JP2005160888A - Gasket for syringe, and manufacturing method for syringe and gasket for syringe - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a gasket for a syringe offering less deterioration in drug strength during its storage time, and high accuracy of flow rate when used for drug administration. <P>SOLUTION: The gasket 1 for the syringe equipped with a plunger mounting part 4, can slide on an inner surface 22 of an outer tube of the syringe. The gasket 1 for the syringe is made of an elastic material into a gasket shape for the syringe, which comprises a core part 2 with a distal annular rib 12a formed on its side surface liquid tightly and air tightly accessible to the inner surface 22 of the outer tube, a lower drug adsorption layer 5 made of poly-p-xylene to coat an apex surface 11 of the core part 2 and a side surface 13 including the distal annular rib 12a, and an elastic material coating layer 6 to coat the distal annular rib 12a coated with the lower drug adsorption layer 5 made of poly-p-xylene. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a syringe gasket having a high drug holding function and high flow rate accuracy (injection characteristics), a syringe using the same, and a method for manufacturing the syringe gasket.

In recent years, prefilled syringes pre-filled with a chemical solution have been used for reasons such as preventing medical errors and preventing bacterial contamination. Prefilled syringes can be administered accurately without any misuse because there is no need to prepare drugs at the medical site, and can be administered quickly in an emergency, and bacterial infection can be avoided. It has many advantages such as.
However, conventionally, when a highly lipid-soluble drug such as nitroglycerin, cyclosporine, or benzodiazepine is filled in a syringe, these drugs are absorbed and adsorbed in the syringe and the drug titer may decrease. In particular, it is not preferable that the drug titer decreases when precise dose control is required, such as cardiac surgery. In addition, when a drug is administered using a precision automatic infusion device, a so-called syringe pump, it is necessary to administer the drug with a high flow rate accuracy without causing great disturbance in the discharge of the drug. Therefore, the prefilled syringe needs to have an injection characteristic that can be administered with high flow accuracy and a container characteristic that can be filled with a drug without a decrease in drug titer.

Therefore, as a gasket for a prefilled syringe, a conventional laminate gasket in which a synthetic resin film that hardly absorbs and adsorbs a drug on the surface of a rubber or elastomer core member has been proposed. The prefilled syringe using this gasket has the advantage that the decrease in drug titer is small.
However, when a laminate gasket is used, the portion in contact with the inner surface of the syringe is a synthetic resin layer laminated on the surface of the core member, so that the air tightness and liquid tightness in the container may be lowered. Specifically, the outer diameter of the gasket is designed to be slightly larger than the inner diameter of the syringe, and the gas tightness and liquid tightness are secured by the gasket being in close contact with the inner surface of the syringe. However, since the laminate portion of the laminate gasket cannot be compressed and deformed like the core member, fine wrinkles are generated in the syringe, and airtightness and liquid tightness cannot be secured.

In order to solve this, there has been proposed a gasket in which a core member is exposed (not laminated) at a contact portion of the laminated gasket with the syringe inner surface (Patent Document 1: Japanese Patent No. 2974883).
As another example, a first molded part that is formed in advance and includes a first molded part on the tip side having a synthetic resin layer on the surface and a second molded part on the base side that does not have a synthetic resin layer. A laminate gasket having a structure in which a second molded portion is formed by insert molding has been proposed (Patent Document 2: JP 2001-190667 A).
Japanese Patent No. 2974883 JP 2001-190667 A

The gasket shown in the above-mentioned Japanese Patent No. 2974883 is excellent in air tightness and liquid tightness, but the end cut portion of the laminate layer present in the portion that contacts the syringe inner surface when sliding on the syringe inner surface is the syringe inner surface. Since contact occurs, knocking occurs and the discharge of the medicine is disturbed, and it is difficult to obtain good injection characteristics.
Moreover, since the site | part which adhere | attaches the outer cylinder inner wall of a 2nd shaping | molding part is not a synthetic resin layer, the gasket of the said Unexamined-Japanese-Patent No. 2001-190667 improves the airtightness in a container, liquid tightness, and the outstanding container characteristic is Although there is a synthetic resin layer that is in close contact with the inner wall of the first molded part when sliding along the inner wall of the outer cylinder, both the fine wrinkles generated in the synthetic resin layer and the outer cylinder are in contact with each other. Knocking due to catching occurs, and the discharge of the medicine is disturbed, so that it is difficult to obtain good injection characteristics.

Both examples have characteristics such as high air tightness and liquid tightness, and little decrease in drug titer due to adsorption and absorption of stored medicine by the container member. However, although the slipperiness when sliding along the inner wall of the outer cylinder is good, there is no great disturbance in the discharge of the medicine, and the injection characteristics administered with high flow accuracy cannot be said to be sufficient. Further, a lower drug adsorbability is desirable.
Accordingly, an object of the present invention is to solve the above-mentioned problems, and to manufacture a syringe gasket, a syringe, a syringe gasket, and a syringe gasket that can be administered with high flow accuracy with very little decrease in drug titer. It is to provide a method.

（６） 前記弾性材料被覆層は、ゴムもしくは熱可塑性エラストマーにより形成されている上記（１）ないし（５）のいずれかに記載のシリンジ用ガスケット。
（７） 前記低薬剤吸着層は、前記コア部の全面を被覆している上記（１）ないし（６）のいずれかに記載のシリンジ用ガスケット。 What achieves the above object is as follows.
(1) A syringe gasket that is slidable on an inner surface of an outer cylinder of a syringe and includes a plunger mounting portion, and the syringe gasket is formed in an elastic material in the shape of the syringe gasket, A core portion having an annular rib capable of being in liquid-tight and air-tight contact with the formed inner surface of the outer cylinder, and a low drug adsorbing layer comprising polyparaxylylene covering the tip surface of the core portion and the side surface including the annular rib And a gasket for a syringe, comprising: an elastic material coating layer that covers the annular rib coated with the low drug adsorption layer.
(2) The syringe gasket according to (1), wherein the annular rib is a distal-side annular rib formed at a distal end portion of a side surface of the core portion.
(3) The core portion includes the front end side annular rib and a rear end side annular rib that is formed at a rear end portion of the side surface of the core portion and is capable of being in liquid-tight and airtight contact with the inner surface of the outer cylinder. The side surface of the core portion including the rear end side annular rib is covered with the low drug adsorption layer, and the rear end side annular rib is not covered with the elastic material coating layer. Gasket for syringe.
(4) The core portion includes the front-end-side annular rib and a rear-end-side annular rib that is formed at a rear-end portion of the side surface of the core portion and is capable of being in liquid-tight and air-tight contact with the inner surface of the outer cylinder. The side surface of the core portion including the rear end side annular rib is covered with the low drug adsorption layer, and the rear end side annular rib is covered with the elastic material coating layer. Gasket for syringe.
(5) The syringe gasket according to any one of (1) to (4), wherein the polyparaxylylene is represented by the following chemical formula.

