JP2001104483A - Prefilled type syringe for drug, and its manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To preserve the slidability between a piston and a resin surface on the internal surface of a barrel, and at the same time, improve the sealability. SOLUTION: This prefilled type syringe for drug is constituted by combining a barrel made of a plastic, a laminated piston and a nozzle cap. In this case, an elastic body section is provided on a piston-sliding surface on the internal surface of the barrel.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pre-filled syringe for medicine comprising a plastic barrel and a laminated piston, and more particularly to a syringe sliding surface on the barrel side for maintaining the sealing property of a drug solution. The present invention relates to a prefilled syringe having an elastic portion.

[0002]

2. Description of the Related Art Injections, which are one of pharmaceutical dosage forms, include:
There are solid dosage forms that are dissolved during administration and liquid dosage forms that are formulated as solutions. In addition, the means for administering an injection into the body include a method of administering a drug solution directly into the body from a syringe and a medical device other than a syringe after mixing with another drug solution held in another drug solution container immediately before administration, for example, There is a method of introducing it into the body via an administration system such as an infusion set.

[0003] By the way, an injection is prepared (filled) in a syringe / container in advance and transported and stored with its end sealed with a sealing stopper. There is a so-called pre-filled syringe that can be attached with a needle or a device for administration, push the sealing stopper toward the distal end and slide in the syringe to allow the injection to flow out from the needle side and administer it. This is because it has various advantages, such as easy operation, accurate dose administration even in an emergency, without misuse of the drug, easy operation of transferring the drug, avoiding microbial contamination and high hygiene. In recent years, it has been widely used from the viewpoint of improving the efficiency of treatment in medical treatment and preventing bacterial contamination. The use of a so-called kit product, which combines a solid preparation with water for injection and a drug solution in one system, is also encouraged for the same reason.

Although the prefilled syringe is convenient as described above, a high sealing property is required at the time of storing the medicine, and at the same time, it is necessary to slide the sealed stopper at the time of administering the medicine, and the sealing property is low. A function having a contradictory characteristic of slidability is required. In conventional syringes, silicone oil was applied to the piston to achieve both sealing and sliding properties.In recent years, however, the drop in potency due to the absorption of active pharmaceutical ingredients by the silicone oil and fine particles that are exfoliated from the silicone oil itself Therefore, there is a problem of chemical contamination and adverse effects on the human body (toxicity of silicone oil) due to this, and the use of silicone oil is being avoided.

[0005] On the other hand, a rubber movable sealing stopper having a main body made of rubber is known, which is formed by laminating a fluororesin film such as tetrafluoroethylene resin on a chemical contact surface (Japanese Utility Model Publication No. 48-8990), and a syringe. There is a rubber sealing stopper for a prefilled syringe (US Pat. No. 4,554,125) in which all parts that come into contact with the inner surface are laminated with a polypropylene resin.

In view of the above-mentioned circumstances, the present inventors have realized a syringe and a syringe / container which have both high sealing performance and high slidability without using silicone oil, and which has high hygiene and safety. Was. For example, Japanese Patent Application Laid-Open No. 62-139668
In JP-A-63-971, a sealing stopper whose surface is coated with a tetraethylene fluoroethylene-ethylene copolymer resin (hereinafter sometimes abbreviated as "ETFE") may be used.
In Japanese Patent Publication No. 73, a sealed stopper coated with a tetrafluoroethylene resin (hereinafter sometimes abbreviated as “PTFE”) film is further sealed with a real plug-in system as disclosed in
JP-B-138455 proposes a sealing stopper having a shape suitable for a pre-filled syringe and laminated with a film made of PTFE, ETFE and ultra-high-molecular-weight polyethylene resin. In addition, there has been proposed a syringe barrel made of a cyclic olefin-based plastic and having both sealing and sliding properties in combination with the sealing stopper (Japanese Patent Application Laid-Open No. 5-293159).

[0007]

The laminated rubber piston according to the prior art described above does not require silicone to be applied to the surface because the laminated film has sufficient surface lubrication, and also requires a chemical solution to prevent interaction with rubber. It has an excellent property that it does not affect the drug solution even if it is in contact for a long time. However, when a resin film is attached to the surface of the laminated piston, the piston surface is hardened, and when the liquid is filled with a chemical having a low viscosity and a small surface tension, liquid leakage may occur. The present invention has been developed based on a completely new idea in order to alleviate the drawbacks of the prior art, and maintains the slidability between the laminated piston and the resin surface of the inner surface of the barrel, improves the sealing performance, and further improves the sealing performance. The purpose is to prevent the sealing property from decreasing over time.

