JP2007202649A - Pre-filled syringe manufacturing method, pre-filled syringe manufacturing tool and pre-filled syringe manufacturing apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pre-filled syringe manufacturing method, a pre-filled syringe manufacturing tool and a pre-filled syringe manufacturing apparatus, quickly and surely deaerating the inner cavity part of a syringe outer cylinder and inserting a plug body in the inner cavity part. <P>SOLUTION: This pre-filled syringe manufacturing method for manufacturing the pre-filled syringe 1 having the syringe outer cylinder 2; the plug body 3 and a medical solution 100, includes: a first process of mounting a tool 4 having a housing space 42 housing the plug body 3 to cover a base end opening 26 of the syringe outer cylinder 2; a second process of deaerating the housing space 42 and deaerating the inner cavity part 24 of the syringe outer cylinder 2 communicated with the housing space 42; and a third process of inserting the plug body 3 into the inner cavity part 24 by the tool 4 in an isolator and supplying axenic air in the isolator to the housing space 42 to recover the housing space 42 to a predetermined pressure. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a prefilled syringe manufacturing method, a prefilled syringe manufacturing jig, and a prefilled syringe manufacturing apparatus.

  A prefilled syringe in which a liquid preparation (chemical solution) is aseptically filled in a syringe (container) is known.

  Such a prefilled syringe is manufactured as follows, for example. That is, first, sterilization with a high-pressure steam sterilization or a sterilization gas such as hydrogen peroxide is performed on each of the syringe and the cap (sealing member) attached to the liquid discharge part (mouth part). Next, a cap is attached to the liquid discharge part of the syringe in a sterile environment, and then the liquid preparation is filled into the syringe. Next, after the inside of the syringe is deaerated, a stopper is attached (plugged) to complete a prefilled syringe (see, for example, Patent Document 1).

  A prefilled syringe manufacturing apparatus for inserting a plug into a lumen of a syringe outer cylinder filled with a liquid preparation is installed at the proximal end of the syringe outer cylinder, and a jig main body having a storage space in which the plug is stored And a jig provided with a stopper for pushing the stopper and inserting it into the lumen of the syringe outer cylinder. This jig is installed in an isolator.

  When the jig main body of the jig is installed at the proximal end of the syringe outer cylinder, the storage space communicates with the inner cavity of the syringe outer cylinder, and air is sucked from the storage space of the jig main body. Then, the lumen of the syringe outer cylinder is evacuated. Next, the stopper is moved downward to press the stopper, and the stopper is inserted into the lumen of the syringe outer cylinder. Next, after moving the stopper plunger upward, the jig body is detached from the proximal end of the syringe outer cylinder. For this purpose, it is necessary to restore the storage space of the jig body to a predetermined pressure. Therefore, the manufacturing apparatus has aseptic air introduction means for introducing aseptic air into the storage space and restoring the pressure of the storage space.

  This aseptic air introduction means is located inside the isolator, a tube whose one end communicates with the storage space of the jig main body, located outside the isolator, air supply means provided on the other end side of the tube, It is composed of a sterilization filter provided in the middle of the tube, and is configured to take in air supplied to the storage space, that is, air used for return pressure from the outside of the isolator through the sterilization filter. .

  However, in the conventional manufacturing apparatus, since the sterilization filter is provided in the middle of the decompression line communicating with the storage space of the jig main body, the storage space of the jig main body and the lumen of the syringe outer cylinder are removed. At the same time, the sterilization filter (return pressure line including the sterilization filter) is degassed at the same time, so that it takes time to depressurize the lumen of the syringe outer cylinder to the target pressure. Also, variations are likely to occur.

  Further, when the storage space of the jig body is restored to a predetermined pressure, the sterilization filter is simultaneously decompressed, and it takes time to restore the pressure.

  Moreover, the structure of the sterile air introduction means (prefilled syringe manufacturing apparatus) is complicated as described above.

JP 2001-171791 A

  An object of the present invention is to provide a prefilled syringe manufacturing method and a prefilled syringe manufacturing jig capable of quickly and surely degassing a lumen portion of a syringe outer cylinder and inserting a plug into the lumen portion. And it is providing the prefilled syringe manufacturing apparatus of a simple structure which can deaerate the lumen | bore part of a syringe outer cylinder reliably, and can insert a plug into the lumen | bore part.

