Gasket for syringe, method for manufacturing the same, and prefilled syringe using the gasket

The present invention relates to a syringe gasket suitable for a prefilled syringe and a prefilled syringe using the gasket.

Currently, the cylinder that serves as the syringe and container is filled with the injection solution in advance, and the tip of the cylinder to which the injection needle is attached is transported and stored in a state of being sealed and sealed with a cap. A so-called prefilled syringe, in which an injection needle is attached to a portion, a piston is pushed toward the tip side, and a gasket is slid to administer an injection solution via the injection needle, is attracting attention.

This prefilled syringe can be administered in an accurate amount without misuse of the injection solution, does not require transfer work of the injection solution, and can prevent microbial contamination of the injection solution due to such work. From the point of view, it has come to be widely used in recent years.

By the way, in the conventional prefilled syringe, the gasket is made of heat vulcanized rubber such as butyl rubber, and in order to improve the slidability of the gasket in the cylinder, silicone grease is applied to the surface of the gasket and the inner surface of the cylinder. It had been. However, in recent years, in a prefilled syringe, when the silicone grease applied to the surface of the gasket is peeled off from the surface and exists as a minute oil ball in the injection solution, and the oil ball is injected into the human body together with the injection solution. Although silicone grease itself is not toxic to the human body, it has been pointed out that it may block peripheral blood vessels in the brain.

When a gasket made of heat-vulcanized rubber is used, the plasticizer, sulfur-based or amine-based cross-linking aid, process oil, pigment, etc. contained in the rubber are leached into the injection solution for injection. There was a risk of lowering the titer of the active ingredient in the liquid or altering the quality of the active ingredient. For this reason, the gasket created to prevent these harmful effects must be cleaned after a complicated cleaning process such as high-temperature strong acid cleaning neutralization high-temperature strong alkali cleaning neutralization sterile water cleaning sterile drying. There is also a problem that it cannot be used and it is difficult to efficiently and economically manufacture a gasket.

Therefore, in order to solve such a problem, a prefilled syringe 2 using a gasket 1 as shown in FIG. 2 has been proposed (see, for example, Patent Document 1). In order to improve the slidability between the cylinder 3 and the gasket 1 made of heat vulcanized rubber, this prefilled syringe 2 has PTFE (polytetrafluoroethylene; tetrafluoride) having an extremely low coefficient of friction on the surface of the gasket body 1a. A resin film 4 made of a (ethylene resin) film or an ultra-high molecular weight polyethylene film is laminated. In FIG. 2, 5 is a cap that seals the tip portion of the prefilled syringe 2 to which the injection needle is attached, and 6 is an injection solution filled inside the prefilled syringe 2. Further, 1b in FIG. 2 is a piston mounting portion to which the tip of a piston (not shown) is screwed.

According to such a technique, the slidability of the gasket 1 in the cylinder 3 can be improved, and it is not necessary to apply silicone grease to the surface of the gasket 1 or the inner surface of the cylinder. Adverse effects can be avoided.<patcit num="1"><text>Japanese Patent No. 3387775</text></patcit>

<p> However, in the above-mentioned prefilled syringe 2, since the gasket 1 is made of heat-vulcanized rubber, it can be used as the gasket 1 only after undergoing the complicated cleaning process as described in detail above. However, it is still difficult to efficiently and economically manufacture the gasket 1 (and thus the prefilled syringe 2).</p><p> Further, when a PTFE film is used as the resin film 4 laminated on the surface of the gasket body 1a, this PTFE is non-adhesive and the bonding force with the gasket body 1a is extremely weak, so that during long-term storage or transportation. The stress applied to the prefilled syringe 2 from the outside propagates to the joint surface between the gasket body 1a and the resin film 4, and the stress disengages the joint between the gasket body 1a and the resin film 4 and deteriorates the slidability of the gasket 1. In addition to this, there is a risk that the injection liquid filled in the cylinder 3 will leak from between the cylinder 3 and the gasket 1.</p><p> Here, in order to improve the adhesiveness between the gasket body 1a and the resin film 4, it is conceivable to surface-treat the resin film 4 with metallic sodium to form a carboxyl group on the surface of the resin film 4, but such a surface When the treatment is performed, the predetermined dissolution test specified by the Japanese Pharmacy cannot be cleared, and the resin film 4 turns brown. Therefore, the surface treatment method for this is such as gasket 1. It cannot be used for medical purposes.</p><p> Therefore, the main subject of the present invention is to provide a gasket for a syringe that can be manufactured efficiently and economically, has excellent slidability, and can be used stably for a long period of time. is there. Further, a further problem of the present invention is that the syringe gasket can be manufactured efficiently and economically by using such a syringe gasket, and the slidability and airtightness of the syringe gasket are impaired even by long-term storage and transportation. No prefilled syringe is to be provided.</p>