[0008]

(1) A pre-filled syringe comprising a combination of a plastic barrel, a laminated piston and a nozzle cap, wherein the syringe has an elastic portion on the piston sliding surface on the inner surface of the barrel. Prefilled syringe for pharmaceuticals. (2) The prefilled syringe for medicine according to the above (1), wherein the elastic portion of the sliding surface is formed integrally with the barrel. (3) The filled syringe for pharmaceuticals according to the above (1), wherein the elastic portion of the sliding surface is incorporated via an adapter. (4) The prefilled syringe for pharmaceuticals according to (3), wherein the adapter has an annular convex backstop on the inner peripheral side of the lower edge of the hollow portion of the mounting flange.

(5) The elastic member has a plastic laminate film on at least a part of its surface.
The prefilled syringe for pharmaceuticals according to any one of (1) to (4). (6) The filled syringe for pharmaceuticals according to any one of (1) to (4) above, wherein the elastic portion has a plastic laminate film on the entire surface thereof.

(7) An elastic body is injection-molded on a predetermined portion of a pin with a first mold, the pin and the elastic body are transferred to a second mold, and the barrel is injection-molded to integrally mold the barrel and the elastic body. (1), (2), (5) or (6), the method for producing a pre-filled syringe for medicine according to (6). (8) The above-mentioned (1), (2), (5) or (6) in which the barrel and the elastic body are integrally molded by fitting the previously molded elastic body into a predetermined position of the molding pin and injection molding the resin of the barrel. )) Manufacturing method for prefilled syringes for pharmaceuticals (manufacturing method in the figure).

(9) An elastic body is injection-molded on a predetermined portion of the pin with the first mold, the pin and the elastic body are transferred to the second mold, and the adapter is molded integrally with the elastic body by injection molding the adapter. (3) or (4), wherein the adapter is incorporated in a barrel to have an elastic body on the piston sliding surface of the barrel.

(10) An adapter molded integrally with the elastic body is prepared by inserting a preformed elastic body into a predetermined position of a molding pin and injection-molding a resin of the adapter, and incorporating the adapter into a barrel.
(3) or (4), the method for producing a pre-filled pharmaceutical syringe according to the above (3) or (4), wherein the barrel has an elastic body on a sliding surface of the piston. (11) The elastic body, adapter, and barrel are separately molded,
The method for producing a pre-filled pharmaceutical injector according to the above (3) or (4), which is produced by assembling these components.

In each of the above-mentioned inventions, an elastic portion is provided on a part of the piston sliding surface of the pre-filled syringe, and the piston is stopped at this portion, thereby sealing the pre-filled syringe as described above. Sex problems can be solved.
That is, a pre-filled syringe using a conventional laminated piston must maintain sealing properties with the laminated film on the piston surface and the resin surface on the inner surface of the barrel, but the laminated film is not sufficiently flexible, and the inner surface of the barrel is not sufficiently flexible. A gap is easily formed between piston surfaces. Therefore, according to the present invention, by making the contact surface of the barrel with the piston an elastic body such as rubber, the sealing property of the contact surface is improved.

[0014]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the above (1) to (10), the width of the elastic portion provided on the piston sliding surface is 1 to 20 mm without a laminate, and 2 to 30 mm with a laminate.
mm is appropriate. This depends on the compression ratio of the piston (gap between the inner diameter of the piston and the sliding surface), the smoothness of the piston film surface, and the like. It is preferable that the length of the sliding surface of the piston be the maximum value. If the width of the elastic body is less than 1 mm, molding is difficult, and if it is too large, the sliding resistance increases.

[0015] The barrel and the adapter are composed of any plastic material. For example, norbornene, ethylidene norbornene, dicyclopentadiene, polymers of alicyclic monomers having a norbornene ring such as tetracyclododecene and olefinic hydrocarbons such as polyethylene, polypropylene, polyester and polycarbonate, an anti-aging agent, processing Examples thereof include those to which an auxiliary agent is added, but the present invention is not limited to these.

