Method for manufacturing a packaged medicament administration device

Abstract

Provided is a method for manufacturing a packaged medicine administering tool comprising: a medicine administering tool provided with an outer cylinder filled with a medicine and a puncture tool 3 for administering the medicine; a cylindrical case 4 for enclosing and holding the medicine administering tool; and a sealed package 7 for housing the medicine administering tool 10 enclosed by the cylindrical case. The manufacturing method comprises: a step for preparing a medicine administering tool enclosed by a cylindrical case; a step for adding hydrogen peroxide to a portion inside the medicine administering tool enclosed by the cylindrical case; a step for housing, in a package, the medicine administering tool enclosed by the cylindrical case; a step for sealing the package in which the medicine administering tool enclosed by the cylindrical case has been housed; and a post-package-sealing preservation step for sterilizing, while the package is sealed, the medicine administering tool enclosed by the cylindrical case by means of a hydrogen peroxide atmosphere formed by the added hydrogen peroxide.

Description

Technical Field

[0001] The present invention relates to a method for manufacturing a packaged drug administration device, and more particularly to a method for manufacturing a packaged drug administration device in which the stored drug administration device is in a sterilized state.

Background Art

[0002] A syringe (a syringe with a needle) is used to administer a drug solution to a patient. As a method of storing a drug solution to be administered to a patient in a syringe, for example, there is a method of sucking out the drug solution from an ampoule or vial in which the drug solution is stored. An ampoule is a container filled with a drug solution and sealed by melting the end of the container with heat. When using the drug solution, it is necessary to fold the neck of the container and insert a syringe needle through the folded part to suck out the drug solution. A vial is a container (bottle) containing a drug solution and stoppered with rubber. When using the drug solution, it is necessary to pierce the rubber stopper with a syringe needle to suck out the drug solution.

[0003] On the other hand, there is a prefilled syringe in which a drug solution is stored in a syringe in advance. With a prefilled syringe, it is not necessary to suck out the drug solution from the container in which the drug solution is stored before drug administration.

[0004] Japanese Patent Publication No. 2018-535042 (Patent Document 1) discloses a drug injection device that provides an automatic mechanism for inserting a needle into a drug cartridge and can reduce the user's manual handling of the needle before injection. In addition, the applicant of the present application has proposed a liquid administration device disclosed in Japanese Patent Application Laid-Open No. 2015-171407 (Patent Document 2).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] In the device of Patent Document 1, a drug cartridge holder that is fixed to the main body and configured to hold a drug cartridge, a needle carrier that supports a needle and is axially movable with respect to the main body, and a first pre-stress applying spring connected to the needle carrier are included. It also includes a rotatable cap at the distal end of the device. The cap is arranged such that the first pre-stress applying spring is released by its rotational movement, thereby causing the needle carrier to move axially toward the proximal end of the device. In such a drug injection device, preparation for administration is easy.

[0007] The liquid administration device 10 of Patent Document 2 includes a structure 40 having a syringe 60 capable of accommodating a liquid therein and a needle tube 66 communicable with the inside of the syringe 60, an operation unit 20 that discharges the liquid inside the syringe 60 from the needle tube 66 by moving in the tip direction with respect to the structure 40, a cover member 30 movable between a protection position covering the needle tube 66 and an exposure position exposing the needle tube 66, a second coil spring 11 that biases the cover member 30 in the tip direction, and a first coil spring 12 that biases the operation unit 20 in the tip direction with respect to the structure 40. The operation unit 20 and the structure 40 have a resistance protrusion 96 and a resistance claw 105 that change the contact position and contact while applying a pressing force when the operation unit 20 moves in the tip direction with respect to the structure 40.

[0008] However, the drug injection device of Patent Document 1 and the liquid administration device of Patent Document 2 are composed of many members, and assembly in a sterile state is difficult. The needle in the drug injection device of Patent Document 1 is covered with a cap, but it is not packaged in a sterile state. Also, since the above-mentioned medical devices are easy to prepare for administration and perform administration operations, they are assumed to be used in a highly microbe-controlled atmosphere such as an operating room or an ICU.

[0009] Therefore, the present invention provides a method for manufacturing a packaged drug administration device composed of a plurality of members, in which the entire part including the needle portion to be punctured of the drug administration device in the package is sterilized and the state can be maintained.

Means for Solving the Problems

[0010] The following achieves the above object. A method for manufacturing a packaged drug administration device including a drug administration device provided with an outer cylinder filled with a drug and a puncture tool for drug administration, a cylindrical case that encloses and holds the drug administration device, and a package that stores and seals the cylindrical case-enclosed drug administration device held by the cylindrical case, a step of preparing the cylindrical case-enclosed drug administration device, a step of adding hydrogen peroxide to a portion inside the cylindrical case of the cylindrical case-enclosed drug administration device, a step of storing the cylindrical case-enclosed drug administration device in the package, a step of sealing the package storing the cylindrical case-enclosed drug administration device, a post-packaging sealing storage step for sterilizing the cylindrical case-enclosed drug administration device by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package is sealed.

Brief Description of the Drawings

[0011]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

DETAILED DESCRIPTION OF THE INVENTION

[0012] The manufacturing method of the packaged drug administration device of the present invention will be described with reference to the drawings. As shown in FIGS. 1 to 6, the manufacturing method of the packaged drug administration device 1 of the present invention includes a drug administration device including an outer cylinder 21 filled with a drug 25 and a puncture tool 3 for drug administration, a cylindrical case 4 that encapsulates and holds the drug administration device, and a packaged drug administration device including a packaging body 7 that houses the cylindrical case-encased drug administration device 10 held by the cylindrical case 4 and is sealed.

[0013] In the manufacturing method of the packaged drug administration device of the present invention, a step of preparing the cylindrical case-encased drug administration device 10, a step of adding hydrogen peroxide to a portion inside the cylindrical case 4 of the cylindrical case-encased drug administration device 10, a step of housing the cylindrical case-encased drug administration device 10 in the packaging body 7, a step of sealing the packaging body 7 housing the cylindrical case-encased drug administration device 10, and a post-packaging sealing storage step of sterilizing the cylindrical case-encased drug administration device 10 by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide are performed in a state where the packaging body 7 is sealed. Therefore, in the above-described post-packaging storage process, hydrogen peroxide gas generated by the added hydrogen peroxide fills the inside of the package, and the inside and outside surfaces of the cylindrical case-encased drug dispenser are sterilized by the filled hydrogen peroxide gas. And since it is already packaged, the sterilized state is maintained until the package is opened after the post-packaging storage process, so it can be used in a highly controlled microbial environment such as an operating room or an ICU.

[0014] The cylindrical case-encased drug dispenser 10 targeted by the present invention comprises a cylindrical case 4 and a drug dispenser held and encapsulated by the cylindrical case 4. As the drug dispenser, one that minimally includes an outer cylinder filled with a drug and a puncture needle for drug administration is used. For example, as the drug dispenser shown in FIGS. 1 to 6, it includes a hollow tubular member 31 having a puncture needle portion at one end side and a connecting needle portion at the other end side, a hub 32 mounted between the puncture needle portion and the connecting needle portion of the hollow tubular member, a puncture needle portion cap 34 mounted on the puncture needle portion side of the hub, a puncture device 3, an outer cylinder, a gasket slidably housed in the outer cylinder, a tip sealing member that seals the tip of the outer cylinder and through which the connecting needle portion can penetrate, a drug 25 filled in the outer cylinder, and a prefilled syringe 2 having a plunger that presses the gasket.

