JP2007209675A - Manufacturing method of prefilled syringe - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a manufacturing method of a prefilled syringe for storing medical solution. <P>SOLUTION: This manufacturing method of the prefilled syringe is characterized in having: (a) a process for sterilizing a cylinder body 12 and a plurality of other components separately; (b) a process for inserting a first plug body 14 into the sterilized cylinder body 12, filling the cylinder body 12 where the first plug body 14 is inserted, with medical solution 18 and storing the medical solution 18 by inserting a second plug body 16 into the cylinder body 12 filled with the medical solution 18; and (c) a process for manufacturing the prefilled syringe 10 by assembling the plurality of other components to the cylinder body 12; wherein the processes (a)-(c) are executed in a through line. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method of manufacturing a syringe already filled with a chemical solution, a so-called prefilled syringe.

  A prefilled syringe is a syringe in which a chemical solution is previously stored. The syringe is filled with the chemical solution in a sterile isolator isolated from the outside air. For example, Patent Document 1 discloses a manufacturing method for filling a syringe with a chemical solution in an isolator. Thereby, a chemical | medical solution is accommodated in the syringe of a sterilized state, and is stored for a long time without deteriorating.

JP 2002-301138 A

  However, even if the syringe is filled with the chemical solution in a sterile isolator, it is difficult to say that the chemical solution does not deteriorate during long-term storage in the syringe unless the sterility of the syringe is sufficiently secured. For example, when a syringe is assembled from a plurality of components at a place different from a filling place (for example, an installation place of an isolator) where a chemical solution is filled, and the syringe is assembled into the filling place, the assembled syringe is sterilized. There is a possibility that the performance is reduced or foreign matter is mixed. As a specific example, a case where a syringe is assembled by a syringe manufacturer and a liquid medicine is filled in the syringe by a pharmaceutical manufacturer is applicable. In this case, the syringe assembled and packaged by the syringe manufacturer is sterilized by the pharmaceutical manufacturer, and is carried into the booth installed in the isolator or in the sterile room. At this time, since the assembled syringe has a large volume, it is difficult to carry in a large amount of syringe without touching the air outside the isolator or the booth, and the possibility of contamination is increased. There is also the possibility of contamination from the packaged foreign body of the assembled syringe.

  Therefore, the present invention provides a method for producing a prefilled syringe that has a very low possibility of foreign matter contamination, sufficiently ensures the sterility of a syringe that contains the drug solution, and can fill the syringe with a sufficiently ensured sterility. The purpose is to provide.

In order to achieve the above object, a method for producing a prefilled syringe according to the present invention comprises:
A manufacturing method of a prefilled syringe configured by assembling a plurality of components,
(A) sterilizing the cylindrical body and a plurality of other components separately;
(B) The first plug is inserted into the sterilized cylindrical body, the chemical body is then filled into the cylindrical body into which the first plug body is inserted, and then the second cylindrical body is filled with the chemical liquid. A step of inserting the plug body and storing the chemical solution;
(C) having a step of producing a prefilled syringe by assembling the plurality of other components to the cylindrical body,
The above-mentioned steps (a) to (c) are performed in a consistent line.

  According to the present invention, the assembly of the syringe, the filling of the syringe with the chemical solution, and the sterilization process of the syringe are performed in an integrated line, and the sterilization process of the syringe is not performed on the assembled syringe but before the assembly. This is done by separately sterilizing the syringe components. Thereby, the chemical solution is stored in a sterile syringe and stored for a long time without deterioration.

  First, the prefilled syringe manufactured by the manufacturing method of the prefilled syringe which concerns on one Embodiment of this invention is demonstrated.

  FIG. 1 is a partial cross-sectional view of a prefilled syringe, and FIG. 2 is an exploded view of the syringe (an exploded view of a syringe with a stopper, a chemical solution, and a plunger rod described later removed from the prefilled syringe).

  A prefilled syringe denoted by reference numeral 10 in FIG. 1 includes a cylindrical body (hereinafter referred to as “barrel”) 12 and two plug bodies (first and second claims described in claims) that are fitted into the barrel 12. 14, 16, chemical solution 18 accommodated between the two plug bodies 14, 16, finger grip 20 attached to one end of the barrel 12, and attached to the other end of the barrel 12 It comprises a hub lock 22 that supports a needle support described later, a needle support 26 that supports an injection needle 24, a protector 28 that protects the injection needle 24, and a plunger rod 30 that is attached to the stopper 16.

