JP2014079373A - Medical rubber plug sealed by cap - Google Patents

Abstract

Disclosed is a medical rubber stopper that is simple in production and excellent in chemical resistance and airtightness.
A rubber cap has an annular protrusion 4 for compression along an outer peripheral edge of a flange portion, and a lower surface of a leg 1 and a flange 2 in contact with a medicine are laminated with a continuous inert film 3 and sealed with a cap. The surface roughness of the medical rubber plug, which has a surface area of 50% or more from the outer edge of the lower surface of the flange of the rubber plug, and the area from 1 to 5 mm starting from the top of the leg side upper part. The present invention relates to a one-stage molded medical rubber stopper having an Ra of 0.1 μm or less.
[Selection] Figure 1

Description

The present invention relates to a medical rubber stopper that is sealed with a cap in which a leg portion in contact with a medicine and a lower surface of a flange are laminated with a continuous inert film.

In order to improve the quality stability of pharmaceuticals, an inert film such as a fluororesin is laminated on a rubber stopper leg that is in contact with a drug. As a method therefor, a two-stage molding method (Patent Document 1) is used. A molding method by one-stage molding is known.

In the two-stage molding, the legs that come into contact with the drug are laminated with a film in the mold for molding the legs, and the molded sheets are punched out individually to produce the plugs. After molding the flange part, the product is individually punched out to produce a rubber plug. Since the flange lower surface and part of the leg base are rubber surfaces, a rubber plug with excellent airtightness can be obtained. . However, after molding the leg plugs and punching them into the mold, after forming the collar part, the molding process is required twice to cut the collar part. Preparation is required, and the leg plug of the one-stage molded sheet and the punching process of the two-stage molded sheet are required twice. Therefore, productivity is poor and the defect rate tends to be high. Furthermore, in the case of an oily preparation, the oily preparation may reach the rubber surface, and the rubber may become wet and swell.

On the other hand, single-stage molding is based on the same molding method as when no film is laminated, and it is possible to laminate a film on the entire bottom surface of the flange. The manufacturing process is almost the same as a conventional non-laminated product and the process is simple. Yes, man-hours are greatly improved, so productivity is excellent. However, the airtightness of the rubber stopper and the vial is such that the base of the rubber stopper leg and the bottom surface of the flange are in close contact with the inner wall of the glass or resin vial, and the diameter of the rubber stopper leg is positively fitted to the inner diameter of the vial. Airtightness is obtained by pressurizing and tightening the rubber stopper flange and the top of the vial mouth with a cap, etc., but the laminated part of the mouth top of the glass vial and the rubber stopper flange is made of hard glass and film. There is a problem of low airtightness.

Japanese Patent Application Laid-Open No. 2004-216753

An object of the present invention is to provide a medical rubber stopper that is simple in production and excellent in chemical resistance and airtightness. More specifically, an object of the present invention is to improve hermeticity in a one-stage molded medical rubber stopper in which a leg portion in contact with a medicine and a lower surface of a flange are sealed with a cap laminated with a continuous inert film.

The present inventors have studied in detail about airtightness. As a result, even when a polytetrafluoroethylene film having a high surface smoothness with a surface roughness Ra of 0.05 μm or less is laminated, a problem arises in airtightness. It was found that despite the fact that the ethylene film was laminated and molded at a molding temperature of 170 ° C., which is 230 ° C. or less, fine irregularities on the mold surface were transferred to the surface of the laminated film and the airtightness was impaired. And it discovered that airtightness could be greatly improved if one-step molding was performed using a mold whose surface roughness Ra was polished to 0.03 μm or less, and the present invention was completed.

That is, the present invention is a medical device that has an annular convex portion for compression along the outer peripheral edge of the flange portion of the rubber plug, and is laminated with an inert film in which the leg portion in contact with the medicine and the lower surface of the flange are continuously laminated, and sealed with a cap. The surface roughness Ra of the rubber plug for the area from 1 to 5 mm starting from the top of the top surface of the leg side surface, with a surface area of 50% or more from the outer edge of the bottom surface of the flange of the rubber plug The present invention relates to a one-stage molded medical rubber stopper having a thickness of 0.1 μm or less.

