JP2016209081A - Gasket, production method of gasket, and syringe - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a gasket capable of reconciling sealability to a drug solution with slidability to a barrel; and to provide a production method of a gasket, and a syringe.SOLUTION: A gasket 13 includes: a gasket body 41 to be inserted slidably into a barrel 12 of a prefilled syringe 10; a laminate film 42 for covering the gasket body 41, in which a sliding surface 21a and a sliding surface 21b sliding in the abutting state on the barrel 12 are roughened; and a silicone coating 43 for covering the laminate film 42.SELECTED DRAWING: Figure 6

Description

  The present invention relates to a gasket that is inserted into a barrel of a syringe.

  Liquid pharmaceutical products (hereinafter referred to as chemical solutions) are provided by being enclosed in vials or ampoules. Since the chemicals provided by vials and ampoules are transferred from these containers to syringes (syringes), they are used for errors such as mistakes and infection when adjusting the chemicals, and contamination of foreign objects such as ampules and rubber stopper fragments. There is danger. For this reason, in recent years, many prefilled syringes pre-filled with a chemical solution have been used. In addition, the prefilled syringe has an advantage that it can be used quickly in an emergency.

  A prefilled syringe is a barrel (injection cylinder) that contains a chemical solution, a gasket that is slidably inserted into the barrel, a plunger that slides the gasket along the barrel, and a cap (rubber that is attached to a nozzle that discharges the chemical solution). Etc.). The chemical solution of the prefilled syringe is sealed in the barrel by a cap and a gasket. When using chemicals, attach the plunger to the gasket and remove the cap from the nozzle. And a chemical | medical solution is discharged from a nozzle by sliding a gasket in the direction of a nozzle with a plunger.

  Since the gasket used for the prefilled syringe needs to be surely sealed with the chemical until the chemical is used, the gasket used for the prefilled syringe has an arithmetic average roughness (sliding surface sliding against the barrel). Ra (also referred to as centerline average roughness) may be required to be 0.05 μm or less (Patent Document 1). Similarly, the gasket having a very small arithmetic average roughness Ra of the sliding surface by setting the arithmetic average roughness Ra of the surface forming the sliding surface out of the mold surface for molding the gasket to 0.03 μm or less. May be formed (Patent Document 2 and Patent Document 3).

Japanese Patent Laid-Open No. 10-314305 JP 2014-047828 A JP 2013-049236 A

  As described above, the gasket used for the prefilled syringe has an arithmetic average roughness Ra of 0.05 μm or less on the sliding surface so that the chemical solution is surely sealed, and the sliding surface is in a so-called mirror-finished state. It is common to smooth. This is mainly because the chemical solution is surely sealed by eliminating the gap between the barrel and the gasket and improving the adhesion.

  More specifically, the barrel is made of a hard resin such as cycloolefin polymer (COP), and the gasket is made of a rubber gasket body, for example, polytetrafluoroethylene, in order to prevent elution of the chemical solution. It is formed by laminating with a soft resin such as ethylene (PTFE: PolyTetraFluoroEthylene). When a soft resin such as PTFE is brought into contact with a hard resin such as COP without a gap, PTFE is adsorbed to the COP and becomes a pseudo-adhesive state. Therefore, the sliding surface of the gasket is mirror-finished, and the gap between the barrel and the gasket is almost eliminated, so that even if the prefilled syringe is stored for a long period of time, chemicals can enter between the barrel and the gasket due to capillary action. Thus, it is possible to reliably prevent problems such as leakage.

  However, if the sliding surface of the gasket is mirror-finished as described above and the barrel and the gasket are in a pseudo-adhesive state, the prefilled syringe is used for users whose sliding resistance is too large and the plunger pressing force is weak. May be difficult. In some cases, the plunger is mechanically pressed by the auto injector to discharge the chemical solution from the nozzle. However, if the sliding surface of the gasket is mirror-finished, the gasket sliding resistance is extremely large. Since the liquid does not move smoothly, even with an auto-injector, the discharge speed of the chemical liquid undulates and the chemical liquid cannot be discharged stably.

  Prefilled syringes are sterilized during the manufacturing process, but the chemicals expand and contract before and after sterilization, and the gasket is automatically pressurized in the barrel by applying a pressure of about 300 kPa (about 3 atm). To slide. For this reason, when the sliding surface of the gasket is mirror-finished and the gasket has a large sliding resistance, the gasket does not move smoothly as in the case of using an auto injector. The gasket is often tilted inside. Of course, when the inclination of the gasket is large, the sterility of the chemical solution cannot be guaranteed and is discarded. Therefore, the yield is deteriorated if the sliding resistance of the gasket is large.

  It is an object of the present invention to provide a gasket, a gasket manufacturing method, and a syringe that have both a sealing property against a chemical solution and a sliding property against a barrel.

  The gasket of the present invention includes a gasket main body that is slidably inserted into a barrel of a syringe, a laminate film that covers the gasket main body and has a roughened sliding surface that slides in contact with the barrel, and a laminate film. And a covering silicone coating.

  The sliding surface preferably includes a groove along the sliding direction.