  The barrel 12 is made of glass, and a chemical solution 18 is accommodated therein. Silicon is applied to the inner peripheral surface of the barrel 12 so that the plugs 14 and 16 can move smoothly in the barrel 12.

  The plug bodies 14 and 16 have a substantially cylindrical shape and are made of an elastic body such as rubber. The plug 16 functions as a piston that pushes the drug solution 18 to the outside when the prefilled syringe 10 is used. Moreover, the plug body 16 has a female thread portion 32 for engaging with the plunger rod 30 as described later. On the other hand, the stopper 14 cooperates with the stopper 16 and the barrel 12 during storage to form a space (container) for storing the drug solution 18.

  The finger grip 20 is a portion where a user's finger is applied when the prefilled syringe 10 is used. The finger grip 20 is made of resin, and includes a grip portion 34 on which a user's finger is hooked and a cylindrical portion 36 into which one end of the barrel 12 is fitted.

  The hublock 22 supports the needle support 26 and is formed so that the other end of the barrel 12 can be fitted therein, and connects the barrel 12 and the needle support 26. Moreover, the hubble lock 22 has the accommodating part 38 in which the stopper 14 is accommodated at the time of use of the prefilled syringe 10 so that it may mention later. On the inner peripheral surface forming the accommodating portion 38, a flow path leading to the needle support 26 so that the drug solution 18 in the barrel 12 flows toward the needle support 26 even when the plug 14 is accommodated in the accommodating portion 38. A groove 42 is formed to connect 40 and the inside of the barrel 12. Hubble lock 22 is made of resin.

  The needle support 26 supports the injection needle 24 and communicates the inside of the injection needle 24 with the flow path 40 of the hubble lock 22. The needle support 26 is made of resin except for the injection needle 24.

  The protector 28 has a cap shape that protects the injection needle 24 until the prefilled syringe 10 is used, and is configured to be detachably engaged with the hubble lock 22.

  The plunger rod 30 has a male screw portion 44 formed at the plug body 16 and engaged with the screw portion 32 at one end, and is thus attached to the plug body 16.

  Note that the plunger rod 30 may be attached to the stopper 16 at the time of use in order to reduce the storage space of the prefilled syringe 10.

  The usage method of the prefilled syringe 10 is demonstrated. First, the protector 28 is removed from the hubble lock 22.

  Subsequently, the plunger rod 30 is pushed into the barrel 12 with the injection needle 24 facing upward. When the plunger rod 30 is pushed in, the plug body 16 that functions as a piston moves upward.

  When the plunger rod 30 is further pushed into the barrel 12, the pressure of the chemical solution 18 accommodated between the two plug bodies 14, 16 increases, and the plug body 14 begins to move toward the accommodating portion 38 of the hubble lock 22. . When the stopper 14 is accommodated in the accommodating part 38 of the hubble lock 22, the drug solution 18 in the barrel 12 flows to the needle support 26 via the groove 42. When the drug solution 18 flows out from the injection needle 24 to the outside, the air in the pull-filled syringe 10 is released, and the pre-filled syringe 10 can be used.

  Next, the manufacturing method of the prefilled syringe 10 is demonstrated with the manufacturing apparatus used. FIG. 3 is a diagram conceptually illustrating an example of the flow of manufacturing the prefilled syringe 10 (flow of the barrel 12 in manufacturing). The method for producing a prefilled syringe according to the present invention is generally composed of five steps A to E, and various processes (for example, other components of the prefilled syringe 10 are applied to the barrel 12 while the barrel 12 is conveyed). (Assembly process for assembling to the barrel 12).

  Although not shown in the drawing, the barrel 12 is supported by, for example, a carrier (a support body that supports the barrel 12 in an upright state in which the opening faces in the vertical direction) at the time of manufacturing the prefilled syringe 10 (in steps A to E). In this state, it is conveyed on the conveyor together with the carrier, or is conveyed while being held by a robot arm, a timing screw, a star wheel, or the like. In addition, in the manufacturing method of the prefilled syringe 10 which concerns on this invention, a conveyance means is not limited.

  The prefilled syringe 10 is manufactured in the clean booth 120 in the isolator 116 or the clean room 102 after the sterilization process. The clean room 102 is maintained in a sterile state.

