JP2011162267A - Manufacturing method for packed pre-filled syringe - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a manufacturing method for a packed medical supply capable of easily and surely manufacturing the medical supply wherein the external surface is sterilized at a packed state, and the packed medical supply manufactured by this manufacturing method. <P>SOLUTION: The manufacturing method for a packed medical supply 1 includes a medical supply external surface sterilization step after packing the medical supply of having a high concentration atmosphere period for maintaining the inside of a packing body 2 at hydrogen peroxide atmosphere concentration capable of sterilizing the external surface of the medical supply 3 while the medical supply 3 is store and sealed in the packing body 2 with a function of adjusting the permeation amount of hydrogen peroxide which permits and regulates permeation caused by diffusion of hydrogen peroxide and a hydrogen peroxide discharge period for making the hydrogen peroxide flow out of the packing body 2 by making use of diffusion of the hydrogen peroxide after the high concentration atmosphere period. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a method for producing a packaged medical article and a packaged medical article produced using the production method.

  Some medical supplies are used in a highly controlled microorganism atmosphere such as an operating room or ICU. As such a medical article, for example, there is a prefilled syringe prefilled with a medicine. In the prefilled syringe, the medicine inside is sterilized at the time of manufacture, but the outer surface of the syringe is usually manufactured in a clean environment such as a clean room, but is not at a level where sterilization can be guaranteed. For this reason, when bringing it into an operating room that requires a high degree of cleanliness, it is necessary to sterilize the outer surface of the syringe with a disinfectant or the like. In order to solve these problems, various products that are brought into the operating room as a kit and packaged have been proposed. Among these medical supplies in a kit, a packaged commercial product is repackaged. Such packaged commercial products will be sterilized again. At this time, it is desirable that the material constituting the medical article is not sterilized again by the same sterilization method in order to prevent deterioration of the material constituting the medical supplies and to reduce the residual of a medium such as gas for sterilization.

On the other hand, some medical supplies or their packaging materials are equipped with electronic parts such as identification IC tags. These kinds of parts are expected to increase in the future. In this case, electron beam sterilization, radiation sterilization such as gamma rays, heat sterilization, etc. cannot be performed.
Thus, it has been proposed to sterilize the autoclave after packaging in advance and sterilize the outer surface of the syringe simultaneously with the sterilization of the internal drug. However, in this case, there is a problem that the sterilizing apparatus for storing and processing them becomes larger in size for the packaging material. Moreover, when performing sterilization processes, such as an autoclave, it is necessary to use the paper and resin nonwoven fabric which have vapor permeability as a packaging material. When paper is used as a packaging material, fine paper dust is generated at the time of opening, which may contaminate the surrounding environment in an operating room or the like. In the case of a resin non-woven fabric, dust generation does not occur, but the cost is increased and the unsealing property is deteriorated, and the convenience during use is lowered.

There has been proposed a method of sterilizing the outer surface of a medical product such as a prefilled syringe prefilled with a drug using hydrogen peroxide. As a sterilization method using hydrogen peroxide, there is one disclosed in JP-A-11-193010 (Patent Document 1). The thing of patent document 1 is a sterilization method which sterilizes the medical supplies enclosed with the packaging container with hydrogen peroxide gas, Comprising: As a packaging container, the container main body made from the synthetic resin which has gas barrier property, and hydrogen peroxide gas The container is made of sterilized paper as a lid that can be permeated at a high level and can be welded to the container body, and after being sterilized with hydrogen peroxide gas, the interior of the packaging container is heated The hydrogen peroxide gas is degassed.
However, the sterilization method using hydrogen peroxide gas as described above requires installation of a large-scale facility such as a hydrogen peroxide gas generator and a chamber for maintaining a gas atmosphere, which also affects the work environment. Also, the process is complicated.

Japanese Patent Laid-Open No. 11-193010

  SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a method for producing a packaged medical product, which can be performed in a packaged state with a sterilized outer surface easily and reliably and without deteriorating the working environment. And a packaged medical article manufactured by the manufacturing method.

What achieves the above object is as follows.
(1) A method of manufacturing a packaged medical product, the method comprising storing the medical product in a hydrogen peroxide permeation amount adjusting functional package that allows and regulates permeation due to diffusion of hydrogen peroxide. In a sealed state, a high concentration atmosphere period in which the outer surface of the medical article is maintained in a sterilizable hydrogen peroxide atmosphere concentration in the package, and after the high concentration atmosphere period, the hydrogen peroxide is diffused using the diffusion. A method of manufacturing a packaged medical product, comprising a post-packaging medical product outer surface sterilization step having a hydrogen peroxide discharge period for flowing out of the package.

(2) The method for producing a packaged medical article according to (1), wherein the high-concentration atmosphere period is immediately after enclosing hydrogen peroxide to 14 days.
(3) The method for producing a packaged medical product according to (1) or (2), wherein the medical product outer surface sterilization step period is 8 hours to 28 days after the hydrogen peroxide is sealed.
(4) The method for manufacturing a packaged medical article according to any one of (1) to (3), wherein the hydrogen peroxide concentration during the high concentration atmosphere period is 0.05 mg / L to 300 mg / L.
(5) The manufacturing method includes adding a hydrogen peroxide solution or filling a hydrogen peroxide gas into a hydrogen peroxide permeation adjustment functional packaging, and the packaging after the hydrogen peroxide addition step is completed. A method for producing a packaged medical article according to any one of the above (1) to (4), comprising a sealing step for sealing the body.

(6) The manufacturing method includes the step of preparing the package, the step of preparing the medical product, the step of storing the medical product in the package, and the package in which the medical product is stored. The hydrogen peroxide adding step of adding hydrogen peroxide water or filling hydrogen peroxide gas, and the sealing step of sealing the package after completion of the hydrogen peroxide addition step (1) Thru | or the manufacturing method of the packaged medical supplies in any one of (4).
(7) The manufacturing method includes a step of preparing a medical product that is stored and sealed in a hydrogen peroxide permeation-adjusting functional packaging, and a hydrogen peroxide solution is added or hydrogen peroxide gas is added to the packaging. A method for producing a packaged medical article according to any one of the above (1) to (4), comprising a hydrogen peroxide addition step for filling.

(8) The said package is provided with the injection | pouring site | part which can connect or puncture a hydrogen peroxide or hydrogen peroxide gas injection | pouring apparatus, and can maintain airtightness after removal of this apparatus (7) A method of manufacturing a packaged medical product according to claim 1.
(9) The packaged medical treatment according to (7) or (8), wherein the manufacturing method performs a sealing step of sealing the hydrogen peroxide addition site of the package after the hydrogen peroxide addition step. A manufacturing method of goods.
(10) The amount of hydrogen peroxide added to the internal volume of the package in the hydrogen peroxide addition step is 0.5 mg / L to 300 mg / L, according to any one of (5) to (9) above. Manufacturing method for packaged medical supplies.
(11) The package body includes a container main body having a storage recess for storing the medical supplies, and a peelable sealing film for sealing the recess opening. (10) The method for producing a packaged medical article according to any one of (10).
(12) The packaged medical product according to any one of (5) to (11), wherein the medical product outer surface sterilization step is performed in a process of storing for 14 days or more after the hydrogen peroxide addition step. Manufacturing method.
(13) The method for manufacturing a packaged medical product according to any one of (1) to (12), wherein the medical product is a prefilled syringe.
(14) The method for manufacturing a packaged medical product according to any one of (1) to (12), wherein a plurality of different medical products packaged individually are stored in the package.
Moreover, what achieves the said objective is as follows.
(15) A packaged medical article manufactured by the manufacturing method according to any one of (1) to (14).