The elastic body used for the elastic body portion and the piston is generally a synthetic rubber such as isoprene rubber, butadiene rubber, styrene butadiene rubber, ethylene propylene rubber, isoprene-isobutylene rubber, nitrile rubber, or a natural rubber. As the main raw material, filler,
Those containing a crosslinking agent and the like are included. Examples of the thermoplastic elastomer include solution-polymerized styrene-butadiene rubber (SBS block copolymer), polyester or polyether urethane rubber, copolymer of polyether aromatic polyester block (polyester rubber), polyolefin block copolymer, and high trans- 1,4-polyisoprene, polyethylene butyl graft copolymer, syndiotactic polybutadiene and the like can also be used. In addition to the above, relatively soft plastics, for example,
Plastics such as copolymer-type polypropylene, low-density polyethylene, ethylene-vinyl acetate copolymer, and the like having a heat resistance almost equal to that of polypropylene (preferably about 130 to 140 ° C.) can also be used. In particular, the rubber band is preferably made of a material softer than the material of the barrel, for example, a soft plastic.

An appropriate plastic film is laminated on the above-mentioned laminated piston. Examples of the plastic film include tetrafluoroethylene resin (PTFE), tetrafluoroethylene-perfluoroethylene copolymer (PFA), and tetrafluoroethylene- Hexafluoropropylene copolymer (FE
P), tetrafluoroethylene-ethylene copolymer (ETFE), trichlorotrifluoroethylene (PC
Fluororesins such as TFE), polyvinylidene fluoride (PVDF) and polyvinyl fluoride (PVF), and ultrahigh molecular weight polyethylene other than fluororesins can also be used.

The elastic portion of the sliding surface may be formed integrally with the barrel by the method described below, or may be incorporated via an adapter. This elastic body portion may be laminated with the plastic film as described above, or may remain rough. In any case, by stopping the piston at this portion, the hermeticity of the chemical held in the barrel can be ensured. When provided by integral molding, there is an advantage that the number of steps is small, but there is a drawback that mass production is difficult. On the other hand, when incorporated via an adapter, the production itself is easy because it is advantageous.

The elastic portion can be laminated on a part of the surface or the entire surface. However, the material of the laminate film may be different between the side of the elastic body portion that contacts the barrel or the adapter and the side of the sliding surface. On the side in contact with the barrel or adapter, one that can attach a film that can be fused with the barrel or adapter to prevent the rubber from rolling up when the piston is moved during use, and that can fix the stopper to the barrel or adapter Good. On the other hand, on the sliding surface side (inside the rubber band 8)
Is to prevent the adhesion when the rubber surface is in contact with the laminated piston for a long period of time because the sliding resistance is low because of the sliding surface. Therefore, as the film material on the surface side in contact with the barrel or the adapter, a resin close to the barrel or the adapter, for example, polyethylene, a polyolefin such as polypropylene, a cyclic unsaturated hydrocarbon resin, or the like is preferable, and as the film material on the sliding surface side, Is preferably the same fluororesin or ultra-high molecular weight polyethylene as the film for the laminated piston. Of course, both sides can be made of the same kind of resin film. In any case, the presence or absence of the lamination or the lamination area can be appropriately selected and set in consideration of the slidability and the sealing property.

A specific example of a pre-filled syringe for medicine according to the present invention will be described below with reference to the accompanying drawings. FIG. 1 is a longitudinal sectional view of a plastic barrel 1 used for a syringe of the present invention. A nozzle 3 is provided at the tip of a syringe barrel 1 and a flange 4 is provided at a rear part thereof so as to be engaged with a stopper 7 of an adapter 5. Is done. FIG. 2A is a longitudinal sectional view of the adapter 5 used in the syringe of the present invention, and FIG. 2C is a plan view thereof. A rubber band 8 is provided at the upper end of the adapter 5.
Is mounted so that its end is partially protruded, and has a flange 6 and a stopper 7 at the lower portion to engage with the flange 4 of the barrel 1. FIG. 2B shows another embodiment, in which a backstop 9 is provided as an annular projection on the inner peripheral side of the lower edge of the hollow portion of the mounting flange 6 to prevent the piston from being pulled out. FIG. 2D is a plan view of FIG. 2B. The backstop 9 is preferably provided as a continuous projection on the entire inner peripheral surface of the hollow portion, but may be partially notched.

FIG. 3 is a perspective view schematically showing the order of assembling the barrel 1, the rubber band 8 and the adapter 5, and FIG. 4 is a longitudinal sectional view of the assembled product. FIG. 5 is a longitudinal sectional view showing a state in which a piston 9 is inserted into a hollow portion of the above-mentioned assembly and fitted to a rubber band (elastic body portion) 8 attached thereto.

