JPH07265421A - Production of double chamber syringe - Google Patents

Abstract

PURPOSE:To support an inside plug segmenting two chambers of a double chamber syringe in a half plugging state. CONSTITUTION:After a medicinal liquid 10a is filled into the chamber 6 on an injection needle mounting port 2a side, the inside plug 4 is supported into a gasket cap 26 fitted onto a holder 22. Next, the holder 22 is carried onto a freeze drying house and is subjected to freeze drying and thereafter, the inside plug 4 is immediately driven into the aperture 2c of an injection cylinder 2 within the freeze drying housing. The inside plug 4 is press fitted into the injection cylinder 2 by a pressure difference between the inside and outside of the injection cylinder 2 when the atm. pressure is restored in the freeze drying housing. In secession, a dissolving liquid 12 is filled into the upper chamber 8 of the inside plug 4 and a mouth plug 20 is driven into the aperture 2c to hermetically seal the inside of the injection cylinder 2. As a result, the inside plug 4 is put into the half plugging state and the freeze drying is executed after the medicinal liquid 10a is filled into the injection cylinder 2 and, therefore, there is no possibility that the medicinal liquid 10a or a dry pharmaceutical prepn. agent 10, etc., re contaminated with general bacteria during the time before the plugging is executed after the freeze drying.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a double-chamber syringe (two-chamber syringe), and in particular, a dry preparation is contained in one of two chambers defined by an inner stopper press-fitted inside a syringe barrel. However, the present invention relates to a method for producing a double-chamber syringe in which the other chamber is filled with a solution such as distilled water for injection for dissolving the dry preparation.

[0002]

2. Description of the Related Art Conventionally, in order to improve the storage stability of a drug, the drug is made into a dry formulation by a freeze-drying method or the like,
Generally, it is generally stored in a vial, and when used, it is generally dissolved in distilled water for injection or the like for administration. The operation of dissolving the above dry preparation at the time of use is
By injecting distilled water for injection into a vial with a syringe to dissolve the above-mentioned dry preparation, and then inhaling the solution in which the drug is dissolved with a syringe,
Since the procedure is complicated, time-consuming, and there is a possibility that various bacteria may be mixed during the operation,
The inside of one syringe is divided into two chambers, and the above-mentioned dry preparation and a solution such as distilled water are separately enclosed in each room. When used, the two preparations communicate with each other to accommodate the dry preparation. A double-chamber syringe (two-chamber syringe) that allows a solution to flow into the chamber has been already proposed (Japanese Patent Laid-Open No. 5-139977).

The double-chamber syringe described in the above publication has a cap attached to the injection needle attachment port at the tip of the injection cylinder, which is sealed and inverted to form a liquid state inside the injection needle attachment port, that is, the lower chamber. After filling this drug with a dry formulation by a freeze-drying method etc., press the inner stopper to the middle part of the syringe barrel, then into the chamber above this inner stopper,
A solvent such as distilled water for injection for dissolving the dry preparation is filled, and then the opening is plugged.

Although the above-mentioned publication specifically describes the manufacture of a drug to be filled in the interior of a double-chamber syringe, it is fitted in the vicinity of the intermediate portion inside the syringe barrel and is inside the syringe barrel. Nothing is disclosed about a manufacturing method including a method of plugging an inner stopper that divides the container into two chambers and a stopper that seals the opening. Generally, in the case of producing a dry preparation by freeze-drying a drug solution, first, the drug solution is filled in a container such as a syringe and then carried into a freeze-drying chamber to carry out freeze-drying, and then the mouth is opened. It is designed to seal the inside of the container by hitting the stopper, and until the stopper is filled after filling the drug solution into the container, the drug solution or the dried preparation after freeze-drying is contaminated with bacteria in the air. May occur.
Therefore, after filling the chemical solution, put the stopper into a half stoppered state (a state in which gas can flow inside and outside the container without completely driving the stopper into the opening of the container) and carry it into the freeze-drying chamber. However, there has been conventionally known a production method in which, after freeze-drying, stoppering is immediately performed in the room to prevent contamination from various bacteria and the like (Japanese Patent Publication No. 49-26878 and Japanese Patent Publication No. 52-72). 21396 publication).