The present invention relates to a method for manufacturing a packaged medical article, the manufacturing method including the medical article in a hydrogen peroxide permeation amount adjusting functional package that allows and regulates permeation due to diffusion of hydrogen peroxide. In the sealed state, a high concentration atmosphere period in which the outer surface of the medical article is maintained in a sterilizable hydrogen peroxide atmosphere concentration in the package, and after the high concentration atmosphere period, the hydrogen peroxide is diffused using the diffusion. And a sterilization step of the outer surface of the medical product after packaging, which has a hydrogen peroxide discharge period for flowing out of the package.
For this reason, according to the manufacturing method of the present invention, it is possible to easily and reliably manufacture a medical product in which the outer surface of the medical product is sterilized and packaged. Since hydrogen is discharged or decomposed, there is no harm caused by sterilization when opened, and it can be used safely.

  Furthermore, according to the manufacturing method of the present invention, since no radiation sterilizer or autoclave is used as a means for sterilizing the outer surface of the medical product, the medical product is not exposed to radiation or heat history. Further, when the entire package is sterilized, these sterilization means require large-scale equipment, and the manufacturing method of the present invention is preferable in this respect as well.

Then, the manufacturing method includes a hydrogen peroxide addition step of adding hydrogen peroxide water or filling hydrogen peroxide gas into the hydrogen peroxide permeation amount adjusting functional packaging, and the packaging body after completion of the hydrogen peroxide addition step. Hydrogen peroxide can be easily and reliably added if the sealing step for sealing is performed.
The manufacturing method includes a step of preparing a sealed medical article that is housed and sealed in a hydrogen peroxide permeation amount adjusting functional package, and a hydrogen peroxide solution is added or filled with hydrogen peroxide gas in the package If it is provided with the hydrogen peroxide addition process to perform, addition of hydrogen peroxide can be performed easily and reliably.
Furthermore, if the packaging body has an injection part that can be connected or punctured with hydrogen peroxide or a hydrogen peroxide gas injection device and can maintain airtightness after removal of the device, The hydrogen peroxide addition process can be easily performed.
Further, if the manufacturing method performs a sealing step for sealing the hydrogen peroxide addition site of the package after the hydrogen peroxide addition step, the outflow from the added hydrogen peroxide addition site is ensured. Can be prevented.
Moreover, if the addition amount of hydrogen peroxide with respect to the internal volume of the package in the hydrogen peroxide addition step is 0.5 mg / L to 300 mg / L, the outer surface of the medical product can be sufficiently sterilized and used until it is used. In addition, hydrogen peroxide is surely decomposed and lost.
Moreover, if the said manufacturing method performs the preservation | save process preserve | saved for 14 days or more after the said hydrogen peroxide addition process, the sterilization of the outer surface of a medical article will be ensured, and even if it uses immediately, hydrogen peroxide There is very little residue.

FIG. 1 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to an embodiment of the present invention. FIG. 2 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to an embodiment of the present invention. FIG. 3 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to an embodiment of the present invention. FIG. 4 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to another embodiment of the present invention. FIG. 5 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to another embodiment of the present invention. FIG. 6 is an explanatory diagram for explaining an experimental method performed on an example of the present invention and a comparative example. FIG. 7 is a table 1 showing the number of viable bacteria by BI installation site at 15 ° C. and 45% RH. FIG. 8 is Table 2 showing the number of viable bacteria by BI installation site at 30 ° C. and 65% RH. FIG. 9 is Table 3 showing the amount of viable cell count reduction on the 14th day. FIG. 10 is a table 4 showing the remaining rate due to the evaporation of hydrogen peroxide in the package.

A method for manufacturing a packaged medical article according to an embodiment of the present invention will be described.
FIG. 1 is an explanatory diagram for explaining a method for manufacturing a packaged medical article according to an embodiment of the present invention. FIG. 2 is a diagram for explaining a method for manufacturing a packaged medical article according to an embodiment of the present invention. FIG. 3 is an explanatory diagram for explaining a method of manufacturing a packaged medical article according to an embodiment of the present invention.
The method for manufacturing a packaged medical product 1 according to the present invention is a state in which the medical product 3 is housed and sealed in a hydrogen peroxide permeation adjustment functional packaging 2 that allows and regulates permeation due to diffusion of hydrogen peroxide. In the package 2, a high concentration atmosphere period in which the outer surface of the medical article 3 is maintained at a sterilizable hydrogen peroxide atmosphere concentration, and after the high concentration atmosphere period, hydrogen peroxide is diffused from the inside of the package 2 using the diffusion. The medical device external surface sterilization process after packaging which has the hydrogen peroxide discharge | emission period to flow out is provided.

Therefore, first, as an embodiment of the manufacturing method of the present invention, the step of storing the medical article 3 in the package 2 and the addition or peroxidation of the hydrogen peroxide solution 41 in the hydrogen peroxide permeation amount adjusting functional package A hydrogen peroxide addition process for filling hydrogen gas, a sealing process for sealing the package 2 after completion of the hydrogen peroxide addition process, and the medical article outer surface sterilization process will be described. And in the manufacturing method of this Example, the process of preparing the hydrogen peroxide permeation amount adjusting functional package 2 and the process of preparing the medical article 3 are performed in advance.
First, the process of preparing the hydrogen peroxide permeation amount adjusting functional package 2 and the process of preparing the medical supplies 3 will be described.
The hydrogen peroxide permeation amount adjusting functional package 2 used in the manufacturing method of this embodiment includes a container body 21 for storing the medical supplies 3 and an opening 22 for sealing the container body 21 so that the opening 22 can be opened. The member 25 is provided. Moreover, as a package, the bag-shaped package which can be sealed and opened may be sufficient. Specifically as a package, a blister packaging container, a soft bag-shaped packaging container, etc. are mentioned. In addition, as a form of a package, what kind of thing may be used as long as it can store medical supplies inside and can be sealed and opened.

In the embodiment shown in FIG. 1, the package 2 includes a container body 21 having a storage recess 23 for storing a medical article 3 and a peelable sealing film (sealing) for sealing the recess opening 22. Member) 25. The packaging body 2 of the Example shown in FIG. 1 is a blister packaging body. The package 2 according to the embodiment of the present invention has a shape that can accommodate a prefilled syringe, which will be described later, which is an example of the medical product 3.
Specifically, as shown in FIG. 1, the packaging body 2 of the present invention is detachably attached to the housing recess 23, the flange forming portion 24 formed around the housing recess 23, and the flange forming portion 24. The sealing film 25 is provided. The storage recess 23 of the package is shaped such that a prefilled syringe, which is an example of a medical product, does not easily move within the container body.