From the uppermost part of the mold part corresponding to the lower surface of the flange part of the rubber plug, the surface area of the mold part corresponding to 50% or more from the outer edge part of the mold part and the upper part of the leg side surface, from 1 to 5 mm Is preferably formed in a single step using a mold polished to a surface roughness Ra of 0.03 μm or less.

It is preferable that the height of the annular protrusion for compression formed along the outer peripheral edge of the flange portion of the rubber plug is 10 to 60% of the thickness of the flange portion where the compression protrusion is not formed. .

The inert film laminated on the rubber plug is preferably a fluorine resin or an olefin resin.

The thickness of the inert film laminated on the rubber plug is preferably a film having a thickness of 200 μm or less.

The rubber plug is preferably surface-coated with a non-reactive silicone or a reactive silicone on the flange top surface or the inert film laminated surface.

The present invention also relates to a vial sealed with the medical rubber stopper, wherein the medicine filled in the container is in the form of powder, solid or liquid.

According to the present invention, a medical device having an annular convex portion for compression along the outer peripheral edge of the flange portion of the rubber plug, the leg portion in contact with the medicine and the bottom surface of the flange being laminated with a continuous inert film, and sealed with a cap. In the rubber plug, the surface roughness Ra of the portion having a surface area of 50% or more from the outer edge portion of the lower surface of the flange of the rubber plug and the portion from 1 to 5 mm starting from the uppermost portion on the upper side of the leg side surface Can be easily provided with a medical rubber stopper having excellent airtightness.

It is a fragmentary sectional view of the medical rubber stopper sealed with the cap of this invention. It is a fragmentary sectional view of the medical rubber stopper sealed with the cap of this invention. It is the top view and AA sectional view taken on the line of the medical rubber stopper of this invention. It is the upper side figure of the medical rubber stopper of the other aspect of this invention, and a BB sectional drawing. It is the upper side figure and CC sectional view taken on the line of the medical rubber stopper of the other aspect of this invention. It is sectional drawing of the medical rubber stopper of this invention by the one-step molding method produced in Examples 1-3, a top view, and a bottom view. It is sectional drawing and the top view of the medical rubber stopper by the one-step molding method produced in Comparative Examples 1-4. It is sectional drawing and the top view of the medical rubber stopper by the two-step molding method produced in the comparative example 3. It is sectional drawing and the top view of the medical rubber stopper by the one-step molding method produced by the comparative examples 1 and 2. It is a fragmentary sectional view showing a vial mouth part. It is explanatory drawing of the manufacturing method of the medical rubber stopper by the one-step molding method of this invention. It is explanatory drawing of the leg part shaping | molding method in the manufacturing method of the medical rubber stopper by a two-stage molding method. It is explanatory drawing of the flange molding method in the manufacturing method of the medical rubber stopper by a two-stage molding method.

The medical rubber plug of the present invention has an annular convex portion for compression along the outer peripheral edge of the flange portion of the rubber plug, and is laminated with an inert film in which a leg portion in contact with the drug and a lower surface of the flange are continuously laminated, and is sealed with a cap. A medical rubber plug that has a surface area of 50% or more than the outer edge of the lower surface of the flange of the rubber plug, and the surface of the region from 1 to 5 mm starting from the top of the leg side upper part A one-stage molded product having a roughness Ra of 0.1 μm or less.

The cap for sealing the medical rubber stopper is not particularly limited, and a known aluminum cap, resin cap, or the like can be used as it is. For example, those described in JP2011-229844A and JP2011-230839A can be suitably used. The aluminum cap is rotated while pressure is applied from above with the rubber cap / aluminum cap on the vial, and the skirt portion of the aluminum cap is bent on the lower surface of the vial flange, and is wound and sealed. On the other hand, the resin cap is sealed by the claw portion of the resin cap being hooked on the lower surface of the vial flange by the pressure from above with the rubber cap / aluminum cap on the vial.

1 and 2 show partial cross-sectional views created based on two orthogonal cross sections of the medical rubber plug of the present invention. A leg portion 1 is provided below the flange 2, and the leg portion in contact with the medicine and the lower surface of the flange are laminated with a continuous inert film 3. Note that the top surface of the flange may also be laminated with an inert film.

