JP2020074834A - Airtight test method of pre-filled syringe - Google Patents

Abstract

To provide an airtight test method that can perform examination of sealability of a pre-filled syringe efficiently and highly accurately.SOLUTION: A pre-filled syringe 10 includes an outer cylinder 11, a plunger 12 inserted into the outer cylinder 11, and a gasket 13 provided at the tip of the plunger 12 and coming in contact with an inner circumference of the outer cylinder 11 in an air-tight manner. A medicinal solution 17 is filled in a medicinal solution storage space 16 between the gasket 13 and the tip end of the outer cylinder 11. In a preparation step, the plunger 12 is moved in the direction separated from the outer cylinder 11, and thereby the medicinal solution storage space 16 is widened and a non-filling space part 16a of negative pressure is formed. This plunger 12 is made immovable to the outer cylinder 11 by a regulation jig 20 (movement regulation means) and is maintained in a predetermined position. In an airtight test step, the pre-filled syringe 10 is sealed up in a workpiece capsule and a test pressure is imparted, and the leakage of the pre-filled syringe 10 is detected on the basis of pressure change in the workpiece capsule.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an airtightness test method for detecting a defect in a syringe prefilled with a drug solution, that is, a prefilled syringe.

  In order to reduce the work at the medical site and prevent accidents during dispensing, in recent years, there has been a rapid increase in demand for syringes (prefilled syringes) prefilled with a dispensed drug solution.

  In the case of the above-mentioned prefilled syringe, since the drug solution is pre-filled, if the airtightness of the syringe is low, problems such as deterioration of the drug solution and mixing of air may occur. Therefore, the airtightness of the syringe is strictly required.

  In Patent Document 1, the sealability between the outer cylinder of the prefilled syringe and the gasket and the sealability between the needle mounting portion of the outer cylinder and the sealing cap are confirmed using electromagnetic waves.

JP, 2013-252177, A

  In Patent Document 1, it is possible to confirm the sealing property of only the selected portion of the prefilled syringe, but it is not possible to confirm the airtightness of the entire space in which the drug solution is stored. Further, if there are a plurality of confirmation points, it takes time and effort for the inspection.

The present invention has been made to solve the above-mentioned problems, and includes an outer cylinder, a plunger inserted in the outer cylinder, and a gasket provided at the tip of the plunger and airtightly contacting the inner circumference of the outer cylinder. In the method for testing the airtightness of a prefilled syringe in which a drug solution is filled in a drug solution containing space between the gasket and the tip of the outer cylinder,
In the preparatory step prior to the airtightness test step, the plunger of the prefilled syringe is held in a predetermined position by being immovable with respect to the outer cylinder by movement restricting means,
In the airtightness test step, the prefilled syringe is sealed in a work capsule to apply a test pressure, and a leak of the prefilled syringe is detected based on a pressure change in the work capsule.

According to the above method, the prefilled syringe is hermetically sealed in the work capsule, leaks can be detected based on the change in test pressure, and the airtightness of the drug solution storage space can be confirmed in one test, which improves the quality of the inspection work. The efficiency can be increased.
Further, in the airtightness test process, since the plunger is immovable with respect to the outer cylinder, the volume of the chemical liquid storage space does not change when the test pressure is applied. Since a pressure change in the work capsule can be generated, the leak can be reliably detected.

  In one aspect, in the preparation step, by moving the plunger in a direction away from the outer cylinder, the chemical liquid storage space is expanded to a negative pressure, and at least the plunger is directed toward the outer cylinder by the movement restricting means. Forbid to move to.

In the above-mentioned one aspect, preferably, the movement restricting means is constituted by a restricting jig inserted between a flange part formed at a base end of the outer cylinder and a pressing part formed at a base end of the plunger. The restriction jig has first and second locking surfaces that lock the surfaces of the flange portion and the pressing portion facing each other.
In the above-mentioned one aspect, since the plunger receives a force toward the outer cylinder due to the negative pressure of the chemical liquid storage space, it is sufficient that the restricting jig prohibits the movement in this direction, and the configuration can be simplified.