  And the package 2 uses a hydrogen peroxide permeation amount adjusting functional package. The hydrogen peroxide permeation amount adjusting functional package indicates a package that allows and regulates permeation due to diffusion of hydrogen oxide. Specifically, it refers to a material that allows permeation due to diffusion of hydrogen peroxide gas but suppresses permeation in a short time. Those that allow permeation of hydrogen peroxide for a short period of time cannot form a sufficiently high concentration atmosphere period of hydrogen peroxide in the external sterilization process of medical supplies after packaging, and do not allow permeation of hydrogen peroxide gas. If it does not penetrate at all, hydrogen peroxide will remain in the package. For this reason, the hydrogen peroxide permeation amount adjusting functional packaging does not include those having pores through which hydrogen peroxide can easily pass, such as paper and porous films.

  The hydrogen peroxide passing function of the package can be evaluated by measuring the transpiration of an aqueous solution containing hydrogen peroxide (hydrogen peroxide solution). When hydrogen peroxide water is enclosed in a packaging body film and left in an environment of room temperature or higher, water and hydrogen peroxide gradually vaporize in the packaging film and fill the packaging film. In parallel with the vaporization and filling of hydrogen peroxide, hydrogen peroxide permeates into the package body and then permeates, but the extent can be grasped by the amount of hydrogen peroxide water drops in the package. In other words, in a porous film that easily allows hydrogen peroxide to pass through, hydrogen peroxide droplets decrease or disappear in a short time, but in a packaging film that allows and regulates permeation due to hydrogen peroxide diffusion, It takes a certain time for the water droplets to decrease or disappear.

As a function of adjusting the hydrogen peroxide permeation amount, the package ² has a container having an internal volume of 0.2 mL per 1 cm ² of the surface area of the package so that the amount of hydrogen peroxide per internal volume of the package is 300 mg / L. After adding the adjusted hydrogen peroxide solution and sealing the container, it is preferable that the period during which the hydrogen peroxide droplets disappear under the conditions of 55 ° C. and 25% RH is in the range of 3 hours to 72 hours. In particular, it is preferable that hydrogen peroxide water droplets of 6 to 24 hours have a disappearance period (transpiration).
Moreover, as the package 2, what has a hydrogen peroxide permeation amount adjusting function as a whole may be used. That is, only the container main body 21 has a hydrogen peroxide permeation adjusting function, the film 25 is a hydrogen peroxide impervious combination, and only the film 25 has a hydrogen peroxide permeation adjusting function. Either a combination that is impermeable to hydrogen peroxide or a combination that has a function of adjusting the permeation amount of hydrogen peroxide for both the container body 21 and the film 25 may be used.

Furthermore, it is preferable that the material of the package is not easily altered by hydrogen peroxide. Moreover, as a material of a package, it is preferable to have waterproofness.
And as a material of the container main body 21, it is preferable to have a certain amount of strength and hardness. The container body 21 is preferably made of a material having a low hydrogen peroxide gas permeability. As the material of the container main body 21, for example, polyolefin such as polypropylene and polyethylene, vinyl chloride resin, polyester resin, polystyrene / polypropylene resin, polyethylene / ionomer (for example, ethylene, styrene, fluorine) / polyethylene are preferably used. In particular, low density polyethylene / ionomer / low density polyethylene is preferable from the viewpoint of the hydrogen peroxide permeation adjusting function.

  Further, among these, a material having transparency is preferable. For example, when the medicine stored in the syringe is easily affected by light, the forming material of the container body may contain various pigments and ultraviolet absorbers. Furthermore, it is preferable that the resin is provided with 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). . Further, it may be composed of three layers of polyethylene terephthalate / ethylene-vinyl alcohol copolymer / polypropylene, or may be composed of polypropylene alone.

Specifically, the sealing film 25 was fixed to at least the outer peripheral portion of the lower surface of the film and a film (base film) that is low in hydrogen peroxide gas permeability or substantially impermeable to hydrogen peroxide gas. What has an adhesive resin layer is preferable, and also it is more preferable to have a surface protective layer provided in the upper surface of the film. As the base film, a metal foil such as aluminum, silver, gold or the like, a metal vapor-deposited film in which aluminum, silver, gold or the like is vapor-deposited on the surface, an inorganic vapor-deposited film in which SiO _X or the like is vapor-deposited on the surface, a gas barrier resin film, For example, a film of polyvinylidene chloride, polyvinylidene chloride-polyvinyl chloride, polyvinylidene chloride-acrylic acid ester copolymer, high-density polyethylene, or the like can be suitably used.

  The adhesive resin layer is for heat-sealing the base film and the container main body 21 so as to be peelable, and various easy peeling mechanisms as described below can be used. For example, when polypropylene is used for the heat seal surface of the container body 21, an olefin resin such as an ethylene-vinyl acetate resin, an ethylene-acrylic acid resin, or a blend of polypropylene and polyethylene is used as the adhesive resin layer. A two-component curable urethane-based dry laminate adhesive can be suitably used. When polyvinyl chloride is used as the container main body 21, an adhesive resin layer is made of an olefin resin such as an ethylene-vinyl acetate resin or an ethylene-acrylic acid resin, and a polystyrene with a styrene-butadiene block copolymer. A blended product, a vinyl chloride-vinyl acetate copolymer, a two-component curable urethane-based dry laminate adhesive, or the like can be suitably used. Furthermore, when using polyester as the container main body 21, olefin resin such as ethylene-vinyl acetate resin and ethylene-acrylic acid resin, copolyester, and two-component curable urethane-based dry laminate adhesive can be suitably used. .

  The surface protective layer is formed by coating a synthetic resin, for example, polyester such as PET, polypropylene, polyethylene, nylon, epoxy resin, polyamide resin, or by laminating the above synthetic resin film or paper. Is preferred. This surface protective layer is printed to describe the necessary items such as the name and size of the medical product to be stored, the name of the medicine filled in the syringe, and the filling amount when the medical product is a prefilled syringe, for example. Can also be used as a layer. A light shielding material such as white ink may be interposed between the surface protective layer and the gas barrier film to form a light shielding film.

Specific examples of the sealing film 25 include four layers of polyethylene terephthalate / polyethylene / polyethylene terephthalate / adhesive resin, polyethylene terephthalate / ethylene-vinyl alcohol copolymer / stretched nylon / adhesive resin, polyethylene terephthalate / stretched One consisting of three layers of nylon / adhesive resin is conceivable.
Examples of medical supplies 3 include syringes, guide wires, females, catheters, sensors, forceps, needles / indwelling needles, suture needles / threads, sanitary materials, drapes, dressings, drugs, infusion routes / extension tubes And a container containing a pharmaceutical solution such as a pre-filled syringe, a container containing physiological saline for washing or an infusion.

In addition, the medical supplies may be medical instrument kits, and the medical kits include operating room, suture, abdominal, thoracotomy, disinfection, drainage, delivery, ophthalmology, urination , For central vein, for local anesthesia, for epidural anesthesia, for angiography, for PTCA, for thoracic surgery, for orthopedics, and for obstetrics and gynecology.
Further, the medical product may be a sterilized medical product. The medical product may be a sterilized and packaged medical product. A plurality of different medical supplies may be stored in the package.
In the embodiment of the present invention, a prefilled syringe is used as a medical product. Examples of the medicine stored in the prefilled syringe include physiological saline, high-concentration sodium chloride injection, drug solutions such as vitamins, minerals, antibiotics, and powdered or lyophilized drugs.