Although it is not freeze-dried,
After filling the syringe barrel with the drug solution, in order to insert the spigot close to the liquid level of the drug solution in the barrel, the syringe barrel filled with the drug solution and the spigot held above it are placed in a vacuum box. There is already known a vacuum stoppering machine which is carried into the inside and capped under a vacuum pressure (Japanese Patent Publication No. 28386/1992).

[0006]

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
No. 26878 and Japanese Examined Patent Publication No. 52-21396), the methods of plugging immediately after freeze-drying are all methods in which a container such as a bottle is filled with a chemical solution and freeze-dried.
Since the mouth is capped,
It is possible to keep the spout in a semi-stopped state, but in the case of the syringe barrel of a syringe, the spout cannot be held directly in the semi-stopped state at its opening. It was impossible to freeze-dry after filling the drug solution with the stopper half-stopped.

Further, in the structure of the publication (Japanese Patent Publication No. 4-28386) in which a vacuum stoppering machine for stoppering a syringe is described, a large number of inner stoppers are held by an inner stopper holding plate and a large number of injection cylinders are attached. The device is complicated and large in size because it is supported on the rack body and both are set in a vacuum box and capped at once, and the work of holding the inner plug on the inner plug gripping plate and filling of the chemical solution are performed. The work to hold the syringe barrel on the rack body is done manually, and moreover,
There is also a problem that work efficiency is poor because it is necessary to take the inside plug holding plate and the rack body in and out of the vacuum box.

The present invention has been made in view of the above problems, and it becomes possible to hold the inner plug in a half stoppered state even in the injection barrel of the syringe, and after filling the syringe with the drug solution, A double-chamber syringe can be manufactured with a compact device that can prevent contamination of chemicals or dried preparations by bacteria etc. while being carried into the freeze-drying chamber and freeze-dried and stoppered. It is an object of the present invention to provide a manufacturing method capable of performing the above.

[0009]

According to the method of manufacturing a double-chamber syringe of the present invention, a cap is attached to an injection needle attachment port of an injection cylinder, and the injection needle attachment port faces downward. After being held in the holder and the drug solution is filled in the syringe barrel, the inner stopper holding means provided on the upper portion of the holder holds the inner stopper. Next, the holder and the syringe are carried into a freeze-drying chamber, and after freeze-drying in this chamber, the inner stopper is driven into the syringe under a predetermined vacuum pressure, and then returned to normal pressure. The inside plug is press-fitted into the inside of the injection cylinder.

[0010]

In the method for manufacturing a double-chamber syringe having the above structure, the holder for holding the syringe is provided with the inner stopper holding means, and after filling the syringe with the medicinal solution, the inner stopper holding means holds the inner stopper. Since the holder and the syringe barrel were brought into the freeze-drying container in the so-called half-stopped state, and the stopper was immediately capped in the freeze-drying chamber after freeze-drying, the drug solution filled in the syringe or frozen. It is possible to prevent the dried preparation after drying from being contaminated with various bacteria.

[0011]

The present invention will be described below with reference to the embodiments shown in the drawings. FIG. 1 shows an example of a double-chamber type syringe (two-chamber injector) manufactured by the method of the present invention, in which an inside of an injection cylinder 2 is an inner plug (first gasket) 4 made of an elastic material such as rubber. Is divided into two upper and lower chambers 6 and 8, and one of these two chambers 6 and 8 (lower chamber 6) accommodates the dry preparation 10 produced by the freeze-drying method,
The other chamber (upper chamber 8) is filled with a solution 12 such as distilled water for injection for dissolving the dry preparation 10.

An injection needle attachment port 2 at the tip (lower end) of the injection cylinder 2.
An inner cap 14, a luer cap 16 and a top cap 18 are sequentially attached to a, and the mounting port 2a
The sides are sealed. The first gasket 4 is press-fitted into substantially the middle portion of the injection barrel 2. This first gasket 4
A plurality of annular seal portions 4a having a diameter slightly larger than the inner diameter of the injection cylinder 2 are provided on the outer periphery of the annular seal portion 4a.
The liquid tightness between the upper and lower chambers 6 and 8 is maintained by a. A groove 2b for a liquid passage that projects outward is formed on the inner surface of the injection cylinder 2 slightly closer to the injection needle mounting port 2a than the position where the first gasket 4 is fitted. The length of the liquid passage groove 2b in the axial direction (vertical direction in the drawing) is slightly larger than the thickness of the first gasket 4, and the first gasket 4 is located on the injection needle attachment port 2a side. When pushed to the position of the groove 2b for the liquid passage,
The chamber 6 on the injection needle attachment port 2a side and the chamber 8 on the opposite side, which are blocked by the first gasket 4, can be communicated with each other.