(6) The syringe gasket according to any one of (1) to (5), wherein the elastic material coating layer is formed of rubber or a thermoplastic elastomer.
(7) The syringe gasket according to any one of (1) to (6), wherein the low drug adsorption layer covers the entire surface of the core portion.

Moreover, what achieves the said objective is as follows.
(8) The syringe gasket according to any one of (1) to (7), an outer cylinder in which the gasket is slidably housed, and a plunger attached to or attachable to the gasket. A syringe characterized by that.
(9) The syringe according to (8), wherein the syringe is a prefilled syringe having a sealing member that seals a distal end opening of the outer cylinder and a medicine stored in the outer cylinder.

Moreover, what achieves the said objective is as follows.
(10) A manufacturing method of a gasket for a syringe that is slidable on the inner surface of the outer cylinder of the syringe and includes a plunger mounting portion, and the manufacturing method of the gasket is formed in the shape of the gasket for the syringe by an elastic material, A step of preparing a core member having an annular rib that can be liquid-tight and airtightly contacted with the inner surface of the outer cylinder formed on a side surface, and a tip surface of the core member and a side surface including the annular rib are made of polyparaxylylene. A low drug adsorbing layer forming step for forming a low drug adsorbing layer, and an elastic material coating layer forming step with an elastic material on the surface of the annular rib of the core member on which the low drug adsorbing layer is formed are performed. A method for manufacturing a gasket for a syringe.
(11) The method for producing a gasket for a syringe according to (10), wherein the low drug adsorption layer forming step is performed by chemical vapor deposition.
(12) After the low drug adsorption layer forming step and before the elastic material coating layer forming step, surface modification for improving the covering property of the elastic material on at least the annular rib surface of the core member. The manufacturing method of the gasket for syringes as described in said (10) or (11) which performs a quality process.
(13) The said surface treatment process is a manufacturing method of the gasket for syringes as described in said (12) which is performed by a corona discharge process, a plasma process, or an ultraviolet irradiation process.
(14) The method for producing a gasket for a syringe according to any one of (10) to (13), wherein the elastic material coating layer forming step is performed by applying and curing a liquid material of the elastic material.

The syringe gasket of the present invention is a syringe gasket that is slidable on the inner surface of the outer cylinder of the syringe and includes a plunger mounting portion, and the syringe gasket is formed into the syringe gasket shape by an elastic material. A core portion having an annular rib formed on the side surface and in liquid-tight and air-tight contact with the inner surface of the outer cylinder, and a polyparaxylylene covering the tip surface of the core portion and the side surface including the annular rib. A low drug adsorption layer, and an elastic material coating layer that covers the annular rib coated with the low drug adsorption layer.
For this reason, the gasket for syringes of the present invention has an extremely low decrease in drug titer during storage, and can administer the drug with high flow accuracy during use.

The method for manufacturing a gasket for a syringe of the present invention is a method for manufacturing a gasket for a syringe that is slidable on the inner surface of the outer cylinder of the syringe and includes a plunger mounting portion. The method for manufacturing the gasket includes an elastic material. Preparing a core member having an annular rib that is formed in the shape of the gasket for the syringe and can be liquid-tightly and air-tightly contacted with the inner surface of the outer cylinder formed on the side surface, and the tip surface of the core member and the annular A low drug adsorption layer forming step of covering the side surface including the rib with polyparaxylylene, and an elastic material coating layer forming step of an elastic material on the surface of the annular rib of the core member on which the low drug adsorption layer is formed Is.
For this reason, the gasket for syringes which has the effect mentioned above can be manufactured easily and reliably.

  The syringe gasket of the present invention will be described with reference to the embodiments shown in the drawings. 1 is a front view of a syringe gasket according to an embodiment of the present invention, FIG. 2 is a cross-sectional view of the syringe gasket shown in FIG. 1, and FIG. 3 is a plan view of the syringe gasket shown in FIG. 1 is a bottom view of the syringe gasket shown in FIG. 1, FIG. 5 is a partially enlarged sectional view of the syringe gasket shown in FIG. 1, and FIG. 6 is a sectional view of a prefilled syringe using the syringe gasket shown in FIG. is there.

  The syringe gasket 1 of the present invention is a syringe gasket that is slidable on the inner surface 22 of the outer cylinder of the syringe and includes the plunger mounting portion 4. The syringe gasket 1 is formed of an elastic material into a syringe gasket shape, and includes a core portion 2 having a tip-side annular rib 12a that can be liquid-tight and air-tightly contacted with an inner surface of an outer cylinder formed on a side surface. The low drug adsorption layer 5 that covers the side surface (in other words, the main body part) 10 including the distal end surface (in other words, the tapered portion) 11 and the distal end side annular rib 12a, and the distal end side annular rib that is coated with the low drug adsorption layer 5 It has the elastic material coating layer 6 which covers 12a.

  As shown in FIGS. 1 and 2, the core portion 2 of the syringe gasket 1 has a main body portion (side surface portion) 10 that extends to substantially the same outer diameter, and is provided on the distal end side of the main body portion 10 and tapers toward the distal end side. A tapered portion (tip surface portion) 11 that is reduced in diameter, a plunger mounting portion 4 provided inside from the proximal end of the main body portion 10 toward the distal end side, an inner surface of the outer cylinder provided on a side surface of the main body portion 10, An annular rib 12 that can be contacted in a liquid-tight and air-tight manner is provided. In the gasket 1 of this embodiment, as the annular rib, a front end side annular rib 12a provided at the front end portion of the side surface of the main body 10 and a rear end side annular rib 12b provided at the rear end portion are provided. Although it is preferable to provide a plurality of annular ribs in this way, only one may be provided.

  As shown in FIGS. 2 and 4, the plunger mounting portion 4 is a substantially cylindrical recess extending from the proximal end to the vicinity of the distal end inside the gasket main body portion 10. A screwing portion 13 is provided which can be screwed with a screwing portion formed at the tip of the screw. The front end surface of the recess is formed substantially flat.