The compression-use annular convex portion 4 formed along the outer peripheral edge of the flange portion can be formed in various shapes as required, for example, as shown in FIGS.
In the mode 1 shown in FIG. 3, the compression-use annular convex portion 4 is formed in a continuous annular shape without a break. In addition, a lower portion 5 lower than other portions is formed at a plurality of locations on the compression annular convex portion, and a space surrounded by the compression annular convex portion 4 is interposed above the lower portion 5. The rubber plug is configured to communicate with the outside, and the rubber plug is prevented from being adsorbed to other objects.

In aspect 2 shown in FIG. 4, as in aspect 1, the compression-use annular convex portion 4 is formed in a continuous annular shape without cuts, but instead of the low-order portion 5 of aspect 1, adhesion to other objects is prevented. An adhesion preventing convex portion 6 is formed on the upper surface of the compression annular convex portion 4. The space surrounded by the compression annular convex portion 4 can communicate with the outside through the space around the adhesion preventing convex portion 6.

In the aspect 3 shown in FIG. 5, the compression-use annular projections 4 are formed in the shape of dots arranged in a ring shape in plan view, and the compression-use annular projections are formed at the lower annular portion 7 than the compression-use annular projections 4. The parts 4 are connected to each other.

The height of the compression-use annular convex portion 4 is preferably 10 to 60% of the thickness of the flange portion where the compression convex portion is not formed, and more preferably 15 to 40%. preferable. If it is less than 10%, the airtightness cannot be maintained due to insufficient pressure-bonding with the container flange surface, and if it exceeds 60%, winding with a sealing member such as an aluminum cap tends to be difficult. Here, the height of the compression annular convex portion 4 and the thickness of the flange portion where the compression convex portion is not formed are represented by h and t, for example, in FIGS.

The rubber stopper described in the above embodiment is exemplified for embodying the technical idea of the present invention, and the shape, dimensions, material, etc. of each part are not limited to those of this embodiment or modification. Rather, various modifications can be made within the scope of the claims of the present invention. For example, in the above aspect, in order to prevent the rubber stopper from falling off the bottle due to the oblique needle, a receiving protrusion corresponding to the rubber stopper compression ring-shaped protrusion may be provided on the lower surface of the upper wall of the cap.

The medical rubber plug of the present invention is 50% or more of the surface area of the mold portion corresponding to the lower surface of the flange of the rubber plug, and the portion from 1 to 5 mm starting from the top of the leg side upper part. The surface roughness Ra is 0.1 μm or less. Here, the cut-off value for calculating the arithmetic average roughness (Ra) is measured at 0.08 mm. The surface roughness Ra is 0.1 μm or less, preferably 0.05 μm or less, and more preferably 0.03 μm or less.

The rubber plug has a surface area of 50% or more from the outer edge of the mold part corresponding to the lower surface of the flange, and 1 to 5 mm starting from the uppermost part of the mold part corresponding to the upper part of the leg side surface. The above-mentioned part is preferably one-step molded using a mold polished to a surface roughness Ra of 0.03 μm or less. Since a rubber plug is manufactured using such a mold, the surface roughness of the corresponding rubber plug portion is reduced.

The portion of the mold polished to an arithmetic average roughness (Ra) of 0.03 μm or less is 50% or more of the surface area from the outer edge of the mold corresponding to the lower surface of the flange, preferably 70 % Or more, more preferably the entire surface. For example, as shown in FIG. 6 (b), the starting point for polishing starts from the flange outer edge portion X. As an example, when not used for the entire surface, for example, when the mold is used for a portion corresponding to 50% of the total surface area of the flange lower surface, it corresponds to the lower surface of the compression annular projection on the flange upper portion. It is preferable to polish the outer peripheral edge. In FIG. 6 (b), the portion of the lower surface of the rubber plug flange corresponding to the polished mold is shown, and the portion of the die corresponding to the lower surface of the rubber plug flange is shown in FIG. It shows with. In this example, a part of the mold part corresponding to the lower surface of the flange is polished.