  It is perpendicular to the sliding direction, and the arithmetic average roughness of the sliding surface measured along the sliding surface is larger than the arithmetic average roughness of the sliding surface measured along the sliding direction. preferable.

  The arithmetic average roughness of the sliding surface that is perpendicular to the sliding direction and is measured along the sliding surface is preferably 0.06 μm or more and less than 3.0 μm.

  The arithmetic average roughness of the sliding surface that is perpendicular to the sliding direction and is measured along the sliding surface is preferably 0.5 μm or more and less than 2.0 μm.

The silicone coating preferably has a kinematic viscosity of 100 mm ² / s to 3000 mm ² / s.

  The laminate film is preferably formed of polytetrafluoroethylene or ethylenetetrafluoroethylene copolymer.

  The gasket manufacturing method of the present invention includes a gasket body that is slidably inserted into a barrel of a syringe, a laminate film that covers the gasket body and has a roughened sliding surface that slides in contact with the barrel, A gasket manufacturing method comprising: a silicone coating that covers a laminate film; a step of molding the laminate film in accordance with the outer shape of the gasket body; and a gasket body covered with the laminate film in a jig whose inner surface is roughened. By passing, the method comprises the steps of roughening the sliding surface in contact with the barrel and applying a silicone coating to the roughened sliding surface.

  The syringe of the present invention includes a barrel for containing a chemical solution, a gasket main body that is slidably inserted into the barrel, a laminate film that covers the gasket main body and has a roughened sliding surface that slides in contact with the barrel. A gasket comprising a laminate film and a silicone coating.

  The chemical solution is preferably sealed in the barrel with a gasket and a cap attached to a nozzle for discharging the chemical solution.

  The barrel is preferably formed of a cycloolefin polymer.

  The gasket, the gasket manufacturing method, and the syringe of the present invention can achieve both a sealing property against a chemical solution and a sliding property with respect to a barrel.

It is sectional drawing of a prefilled syringe. It is an external view of a gasket. It is a partially enlarged view of a sliding surface. It is a graph showing the surface shape of the sliding surface of the direction perpendicular | vertical to a sliding direction and the direction along the outer periphery of a gasket. It is a graph showing the surface shape of the sliding surface along a sliding direction. It is sectional drawing of a gasket. It is a flowchart which shows the manufacturing method of a gasket. It is explanatory drawing of the step which shape | molds a laminate film. It is explanatory drawing of the step which shape | molds a laminate film. It is explanatory drawing of the step which shape | molds a gasket main body. It is explanatory drawing of the step which shape | molds a gasket main body. It is sectional drawing of a semi-finished product. It is explanatory drawing of the step which roughens a sliding surface. It is an expanded sectional view of a sliding surface. It is sectional drawing to which the sliding surface of the conventional gasket was expanded. It is an expanded sectional view of a sliding surface when arithmetic surface roughness is large. It is a table | surface which shows the structure and performance of an Example and a comparative example.

  As shown in FIG. 1, the prefilled syringe 10 is a syringe (syringe) that is stored in a state in which a drug solution 11 is pre-filled, and includes a barrel 12 that holds the drug solution 11, a gasket 13 that is inserted into the barrel 12, and a barrel 12. The cap 14 attached to the nozzle 16 and the plunger 15 are provided. The drug solution 11 is, for example, an X-ray imaging angiographic agent (iohexol or the like).

  The barrel 12 is made of, for example, a synthetic resin that can withstand sterilization such as cycloolefin polymer (COP) and cycloolefin copolymer (COC), which is a copolymer of cycloolefin polymer. The barrel 12 has a substantially cylindrical shape, and a nozzle 16 and a luer lock 17 for discharging the chemical solution 11 are formed at the distal end portion, and a flange 18 is formed at the proximal end portion. The nozzle 16 is provided with an opening 16a, and the nozzle 16 discharges the chemical solution 11 from the opening 16a. The luer lock 17 is a female connector provided with a screw groove on the inner peripheral surface, and is screwed into a male connector provided with a screw groove on the outer peripheral surface when the drug solution 11 is infused into the subject. Thus, the nozzle 16 is securely connected to the infusion channel. The flange 18 protrudes from the outer periphery of the barrel 12 and becomes a handle of the barrel 12 when the plunger 15 is pressed.

  The gasket 13 and the cap 14 are rubber sealing members. The gasket 13 is inserted into the barrel 12 to seal the proximal end side of the barrel 12. The cap 14 seals the distal end side of the barrel 12 by being attached to the nozzle 16. That is, the chemical solution 11 filled in the barrel 12 in advance is sealed and held in the barrel 12 by the gasket 13 and the cap 14. Further, when the cap 14 is attached to the nozzle 16, the cap 14 is fitted to the luer lock 17.

  When the gasket 13 is inserted into the barrel 12, the gasket 13 comes into contact with the barrel 12 at the sliding surface 21 a and the sliding surface 21 b, but the gasket 13 is slidable within the barrel 12. The gasket 13 is provided with a screw portion 19 for screwing the plunger 15. The plunger 15 is screwed to the screw portion 19, and the plunger 15 is pushed or pulled out using the plunger head 15 a. 13 can slide inside the barrel 12. When using the chemical solution 11 of the prefilled syringe 10, the plunger 15 is attached as described above, and the cap 14 is removed from the nozzle 16. After that, the drug solution 11 can be discharged from the nozzle 16 by pressing the plunger 15 and sliding the gasket 13 toward the front end side of the barrel 12.