Such an object is achieved by the present inventions (1) to (10) below.
(1) Manufacture a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug. A prefilled syringe manufacturing method comprising:
A first step of mounting a jig having a storage space in which the stopper is stored so as to cover a proximal end opening of the syringe outer cylinder;
A second step of degassing the storage space and degassing a lumen of the syringe outer cylinder communicating with the storage space;
In the space in which sterility is maintained, the stopper is inserted into the inner cavity of the syringe outer cylinder by the jig, and at least sterilized air in the space in which the sterility is maintained is supplied to the storage space. And a third step of returning the storage space to a predetermined pressure.

  (2) In the third step, together with the storage space, through the storage space, sterile air in the space in which the sterility is maintained is supplied to the inner cavity of the syringe outer tube, and the syringe outer cylinder The prefilled syringe manufacturing method according to the above (1), in which the lumen portion is restored to a predetermined pressure.

(3) The jig includes a jig body having the storage space;
Installed in the jig body, pressing the plug so as to be inserted into the lumen of the syringe outer cylinder, and a pressing member having a communication path,
The prefilled syringe manufacturing method according to (1) or (2), wherein the supply of sterile air in the space in which the sterility is maintained in the third step is performed through the communication path.

  (4) The prefilled syringe manufacturing method according to (3), wherein the communication path is a groove formed on an outer peripheral surface of the pressing member.

(5) The prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug. A prefilled syringe manufacturing jig used when inserting the plug into the lumen of the syringe outer cylinder in a space in which sterility is maintained,
A jig body that is mounted so as to cover the proximal end opening of the syringe outer cylinder and has a storage space in which the stopper can be stored;
A pressing member that is installed in the jig main body and presses the stopper so as to be inserted into the lumen of the syringe outer cylinder;
The jig body communicates with the storage space, and has a vent hole for exhausting from the storage space.
When the plug body is stored in the storage space, a gap is formed between the inner wall of the jig body and the plug body so as to allow ventilation.
The pressing member has a communication path, and a first position that does not allow communication between the storage space and the space in which the sterility is maintained in which the prefilled syringe manufacturing jig is placed, and the communication path. A jig for producing a prefilled syringe, wherein the jig is configured to move to a second position where the storage space and the space in which sterility is maintained are communicated.

  (6) The pre-filled syringe manufacturing jig according to (3), wherein the communication path is a groove formed on an outer peripheral surface of the pressing member.

(7) Manufacture a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug. A prefilled syringe manufacturing apparatus comprising:
Used in a space in which sterility is maintained, is mounted so as to cover the proximal end opening of the syringe outer cylinder, and is installed in the jig body having a storage space capable of storing the stopper, A jig provided with a pressing member that presses the stopper so as to be inserted into the lumen of the syringe outer cylinder;
Degassing means for degassing the storage space and degassing the lumen of the syringe outer cylinder communicating with the storage space;
A pressing member driving means for driving the pressing member when the stopper is inserted into the lumen of the syringe outer cylinder by the jig;
An apparatus for producing a prefilled syringe, comprising: a return pressure means for supplying aseptic air in a space in which the sterility is maintained to at least the storage space to return the storage space to a predetermined pressure.

(8) Manufacture a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug. A prefilled syringe manufacturing device comprising:
Used in a space in which sterility is maintained, and the jig for producing a prefilled syringe according to (5) or (6),
Degassing means for degassing the storage space and degassing the lumen of the syringe outer cylinder communicating with the storage space;
A pressing member driving means for driving the pressing member when the stopper is inserted into the lumen of the syringe outer cylinder by the jig;
An apparatus for producing a prefilled syringe, comprising: a return pressure means for supplying aseptic air in a space in which the sterility is maintained to at least the storage space to return the storage space to a predetermined pressure.

(9) The return pressure means and the pressing member driving means have a common actuator,
By the actuator, the pressing member moves to press the stopper, and the stopper is inserted into the inner cavity of the syringe outer cylinder. At this time, the pressing member reaches the second position, The storage space communicates with the space in which sterility is maintained through the communication path, and at least the storage space is supplied with aseptic air in the space in which the sterility is maintained, and the storage space has a predetermined pressure. The prefilled syringe manufacturing apparatus according to (8), wherein the prefilled syringe manufacturing apparatus is configured to return the pressure to a predetermined pressure.

  (10) The return pressure means supplies the sterile air in the space in which the sterility is maintained to the inner cavity of the syringe outer cylinder through the storage space together with the storage space, The prefilled syringe manufacturing apparatus according to any one of (7) to (9), wherein the lumen portion is configured to return the pressure to a predetermined pressure.