  As shown in FIG. 3, the prefilled syringe 3 used in the embodiment of the present invention is provided with a nozzle 32 at the front end and an outer cylinder 31 having a flange 33 at the rear end, and slides in the outer cylinder. A gasket 34, a plunger (presser) 35 attached to the gasket 34, a seal cap 36 attached to the distal end portion of the outer cylinder 31, and a medicine 39 stored in the outer cylinder 31 are provided. Further, an outer cylinder side screwing portion that is screwed with a cap side screwing portion provided in the seal cap 36 is formed at the base end portion of the nozzle. Further, an outer cylinder side engaging portion that engages with a cap side engaging portion provided in the seal cap 36 is formed near the tip of the outer cylinder main body.

The seal cap 36 can be inserted with an insertion needle. The seal cap includes a seal cap body and a seal member. The seal cap body is a cylindrical member that is open on one end side and the other end side, and the one end side opening is closed by a seal member. The seal cap body is manufactured in a cap shape, and includes a nozzle body housing portion, a cap side screwing portion, and a seal cap side engaging portion. The seal member is for sealing the nozzle portion tip opening in a liquid-tight manner. The nozzle portion is liquid-tightly sealed by the nozzle portion tip opening being in contact with the seal member. Further, the seal member is formed of an elastic material that can be pierced by a liquid passing needle. The seal member is for sealing the nozzle portion tip opening in a liquid-tight manner. Further, the seal member is formed of an elastic material that can be pierced by a liquid passing needle. The seal member is attached to the distal end portion of the cap 36 by a seal member holding portion.
Examples of the material for forming the seal member include natural rubber, isoprene rubber, butadiene rubber, fluororubber, silicone rubber and other synthetic rubbers, SBS elastomers, SEBS elastomers and other styrenic elastomers, and ethylene-α-olefin copolymer polyolefins. It is preferable to use a thermoplastic elastomer such as a base elastomer.

As shown in FIG. 3, the plunger 35 includes a main body portion 35 a having a cross-shaped cross section and a screwing portion 35 b that is provided at the tip of the main body portion 35 a and is screwed with the gasket 34. In addition, disc-shaped ribs 35c and 35d are formed at the tip of the main body 35a, and ribs are also formed near the center of the main body 35a.
Further, as shown in FIG. 3, the gasket 34 has a threaded recess 34 a that is threadedly engaged with a threaded portion 35 b provided at the tip of the plunger 35. In the embodiment of the present invention, the gasket 34 has an enlarged diameter near the distal end and the proximal end, and is in contact with the inner surface of the outer cylinder at this portion. In the embodiment of the present invention, the gasket is provided with ribs in the vicinity of the front end portion, the central portion, and the base end portion, and in contact with the inner surface of the outer cylinder.

  The outer cylinder 31 preferably has gas barrier properties, and examples of the forming material include polypropylene, polyethylene, polystyrene, polyamide, polycarbonate, polyvinyl chloride, poly- (4-methylpentene-1), acrylic resin, and acrylonitrile. -Various resins such as butadiene-styrene copolymers, polyesters such as polyethylene terephthalate, and cyclic polyolefins. Among them, resins such as polypropylene and cyclic polyolefins are preferable because they are easy to mold and have heat resistance. With these resins, sufficient gas barrier properties can be imparted by the thickness of the outer cylinder that is usually used.

Examples of the material for forming the seal cap 36 include polypropylene, polyethylene, polystyrene, polyamide, polycarbonate, polyvinyl chloride, poly- (4-methylpentene-1), acrylic resin, acrylonitrile-butadiene-styrene copolymer, polyethylene terephthalate. Various resins such as polyester and cyclic polyolefin can be used, and among them, resins such as polypropylene and cyclic polyolefin are preferable because they are easy to mold and have heat resistance.
As a material for forming the gasket 34, rubber having elasticity (for example, butyl rubber, latex rubber, silicone rubber, etc.), synthetic resin (for example, styrene elastomer such as SBS elastomer, SEBS elastomer, ethylene-α olefin copolymer elastomer, etc.) It is preferable to use olefin-based elastomers). A well-known thing is used as a prefilled syringe.

In the manufacturing method of the medical article of this embodiment, a step of sterilizing the above-described medical article is provided before the hydrogen peroxide adding step. Examples of the sterilization method include autoclave sterilization, radiation sterilization, and electron beam sterilization. In an embodiment of the present invention, a prefilled syringe that is a medical product is autoclaved. Autoclave sterilization is carried out at 120 ° C. and 0.8 to 2.0 kg / cm ² for about 30 minutes.

Next, the process of storing the medical supplies 3 in the package 2 is performed.
Thereafter, a hydrogen peroxide addition step is performed in which hydrogen peroxide solution is added or hydrogen peroxide gas is filled in the package 2 in which the medical supplies 3 are stored.
The hydrogen peroxide addition step is performed without sealing the package. In the embodiment shown in FIG. 1, the storage recess 23 of the container body 21 is performed without being sealed with the sealing film 25.
In the embodiment of the present invention, the step of storing the medical article 3 in the container main body 21 is performed before the hydrogen peroxide solution adding step, and the medical article 3 is added to the container main body 21 after the hydrogen peroxide is added. It may be stored.
When the medical article 3 is a syringe (prefilled syringe), it is preferable to add the hydrogen peroxide solution around the base end portion of the plunger. In the embodiment of the present invention, as shown in FIG. 3, the hydrogen peroxide 41 is added to the proximal end side of the plunger 35. Further, it is preferable to add several portions of the hydrogen peroxide solution as shown in FIG. Hydrogen peroxide is preferably added so as not to come into direct contact with the medical supplies from the viewpoint of preventing the deterioration of the medical supplies. Further, the hydrogen peroxide solution may be added evenly around the medical supplies. The hydrogen peroxide addition step may be performed by sealing except for a part of the opening of the container body, and adding hydrogen peroxide water from an unsealed portion. Specifically, the container body 21 may be sealed except for the plunger side portion of the opening 22, and hydrogen peroxide solution may be added from the unsealed opening portion.

Hydrogen peroxide may be added by spraying hydrogen peroxide water into the package.
The hydrogen peroxide solution added by the production method of the present invention is preferably 1.0 to 6.0 w / v%, particularly 2.0 to 4.0 w / v%. The addition amount (drop amount) is 2 mg / L to 300 mg / L, preferably 15 to 100 mg / L as the amount of hydrogen peroxide per inner volume of the package. Specifically, it is preferable to add 0.01 to 0.10 mL of 1.0 to 6.0 w / v% hydrogen peroxide solution to a 20 to 45 mL package. Preferably, it is preferable to add 0.03 mL to 0.06 mL of hydrogen peroxide water of 2.0 to 4.0 w / v% to a package of 20 mL to 45 mL.