In the one aspect, preferably, the test pressure in the airtightness test step is a positive pressure.
According to this, a positive pressure of the test pressure and a negative pressure of the chemical liquid storage space can surely cause a leak with a large pressure difference, and a highly accurate leak inspection can be performed.

In the above aspect, the drug solution containing space of the prefilled syringe is filled with a drug solution 100%, and the drug solution is not filled in the drug solution containing space by moving the plunger in a direction away from the outer cylinder. Form an unfilled space of pressure.
Even if the drug solution storage space is 100% filled with the drug solution, the airtightness test can be performed by moving the plunger in the direction away from the outer cylinder to form the negative pressure non-filled space part.

  In the one aspect, in the drug solution storage space of the prefilled syringe, there is a non-filled space portion that is not filled with a drug solution, and in the preparing step, by moving the plunger in a direction away from the outer cylinder, The non-filled space portion of the chemical liquid storage space is widened to a negative pressure.

  In another aspect, a non-filled space portion in which the drug solution is not filled is present in the drug solution storage space of the prefilled syringe, and the drug solution is moved by moving the plunger toward the outer cylinder in the preparation step. The non-filling space portion of the accommodation space is narrowed to a positive pressure, and the movement restricting means prohibits at least the plunger from moving in a direction away from the outer cylinder.

In the other aspect, the movement restricting means is constituted by a restricting jig, and the restricting jig includes a flange portion formed at the proximal end of the outer cylinder and a pressing portion formed at the proximal end of the plunger. It has first and second locking surfaces for locking the surfaces that face in the opposite direction.
In the other mode, the plunger receives a force in the direction away from the outer cylinder due to the positive pressure in the chemical liquid storage space, so that the regulation jig only needs to prohibit movement in this direction, and the configuration can be simplified.

In the above other aspect, preferably, the test pressure in the airtightness test step is a negative pressure.
Due to the negative pressure of the test pressure and the positive pressure of the chemical liquid storage space, it is possible to reliably generate a leak with a large pressure difference, and it is possible to perform a highly accurate leak test.

  In still another aspect, a non-filled space portion in which the drug solution is not filled is present in the drug solution storage space of the prefilled syringe, and in the preparation step, the plunger of the plunger in the natural state of the prefilled syringe is used with respect to the outer cylinder. The position is maintained as it is by the movement restricting means, and the movement restricting means prohibits the movement of the plunger in both the direction toward the outer cylinder and the direction away from the outer cylinder.

  According to the present invention, it is possible to efficiently and highly accurately check the airtightness of a prefilled syringe.

In the airtightness test method which concerns on one Embodiment of this invention, it is a schematic longitudinal cross-sectional view of the prefilled syringe explaining a preparatory process in order before an airtightness test process, (A) is a natural state of a prefilled syringe, (B) is The state where the negative pressure non-filling space is formed in the drug solution containing space by pulling the plunger of the prefilled syringe and (C) shows the state where the plunger is fixed in position by using the restricting jig. (A), (B) is a cross-sectional view showing a different example of the restriction jig used in the preparation step. It is a circuit block diagram of the airtightness test apparatus for performing an airtightness test process with respect to the prefilled syringe which completed the said preparation process. In the airtightness test method according to another embodiment of the present invention, it is a schematic vertical cross-sectional view of a prefilled syringe, which sequentially explains the preparatory steps before the airtightness test step, (A) is a natural state of the prefilled syringe, (B) Shows a state in which the plunger of the prefilled syringe is pushed in to make the non-filling space portion of the drug solution storage space a positive pressure, and (C) shows a state in which the plunger is fixed in position by using a restricting jig. In the airtightness test method concerning further another embodiment of the present invention, it is an outline longitudinal section of a prefilled syringe explaining a preparatory process before an airtightness test process. It is a circuit block diagram of the airtightness test apparatus used in the airtightness test process of the prefilled syringe of FIG.

Hereinafter, an airtightness test method for a prefilled syringe according to an embodiment of the present invention will be described with reference to FIGS. 1 to 3.
First, the prefilled syringe 10 to be tested in this embodiment will be described with reference to FIG. Note that FIG. 1A is a schematic vertical cross-sectional view, in which components are exaggerated for ease of understanding, and actual dimensions and shapes are different.