[0015] The cylindrical case-encased drug dispenser 10 used in this embodiment comprises a puncture device 3, a prefilled syringe 2, a cylindrical case 4 that houses both such that the tip of the connecting needle portion 31b of the puncture device 3 faces the tip of the prefilled syringe 2, and a stopper 5.

[0016] As shown in FIGS. 4 and 5, the puncture device 3 includes a hollow tubular member 31 having a puncture needle portion 31a and a connecting needle portion 31b, a hub 32 mounted between the puncture needle portion 31a and the connecting needle portion 31b of the hollow tubular member 31, an elastic sleeve 33 having one end mounted on the hub 32, a closed rear end, and covering the connecting needle portion 31b, and a puncture needle portion cap 34 having a rear end mounted on the hub 32, a closed tip, and covering the puncture needle portion 31a.

[0017] Further, the tip opening of the puncture needle portion 31a is an opening having a blade surface, and the rear end opening of the connecting needle portion 31b is also an opening having a blade surface, so that it is a so-called double-ended needle. When the elastic sleeve 33 is pressed in the direction of the hub 32, it elastically deforms and can be penetrated by the connecting needle portion 31b, and the connecting needle portion 31b protrudes by penetrating the sleeve 33.

[0018] The prefilled syringe 2 includes an outer cylinder 21 having an outer surface protrusion 26 at the rear end, a sealing member 24 that seals the tip of the outer cylinder 21 and through which the connecting needle portion 31b of the puncturing device 3 can penetrate, and a gasket 22 that can slide in the outer cylinder 21 in a liquid-tight state.

[0019] In the cylindrical case-encased drug administration device 10, the cylindrical case 4 houses the puncturing device 3 so that it cannot move and the tip of the puncture needle portion 31a protrudes, and houses the prefilled syringe 2 so that it can move in the direction of the puncturing device 3 within the cylindrical case 4. Further, side openings 43a and 43b are provided at the rear end.

[0020] The cylindrical case-encased drug administration device 10 includes a biasing member 11 that abuts against the outer cylinder 21 and biases the prefilled syringe 2 in the direction of the connecting needle portion 31b, and a stopper 5 that is detachably inserted into the side openings 43a and 43b of the cylindrical case 4, abuts against the outer surface protrusion 26 of the outer cylinder 21, and restricts the movement of the prefilled syringe 2 in the direction of the puncturing device 3. After the stopper 5 is removed, the cylindrical case-encased drug administration device 10 moves the prefilled syringe 2 in the direction of the puncturing device 3 by the pressing of the biasing member 11, and the sealing member 24 of the prefilled syringe 2 is in a penetrated state by the connecting needle portion 31b.

[0021] In other words, after the stopper 5 is removed, the biasing member 11 presses the prefilled syringe so that the sealing member 24 of the prefilled syringe 2 is in a penetrated state by the connecting needle portion 31b of the puncturing device 3. The prefilled syringe 2 is composed of an outer cylinder 21, a sealing member (sealing cap) 24 attached to the nozzle portion of the outer cylinder 21, a gasket 22 slidably housed inside the outer cylinder, and a plunger 23 attached to the gasket 22.

[0022] The outer cylinder 21 is a cylindrical body formed of a transparent or translucent material, preferably a material with low permeability to oxygen, water vapor, and particularly hydrogen peroxide gas. The outer cylinder 21 includes an outer cylinder main body portion and a nozzle portion 21a provided on the tip side of the outer cylinder main body portion. The nozzle portion 21a is located at the tip of the outer cylinder 21, has an opening at the tip for discharging the chemical solution or the like inside the outer cylinder, and is formed to have a reduced diameter in a tapered shape toward the tip. The nozzle portion 21a includes a sealing member mounting portion.

[0023] As shown in FIGS. 4 and 5, the sealing member 24 includes a cylindrical sealing member main body and a sealing member 27 housed inside the sealing member main body. The sealing member 24 includes a nozzle portion housing portion and an outer cylinder mounting portion 24a on the sealing member side. In this embodiment, the cylindrical sealing member main body is a cylindrical member with openings at one end side and the other end side, and has an opening portion 24b that expands in a tapered shape for mounting the connection needle portion 31b on the tip side. And the sealing member 27 is housed behind this opening portion 24b. One end of the sealing cap is closed by the sealing member 27.

[0024] The sealing member 27 is for liquid-tightly sealing the tip opening of the nozzle portion. When the tip opening of the nozzle portion abuts against the sealing member 27, the nozzle portion 21a is liquid-tightly sealed. Further, the sealing member 27 is formed of an elastic material that can be pierced by the connection needle portion 31b. Also, the sealing member 27 is formed of an elastic material and preferably has low hydrogen peroxide permeability.

[0025] As shown in FIG. 5, the gasket 22 includes a main body portion extending with substantially the same outer diameter and a plurality of annular ribs provided on this main body portion, and these ribs are in liquid-tight contact with the inner surface of the outer cylinder 21. As the forming material of the gasket 22, elastic rubber (for example, butyl rubber, latex rubber, silicone rubber, etc.), synthetic resin (for example, styrene-based elastomers such as SBS elastomer and SEBS elastomer, olefin-based elastomers such as ethylene-α-olefin copolymer elastomer, etc.) can be used. Further, the gasket 22 is preferably hardly permeable to hydrogen peroxide.

[0026] In the cylindrical case encapsulated drug injector 10 of this embodiment, the gasket 22 includes a plunger 23 whose rear part protrudes from the cylindrical case. The plunger 23 has a protruding part that protrudes cylindrically at the tip, and a male thread is formed on the outer surface of the protruding part. Further, the plunger 23 includes a shaft part extending in the axial direction with a cross-sectional cross shape, a disk part for pressing provided at the rear end part, and a rib provided in the middle of the shaft part.

[0027] The prefilled syringe 2 is filled with a drug (drug solution) 25. As the drug (drug solution) 25, an adrenaline injection preparation (vasoconstrictor) which is an anti-anaphylactic shock drug, an antiarrhythmic agent (for example, lidocaine), an anticholinergic agent (for example, atropine), an antispasmodic agent (for example, diazepam), a rocuronium bromide injection preparation, nitroglycerin, physiological saline and other emergency administration drugs, cyclosporine, benzodiazepine drugs, high-concentration sodium chloride injection, vitamin agents, minerals, drug solutions such as antibiotics, vitamin agents (comprehensive vitamin agents), various amino acids, antithrombotic agents such as heparin, insulin, antitumor agents, analgesics, cardiac stimulants, intravenous anesthetics, antiparkinson agents, ulcer treatment agents, adrenal cortical hormone agents, antiarrhythmic agents, corrective electrolytes, antiviral agents, immunostimulants, etc. can be considered.

[0028] As shown in FIGS. 3 to 6, the cylindrical case 4 is formed by a connecting body of a first case member 41 and a second case member 42, and has an elliptical cylindrical shape. The first case member 41 and the second case member 42 are semi-cylindrical members, and the inner peripheral edge serving as the contact portion is provided with a plurality of protrusions 49a and recesses 49b. As shown in FIG. 3, when the two are engaged, they form a connecting body.

[0029] The cylindrical case 4 is an elliptical cylinder that can accommodate the outer surface protrusion 26 of the prefilled syringe 2. The cylindrical case 4 has a prefilled syringe storage portion inside, and a hollow tubular member mounting portion 47 that protrudes inward from the inner surface. The guide portions 14a and 14b are in contact with the outer surface of the outer cylinder 21 of the prefilled syringe 2 and guide the sliding of the prefilled syringe 2. As the guide portions 14a and 14b, they are formed to protrude inward from the inner surface of the cylindrical case 4 at a position corresponding to the cylindrical main body of the stored prefilled syringe 2, and the inner shape is preferably slightly larger than the outer shape of the prefilled syringe 2.