  As shown in FIGS. 2 and 5, the front end side annular rib 12 a is formed to be continuous with the rear end portion of the tapered portion 11. Further, the proximal end portion of the distal end side annular rib 12a from the contact portion 12c has a curved shape in which the cross section protrudes radially inward toward the proximal end side. The cross-sectional shape of the contact portion between the annular rib 12a and the inner surface 22 of the outer cylinder 21 may be either a curved surface shape or a flat shape. The rear end side annular rib 12 b is provided at the rear end portion of the syringe gasket 1. The rear end side annular rib 12b is preferably provided at the rear end of the syringe gasket 1. The distal end portion of the annular rib 12b has a curved shape whose cross section protrudes radially inward toward the proximal end side.

  The cross-sectional shape of the contact portion between the annular rib 12b and the inner surface 22 of the outer cylinder may be either a curved surface shape or a planar shape. Moreover, since the outer diameter of the contact part of the front end side annular rib 12a is made slightly larger than the syringe inner diameter, the contact part is compressed and deformed in the syringe. Similarly, since the outer diameter of the contact portion of the rear end side annular rib 12b is made slightly larger than the syringe inner diameter, the contact portion is compressed and deformed in the syringe. In this embodiment, two ribs are formed, but three or more ribs may be formed.

  Further, at least the distal end surface and the side surface of the outer surface of the core portion 2 of the syringe gasket 1 are covered with the low drug adsorption layer 5. In particular, in the gasket 1 of this embodiment, as shown in FIGS. 2 and 5, the low drug adsorption layer 5 is provided on the entire surface of the core portion 2. Further, the annular rib coated with the low drug adsorption layer is coated with the elastic material coating layer 6. In the gasket 1 of this embodiment, the front end side annular rib 12 a is covered with the low drug adsorbing layer 5 and with the elastic material covering layer 6. In the gasket 1 of this embodiment, the rear-end-side annular rib 12b is covered with the low drug adsorption layer 5, but is not covered with the elastic material coating layer 6. However, the rear-end-side annular rib 12 b covered with the low drug adsorption layer 5 may be covered with the elastic material coating layer 6.

  As a constituent material of the core part 2, the well-known thing conventionally used for the gasket for syringes can be used. Examples thereof include rubber, elastomer, polyolefin resin, fluorine resin, and polyester resin. As the rubber, for example, natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, and silicone rubber are preferable, and vulcanized rubber is particularly preferable. As the elastomer, for example, a polyvinyl chloride elastomer, a polyolefin elastomer, a styrene elastomer, a polyester elastomer, a polyamide elastomer, a polyurethane elastomer, and a mixture thereof are preferable.

  Among the above rubbers and elastomers, styrene-butadiene rubber, butyl rubber, and styrene elastomer are particularly preferable because they have suitable hardness and elastic properties and can be γ-ray sterilized, electron beam sterilized, and high-pressure steam sterilized. Further, as the polyolefin resin, for example, polypropylene, poly (4-methylpentene-1) and cyclic polyolefin are preferable, and as the fluorine resin, for example, polytetrafluoroethylene, tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer Polymers, tetrafluoroethylene / hexafluoropropylene copolymers are preferred, and polyester resins are preferably, for example, polyethylene phthalate, polyethylene naphthalate, and amorphous arylate, which have a glass transition point of 110 ° C. or higher, or a melting point. It is the material which has. Among the polyolefin resins, fluororesins, and polyester resins, in particular, polypropylene, poly (4-methylpentene-1), cyclic polyolefin, and polyethylene naphthalate have little drug adsorption and absorption, and γ-ray sterilization, electronic Wire sterilization and high-pressure steam sterilization are possible, and it is preferable because of excellent thermoformability.

In the gasket 1 of this embodiment, the low drug adsorption layer 5 covers the tip surface 11 and the side surface 10 of the core portion 2 as shown in FIG. In addition, the inner surface of the core part 2 and the rear-end surface of the core part 2 may also be coat | covered with the low chemical | medical agent adsorption layer.
The thickness of the low drug adsorption layer 5 is preferably uniform. In particular, it is preferable that the thickness of the low drug adsorption layer 5 covering the portion of the gasket 1 that can come into contact with the drug is uniform. With such a configuration, the drug 32 stored in the drug storage unit 31 is less likely to be adsorbed and absorbed by the syringe gasket 1 that forms the drug storage unit 31 together with the inner surface 22 of the outer cylinder, so that the drug titer is unlikely to decrease. Therefore, the gasket for syringes of the present invention has a high drug storage property.

本発明に使用されるポリパラキシリレンとしては、芳香族環に官能基が置換していないポリ（パラキシリレン）、芳香族環もしくはメチレン基に官能基が導入されたもののいずれでもよい。例えば、芳香族環に塩素が置換されたポリ（クロロパラキシリレン）、芳香族環にメチル基が置換されたポリメチルパラキシリレン、メチレン基にフッ素が置換されたポリフルオロパラキシリレンなどのいずれでもよい。また、上記のポリパラキシリレン単独で構成されるホモポリマーだけでなく、パラキシリレンモノマーと共重合可能なモノマーとの共重合体であってもよい。特に、好ましくは、芳香族環に官能基が置換していないポリ（パラキシリレン）、ポリ（クロロパラキシリレン）である。なお、低薬物吸着層５は、上記ポリパラキシリレンもしくは共重合体の単層で形成されていてもよく、上記ポリパラキシリレンおよび／もしくは共重合体の多層で形成されていてもよい。
本明細書において、ポリパラキシリレンは、芳香族環に官能基が置換していないポリ（パラキシリレン）のみを示すものではなく、上記の化学式１によって示されるものを意味する。 As polyparaxylylene, those represented by the following chemical formula can be preferably used.

The polyparaxylylene used in the present invention may be any of poly (paraxylylene) in which an aromatic ring is not substituted with a functional group, and an aromatic ring or a group in which a functional group is introduced into a methylene group. For example, poly (chloroparaxylylene) having an aromatic ring substituted with chlorine, polymethylparaxylylene having an aromatic ring substituted with a methyl group, polyfluoroparaxylylene having a methylene group substituted with fluorine, etc. Either is acceptable. Moreover, it may be a copolymer of not only a homopolymer composed of the above polyparaxylylene alone but also a monomer copolymerizable with a paraxylylene monomer. Particularly preferred are poly (paraxylylene) and poly (chloroparaxylylene) whose aromatic ring is not substituted with a functional group. The low drug adsorption layer 5 may be formed of a single layer of the above polyparaxylylene or copolymer, or may be formed of a multilayer of the above polyparaxylylene and / or copolymer.
In the present specification, polyparaxylylene does not indicate only poly (paraxylylene) in which an aromatic ring is not substituted with a functional group, but means one represented by the above chemical formula 1.

