JP3038699B2 - Rubber stopper for medical container - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical container, and more particularly to a rubber stopper for an injection moldable medical container for closing an opening of a vacuum blood collection tube.

[0002]

2. Description of the Related Art Conventionally, styrene-butadiene rubber has been used to close the mouth of a medicine bottle or a vacuum blood collection tube for accommodating a medicine or a drug solution to shut off the contents from the external atmosphere or to maintain the degree of internal vacuum. Rubber stoppers made of synthetic rubber such as chloroprene rubber and butyl rubber have been used. However, since such rubber stoppers are vulcanized and formed by adding additives such as a vulcanization accelerator and a vulcanization activator, at the time of sterilization, these additives exude and migrate to the drug or drug solution side, or There has been a problem that blood clots adhere to rubber stoppers and hinder blood component testing.

[0003] Japanese Patent Application Laid-Open No. 58-58057 discloses a rubber plug which has been improved in that the conventional rubber plug material has a disadvantage in that it has a problem in contact with a drug, a drug solution or blood. A plug for a medical container comprising a polymer mixture of the above has been proposed. This rubber stopper does not contain additives such as sulfur, vulcanization accelerator, vulcanization activator etc. in rubber, does not require long time for vulcanization molding, and can be injection molded in a short time with a thermoplastic processing machine To form a rubber stopper. Further, since the rubber stopper has good gas barrier properties, the degree of vacuum in the medical container can be maintained for a long period of time, and has properties suitable as a rubber stopper for vacuum blood collection tubes.

[0004]

However, such a rubber stopper lacks toughness, and rubber fragments and fine particles fall when the rubber stopper is inserted into the mouth of the medical container or when the injection needle is punctured into the rubber stopper. Or mixing with the contents contained in the medical container. As an improvement over the disadvantages of such rubber stoppers, Japanese Patent Application Laid-Open No. 60-144346 discloses a rubber stopper for pharmaceuticals obtained by vulcanizing a mixture of butyl rubber and high molecular weight polyethylene. Since it is manufactured by vulcanization, it takes a long time to form a rubber stopper, and because of its large compression set, there is a problem in resealing after puncturing when puncturing with a large-diameter needle or the like. there were. The present applicant has already filed an application for a rubber stopper made of a dynamically crosslinked thermoplastic elastomer of crystalline polypropylene and butyl rubber as a rubber stopper that has solved the conventional drawbacks. To maintain it, the thickness of the rubber stopper had to be slightly increased. The object of the present invention is that the injection resistance of the needle is small, there is no problem in the re-sealing property after the needle is pierced, the gas barrier property is good, the mechanical properties are strong and the rubber elasticity is excellent. It is to provide a rubber stopper for a medical container.

[0005]

SUMMARY OF THE INVENTION The present invention relates to a dynamically crosslinked thermoplastic resin comprising 10 to 45% by weight of a crystalline polypropylene and 55 to 90% by weight of an almost completely crosslinked halogenated butyl rubber having a particle diameter of 0.1 to 4 .mu.m. It is a rubber stopper for a medical container made of an elastomer. Further, the present invention is the rubber stopper for medical containers, wherein the halogenated butyl rubber is chlorinated butyl rubber or brominated butyl rubber. Further, the present invention is the rubber stopper for medical containers, wherein the thickness of the rubber stopper at the needle puncturing portion is 2.0 to 6.0 mm.

The crystalline polypropylene used in the present invention is a polypropylene having a crystallinity of 90% or more, and preferably 10 to 45% by weight based on the total weight of the polypropylene and the crosslinked halogenated butyl rubber. . The higher the crystallinity of the polypropylene, the more preferable it is because the polypropylene crystal is entangled with the molecular chain of the crosslinked halogenated butyl rubber and the strength of the elastomer is high. If the amount of polypropylene in the elastomer is less than 10% by weight and the crosslinked halogenated butyl rubber becomes 90% by weight or more, the elastomer becomes
In this case, since polypropylene disperses without forming a continuous phase, the residual strain increases, and the rubber plug tends to have difficulty in resealing after needle piercing. Also, if the amount of polypropylene is 45
55% by weight of halogenated butyl rubber cross-linked exceeding 55% by weight
Below, the elastomer becomes less elastic and the rubber stopper tends to have poor needle puncture properties.