At the opening (upper end in the figure) 2c on the opposite side of the injection needle mounting port 2a of the injection cylinder 2, the first gasket 4 is inserted.
The second gasket 20 made of an elastic material such as rubber in the same manner as
Is fitted. On the outer circumference of the second gasket 20, an annular seal portion 20 having a diameter slightly larger than the inner diameter of the injection cylinder 2.
A plurality of b are provided, and the inside of the syringe barrel 2 is sealed by the annular seal portion 20b.
Further, a female screw portion 20a is formed in the central portion on the upper surface side of the second gasket 20, and the tip portion of a pusher (not shown) can be screwed and fixed when using this syringe. . A flange 2d is formed around the upper end opening 2c of the injection cylinder 2.

Next, the manufacturing process of the double chamber type syringe having the above construction will be described with reference to FIGS. The injection cylinder 2 having the above-described shape has the caps 14, 16 and 18 attached to the injection needle attachment port 2a at the tip,
The syringe needle mounting port 2a is directed downward and inserted into the holder 22 for transporting the syringe barrel. This holder 22 is a syringe
A central hole 22a in which a groove 2b for a liquid passage is formed in the main body portion and the inner surface of the body and a portion protruding to the outer surface side is accommodated;
A small-diameter hole 22b for inserting the injection needle attachment port 2a, which is continuously formed below the central hole 22a, and a central hole 22a.
And a large-diameter recess 22c on which the flange 2d of the injection cylinder 2 is placed.

The syringe barrel 2 is inserted in the holder 22 having the above-mentioned shape.
It is inserted and held so that the injection needle attachment port 2a faces downward. The holder 22 holding the syringe 2 is sent to a filling device (not shown), and the filling nozzle 24 is inserted into the syringe 2 from above to fill a predetermined amount of the drug solution 10a (see FIG. 2). After the filling of the chemical liquid 10a is completed, the gasket cap 26 is fitted on the upper surface of the holder 22 (see FIG. 3). The gasket cap 26 has the first gasket 4 at the center.
A gasket support portion 26a for mounting the is formed.
Although not shown in detail, around the gasket support portion 26a, gas can flow between the inside of the holder 22 (that is, the inside of the injection tube 2) and the outside.

Next, the first gasket 4 is mounted and supported in the gasket support portion 26a provided in the center of the gasket cap 26. This first gasket 4
Is a part of the lower part of the support portion 2 of the gasket cap 26.
6a is fitted in and the upper part thereof projects upward (see FIG. 4).

The holder 22 in the state shown in FIG. 4 in which the injection cylinder 2 is inserted into the inner holes 22a, 22b, 22c, and the first gasket 4 is supported by the gasket cap 26 fitted on the upper end thereof, Carry it into the freeze-drying cabinet. In the freeze-drying chamber, there are provided a support plate 28 that supports the lower surface of the holder 22, and a lift plate 30 that is arranged above the holder 22 mounted on the support plate 28 and that can be lifted and lowered. With the plate 30 raised, the holder 22 is carried in and placed on the support plate 28. A conventionally well-known freeze-drying process is performed in this freeze-drying chamber. That is, the drug solution 10a is frozen while evacuating, and then dried to obtain a powdered dry formulation 10 (see FIG. 5).