The polyparaxylylene used in the present invention is formed by polymerization of a paraxylylene monomer obtained by thermally decomposing this paraxylylene dimer using the paraxylylene dimer represented by the above chemical formula 1 as a raw material. It is preferable that it is a laminated film. If it is such, as a low chemical | medical agent adsorption | suction layer, there will be no generation | occurrence | production of a pinhole and it will become a stable film thickness. In addition, it is not restricted to this method, What was formed using the well-known various coating methods may be used. For example, a low drug adsorption layer may be formed by forming a sheet previously formed of polyparaxylylene and laminating the sheet.
The low drug adsorption layer 5 is preferably formed to a thickness of 2 μm to 15 μm, particularly 4 μm to 8 μm. If the thickness is 2 μm or more, the drug adsorption can be sufficiently suppressed. Moreover, if it is 15 micrometers or less, a big wrinkle will not arise in the low chemical | medical agent adsorption layer 5, and neither airtightness nor liquid-tightness will fall. The thickness of the low drug adsorption layer 5 made of the polyparaxylylene of the present invention can be calculated by the following method. The weight increase of the gasket 1 after coating the low drug adsorption layer 5 with respect to the weight of the gasket 1 before coating the low drug adsorption layer 5 is W, the specific gravity of the low drug adsorption layer 5 is D, and the total surface area of the gasket 1 Is S, the thickness T of the low drug adsorption layer 5 is:
T = W / (D × S).
For example, when the polyparaxylylene is poly (chloroparaxylylene) (specific gravity: 1.3 g / cm ³ ), the weight increase of the gasket 1 after coating this is 38 mg, and the total surface area of the gasket 1 is 44 cm ^2. Then, the thickness of the low drug adsorption layer 5 is calculated to be 6.6 μm. The specific gravity of poly (paraxylylene) is 1.1 g / cm ³ .

  The elastic material coating layer 6 covers the tip-side annular rib coated with the low drug adsorption layer 5. The elastic material covering layer 6 continuously and annularly covers the entire annular apex portion of the tip side annular rib 12a. With such a configuration, the syringe gasket 1 contacts the outer cylinder inner surface 22 in the elastic material coating layer 6, and the elastic material coating layer 6 is appropriately compressed and deformed in the outer cylinder inner surface 22. It can be hermetically sealed and has high flow accuracy because it slides smoothly on the inner surface of the outer cylinder without large knocking. Therefore, the gasket for syringes of the present invention has high injection characteristics. In the gasket 1 of this embodiment, as described above, both the front-end-side annular rib 12a and the rear-end-side annular rib 12b are covered with the low drug adsorbing layer 5, and the front-end-side annular rib 12a is further formed of the elastic material coating layer. 6 is covered.

  As the material of the elastic material covering layer 6, an elastic material such as rubber or elastomer is used. As the rubber, natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, silicone rubber and the like are used, and those obtained by vulcanization treatment, thermal crosslinking treatment, photocrosslinking treatment and the like are preferable. As the elastomer, a thermoplastic elastomer is preferable, and for example, a polyvinyl chloride elastomer, a polyolefin elastomer, a styrene elastomer, a polyester elastomer, a polyamide elastomer, a polyurethane elastomer, and a mixture thereof are used. In particular, silicone rubber, styrene-butadiene rubber, butyl rubber, and styrene elastomer are preferable because they have suitable hardness and elastic properties and can be sterilized by γ rays, sterilized by electrons, and sterilized by high pressure steam.

  The thickness of the elastic material coating layer 6 is preferably 5 to 1,000 μm. If the thickness of the elastic material coating layer is 5 μm or more, it can be compressed and deformed when in contact with the inner surface 22 of the outer cylinder, and the medicine container 31 can be sealed in a liquid-tight and air-tight manner. There is no occurrence of knocking during sliding of the gasket 1 in the outer cylinder due to the continuous formation of fine wrinkles generated in the low drug adsorption layer 5 formed on the side. Moreover, if it is 1,000 micrometers or less, the quantity of the chemical | medical agent adsorb | sucked and absorbed by elastic material coating layer itself is very small, and a chemical | medical agent titer does not fall during a predetermined storage period.

  More preferably, the thickness of the elastic material coating layer is 10 to 300 μm, and in such a range, excellent airtightness, liquid tightness, and excellent container characteristics with little decrease in drug titer can be obtained, In addition, there is no significant disturbance in the discharge of the medicine, and an injection characteristic for administration with high flow accuracy can be obtained. Further, the width of the elastic material covering layer 6 varies depending on the width of the annular rib, but covers at least 50 to 110% of the width of the annular rib (centering on the maximum diameter portion) with the apex portion as the center. For example, when the annular rib width is 1.5 mm, 0.75 to 1.65 mm is preferable.

Next, the manufacturing method of the gasket 1 for syringes which is an Example of this invention is demonstrated using FIG.
The manufacturing method of the gasket 1 for syringes of this invention is a manufacturing method of the gasket for syringes which can slide the outer cylinder inner surface of a syringe, and is provided with a plunger attachment part. And the manufacturing method of a gasket is the core member (in other words, core part) which has the annular rib formed in the shape of a gasket for syringes with an elastic material, and can be liquid-tightly and airtightly contacted with the inner surface of the outer cylinder formed on the side surface 2 on the surface of the annular rib of the core member on which the low drug-adsorbing layer is formed, a step of forming a low-drug-adsorbing layer in which the tip surface of the core member and the side surface including the annular rib are coated with polyparaxylylene An elastic material covering layer forming step using an elastic material is performed.
The step of preparing the core member 2 (in other words, the core part) is produced by injection molding using the constituent material of the core part described above. As a shape and constituent material of the core part 2, the thing of the core part 2 mentioned above is preferable.