[0007] The elastomer used in the present invention has a structure in which a crosslinked fine-particle halogenated butyl rubber is dispersed in a continuous phase of polypropylene. Examples of the halogenated butyl rubber include chlorinated butyl rubber, brominated butyl rubber, and the like. Commercially available chlorobutyl (manufactured by Exxon Chemical Co., Ltd.), MD-551 (manufactured by Enjay), and Hiker-2202 (manufactured by Goodrich) are used. You. The particle size of the halogenated butyl rubber is preferably from 0.1 to 4 μm. If the particle size exceeds 4 μm, the strength of the elastomer tends to be low and injection molding tends to be difficult. The smaller the particle size, the higher the strength of the elastomer is preferable, but it is difficult to form only particles of butyl rubber of at most about 0.1 μm with the current kneader. It is preferable that the halogenated butyl rubber fine particles are almost completely crosslinked in the continuous phase of polypropylene because the strength of the elastomer becomes high and the permanent elongation becomes low. That is, the elastomer was placed in xylene at 155 ° C and 30 ° C.
The residual amount after Soxhlet extraction for 10 minutes is 10% by weight or less, especially 5% by weight based on the halogenated butyl rubber
It is preferred that:

To prepare the dynamically crosslinked thermoplastic elastomer used in the present invention, a vulcanizing activator such as polypropylene, halogenated butyl rubber and zinc white, stearic acid or magnesium oxide is added to the total weight of polypropylene and butyl rubber. 0.1 to 3% by weight of the mixture,
Heat to a temperature of 80-220 ° C to melt the polypropylene. Then, the molten mixture was stirred at a high shear rate of 60 rpm or more, preferably 100 rpm or more with a pravender mixer, a Banbury mixer or a twin-screw kneading extruder, whereby the halogenated butyl rubber fine particles were dispersed in the polypropylene melt. State. 0.1 to 3% by weight of a vulcanizing agent such as sulfur, a quinoid vulcanizing agent, a silane vulcanizing agent, an amine vulcanizing agent, a phenolic vulcanizing agent and a dithiocarbamic acid-based xanthogen By simultaneously adding 0.1 to 3% by weight of a vulcanization accelerator such as an acid type, a thiuram type, a sulfenamide type, and a guanidine type, or adding the vulcanization accelerator several minutes after adding the vulcanization agent, The dispersed halogenated butyl rubber fine particles are crosslinked. The crosslinking time varies depending on the temperature at the time of crosslinking, but is usually 1 to 10 minutes. The molten mixture in which the crosslinking has been almost completely completed, or the molten mixture immediately before the completion of the crosslinking, is extruded into water in a sheet form using a twin-screw kneading extruder and quenched.
Next, the elastomer is formed by molding into a pellet.
Be commercialized as. Before the elastomer of the present invention is formed into a rubber stopper after cross-linking or after pellet formation, pigments, dyes, stabilizers, plasticizers, antioxidants, processing aids, extender oils harmless to blood, chemicals or drugs, Elastomers may be modified into properties suitable for the purpose by adding small amounts of additives such as reinforcing agents and fillers.