As for the side surface of the rubber plug leg portion, the entire surface corresponding to the side portion may be polished or partially polished. Polishing the upper part of the side of the leg is effective for securing airtightness until the cap is sealed after the rubber stopper is plugged. When a part is polished, it is necessary that a part of 1 to 5 mm is polished from the uppermost part of the mold part corresponding to the upper part of the leg side surface. The end point to be polished is, for example, as shown in FIG. 6B, up to a point corresponding to 1 to 5 mm starting from the leg portion side surface upper portion Y. The end point is 1 mm or more starting from the uppermost part of the mold part, but is preferably polished by 1.5 mm or more. The upper limit is 5 mm or less in terms of cost, but 4 mm or less is preferable. The preferable range for polishing varies depending on the size of the rubber plug, and is preferably about 1 to 3 mm for a small size (50 ml or less) and about 2 to 5 mm for a large size (50 ml or more). In FIG. 6 (b), the portion of the side surface of the rubber stopper leg corresponding to the polished mold is shown, and the portion of the mold corresponding to the side surface of the rubber stopper leg in FIG. And M.

Even if a PTFE (polytetrafluoroethylene) film having a surface roughness Ra of 0.05 μm or less is laminated and molded at a temperature below the melting point of PTFE of 330 ° C. (such as 170 ° C.), fine irregularities on the mold surface are formed on the surface of the laminated film. The marks may be transferred to adversely affect the sealing performance, resulting in liquid leakage problems. Here, the cause of fine cutting trace generation of the mold is due to the vibration generated between the equipment tool and the mold, the sharpness of the cutting tool, the nature of the mold material, the cutting conditions, It is considered that the surface roughness is deteriorated due to partial unevenness such as a circumferential processed eye, a yuzu skin, etc. on the surface of the workpiece, thereby impairing smoothness.

Usually, polishing and polishing are performed after cutting, but the surface of the conventional mold has microscopic unevenness, and laminated rubber members molded with such a mold are Even if the film before lamination is smooth such as Ra 0.05 μm or less, the roughness of the mold surface adversely affects the sealing performance. On the other hand, in the present invention, since the mirror surface finish for adjusting the Ra of the mold surface is applied, even when laminated with a skiving film with Ra exceeding 0.05 μm, a laminated gasket excellent in sealing properties is manufactured. it can.

FIG. 11 shows a manufacturing method by one-stage molding, which is a manufacturing method of the rubber plug of the present invention. In the drawing, the compression-use annular convex portion is omitted. The molding die includes an upper mold 8 that forms a flange portion and a lower mold 9 that forms a leg portion, and a heater (not shown) is connected so that each can be heated. As the heat source of the heater, for example, an electric heater, steam, oil or the like can be used. According to this one-stage molding, a rubber stopper in which an inert film is laminated on the lower surface of the flange can be manufactured.

The material used for the mold is not particularly limited, and a known mold material can be used, but carbon steel and precipitation stainless steel are preferable. The molding die can be manufactured using a cutting method such as a method of performing polishing or mirror polishing after cutting with a cemented carbide tool, a coated cemented carbide, a cBN sintered body or the like.

A recess is formed in the mold so as to be recessed inward. The recess is formed corresponding to the shape of the rubber plug. A convex portion forming portion corresponding to the shape of the annular convex portion for compression of the rubber stopper is formed in the concave portion of the upper mold 8 (not shown).

A leg forming portion corresponding to the shape of the leg portion of the rubber plug is formed in the concave portion of the lower mold 9. In the leg forming portion, the mold surface corresponding to the side surface of the leg is subjected to a mirror finish so that the arithmetic average roughness Ra measured at a cutoff value of 0.08 mm is 0.03 μm or less. The mirror finish does not need to be processed on the entire mold surface corresponding to the leg side surface, and may be a part.

The recess can be produced, for example, by a method in which the cavity of the gasket is cut with an overall shape tool of a carbide tool, and each annular protrusion is undercut. Another method includes electric discharge machining.

In the cutting process, a high-speed cutting method is employed in which the cutting tools of these cemented carbide tools, coated cemented carbides, and cBN sintered bodies are cut at a higher speed than usual (such as a speed exceeding 100,000 rpm). This makes it possible to reduce the depth of mirror polishing after cutting by making the cutting depth of the cutting blade shallow.

In addition, there is a method called electroforming. The electroforming method is a method of polishing an area that becomes an under part in a normal cutting process and cannot be visually observed. In the electroforming method, polishing is performed at the time of making the cavity piece master, so the convex part that hits the same seal part as the rubber stopper becomes the outside polishing work, so it is easy to check the state of the polishing process and has excellent work efficiency Yes.