Next, the low drug adsorption layer forming step will be described.
The low drug adsorption layer forming step comprising polyparaxylylene is preferably formed by polymerizing the above-described paraxylylene monomer of Formula 1 on the surface of the core portion 2. In addition, the low drug adsorption layer forming step is preferably performed by forming a polyparaxylylene thin film by a chemical vapor deposition method (CVD method), a sputtering method, an ion plating method, or the like. In particular, polymerization and film formation are performed simultaneously and on the surface of the core part 2 by chemical vapor deposition of the core part 2 using paraxylylene monomer. For this reason, the polyparaxylylene film formed by chemical vapor deposition is uniformly formed on the surface of a structure having a complicated three-dimensional shape such as the core 2.

  As the polyparaxylylene film forming apparatus, an apparatus including a paraxylylene dimer vaporization chamber, a paraxylylene dimer thermal decomposition chamber, and a polyparaxylylene vapor deposition chamber is used. For forming a polyparaxylylene film, for example, a core member is placed in a vapor deposition chamber, the inside of the apparatus is depressurized to 5 to 50 mTorr, preferably 10 to 30 mTorr, and the paraxylylene dimer as a raw material is 100 in the vaporization chamber. Vaporization is carried out at ˜200 ° C., and then the pyroxylylene dimer is thermally decomposed into paraxylylene monomer by heating at 650 to 700 ° C. in the pyrolysis chamber, and then the monomer is introduced into the core part 2. Upon contact, polymerization occurs at the interface to form a polyparaxylylene film. The polyparaxylylene film obtained in this way is excellent in chemical resistance and gas barrier properties, is uniformly and continuously formed on the surface of the core, and does not generate pinholes. Can be suppressed. The thickness of the polyparaxylylene layer can be controlled by the degree of pressure reduction, the temperature of the vaporization chamber, and the deposition time.

The low drug adsorption layer forming step may be performed by thinly applying a liquid or paste of polyparaxylylene to the surface and / or inner surface of the core member 2 to form a thin film. The low drug adsorption layer forming step is performed by sticking a film or thin film made of polyparaxylylene to the outer surface and / or inner surface of the core portion 2 by heat fusion, high frequency fusion, adhesive, or the like. Also good.
Moreover, it is preferable to perform the low chemical | medical agent adsorption layer formation process so that the low chemical | medical agent adsorption layer 5 formed may become substantially uniform thickness. The thickness of the low drug adsorption layer 5 is preferably 2 μm to 15 μm, particularly 4 to 8 μm. Polyparaxylylene has chemical resistance.

Next, an elastic material coating layer forming step using an elastic material will be described on the surface of the distal end side annular rib 12a of the core member 2 on which the low drug adsorption layer is formed.
The elastic material coating layer forming step is preferably performed by applying a liquid material of an elastic material to the surface of the tip-side annular rib 12a and curing it. As the elastic material used for forming the elastic material coating layer, rubber and elastomer are preferable, and those described above can be used. An elastic material coating layer may also be formed on the rear end side annular rib 12b.

In the case where rubber is used as the elastic material, the liquefied product of the elastic material can be prepared by adding a softener, a crosslinking agent, a crosslinking accelerator, a filler, or the like to the rubber material.
In addition, when a thermoplastic elastomer is used as the elastic material, the liquefied product of the elastic material is prepared by heating the thermoplastic elastomer or adding it to a solvent that can dissolve and volatilize the thermoplastic elastomer. be able to.
The liquefied material of the elastic material is applied to the core member using an application member such as a roller. The liquefied material may be applied while rotating the core member.

  Further, when rubber is used as the elastic material, the elastic material coating layer 6 is produced by applying a liquefied product and then performing a curing process such as a vulcanization process, a thermal crosslinking process, and a photocrosslinking process. When a thermoplastic elastomer is used as the elastic material, the elastic material coating layer 6 is produced by cooling or drying after applying the liquefied material. The thickness of the formed elastic material coating layer is preferably 5 to 1000 μm, more preferably 10 to 300 μm. In this embodiment, the elastic material coating layer 6 is formed only on the tip-side annular rib 12a. However, the present invention is not limited to this, and the non-contact portion with the drug of the core portion 2 may be covered. Good.

  Then, after the low drug adsorption layer formation step and before the elastic material coating layer formation step, a surface modification step for improving the covering property of the elastic material on at least the annular rib surface of the core member may be performed. preferable. By carrying out such a surface modification step, the surface of the low drug adsorption layer has a reactive group such as a hydroxyl group or a carboxyl group or a highly polar functional group, resulting in high wettability (hydrophilicity), and coating with an elastic material. Adhesiveness with the layer forming material is increased.

  The surface treatment step is performed by, for example, plasma treatment, corona discharge treatment, or ultraviolet irradiation treatment. In particular, corona discharge treatment is preferable. Furthermore, the surface treatment step is performed so that the relationship between the surface tension γ1 of the surface of the core member after the surface treatment and the surface tension γ2 of the liquid material of the elastic material used in the elastic material coating step satisfies γ1 ≧ γ2. Is preferred. The surface treatment step may be performed only on the annular rib that covers the elastic material, or may be performed on the entire core member 2.

  The conditions of the corona discharge treatment are the surface tension γ1 (mN / m) of the surface of the low drug adsorption layer after the treatment and the surface tension γ2 (mN / m) of the liquid or paste-like material of rubber or thermoplastic elastomer. It is preferable to appropriately adjust the corona strength, the corona discharge treatment time, the working distance, etc. so that the relationship becomes γ1 ≧ γ2. If γ1 ≧ γ2, the film has sufficient wettability, and a good coating layer can be formed from the elastic material coating layer forming material.

Next, the syringe of the present invention will be described.
The syringe 20 of the present invention includes the above-described syringe gasket 1, an outer cylinder 22 that slidably accommodates the gasket, and a plunger 28 that is attached to or attachable to the gasket 1. Specifically, the syringe 20 houses the syringe gasket 1, the plunger 28 having a tip attached to the rear end side of the syringe gasket 1, and the gasket 1 slidably in a liquid-tight and air-tight state. In addition, an outer cylinder 21 provided with an injection needle mounting portion 23 or an injection needle is provided at the tip. Moreover, the prefilled syringe 30 which accommodated the chemical | medical agent 32 inside may be sufficient as the syringe 20 of this invention, as shown in FIG.

Then, it demonstrates using the Example which applied the syringe of this invention to the prefilled syringe 30. FIG.
As shown in FIG. 6, the prefilled syringe 30 includes the above-described syringe gasket 1, an outer cylinder 21 in which the gasket 1 is slidably housed, a plunger 28 attached to or attachable to the gasket 1, A sealing member for sealing the distal end opening of the tube 21 and a medicine 32 stored in the outer tube 21 are provided.

