber plug whose main component is a crosslinked product formed by oxide crosslinking.