The prefilled syringe 10 includes an outer cylinder 11, a plunger 12, and a gasket 13 as main components.
An annular flange portion 11a is formed at the base end of the outer cylinder 11 so as to project radially outward, and a needle mounting portion 11b is formed at the tip end.
A needle 14 is attached to the needle mounting portion 11b, and a tip of the needle 14 is inserted into a rubber cap 15 attached to the needle mounting portion 11b to be sealed.
In the case where the prefilled syringe 10 is a type in which a needle is not attached (a type in which a needle is attached at a medical site), another sealing cap is attached to the needle attachment part 11b to close the opening of the needle attachment part 11b.

  The plunger 12 is inserted into the outer cylinder 11 coaxially with the outer cylinder 11. A large-diameter pressing portion 12a is formed at the base end of the plunger 12, and a gasket 13 is fixed at the tip thereof.

  The gasket 13 is airtightly joined to the inner circumference of the outer cylinder 11 and is movable in the axial direction. A sealed space between the gasket 12 and the tip of the outer cylinder 11 is provided as a drug solution storage space 16. The chemical solution storage space 16 is filled with the chemical solution 17. In the present embodiment, the chemical liquid storage space 16 is completely filled with the chemical liquid 17.

<Preparation process>
A preparatory process executed before the airtightness test process will be described. As shown in FIG. 1 (B), by pulling the plunger 12 of the prefilled syringe 10 having the above-described configuration (moving in a direction away from the outer cylinder 11), the drug solution storage space 16 is not filled with the drug 17 under a negative pressure. The non-filled space portion 16a is formed. Note that the movement amount of the plunger 12 is exaggerated in FIG. 1 (B).

Next, as shown in FIG. 1C, a regulation jig 20 (movement regulation means) is inserted between the flange portion 11a of the outer cylinder 11 and the pressing portion 12a of the plunger 12. The regulation jig 20 has a C-shaped cross section as shown in FIG. 2A and can be inserted from the side of the plunger 12.
Both axial end surfaces of the restricting jig 20 are a first locking surface 21 and a second locking surface 22 which are respectively locked to the facing surfaces of the flange portion 11a of the outer cylinder 11 and the pressing portion 12a of the plunger 12. Provided as. The restricting jig 20 prevents the plunger 12 from being pulled back by the negative pressure of the non-filling space 16a and returning to the original position, and a predetermined position (the pressing portion 12a from the flange portion 11a of the outer cylinder 11 to the restricting jig). 20 axial positions apart).

  Various forms of the regulation jig 20 can be adopted. For example, like the regulation jig 25 shown in FIG. 2B, one end of a half-split body 25a having a semicircular arc cross section is connected by a hinge 25b, The other end may be detachably connected by the clamp 25c.

<Airtightness test process>
The airtightness test is performed on the prefilled syringe 10 with the regulation jig 20 produced in the above-mentioned preparation step. An example of the apparatus 50 used in this airtightness test process is shown in FIG.
The airtightness testing device 50 is a known device, and includes a common passage 51, and a branch passage 52a and a branch passage 52b that are connected to the downstream ends of the common passage 51, respectively. A test pressure source 53 is connected to the upstream end of the common passage 51. The test pressure in this embodiment is a positive pressure. A three-way valve 54 is provided in the common passage 51.

Open / close valves 55a and 55b are provided in the branch passages 52a and 52b, respectively.
In the branch passages 52a and 52b, two ports of a differential pressure sensor 56 (pressure sensor) are connected to the downstream sides of the on-off valves 55a and 55b, respectively, so that the differential pressure between the branch passages 52a and 52b is detected. be able to.

  A work capsule 57a is connected to the downstream end of the branch passage 52a, and a master capsule 57b is connected to the downstream end of the branch passage 2b. The work capsule 57a can be hermetically sealed in a state in which the prefilled syringe 10 with the regulation jig 20 to be tested is accommodated. The master capsule 57b has substantially the same volume as the work capsule 57a.