  According to the present invention, when the storage space of the jig body of the jig is restored to a predetermined pressure, aseptic air in the space in which the sterility is maintained is supplied to the storage space. Therefore, it is not necessary to provide a sterilizing filter, and the lumen portion of the syringe outer cylinder can be quickly evacuated and the plug can be inserted into the lumen portion.

  That is, compared with the conventional manufacturing apparatus described in the background art, when degassing the storage space of the jig body and the lumen of the syringe outer cylinder, a target amount of air is discharged from the lumen of the syringe outer cylinder. The time until the lumen of the syringe outer cylinder is reduced to the target pressure is short, and the pressure becomes uniform.

  In addition, the time required for restoring the storage space of the jig body to a predetermined pressure is shorter than that of the conventional manufacturing apparatus described in the background art.

  Further, the prefilled syringe manufacturing apparatus has a simpler configuration than the conventional manufacturing apparatus described in the background art.

  Hereinafter, the prefilled syringe manufacturing method, the prefilled syringe manufacturing jig, and the prefilled syringe manufacturing apparatus of the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings. Before that, first, an example of the prefilled syringe will be described. explain.

  FIG. 5 is a partial cross-sectional view showing a configuration example of a prefilled syringe. In the following, for convenience of explanation, the upper side in FIG. 5 is referred to as “base end” and the lower side is referred to as “tip”.

  A prefilled syringe (hereinafter simply referred to as “syringe”) 1 shown in FIG. 5 is one in which a drug solution 100 is stored in advance inside the syringe 1 (lumen portion 24). The syringe 1 is provided at a syringe outer cylinder (outer cylinder) 2, a plug 3 inserted into the lumen portion 24 of the syringe outer cylinder 2, and a distal end portion (mouth portion 22) of the syringe outer cylinder 2. The liquid medicine filled in the space (inner cavity part 24) formed by the lock adapter (connecting member) 23, the cap 25 connected (screwed) to the lock adapter 23, the syringe outer cylinder 2 and the plug body 3. 100.

The syringe outer cylinder 2 is composed of a bottomed cylindrical member having a bottom portion 211.
At the center of the bottom 211 of the syringe outer cylinder 2, a mouth 22 having a reduced diameter with respect to the body of the syringe outer cylinder 2 is integrally formed.

  A flow path 221 through which the chemical solution 100 can pass is formed inside the mouth portion 22, and the flow path 221 communicates with the lumen portion 24 of the syringe outer cylinder 2.

  A cylindrical lock adapter 23 is provided on the outer peripheral portion of the mouth portion 22, and a female screw (not shown) is formed on the inner peripheral surface of the lock adapter 23.

  The cap 25 is composed of a bottomed cylindrical member, and a male screw (not shown) that engages with a female screw of the lock adapter 23 is formed on the outer peripheral surface thereof.

  By screwing the male screw of the cap 25 and the female screw of the lock adapter 23, the cap 25 and the lock adapter 23 are connected, that is, the cap 25 is attached to the mouth portion 22 of the syringe outer cylinder 2. Thereby, the front end opening of the mouth portion 22 can be sealed, and therefore, the filled chemical solution 100 can be prevented from leaking (discharging) from the front end opening of the mouth portion 22.

  A plug body 3 made of an elastic material is accommodated (inserted) in the syringe outer cylinder 2. Two ring-shaped protrusions 31 and 32 are formed on the outer peripheral portion of the plug body 3 at predetermined intervals along the axial direction. Since the protrusions 31 and 32 are in close contact with the inner peripheral surface 21 of the syringe outer cylinder 2, airtightness (liquid tightness) can be reliably maintained.

  In addition, as a constituent material of the syringe outer cylinder 2 (including the lock adapter 23) and the cap 25, for example, various hard resin materials, various glass materials, and the like can be used.

  Moreover, it is preferable that the constituent material of the syringe outer cylinder 2 is substantially transparent in order to ensure the internal visibility.

  Further, as the constituent material of the plug body 3, for example, various rubber materials (particularly those vulcanized) such as natural rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, butyl rubber, styrene-based, polyolefin-based, etc. These thermoplastic elastomers and the like can be mentioned, and one or more of these can be mixed and used.

  Examples of the drug solution 100 include electrolyte correction injection solutions such as sodium chloride and potassium lactate, vitamin preparations, vaccines, antibiotic injection solutions, steroid agents, proteolytic enzyme inhibitors, fat emulsions, various protein preparations, anticancer agents, Examples include anesthetics, stimulants, various chemical solutions such as narcotics, various diagnostic agents, and the like.