<p> The invention described in claim 1 is (a) A syringe gasket 10 formed by co-molding a PTFE film 14 on the surface of a gasket body 12 made of crosslinked silicone rubber. (b) A silica fine particle layer 16 is provided on the joint surface of the PTFE film 14 with the gasket body 12. (c) Syringe gasket 10.</p><p> In the present invention, unlike the heat vulcanized rubber, the gasket body 12 is harmless to the human body because there is no concern that plasticizers, cross-linking aids such as sulfur and amines, process oils and pigments will seep into the injection solution. Since it is made of a cross-linked silicone rubber, it can be used as it is as a product without going through a complicated cleaning process after molding the gasket body 12.</p><p> Further, since the silica fine particle layer 16 is provided on the bonding surface of the non-adhesive PTFE film 14 with the gasket body 12, the affinity of the silica fine particles 16b arranged in the silica fine particle layer 16 with respect to the crosslinked silicone rubber and Due to the anchor effect, the gasket body 12 made of crosslinked silicone rubber and the PTFE film 14 can be firmly bonded. Moreover, the silica fine particle layer 16 can clear a predetermined dissolution test specified by the Japanese Pharmacopoeia.</p><p> The invention described in claim 2 is a thermosetting crosslinked silicone rubber in which the crosslinked silicone rubber is crosslinked with a peroxide or a platinum-based curing agent in the gasket 10 for a syringe according to claim 1. This makes it possible to impart high heat resistance that can sufficiently withstand steam disinfection.</p><p> The invention according to claim 3 relates to the method for manufacturing the gasket 10 for a syringe according to claim 1 or 2, and "joins the surface of the gasket body 12 made of crosslinked silicone rubber with the gasket body 12". A method for manufacturing a gasket 10 for a syringe that co-molds a PTFE film 14 having a silica fine particle layer 16 on its surface. A PTFE aqueous dispersion in which silica fine particles 16b are dispersed is applied to the surface of the PTFE film 14 and dried. After that, this is fired at 250 to 360 ° C to form the silica fine particle layer 16. This is a method for manufacturing a gasket 10 for a syringe.</p><p> The invention according to claim 4 also relates to the method for manufacturing the gasket 10 for a syringe according to claim 1 or 2, and "joins the surface of the gasket body 12 made of crosslinked silicone rubber with the gasket body 12". A method for producing a gasket 10 for a syringe in which a PTFE film 14 having a silica fine particle layer 16 provided on its surface is co-molded. A solution prepared by dissolving an amorphous perfluorofluororesin in a perfluoro solvent on the surface of the PTFE film 14. This is a method for manufacturing a gasket 10 for a syringe, which comprises applying a varnish having silica fine particles 16b dispersed therein to form the silica fine particle layer 16.</p><p> The invention described in claim 5 is (1) A prefilled syringe A in which a cylinder C filled with a drug is sealed with a syringe gasket 10. (2) The syringe gasket 10 is formed by co-molding a PTFE film 14 on the surface of a gasket body 12 made of crosslinked silicone rubber, and at the same time. (3) The silica fine particle layer 16 is provided on the joint surface of the PTFE film 14 with the gasket body 12. (4) Prefilled syringe A.</p><p> In the present invention, the prefilled syringe A can be efficiently and economically manufactured by using the syringe gasket 10 according to claim 1. Further, since the gasket body 12 constituting the syringe gasket 10 and the PTFE film 14 are firmly bonded to each other, the stress applied to the prefilled syringe A from the outside during long-term storage or transportation is applied to the gasket body 12 and the PTFE film. Even if it propagates to the joint surface with 14, there is no concern that the joint between the gasket body 12 and the PTFE film 14 will come off due to the stress, and it is necessary to prevent deterioration of the slidability of the gasket for syringe 10 and leakage of liquid. Can be done.</p>

<p> According to the present invention, it is possible to provide a gasket for a syringe that can be manufactured efficiently and economically, has excellent slidability, and can be used stably for a long period of time.</p><p> Further, the present invention provides a prefilled syringe that can be efficiently and economically manufactured by using such a gasket for a syringe, and the slidability and airtightness of the gasket for a syringe are not impaired even by long-term storage and transportation. be able to.</p>

Hereinafter, the present invention will be described in detail according to the illustrated examples. FIG. 1 is a schematic cross-sectional view showing a prefilled syringe A to which the syringe gasket 10 of the embodiment of the present invention is applied. As shown in this figure, the prefilled syringe A of the present invention is roughly composed of a cylinder C, a piston P, a syringe gasket 10 (hereinafter, simply referred to as gasket 10), and a cap K. In the figure, M is an injection solution pre-filled in the syringe A.