  Specifically, the prefilled syringe 30 includes an outer cylinder 21 provided with a syringe needle mounting portion 23 that is a distal end opening portion at a distal end portion, and a seal cap 26 that is a sealing member that seals the syringe needle mounting portion 23. The syringe gasket 1 capable of sliding in a liquid-tight and air-tight manner in the outer cylinder 21, a plunger 28 having a tip attached to the rear end of the syringe gasket 1, a sealing member 26, and an inner surface 22 of the outer cylinder And a medicine storage part formed between the syringe gasket 1 and a medicine 32 stored in the medicine storage part.

As the gasket 1, those described above are used.
As shown in FIG. 6, the outer cylinder 21 is a cylindrical body, and an injection needle mounting portion 23 that is open at the front end and is tapered toward the front end is paired at the rear end. Are provided opposite to each other. The outer cylinder 21 is made of a transparent or translucent material, preferably a material having low oxygen permeability and water vapor permeability.

  Examples of the material for forming the outer cylinder 21 include polypropylene, polyethylene, polystyrene, polyamide, polycarbonate, polyvinyl chloride, poly- (4-methylpentene-1), acrylic resin, acrylonitrile-butadiene-styrene copolymer, and polyethylene. Various resins such as polyesters such as terephthalate and cyclic polyolefins may be mentioned. Among them, resins such as polypropylene and cyclic polyolefins are preferred because they are easy to mold and have heat resistance.

  Further, a seal cap 26 as a sealing member is provided on the injection needle mounting portion 23 of the outer cylinder 21. An injection needle (not shown) may be attached instead of the seal cap. Further, known seal caps and injection needles are used. Moreover, you may attach an injection needle directly to the front-end | tip part of an outer cylinder. A screwing portion for attaching a seal cap or the like may be provided on the outer surface of the proximal end portion of the injection needle attachment portion 23.

  The seal cap 26 includes a cap main body 33 and a seal member 34 provided to close the opening of the cap main body 33. An internal thread portion is formed on the inner surface of the base end portion of the cap body portion 33 so as to be screwed with the external thread portion formed on the outer surface of the distal end portion of the outer cylinder 21. And both are screwed together strongly. For this reason, the sealing member 34 is closely attached to the distal end surface of the injection needle mounting portion of the outer cylinder 21 and hermetically seals the distal end opening of the outer cylinder 21. As the material for forming the seal member 34, the material described in the core portion of the gasket can be suitably used. Furthermore, it is preferable to provide a low drug adsorption layer on the drug contact surface of the seal member 34. As polyparaxylylene, those described above can be used.

The seal cap 26 is preferably of a type that allows a double-ended needle to be directly inserted as shown in FIG. For this reason, the main body portion 33 of the seal cap 26 has an opening at the center of the distal end portion, and the opening is closed by a seal member 34. Further, the seal member 34 is pierced by a double-ended needle type injection needle (not shown). It is possible.
In the prefilled syringe 30, the medicine 32 is stored in a space formed by the outer cylinder 21, the gasket 1, and the seal cap 26. As the drug, nitroglycerin, cyclosporine, benzodiazepine drugs, high-concentration sodium chloride injection, vitamins, minerals, antibiotics and other drug solutions, and powdered or lyophilized drugs are used.

  The plunger 28 includes a main body portion extending in the axial direction, an attachment portion to the plunger attachment portion 4 provided at the front end portion, and a pressing disc portion provided at the rear end. Specifically, the plunger 28 includes a main body portion extending in the axial direction having a cross-shaped cross section, and a plunger side screwing portion that is detachably attached to the screwing portion 13 of the plunger mounting portion 4 provided at the tip portion. 27, a pressing disk provided at the rear end, and a rib provided in the middle of the main body.

And as a constituent material of the plunger 28 and the seal cap, it is preferable to use hard or semi-hard resin such as high density polyethylene, polypropylene, polystyrene, polyethylene terephthalate.
And the gasket 1 for syringes of this invention may be used for chemical | medical solution injection | pouring apparatuses other than a syringe. Furthermore, you may use the syringe of this invention for syringes other than a prefilled syringe.

(Example 1)
Styrene-butadiene rubber (SBR) as the core material, and polyparaxylylene forming the low drug adsorption layer include dichloro- (2,2) -paracyclophane (trade name: dix-c, manufactured by Sansei Kasei Co., Ltd.) ) Was used to prepare the core part and the low drug adsorption layer shown in FIGS. 1 and 2. More specifically, a styrene butadiene rubber having the shape shown in FIG. 2 using a chemical vapor deposition apparatus (model S, tumbler capacity 25L, manufactured by Sansei Kasei Co., Ltd.) comprising a vaporization chamber, a pyrolysis furnace, and a vapor deposition chamber. A poly (chloroparaxylylene) film (low drug adsorption layer) was formed on the surface of the core member made of (SBR).

  Specifically, 12 g of dichloro- (2,2) -paracyclophane, which is a dimer, was introduced into the vaporization chamber, and the inside of the apparatus was adjusted to a vacuum degree of 25 mTorr. Next, it is heated to 150 to 170 ° C. to sublimate dichloro- (2,2) -paracyclophane, which is a dimer in the vaporization chamber, and then the dimer is passed through a pyrolysis furnace at 650 to 690 ° C. to heat the monomer. The monomer was introduced into a vapor deposition chamber (room temperature) equipped with a tumbler containing 250 core members and finally treated for 100 minutes to form a low drug adsorbing layer. The tumbler was rotated at 2 rpm, and the low drug adsorption layer was formed while stirring the core member. After the formation of the low drug adsorption layer, 30 core members were arbitrarily selected and the weight change before and after the formation of the low drug adsorption layer was measured. The average weight change was 22 mg / piece, and the average thickness of the low drug adsorption layer was Was 4 μm.

The core part has a length of 22.4 mm, an outer diameter of 29.6 mm at the front and rear end side annular rib portions, a conical tip part length of 5 mm, and a conical tip part (drug contact part) area of 694 mm. ^2. Plunger having a length of 16 mm between the center of the front end side annular rib and the center of the rear end side annular rib, an outer diameter of 27 mm at the same outer diameter portion between the front end side annular rib and the rear end side annular rib, and an internal thread portion inside The length (depth) of the concave portion for mounting was 12 mm, the inner diameter was 17 mm on the front end side of the concave portion for mounting the plunger, and the inner diameter was 22 mm on the rear end side.