  The prefilled syringe manufacturing method of the present invention is a method for manufacturing the prefilled syringe 1 as described above. Moreover, the prefilled syringe manufacturing method of this invention is implemented using the prefilled syringe manufacturing apparatus 10 provided with the jig | tool 4 for prefilled syringe manufacture of this invention.

  Next, the prefilled syringe manufacturing jig and the prefilled syringe manufacturing apparatus of the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.

First, the prefilled syringe manufacturing apparatus of this invention is demonstrated.
FIG. 1 is a schematic diagram (mainly a cross-sectional view) showing an embodiment of the prefilled syringe manufacturing apparatus of the present invention, and FIG. 2 is a block diagram showing the main part of the prefilled syringe manufacturing apparatus shown in FIG. These are the figures (sectional drawing) for demonstrating later the process at the time of manufacturing a prefilled syringe with the prefilled syringe manufacturing apparatus shown in FIG. 1, respectively. In the following, for convenience of explanation, the upper side of FIGS. 1, 3 and 4 is referred to as a “base end” and the lower side is referred to as a “tip”.

  As shown in FIGS. 1 and 2, a prefilled syringe manufacturing apparatus (hereinafter simply referred to as “manufacturing apparatus”) 10 includes a prefilled syringe manufacturing jig (hereinafter simply referred to as “jig”) 4 and an outside of the syringe. A pump (deaeration means) 51 that degass (exhausts) the lumen portion 24 of the cylinder 2 and a pressing member (described later) of the jig 4 when the plug 3 is inserted into the lumen portion 24 of the syringe outer cylinder 2. Actuator 71 for moving (driving) plunger (plunging plunger) 43, valve (flow channel opening / closing means) 9, jig moving mechanism 20 for moving jig 4, and control means for controlling the operation (drive) of each part. 8 and.

  As shown in FIG. 1, the main part including the jig 4 of the manufacturing apparatus 10 is a space in which sterility is maintained (sterile space), in this embodiment, in an isolator (sterile isolator) 30 (inside the isolator 30). And is installed (stored) in the isolator 30. The manufacture of the prefilled syringe 1 such as the insertion of the plug 3 into the lumen 24 of the syringe outer cylinder 2 is performed in the isolator 30. The pump 51 and the valve 9 are installed outside the isolator 30, respectively.

  A pair of globes 301 and an air supply blower 302 with a built-in HEPA (High Efficiency Paticulate Air) filter are attached to the isolator 30.

  The globe 301 is provided on the wall portion, the bottom portion, and the like of the isolator 30, and the operator attaches the globe 301 to enter the jig 4 or the like from the outside of the isolator 30 without entering the isolator 30. Equipment installed (stored) in the isolator 30 can be operated.

  The air supply blower 302 ejects a sterilizing gas such as hydrogen peroxide introduced through a valve (channel opening / closing means) 303 into the isolator 30. The inside of the isolator 30 is sterilized periodically by a sterilizing gas ejected from the air supply blower 302 and sterilized when necessary (if necessary). The frequency of the regular sterilization operation is not particularly limited, but the sterilization operation is performed at a frequency of about once a week, for example. As described above, the interior of the isolator 30 is sterilized, so that aseptic air is stored (exists) in the isolator 30. Therefore, the internal space of the isolator 30 constitutes a space in which sterility is maintained.

  The gas used for sterilization in the isolator 30 is not limited to the hydrogen peroxide gas, and it goes without saying that other methods may be used as a sterilization method.

  The manufacturing apparatus 10 has a tube (tube) 91 connected to the jig body 41 so that one end side thereof communicates with a vent hole 44 of a jig body 41 described later of the jig 4. The tube 91 penetrates the wall portion of the isolator 30, and a valve 9 and a pump 51 that open and close a flow path (lumen) in the tube 91 are provided in this order on the other end side of the tube 91. ing. That is, the pump 51 is connected to the vent hole 44 of the jig 4 through the tube 91.

  The pump 51 is not particularly limited as long as it can suck gas, and for example, a syringe pump, a gear pump, a vacuum pump, or the like can be used.

  The valve 9 is not particularly limited, and for example, a solenoid valve (electromagnetic valve) or the like can be used.

  The actuator 71 is installed on the base end side of a pressing member 43 (described later) of the jig 4 and is connected (connected) to the base end 431 of the pressing member 43.

  By the operation (drive) of the actuator 71, the pressing member 43 moves (drives) in the distal direction or the proximal direction along the longitudinal direction (vertical direction in FIG. 1). That is, when the actuator 71 is driven (expanded) in the distal direction, the pressing member 43 is pressed in the distal direction and moved in the distal direction, and when the actuator 71 is driven (contracted) in the proximal direction, The pressing member 43 is pulled in the proximal direction and moves in the proximal direction.