[0030] The cylindrical case 4 is provided with an engaging portion with a stopper 5 described later. In this embodiment, the engaging portion of the cylindrical case with the stopper 5 is formed by two side openings (through openings) 43a and 43b formed to face each other. Note that the engaging portion with the stopper 5 may be provided with only one side opening, and a recess that can engage with the stopper (one end portion) is provided at a position facing it. Also, only one side opening may be provided, and an inner surface rib that can engage with the stopper (one end portion) and does not hinder the movement of the prefilled syringe may be provided on the inner surface of the cylindrical case at a position facing it and slightly on the tip side.

[0031] In a state where the prefilled syringe is locked by the stopper 5, the cylindrical case 4 includes a first storage portion 45 that houses the outer surface protrusion 26 of the prefilled syringe, the biasing member 11 in a compressed state, and the stopper 5. After the stopper 5 is removed and the prefilled syringe moves forward, the cylindrical case 4 includes a second storage portion 46 that houses the outer surface protrusion 26 of the prefilled syringe. Further, the tip side portion of the extended biasing member is housed in the second storage portion.

[0032] Further, after the stopper 5 is detached, the cylindrical case 4 has an abutting portion 46a that abuts against the tip surface of the outer surface protrusion 26 of the prefilled syringe 2 and restricts movement after the sealing member 24 of the prefilled syringe 2 is pierced by the connection needle portion 31b of the puncturing device 3. In this embodiment, the movement restricting abutting portion 46a is formed by the tip surface of the second storage portion 46.

[0033] Also, as shown in FIGS. 4 and 5, the cylindrical case 4 is provided with slit-shaped side openings (through openings) 43a and 43b provided at the rear end portion. The stopper 5 is inserted so as to penetrate through the side openings (through openings) 43a and 43b. The stopper 5 is removable. The rear surface of the stopper 5 abuts against the front surface of the outer surface protrusion 26 of the prefilled syringe 2 and restricts the forward movement of the prefilled syringe 2.

[0034] The cylindrical case 4 preferably has transparency or translucency that allows the housed puncturing device 3 and prefilled syringe 2 to be visible. Also, as shown in FIG. 5, the biasing member 11 housed in the first storage portion 45 of the cylindrical case 4 is in a compressed state between the rear end portion 48 of the cylindrical case 4 and the rear surface of the outer surface protrusion 26 of the prefilled syringe 2. In this embodiment, the biasing member 11 is a coil spring, and the plunger 23 of the prefilled syringe 2 passes through the biasing member 11. Further, in this embodiment, the rear end portion of the biasing member 11 is housed and fixed in an annular recess provided at the rear end portion of the cylindrical case 4.

[0035] As shown in FIGS. 4 to 6, the stopper 5 includes a base portion 54, two extending portions 52 and 53 that extend forward from the base portion 54 and face each other, a notch portion 55 for penetrating the main body portion of the outer cylinder 21 formed between the two extending portions 52 and 53 and the base portion 54, and a gripping portion 51 provided behind the base portion 54.

[0036] The cylindrical case 4 is provided with engaging portions with the two extending portions 52 and 53. When the stopper 5 is attached to the cylindrical case 4, the base portion 54 engages with one side opening 43b of the cylindrical case 4, and the tip portions of the two extending portions 52 and 53 engage with the engaging portion of the cylindrical case 4. Further, the proximal end portion of the base portion 54 protrudes from the side opening of the cylindrical case.

[0037] Specifically, the gripping portion 51 is a bulging portion. In this embodiment, the stopper 5 has a U-shaped form, penetrates the cylindrical case 4, sandwiches the outer cylinder 21 of the prefilled syringe 2 inside the U shape, and further inserts through the two side openings, thereby suppressing the axial movement of the prefilled syringe.

[0038] As shown in FIGS. 3 and 6, when the stopper 5 is attached to the cylindrical case 4, the gripping portion 51 protrudes from one opening 43b of the side opening (through opening) of the cylindrical case 4, and the tip portions of the two extending portions 52 and 53 protrude from one opening 43a of the side opening (through opening). Further, as shown in FIGS. 5 and 6, the lower surfaces of the base portion 54 of the stopper 5 and the two extending portions 52 and 53 abut against the upper surface of the outer surface protruding portion 26 of the prefilled syringe 2, the upper surface of the base portion 54 of the stopper 5 abuts against the upper edge portion of one opening 43b of the cylindrical case 4, and the upper surfaces of the two extending portions 52 and 53 abut against the upper edge portion of the other opening 43a of the cylindrical case 4. Thereby, the stopper 5 is sandwiched between the upper edge portions of the openings 43a and 43b of the cylindrical case 4 and the outer surface protruding portion 26 of the prefilled syringe 2 within the side opening (through opening) of the cylindrical case 4 and is not easily detached.

[0039] In the cylindrical case encapsulated drug administration device 10 of the present invention, as shown in FIG. 7, when the stopper 5 is detached (removed) from the cylindrical case encapsulated drug administration device 10, the locking state of the outer surface protruding portion 26 of the prefilled syringe 2 by the stopper 5 is released. Thereby, the prefilled syringe 2 is pressed by the biasing member 11 so that the outer surface protruding portion 26 is pressed from the rear and moves forward (in the direction of the puncturing device 3).

[0040] The prefilled syringe 2 (specifically, the sealing member 24) of this embodiment and the puncturing device 3 are housed in the cylindrical case 4 such that their central axes are substantially the same. Further, even when the prefilled syringe 2 moves due to the pressing of the biasing member 11, the central axis of the prefilled syringe 2 (specifically, the sealing member 24) and the central axis of the puncturing device 3 slide forward (in the direction of the puncturing device 3) while maintaining substantially the same state by means of the guide portions 14a, 14b, etc.

[0041] The biasing force of the biasing member 11 on the prefilled syringe 2 is at least such that, after the separation of the stopper 5, the sealing member 27 of the sealing member 24 of the prefilled syringe 2 presses the prefilled syringe so that it is pierced by the connection needle portion 31b of the puncturing device 3. Also, the biasing force of the biasing member 11 on the prefilled syringe 2 allows the prefilled syringe 2 to move forward (in the direction of the puncturing device 3) until the outer surface protrusion 26 of the prefilled syringe 2 abuts against the movement restricting abutting portion 46a of the second housing portion 46 of the cylindrical case 4, and further presses the prefilled syringe 2 after the outer surface protrusion 26 of the prefilled syringe 2 abuts against the movement restricting abutting portion 46a of the second housing portion 46 of the cylindrical case 4.

[0042] Then, as shown in FIG. 7, the sealing member 27 of the sealing member 24 of the prefilled syringe 2 that has moved forward is pierced by the connection needle portion 31b of the puncturing device 3. Thereby, the inside of the hollow tubular member 31 of the puncturing device 3 communicates with the inside of the prefilled syringe 2. In the communicating state, the rear side portion including the pressing operation portion 23a of the plunger 23 protrudes from the cylindrical case 4 by a predetermined length.

[0043] Then, by removing the cap 34 of the puncturing device 3, the preparation for drug administration is completed. Also, the plunger 23 can be pressed until the pressing operation portion 23a abuts against the rear end surface of the cylindrical case 4, and the drug can be discharged by the amount of movement of the plunger 23.