First, a mold piece-shaped master serving as a product part is made of brass or an aluminum alloy, and master polishing is performed at this point. Next, hard chrome plating is adhered to the master, and further, it is meat-coated with a nickel cobalt alloy. The master part is centered, and the dimensions of the fleshed part are cut to finish the external dimensions. The master part is melted away to make a cavity piece.

In the mirror finish on the side of the leg part, polishing methods that do not use an abrasive include polishing with a high-power ultrasonic polishing machine, electrolytic polishing that preferentially dissolves fine projections on the mold surface, and processing the uneven parts with a processing solution. There is chemical polishing that dissolves and smoothes.

Examples of the electrolytic polishing include “Aluminum Handbook”, 6th edition, edited by Japan Aluminum Association, 2001, p. 164-165; various methods described in US Pat. No. 2,708,655; “Practical Surface Technology”, vol. 33, no. 3, 1986, p. The method described in 32-38;

As chemical polishing, for example, “Aluminum Handbook”, 6th edition, edited by Japan Aluminum Association, 2001, p. Examples thereof include various methods described in 164 to 165. In addition, a phosphoric acid-nitric acid method, an Alupol I method, an Alupol V method, an Alcoa R5 method, an H ₃ PO ₄ —CH ₃ COOH—Cu method, and an H ₃ PO ₄ —HNO ₃ —CH ₃ COOH method are also suitable.

On the other hand, the polishing method using an abrasive is appropriately changed according to the difference in the mold material and the degree of quenching, and includes manual polishing and mechanical polishing. After wet or dry buff polishing, mirror polishing is performed. Mirror surface polishing and super mirror surface polishing for removing the cutting edges of the tool cutting are performed by rotating a workpiece or a grindstone on a rotating buff, or by manual processing.

As a polishing tool, use soft wood and felt, synthetic fiber, acrylic fiber buff, etc., attach abrasive grains to this, and in order from hard to soft polishing tool, change from coarse paste to fine grade paste, Mirror finish.

Abrasives such as diamond, alumina, silicon carbide, cubic boron nitride, boron carbide, zirconium oxide, manganese oxide, colloidal silica, and the like are used as polishing agents used for mold polishing and mirror finishing. Examples of alumina include corundum abrasives such as white fused alumina, brown fused alumina, alumina-zirconia, pulverized alumina, and sintered alumina. Abrasive grains having a grain size of # 600 to # 15000 are suitable (more preferably # 8000 or more), and can be used as fine particles or paste. Specifically, a polishing agent such as diamond, alumina, silicon carbide or the like is used as an abrasive paste with vegetable oil, and the polishing is performed by making the abrasive grains finer in order from a soft wood such as a willow or a balsa or a buff.

In addition, by pressing the cut mold surface against the mold surface with a diamond burnishing bit in the same manner as normal biting, the convex part is smoothed without cutting powder and surface roughness is improved. There is also a method of processing to 0.01 mm or less in diameter.

In some cases, the mold is plated in order to improve mold contamination during molding and reduce the number of times the mold is washed. The plating thickness is preferably 15 μm or less, and more preferably 10 μm or less. If it exceeds 15 μm, there may be a problem in dimensional accuracy in the annular projection diameter, valley diameter, and thread diameter.

The mirror surface finish of the mold provides a smooth mold surface with an arithmetic average roughness Ra of 0.03 μm or less measured at a cutoff value of 0.08 mm of the corresponding portion, and Ra is preferably 0.02 μm or less. Preferably it is 0.015 micrometer or less. In the present invention, at least a part of the lower surface of the flange or the side surface of the leg is mirror-finished so that Ra is adjusted to a specific value or less, but the other mold surface of the recess may be similarly adjusted, and the entire surface is mirror-finished. May be applied to adjust Ra. After molding, when the mold is released from the mold, it is forcibly released from the valley of the cavity whose diameter is reduced, so that the surface of the annular protrusion may be easily scratched. The entire side surface is preferably mirror-finished.
In the present invention, the arithmetic average roughness (Ra) is measured according to JIS B0601-2001.