  As shown in FIG. 2, the control unit 8 includes a CPU (Central Processing Unit) 81 and a storage unit (storage unit) 82. The storage unit 82 includes a storage medium (recording medium) that can be read by the CPU 81. This storage medium is, for example, a magnetic recording medium, an optical recording medium, an optical and magnetic recording medium, or a semiconductor memory. It consists of The control means 8 controls the operation (drive) of the moving mechanism 20, the pump 51, the valve 9, the actuator 71, and the like.

  When the plug 3 is inserted into the lumen 24 of the syringe outer cylinder 2 by the actuator 71, the main part of the pressing member driving means that moves (drives) the pressing member 43, and at least the isolator in the storage space 42. The main part of the decompression means which supplies aseptic air in 30 (space in which sterility is maintained) and returns the storage space 42 to a predetermined pressure is configured. That is, the actuator 71 is a common actuator for the pressing member driving means and the return pressure means.

Next, the jig for manufacturing a prefilled syringe of the present invention will be described.
As shown in FIG. 1, the jig 4 includes a jig body 41 that is mounted so as to cover the proximal end opening 26 of the syringe outer cylinder 2, and a pressing member 43 that presses the stopper 3.

  The jig main body 41 is formed with a storage space 42 in which the plug body 3 can be stored and a vent hole 44 communicating with the storage space 42.

  The storage space 42 has a substantially circular cross-sectional shape and is configured such that the diameter (inner diameter) is substantially equal to or slightly smaller than the diameter of the plug 3 (protrusions 31 and 32).

  Further, when the plug body 3 is stored in the storage space 42, an air-permeable gap 45 is formed between the inner wall 411 of the jig body 41 and the plug body 3. That is, when the stopper 3 is stored in the storage space 42 and the jig 4 is attached to the syringe outer cylinder 2, the inner space of the storage space 42 and the syringe outer cylinder 2 is interposed via the gap 45. 24 communicates.

The gap 45 is constituted by a plurality of ventilation grooves 451 formed in the inner wall 411 of the jig body 41. The number of ventilation grooves 451 is not particularly limited, but is preferably 2 to 8, and more preferably 4 to 6.
The ventilation groove 451 extends along the moving direction of the plug body 3 (vertical direction in FIG. 1).

  The gap 45 (ventilation groove 451) having such a configuration allows the gas on the distal end side of the plug body 3 and the gas on the proximal end side of the plug body 3 to come and go (move from one to the other and from the other to the other). it can.

  The vent hole 44 is formed on the side of the jig main body 41, extends along the left-right direction in FIG. 1, and penetrates the wall portion (side wall) of the jig main body 41. As described above, one end side of the tube 91 is connected to the vent hole 44.

  Thereby, the exhaust from the storage space 42, that is, the exhaust from the storage space 42 and the lumen portion 24 of the syringe outer cylinder 2 can be performed via the vent hole 44. In other words, the storage space 42 and the lumen 24 of the syringe outer cylinder 2 can be degassed via the vent hole 44 (it can be depressurized to a predetermined pressure).

  As shown in FIG. 1, the pressing member 43 is a member (member) that presses the stopper 3 to be inserted into the lumen 24 of the syringe outer cylinder 2 by the operation of the actuator 71. It has a cylindrical shape (bar shape).

  A groove 432 is formed on the outer peripheral surface (outer surface) of the pressing member 43 as a communication path that allows the storage space 42 to communicate with the internal space of the isolator 30 (a space in which sterility is maintained). The groove 432 extends along the longitudinal direction of the pressing member 43, that is, the moving direction of the pressing member 43 (vertical direction in FIG. 1). The groove 432 is not formed at the distal end and the proximal end of the pressing member 43, but is formed in the middle portion of the pressing member 43.

  The pressing member 43 is installed on the central axis of the jig body 41 and is installed so as to be movable along the central axis (longitudinal direction).

  That is, the pressing member 43 has a first position where the storage space 42 and the internal space of the isolator 30 are not communicated with each other, and a second position where the storage space 42 and the internal space of the isolator 30 are communicated via the groove 432. It can move.

  Thereby, when the position of the pressing member 43 is the first position, the storage space 42 and the lumen 24 of the syringe outer cylinder 2 can be deaerated through the vent hole 44 as described above. . When the position of the pressing member 43 is the second position, aseptic air in the isolator 30 is supplied (introduced) to the storage space 42 via the groove 432, and the storage space 42 has a predetermined pressure (for example, Return to atmospheric pressure.