[0044] And the method for manufacturing the packaged drug administration device of the present invention includes a step of preparing the tubular case-encased drug administration device 10, a step of adding hydrogen peroxide to a portion inside the tubular case 4 of the tubular case-encased drug administration device 10, a step of storing the tubular case-encased drug administration device 10 in the package 7, a step of sealing the package 7 containing the tubular case-encased drug administration device 10, and a post-packaging sealing storage step of sterilizing the tubular case-encased drug administration device 10 by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package 7 is sealed.

[0045] In the step of preparing the tubular case-encased drug administration device 10, the above-described tubular case-encased drug administration device 10 is prepared. Specifically, as shown in FIG. 4, a puncture device 3, a prefilled syringe 2 filled aseptically, a tubular case 4 that houses both such that the tip of the connecting needle portion 31b of the puncture device 3 faces the tip of the prefilled syringe 2, a stopper 5, and a biasing member 11 are prepared and assembled in the state shown in FIGS. 3 and 5. This tubular case-encased drug administration device 10 can administer a drug in a state of being encased in the tubular case 4 after connecting the prefilled syringe 2 and the puncture device 3 during use.

[0046] Next, a step of adding hydrogen peroxide to a portion inside the tubular case 4 of the tubular case-encased drug administration device 10 is performed. The tubular case-encased drug administration device 10 is assumed to be used, for example, for emergency adrenaline injection when anaphylactic shock occurs due to a drug or the like in an operating room or the like. For this reason, it is necessary to maintain the sterilization of the entire tubular case-encased drug administration device 10 until the package is opened.

[0047] In the cylindrical case-encased drug administration device 10, the puncturing device 3 is of a type equipped with a so-called double-ended needle. The puncturing needle portion 31a is covered by a cap 34, and the connecting needle portion 31b is covered by an elastic sleeve 33. As a result of the applicant's intensive studies, it was confirmed by a test in which a biological indicator was installed inside the cap and sterilization was carried out in a hydrogen peroxide atmosphere that it is not easy to reliably sterilize the inner surfaces of the puncturing needle portion 31a and the cap 34. Although the cap 34 is fitted to the hub, although there is a gap between the two, it was found that this is due to the small gap and insufficient flow of the sterilizing gas.

[0048] In addition, the cylindrical case-encased drug administration device 10 has a large number of parts and also requires an assembly operation, and it is difficult to assemble and package it aseptically. Also, since the prefilled syringe is filled with a drug, it is also difficult to perform electron beam sterilization or radiation sterilization after assembly and packaging.

[0049] In view of the above circumstances, it was found that the addition of hydrogen peroxide (hydrogen peroxide solution) in the step of adding hydrogen peroxide is preferably performed by adding hydrogen peroxide (hydrogen peroxide solution) inside the cylindrical case 4 of the cylindrical case-encased drug administration device 10, particularly between the puncturing needle portion cap 34 (specifically, the rear end portion of the puncturing needle portion cap 34) and the hub 32 (P) (for example, by dropping). Furthermore, the addition of hydrogen peroxide (hydrogen peroxide solution) may be performed not only at the above location but also at another site. In that case, it is preferably performed on the plunger, for example, on the side surface of the shaft portion of the plunger. The addition of hydrogen peroxide (hydrogen peroxide solution) to the plunger is preferably at a site located inside the cylindrical case 4, but it may also be performed at a site exposed from the cylindrical case 4. Particularly preferably, it is preferably performed on the side surface of the shaft portion of the plunger located inside the cylindrical case 4.

[0050] This step of adding hydrogen peroxide is preferably performed by adding hydrogen peroxide (hydrogen peroxide solution) between the puncturing needle portion cap 34 and the hub 32 (P) inside the cylindrical case-encased drug administration device 10 after the preparation step of the above-described cylindrical case-encased drug administration device 10. Incidentally, the step of adding this hydrogen peroxide may be carried out in parallel with the above-described preparation step of the cylindrical case-encased drug administration device 10. For example, it may be carried out by mounting the prefilled syringe 2 in the cylindrical case 4 and mounting the puncture device 3 in which hydrogen peroxide has been added between the puncture needle part cap 34 and the hub 32 (P) into the cylindrical case 4. Further, when adding hydrogen peroxide to the plunger 23 of the prefilled syringe 2, it may be carried out before mounting the prefilled syringe 2 into the cylindrical case 4, after mounting, or even after assembling the cylindrical case-encased drug administration device 10.

[0051] Next, a step of storing the cylindrical case-encased drug administration device 10 in the package 7 is performed. This step is performed by disposing the cylindrical case-encased drug administration device 10 in the package 7. Incidentally, either this storage step or the above-described step of adding hydrogen peroxide may be performed first. When performing the storage step first, after disposing the cylindrical case-encased drug administration device 10 in the package 7, before sealing the package, the above-described step of adding hydrogen peroxide is performed. Also, when performing the storage step later, it is performed by disposing the cylindrical case-encased drug administration device 10 to which the above-described hydrogen peroxide has been added in the package 7.

[0052] As the package 7, one that is hardly permeable to hydrogen peroxide may be used, but it is preferable to prepare a hydrogen peroxide permeation amount-adjusting functional package that allows and regulates permeation due to the diffusion of hydrogen peroxide.

[0053] In the embodiments shown in FIGS. 1 and 2, the package 7 includes a container body 71 that stores the cylindrical case-encased drug administration device 10 and a sealing member 75 that sealably seals the opening of the container body 71. Also, as the package, a sealable and openable bag-shaped package may be used. Specifically, examples of the package include a blister packaging container, a soft bag-shaped packaging container, etc. Incidentally, as the form of the package, any form may be used as long as it can store the cylindrical case-encased drug administration device 10 inside and is sealable and openable.

[0054] In the embodiments shown in FIGS. 1 and 2, the package 7 includes a container body 71 having a storage recess 73 for storing the cylindrical case-encapsulated drug dispenser 10, and a peelable sealing film (sealing member) 75 for sealing the recess opening. The package 7 of the embodiments shown in FIGS. 1 and 2 is a blister package. Specifically, the container body 71 of the present package 7 includes a storage recess 73 and a flange-forming portion 74 formed around the storage recess 73, and the sealing film 75 is detachably attached to the flange-forming portion 74 of the container body 71. Further, the storage recess 73 of the container body 71 is shaped such that the cylindrical case-encapsulated drug dispenser 10 does not move easily within the container body.

[0055] And in the package 7 of this embodiment, a hydrogen peroxide permeation amount-adjusting functional package is used. The hydrogen peroxide permeation amount-adjusting functional package refers to a package that allows and regulates the permeation due to the diffusion of hydrogen peroxide. Specifically, it refers to a package that allows the permeation due to the diffusion of hydrogen peroxide gas but suppresses the permeation in a short time.

[0056] The hydrogen peroxide permeation function of the package can be evaluated by measuring the evaporation property of an aqueous solution (hydrogen peroxide solution) containing hydrogen peroxide. When hydrogen peroxide solution is enclosed in the package film and left in an environment at room temperature or higher, water and hydrogen peroxide gradually vaporize in the package film and fill the package film. In parallel with the vaporization and filling of hydrogen peroxide, hydrogen peroxide penetrates and then permeates into the package film body, and the degree can be grasped by the decrease amount of hydrogen peroxide water droplets in the package. That is, in a porous film or the like that allows hydrogen peroxide to pass through easily, the hydrogen peroxide water droplets decrease and disappear in a short time, but in a package film that allows and regulates the permeation due to the diffusion of hydrogen peroxide, it takes a certain time for the hydrogen peroxide water droplets to decrease and disappear.