  As shown in FIG. 2, the gasket 13 has a substantially cylindrical shape, and includes a tip surface 23, a sliding surface 21 a and a sliding surface 21 b, a non-sliding surface 22, and a bottom surface 24. The tip surface 23 is a surface that comes into contact with the chemical solution 11 when the gasket 13 is inserted into the barrel 12. The sliding surface 21 a and the sliding surface 21 b are side surfaces that slide in contact with the barrel 12 when the gasket 13 is inserted into the barrel 12. The non-sliding surface 22 is a side surface that does not contact the barrel 12 among the side surfaces of the gasket 13. The bottom surface 24 exposes the screw portion 19 on the proximal end side of the barrel 12 when the gasket 13 is inserted into the barrel 12.

  The gasket 13 roughens the sliding surface 21a and the sliding surface 21b among the above surfaces. Specifically, as shown in FIG. 3 in which a part of the sliding surface 21a is enlarged, the sliding surface 21a and the sliding surface 21b are along the sliding direction Ds of the gasket 13 (Z-axis direction). A plurality of grooves 30 (so-called “vertical stripes”) are provided. These grooves 30 continue from the bottom surface 24 side to the front end surface 23 side of the sliding surface 21a. Similarly, the groove 30 of the sliding surface 21b continues from the bottom surface 24 side to the tip surface 23 side.

  On the other hand, the interval between the grooves 30 has no fixed periodicity and is almost random. Therefore, the “roughness” of the sliding surface 21a and the sliding surface 21b has directionality. More specifically, the sliding surface 21a that is perpendicular to the sliding direction Ds and that is measured along the outer periphery of the gasket 13 (the direction that curves along the surfaces of the sliding surface 21a and the sliding surface 21b) and The arithmetic average roughness Ra1 of the sliding surface 21b is larger than the arithmetic average roughness Ra2 of the sliding surface 21a and the sliding surface 21b measured along the sliding direction Ds (Ra1> Ra2).

  The Z-axis is taken along the sliding direction Ds of the gasket 13, the direction is perpendicular to the sliding direction Ds, and the direction along the outer periphery of the gasket 13 is the X-axis, and the direction perpendicular to the Z-axis and the Y-axis (that is, The direction perpendicular to the surfaces of the sliding surface 21a and the sliding surface 21b) is taken as the Y axis. In this case, the arithmetic average roughness Ra1 is the arithmetic average roughness in the X-axis direction. As shown in FIG. 4, the surface shape of the sliding surface 21a or the sliding surface 21b is measured and the surface relative to the position on the X-axis is measured. Assuming that F (X) is a function of the height of λ, and integration is performed for an arbitrary unit length L, it can be calculated by Ra1 = (1 / L) × ∫ | F (X) | dX. In the gasket 13, the arithmetic average roughness Ra1 is 0.06 μm or more and less than 3.0 μm, preferably 0.5 μm or more and less than 2.0 μm, particularly preferably 0.6 μm or more and less than 1.0 μm. . If the arithmetic average roughness Ra1 is within these ranges, the sliding property and the sealing property are compatible, and the manufacturing suitability of the gasket 13 is high. Similarly, the arithmetic average roughness Ra2 is an arithmetic average roughness measured along the Z-axis direction. As shown in FIG. 5, a function of the surface height with respect to the position on the Z-axis is defined as G (Z). By integrating over an arbitrary unit length L, it can be calculated by Ra2 = (1 / L) × ∫ | G (Z) | dZ. In the gasket 13, the arithmetic average roughness Ra2 is set to about 0 μm or more and less than 0.5 μm. However, if the arithmetic average roughness Ra2 is smaller than the arithmetic average roughness Ra1, the arithmetic average roughness Ra2 may be 0.5 μm or more. . The zero point (origin) of the Z axis and the X axis is arbitrary, and the zero point of the Y axis is the surface of the designed sliding surface 21a and sliding surface 21b. Arithmetic average roughness is also called centerline average roughness.

  As shown in FIG. 6, the gasket 13 is formed by a gasket body 41, a laminate film 42, and a silicone coating 43. The gasket body 41 is made of rubber. For example, butyl rubber, chlorinated butyl rubber, butadiene rubber, acrylonitrile butadiene rubber, and isoprene rubber are preferable as the material for forming the gasket main body 41, but the gasket main body 41 is formed using chlorinated butyl rubber that has a proven track record for medical use. It is preferable to do. At the time of manufacturing the gasket main body 41, an organic peroxide vulcanizing agent or sulfur vulcanizing agent, a hardness adjusting filler, an antioxidant, and a processing aid are used as a compounding agent in addition to the main raw material chlorinated butyl rubber. As these mixing and kneading methods, a roll kneader, a Banbury kneader, a pressure kneader, or a combination thereof can be used.