FIGS. 6 (a), 6 (b) and 6 (c) are partial longitudinal sectional views of the barrel showing positions where the piston 9 is fitted to the elastic portion 8, respectively. The piston 9 has a contact surface with the barrel 1. FIG. Is stopped at a position where the rubber band is partially or entirely hung.
That is, any of the above (a) to (c). Desirably, between (a) and (b), the contact area between the chemical solution and the rubber band is the minimum, and the sealability is ensured. FIG. 7 is a longitudinal sectional view showing a standard shape in which the rubber band 8 is mounted on the inner wall of the barrel without using the adapter.

Hereinafter, a specific example of the method for producing a pre-filled syringe for medicine of the present invention will be described with reference to FIGS. Manufacturing method [corresponding to the above (7)] First, as shown in FIG. 8, rubber is injected into a predetermined portion of the first mold 10, that is, a ring-shaped groove 12 by using a combination of the first mold 10 and the pin 11. And injection molding. Next, the molded pin 11 having an elastic body is transferred to the second mold 13, resin is injected, and the barrel is injection molded to integrally mold the barrel and the elastic body. Here, the first mold is a split mold that can be divided at an appropriate position, and the pin 11 is taken out after integral molding. A barrel having the elastic portion 8 of the standard shape shown in FIG. 7 is obtained.

Manufacturing method (corresponding to the above (8)) As shown in FIG. 9, a rubber band 8 molded in advance at a predetermined position of a pin 11 is transferred to a fitting die 13 to injection-mold a resin for a barrel. And integrally molded. A barrel having the elastic portion 8 of the standard shape shown in FIG. 7 is obtained.

Manufacturing method [corresponding to the above (9)] As shown in FIG. 10, first, a first mold 14 and a pin 15 are used, and a predetermined portion of the pin 15, that is, a rubber groove 13 is formed in the first mold ring-shaped groove 13. And injection molding [FIG.
(A)]. Next, the pin 15 having the molded elastic body 18
Is transferred to the second mold 16 and the adapter 17 is injection-molded to form the adapter 17 integrally formed with the elastic body 18 (FIG. 10B). The obtained adapter 17 [FIG. 10 (c)] is combined with a separately formed barrel 19 [FIG. 10 (d)] to form a set having an elastic body on the piston sliding surface of the barrel shown in FIG. A three-dimensional structure is obtained, or a resin is injected into the third mold 20 and the barrel 19 is integrally formed to obtain the assembly shown in FIG. 4 (FIG. 10E).

Manufacturing method (corresponding to the above (10)) A preformed elastic body (rubber band) 18 is
5 (FIG. 11A), and the first mold 16
And the adapter 17 is injection molded [FIG.
(A), (b)]. In this way, an adapter 17 integrally formed with the elastic body is produced (FIG. 11C), and then assembled into a separately molded barrel 19 in the same manner as in the manufacturing method [FIG.
1 (d)], an assembly having an elastic body on the piston sliding surface of the barrel as shown in FIG.
0, resin is injected, and the barrel 19 is integrally formed to obtain the assembly shown in FIG. 4 (FIG. 11E).

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

(Example 1) An example of manufacturing a pre-filled pharmaceutical syringe having a standard shape shown in Fig. 7 and having an elastic portion on the piston sliding surface on the inner surface of the barrel will be described. FIG.
Was carried out. A preformed rubber band 8 made of butyl rubber was fitted into a predetermined position of the pin 11, transferred to a mold 13, and injection molded with a cyclic olefin resin to form the barrel 1 having the elastic portion 8.

On the other hand, a product made by laminating a film made of fluororesin on a piston made of butyl rubber is prepared, and after injecting a chemical solution into the barrel 1, it is pushed into an injection cylinder and stopped on the elastic portion 8, and sealing and sliding properties are obtained. Tested. Here, the length of the injection cylinder 1 is 100 mm and the inner diameter is 20 m
m, the outer diameter was 24 mm, and the length of the elastic portion was 15 mm. The length of the piston is 15 mm, of which 3 mm is the length of the portion that comes into contact with the barrel to ensure the sealing property, and the outer diameter is 2 mm.
1 mm. Here, the sealability test is performed in accordance with the test method described in the pressure test of the sterilized syringe test standard based on Article 42, Paragraph 2 of the Pharmaceutical Affairs Law, and the slidability test is a test method unique to the present invention. Depended on. As a result of the above-mentioned test, the sealing property of the conventional product was found to leak to about 10%, but the product of the present invention was not found at all. On the other hand, the sliding property of the conventional product is about 2
In contrast to 0N, the product of the present invention increased by 10 to 20% (approximately 22 to 24N), which was practically no problem.