[0057] As a hydrogen peroxide permeation amount adjustment function, the package 7 is added with hydrogen peroxide water adjusted to 300 mg / L as the hydrogen peroxide amount per unit volume of the package. After enclosing the container, it is preferable that the period during which hydrogen peroxide water droplets disappear is in the range of 3 hours to 72 hours under the conditions of 55°C and 25% RH. In particular, it preferably has a hydrogen peroxide water droplet disappearance period (evaporation property) of 6 hours to 24 hours. Here, as the package, a container with a content volume of 0.2 mL per 1 cm 2 of the surface area of the package is assumed.

[0058] Further, as the package 7, any combination may be used as long as it has a hydrogen peroxide permeation amount adjustment function as a whole. That is, a combination in which only the container body 71 has a hydrogen peroxide permeation amount adjustment function and the film 75 is hydrogen peroxide impermeable, a combination in which only the film 75 has a hydrogen peroxide permeation amount adjustment function and the container body 71 is hydrogen peroxide impermeable, or a combination in which both the container body 71 and the film 75 have a hydrogen peroxide permeation amount adjustment function may be used.

[0059] Furthermore, as the material of the package, it is preferably one that is not easily deteriorated by hydrogen peroxide. Also, as the material of the package, it is preferably waterproof.

[0060] And as the material of the container body 71, it is preferably one having a certain degree of strength and hardness. Also, the container body 71 is preferably made of a material having low hydrogen peroxide gas permeability. As the material of the container body 71, for example, polyolefins such as polypropylene and polyethylene, vinyl chloride resin, polyester resin, polystyrene / polypropylene resin, polyethylene / ionomer (for example, ethylene-based, styrene-based, fluorine-based) / polyethylene, etc. can be preferably used. In particular, from the viewpoint of the hydrogen peroxide permeation amount adjustment function, low-density polyethylene / ionomer / low-density polyethylene is preferable.

[0061] Furthermore, among these, it is preferably made of a material having transparency. Also, for example, when the drug stored in the syringe is susceptible to the influence of light, various pigments and ultraviolet absorbers may be contained in the material forming the container body. Further, it is preferable to provide a layer having a thickness of about 30 to 70 μm made of a resin having low oxygen permeability and low water vapor permeability (for example, polyvinylidene chloride, ethylene-vinyl alcohol copolymer, polyethylene terephthalate) on the resin. Also, it may be composed of three layers of polyethylene terephthalate / ethylene-vinyl alcohol copolymer / polypropylene or made of polypropylene alone.

[0062] Specifically, the sealing film 75 preferably has a film (base film) with low hydrogen peroxide gas permeability or substantially non-permeable to hydrogen peroxide gas, and an adhesive resin layer fixed to at least the outer peripheral portion of the lower surface of this film. Further, it is more preferable to have a surface protective layer provided on the upper surface of the film. As the base film, metal foils such as aluminum, silver, and gold, or metal vapor deposition films with aluminum, silver, gold, etc. vapor-deposited on the surface, inorganic vapor deposition films with SiO X etc. vapor-deposited on the surface, gas barrier resin films, for example, films such as polyvinylidene chloride, polyvinylidene chloride-polyvinyl chloride, polyvinylidene chloride-acrylic acid ester copolymer, and high-density polyethylene can be preferably used.

[0063] The adhesive resin layer is for heat-sealing the base film and the container body 71 in a peelable manner, and various easy-peeling mechanisms as follows can be utilized. For example, when polypropylene is used for the heat-sealing surface of the container body 71, as the adhesive resin layer, olefin resins such as ethylene-vinyl acetate resin, ethylene-acrylic acid resin, and a blend of polypropylene and polyethylene, or two-component curable urethane dry laminate adhesives can be preferably used.

[0064] In addition, when polyvinyl chloride is used as the container body 71, as the adhesive resin layer, olefin resins such as ethylene-vinyl acetate resin and ethylene-acrylic acid resin, polystyrene blended with styrene-butadiene block copolymer, vinyl chloride-vinyl acetate copolymer, and two-component curable urethane-based dry laminate adhesives can be preferably used. Further, when polyester is used as the container body 71, olefin resins such as ethylene-vinyl acetate resin and ethylene-acrylic acid resin, copolyesters, and two-component curable urethane-based dry laminate adhesives can be preferably used.

[0065] As the surface protection layer, it is preferable to form it by coating a synthetic resin, for example, a polyester such as PET, polypropylene, polyethylene, nylon, epoxy resin, or polyamide resin, or by laminating the above synthetic resin films, paper, etc. And this surface protection layer can also be used as a printing layer for recording necessary items such as the name, filling amount, and concentration of the drug filled in the prefilled syringe of the cylindrical case-encapsulated drug dispenser 10. Note that a light-shielding material such as white ink may be interposed between the surface protection layer and the gas barrier film to form a light-shielding film.

[0066] Specific examples of the sealing film 75 include those composed of four layers of polyethylene terephthalate / polyethylene / polyethylene terephthalate / adhesive resin, polyethylene terephthalate / ethylene-vinyl alcohol copolymer / stretched nylon / adhesive resin, and those composed of three layers of polyethylene terephthalate / stretched nylon / adhesive resin.

[0067] In addition, the hydrogen peroxide solution added in the production method of the present invention is preferably 1.0 to 6.0 w / v%, particularly preferably 2.0 to 4.0 w / v%. The addition amount (dropping amount), in terms of the hydrogen peroxide amount per unit volume of the package, is 2 mg / L to 300 mg / L, preferably 15 to 100 mg / L. Specifically, for a package with a volume of 20 mL to 45 mL, it is preferable to add 0.01 mL to 0.10 mL of a 1.0 to 6.0 w / v% hydrogen peroxide solution. Preferably, for a package with a volume of 20 mL to 45 mL, it is preferable to add 0.03 mL to 0.06 mL of a 2.0 to 4.0 w / v% hydrogen peroxide solution. In addition, the hydrogen peroxide solution added in the production method of the present invention may be 1.0 to 30.0 w / v%. When the hydrogen peroxide discharge period (hereinafter referred to as the "hydrogen peroxide discharge period") for allowing hydrogen peroxide to flow out from inside the package by utilizing the diffusion of hydrogen peroxide in the package can be made long [specifically, two and a half weeks (420 hours) or more, more specifically, three weeks (504 hours) or more], the hydrogen peroxide solution is preferably 3.0 to 30.0 w / v%, particularly preferably 15 to 30 w / v%. When the hydrogen peroxide discharge period cannot be made long [specifically, less than two and a half weeks, more specifically, two weeks (336 hours) or less], as described above, the hydrogen peroxide solution is preferably 1.0 to 6.0 w / v%, particularly preferably 2.0 to 4.0 w / v%. The addition amount (dropping amount) of the hydrogen peroxide solution, in terms of the hydrogen peroxide amount per unit volume of the package, may be 2 mg / L to 750 mg / L. When the hydrogen peroxide discharge period can be made long [specifically, two and a half weeks (420 hours) or more, more specifically, three weeks (504 hours) or more], the addition amount (dropping amount) of the hydrogen peroxide solution, in terms of the hydrogen peroxide amount per unit volume of the package, is preferably 6 to 750 mg / L, particularly preferably 100 to 700 mg / L. When the hydrogen peroxide discharge period cannot be made long [specifically, less than two and a half weeks, more specifically, two weeks (336 hours) or less], the addition amount (dropping amount) of the hydrogen peroxide solution, in terms of the hydrogen peroxide amount per unit volume of the package, is preferably 2 to 300 mg / L, particularly preferably 15 to 100 mg / L.