Further, according to the present invention, since the hydrogen peroxide solution is dropped directly into the package, the safety of the operator can be ensured. Moreover, according to the production method of the present invention, hydrogen peroxide can be added with simple equipment. Moreover, according to this invention, since hydrogen peroxide is added in a package, corrosion of an installation can be prevented.
Further, hydrogen peroxide may be added in the form of a gas in the package.
When the hydrogen peroxide addition step is performed using hydrogen peroxide gas, the amount of hydrogen peroxide added to the internal volume of the package 2 is 0.5 mg / hydrogen peroxide amount per volume of the package. About L to 5 mg / L, particularly about 1.0 to 2.5 mg / L is preferable.
If the amount of hydrogen peroxide in the package 2 is such, it is possible to reliably sterilize the package 2 and the packaged medical supplies 3, and almost transfer hydrogen peroxide to medical drugs. There is nothing. In addition, the medical supplies are not deformed, discolored, or altered, and there is almost no residual during use.

And as a method of filling the package with hydrogen peroxide, it is preferably performed by sealing with a sealing film except for a part, filling with hydrogen peroxide water from the opening gap, and sealing. . Specifically, the medical product (prefilled syringe in this embodiment) is accommodated in the package, sealed with a small unfused portion into which a nozzle for injecting hydrogen peroxide solution can be inserted, and this unfused It is good also as what inserts a nozzle in a landing part and adds hydrogen peroxide water or gas.
Further, when the package is filled with hydrogen peroxide gas, it may be performed by sealing an unsealed package in a hydrogen peroxide gas atmosphere.
And after adding hydrogen peroxide, as shown in FIG. 1, FIG. 2, the package body 2 is sealed by sealing the recessed part opening of the container main body 21 with the sealing film 25. FIG. As shown in FIG. 2, the sealing is performed by sealing the sealing film 25 to the flange forming portion 24 of the container main body 21 by heat fusion, high frequency fusion or the like. As described above, the hydrogen peroxide addition step is preferably performed after the medical product is stored, but after the hydrogen peroxide is added into the package 2, the medical product 3 is stored, and then the packaging is performed. The body 2 may be sealed.

  And the medical article outer surface sterilization process after packaging is performed. In this medical product outer surface sterilization process, in a state where the medical product 3 is housed and sealed, a high concentration atmosphere period in which the outer surface of the medical product 3 is maintained at a sterilizable hydrogen peroxide atmosphere concentration in the package 2 and a high concentration atmosphere After the period, the hydrogen peroxide is discharged so that the hydrogen peroxide is discharged from the package 2 using diffusion.

  After hydrogen peroxide is added and sealed, the package 2 is placed under conditions that allow hydrogen peroxide water to gasify. Specifically, it is performed by placing it in a temperature environment where hydrogen peroxide water is gasified. Usually, it can be carried out by keeping it at room temperature, but it is kept warm when it is extremely cold. Then, as the gasification of the hydrogen peroxide solution proceeds, the package body reaches a hydrogen peroxide atmosphere concentration capable of sterilizing the outer surface. The package 2 has a low permeability of hydrogen peroxide and permeation due to diffusion of hydrogen peroxide from the package, but the gasification rate is faster. The outer surface reaches a sterilizable hydrogen peroxide atmosphere concentration, and the concentration further increases, reaching a maximum concentration when or just before all hydrogen peroxide is gasified. After reaching the maximum concentration, hydrogen peroxide gradually flows out of the package according to the hydrogen peroxide permeation ability of the package. In this invention, since the package body from which hydrogen peroxide flows out by diffusion without pores is used, the outflow rate is slow. Then, due to the outflow of hydrogen peroxide, the package will eventually have a lower concentration than the hydrogen peroxide atmosphere concentration capable of sterilizing the outer surface of the medical product. The period from when the package reaches the hydrogen peroxide atmosphere concentration that allows the outer surface to be sterilized until the outer surface becomes lower than the hydrogen peroxide atmosphere concentration that allows the outer surface to be sterilized is the high concentration atmosphere period. Effective sterilization period. The high-concentration atmosphere period is preferably about 14 days immediately after enclosing hydrogen peroxide, and particularly preferably about 7 days immediately after enclosing hydrogen peroxide. Moreover, as a minimum density | concentration in a high concentration atmosphere period, 0.05 mg / L-2.0 mg / L is preferable, and 0.5 mg / L-1.0 mg / L is especially preferable. Further, the maximum concentration in the high concentration atmosphere period is preferably 10 mg / L to 300 mg / L, and particularly preferably 50 mg / L to 100 mg / L. Further, it is preferable to change the atmosphere in the package by performing top-to-bottom reversal and swinging of the sealed package during this high-concentration atmosphere period. By doing in this way, the contact of the hydrogen peroxide to the outer surface of a medical article becomes more reliable. Specifically, this period is preferably performed at 1 to 30 ° C. Moreover, it is preferable that preservation | save is hold | maintained at 10-80% RH, especially 20-60% RH. Further, when the medical supplies are prefilled syringes, it is preferable to store them at such an angle that the entire packaging container is filled with hydrogen peroxide during this period, and in particular, the prefilled syringes can be stored in a horizontal state. preferable. If stored in such an orientation, the hydrogen peroxide gas spreads throughout the package, so that the package and medical supplies are reliably sterilized. The prefilled syringe may be stored in a vertical state. Moreover, you may heat in this period. Heating is preferably 30 to 100 ° C, particularly 40 to 80 ° C. The warming time is preferably 10 to 120 min, particularly 20 to 60 min.

  And even after the inside of the package becomes lower than the hydrogen peroxide atmosphere concentration capable of sterilizing the outer surface of the medical product, the outflow due to the diffusion of hydrogen peroxide from the package continues, and eventually, almost from the inside of the package 2. All hydrogen peroxide flows out. The period from when the inside of the package becomes lower than the hydrogen peroxide atmosphere concentration that can sterilize the outer surface of the medical supplies until the concentration of hydrogen peroxide in the package reaches the allowable residual concentration is the hydrogen peroxide discharge period It is. The 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 to 7 days. The allowable residual concentration of the hydrogen peroxide concentration is preferably 0.05 ppm or less. Moreover, you may carry to the utilization place of the packaged medical supplies during this hydrogen peroxide discharge | emission period.

Further, an oxygen scavenger may be housed inside a package of medicine or the like that is easily affected by oxygen. This absorbs oxygen in the sealed package and prevents the drug from being oxidized. When hydrogen peroxide is encapsulated in a packaging material containing an oxygen scavenger, the hydrogen peroxide is decomposed by the oxygen scavenger, so it is desirable that the amount of hydrogen peroxide be larger than when no oxygen scavenger is added. Moreover, the hydrogen peroxide enclosed can be decomposed at an early stage by the oxygen scavenger to prevent hydrogen peroxide from remaining.
Moreover, you may perform the trimming cut of the packaged medical supplies 3 and a unit box after the hydrogen peroxide addition process. Further, the operation may be performed by packing the unit box into the shipping box. In addition, as the unit box and the shipping box, those having hydrogen peroxide permeability such as a paper box and a cardboard box which are normally distributed are used.