The cylinder C is a so-called injection cylinder provided with a needle mounting portion c1 at the tip, a finger hook portion c2 at the rear end, and a tubular injection liquid loading portion c3 between them. In this example, the cylinder C is made of cyclic polyolefin, but the cylinder C is not particularly limited to this resin, and resins such as polypropylene and glass can also be mentioned as suitable ones.

The piston P is a rod-shaped member provided with a gasket mounting portion p1 at the tip end and a finger contact portion p2 at the rear end. A male screw for mounting the gasket 10, which will be described later, is formed on the gasket mounting portion p1 of the piston P. The joining of the piston P and the gasket 10 is not limited to screw mounting, and may be press-fitting, for example. Further, the piston P is also made of a resin such as cyclic polyolefin, polycarbonate or polypropylene, glass or the like, like the cylinder C described above.

When both the cylinder C and the piston P are made of a thermoplastic resin, they can be easily manufactured by injection molding. The injection material is preferably cyclic polyolefin, but is not particularly limited thereto.

As shown in FIG. 1, the gasket 10 is composed of a gasket body 12, a PTFE film 14, and a silica fine particle layer 16.

The gasket body 12 is composed of a body portion 12a made of crosslinked silicone rubber and one or a plurality of rows (three rows in this embodiment) of elastic sliding contact portions 12b integrally provided on the outer periphery thereof. There is. Further, on the rear end side of the body portion 12a, a female screw portion 12a1 to which the gasket mounting portion p1 described above is screwed is provided.

Here, as the crosslinked silicone rubber constituting the gasket body 12, a thermoplastic isobutylene-based partially crosslinked elastomer, a thermosetting crosslinked silicone rubber that is crosslinked with a peroxide or a platinum-based curing agent, or the like is used. be able to. When a thermosetting crosslinked silicone rubber is used as the crosslinked silicone rubber, it is possible to impart high heat resistance to the gasket 10 so as to sufficiently withstand steam disinfection.

The PTFE film 14 is for imparting slidability to the gasket body 12 made of silicone rubber. The thickness of the PTFE film 14 is preferably in the range of 20 μm to 80 μm. If the thickness of the PTFE is less than 20 μm, it becomes difficult to obtain the PTFE film 14 economically. On the contrary, if the thickness of the PTFE is larger than 80 μm, the elasticity of the gasket body 12 should be sufficiently exhibited. This is because it becomes impossible.

Further, the PTFE film 14 is used so that the gasket 10 can be suitably manufactured mainly by compression molding or injection molding, which will be described later, and further, in order not to hinder the rubber elasticity of the gasket body 12 made of silicone rubber. It needs to exhibit at least 150% to 300% elongation (more specifically, breaking elongation).

The PTFE film 14 can be obtained by molding PTFE into a sheet by compression molding, forming it into a block shape and then cutting it with a cutting tool, or slicing. It may be manufactured by the method.

A silica fine particle layer 16 is provided on the joint surface of the PTFE film 14 with the gasket body 12.

The silica fine particle layer 16 contains a binder 16a and silica (SiO).₂) Composed of fine particles 16b, the gasket body 12 of the PTFE film 14 is used to firmly bond the non-adhesive PTFE film 14 and the gasket body 12 due to the affinity of the silica fine particles 16b with the crosslinked silicone rubber and the anchor effect. It is a layer formed on the joint surface with. The silica fine particles 16b constituting the silica fine particle layer 16 are adhered to the surface of the PTFE film 14 in a state of being exposed to some extent by the binder 16a, and the exposed portion bites into the surface of the gasket body 12 to provide an anchor effect. Demonstrate.

Specific examples of the method for forming the silica fine particle layer 16 on the surface of the PTFE film 14 include the following two methods.

The first method is to use a PTFE resin as the binder 16a for fixing the silica fine particles 16b to the surface of the PTFE film 14. Specifically, the silica fine particles 16b and the surfactant are added to the aqueous dispersion of the PTFE resin 16a. The mixed dispersion obtained by mixing and stirring is uniformly applied to one side of the PTFE film 14 using a known coating method (for example, a spray method or a roll coating method), and introduced into a furnace (not shown) at 100 ° C. After drying with C, the PTFE resin is fired at 250 to 360 ° C using a device capable of retaining the shape of the PTFE film 14.

As a result, the PTFE resin, which is the binder 16a, is integrated with the PTFE film 14, and the silica fine particles 16b can be firmly fixed to the surface of the PTFE film 14. Further, by firing in a device capable of maintaining the above shape and in a temperature range, it is possible to prevent the elongation of the PTFE film 14 from being lowered, and as a result, the gasket 10 is suitably manufactured by compression molding or injection molding ( That is, co-molding) becomes possible, and it is possible to prevent the PTFE film 14 from inhibiting the rubber elasticity of the gasket body 12.