In the molding process, the upper mold and the lower mold are heated in advance before the rubber plug is molded. The preheating temperature is preferably about 155 to 200 ° C.

Next, a stack of an inert film 3 and a kneaded sheet 10 (unvulcanized rubber sheet) made of a rubber plug body material is placed on the upper surface of the lower mold 9. In this case, the upper mold may be on the bottom and the lower mold may be on the top, or an unvulcanized rubber sheet having a laminated film stacked thereon may be placed on the upper mold.

The resin constituting the inactive film 3 is not particularly limited, but tetrafluoroethylene / ethylene copolymer (ETFE), polytetrafluoroethylene (PTFE), polychlorotetratetraacetic acid is obtained because good chemical resistance is obtained. At least one fluororesin or olefin resin selected from the group consisting of fluoroethylene (PCTFE) is preferred. Further, as a sterilization method for medical containers, steam sterilization, ethylene oxide gas sterilization, and gamma ray sterilization are performed, but PTFE has low resistance to gamma rays. Therefore, ETFE, modified ETFE, and PCTFE, which have high resistance to gamma sterilization, are particularly preferable.

Here, ETFE is a copolymer of ethylene and tetrafluoroethylene in a molar ratio of 30/70 to 70/30, and there is a modified ETFE obtained by copolymerizing other components for the purpose of modification. Examples of other components include fluorine-containing olefins and hydrocarbon olefins. Specific examples include α-olefins such as propylene and butene, fluorine-containing olefins such as hexafluoropropylene, vinylidene fluoride, perfluorobutylethylene, and trifluorochloroethylene, ethylene vinyl ether, perfluoromethyl vinyl ether, and perfluoropropyl vinyl ether. Vinyl ethers, fluorine-containing acrylates, and the like, which are copolymerized by about 2 to 10 mol% to modify ETFE.

As the modified ETFE, ETFE having a functional group imparting adhesiveness can be suitably used. Examples of the functional group include a carboxyl group, an anhydrous carboxyl group, an epoxy group, a hydroxyl group, an isocyanate group, an ester group, and an amide group. Aldehyde group, amino group, cyano group, carbon-carbon double bond, sulfonic acid group, ether group and the like. Moreover, as a commercial item of modified ETFE, Asahi Glass Co., Ltd. full-on AH-2000 etc. are mentioned.

Examples of the olefin resin include polyethylene, ethylene-propylene copolymer, ethylene-propylene-nonconjugated diene copolymer, ethylene-butene copolymer, ethylene-hexene copolymer, ethylene-octene copolymer, ethylene-acetic acid. Vinyl copolymers, ethylene-vinyl alcohol copolymers, ethylene-ethyl acrylate copolymers, polyethylene resins such as chlorinated polyethylene, polypropylene, propylene-ethylene random copolymers, propylene-ethylene block copolymers, chlorinated Examples thereof include polypropylene resins such as polypropylene, polybutene, polyisobutylene, polymethylpentene, and cyclic olefin copolymers, and polyethylene (particularly, ultrahigh molecular weight polyethylene (UHMWPE)) is preferable. The olefin resin may contain fluorine.

The thickness of the inert film 3 may be appropriately adjusted according to the shape and size of the gasket, but the upper limit is preferably 200 μm or less, and more preferably 100 μm or less. The lower limit is preferably 50 μm.

In addition, the arithmetic average roughness Ra of the inert film 3 is from 0.01 to 0.03 μm of a casting method film or an extruded film to 0.10 μm of a skiving film, and the surface roughness of the mold. By setting the thickness to 0.03 μm or less, a laminated gasket excellent in liquid adhesion and airtightness can be obtained. The lower limit of Ra of the inert film itself is not particularly limited.

The inert film 3 is preferably subjected to a treatment for improving the adhesion with rubber or the like. Examples of the treatment for improving the adhesion include chemical treatment, treatment for roughening the surface of the film, and combinations thereof. Specific examples include sodium treatment, glow discharge treatment, under atmospheric pressure or under vacuum. And plasma treatment (discharge treatment), excimer laser treatment (discharge treatment), and ion beam treatment.