The dynamically crosslinked thermoplastic elastomer pellets of the present invention are heated and melted at 190 to 230 ° C., for example, as shown in FIG.
Injection molded into the shape of a rubber stopper. FIG. 1 is a sectional view of a rubber stopper showing an example of a rubber stopper for a vacuum blood collection tube. In the figure, 1 is a torso, 2 is a flange, 3 is a leg, 4 is a top, 5 is a bottom, and 6 is a vacuum blood collection tube. The rubber plug fitted from the opening of the vacuum blood collection tube 6 is pushed until the flange 2 reaches the opening of the vacuum blood collection tube 6 while the side walls of the body 1 and the leg 3 press against the inner wall of the vacuum blood collection tube 6. Then, the vacuum blood collection tube 6 is sealed, and the inside of the vacuum blood collection tube 6 is evacuated to maintain the degree of vacuum. The outer diameter of the body 1 is slightly larger than the inner diameter of the vacuum blood collection tube 6, and the rubber stopper is compressed and fitted into the vacuum blood collection tube 6.
A needle, for example, one of the double-ended needles penetrates the torso 1 from the top surface part 4 and penetrates into the inside of the vacuum blood collection tube 6 from the bottom part 5, and punctures the blood vein of the blood collector to supply blood supplied from the other needle. It is housed inside the vacuum blood collection tube 6 which is under reduced pressure. The thickness D of the rubber plug of the needle puncture portion from the top surface portion 4 to the bottom portion 5 is 2.0 to
7.0 mm is preferred. If the thickness D of the rubber stopper is less than 2.0 mm, it tends to be difficult to maintain the degree of vacuum inside the vacuum blood collection tube. If the thickness D of the rubber stopper exceeds 6.0 mm, the puncture resistance of the needle to the rubber stopper tends to increase, and it tends to be difficult to puncture easily. The outer wall or the bottom 5 and the surface of the leg 3 on the vacuum blood collection tube 6 side of the rubber stopper of FIG.
Film or sheet made of resin with excellent gas barrier properties such as polyvinylidene chloride, ethylene / vinyl acetate copolymer, etc.
By laminating the resin or coating these resins, the degree of vacuum retention inside the vacuum blood collection tube by the rubber stopper can be further improved. Further, another resin or rubber may be mixed with the polymer mixture of polypropylene and halogenated butyl rubber as required.

[0010]

The elastomer, which is the rubber stopper material of the present invention, is obtained by dispersing crosslinked halogenated butyl rubber fine particles in a continuous phase of polypropylene, and intermingling the molecular chain of the crosslinked halogenated butyl rubber with the crystal of the polypropylene to form a halogen. The crosslinked density of the butyl rubber dispersed phase has a high molecular structure, and it has tough mechanical properties and excellent rubber elasticity.
The elastomer can be stored in the form of a pellet and molded into a rubber stopper by injection molding. A rubber stopper molded from such an elastomer has a low puncture resistance of the injection needle and has no problem in re-sealing after the needle is pierced. Moreover, this elastomer
Has a good gas barrier property, so that when a rubber stopper is used to close the mouth of a medicine bottle or a vacuum blood collection tube, the contents can be shielded from the external atmosphere and the degree of internal vacuum can be maintained for a long time.

[0011]

EXAMPLES Examples of the present invention will be described below with reference to examples.

[Example 1] Polypropylene 25% by weight, chlorobutyl 10
66 (75% by weight of chlorinated butyl rubber, 3% by weight of zinc white, and 1% by weight of stearic acid manufactured by Caxon Chemical Co., Ltd.) are heated to a temperature of 205 ° C. and melted.
At a shear rate of. While stirring this melt, 2.0% by weight of tetramethylthiuram disulfide was added,
Next, 2.0% by weight of sulfur was added to crosslink the fine particles of chlorobutyl dispersed in polypropylene to produce an elastomer. The melted elastomer was extruded into a cooling roll in a sheet form by an extruder to form a sheet having a thickness of 2 mm, and the sheet was pulverized into pellets of 2 mm square. The pellets were injection molded at a temperature of 220 ° C. into the shape of a rubber stopper shown in FIG. The puncture resistance of the rubber stopper when the thickness D of the needle puncture part of the rubber stopper of FIG. 1 is variously changed, and these rubber stoppers are inserted into the opening of the vacuum blood collection tube to close the vacuum blood collection tube and depressurize the inside. Table 1 shows the degree of vacuum retention inside the vacuum blood collection tube when the vacuum blood collection tube was kept in vacuum for 2 years after the test. The puncture resistance of the rubber stopper is the highest point (unit: Kg) measured using a Shimadzu Autograph S-500D machine at a pulling speed of 100 mm / min. Two years later, a 7-ml glass blood collection tube was closed with a rubber stopper, and the inside of the blood collection tube was depressurized to an initial blood collection volume of 5 ml. After leaving at room temperature for 2 years, blood was collected and the amount of blood collected was measured, and the degree of vacuum retention (unit%) was calculated as a ratio to the initial amount of blood collected.