The second method is to use a perfluorofluororesin as the binder 16a for fixing the silica fine particles 16b to the surface of the PTFE film 14. Specifically, the perfluorofluororesin and the silica fine particles 16b are used as a perfluoro solvent ( For example, silica obtained by dispersing in CT-solv.100 manufactured by Asahi Glass Co., Ltd.) is uniformly applied and dried on one side of a PTFE film 14 surface-treated with plasma or the like using a known coating method. To form.

According to this method, unlike the case where the PTFE resin is used as the binder 16a, firing is not required, so that the silica fine particle layer 16 can be efficiently formed on the surface of the PTFE film 14.

Here, the thickness of the silica fine particle layer 16 formed by each method as described above is preferably in the range of 0.5 μm to 10 μm. This is because, within such a range, the two can be firmly bonded without hindering the elongation of the PTFE film 14 and the elasticity of the gasket body 12.

The average particle size of the silica fine particle 16b constituting the silica fine particle layer 16 is preferably in the range of 0.1 μm to 10 μm, more preferably in the range of 0.5 μm to 2 μm. When the average particle size of the silica fine particles 16b is less than 0.1 μm, it becomes difficult to handle the silica fine particles 16b and it becomes difficult to economically produce the silica fine particles 16b. This is because when the average particle size is larger than 10 μm, the specific surface area of the silica fine particles 16b becomes small, and a sufficient anchoring effect cannot be exhibited on the gasket body 12 made of silicone rubber.

When manufacturing the gasket 10 of the present invention configured as described above, first, as described above, the PTFE film 14 having the silica fine particle layer 16 formed on the bonding surface with the gasket body 12 has a predetermined size. Cut it out.

When the crosslinked silicone rubber is a thermosetting crosslinked silicone rubber, the PTFE film 14 having the bonding layer 16 formed on the surface (more specifically, the bonding surface with the gasket body 12) is applied to the gasket body 12. It is placed in a molding mold together with a compound of silicone rubber which is a base material of the above, and compression molded by applying a predetermined temperature and pressure to shape it into a predetermined gasket shape.

On the other hand, when the crosslinked silicone rubber is an elastomer having thermoplasticity, the PTFE film 14 having the bonding layer 16 formed on its surface is placed in the molding mold, and the silicone melted in the molding mold. After injecting rubber, pressurize and cool to obtain a gasket 10 having a predetermined shape.

In the gasket 10 formed as described above, there is a concern that the gasket body 12 may seep plasticizers, cross-linking aids such as sulfur and amines, process oils and pigments into the injection solution like heat-vulcanized rubber. Since it is made of crosslinked silicone rubber that is harmless to the human body, it can be used as it is without going through a complicated cleaning process after molding the gasket 10.

The cap K has a shape as shown in FIG. 1 in this example, and has a bottomed tubular insertion hole k1 in the center for inserting the needle mounting portion c1 at the tip of the cylinder C. The outer cylinder portion k2 is connected to the hole portion k1.

In the cap K, the wall thickness of the tubular portion of the insertion hole portion k1 is formed so as to gradually decrease from the bottom side to the opening side. Moreover, the insertion hole portion k1 is formed as a tapered hole, and the hole diameter near the bottom portion is adjusted to be slightly smaller than the outer diameter of the tip of the needle mounting portion c1 of the cylinder C.

This cap K can also be easily constructed by injection molding, like the cylinder C and the piston P described above. Cyclic polyolefin is preferable as the injection material, but the injection material is not particularly limited to this, and thermoplastics such as polypropylene and polycarbonate can also be mentioned as suitable.

According to the prefilled syringe A of the present embodiment configured as described above, the gasket body 12 and the PTFE film 14 constituting the gasket 10 are firmly bonded to each other via the silica fine particle layer 16, so that the gasket can be stored for a long period of time. Even if the stress applied to the prefilled syringe A from the outside during transportation propagates to the joint surface between the gasket body 12 and the PTFE film 14, there is no concern that the joint between the gasket body 12 and the PTFE film 14 will come off due to the stress. , It is possible to prevent deterioration of the slidability of the gasket 10 and leakage of liquid.

<figref num="1">It is schematic cross-sectional view which shows an example of the prefilled syringe to which the gasket for syringe of this invention was applied.</figref><figref num="2">It is sectional drawing which shows an example of the conventional prefilled syringe.</figref>

Code description

10 ... Gasket for syringe 12 ... Gasket body 14 ... PTFE film 16 ... Silica fine particle layer 16a ... binder 16b ... silica fine particles A ... Prefilled Syringe C ... Cylinder P ... piston K ... cap M ... injection