[0029]

According to the prefilled syringe of the present invention, an elastic portion such as rubber is mounted on the piston sliding surface on the inner surface of the barrel.
By stopping the laminate piston at the elastic portion after filling with the chemical solution, contradictory properties such as sealing performance with the barrel, slidability, and hygiene can be exhibited in a well-balanced manner.

[Brief description of the drawings]

FIG. 1 is a longitudinal section of a plastic barrel 1 used in a syringe of the present invention.

FIG. 2 (a) is a longitudinal sectional view of an adapter 5 used in the syringe of the present invention, and FIG. 2 (c) is a plan view thereof. FIG. 2B is a longitudinal sectional view of another embodiment of the adapter 5 used in the syringe of the present invention.
(D) is a plan view thereof.

FIG. 3 is a perspective view schematically showing an order of assembling the barrel, the rubber band, and the adapter.

FIG. 4 is a longitudinal sectional view of an assembly comprising a barrel, a rubber band, and an adapter.

FIG. 5 is a longitudinal sectional view showing a state in which a piston 9 is inserted into a hollow portion of the above-mentioned assembly and fitted to a rubber band (elastic body portion) 8 attached thereto.

6 (a), 6 (b) and 6 (c) are each a partial longitudinal sectional view of a barrel showing a position where a piston 9 is fitted to an elastic body portion 8. FIG.

FIG. 7 is a longitudinal sectional view showing a standard shape in which a rubber band 8 is mounted on an inner wall of a barrel without using the adapter.

FIG. 8 is a process chart illustrating a method for producing a prefilled syringe for medicine of the present invention.

FIG. 9 is a process diagram illustrating a method for producing a prefilled syringe for medicine of the present invention.

FIG. 10 is a process diagram illustrating a method for producing a prefilled syringe for medicine of the present invention.

FIG. 11 is a process diagram illustrating a method for producing a prefilled syringe for medicine of the present invention.

Claims (11)

[Claims] 1. A pre-filled syringe comprising a combination of a plastic barrel, a laminated piston, and a nozzle cap, wherein the pre-filled syringe has an elastic portion on the piston sliding surface on the inner surface of the barrel. . 2. The pre-filled syringe for pharmaceuticals according to claim 1, wherein the elastic portion of the sliding surface is formed integrally with the barrel. 3. The prefilled syringe for pharmaceuticals according to claim 1, wherein the elastic portion of the sliding surface is incorporated via an adapter. 4. The prefilled syringe for pharmaceuticals according to claim 3, wherein the adapter has an annular convex backstop on the inner peripheral side of the lower edge of the hollow portion of the mounting flange. 5. The prefilled syringe for pharmaceuticals according to claim 1, wherein the elastic portion has a plastic laminate film on at least a part of its surface. 6. The prefilled syringe for pharmaceuticals according to claim 1, wherein the elastic portion has a plastic laminate film on the entire surface. 7. The barrel and the elastic body are integrally formed by injection-molding an elastic body at a predetermined portion of the pin with the first mold, transferring the pin and the elastic body to the second mold, and injection-molding the barrel. 7. The method for producing a prefilled syringe for pharmaceuticals according to 1, 2, 5, or 6. 8. The medical device according to claim 1, wherein the barrel and the elastic body are integrally molded by inserting a previously molded elastic body into a predetermined position of a molding pin and injection molding a resin of the barrel. Manufacturing method of filling type syringe. 9. An adapter formed integrally with the elastic body by injection-molding an elastic body at a predetermined portion of the pin with the first mold, transferring the pin and the elastic body to the second mold, and injection-molding the adapter. 5. The method for producing a prefilled syringe for pharmaceuticals according to claim 3, wherein the adapter is incorporated in a barrel to have an elastic portion on a piston sliding surface of the barrel. 10. An adapter molded integrally with an elastic body is prepared by inserting a preformed elastic body into a predetermined position of a molding pin, and injection-molding a resin of the adapter, and incorporating the adapter into a barrel. 5. The piston sliding surface according to claim 3, further comprising an elastic portion.
5. The method for producing a pre-filled syringe for pharmaceuticals according to the above. 11. The method for producing a filled syringe for pharmaceuticals according to claim 3, wherein the elastic body, the adapter, and the barrel are separately formed, and are produced by assembling them.