  Further, a sealing member (gasket) 46 is installed at the tip of the jig body 41 so as to surround the tip opening 412 of the jig body 41. Thereby, when the jig | tool main body 41 (jig 4) is mounted | worn with the syringe outer cylinder 2, the lumen | bore part 24 of the syringe outer cylinder 2 can be sealed airtight (liquid-tight).

  Next, the operation of the manufacturing apparatus 10, that is, the process when manufacturing the prefilled syringe 1 by the manufacturing apparatus 10 (the prefilled syringe manufacturing method of the present invention) will be described with reference to FIG. 3 and FIG. Further, as described above, the following steps are performed by the control of the control unit 8, but the present invention is not limited to this, and for example, a part of the steps may be performed manually by the operator.

[1] Jig mounting process (first process)
First, in a state where aseptic air is stored in the isolator 30, the pressing member 43 is stored above the proximal end of the syringe outer cylinder 2 in which the chemical solution 100 is contained (filled) by the jig moving mechanism 20. The jig 4 which is located at the first position where the space 42 and the internal space of the isolator 30 do not communicate with each other and the plug 3 is stored in the storage space 42 is moved.

  Thereafter, as shown in FIG. 3A, the jig 4 is lowered by the jig moving mechanism 20 so that the jig main body 41 covers the proximal end opening 26 of the syringe outer cylinder 2. A jig body 41) is mounted. As a result, the lumen 24 (including the storage space 42 of the jig 4) of the syringe outer cylinder 2 is blocked from the outside of the syringe outer cylinder 2 (internal space of the isolator 30). Further, the storage space 42 and the lumen portion 24 of the syringe outer cylinder 2 communicate with each other through the gap 45.

[2] Deaeration process (second process)
Next, the valve 9 is opened to open (open) the flow path in the tube 91, and with the jig 4 mounted, the pump 51 is operated as shown in FIG. The lumen 24 of the syringe outer cylinder 2 is degassed (depressurized) through the tool 4. That is, the pump 51 is operated to exhaust air from the storage space 42, and the storage space 42 and the lumen 24 of the syringe outer cylinder 2 are deaerated. Thereby, the storage space 42 and the lumen portion 24 of the syringe outer cylinder 2 are decompressed to a predetermined pressure.

[3] Capping and decompression process (third process)
Next, after the deaeration is finished, the valve 9 is closed to close (close) the flow path in the tube 91, and the actuator 71 is operated as shown in FIG. Move to (descent). Thereby, the plug 3 is pressed in the distal direction by the pressing member 43 and moves in the distal direction.

  During the movement of the pressing member 43, that is, the protrusion 31 of the stopper 3 is inserted into the lumen 24 of the syringe outer cylinder 2, the lumen 24 on the distal end side of the stopper 3 is sealed, and the protrusion 32 is located above the lumen portion 24 and is not inserted into the lumen portion 24, the leading end side of the groove 432 communicates with the storage space 42, whereby the storage space 42 and the isolator 30 are connected via the groove 432. Communication with the internal space. As a result, aseptic air in the isolator 30 is supplied (introduced) to the storage space 42 via the groove 432, and the space between the storage space 42 and the protrusions 31 and 32 of the plug body 3 has a predetermined pressure. The pressure is restored to (for example, atmospheric pressure).

  3D, the plug body 3 is further pressed in the distal direction by the pressing member 43 to move in the distal direction, and is detached from the storage space 42 of the jig 4, so that the plug body 3 is removed. Is inserted into the lumen 24 of the syringe outer cylinder 2 (the plug 3 is attached to the syringe outer cylinder 2).

  Next, in a state where the storage space 42 is restored to a predetermined pressure, as shown in FIG. 3E, the actuator 71 is operated to move (lift) the pressing member 43 in the proximal direction. Thereafter, the jig moving mechanism 20 raises the jig 4 and removes it from the syringe outer cylinder 2.

By passing through the above processes, the prefilled syringe 1 is manufactured.
As described above, according to the manufacturing apparatus 10, there is no need to provide aseptic air introducing means having a sterilizing filter or the like as in the conventional manufacturing apparatus described in the background art. As compared with the above, when the storage space 42 of the jig body 41 and the lumen 24 of the syringe outer cylinder 2 are degassed, a target amount of air is discharged from the lumen 24 of the syringe outer cylinder 2 (the syringe outer cylinder 2 The time until the lumen 24 is reduced to the target pressure) can be shortened, and the pressure can be made uniform. Furthermore, as compared with the conventional manufacturing apparatus, the time required to return the storage space 42 of the jig body 41 to a predetermined pressure can be shortened. That is, it is possible to quickly and surely deaerate the lumen portion 24 of the syringe outer cylinder 2 and insert the plug 3 into the lumen portion 24.