After performing the above freeze-drying process, nitrogen gas is injected into the freeze-drying chamber while maintaining the humidity in the freeze-drying chamber at 10% or less, and the vacuum pressure in the freeze-drying chamber is increased to about 200 Torr. . Under the vacuum pressure, the lift plate 30 is lowered to the upper surface of the gasket cap 26. It should be noted that the distance L ₁ between the upper surface of the flange 2d of the injection cylinder 2 fitted in the large-diameter recess 22c formed in the upper portion of the holder 22 and the upper surface of the gasket cap 26 fitted to the upper end of the holder 22 ( The thickness L ₂ (see FIG. 4) of the first gasket 4 is larger than that (see FIG. 3) (L ₁ <L ₂ ), and when the elevating plate 30 descends and comes into close contact with the upper surface of the gasket cap 26. The first gasket 4 descends while being held in the gasket support portion 26a of the gasket cap 26, the upper end thereof is held in the gasket support portion 26a of the gasket cap 26, and the lower portion is the syringe barrel. 2 is press-fitted into the upper opening 2c (see FIG. 6). As described above, the first gasket 4 is maintained while maintaining the humidity in the freeze-dryer at 10% or less.
Is injected into the opening 2c of the injection cylinder 2 to seal the inside of the injection cylinder 2, so that the dry preparation 10 in the chamber 6 on the injection needle attachment port 2a side is sealed.
Does not have the risk of absorbing water in the gas and dissolving.

Next, the inside of the freeze-drying chamber is returned to normal pressure.
Then, due to the pressure difference between the pressure in the syringe barrel 2 and the atmospheric pressure,
The first gasket 4 is pushed into the inside of the syringe barrel 2 (see FIG. 7). When the first gasket 4 was press-fitted into the upper end of the syringe barrel 2, the vacuum pressure in the freeze-drying chamber was about 200 Torr as described above, so that the nitrogen gas remaining in the syringe barrel 2 remained unchanged. As a result, the first gasket 4 is pushed to almost the middle portion of the syringe barrel 2 and stopped. Conversely speaking, the vacuum pressure in the freeze-drying chamber at the time of stoppering is such that the first gasket 4 stops slightly above the liquid passage groove 2b in the middle of the syringe barrel 2. The nitrogen gas is set to remain in the syringe barrel 2.

After the stoppering (temporary stoppering at this time) of the first gasket 2 is completed, the holder 22 holding the syringe barrel 2 is carried out from the freeze-drying chamber (see FIG. 8). Next, positioning is performed so that the lower end surface of the first gasket 4 is located at the upper end of the liquid passage groove 2b in the injection cylinder 2 (see FIG. 9). In this embodiment, the vertically movable positioning rod 32 is inserted into the syringe barrel 2 from above, and the first gasket 4 is inserted.
Is above the above position, this first
The gasket 4 is pushed down and lowered to the above position. Therefore, in the stoppering process shown in FIGS. 6 and 7, the first gasket 4 is press-fitted to almost the middle portion of the injection cylinder 2, but the lower end surface of the first gasket 4 is used for the liquid passage in the injection cylinder 2. The groove 2b is prevented from being pushed below the upper end, and is stopped slightly above this position.

After the first gasket 4 is accurately positioned, the gasket cap 26, which supports the gasket 4 above the injection tube 2 during freeze-drying of the first filling liquid (chemical liquid) 10a, is held in the holder. 22 Remove from above.
The gasket cap 26 is removed by suction by suction means 34 that moves up and down integrally with the positioning rod 32, or by suction means that moves up and down independently of the positioning rod 32.

The holder 22 that has been carried out from the freeze-drying chamber and from which the gasket cap 26 has been removed is carried into a filling device (not shown) for the second filling. Here, the filling nozzle 36 of the second filling device is inserted to a position higher than the first gasket 4 of the injection cylinder 2, and the dry formulation 10
Is filled with a solution such as distilled water 12 for injection to dissolve the water (see FIG. 10).

The injection cylinder 2 divided into the upper and lower chambers 6 and 8 by the first gasket 4 is obtained by the above-mentioned steps.
In the chamber 6 below that, a dry preparation 10 produced by freeze-drying the filled drug solution 10a is housed,
The upper chamber 8 is filled with distilled water 12 for injection that dissolves the dried preparation 10. After that, the second gasket 20 is plugged into the opening 2c at the upper end of the syringe barrel 2. The inside of the injection cylinder 2 is completely sealed (see FIG. 11). In the present embodiment, since the stopper of the second gasket 20 is performed under normal pressure, the stopper is adapted to discharge the air in the chamber 8 above the first gasket 4 in the syringe barrel 2. There is.