  First, the barrel 12 manufactured outside the clean room 102 is cleaned by a cleaning machine (not shown) in the clean room 102 or in a room adjacent to the isolator 116, and then dried (cleaning step A).

  The barrel 12 that has undergone the cleaning process A is coated with silicon 104 on its inner peripheral surface by a silicon coating apparatus (not shown) (silicon coating process B).

  The barrel 12 that has undergone the silicon coating process B is sterilized by a tunnel-type transport sterilizer (not shown) (sterilization process C).

  The tunnel type transport sterilization apparatus has a sterilization tunnel 106 and sterilizes using a high-temperature dry air stream while conveying the barrel 12 in the sterilization tunnel 106 (hereinafter, a sterilization process using a dry air stream is referred to as “ This is referred to as “dry heat sterilization”). The tunnel-type transport sterilizer has a conveyor (not shown) in the sterilization tunnel 106 that transports the barrel 12 from the inlet 108 to the outlet 110 of the sterilization tunnel 106.

  The inside of the sterilization tunnel 106 is divided into a space 112 on the inlet 108 side and a space 114 on the outlet 110 side. When the barrel 12 transported by a conveyor (not shown) is in the space 112, the tunnel-type transport sterilizer sterilizes the barrel 12 by dry heat sterilization by drying it in the space 114, and dries in the space 114. It is configured to remove heat from the barrel 12 that has been heated to a high temperature.

  In dry heat sterilization performed in the space 112 of the sterilization tunnel 106, a dry air current of about 300 ° C. is blown to the barrel 12. Since the barrel 12 is made of glass, it may be sterilized with a dry airflow at a temperature close to the endurance temperature of the glass. It is sufficient to spray the barrel 12. In addition, by dry heat sterilization for several minutes with a dry air current of about 300 ° C., pyrogens (pyrogenic substances) attached during cleaning, for example, are removed from the barrel 12 in addition to bacteria. By performing such dry heat sterilization on the barrel 12, the sterility of the barrel 12 is sufficiently ensured.

  Further, the tunnel type transport sterilizer is connected to an isolator 116 at the outlet 110 thereof. Specifically, the internal space of the sterilization tunnel 106 and the internal space of the isolator 116 are communicated, and the barrel 12 is conveyed from the sterilization tunnel 106 into the isolator 116 without being put out into the clean room 102. However, the air in the sterilization tunnel 106 is maintained, for example, by maintaining the air pressure in the isolator 116 at a pressure higher than the pressure in the sterilization tunnel 106 or by generating an air flow from the isolator 116 toward the sterilization tunnel 106 with a blower (not shown). Is prevented from flowing into the isolator 116. This is to maintain a high level of sterility within the isolator 116.

  The barrel 12 that has undergone the sterilization step C is filled with the chemical solution 18 in the isolator 116 (chemical solution filling step D). The isolator 116 is maintained at a higher level of sterility than the clean room 102. In filling the barrel 12 with the chemical solution 18, first, the stopper 14 that has been cleaned and sterilized before being loaded into the isolator 116 is inserted into the barrel 12 by a stopper (not shown).

  Next, the drug solution 18 is filled in the barrel 12 in which the plug body 14 is inserted by a filling machine (not shown).

  Subsequently, the stopper 16 that has been cleaned and sterilized before being loaded into the isolator 116 is inserted into the barrel 12 filled with the chemical solution 18 by a stopper (not shown). Thereby, the barrel 12 in which the chemical liquid 18 is accommodated is completed in the isolator 116. The barrel 12 in which the chemical solution 18 is stored is transported outside the isolator 116.

  The finger grip 20 and the front assembly 118, which are other components constituting the syringe, are placed in the barrel 12 containing the chemical solution after the chemical solution filling step D, in order to prevent foreign matter from being mixed and maintain a sterile environment. It is attached in the booth 120 (syringe assembly process E). The front assembly 118 is a state in which the hubble lock 22, the needle support body 26, and the protector 28 are assembled in advance. The finger grip 20 and front assembly 118 are sterilized before being attached to the barrel 12. As these sterilization treatments, for example, wet heat sterilization or EOG (ethylene oxide gas) sterilization using an autoclave (not shown) is performed.

  The finger grip 20 and the front assembly 118 are assembled to the barrel 12 by handling means (not shown) such as a robot arm. Although not shown, the plunger rod 30 is attached to the plug body 16. Thereby, the prefilled syringe 10 is completed.