  The laminate film 42 is made of, for example, a fluororesin and covers the gasket body 41. More specifically, the laminate film 42 covers the gasket main body 41 at least on the side surface of the gasket 13 including the tip surface 23 of the gasket 13 and the sliding surface 21 a, the sliding surface 21 b, and the non-sliding surface 22. For this reason, when the gasket 13 is inserted into the barrel 12, it is the laminate film 42 that contacts the chemical solution 11. Therefore, in order to prevent the rubber component of the gasket body 41 from eluting into the chemical solution 11 when the gasket 13 comes into contact with the chemical solution 11, the laminate film 42 is easy to process and has high chemical solution resistance. PTFE) or ethylene tetrafluoroethylene copolymer (ETFE: Ethylene TetraFluoroEthylene copolymer) is preferable.

  In addition, when the gasket 13 is inserted into the barrel 12, it is not the gasket body 41 but the laminate film 42 that contacts the barrel 12 on the sliding surface 21 a and the sliding surface 21 b. For this reason, the groove | channel 30 which roughens the sliding surface 21a and the sliding surface 21b is formed in the surface of the laminate film 42. FIG. In the present embodiment, the side surface of the gasket body 41 is formed flat compared to the arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b. Irregularities or the like for forming the groove 30 may be formed on the side surface to be the surface 21b.

The silicone coating 43 is a lubricant that adjusts the frictional force between the gasket 13 and the barrel 12. The silicone coating 43 has a kinematic viscosity at 25 ° C. of 100 mm ² / s (100 cSt) or more and 3000 mm ² / s (3000 cSt) or less. If the kinematic viscosity is the silicone coating 43 in this range, the prefilled syringe 10 is prevented from entering the chemical solution 11 between the barrel 12 and the sliding surface 21a and the sliding surface 21b during sterilization processing or storage, and is ineffective. The sliding resistance of the gasket 13 in the barrel 12 can be maintained to such an extent that the user can use the prefilled syringe 10.

  As shown in FIG. 7, the gasket 13 includes a step S11 for forming a laminate film 42, a step S12 for forming the gasket body 41, a step S13 for roughening the sliding surface 21a and the sliding surface 21b, It can manufacture by step S14 which applies the silicone coating 43.

  As shown in FIG. 8, the mold 51 has a cavity 51a formed in the shape of the gasket body 41 and an exhaust passage 51b connected to the cavity 51a. In step S <b> 11 for forming the laminate film 42, surface treatment such as corona treatment or plasma treatment is performed on the laminate film 42 by corona treatment or plasma treatment, and adhesion with the rubber or the silicone coating 43 forming the gasket body 41 is enhanced. The surface-treated laminate film 42 is stretched on the mold 51 to cover the cavity 51a. Thereafter, the laminate film 42 is heated to a temperature at which it can be easily stretched by a ceramic heater or the like, and the cavity 51a is evacuated through the exhaust passage 51b. Thereby, the laminate film 42 is stretched, and the laminate film 42 is formed into a shape along the cavity 51a as shown in FIG.

  As shown in FIG. 10, in step S12 of molding the gasket body 41, a rubber cloth 55 forming the gasket body 41 is inserted into the cavity 51a of the mold 51 covered with the laminate film 42, as shown in FIG. Further, the rubber cloth 55 is vulcanized and molded by the mold 51 and the second mold 56, thereby forming the rubber cloth 55 integrally with the laminate film 42 into the shape of the gasket body 41. Then, the laminate film 42 remaining between the mold 51 and the second mold 56, the burrs of the rubber cloth 55, the excess rubber cloth 55 entering the escape portion 57 of the second mold 56, and the like are removed. Thus, as shown in FIG. 12, a gasket body 41 covered with a laminate film 42 is formed. Thus, the gasket main body 41 covered with the laminate film 42 formed in step S11 has the same outer shape as the gasket 13, and includes a tip surface 23, a sliding surface 21a, a sliding surface 21b, a non-sliding surface 22, and a bottom surface 24. And a screw portion 19 are formed. However, the sliding surface 21a and the sliding surface 21b are semi-finished products 59 which have not been roughened yet and the silicone coating 43 is not applied.

  In the next step S13, as shown in FIG. 13, the plunger 61 is attached to the semi-finished product 59, and the sliding surface 21a and the sliding surface 21b that come into contact with the barrel 12 are roughened by passing through the metal jig 63. Turn into. The jig 63 is generally formed in an annular shape, and has a guide receiving portion 63a having a taper for receiving the semi-finished product 59, and a diameter of 0.05 mm to 0.30 mm smaller than the diameter of the semi-finished product 59, and an inner surface 63c. Has a roughened portion 63b roughened by blasting. When the semi-finished product 59 is passed once straight through the jig 63, the sliding surface 21a and the sliding surface 21b rub against the inner surface 63c of the roughened portion 63b, and the sliding surface 21a and the sliding surface 21b slide in the sliding direction Ds. A plurality of grooves 30 are formed along. The plunger 61 is for manufacturing having a length suitable for passing the semi-finished product 59 through the jig 63 and is different from the plunger 15 used by the user, but the plunger 15 used by the user is used. Thus, the semi-finished product 59 can be passed through the jig 63.