Next, a corona discharge treatment was performed on the surface of the core member using a corona discharge system (MultiDyne1, manufactured by 3DT) under conditions of an arc irradiation time of 3 seconds and a working distance (distance between the apparatus irradiation head and the core member) of 1 cm.
Subsequently, a screen printing apparatus (NSP-23-U, manufactured by Navidas), stainless mesh screen (mesh 70 mesh, mesh thickness 300 μm, slit width 1.5 mm, slit length 9.5 mm), thermosetting silicone ink [ME60-B (manufactured by GE Toshiba Silicone) and KE-1820 (manufactured by Shin-Etsu Chemical Co., Ltd.), ME60-B: KE-1820 = 80 parts by weight: 20 parts by weight] The pre-curing paste was applied to the tip-side annular rib portion of the treated core member, and an ink coating layer having a width of 1.5 mm was formed on the entire circumference of the annular rib portion. Then, the said coating layer was hardened by heating a core member at 150 degreeC for 30 minute (s) using heating oven, and the elastic material coating layer which consists of silicone hardened | cured material was formed. The thickness of the elastic material coating layer was 120 μm at the thickest part. A gasket was produced by the above method.

(Example 2)
The same operation as in Example 1 was conducted except that 21 g of the above-mentioned dichloro- (2,2) -paracyclophane was put into the vaporization chamber of the vapor deposition apparatus. After the formation of the low drug adsorption layer, 30 core members were arbitrarily selected and the weight change before and after the formation of the low drug adsorption layer was measured. The average weight change was 40 mg / piece, and the average thickness of the low drug adsorption layer was Was 7 μm.

(Example 3)
The same operation as in Example 1 was conducted except that 33 g of the above-mentioned dichloro- (2,2) -paracyclophane was put into the vaporization chamber. After the formation of the low drug adsorption layer, 30 core members were arbitrarily selected and the weight change before and after the formation of the low drug adsorption layer was measured. The average weight change was 40 mg / piece, and the average thickness of the low drug adsorption layer was Was 11 μm.

(Comparative Example 1)
A gasket was produced in the same manner as in Example 1 except that the low drug adsorption layer was not formed.

(Comparative Example 2)
A gasket was produced in the same manner as in Example 1 except that the elastic material coating layer was not formed by corona discharge treatment and screen printing in Example 1.

(Experiment)
The following evaluation tests were performed using the gaskets of the examples and the gaskets of the comparative examples. In the evaluation, the outer cylinder (inside diameter 29.2 mm, inner diameter 29.2 mm, made of cyclic polyolefin (Appel: registered trademark, manufactured by Mitsui Chemicals, Inc.) in which the gaskets of Examples and Comparative Examples were preliminarily attached with silicone oil as a lubricant on the inner surface thereof. The body length was 125.5 mm and the volume was 50 ml), and the syringe shown in FIG. 6 was assembled.

(Experiment 1: drug adsorption test)
A syringe was filled with a nitroglycerin aqueous solution (millisrol, nitroglycerin concentration 50 mg / 100 mL, Nippon Kayaku Co., Ltd.) and capped, and then autoclaved at 110 ° C. for 10 minutes, and this was treated at 40 ° C. and 75% RH. And stored for 6 months. The nitroglycerin concentration of the filling liquid at the time of filling and after storage for 6 months was measured using high performance liquid chromatography. From the measurement chart, the peak area (a) of the nitroglycerin at the time of filling and the peak area (b) of the nitroglycerin after storage for 6 months are read, and the nitroglycerin concentration maintenance ratio (b / a × 100 in the syringe after 6 months storage) %) Was calculated as shown in Table 1 below. In addition, the one where the said nitroglycerin density | concentration maintenance rate is high is preferable, and it can be said that the syringe is advantageous for the guarantee storage of a chemical | medical agent prescribed amount. The nitroglycerin concentration maintenance rates of the gaskets produced in the examples and comparative examples are as follows, and it was confirmed that the gaskets had excellent drug low adsorption characteristics.

(Experiment 2: Liquid tightness test)
After filling the syringe with 50 mL of purified water and capping it, autoclaving it at 110 ° C. for 10 minutes, and inside the syringe, in the gap between the center of the front end-side annular rib and the rear end-side annular rib of the gasket in the outer cylinder It was confirmed by visual observation whether or not water that leaked out from the water existed, and the results were as shown in Table 1 below [◯: not present (no leak), ×: present (leaky)].

(Experiment 3: Discharge characteristic evaluation test using a syringe pump)
Using a syringe pump (TE-331, manufactured by Terumo Corporation) 41, the discharge characteristics of the syringe were evaluated. Specifically, using the experimental apparatus 40 shown in FIG. 7, the syringe 20 filled with 50 mL of purified water is set in the syringe pump 41, and purified water is discharged at a discharge rate of 1 mL / h for 2 hours, and an electronic balance is used. When the measured weight was measured over time at intervals of 30 seconds using 42, the results shown in Table 1 below were obtained (◯: ejection stable, x: ejection unstable).

  Moreover, the discharge characteristic results of the syringe are shown in FIGS. 8A and 8B for Example 1, FIGS. 9A and 9B for Example 2, and FIG. 10A for Example 3. 11 (b) and Comparative Example 1 were as shown in FIGS. 11 (a) and 11 (b), and Comparative Example 2 was as shown in FIGS. 12 (a) and 12 (b). In the discharge amount temporal change profile (a in each figure) and the discharge speed (mL / h, 0 <t <2h) profile (each figure b) at time t calculated from the chart, in particular, from the discharge speed profile, 1 mL / h The smaller the amplitude around the set value, the smoother the gasket slides and the more stable the discharge. The larger the amplitude, the less stable the discharge, that is, the gasket slides with knocking. It represents that.