  Further, since the manufacturing apparatus 10 is not provided with aseptic air introduction means having a sterilization filter or the like as in the conventional manufacturing apparatus, the configuration is simple.

  Here, in the present invention, in the above-described plugging / restoring step (third step), the lumen portion of the syringe outer cylinder 2 is disposed by the decompression means together with the housing space 42 and the gap 45 together with the housing space 42. 24 may be supplied with aseptic air in the isolator 30 (sterile air in a space in which sterility is maintained) to restore the lumen 24 of the syringe outer cylinder 2 to a predetermined pressure.

  As described above, the prefilled syringe manufacturing method, the prefilled syringe manufacturing jig, and the prefilled syringe manufacturing apparatus of the present invention have been described based on the illustrated embodiment, but the present invention is not limited thereto, and the configuration of each part is as follows. It can be replaced with any configuration having a similar function. Moreover, other arbitrary structures and processes may be added to the present invention.

  In the present invention, the number of grooves (communication paths) is not limited to one, and a plurality of grooves (communication paths) may be formed in the pressing member.

In the present invention, the communication path is not limited to a groove, and may be, for example, a through hole.
In the present invention, the number of vent holes for exhausting from the storage space (deaeration of the storage space and the inner cavity of the syringe outer cylinder) is not limited to one, and a plurality of vent holes are passed through the jig body. Pores may be formed.

  Further, the decompression means in the present invention is not limited to the configuration of the above-described embodiment, and may be, for example, the following configuration.

  That is, a vent hole for supplying (introducing) sterile air into the storage space is provided in the jig body of the prefilled syringe manufacturing jig (jig), and one end of the tube (tube) is connected to this vent hole. Then, the other end of the tube is opened to the internal space of the isolator (a space in which sterility is maintained). And the valve (flow path opening / closing means) which opens and closes the flow path in the tube is provided. When the valve is opened and the flow path in the tube is opened (opened), aseptic air in the isolator (a space in which sterility is maintained) is supplied to the storage space, and the storage space is restored to a predetermined pressure. In this case, aseptic air in the isolator may be supplied to the storage space and the lumen of the syringe outer cylinder, and the storage space and the lumen of the syringe outer cylinder may be restored to a predetermined pressure.

  According to this return pressure means, aseptic air can be supplied to the storage space easily and reliably at any time by opening and closing the valve. For this reason, there exists an advantage that the operation | work which sets various conditions (relationship), such as the moving distance and position of a press member, and the length and position of a groove | channel, becomes unnecessary.

It is a schematic diagram (mainly sectional drawing) showing an embodiment of a prefilled syringe manufacturing device of the present invention. It is a block diagram which shows the principal part of the prefilled syringe manufacturing apparatus shown in FIG. It is a figure (sectional drawing) for demonstrating later the process at the time of manufacturing a prefilled syringe with the prefilled syringe manufacturing apparatus shown in FIG. It is a figure (sectional drawing) for demonstrating later the process at the time of manufacturing a prefilled syringe with the prefilled syringe manufacturing apparatus shown in FIG. It is a fragmentary sectional view showing an example of composition of a prefilled syringe.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Prefilled syringe 2 Syringe outer cylinder 21 Inner peripheral surface 211 Bottom part 22 Mouth part 221 Flow path 23 Lock adapter 24 Lumen part 25 Cap 26 Base end opening 3 Plug body 31, 32 Protrusion part 4 Jig for prefilled syringe (jig) )
41 Jig body 411 Inner wall 412 Front end opening 42 Storage space 43 Press member 431 Base end 432 Groove 44 Vent hole 45 Gap 451 Vent groove 46 Sealing member 51 Pump 71 Actuator 8 Control means 81 CPU
82 storage unit 9 valve 91 tube 10 prefilled syringe manufacturing apparatus (manufacturing apparatus)
20 Jig Moving Mechanism 30 Isolator 301 Globe 302 Air Supply Blower 303 Valve 100 Chemical Solution

Claims (10)