  Then, the gasket 13 is completed by applying the silicone coating 43 to the semi-finished product 59 in which the sliding surface 21a and the sliding surface 21b are roughened by passing the jig 63 in step S14. For example, the silicone coating 43 is specifically prepared by dissolving medical silicone (for example, Toray Dow Corning Medical Grade Oil 360 Medical Fluid viscosity 1000 cSt) in n-hexane to 1 wt%. The semi-finished product 59 with the sliding surface 21a and the sliding surface 21b roughened is dipped for 30 seconds, dried with 100 ° C. dry air for about 1 hour, and coated by evaporating n-hexane. In addition, the silicone coating 43 can be applied by spraying or brushing. The concentration of medical silicone in the solution is preferably 0.5 wt% or more and 10 wt%.

  As shown in FIG. 14, on the sliding surface 21a of the gasket 13 formed as described above (the sliding surface 21b is the same), the top portion 71 between the grooves 30 is linear along the sliding direction Ds in the barrel 12. The groove 30 is filled with the silicone coating 43 without a gap. Since there is almost no friction between the silicone coating 43 and the barrel 12, the friction between the top 71 and the barrel 12 becomes the sliding resistance of the gasket 13. The gasket 13 is provided with a groove 30 on the sliding surface 21a, and is roughened within a range in which the arithmetic average roughness Ra1 falls within a range of 0.06 μm or more and less than 3.0 μm. Adjust the balance of the groove 30 that does not contact 12, and set the sliding resistance of the gasket 13 within the range in which the prefilled syringe 10 can be used even by a powerless user who can withstand internal pressure from the chemical solution 11 during sterilization. Yes. Usable sliding resistance of the prefilled syringe 10 even by a non-powerful user is less than about 50N.

  As shown in FIG. 15, in the conventional gasket, the sliding surface 72 has a mirror finish with an arithmetic average roughness Ra1 of less than 0.06 μm. In some cases, an area 73 where the laminate film 42 contacts the barrel 12 on its surface appears. When the laminate film 42 comes into contact with and adsorbs to the barrel 12 and is in a pseudo-adhesive state, a large sliding resistance of 50 N or more is generated, so that the prefilled syringe 10 cannot be used by a powerless user. Further, when the laminating film 42 and the barrel 12 are brought into contact with each other on the sliding surface 72 to generate a large sliding resistance, the chemical solution 11 cannot be stably discharged even if an autoinjector is used.

  As described above, the conventional gasket is in contact with the barrel 12 on the surface and is likely to be in a pseudo-bonded state. On the other hand, in the case of the gasket 13, the top portion 71 may be adsorbed to the barrel 12, but the gasket 13 comes into linear contact with the barrel 12 at the top portion 71. There is no pseudo-adhesive state that causes sliding resistance.

  As described above, the gasket 13 of the present invention has a sliding resistance within an appropriate range by roughening the sliding surface 21a and the sliding surface 21b. Since the groove 30 for roughening the surface has a depth within a range where the arithmetic average roughness Ra1 falls within the range of 0.06 μm or more and less than 3.0 μm, the groove 30 is filled with the silicone coating 43 without excess or deficiency. The For this reason, since there is almost no gap between the groove 30 and the barrel 12, the gasket 13 roughens the sliding surface 21 a and the sliding surface 21 b, but the chemical solution 11 does not leak. As shown in FIG. 16, when the groove 30 has a depth at which the arithmetic surface roughness Ra1 is 3.0 μm or more, a gap 76 is formed between the silicone coating 43 filling the groove 30 and the barrel 12. Leakage such as the chemical solution 11 entering the gap 76 may occur.

  Hereinafter, configurations and performances of Examples 1 to 4 and Comparative Examples 1 to 3 shown in the table of FIG. 17 will be described. Each of Examples 1 to 4 is the gasket 13 of the present invention in which the sliding surface 21 a and the sliding surface 21 b are provided with the grooves 30 and the silicone coating 43 is applied. The difference between Examples 1 to 4 is the value of the arithmetic average roughness Ra1 measured along the sliding surface 21a and the sliding surface 21b and perpendicular to the sliding direction Ds, and the kinematic viscosity of the silicone coating 43. Note that the arithmetic average roughness Ra1 is preferably measured in a non-contact manner because the change due to the contact of the measuring device is not preferable. For this reason, arithmetic average roughness Ra1 was measured with non-contact three-dimensional shape measuring apparatus NH-3N (made by Mitaka Kogyo Co., Ltd.) based on JIS B 0601: 2001 standard. In addition, Keyence Corporation's laser microscope VK-X series is suitable for the purpose. The kinematic viscosity of the silicone coating 43 can be measured using, for example, a glass capillary viscometer defined in a JIS K2283 kinematic viscosity tester. The kinematic viscosity of the silicone coating 43 shown herein is a value at 25 ° C.