[0068] Then, the addition of hydrogen peroxide may be performed by sealing the package 7 containing the cylindrical case-encased drug dispenser 10 except for a part thereof, and adding hydrogen peroxide solution from the unsealed portion using a nozzle or the like.

[0069] Next, a step of sealing the package 7 containing the cylindrical case-encased drug dispenser 10 is performed. This step is performed by sealing the unsealed portion of the package 7 containing the cylindrical case-encased drug dispenser 10.

[0070] Specifically, as shown in FIGS. 1 and 2, it is performed by sealing the concave opening of the container body 71 of the package 7 containing the cylindrical case-encased drug dispenser 10 to which hydrogen peroxide has been added with a sealing film 75. The sealing is performed by sealing the sealing film 75 to the flange forming portion 74 of the container body 71 by heat fusion, high-frequency fusion, or the like.

[0071] Next, in a state where the package 7 is sealed, a post-package-sealing storage step of sterilizing the cylindrical case-encased drug dispenser 10 by the hydrogen peroxide atmosphere formed by the added hydrogen peroxide is performed.

[0072] And in the post-package-sealing storage step, it is preferable to perform sterilization of the cylindrical case-encased drug dispenser by the hydrogen peroxide atmosphere and hydrogen peroxide discharge to allow hydrogen peroxide to flow out of the package by utilizing the diffusion of hydrogen peroxide in the package.

[0073] In the post-package-sealing storage step, the sealed one containing the cylindrical case-encased drug dispenser 10 inside is placed in the package 7 under conditions where the hydrogen peroxide solution gasifies. Specifically, it is performed by placing it in a temperature environment where the hydrogen peroxide solution gasifies. Usually, it can be performed by maintaining at room temperature, but in severe cold, it is maintained in a heated state. Then, as the gasification of the hydrogen peroxide solution progresses, the inside of the package reaches a hydrogen peroxide atmosphere concentration capable of sterilizing the contact portion.

[0074] Note that the package 7 has low or poor permeability to hydrogen peroxide, and although some permeation occurs due to the diffusion of hydrogen peroxide from inside the package, since the gasification rate is faster, the inside of the package reaches a hydrogen peroxide atmosphere concentration at which the cylindrical case-encapsulated drug dispenser 10 can be sterilized. Furthermore, the concentration increases and reaches the maximum concentration when all of the hydrogen peroxide has gasified or slightly before that, and sterilization proceeds.

[0075] In this example, since a package having a hydrogen peroxide permeation amount adjustment function is used, after reaching the maximum concentration, hydrogen peroxide gradually flows out from the package according to the hydrogen peroxide permeation ability of the package, but the outflow rate is slow. Then, due to the outflow of hydrogen peroxide, eventually, the inside of the package becomes a lower concentration than the hydrogen peroxide atmosphere concentration at which the cylindrical case-encapsulated drug dispenser 10 can be sterilized. The period from when the inside of the package reaches the hydrogen peroxide atmosphere concentration at which the outer surface can be sterilized to when it becomes a lower concentration than the hydrogen peroxide atmosphere concentration at which the outer surface can be sterilized is the high-concentration atmosphere period and is the effective sterilization period of the cylindrical case-encapsulated drug dispenser 10. As the high-concentration atmosphere period, about immediately after hydrogen peroxide encapsulation to about 14 days is preferable, and in particular, about immediately after hydrogen peroxide encapsulation to about 7 days is more preferable.

[0076] Also, as the minimum concentration during the high-concentration atmosphere period, 0.05 mg / L to 2.0 mg / L is preferable, and in particular, 0.5 mg / L to 1.0 mg / L is more preferable. Also, as the maximum concentration during the high-concentration atmosphere period, 10 mg / L to 300 mg / L is preferable, and in particular, 50 mg / L to 100 mg / L is more preferable. Also, as the minimum concentration during the high-concentration atmosphere period, 0.05 mg / L to 10 mg / L is preferable. And when the above-mentioned hydrogen peroxide discharge period can be long [specifically, two and a half weeks (420 hours) or more, more specifically, three weeks (504 hours) or more], as the minimum concentration during the high-concentration atmosphere period, 0.15 mg / L to 10 mg / L is preferable, and particularly, 2.5 mg / L to 5.0 mg / L is preferable. Also, when the hydrogen peroxide discharge period cannot be long [specifically, less than two and a half weeks, more specifically, two weeks (336 hours) or less], as the minimum concentration during the high-concentration atmosphere period, 0.05 mg / L to 2.0 mg / L is preferable, and particularly, 0.5 mg / L to 1.0 mg / L is preferable. Also, as the maximum concentration during the high-concentration atmosphere period, 10 mg / L to 750 mg / L is preferable. And when the above-mentioned hydrogen peroxide discharge period can be long [specifically, two and a half weeks (420 hours) or more, more specifically, three weeks (504 hours) or more], as the maximum concentration during the high-concentration atmosphere period, 30 mg / L to 750 mg / L is preferable, and particularly, 375 mg / L to 700 mg / L is preferable. Also, when the hydrogen peroxide discharge period cannot be long [specifically, less than two and a half weeks, more specifically, two weeks (336 hours) or less], as the maximum concentration during the high-concentration atmosphere period, 10 mg / L to 300 mg / L is preferable, and particularly, 50 mg / L to 100 mg / L is preferable.

[0077] Also, during this high-concentration atmosphere period, it is preferable to perform actions such as turning the sealed package upside down and rocking it to change the atmosphere inside the package. By doing so, the contact of hydrogen peroxide with the cylindrical case-encapsulated drug dispenser 10 becomes more reliable. Specifically, this period is preferably carried out at 1 to 30°C. Also, the storage is preferably maintained at 10 to 80% RH, particularly, 20 to 60% RH.

[0078] Also, during this period, it is preferable to store the packaging container at an angle such that hydrogen peroxide fills the entire interior. In particular, it is preferable to store the cylindrical case-encased drug dispenser 10 horizontally. By storing it in such an orientation, hydrogen peroxide gas will spread throughout the interior of the package, ensuring that the interior of the package and the cylindrical case-encased drug dispenser 10 are sterilized. Note that the prefilled syringe may be stored vertically. Also, during this period, it may be heated. The heating is preferably at 30 to 100°C, particularly preferably at 40 to 80°C. The heating time is preferably 10 to 120 minutes, particularly preferably 20 to 60 minutes.

[0079] And even after the interior of the package has reached a concentration lower than the hydrogen peroxide atmosphere concentration at which the cylindrical case-encased drug dispenser 10 can be sterilized, the outflow due to the diffusion of hydrogen peroxide from the package continues, and eventually, almost all of the hydrogen peroxide flows out from within the package 7. The period from when the interior of the package has reached a concentration lower than the hydrogen peroxide atmosphere concentration at which the cylindrical case-encased drug dispenser 10 can be sterilized until the hydrogen peroxide concentration within the package reaches the allowable residual concentration is the hydrogen peroxide discharge period. This hydrogen peroxide discharge period varies depending on the hydrogen peroxide permeation rate of the package and the temperature and humidity during storage, but is preferably about 8 hours to 28 days. In particular, it is preferably about 1 day to 7 days. Also, the allowable residual concentration of the above hydrogen peroxide concentration is preferably 0.05 ppm or less. Also, during this hydrogen peroxide discharge period, the packaged cylindrical case-encased drug dispenser 10 may be transported to the place of use.