  The valves 54, 55a and 55b are sequence-controlled by a controller (not shown). The controller also opens and closes the work capsule 57a and the master capsule 57b, and determines whether the test target is good or bad (determines whether there is a leak) based on the differential pressure detected by the differential pressure sensor 56.

The airtightness test process is performed as follows. The pre-filled syringe 10 to be tested is housed in the work capsule 57a, the work capsule 57a and the master capsule 57b are sealed, and then the three-way valve 54 is turned on. It is supplied to the work capsule 57a and the master capsule 57b via 52a and 52b. Next, the on-off valves 55a and 55b are closed, and the branch passages 52a and 52b on the downstream side are isolated from each other.
Even if a positive test pressure is applied to the work capsule 57a, the regulation jig 20 prohibits the plunger 12 from being pushed into the outer cylinder 11, and the predetermined position is maintained.

The differential pressure detected by the differential pressure sensor 56 after a lapse of a predetermined time after the opening / closing valves 55a and 55b are closed is compared with a threshold value.
In the case where the prefilled syringe 10 has a minute defect in the configuration surrounding the drug solution storage space 16, for example, a defective joint between the outer cylinder 11 and the gasket 13, a pinhole of the outer cylinder 11, and a needle mounting portion 11b of the outer cylinder 11 are sealed. When there is a sealing failure or the like, the pressurized air in the work capsule 57a enters the chemical liquid storage space 16 of the prefilled syringe 10 (a minute leak occurs), and the pressure in the work capsule 57a gradually decreases from the test pressure. In the prefilled syringe 10 of the present embodiment, the drug solution storage space 16 is 100% filled with the drug solution in the natural state, but by pulling the plunger 12 in the above-described preparation process, the drug solution storage space 16 is not filled with a negative pressure. Therefore, the pressurized air can enter the chemical solution containing space 16 if there is such a minute defect as described above.

  Since the plunger 12 is maintained at a predetermined position by the regulation jig 20, the actual volume in the work capsule 57a (volume obtained by removing the volume of the prefilled syringe 10 from the volume of the work capsule 57a) does not change, and as described above. When a minute leak occurs, a pressure drop in the work capsule 57a corresponding to the minute leak occurs without fail.

  On the other hand, the test pressure is maintained in the master container 57b. As a result, a difference occurs between the pressure inside the work capsule 57a and the pressure inside the master container 57b. The differential pressure (change in pressure of the work capsule 57a) is detected by the differential pressure sensor 56. When the detected differential pressure is larger than the first threshold value, it is determined that there is a minute leak, and when the detected differential pressure is smaller than the first threshold value, the prefilled syringe 10 is determined as a non-defective product with no minute leak.

  As described above, it is possible to confirm whether or not there is a minute defect in the structure surrounding the chemical liquid storage space 16 by one airtightness test. Further, since the plunger 12 is maintained at the predetermined position and the pressure drop of the work capsule 57a corresponding to the leakage occurs, the leakage inspection can be performed with high accuracy.

  Since the test pressure is positive in the above-described embodiment, the pressure difference from the negative pressure in the non-filling space 16a is large, a large pressure change due to leakage can occur, and the inspection accuracy can be further improved. In principle, the test pressure may be atmospheric pressure or negative pressure (negative pressure different from the non-filling space 16a).

  In the above-described embodiment, the prefilled syringe 10 in which the drug solution storage space 16 is 100% filled with the drug solution is the test target. However, as shown in FIG. The prefilled syringe 10 in which the non-filled space 16b of atmospheric pressure remains may be used as a test target. In this case, when the plunger 12 is pulled, as in the above-described embodiment, the volume of the non-filling space 16b increases and the pressure becomes negative. The subsequent mounting of the regulation jig 20 and the airtightness test process are the same as those in the above-described embodiment, and thus the description thereof is omitted.