In the gasket 13 of Example 1, the arithmetic average roughness Ra1 is 0.5 μm, and the kinematic viscosity of the silicone coating 43 is 1000 mm ² / s. In the gasket 13 of Example 2, the arithmetic average roughness Ra1 is 2.0 μm, and the kinematic viscosity of the silicone coating 43 is 1000 mm ² / s. In the gasket 13 of Example 3, the arithmetic average roughness Ra1 is 2.0 μm, and the kinematic viscosity of the silicone coating 43 is 3000 mm ² / s. In the gasket 13 of Example 4, the arithmetic average roughness Ra1 is 0.5 μm, and the kinematic viscosity of the silicone coating 43 is 100 mm ² / s.

  On the other hand, Comparative Examples 1 to 3 are comparative gaskets in which the sliding surface 21 a and the sliding surface 21 b are not roughened or the silicone coating 43 is not applied. Comparative Example 1 is a gasket in a state of a semi-finished product 59 in which the sliding surface 21a and the sliding surface 21b are not roughened and the silicone coating 43 is not applied. The comparative gasket of Comparative Example 1 has an arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b of 0.05 μm, and is almost in a mirror finished state.

In Comparative Example 2, the sliding surface 21a and the sliding surface 21b are not roughened, but the silicone coating 43 is a comparative gasket coated. The comparative gasket of Comparative Example 2 has an arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b of 0.05 μm, and is almost in a mirror finished state. In the comparative gasket of Comparative Example 2, the kinematic viscosity of the silicone coating 43 is 1000 mm ² / s.

  Comparative Example 3 is a comparative gasket in which the sliding surface 21a and the sliding surface 21b are roughened in the same manner as the gasket 13 of the present invention, but the silicone coating 43 is not applied. In the comparative gasket of Comparative Example 3, the arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b is 0.5 μm, which is equal to the gasket 13 of Example 1 and Example 4.

  About the performance of the gasket 13 of the said Example 1- Example 4 and the gasket for the comparison of Comparative Example 1- Comparative Example 3, "sliding resistance", "sealing property (chemical solution leak)", and after sterilization processing, respectively The performance was evaluated with respect to three points of “tilt” in the barrel 12.

  The sliding resistance is obtained by filling the barrel 12 with an electrolyte infusion “Otsuka raw food injection” manufactured by Otsuka Pharmaceutical as the chemical solution 11, inserting each gasket into the barrel 12, and removing the cap 14. The pressing force required for pressing (that is, the pressing force required for sliding the gasket) was measured. In the measurement of the sliding resistance, a tensile tester (manufactured by Shimadzu Autograph AGS-X) and a jig for converting the tensile direction of the tensile tester into the pressing direction of the plunger 15 were used. The pressing force with which any user can easily use the prefilled syringe 10 is less than about 40 N, and the pressing force with which a non-powerful user can use the prefilled syringe 10 is less than about 50 N. Therefore, as a result of measurement, when the pressing force is less than 40N, “A” (especially easy to use), when the pressing force is 40N or more and less than 50N, “B” (usable), the pressing force is 50N or more In some cases, it was evaluated as “C” (some users may find it difficult to use). FIG. 17 shows the sliding resistance (pressing force) in parentheses together with the above evaluation.

  For the measurement of the sealing property (chemical solution leakage), a pseudo chemical solution made easier to observe by adding a red dye to distilled water for injection that easily enters between the barrel 12 and the gasket 13 than the chemical solution 11 was used. The chemical liquid leak is filled with the pseudo chemical liquid in the barrel 12, sealed with the gasket 13 and the cap 14, and after applying a pressure of 300 kPa to the gasket 13 for 20 minutes with a tensile tester used for measuring the sliding resistance, it is visually and magnified. The sliding surface 21a on the tip side of the gasket 13 was observed with a 20 × microscope. And in visual observation and microscopic observation, when the penetration of the pseudo chemical solution between the barrel 12 and the gasket 13 is not recognized, “A” (particularly good state with high sealing performance and no leakage), “B” (can be used) when no intrusion is detected by microscopic observation, but “C” (cannot be used due to chemical leakage) when intrusion of simulated chemical liquid is observed by visual observation (and microscopic observation) ). The pressure of 300 kPa (about 3 atm) is an internal pressure applied from the chemical solution 11 during the sterilization process in which heating is performed at 121 ° C. for 20 minutes in an autoclave.

  As for the inclination of the gasket 13, the barrel 12 filled with the pseudo chemical solution is sterilized by heating at 121 ° C. for 20 minutes in an autoclave, and then the depth from the flange 18 to the bottom surface 24 of the gasket 13 is set at eight locations (45 And measure the difference between the maximum depth and the minimum depth, and perform this measurement on 10 prefilled syringes 10 to obtain the average value of the difference between the maximum depth and the minimum depth. Was calculated and evaluated based on the average value of the difference between the maximum depth and the minimum depth. When the average difference between the maximum depth and the minimum depth is less than 0.6 mm, “A” (substantially no inclination), and when it is 0.6 mm or more and less than 0.8 mm, “B” (slight inclination) However, the sterility of the chemical solution 11 can be guaranteed), and when it is 0.8 mm or more, it was evaluated as “C” (the inclination is large and the sterility of the chemical solution 11 cannot be guaranteed). FIG. 17 shows the average value of the difference between the maximum depth and the minimum depth in parentheses together with the above evaluation.