(Table 1)
┌──────┬──────┬─────┬──────┐
│ │ Drug adsorption test │ Liquid tightness test │ Discharge characteristics effect │
├──────┼──────┼─────┼──────┤
│ Example 1 │ 92% │ ○ │ ○ │
├──────┼──────┼─────┼──────┤
│ Example 2 │ 96% │ ○ │ ○ │
├──────┼──────┼─────┼──────┤
│ Example 3 │ 98% │ ○ │ ○ │
├──────┼──────┼─────┼──────┤
│ Comparative Example 1 │ 27% │ ○ │ ○ │
├──────┼──────┼─────┼──────┤
│ Comparative Example 2 │ 94% │ × │ × │
└──────┴──────┴─────┴──────┘

(Examples 4 to 6)
Instead of poly (chloroparaxylylene) used in Example 1 above, poly (paraxylylene) was used. Specifically, the gasket of the present invention and the gasket were used in the same manner as in Example 1 except that (2,2) -paracyclophane (trade name: diX-N, manufactured by Sansei Kasei Co., Ltd.) was used. A syringe having The amount of the paraxylylene dimer introduced into the vaporization chamber of the vapor deposition apparatus is as shown in Table 2. And when the weight change of the core member before and after formation of the low chemical | medical agent adsorption layer was measured similarly to the said Example 1, the average weight change was 20 mg / piece, 35 mg / piece, and 55 mg / piece, respectively. The thickness of the low drug adsorption layer calculated from this is shown in Table 2. Also in these examples, as in Example 1 using poly (chloroparaxylylene), all of the drug adsorption, airtightness, and ejection characteristics were good.

(Table 2)
┌──────┬──────┬───────┐
│ │ Input amount │ Low drug adsorption layer thickness │
├──────┼──────┼───────┤
│ Example 4 │ 18g │ 4μm │
├──────┼──────┼───────┤
│ Example 5 │31.5g │ 7μm │
├──────┼──────┼───────┤
│ Example 6 │4935g │ 11μm │
└──────┴──────┴───────┘

FIG. 1 is a front view of a syringe gasket according to an embodiment of the present invention. 2 is a cross-sectional view of the syringe gasket shown in FIG. FIG. 3 is a plan view of the syringe gasket shown in FIG. 1. FIG. 4 is a bottom view of the syringe gasket shown in FIG. 1. FIG. 5 is a partially enlarged sectional view of the syringe gasket shown in FIG. 1. FIG. 6 is a cross-sectional view of a prefilled syringe using the syringe gasket shown in FIG. FIG. 7 is an explanatory diagram of an experimental apparatus used for measuring the discharge characteristic result of the prefilled syringe according to the embodiment of the present invention. FIGS. 8A and 8B are diagrams showing discharge characteristic results of the prefilled syringe of the example of the present invention. FIGS. 9A and 9B are diagrams showing discharge characteristic results of the prefilled syringe of the example of the present invention. 10 (a) and 10 (b) are diagrams showing the discharge characteristic results of the prefilled syringe of the example of the present invention. FIGS. 11A and 11B are diagrams showing discharge characteristic results of the prefilled syringe of the comparative example. FIGS. 12A and 12B are diagrams showing the discharge characteristic results of the prefilled syringe of the comparative example.

Explanation of symbols

1 Gasket for syringe 2 Core part (core member)
5 Low drug adsorption layer made of polyparaxylylene 6 Elastic material coating layer 20 Syringe 21 Outer cylinder 26 Seal cap 28 Plunger 30 Prefilled syringe

Claims (14)

A syringe gasket that is slidable on an inner surface of an outer cylinder of a syringe and includes a plunger mounting portion, wherein the syringe gasket is formed into a shape of the syringe gasket by an elastic material and is formed on a side surface. A core part having an annular rib capable of being liquid-tightly and airtightly contacted with the inner surface of the outer cylinder, a low drug adsorbing layer made of polyparaxylylene covering the tip surface of the core part and the side surface including the annular rib, A gasket for a syringe, comprising: an elastic material coating layer that covers the annular rib coated with a low drug adsorption layer. The syringe gasket according to claim 1, wherein the annular rib is a distal-side annular rib formed at a distal end portion of a side surface of the core portion. The core portion includes the front-end-side annular rib and a rear-end-side annular rib that is formed at a rear-end portion of a side surface of the core portion and is capable of being liquid-tight and air-tightly contacting the inner surface of the outer cylinder. The gasket for a syringe according to claim 2, wherein the side surface of the core portion including the side annular rib is covered with the low drug adsorption layer, and the rear end side annular rib is not covered with the elastic material covering layer. . The core portion includes the front-end-side annular rib and a rear-end-side annular rib that is formed at a rear-end portion of a side surface of the core portion and is capable of being liquid-tight and air-tightly contacting the inner surface of the outer cylinder. 3. The syringe gasket according to claim 2, wherein a side surface of the core portion including the side annular rib is covered with the low drug adsorption layer, and the rear end side annular rib is covered with the elastic material covering layer. . The syringe gasket according to any one of claims 1 to 4, wherein the polyparaxylylene is represented by the following chemical formula.

The syringe gasket according to any one of claims 1 to 5, wherein the elastic material coating layer is formed of rubber or thermoplastic elastomer. The syringe gasket according to claim 1, wherein the low drug adsorption layer covers the entire surface of the core portion. A syringe comprising the syringe gasket according to any one of claims 1 to 7, an outer cylinder in which the gasket is slidably housed, and a plunger attached to or attachable to the gasket. . The syringe according to claim 8, wherein the syringe is a prefilled syringe having a sealing member that seals a distal end opening of the outer cylinder and a medicine stored in the outer cylinder. A method of manufacturing a gasket for a syringe that is slidable on an inner surface of an outer cylinder of a syringe and includes a plunger mounting portion. The method for manufacturing the gasket is formed in the shape of the gasket for the syringe by an elastic material and formed on a side surface. Preparing a core member having an annular rib capable of being in liquid-tight and air-tight contact with the inner surface of the outer cylinder, and a low drug adsorption made of polyparaxylylene on the tip surface of the core member and the side surface including the annular rib A syringe gasket comprising: a low drug adsorbing layer forming step of forming a layer; and an elastic material coating layer forming step of an elastic material on the surface of the annular rib of the core member on which the low drug adsorbing layer is formed Manufacturing method. The method for producing a syringe gasket according to claim 10, wherein the low drug adsorption layer forming step is performed by chemical vapor deposition. After the low drug adsorption layer forming step and before the elastic material coating layer forming step, at least a surface modification step for improving the covering property of the elastic material on the surface of the annular rib of the core member The manufacturing method of the gasket for syringes of Claim 10 or 11 which is performed. The method for producing a gasket for a syringe according to claim 12, wherein the surface treatment step is performed by corona discharge treatment, plasma treatment, or ultraviolet irradiation treatment. The method for producing a gasket for a syringe according to any one of claims 10 to 13, wherein the elastic material coating layer forming step is performed by applying and curing a liquid material of the elastic material.

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