The kneading sheet 10 forms a rubber plug body and is made of an elastic material. The elastic material of the rubber plug body is not particularly limited. For example, various rubber materials such as natural rubber, butyl rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, silicone rubber, epichlorohydrin rubber, ethylene propylene rubber, nitrile rubber, And various thermoplastic elastomers such as polyurethane, polyester, polyamide, olefin, and styrene. These elastic materials can be used alone or by blending a plurality of components. Among these, a material that can obtain elasticity by vulcanization is preferable. In the case of a vulcanized material, known compounding agents in the rubber industry such as a vulcanizing agent such as sulfur and a vulcanization accelerator can be appropriately added.

The kneaded sheet 10 is a sealed kneader, an open roll kneader or the like, and a kneaded product obtained by kneading the blended material at a predetermined blending ratio is made into an unvulcanized rubber sheet with a calendar or a sheet molding machine. Next, an unvulcanized rubber sheet having a constant weight and size and an inert film are stacked and placed in a mold and molded by a vacuum press, whereby a laminated gasket molded sheet can be obtained.

The molding conditions are not particularly limited and may be set as appropriate. The molding temperature is preferably 155 to 200 ° C, more preferably 165 to 190 ° C, and the molding time is preferably 3 to 15 minutes, more preferably. 5-10 minutes.

Thereafter, unnecessary parts are cut and removed from the molded product of the rubber plug, and then washed, sterilized, dried and visually inspected to obtain a finished product of the rubber plug.

The medical rubber stopper sealed with the cap manufactured as described above has an annular convex portion 4 for compression along the outer peripheral edge of the flange portion, and an inactive film in which the leg portion 1 in contact with the medicine and the lower surface of the flange are continuous. 3 are stacked.

In the rubber stopper of the present invention, the top surface of the flange or the inert film laminated surface is preferably surface-coated with non-reactive silicone or reactive silicone.

The vial of the present invention is suitably applied to a vial sealed with the medical rubber stopper, wherein the form of the medicine filled in the container is powder, solid or liquid (liquid or oil). be able to. Moreover, it is applicable also to the use for freeze-drying.

The present invention will be specifically described based on examples, but the present invention is not limited to these examples.

Examples 1-3, Comparative Examples 1-4
As shown in Table 1, an unvulcanized rubber sheet (JISA hardness 45) containing 50 parts by mass of a silica-based filler with 100 parts by mass of chlorinated butyl rubber was bonded to an inert film having a thickness of 75 μm shown below. Using a molding die, molding was performed while vulcanizing and bonding at 175 ° C. for 10 minutes with a vacuum press, and rubber plugs having the following shapes were produced. The top view and sectional view of each rubber plug are shown in FIGS. 6 (Examples 1 to 3) and 7 (Comparative Examples 1 to 4). Here, as the vulcanized rubber sheet, a curable silicone spray-coated one only on the flange top surface side and one coated on both surfaces were produced, and then the burr portion was punched out and subjected to a cleaning sterilization drying process.
In addition, the height of the annular convex portion for compression is set to 0.8 mm in the annular convex portion height for compression in Examples 1 to 3 (27% of the thickness where the compressed convex portion is not formed), and 1.5 mm in width. In the comparative example and the control example, the protrusion height was 0.3 mm (there was no compression protrusion on the outer peripheral edge of the flange upper surface).

Inactive film: Modified ETFE, manufactured by Asahi Glass Co., Ltd., trade name “Aflex”, thickness 75 μ, surface roughness Ra (μm) 0.02 to 0.03 (cutoff value 0.08, evaluation length 0) .25mm)

Basic rubber plug shape flange diameter: 19.0mm
Maximum leg diameter: 13.0mm
Flange thickness t: 3.0mm
Needle stick thickness: 2.0mm

Mold used: Stainless steel mold materials Examples 1 to 3, Comparative Examples 1 to 2: Polishing of the lower surface of the flange and the area up to 2 mm from the uppermost surface of the leg side surface.
Comparative Example 4, Control Examples 1 to 3: The flange lower surface and the entire leg were blasted.
Here, the bottom surface of the rubber plug flange and the leg are the same lower mold part, but the selection of whether or not to polish 1 to 5 mm from the uppermost part of the bottom surface of the flange and the side of the leg depends on the processing method and masking. It is possible to change the surface roughness.