  In the comparative gasket of Comparative Example 1, the sliding surface 21a and the sliding surface 21b are not roughened, have a mirror finish, and the silicone coating 43 is not applied. Evaluation is “C”, and when the comparative gasket of Comparative Example 1 is used, it is difficult for some users to use the prefilled syringe 10. In addition, the evaluation of the inclination of the comparative gasket of Comparative Example 1 is “C”, and if the comparative gasket of Comparative Example 1 is used, the sterility of the chemical solution 11 cannot be guaranteed, so it must be discarded after sterilization. There are many prefilled syringes 10 and the yield is also poor.

  Further, the comparative gasket of Comparative Example 2 is not roughened on the sliding surface 21a and the sliding surface 21b and has a mirror finish, but is coated with the silicone coating 43. The sliding resistance is lower than that of the comparative gasket. However, the evaluation of the sliding resistance is “C”, and it is still difficult for some users to use the prefilled syringe 10. Further, the comparative gasket of Comparative Example 2 has a smaller inclination after sterilization compared to the comparative gasket of Comparative Example 1, but the evaluation of the inclination remains “C” and must be discarded after the sterilization treatment. There are many prefilled syringes 10 that must be processed, and the yield is still poor.

  On the other hand, the comparative gasket of Comparative Example 3 has the sliding surface 21a and the sliding surface 21b roughened, so the sliding resistance is evaluated as “B” compared with the comparative gaskets of Comparative Example 1 and Comparative Example 2. Can be reduced. In addition, the evaluation of the inclination is “B”, and there are more prefilled syringes 10 that have a slight inclination but can guarantee the sterility of the drug solution 11. However, the comparative gasket of Comparative Example 3 has a sealing performance evaluation of “C”. This is because the silicone coating 43 is not applied although the sliding surface 21a and the sliding surface 21b are roughened, so that the chemical solution 11 enters the grooves 30 of the sliding surface 21a and the sliding surface 21b. Because it does.

  As can be seen from a comparison between Comparative Example 3 and Comparative Examples 1 and 2, the groove 30 of the sliding surface 21a and the sliding surface 21b has an effect of greatly reducing the sliding resistance. However, since the groove 30 of the sliding surface 21a and the sliding surface 21b forms a gap between the barrel 12 and the gasket 13, the sealing performance is deteriorated, and chemical leakage is likely to occur. On the other hand, as can be seen from a comparison between Comparative Example 1 and Comparative Example 2, the coating of the silicone coating 43 is not only due to the effect of reducing the sliding resistance, but also due to the water repellency of the silicone coating 43 and the like. There is also an effect of increasing the substantial sealing performance of 12 and preventing chemical leakage. For this reason, the sealing performance deteriorated by forming the groove 30 in the sliding surface 21 a and the sliding surface 21 b can be supplemented by the silicone coating 43.

  The evaluations of the sliding resistance of the gaskets 13 of Examples 1 to 4 are all “A”, the evaluations of chemical leakage are also “A” to “B”, and the evaluations of the inclination are all “A”. Yes, both sealing performance and slidability can be achieved. As described above, this is aggravated by forming the groove 30 on the sliding surface 21a and the sliding surface 21b to lower the sliding resistance and forming the groove 30 on the sliding surface 21a and the sliding surface 21b. This is because the silicone coating 43 supplements the sealing performance.

As can be seen from a comparison between Example 1 and Example 2, when the arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b increases, the sealing performance decreases, but as shown in Example 3, If the kinematic viscosity of the silicone coating 43 is increased, the sealing property can be supplemented. Further, as can be seen from a comparison between Example 1 and Example 4 (or Example 2 and Example 3), even though the arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b is the same, the silicone coating 43 When the kinematic viscosity is reduced, the sealing performance is lowered. However, if the kinematic viscosity of the silicone coating 43 is too high, it is difficult to obtain an effect of the silicone coating 43 reducing the sliding resistance as a lubricant. Therefore, when the arithmetic average roughness Ra1 of the sliding surface 21a and the sliding surface 21b is 0.06 μm or more and less than 3.0 μm, the kinematic viscosity of the silicone coating 43 is 100 mm ² / s or more and 3000 mm ² / s or less. Preferably, it is 500 mm ² / s or more and 2000 mm ² / s or less, and particularly preferably 750 mm ² / s or more and 1500 mm ² / s or less.

  In the above-described embodiment and examples, the groove 30 along the sliding direction Ds is formed on the sliding surface 21a and the sliding surface 21b. However, the direction of the groove 30 is not strictly parallel to the sliding direction Ds. Also good. For example, the groove 30 may be inclined with respect to the sliding direction Ds, or the groove 30 may be a curve. That is, if the condition that the arithmetic average roughness Ra1 is larger than the arithmetic average roughness Ra2 (Ra1> Ra2) is satisfied, the inclination of the groove 30 with respect to the sliding direction Ds and the shape of the groove 30 can be changed almost arbitrarily. it can. Of course, in order to obtain excellent manufacturing suitability and to obtain the operation of the present invention most easily, the groove 30 is formed substantially parallel to the sliding direction Ds and the sliding surface 21a and It is preferable to roughen the sliding surface 21b.