A prefilled syringe for manufacturing a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug A manufacturing method comprising:
A first step of mounting a jig having a storage space in which the stopper is stored so as to cover a proximal end opening of the syringe outer cylinder;
A second step of degassing the storage space and degassing a lumen of the syringe outer cylinder communicating with the storage space;
In the space in which sterility is maintained, the stopper is inserted into the inner cavity of the syringe outer cylinder by the jig, and at least sterilized air in the space in which the sterility is maintained is supplied to the storage space. And a third step of returning the storage space to a predetermined pressure.   In the third step, together with the storage space, through the storage space, sterile air in the space in which the sterility is maintained is supplied to the inner cavity of the syringe outer cylinder, and the lumen of the syringe outer cylinder The prefilled syringe manufacturing method according to claim 1, wherein the pressure is restored to a predetermined pressure. The jig includes a jig body having the storage space;
Installed in the jig body, pressing the plug so as to be inserted into the lumen of the syringe outer cylinder, and a pressing member having a communication path,
The prefilled syringe manufacturing method according to claim 1 or 2, wherein the supply of sterile air in the space in which the sterility is maintained in the third step is performed through the communication path.   The prefilled syringe manufacturing method according to claim 3, wherein the communication path is a groove formed on an outer peripheral surface of the pressing member. The syringe outer cylinder in a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug A prefilled syringe manufacturing jig used when performing insertion of the plug into the lumen part of the cavity in a space where sterility is maintained,
A jig body that is mounted so as to cover the proximal end opening of the syringe outer cylinder and has a storage space in which the stopper can be stored;
A pressing member that is installed in the jig main body and presses the stopper so as to be inserted into the lumen of the syringe outer cylinder;
The jig body communicates with the storage space, and has a vent hole for exhausting from the storage space.
When the plug body is stored in the storage space, a gap is formed between the inner wall of the jig body and the plug body so as to allow ventilation.
The pressing member has a communication path, and a first position that does not allow communication between the storage space and the space in which the sterility is maintained in which the prefilled syringe manufacturing jig is placed, and the communication path. A jig for producing a prefilled syringe, wherein the jig is configured to move to a second position where the storage space and the space in which sterility is maintained are communicated.   The pre-filled syringe manufacturing jig according to claim 3, wherein the communication path is a groove formed on an outer peripheral surface of the pressing member. A prefilled syringe for manufacturing a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug Manufacturing equipment,
Used in a space in which sterility is maintained, is mounted so as to cover the proximal end opening of the syringe outer cylinder, and is installed in the jig body having a storage space capable of storing the stopper, A jig provided with a pressing member that presses the stopper so as to be inserted into the lumen of the syringe outer cylinder;
Degassing means for degassing the storage space and degassing the lumen of the syringe outer cylinder communicating with the storage space;
A pressing member driving means for driving the pressing member when the stopper is inserted into the lumen of the syringe outer cylinder by the jig;
An apparatus for producing a prefilled syringe, comprising: a return pressure means for supplying aseptic air in a space in which the sterility is maintained to at least the storage space to return the storage space to a predetermined pressure. A prefilled syringe for manufacturing a prefilled syringe having a syringe outer cylinder, a plug inserted into a lumen portion of the syringe outer cylinder, and a drug solution filled in a space formed by the syringe outer cylinder and the plug Manufacturing equipment,
A prefilled syringe manufacturing jig according to claim 5 or 6, which is used in a space where sterility is maintained,
Degassing means for degassing the storage space and degassing the lumen of the syringe outer cylinder communicating with the storage space;
A pressing member driving means for driving the pressing member when the stopper is inserted into the lumen of the syringe outer cylinder by the jig;
An apparatus for producing a prefilled syringe, comprising: a return pressure means for supplying aseptic air in a space in which the sterility is maintained to at least the storage space to return the storage space to a predetermined pressure. The return pressure means and the pressing member driving means have a common actuator,
By the actuator, the pressing member moves to press the stopper, and the stopper is inserted into the inner cavity of the syringe outer cylinder. At this time, the pressing member reaches the second position, The storage space communicates with the space in which sterility is maintained through the communication path, and at least the storage space is supplied with aseptic air in the space in which the sterility is maintained, and the storage space has a predetermined pressure. The prefilled syringe manufacturing apparatus according to claim 8, wherein the prefilled syringe manufacturing apparatus is configured to return the pressure to a predetermined pressure. The return pressure means supplies the sterile air in the space in which the sterility is maintained to the lumen portion of the syringe outer cylinder through the storage space together with the storage space to supply the lumen portion of the syringe outer cylinder. The prefilled syringe manufacturing apparatus according to any one of claims 7 to 9, wherein the pressure is restored to a predetermined pressure.

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