[0080] Also, when the cylindrical case-encased drug dispenser uses a drug or the like that is easily affected by oxygen, an oxygen absorber may be stored inside the package. This absorbs the oxygen within the sealed package and prevents the oxidation of the drug. When hydrogen peroxide is enclosed in a packaging material containing an oxygen absorber, decomposition of the hydrogen peroxide by the oxygen absorber occurs, so it is desirable to have a larger amount of hydrogen peroxide than when no oxygen absorber is used. Also, the oxygen absorber can decompose the enclosed hydrogen peroxide early and prevent the residual of hydrogen peroxide.

[0081] In addition, as the cylindrical case-encased drug administration device used in the present invention, a cylindrical case-encased drug administration device 100 as shown in FIGS. 8 and 9 may be used. This cylindrical case-encased drug administration device 100 includes a prefilled syringe having an outer cylinder 70 with a puncture needle, a seal cap (puncture needle cap) 80 that seals the tip of the puncture needle 60 of the outer cylinder 70, a slidable gasket 22 housed inside the outer cylinder, and a drug 25 filled inside the outer cylinder 70, and an autoinjector mechanism housed inside the cylindrical case and having a biasing member for pressing the gasket and to which the prefilled syringe is attached.

[0082] The cylindrical case-encased drug administration device 100 of this embodiment includes an autoinjector and the above-described prefilled syringe attached to the autoinjector. The autoinjector of this cylindrical case-encased drug administration device 100 includes a cylindrical case 106, a gasket pressing means 102 housed inside the cylindrical case 106, a protector 103 for housing the prefilled syringe, and a regulating means 107 for regulating the movement of the gasket pressing means 102.

[0083] Furthermore, the cylindrical case-encased drug administration device 100 can take a state where the protector 103 houses the needle tip 61 of the puncture needle 60 (first state), a state where the cylindrical case 106 moves to the distal end side, the needle tip 61 protrudes from the protector 103, and the gasket 22 can move in the distal end direction by the gasket pressing means 102 (in other words, a state where preparation for liquid discharge is complete, second state), a state where the gasket 22 moves in the distal end direction by the pressing by the gasket pressing means 102 and the drug 25 is discharged from the puncture needle 60 (in other words, a liquid discharge state, third state), and a state where the cylindrical case 106 moves to the proximal end side and the needle tip 61 of the puncture needle 60 is housed inside the protector 103 (fourth state).

[0084] In addition, the cylindrical case-encased drug administration device 100 has a puncture needle cap 80 attached to the outer cylinder 70 with a puncture needle. The tip 61 of the puncture needle 60 is inserted into the puncture needle cap 80. Further, the cylindrical case-encased drug administration device 100 includes a tip cap 90 attached to the tip of the cylindrical case 106. The tip cap 90 holds the puncture needle cap 80. Therefore, when the tip cap 90 is detached from the cylindrical case 106, the puncture needle cap 80 is detached from the outer cylinder 70 with the puncture needle together with the tip cap 90.

[0085] In such a cylindrical case-encased drug administration device 100, the step of adding hydrogen peroxide to the part inside the cylindrical case 106 is preferably performed by preparing the cylindrical case-encased drug administration device 100 with only the tip cap 90 not attached, adding hydrogen peroxide inside the tip cap 90, and attaching the tip cap 90 to the cylindrical case 106. Further, it is preferable to add hydrogen peroxide to the outer surface of the cylindrical case-encased drug administration device 100 before and after its placement in the package.

[0086] And in the cylindrical case-encased drug administration device 100 of this embodiment, at the time of use, the puncture needle cap 80 is removed together with the tip cap 90. In that state (the puncture needle cap 80 is in a state of being detached from the tip cap 90 in FIG. 9), the entire puncture needle 60 including the tip 61 is housed in a protector 103 that constitutes the tip of the cylindrical case-encased drug administration device 100. The tip 61 is located inside the cylindrical tip 136 of the protector 103.

[0087] Then, by pressing the cylindrical tip 136 of the cylindrical case-encased drug administration device 100 against the administration target site and pushing the cylindrical case 106 in the direction of the administration target site with a force exceeding the biasing force of the second biasing member 105, the cylindrical case 106 moves toward the tip side. In other words, when viewed from the whole of the cylindrical case-encased drug administration device, relatively, the protector 103 retreats in the proximal direction. As a result, the cylindrical case 106, the first restricting member 171 fixed thereto, the gasket pressing means 102, and the prefilled syringe move forward, the puncture needle 60 protrudes, and the administration target site is punctured.

[0088] At the same time, the movement restriction of the gasket pressing member 124 by the second restricting member 172 is released, and the gasket pressing member 124 is pressed by the first biasing member 104 to move forward, pressing the gasket 4, and the drug 25 in the prefilled syringe passes through the puncture needle 60 and is injected into the living body. After the administration is completed, by releasing the pressing of the cylindrical case 106 against the puncture target site, the syringe is pushed back by the second biasing member 105 and moves to the proximal end side. As a result, the puncture needle 60 is again housed in the protector 103.

[0089] The manufacturing method of the packaged drug administration device of the present invention is a manufacturing method of a packaged drug administration device including an outer cylinder filled with a drug, a drug administration device having a puncture needle for drug administration, a cylindrical case that encloses and holds the drug administration device, and a package that houses the cylindrical case-enclosed drug administration device and is sealed. The manufacturing method of the packaged drug administration device of the present invention includes a step of preparing a cylindrical case-enclosed drug administration device, a step of adding hydrogen peroxide to a portion inside the cylindrical case of the cylindrical case-enclosed drug administration device, a step of housing the cylindrical case-enclosed drug administration device in a package, a step of sealing the package housing the cylindrical case-enclosed drug administration device, and a post-packaging sealing storage step for sterilizing the cylindrical case-enclosed drug administration device by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package is sealed. Therefore, in the post-packaging sealing storage step described above, hydrogen peroxide gas generated by the added hydrogen peroxide fills the inside of the package, and the inside and outer surfaces of the cylindrical case-enclosed drug administration device are sterilized with the filled hydrogen peroxide gas. And since it is already packaged, the sterilized state is maintained until the package is opened after the post-packaging sealing storage step, so it can be used in a highly microorganism-controlled atmosphere such as an operating room or an ICU.

Industrial Applicability

[0090] The manufacturing method of the packaged drug administration device of the present invention is as follows. What achieves the above object is as follows. (1) A method for manufacturing a packaged drug administration device, comprising a drug administration device having an outer cylinder filled with a drug and a puncture device for drug administration, a cylindrical case that encloses and holds the drug administration device, and a package that stores and seals the cylindrical case-encased drug administration device held by the cylindrical case, a step of preparing the cylindrical case-encased drug administration device, a step of adding hydrogen peroxide to a portion inside the cylindrical case of the cylindrical case-encased drug administration device, a step of storing the cylindrical case-encased drug administration device in the package, a step of sealing the package containing the cylindrical case-encased drug administration device, and a post-packaging sealing storage step of sterilizing the cylindrical case-encased drug administration device by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package is sealed.

[0091] This method for manufacturing a packaged drug administration device is a method for manufacturing a packaged drug administration device comprising a drug administration device having an outer cylinder filled with a drug and a puncture needle for drug administration, a cylindrical case that encloses and holds the drug administration device, and a package that stores and seals the cylindrical case-encased drug administration device held by the cylindrical case. This method for manufacturing a packaged drug administration device includes a step of preparing a cylindrical case-encased drug administration device, a step of adding hydrogen peroxide to a portion inside the cylindrical case of the cylindrical case-encased drug administration device, a step of storing the cylindrical case-encased drug administration device in a package, a step of sealing the package containing the cylindrical case-encased drug administration device, and a post-packaging sealing storage step of sterilizing the cylindrical case-encased drug administration device by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package is sealed. Therefore, in the above-described step of storing the sealed package, hydrogen peroxide gas generated by the added hydrogen peroxide fills the package, and the inside and outside surfaces of the cylindrical case-encased drug dispenser are sterilized with the filled hydrogen peroxide gas. And since it is already packaged, the sterilized state is maintained until the package is opened after the step of storing the sealed package, so it can be used in a highly microbe-controlled atmosphere such as an operating room or an ICU.