[0012]

[Table 1]

As is clear from Table 1, when the thickness D of the needle puncture portion of the rubber stopper is 2.0 to 6.0 mm, the puncture resistance of the rubber stopper is small, and the degree of vacuum retention after two years is 90% or more. Is preferred. On the other hand, the thickness D of the needle puncture part is 2.0 mm
In the case of a rubber stopper with a thickness of less than 6.0 mm, the retention rate of the degree of vacuum inside the vacuum blood collection tube after 2 years drops to less than 90%. In this case, the puncture resistance of the needle is 0.8 kg or more, which is not preferable.

[0014]

Example 2 The thermoplastic elastomer used in Example 1
Was melted at a temperature of 220 ° C. and injection-molded into a sheet having a thickness of 6 mm. Table 2 shows the gas permeability and puncture resistance of this sheet.

[0015]

Comparative Examples 1 to 4 Using various thermoplastic elastomers shown in Table 1, the thickness was 6 mm with the injection molding machine used in Example 2.
Was injection molded. Table 2 shows the gas permeability and puncture resistance of this sheet.

[0016]

[Table 2]

In the polymer components shown in Table 2, PP is polypropylene, EPDM is ethylene propylene dienter polymer, and BR is polybutadiene. The gas permeability in Table 1 was measured using a Toyo Seiki M-C3 measuring device.
It was measured by the method A of JIS-K-7126. (Unit ml ・ mm / m
^2. day • atm) The puncture resistance was measured by the same measurement method as in Example 1.
As is clear from Table 2, the sheet of Example 2 of the present invention has a gas permeability and a puncture resistance of 100 ml · mm / m ² · day · atm, which are the standard values of a rubber stopper, and puncture. Although the resistance satisfies the resistance of 0.8 kg / 6 mm, any one or both of the rubber materials of Comparative Examples 1 to 4 do not satisfy the standard value.

[0018]

The rubber stopper for a medical container of the present invention has strong mechanical properties, so that it can be used when a rubber stopper is inserted into the mouth of a medical container or when a syringe needle is punctured into a rubber stopper. Rubber pieces and fine particles do not fall and mix with the contents of the medical container. In addition, the rubber stopper for medical containers of the present invention has excellent rubber elasticity and small compressive strain, so that the puncture resistance of the injection needle is small, and the re-sealing property after needle puncture is good, and the drug solution injected into the container. There is no problem of blood leaking. Further, the rubber stopper material for medical containers of the present invention can be stored in pellet form and can be molded into a rubber stopper by injection molding, so that the rubber stopper can be manufactured in a shorter time than the conventional rubber stopper produced by vulcanization molding. . Furthermore, since the rubber stopper material for medical containers of the present invention has good gas barrier properties, when the rubber stopper is used for closing the mouth of a medicine bottle or a vacuum blood collection tube, the contents are blocked from the external atmosphere, or the inside is protected. The degree of vacuum can be maintained for a long time.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view of a rubber stopper showing an example of the rubber stopper for a vacuum blood collection tube of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Body 2 Flange part 3 Leg part 4 Top surface part 5 Bottom part 6 Vacuum blood collection tube

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) A61J 1/05 A61J 1/06 A61B 5/15 A61M 5/14 B65D 39/04 C08L 23/00-23 / twenty two

Claims (3)

(57) [Claims] 1 to 10 to 45% by weight of crystalline polypropylene,
A rubber stopper for a medical container comprising a dynamically crosslinked thermoplastic elastomer in which 55 to 90% by weight of a nearly completely crosslinked halogenated butyl rubber having a particle diameter of 0.1 to 4 μm is dispersed. 2. The rubber stopper for a medical container according to claim 1, wherein the halogenated butyl rubber is chlorinated butyl rubber or brominated butyl rubber. 3. The thickness of the rubber stopper at the needle puncture part is 2.0 to 6.0 mm.
The rubber stopper for a medical container according to claim 1 or 2, wherein