Control Examples 1-3
Control examples 1 and 2 were prepared in the same manner as in the examples and comparative examples except that the inert film was not laminated. In Control Example 3, it was produced by a two-stage molding method. A top view and a cross-sectional view of each rubber plug are shown in FIGS.

The following tests were conducted using the rubber plugs obtained in the examples, comparative examples and control examples.
(Surface roughness Ra)
The surface roughness of the film, the surface roughness of the mold, and the surface roughness of the laminated rubber plug were measured according to JIS B0601 2001 using a leather microscope (manufactured by Keyence Corporation, VK-9710) and a lens magnification of 50 times. Measured with

(Airtightness test method)
There are various types of glass tube bottles, A to G, but the upper surface of the bottle mouth is flat, the inside diameter of the upper side of the bottle mouth is made small, the rubber stopper rises after stoppering, and the closure stopper tube bottle B (mouth An inner diameter of 12.45 mm and a full capacity of 14.2 ml) or a shape E in which the upper surface of the tube bottle mouth is lowered toward the outer peripheral surface (a mouth inner diameter of 12.50 mm and a full capacity of 18.4 ml) was used.
0.62 g / 1 tablet type silica gel desiccant (manufactured by Yamajin Pharmaceutical Co., Ltd.) is accurately weighed, placed in a clean, clean 10 ml vial, and wrapped with an aluminum cap at normal pressure. Temperature 40 ° C. Humidity 75% / 1 month and 3 months After storing in a thermostatic bath, the silica gel desiccant was taken out, accurately weighed, and the weight increase (change in hygroscopic weight of silica gel desiccant) was determined.

From the test results shown in Table 1, the effect of the surface roughness of the lower surface of the flange and the annular rib around the outer periphery of the flange upper portion is recognized. The medical rubber stopper of the present invention has almost the same level of airtightness as that of Comparative Examples 1 to 3, in which an inert film is not laminated on the lower surface of the flange having the most excellent airtightness. Considering that the chemical resistance is improved with respect to these control examples, the medical rubber plug of the present invention is excellent as a medical rubber plug sealed with a cap.
In Comparative Example 3, because the two-stage molding is used, the lower surface of the flange is not laminated, and the surface roughness is rough, but the unevenness of the rubber surface is crushed by crimping, and airtightness can be secured on the lower surface of the flange. ing.

DESCRIPTION OF SYMBOLS 1 Leg part 2 Flange 3 Inactive film 4 Compression annular convex part 5 Low position part 6 Anti-adhesion convex part 7 Low annular part 8 Upper mold 9 Lower mold 10 Kneading sheet h Height of annular convex part t for compression Flange thickness

Claims (7)

A medical rubber plug sealed with a cap, having an annular convex part for compression along the outer peripheral edge of the flange part of the rubber plug, wherein the leg part in contact with the medicine and the lower surface of the flange are laminated with a continuous inert film. ,
The rubber plug has a surface area of 50% or more from the outer edge of the lower surface of the flange, and a surface roughness Ra of 1 to 5 mm starting from the uppermost part of the upper part of the leg side surface is 0.1 μm or less. One-stage molded medical rubber stopper. From the uppermost part of the mold part corresponding to the lower surface of the flange part of the rubber plug, the surface area of the mold part corresponding to 50% or more from the outer edge part of the mold part and the upper part of the leg side surface, from 1 to 5 mm The medical rubber plug according to claim 1, wherein the region is molded in one step using a mold polished to a surface roughness Ra of 0.03 μm or less. The height of the compression-use annular convex portion formed along the outer peripheral edge of the flange portion of the rubber plug is 10 to 60% of the thickness of the flange portion where the compression convex portion is not formed. Or the medical rubber stopper of 2. The medical rubber plug according to any one of claims 1 to 3, wherein the inert film laminated on the rubber plug is a fluororesin or an olefin resin. The medical rubber plug according to any one of claims 1 to 4, wherein the inert film laminated on the rubber plug has a thickness of 200 µm or less. The medical rubber plug according to any one of claims 1 to 5, wherein the rubber plug is coated with a non-reactive silicone or a reactive silicone on a flange top surface or an inert film laminated surface. A vial sealed with the medical rubber stopper according to any one of claims 1 to 6, wherein the form of the medicine filled in the container is powder, solid or liquid.

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