[0092] Also, the above-described embodiments may be as follows. (2) The method for manufacturing the packaged drug dispenser is the method for manufacturing the packaged drug dispenser according to (1) above, which includes a package preparation step of preparing, as the package, a hydrogen peroxide permeation amount-adjusting functional package that allows and regulates permeation by diffusion of hydrogen peroxide. (3) The step of storing the sealed package is the method for manufacturing the packaged drug dispenser according to (2) above, which includes sterilizing the cylindrical case-encased drug dispenser with the hydrogen peroxide atmosphere and discharging hydrogen peroxide by utilizing diffusion of the hydrogen peroxide in the package to cause the hydrogen peroxide to flow out of the package. (4) The hydrogen peroxide permeation amount-adjusting functional package is the method for manufacturing the packaged drug dispenser according to (2) or (3) above, in which 300 mg / L of hydrogen peroxide solution is dropped per unit internal volume of the package, and after the package is sealed, the period during which the dropped added hydrogen peroxide solution disappears is in the range of 3 hours to 72 hours under the conditions of 55°C and 25% RH. (5) The method for manufacturing the packaged drug dispenser according to any one of (1) to (4) above, wherein the cylindrical case-encased drug dispenser can administer a drug while being held and encased in the cylindrical case. (6) The cylindrical case-encased drug dispenser includes a prefilled syringe and a puncture device that is attached to the prefilled syringe during use. The puncture device includes a hollow tubular member having a puncture needle portion at one end and a connecting needle portion at the other end, a hub disposed between the puncture needle portion and the connecting needle portion of the hollow tubular member, and a puncture needle portion cap attached to the puncture needle portion side of the hub. The prefilled syringe includes the outer cylinder, a gasket slidably housed in the outer cylinder, a tip sealing member that seals the tip of the outer cylinder and through which the connecting needle portion can penetrate, the drug filled in the outer cylinder, and a plunger that presses the gasket. The method for manufacturing a packaged drug administration device according to any one of (1) to (5) above, wherein the addition of the hydrogen peroxide in the step of adding the hydrogen peroxide is performed by adding the hydrogen peroxide between the puncture needle portion cap and the hub. (7) The tubular case-encapsulated drug administration device includes a biasing member that abuts against the outer cylinder and biases the prefilled syringe in the direction of the connecting needle portion, and a stopper that is detachably inserted into the side opening of the tubular case, abuts against the outer surface protruding portion of the outer cylinder, and restricts the movement of the prefilled syringe in the direction of the hollow tubular member. After the detachment of the stopper, the prefilled syringe moves in the direction of the hollow tubular member by the pressing of the biasing member, and the sealing member of the prefilled syringe is brought into a penetrating state by the connecting needle portion. The method for manufacturing a packaged drug administration device according to (6) above. (8) The tubular case-encapsulated drug administration device includes a prefilled syringe having a puncture needle-equipped outer cylinder, a seal cap that seals the tip of the puncture needle of the outer cylinder, a slidable gasket housed in the outer cylinder, and a drug filled in the outer cylinder, and an auto-injector mechanism housed in the tubular case and having a biasing member for pressing the gasket, and the prefilled syringe is mounted thereon. The method for manufacturing a packaged drug administration device according to any one of (1) to (5) above.

Claims

1. A method for manufacturing a packaged drug administration device, comprising: a drug administration device including an outer cylinder filled with a drug and a puncture device for drug administration; a cylindrical case that encloses and holds the drug administration device; and a package that stores and seals the cylindrical case-enclosed drug administration device. The method includes: a step of preparing the cylindrical case-enclosed drug administration device; a step of adding hydrogen peroxide to a portion inside the cylindrical case of the cylindrical case-enclosed drug administration device; a step of storing the cylindrical case-enclosed drug administration device in the package; a step of sealing the package storing the cylindrical case-enclosed drug administration device; and a post-sealing storage step of sterilizing the cylindrical case-enclosed drug administration device by a hydrogen peroxide atmosphere formed by the added hydrogen peroxide in a state where the package is sealed.

2. The method for manufacturing a packaged drug administration device according to claim 1, further comprising a package preparation step of preparing, as the package, a hydrogen peroxide permeation amount-adjusting functional package that allows and regulates permeation by diffusion of hydrogen peroxide.

3. The post-sealing storage step according to claim 2 includes sterilizing the cylindrical case-enclosed drug administration device by the hydrogen peroxide atmosphere and discharging hydrogen peroxide from inside the package by utilizing diffusion of the hydrogen peroxide in the package.

4. For the hydrogen peroxide permeation amount-adjusting functional package, when 300 mg / L of hydrogen peroxide solution is dropped per unit internal volume of the package, and after the package is sealed, the period during which the dropped added hydrogen peroxide solution disappears is in the range of 3 hours to 72 hours under the conditions of 55°C and 25% RH. The method for manufacturing a packaged drug administration device according to claim 2 or 3.

5. The cylindrical case-enclosed drug administration device according to any one of claims 1 to 4 is capable of administering a drug while being enclosed and held by the cylindrical case.

6. The cylindrical case-enclosed drug administration device includes a prefilled syringe and a puncture device attached to the prefilled syringe during use. The puncturing instrument includes a hollow tubular member having a puncturing needle portion at one end side and a connecting needle portion at the other end side, a hub disposed between the puncturing needle portion and the connecting needle portion of the hollow tubular member, and a puncturing needle portion cap attached to the puncturing needle portion side of the hub. The prefilled syringe includes the outer cylinder, a gasket slidably accommodated in the outer cylinder, a tip sealing member that seals the tip of the outer cylinder and through which the connecting needle portion can penetrate, the drug filled in the outer cylinder, and a plunger that presses the gasket. The method for manufacturing a packaged drug administration device according to any one of claims 1 to 5, wherein the addition of hydrogen peroxide in the step of adding hydrogen peroxide is performed by adding hydrogen peroxide between the puncturing needle portion cap and the hub.

7. The tubular case-encapsulated drug administration device includes a biasing member that abuts against the outer cylinder and biases the prefilled syringe in the direction of the connecting needle portion, and a stopper that is detachably inserted into a side opening of the tubular case and abuts against a protruding portion on the outer surface of the outer cylinder to restrict the movement of the prefilled syringe in the direction of the hollow tubular member. After the detachment of the stopper, the drug administration device moves the prefilled syringe in the direction of the hollow tubular member by the pressing of the biasing member, and the sealing member of the prefilled syringe is penetrated by the connecting needle portion. The method for manufacturing a packaged drug administration device according to claim 6.

8. The tubular case-encapsulated drug administration device includes a prefilled syringe having a puncturing needle-equipped outer cylinder, a seal cap that seals the tip of the puncturing needle of the outer cylinder, a slidable gasket accommodated in the outer cylinder, and a drug filled in the outer cylinder, and an auto-injector mechanism that is accommodated in the tubular case, has a biasing member for pressing the gasket, and is equipped with the prefilled syringe. The method for manufacturing a packaged drug administration device according to any one of claims 1 to 5.

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