Next, a method of plugging the second gasket 20 will be described. FIG. 12 shows an example of a capping device for capping the spout (second gasket) 20 on the side of the upper opening 2 c of the injection cylinder 2, which is located above the injection cylinder 2 housed in the holder 22. A capping rod 40 for adsorbing and holding the second gasket 20 and moving up and down is arranged with its axis aligned with the axis of the injection cylinder 2. Inside the tapping rod 40, a passage 40a whose upper part is connected to a negative pressure source (not shown)
Is formed, and by introducing a negative pressure through the passage 40a, the stopper rod 40 is moved to the second gasket 2
Hold 0 by adsorption.

A gap pin 42 that moves up and down integrally with the stopper rod 40 is arranged adjacent to the stopper rod 40. The tip 42a of the gap pin 42 extends below the lower end portion 40b of the tapping rod 40, and when the tapping rod 40 and the gap pin 42 are integrally lowered, they are attracted to the tapping rod 40. The tip 42a of the gap pin 42 is inserted into the inside of the injection tube 2 before the second gasket 20 that is held. The stopper rod 40 and the gap pin 42 are guided to move up and down by guide holes 44a and 44b formed in a disc 44.

When the second gasket 20 is stoppered in the opening 2c at the upper end of the injection cylinder 2 by the stoppering device,
First, as shown in FIG. 12, the lower end portion 4 of the stopper rod 40
The second gasket 20 supplied from the gasket supply mechanism (not shown) is adsorbed and held on the unit 0b. Then, the stopper rod 40 and the gap pin 42 are integrally lowered. Both of these 40 and 42 are provided with guide holes 44 of a disc 44, respectively.
Guided by a and 44b, it descends and the tip 4 of the gap pin 42
2a is inserted into the opening 2c of the injection cylinder 2 first. Subsequently, the second gasket 20 held by the stopper rod 42 is pressed into the opening 2c of the injection cylinder 2. When the second gasket 20 is press-fitted into the syringe barrel 2, the tip 42a of the gap pin 42 is sandwiched between the second gasket 20 and the inner surface of the syringe barrel 2 that have descended from the rear, and the second gasket 20 is removed. It is inserted together with the gasket 20 into the inside of the injection cylinder 2. At this time,
Since the outer peripheral surface of the second gasket 20 which is in contact with the gap pin 42 is elastically deformed following the outer shape of the gap pin 42,
A gap is created between the elastically deformed portion and the gap pin 42. Since the inside and the outside of the injection cylinder 2 communicate with each other due to the formation of this gap, when the second gasket 20 is press-fitted, the internal air can be discharged and the press-fitting can be smoothly performed (see FIG. 13). As described above, the syringe 2
A double-chamber type syringe (two-chamber syringe) is completed by press-fitting the second gasket 20 into the opening 2c. The plugging method of the second gasket 20 is not limited to the one using the above-mentioned plugging device, and may be plugged by other methods.
For example, the stopper rod 40 and the gap pin 42 are configured to be able to move up and down separately, and the gap pin 42 is first lowered to make the injection barrel 2
And then the tapping rod 40 is lowered to the second position.
The gasket 20 may be press-fitted into the syringe barrel 2 so that the gap pin 42 is sandwiched between the second gasket 20 and the inner surface of the syringe barrel 2. Further, the gap pin 42 may be a solid pin as in the above embodiment, or may be a tubular pin having a narrow passage inside.

In this embodiment, with the gasket cap 22 fitted on the upper surface of the holder 22 holding the inner plug (first gasket) 4, the syringe barrel 2 is carried into the freeze-drying chamber and freeze-dried. Since the inner stopper (first gasket) 4 is immediately driven in the freeze-drying chamber after performing the process, the inner stopper (first gasket) 4 is filled with the drug solution in the syringe barrel 2 before the stopper is performed. There is no risk that the drug solution or the dried preparation after freeze-drying will be contaminated with various bacteria. Also,
A double chamber syringe can be manufactured by a device having a simple structure and a compact structure.