Moreover, this invention is the packaged medical supplies manufactured by the said manufacturing method.
For this reason, the medical supplies of the present invention are reliably sterilized with hydrogen peroxide. The manufacturing method is as described above. The medical supplies are as described above. In an embodiment of the present invention, the medical article is a prefilled syringe. Moreover, the chemical | medical agent accommodated in the inside is heparin. As the package, those described above are preferable. In the embodiment of the present invention, the packaging body 2 includes the storage recess 23 for storing the medical article 3 and the peelable sealing film 25 for sealing the recess opening 22 as described above. ing.

In the present invention, the medical article 3 has a drug inside, and the amount of hydrogen peroxide transferred to the drug is preferably 0.05 ppm or less, particularly preferably 0.01 ppm or less.
Further, the production method of the present invention includes a step of preparing at least one of a sterilized medical article, a sterilized and packaged medical article, and a non-sterilized medical article, a step of preparing a package, You may provide the process of accommodating medical supplies, and the hydrogen peroxide addition process of adding hydrogen peroxide water or filling hydrogen peroxide gas in the hydrogen peroxide permeation amount adjusting functional package.

In addition, you may perform a hydrogen peroxide addition process, before storing medical supplies in a package.
As such a manufacturing method, for example, at least one kind of sterilized medical supplies, sterilized medical supplies, and non-sterile medical supplies are placed on the tray, and hydrogen peroxide solution is added to the bottom of the tray. And it is preferable that it is housed in a package and sealed. In addition, it is preferable that hydrogen peroxide is added at a position where it does not come into contact with medical supplies.

Next, a method for manufacturing a packaged medical product according to another embodiment of the present invention will be described. FIG. 4 is an explanatory diagram for explaining a method of manufacturing a packaged medical product according to another embodiment of the present invention.
The manufacturing method of the packaged medical article 50 of this embodiment is similar to the above-described method in which the hydrogen peroxide permeation amount adjusting functional package 2 that allows and regulates the permeation due to the diffusion of hydrogen peroxide. In a state in which the product 3 is stored and sealed, a high concentration atmosphere period in which the outer surface of the medical product 3 is maintained at a sterilizable hydrogen peroxide atmosphere concentration in the package 2 and hydrogen peroxide is diffused after the high concentration atmosphere period. A medical product external surface sterilization step after packaging having a hydrogen peroxide discharge period for flowing out of the package 2 by use is provided.

In the manufacturing method of this embodiment, the step of preparing the medical article 3 which is stored in the hydrogen peroxide permeation amount adjusting functional package 2 and sealed, and the hydrogen peroxide solution is added to the package 2. Alternatively, a hydrogen peroxide addition step for filling hydrogen peroxide gas and a medical product outer surface sterilization step after packaging are performed. Even such a manufacturing method has the same effect as the above-described embodiment.
The manufacturing method of this embodiment is different from the manufacturing method of the above-described embodiment in that hydrogen peroxide is added into the packaging body in a state where the packaging body 2 is sealed. Hereinafter, the difference will be mainly described.
First, a process of preparing a medical product that is stored in the hydrogen peroxide permeation amount adjusting functional package 2 and sealed will be described. As the medical supplies 3 used in this manufacturing method, it is preferable to use those described above. The medical product 3 shown in FIG. 4 is a prefilled syringe.

  The packaging body 2 is a hydrogen peroxide permeation amount adjusting functional packaging body that allows and regulates permeation due to diffusion of hydrogen peroxide, as described above, and further includes a hydrogen peroxide or hydrogen peroxide gas injection device. It is possible to connect or puncture and to provide an injection site 53 capable of maintaining airtightness after removing the device. The basic configuration of the hydrogen peroxide permeation amount adjusting functional package 2 is preferably the same as the above-described package. The packaging body 2 of the embodiment shown in FIG. 4 includes a container body 21 having a storage recess 23 for storing medical supplies, and a peelable sealing film 25 for sealing the recess opening 22. It is preferable that The plunger side portion of the sealing film 25 is provided with an injection site 53 that can puncture the injection device and can maintain airtightness after the device is removed. The injection site 53 is preferably provided at least on the proximal end portion of the plunger. Moreover, the whole sealing film may be an injection | pouring site | part.

The injection site 53 of the embodiment of the present invention is configured by a member that can be inserted through a needle tube or the like. Examples of the material constituting the injection site include rubber materials such as natural rubber, isoprene rubber, chloroprene rubber, and silicone rubber, or resins such as thermoplastic elastomers such as styrene-butadiene-styrene (SBS) block copolymers. Can be used. With such a member, a hydrogen peroxide injection device can be inserted, and airtightness can be maintained after the injection device is removed. The puncturable injection site is preferably produced by providing a puncturable site in part or all of the sealing film or by attaching a puncturable member to the sealing film.
Moreover, as an injection | pouring site | part which can connect an injection device and can maintain airtightness after removal of an apparatus, the non-return valve which can insert an injection device is mentioned, for example. Moreover, as such an injection | pouring site | part, you may have a structure opened by inserting an injection device and obstruct | occluding when an injection device is extracted.

The prefilled syringe 3 is accommodated in the container main body 21 as described above, and the medical supplies 50 sealed by heat sealing or the like as described above can be obtained by using the sealing film 25 on the concave opening 22 of the container main body 21. .
Next, a hydrogen peroxide addition step for filling the package with hydrogen peroxide solution or hydrogen peroxide gas is performed.
For the addition of hydrogen peroxide, hydrogen peroxide solution or hydrogen peroxide gas injection device (not shown) is punctured or connected to the injection site 53 and hydrogen peroxide solution or hydrogen peroxide gas is injected into the container body 21. Is done. Specifically, when the distal end portion of the injection device has a puncture needle, the injection is performed by inserting the puncture needle through the injection site 53 where puncture is possible. The injection of hydrogen peroxide solution or hydrogen peroxide gas is preferably as described above.

Then, after adding hydrogen peroxide water or injecting hydrogen peroxide gas into the package 2, the injection device is pulled out from the injection site 53, and the hydrogen peroxide addition step is completed. After removing the injection device, the package 2 is again sealed.
As described above, the amount of hydrogen peroxide added to the internal volume of the package in the hydrogen peroxide addition step is such that when hydrogen peroxide is added, the concentration of hydrogen peroxide is 1.0 to 6.0 w. / V%, and particularly preferably 2.0 to 4.0 w / v%. The addition amount (drop amount) is 2 mg / L to 300 mg / L, preferably 15 to 100 mg / L with respect to the volume of the package. Specifically, it is preferable to add 0.01 to 0.10 mL of 1.0 to 6.0 w / v% hydrogen peroxide solution to a 20 to 45 mL package. Preferably, it is preferable to add 0.03 mL to 0.06 mL of hydrogen peroxide water of 2.0 to 4.0 w / v% to a package of 20 mL to 45 mL.

  Further, according to the present invention, since the hydrogen peroxide solution is dropped directly into the package, the safety of the operator can be ensured. Moreover, according to the production method of the present invention, hydrogen peroxide can be added with simple equipment. Moreover, according to this invention, since hydrogen peroxide is added in a package, corrosion of an installation can be prevented.

