EP0172613A2

EP0172613A2 - Resin-laminated rubber plug

Info

Publication number: EP0172613A2
Application number: EP85304005A
Authority: EP
Inventors: Denpei Sudo
Original assignee: Daikyo Gomu Seiko KK
Current assignee: Daikyo Gomu Seiko KK
Priority date: 1984-07-31
Filing date: 1985-06-05
Publication date: 1986-02-26
Also published as: JPS6131441U; JPH0340297Y2; EP0172613A3

Abstract

A resin-laminated rubber plug for a medical vial or bottle is free from the resin coating at the upper part of the body, where the rubber surface is exposed for contacting the inside of the mouth of the bottle or vial.

Description

"RESIN-LAMINATED RUBBER PLUG"

This invention relates to a resin-laminated rubber plug for a medical bottle or vial and more particularly it is concerned with a rubber plug having a body part for insertion into the mouth of a bottle or vial, which body part has a surrounding lamina of chemical-resistant resin.

BACKGROUND

Lately, high quality or high efficiency medical drugs have been developed and accordingly, the techniques for the prodution thereof have made remarkable progress. That is, it has been required to keep the optimum conditions, not only during the production of medical drugs, but also during storage thereof so as to maintain this efficacy and purity.
For example, it is said that a rubber plug made of isoprene-isobutylene rubber whose surface for engagement with the inner surface of the mouth of a bottle is laminated with a fluorine resin is an excellent sealant because the rubber, which is gas impermeable and resistant to water absorbtion, is laminated with a resin having a chemical inactivity and low adsorptivity. Such a plug is disclosed in Japanese Patent Publication No. 53184/1982. However, such a laminated rubber plug has encountered a problem of airtightness depending upon the process for preparing a medical drug, and it has thus been proposed to provide a small annular protrusion on the lower annular surface area of the rubber plug in contact with the annular front surface of a medical vial (US Patent No. 4,441,621). This structure is effective under some conditions, but the airtightness diminishes, depending on the degree of vacuum in the medical vial and the passage of time, after fitment of the rubber plug into the vial mouth, unless an aluminum or other fastening cap is used.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improved resin-laminated rubber plug or closure for a medical bottle or vial, and in particular to improve the airtightness of such a plug, which may be pierceable (for example by the needle of a syringe).
The invention is characterised in that the body part is free from the chemically-resistant resin at its upper end, where the surface of the rubber is exposed for contacting the adjacent part of the inner surface of the mouth of the bottle or vial.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a side sectional view of a medical vial closed by a rubber plug with an aluminum sealing cap secured thereto.
Fig. 2 is a side sectional view, on an enlarged scale, of the mouth of a medical vial closed by a rubber plug of the prior art.
Fig. 3 is a side sectional view, on an enlarged scale, of the mouth of a medical vial closed by a rubber plug according to the present invention.
Fig. 4 is a side sectional view, on an enlarged scale, of the mouth of a medical vial closed by a rubber plug according to the present invention with an aluminum sealing cap secured thereto.
Fig. 5 is a side sectional view, on an enlarged scale, of another embodiment of a rubber plug according to the present invention.
Fig. 6 to Fig. 10 are side sectional views, on an enlarged scale, of various embodiments of the characteristic part of rubber plugs according to the present invention.
Fig. 11 and Fig. 12 are side sectional views similar to Fig. 6 to Fig. 10 but showing examples of the prior are.