FIGS. 14 and 15 show the above-mentioned gasket support means for supporting the first gasket 4 above the holder 22 while freeze-drying the first filling liquid (medicinal liquid) 10a filled in the injection cylinder 2. Instead of the gasket cap 26 fitted on the holder 22, the holder 22 is integrally provided inside. The gasket support means is provided with a vertical cutout 22 formed inside the holder 22.
A plurality of (three in this embodiment) rocking arms 50 arranged in d are provided. These swing arms 50 are
The fulcrum pin 52 arranged horizontally supports the holder 22 so as to be swingable toward the center thereof. The upper ends of the swing arms 50 are provided with support claws 50 a that can project into the holes of the holder 22 and support the first gasket 4 when the upper part thereof rotates toward the center of the holder 22. ing. In addition, at the lower end of the swing arm 50,
When the syringe barrel 2 is inserted into the holder 22, there is provided an engaging portion 50b that is pushed outward by the syringe barrel 2 and shakes when the engaging portion 50b is pushed outward. The movable arm 50 rotates clockwise in FIG. 14 to move the support claw 50a to the gasket support position. Holder 2 with gasket support means of this embodiment
When 2 is used, it is not necessary to attach and detach the gasket cap 26 as in the above-described embodiment, and the gasket supporting means is formed only by inserting the injection cylinder 2 into the holder 22, which reduces the number of steps. The work time can be shortened.

[0029]

As described above, according to the present invention, after the injection cylinder held in the holder is filled with the drug solution, the inside plug holding means provided at the upper portion of the holder holds the inside plug, So-called half-stoppered state, then carried into the freeze-drying chamber,
After performing freeze-drying in this chamber, the inner stopper was driven into the syringe under a predetermined vacuum pressure.Therefore, after filling the syringe with the drug solution, until the stopper is removed, There is no risk that the dried product will be contaminated by various bacteria.
In addition, the double chamber syringe can be manufactured by a device having a simple structure and a compact structure.

[Brief description of drawings]

FIG. 1 is a vertical cross-sectional view showing an example of a double chamber syringe manufactured by a manufacturing method according to an embodiment of the present invention.

FIG. 2 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 3 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 4 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 5 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 6 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 7 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 8 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 9 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 10 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 11 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 12 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 13 is a vertical cross-sectional view showing steps of a manufacturing method according to an embodiment of the present invention.

FIG. 14 is a vertical cross-sectional view showing another example of a holder for accommodating and holding an injection cylinder and an inner stopper holding means.

FIG. 15 is a plan view of the holder and the inner stopper support means of FIG.

[Explanation of symbols]

 2 injection cylinder 2a injection needle attachment port 2b groove for liquid passage 4 inner plug (first gasket) 10 dry formulation 10a drug solution 12 dissolution liquid 14 injection needle attachment port cap 20 cap (second gasket) 22 holder 26 inner plug Holding means (gasket cap)

Claims (3)

[Claims] 1. A cap is attached to a mounting port of an injection needle, and a liquid medicine is filled into an injection cylinder held in the holder with the mounting port facing downward, and then an inner stopper holding member provided on an upper part of the holder. By holding the inner stopper in the means, carrying it into the freeze-drying chamber, performing freeze-drying in this chamber, driving the inner stopper into the syringe under a predetermined vacuum pressure, and then returning to normal pressure. A method for manufacturing a double-chamber syringe, characterized in that the inner stopper is press-fitted into the syringe barrel. 2. An injection cylinder, a cap attached to the injection needle mounting opening of the injection cylinder, an inner plug fitted around the middle of the inside of the injection cylinder, and a reverse of the injection needle mounting opening of the injection cylinder. The injection needle is provided with a mouth plug fitted in the opening on the side, and a groove for a liquid passage projecting outwardly on the inner wall of the injection cylinder slightly closer to the mounting opening than the inner plug. A method for producing a double-chamber syringe in which a dry preparation is housed in a room between an attachment port and an inner stopper, and a solution for dissolving the dry preparation is filled in the room between the inner stopper and the stopper. After filling the drug solution into the chamber on the side of the injection needle of the syringe barrel, the inner stopper is held by the inner stopper holding means provided on the upper part of the holder, and then the holder and the syringe are carried into the freeze-drying chamber. Freeze-drying is performed, and inside the freeze-drying chamber, the inner stopper is driven into the opening of the syringe under a predetermined vacuum pressure. The method for producing a double-chamber syringe is characterized in that the lyophilization chamber is then returned to normal pressure so that the inner plug is inserted into the syringe barrel due to the pressure difference between the inside and outside of the syringe barrel. 3. The inner plug holding means is fitted to the upper surface of a holder, has a holding portion for holding the inner plug in the center, and a portion around the holding portion is between the inside and the outside of the holder. The method for manufacturing a double-chamber type syringe according to claim 1 or 2, wherein the gas is allowed to flow.