  As shown in FIG. 4 (A), when the prefilled syringe 10 in which the non-filled space 16b at atmospheric pressure remains in the drug solution storage space 16 is a test target, the plunger 12 may be pushed in as shown in FIG. 4 (B). (It may be moved toward the outer cylinder 11). As a result, the volume of the non-filled space portion 16b decreases and the pressure becomes positive. In this state, as shown in FIG. 4C, the restricting jig 30 is mounted between the flange portion 11a of the outer cylinder 11 and the pressing portion 12a of the plunger 12. The restriction jig 30 prohibits the plunger 12 from moving in the direction away from the outer cylinder 11 and returning to the original position by the positive pressure of the non-filling space 16a, and keeps the plunger 12 at a predetermined position. The regulation jig 30 can be mounted from the side of the plunger 12 like the regulation jig 20, and is locked to one surface of the flange portion 11a of the outer cylinder 11 (the surface opposite to the pressing portion 12a). Has a first locking surface 31 and a second locking surface 32 that is locked to one surface of the pressing portion 12a of the plunger 12 (the surface opposite to the flange portion 11a).

  When the prefilled syringe 10 with the regulation jig 30 is to be tested, it is preferable that the test pressure of the airtightness testing device 50 is a negative pressure. This is because the pressure difference from the positive pressure in the non-filled space 16b is large, a large pressure change occurs due to leakage, and the detection sensitivity is increased. However, in principle, the test pressure may be atmospheric pressure or positive pressure (a positive pressure different from the non-filling space 16b).

  As shown in FIG. 4 (A), when the prefilled syringe 10 in which the non-filled space portion 16b at atmospheric pressure remains in the chemical liquid storage space 16 is a test target, pull or push the plunger 12 as in the above-described embodiment. Alternatively, the plunger 12 may be fixed to the outer cylinder 11 at a position close to the natural state. As shown in FIG. 5, the restriction jig 40 used in this embodiment includes a first chuck portion 41 that holds the flange portion 11 a of the outer cylinder 11 and a second chuck portion 42 that holds the pressing portion 12 a of the plunger 12. Have. As a result, the plunger 12 is prohibited from moving in either axial direction.

  When the prefilled syringe 10 with the regulation jig 40 is used as a test target, a large leak detection (detection of a large defect) can be performed by using the airtightness test apparatus 50A shown in FIG.

  The airtightness test apparatus 50A of FIG. 6 is obtained by adding the following configuration to the airtightness test apparatus 50 of FIG. In the branch passages 52a, 52b, auxiliary passages 52a ', 52b' are connected to the downstream sides of the on-off valves 55a, 55b, respectively, and the auxiliary passages 52a ', 52b' are provided with the on-off valves 58a, 58b, respectively. Volume tanks 59a and 59b are connected to each other.

  The minute leak detection step is executed in the same manner as the above-described embodiment. If the test pressure is a positive pressure, the pressurized air in the work capsule 57a will enter the non-filled space 16b at atmospheric pressure due to a minute defect in the prefilled syringe 10, and minute leakage can be detected. If the test pressure is negative, air in the non-filled space 16b at atmospheric pressure leaks into the work capsule 57a at negative pressure due to minute defects in the prefilled syringe 10, and minute leakage can be detected.

  Subsequent to the minute leak step, a large leak detection step is executed. The case where the test pressure is a positive pressure will be described. When the prefilled syringe 10 has a large defect, pressurized air of the test pressure enters the chemical liquid accommodation space 16 (large leakage) simultaneously with the supply of the test pressure.

In the large leak detection step, the opening / closing valves 58a and 58b are opened to connect the tanks 59a and 59b to the branch passage 52a and the branch passage 52b, respectively. Since the tanks 59a and 59b are at atmospheric pressure, the test pressure in the work capsule 57a and the master capsule 57b escapes to the tanks 59a and 59b and is divided. When there is a large leak, the pressure in the work side passage 2a becomes higher than the pressure in the master side passage 2b by the amount of the pressurized air in the chemical liquid storage space 16. This differential pressure is compared with the second threshold value by the differential pressure sensor 56, and if it exceeds the second threshold value, it is determined that there is a large leak in the prefilled syringe 10.
Since the same applies to the case of negative pressure, the description is omitted.

  The present invention is not limited to the embodiment described above, and various modifications can be made without departing from the spirit of the invention.