Further, hydrogen peroxide may be added in the form of a gas in the package.
The concentration of hydrogen peroxide gas to be used is preferably about 0.5 mg / L to 5.0 mg / L%, particularly about 1.0 mg / L to 2.5 mg / L%. Moreover, when performing a hydrogen peroxide addition process using hydrogen peroxide gas, it is preferable that the addition amount of hydrogen peroxide with respect to the internal volume of the package 2 is 0.5 mg / L to 5 mg / L. If the amount of hydrogen peroxide in the package 2 is such, it is possible to reliably sterilize the package 2 and the packaged medical supplies 3, and almost transfer hydrogen peroxide to medical drugs. There is nothing. In addition, the medical supplies are not deformed, discolored, or altered, and there is almost no residual during use. Particularly preferably, it is 1.0 mg / L to 2.5 mg / L.
Moreover, as a manufacturing method of this Example, the sealing process which seals the hydrogen peroxide addition site | part of a package may be performed after a hydrogen peroxide addition process. In this case, the package 2 is provided with an injection portion 53 that can be connected to or punctured with hydrogen peroxide or a hydrogen peroxide gas injection device and can maintain airtightness after the device is removed. Is preferable, but may not be provided. As the seal, for example, as shown in FIG. 5, it is preferable to affix a seal material 63 that seals the puncture site of the injection device. Further, the sealing may be performed by applying a molten resin, an adhesive, or a sealing agent.

As the seal used for sticking the seal, it is preferable to stick the same film as the package forming material or a flexible film. As a film forming material, polyolefin such as polyethylene and polypropylene, polyester such as polyethylene terephthalate, and the like are preferable.
As the molten resin, a liquid resin that has adhesiveness with the surface forming material of the package and is cured after application can be used. For example, elastic materials such as rubber and elastomer are preferable. As the rubber, natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, silicone rubber and the like are used. The elastomer is preferably a thermoplastic elastomer, and for example, a polyvinyl chloride elastomer, a polyolefin elastomer, a styrene elastomer, a polyester elastomer, a polyamide elastomer, a polyurethane elastomer, and a mixture thereof are used. In particular, silicone rubber, styrene-butadiene rubber, butyl rubber, and styrene elastomer are preferable because they have suitable hardness and elastic properties.

  Further, the packaged medical product to which hydrogen peroxide has been added is subjected to a medical product outer surface sterilization step after packaging, as in the above-described embodiment. In this medical product outer surface sterilization process, in a state where the medical product 3 is housed and sealed, a high concentration atmosphere period in which the outer surface of the medical product 3 is maintained at a sterilizable hydrogen peroxide atmosphere concentration in the package 2 and a high concentration atmosphere After the period, the hydrogen peroxide is discharged so that the hydrogen peroxide is discharged from the package 2 using diffusion. The medical product outer surface sterilization step is preferably performed in the same manner as in the above-described embodiment.

Next, specific contents of the present invention will be described.
(Adjustment of hydrogen peroxide water)
Hydrogen peroxide solution stock solution (30%) (special reagent grade, manufactured by Wako Pure Chemical Industries, Ltd.) and cooled water for injection are mixed so that the concentration of hydrogen peroxide solution becomes 2.0 to 4.0 w / v%. It has been adjusted. The adjusted hydrogen peroxide solution was supplied to the dropping device.
(Preparation of prefilled syringe and package)
A prefilled syringe containing 10 mL of heparin saline (100 units / mL) was prepared. The outer cylinder of the syringe was made of polypropylene.
Moreover, as shown in FIG. 1, the blister pack which consists of a container main body provided with the recessed part for prefilled syringes and a flange formation part, and the sealing film which seals a container main body so that peeling is possible was prepared. The sealing film is made of a multilayer laminate film of polyethylene terephthalate / polyethylene / crosslinked foamed polyethylene (Dai Nippon Printing). The container body is made of a low-density polyethylene / ionomer / low-density polyethylene multilayer laminate film (Dai Nippon Printing). The capacity of the package was 36 to 45 mL.

(Example and Experiment 1)
A sealing film was placed on the container body of the package, and heat sealing was performed on the container body, leaving about 2 cm from the end on the plunger side of the prefilled syringe that houses the film.
As shown in FIG. 1, biological indicators (Bacillus stearothermophilus ATCC 12980 10 ⁶ / piece) were installed on the cap tip A of the prefilled syringe, the inside B of the pusher cylinder, and the outside C of the pusher cylinder. And the prefilled syringe which installed the indicator was accommodated in the package.
And with the micro syringe, hydrogen peroxide water was dripped behind the push button of the plunger of the recessed part for accommodation. The hydrogen peroxide solution was dropped in three amounts of 15 mg / L, 20 mg / L, and 25 mg / L as the amount of hydrogen peroxide per inner volume of the package. Thereafter, the opening of the package is sealed with a heat sealer, and three types of measurement samples (15 mg / L, 20 mg / L) of a prefilled syringe-containing blister pack to which three types of hydrogen peroxide are added. 25 mg / L).

As shown in FIG. 6, the above-described measurement samples (15 mg / L, 20 mg / L, 25 mg / L added) and dummy samples (25 mg / L hydrogen peroxide added) are alternately packed in 50 unit boxes. (25 measurement samples + 25 dummy samples). A unit box packed with 50 dummy samples was prepared. These unit boxes were packed in a shipping box as shown in FIG. The unit box is made of white coat 550 g / m ² , and the cardboard is made of cardboard AF; K180 / S160 / K180 in which four unit boxes are housed as shown in FIG.

Thereafter, the shipping box was stored under conditions of 15 ° C. and 45% RH (Table 1 shown in FIG. 7) and under conditions of 30 ° C. and 65% RH (Table 2 shown in FIG. 8). The storage was performed so that the hydrogen peroxide addition position of the sample was on the lower side.
And the sample stored as mentioned above was taken out on the 7th and 14th day after addition of hydrogen peroxide, and the number of bacteria was measured.
The number of bacteria was measured by the following method.
First, the biological indicator was aseptically removed, and 10 mL of a sterilized cleaning solution (peptone 5%, sodium chloride 0.9%, Tween 80 0.1%) was added to extract and collect the attached bacteria.
This washing solution was diluted 10 ⁻⁰ (1 ×) as appropriate, then plate-mixed on a tryptospeptone agar medium (manufactured by Kyokuto Pharmaceutical Co., Ltd.), and cultured at 55 ° C. for 2 days. After culturing, the number of colonies that appeared was counted, and the number of bacteria was logarithmically labeled. The measurement was shown by the average value of each of three samples. As a result of the measurement, the results shown in Table 1 shown in FIG. 7, Table 2 shown in FIG. 8, and Table 3 shown in FIG. 9 were obtained.