  In the above-described embodiment and the modification, the vertical streak-like groove 30 is formed substantially along the sliding direction Ds on the sliding surface 21a and the sliding surface 21b, and the arithmetic average of the sliding surface 21a and the sliding surface 21b is formed. Although the roughness Ra1 is larger than the arithmetic average roughness Ra2 (Ra1> Ra2), random and isotropic irregularities are formed on the sliding surface 21a and the sliding surface 21b, and the arithmetic average roughness Ra1 and When the arithmetic average roughness Ra2 is equal (Ra1 = Ra2), or the horizontal streak-shaped grooves along the direction perpendicular to the sliding direction Ds are formed on the sliding surface 21a and the sliding surface 21b, the arithmetic average roughness Even when Ra1 is smaller than the arithmetic average roughness Ra2 (Ra1 <Ra2), the pseudo-adhesion state between the gasket 13 and the barrel 12 is prevented, and the sliding surface 21a and the sliding surface 21b are not roughened. Reduce sliding resistance of gasket 13 It is possible.

  However, although random and isotropic unevenness can be formed by blasting or the like, it is difficult to form unevenness having a sharp depth like the vertical stripe-shaped groove 30, so it is compared with the vertical stripe-shaped groove 30. Then, it is difficult to prevent the pseudo-adhesion state between the gasket 13 and the barrel 12. In addition, when a horizontal stripe-shaped groove is formed on the sliding surface 21a and the sliding surface 21b, the total length of the top portion between the grooves becomes a resistance component perpendicular to the sliding direction. As compared with, the sliding resistance of the gasket 13 tends to increase. Therefore, the slide surface 21a and the slide surface 21b may be formed with random and isotropic unevenness and horizontal stripe-shaped grooves. However, as in the above-described embodiment and example, the slide surface 21a and the slide surface 21b are formed. It is preferable to form a vertical streak-like groove 30 along the sliding direction Ds on the moving surface 21b.

  In the said embodiment, although an example of the suitable manufacturing method of the gasket 13 is mentioned, shaping | molding of the laminate film 42 (step S11) and shaping | molding of the gasket main body 41 (step S12) can be performed by another method. For example, in the above embodiment, after the laminate film 42 is vacuum-formed, the gasket body 41 is insert-molded. However, the rubber cloth 55 is placed on the laminate film 42 and the semi-finished product 59 is formed by a single press. You can also. Alternatively, the semifinished product 59 can be manufactured by forming the gasket body 41 and forming a laminate film 42 around the gasket body 41.

DESCRIPTION OF SYMBOLS 10 Prefilled syringe 11 Chemical solution 12 Barrel 13 Gasket 14 Cap 16 Nozzle 17 Luer lock 21a, 21b Sliding surface 30 Groove 41 Gasket body 42 Laminate film 43 Silicone coating

Claims (11)

A gasket body slidably inserted into the barrel of the syringe;
A laminate film that covers the gasket body and has a roughened sliding surface that slides in contact with the barrel;
A silicone coating covering the laminate film;
A gasket comprising:   The gasket according to claim 1, wherein the sliding surface includes a groove along a sliding direction.   The arithmetic average roughness of the sliding surface that is perpendicular to the sliding direction and that is measured along the sliding surface is greater than the arithmetic average roughness of the sliding surface that is measured along the sliding direction. The gasket according to claim 1 or 2, wherein the gasket is large.   The arithmetic mean roughness of the sliding surface that is perpendicular to the sliding direction and that is measured along the sliding surface is 0.06 μm or more and less than 3.0 μm. The gasket according to item 1.   The gasket according to claim 4, wherein the gasket is perpendicular to the sliding direction and has an arithmetic average roughness of the sliding surface measured along the sliding surface of 0.5 μm or more and less than 2.0 μm. The silicone coating, the gasket according to any one of claims 1 to 5 the kinematic viscosity is less than 100 mm ² / s or more 3000 mm ² / s.   The gasket according to any one of claims 1 to 6, wherein the laminate film is formed of polytetrafluoroethylene or ethylenetetrafluoroethylene copolymer. A gasket body that is slidably inserted into a barrel of a syringe, a laminate film that covers the gasket body and has a roughened sliding surface that slides in contact with the barrel, and a silicone coating that covers the laminate film In a method for manufacturing a gasket comprising:
Molding the laminate film to match the outer shape of the gasket body;
Roughening the sliding surface in contact with the barrel by passing the gasket body covered with the laminate film through a jig whose inner surface is roughened;
Applying a silicone coating to the roughened sliding surface;
A method for manufacturing a gasket comprising: A barrel for chemicals,
A gasket main body that is slidably inserted into the barrel; a laminate film that covers the gasket main body and has a roughened sliding surface that contacts and slides on the barrel; and a silicone coating that covers the laminate film; A gasket comprising,
Syringe.   The syringe according to claim 9, wherein the chemical liquid is sealed in the barrel by the gasket and a cap attached to a nozzle for discharging the chemical liquid.   The syringe according to claim 9 or 10, wherein the barrel is formed of a cycloolefin polymer.

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