  The prefilled syringe 10 completed through the syringe assembly process E is transported by a transport means (not shown), and then stored in a storage housing case by, for example, an operator's manual work.

  The reason for configuring the prefilled syringe manufacturing method as described above and the effects obtained thereby will be described.

  As in the present embodiment, the syringe is configured by assembling a plurality of components, and the components that may be deformed at a high temperature in the plurality of components (for example, resin finger grips in the above-described embodiments) Or a hubble lock), a fully assembled syringe cannot be sterilized at high temperatures.

  Therefore, the barrel is sterilized at a high temperature, the chemical solution is then stored in the barrel sterilized at a high temperature via two plugs, and then the other components of the syringe are assembled to the barrel containing the chemical solution. The prefilled syringe is manufactured by performing as a consistent line. Thereby, there is little mixing of the foreign material derived from a syringe packaging, and since a chemical | medical solution is reliably accommodated in the aseptic syringe, it is stored for a long time without deteriorating.

  Further, as in the present embodiment, if a plurality of prefilled syringe manufacturing processes other than the manufacturing process of each of the plurality of constituent elements of the syringe are performed by an integrated line, for example, a filling place (for example, an isolator installation place) filled with a chemical solution Compared to the case where the syringe is manufactured by combining multiple components at a different location from the above and is carried into the filling location, it is a leap forward to prevent the risk of foreign contamination and bacteria from entering the syringe. Effects are expected.

  As mentioned above, although the above-mentioned embodiment was mentioned and the manufacturing method of the prefilled syringe which concerns on this invention was demonstrated, this invention is not limited to the above-mentioned embodiment.

  For example, in the above-described embodiment, the barrel is sterilized by dry heat in the sterilization tunnel, but the barrel subjected to dry heat sterilization is transported into an isolator filled with a chemical without touching the outside air. If there is, it does not depend on the difference in the sterilization method.

  Further, the timing of assembling the finger grip and the front assembly to the barrel may be performed before the barrel is sterilized by the tunnel type transport sterilizer and filled with the chemical solution in the isolator. Alternatively, the finger grip may be assembled before the barrel is sterilized by the tunnel type transfer sterilizer and the chemical solution is filled in the isolator, and the front assembly may be assembled after the chemical solution is filled. The timing of assembling the finger grip and the front assembly to the barrel is appropriately determined depending on, for example, the type of the chemical solution, the material of the prefilled syringe component such as the barrel, the size of the clean room, and the device to be used. However, in order for the prefilled syringe to be sufficiently sterilized, that is, to prevent foreign substances and germs from being mixed into the syringe, the timing of assembly of the finger grip and front assembly to the barrel is such that the chemical solution is passed through the barrel through two plugs. Preferably after being housed.

It is a fragmentary sectional view of the prefilled syringe which concerns on this invention. It is an exploded view of the prefilled syringe which concerns on this invention. It is a figure which shows notionally the manufacturing method of the prefilled syringe which concerns on this invention.

Explanation of symbols

10: Prefilled syringe 12: Cylindrical body (barrel)
14: First plug body 16: Second plug body 18: Chemical solution

Claims (5)

A manufacturing method of a prefilled syringe configured by assembling a plurality of components,
(A) sterilizing the cylindrical body and a plurality of other components separately;
(B) The first plug is inserted into the sterilized cylindrical body, the chemical body is then filled into the cylindrical body into which the first plug body is inserted, and then the second cylindrical body is filled with the chemical liquid. A step of inserting the plug body and storing the chemical solution;
(C) having a step of producing a prefilled syringe by assembling the plurality of other components to the cylindrical body,
A method for producing a prefilled syringe, wherein the steps (a) to (c) are performed in an integrated line.   The method for producing a prefilled syringe according to claim 1, wherein the step (b) is performed following the step (a), and the step (c) is performed following the step (b).   The method for producing a prefilled syringe according to claim 1, wherein the step (c) is performed following the step (a), and the step (b) is performed following the step (c).   The step (c) includes the step of assembling at least one of the plurality of other components to the cylindrical body before the step (b) is performed, and the step (b) performs the remaining other components. The method for producing a prefilled syringe according to claim 1, comprising a step of assembling the cylindrical body after breaking. 5. The cylindrical body according to claim 1, wherein the cylindrical body is made of a material that has been sterilized at a higher temperature than the plurality of other components in the step (a) and can withstand the high temperature sterilization. The manufacturing method of the prefilled syringe as described in any one.

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