  INDUSTRIAL APPLICABILITY The present invention can be applied to an airtightness test method for a prefilled syringe.

10 Prefilled Syringe 11 Outer Cylinder 11a Cylinder 12 Plunger 12a Pressing 13 Gasket 16 Chemical Solution Storage Spaces 16a, 16b Non-Filled Space 17 Chemicals 20, 25, 30, 40 Regulation Jig (Movement Regulation Means)
21, 31 First locking surface 22, 32 Second locking surface 50, 50A Airtightness test device 53 Test pressure source 56 Differential pressure sensor (pressure sensor)
57a Work capsule

Claims (10)

An outer cylinder, a plunger inserted in the outer cylinder, and a gasket provided at the tip of the plunger and airtightly contacting the inner circumference of the outer cylinder, and a chemical liquid between the gasket and the tip of the outer cylinder. In the method of testing the airtightness of a prefilled syringe in which a storage space is filled with a drug solution,
In the preparatory step prior to the airtightness test step, the plunger of the prefilled syringe is held in a predetermined position by being immovable with respect to the outer cylinder by movement restricting means,
In the airtightness test step, the prefilled syringe is sealed in a work capsule to apply a test pressure, and based on a pressure change in the work capsule, a leak of the prefilled syringe is detected, which is characterized in that the prefilled syringe is detected. Airtightness test method.   In the preparation step, by moving the plunger in a direction away from the outer cylinder, the chemical liquid storage space is widened to a negative pressure, and at least the plunger is moved in the direction toward the outer cylinder by the movement restricting means. The airtightness test method for a prefilled syringe according to claim 1, wherein The movement restricting means is composed of a restricting jig that is inserted between a flange part formed at the base end of the outer cylinder and a pressing part formed at the base end of the plunger,
The airtightness test of the prefilled syringe according to claim 2, wherein the restriction jig has first and second locking surfaces that lock surfaces of the collar portion and the pressing portion that face each other. Method.   4. The airtightness test method for a prefilled syringe according to claim 2, wherein the test pressure in the airtightness test step is a positive pressure.   The drug solution storage space of the prefilled syringe is 100% filled with the drug solution, and by moving the plunger in the direction away from the outer cylinder, the drug solution storage space is not filled with the drug solution and is a negative pressure non-filled space. A part is formed, The airtightness test method of the prefilled syringe in any one of Claims 2-4 characterized by the above-mentioned. In the drug solution containing space of the prefilled syringe, there is a non-filled space portion that is not filled with drug solution,
In the said preparatory process, by moving the said plunger in the direction which separates from the said outer cylinder, the said non-filling space part of the said chemical | medical solution storage space is expanded and it is set as negative pressure. The method for testing the airtightness of a prefilled syringe as described in 1. In the drug solution containing space of the prefilled syringe, there is a non-filled space portion that is not filled with drug solution,
In the preparing step, by moving the plunger toward the outer cylinder, the non-filling space portion of the drug solution containing space is narrowed to a positive pressure, and at least the plunger is separated from the outer cylinder by the movement restricting means. 2. The method for testing the airtightness of a prefilled syringe according to claim 1, wherein it is prohibited to move in a direction.   The movement restricting means is composed of a restricting jig, and the restricting jig engages surfaces of the flange portion formed at the base end of the outer cylinder and the pressing portion formed at the base end of the plunger, which face in mutually opposite directions. The airtightness test method for a prefilled syringe according to claim 7, which has first and second locking surfaces for stopping.   9. The method for testing the airtightness of a prefilled syringe according to claim 7, wherein the test pressure in the airtightness testing step is a negative pressure. In the drug solution containing space of the prefilled syringe, there is a non-filled space portion that is not filled with drug solution,
In the preparatory step, the position of the plunger in the natural state of the prefilled syringe with respect to the outer cylinder is maintained as it is by the movement restricting means,
The airtightness test method for a prefilled syringe according to claim 1, wherein the movement restricting means inhibits the movement of the plunger in both a direction toward the outer cylinder and a direction away from the outer cylinder.

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