DETAILED DESCRIPTION OF THE INVENTION

The rubber for a plug, according to the invention, may be a natural rubber or a synthetic rubber such as iroprene-isobutylene rubber, isoprene rubber, butadiene rubber, ethylene-propylene rubber or a rubber obtained by polymerizing terpolymer solutions. For the chemical-resistant resin, there may be used a tetrafluoroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymers, tetrafluoroethylene-pentafluoropropylene copolymers, tetrafluoroethylene-ethylene copolymers, tetrafluoroethylene-propolymers, chlorotrifluoroethylene polymer and other fluoro-resins, and polyethylene, polypropylene or other resins.
Limination of such a resin can be carried out in known manner, for example, by a method described in Japanese Patent Publication No. 53184/1982.
The present invention will now be explained by reference to the accompanying drawings. In order to store medicaments or injection liquids without deterioration for a long time, it is generally required to keep them in a cold and dark place and to keep vials therefor evacuated or sealed with an inert gas G. When these conditions were examined in detail in a process for preparing a medicament and in a method of sealing a vial, it was found necessary to charge a medicament E in a vial B, toevacuate the vial B or rinse it with a gas and to ascertain the contacted state of a rubber plug A with the inner surface of the vial mouth at locations 2, 3 and 4 as shown in Fig. 3. In the case of the state as shown in Fig. 2, change of the degree of vacuum and leakage of the filled gas 5 and 6 take place while a rubber plug A is plugged into the vial mouth and fastened firmly by an aluminum cap D, since a fluoro-resin C coated onto the body part 2 of the rubber plug A has a hard and smooth surface and an inferior adhesion to the inner surface of the vial mouth.
Generally, a rubber plug is so designed that the diameter w of the body part to be inserted into the vial mouth is 1-10% larger than that of the vial's mouth. The sealing of the vial mouth is considered to be improved by increasing this fraction to increase the pressure of the outer surface of the body part on the inner surface of the vial mouth at positions 2 and 3, but in the case of using a resin-laminated rubber plug, this consideration is not correct, i.e. there is found no such effect. Even if the rubber plug is completely plugged into the vial mouth, changes in the passage of time, i.e. the lowering of vacuum degree or the leakage of gas after rinsing cannot be prevented (unless the plug is firmly fastered by an aluminum cap) because of the smoothness and hardness of the resin surface.
According to the present invention, it is found that the retention of vacuum or a sealed gas can surprisingly be improved by keeping the rubber surface exposed within a range (x) of 0.1 to 5 mm at the upper end of the body part as shown in Fig. 6, 7 and 8 or by providing one or two small annular protrusions on the rubber surface in this range as shown in Fig. 5, 9 and 10. Preferably, the small protrusion has a width (along the body) of at most 3 mm and a height z (laterally of the body) of at most 0.8 mm in cross section. Under the above described conditions, a plugging operation of the rubber plug can also be carried out in smooth manner.
Preparation of the rubber plug of the present invention is carried out as follows: A chemical-resistant resin film to be laminated is placed on a lower metal mould having a plurality of recesses for forming an annular body part of a rubber plug to be inserted into the mouth of a vial. On the lower metal mould a vulcanizable compound rubber and an upper metal mould are stacked, and the lower metal mould and upper metal mould are heated and pressed at a predetermined temperature to form the body part and laminate the resin film thereto. Then, the thus formed body part is punched in a predetermined dimension and placed in the lower metal mould, on which the same compound rubber as described above and an upper metal mould having a recess for forming a flanged cap part of the rubber plug are placed, and the lower metal mould and upper metal mould are heated and pressed to vulcanize the rubber and simultaneously combine the cap part and body part, followed by punching to obtain a finished laminated rubber plug.
The rubber plug of the present invention can be applied to various containers, for example, glass bottles or vials and plastics-laminated bottles or vials for medicaments or injection liquids of interferon, antibiotics, vitamines, vaccines, sugars, basic amino acids and the like.
Charging of a vial or bottle with a medicament may be carried out by the freeze-drying method, liquid charging method or powder charging method, and in any method the rubber plug of the present invention provides an excellent airtight seal.
Depending on these methods, the shape of the body part of a rubber plug can be varied, but in general, the size of the rubber plug is such that the maximum diameter w of the body part is 7 to 30 mm and the length (x + y) of the body part comprises the length x (0.1 to 5 mm) of a rubber-surfaced portion and the length y of a portion bearing the chemically resistant resin film, y being 3 to 15 mm and x/(x + y) being preferably not greater than o.5, more preferably between 0.1 and 0.35.
The following examples are given in order to illustrate the present invention without limiting the same.

Examples

Sealing tests were carried out using a rubber (V10-F7) plug of the present invention, having a body part with a diameter of 13.1 ± 0.1 mm and a tubular bottle (JIS R 3523-(1978)) for an injection liquid TB 6, having a volume of 31.0 ml and a mouth of inner diameter of 12.5 + 0.2 mm.
In each test, the above described tubular bottle was charged in a vacuum plugging machine which was then adjusted to a vacuum degree of 10 + 1 Torr. A rubber plug was plugged into the mouth of the bottle. The plugged bottle was allowed to stand in air for 360 + 5 minutes, during which the degree of vacuum in the tubular bottle was measured by means of an electron manometer (TOYOTA-MANOMETER-AA 2472 manufactured by Toyota Koki KK). The test was carried out on rubber plugs of the present invention (Tests Nos. 1-4 corresponding to Fig. 6-9) and rubber plugs of the prior art (Test Nos. 5-7 corresponding to Fig. 11-13), thus obtaining results shown in the following table:
As is evident from these results, the degree of vacuum can substantially be maintained in spite of allowing the sample bottle to stand in the air for about 6 hours in the cases of Test Nos. 1-4 wherein the outer circumference of the upper end of the leg part is not laminated to expose the rubber surface (x) according to the present invention. In the case of Test Nos. 11-13 wherein the lamina reaches the annular front face of the cap part of the rubber plug as in the prior art, on the other hand, the sealing is not sufficient because of leakage of air through the gap 2, 3 and 4 between the lamina and the mouth of the bottle.

Claims

1. A resin-laminated rubber plug for a medical vial or bottle, having a rubber body part for insertion into the mouth of the vial or bottle, the body part being surrounded by a chemically-resistant resin coating, characterised in that the surface of the body part is free from the chemical-resistant resin at its upper end, where the surface of the rubber is exposed for contacting the adjacent part of the inner surface of the mouth.

2. A plug as claimed in Claim 1, wherein the said exposed rubber surface has a length of 0.1 to 5 mm.

3. A plug as claimed in Claim 1, wherein the exposed rubber surface is provided with at least one annular protrusion.

4. A plug as claimed in Claim 3, wherein the protrusion has a width of at most 3 mm and a height of at most 0.8 mm.

5. A plug as claimed in any foregoing claim, wherein the body part has an outer diameter of 7 to 30 mm.

6. A plug as claimed in any foregoing claim, wherein the length of the exposed rubber surface is from 0.1 to 5 mm and the length of the coating is from 3 to 15 mm.

7. A plug as claimed in Claim 6, wherein the ratio of the length of the exposed rubber surface to that of the resin coating is at most 0.5.

8. A plug as claimed in any foregoing claim, wherein the chemical-resistant resin comprises any one of a tetrafluoroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymers, tetrafluoroethylene-pentafluoropropylene copolymers, tetrafluoroethylene-ethylene copolymers, tetrafluoroethylene-propylene copolymers, chlorotrifluoroethylene polymers, polyethylene or polypropylene.

9. A plug as claimed in Claim 1, wherein the body part is notched at two positions to form two legs.