(Result 1)
According to Tables 1 and 2, on the 14th day, the hydrogen peroxide addition amounts at 15 ° C./45% RH and 30 ° C./65% RH were all 15 mg / L, 20 mg / L, and 25 mg / L. In this case, the bacteria installed in the inner side B of the presser cylinder and the outer side C of the presser cylinder were completely killed (a mortality of 6 logs or more was confirmed). In addition, at the cap tip A, a decrease of 4 log or more was observed. The reason why 6 log was not reached is thought to be because hydrogen peroxide having a density higher than that of air did not reach the upper part of the packaging container sufficiently because the sample was stored so that the hydrogen peroxide addition position was on the lower side. Therefore, in this experimental system, the place with the lowest sterility (cold spot) is the place that is located above the hydrogen peroxide solution dropping position. It is considered that if the sample is stored at an angle at which hydrogen peroxide reaches the tip of the tip cap, or if the sample is overturned or shaken, the bacteria at the tip of the cap will be killed.
Moreover, according to Table 1, Table 2, and Table 3, it is considered that the number of viable bacteria generally decreases as the amount of hydrogen peroxide added increases.

(Experiment 2)
A blister pack containing a prefilled syringe with the same biological indicator used in Experiment 1 at the cap tip A, which is a cold spot, and 20 mg / L added as the amount of hydrogen peroxide per internal volume of the package Sixty pieces were packed in the unit box described above and stored in a shipping box. In the shipping box, three unit boxes filled with 60 dummy samples to which 20 mg / L of hydrogen peroxide was added were stored in addition to the sample unit box. In this experiment, it is considered that the blister pack is compressed and deformed, and the gas distribution of the hydrogen peroxide solution in the package is uneven. The shipping box was stored for 14 days under conditions of 30 ° C. and 65% RH.
Thereafter, a sample was taken out and the number of bacteria was measured as described above.
(Result 2)
When the number of bacteria was measured, at the tip of the cap A, 6 log or more of fungicidal properties were observed.

(Experiment 3)
As a package, a container prepared using a low-density polyethylene single-layer film (Dai Nippon Printing) so that the outer surface area is 160 cm ² was used. The capacity of the package was 40 mL.
A part of the package seal was peeled off, and the same biological indicator used in Experiment 1 was installed. The biological indicator was fixed so as not to be shaken in the package. And hydrogen peroxide water was dripped at the biological indicator installation side opposite surface with the micro syringe. The amount of hydrogen peroxide solution dropped was 20 mg / L as the amount of hydrogen peroxide per inner volume of the package. Thereafter, the opening of the package was sealed with a heat sealer to prepare a measurement sample.
Samples were stored under conditions of 30 ° C. and 65% RH. The storage was performed so that the hydrogen peroxide addition position of the sample was on the lower side.
And the sample stored as mentioned above was taken out 14 days after hydrogen peroxide addition dripping, and the number of bacteria was measured.
(Result 3)
When the number of bacteria was measured, 6 logs or more of fungicidal properties were observed.

(Experiment 4)
A container having a surface area of 50 cm ² and an internal volume of 10 mL is prepared with the following packaging material, and 50 μL of 6.0 w / v% hydrogen peroxide solution is dropped and sealed, and then timed under conditions of 55 ° C. and 25% RH. The amount of transpiration of hydrogen peroxide water droplets was measured.
Package 1. Polypropylene / polyethylene / stretched nylon / adhesive resin / aluminum-deposited polyethylene terephthalate / cross-linked polyethylene / 160
Package 2. Polyethylene terephthalate / ethylene-vinyl alcohol copolymer / nylon / polypropylene / 124
Package 3. Polyethylene terephthalate / polyethylene / crosslinked foamed polyethylene / 70
Package 4. Polyethylene single layer film / 70
Package 5 Polyethylene non-woven fabric (Tyvek (registered trademark))
(Result 4)
As shown in Table 4 shown in FIG. 10, in the package 1, the hydrogen peroxide solution in the package did not evaporate even after 80 hours or longer. In the package 2, the package 3, and the package 4, 10 to 24 hours were required for complete evaporation of the hydrogen peroxide solution.

1 Packaged medical supplies 2 Package 3 Medical supplies 41 Hydrogen peroxide solution

Claims (15)

A method of manufacturing a packaged medical article, wherein the manufacturing method is a state in which the medical article is housed and sealed in a hydrogen peroxide permeation adjustment functional package that allows and regulates permeation due to diffusion of hydrogen peroxide. In the package, a high-concentration atmosphere period in which the outer surface of the medical product is maintained at a sterilizable hydrogen peroxide atmosphere concentration, and after the high-concentration atmosphere period, the hydrogen peroxide is diffused in the package using the diffusion. A method for producing a packaged medical product, comprising a packaged medical product external surface sterilization step having a hydrogen peroxide discharge period for further outflow. The method of manufacturing a packaged medical article according to claim 1, wherein the high concentration atmosphere period is from immediately after hydrogen peroxide encapsulation to 14 days. The method for manufacturing a packaged medical product according to claim 1 or 2, wherein the external sterilization period of the medical product is 8 hours to 28 days after the hydrogen peroxide is sealed. The method for producing a packaged medical article according to any one of claims 1 to 3, wherein the concentration of hydrogen peroxide during the high concentration atmosphere period is 0.05 mg / L to 300 mg / L. In the manufacturing method, a hydrogen peroxide permeation adjustment functional packaging body is added with a hydrogen peroxide solution or a hydrogen peroxide gas filling step, and the packaging body is sealed after completion of the hydrogen peroxide addition step. The method for producing a packaged medical article according to any one of claims 1 to 4, further comprising a sealing step for stopping. The manufacturing method includes the step of preparing the package, the step of preparing the medical product, the step of storing the medical product in the package, and the hydrogen peroxide in the package in which the medical product is stored. The hydrogen peroxide addition step of adding water or filling with hydrogen peroxide gas and the sealing step of sealing the package after completion of the hydrogen peroxide addition step are performed. A method for producing the packaged medical product according to claim 1. The manufacturing method includes the steps of preparing a medical product that is housed and sealed in a hydrogen peroxide permeation-adjusting functional package, and adding hydrogen peroxide water or filling hydrogen peroxide gas into the package. The method for manufacturing a packaged medical article according to any one of claims 1 to 4, further comprising a hydrogen oxide addition step. The package according to claim 7, wherein the package includes an injection site to which a hydrogen peroxide or hydrogen peroxide gas injection device can be connected or punctured and the airtightness can be maintained after the device is removed. Manufacturing method for medical supplies. The said manufacturing method is a manufacturing method of the packaged medical supplies of Claim 7 or 8 which performs the sealing process which seals the hydrogen peroxide addition site | part of the said package after the said hydrogen peroxide addition process. The packaged medical article according to any one of claims 5 to 9, wherein the amount of hydrogen peroxide added to the internal volume of the package in the hydrogen peroxide addition step is 0.5 mg / L to 300 mg / L. Production method. The said package is provided with the container main body which has the recessed part for accommodation for accommodating the said medical supplies, and the peelable sealing film for sealing this recessed part opening. A method of manufacturing a packaged medical product according to claim 1. The method for producing a packaged medical product according to any one of claims 5 to 11, wherein the external sterilization step of the medical product is performed in a process of storing for 14 days or more after the hydrogen peroxide addition step. The method for manufacturing a packaged medical article according to any one of claims 1 to 12, wherein the medical article is a prefilled syringe. The method for manufacturing a packaged medical product according to any one of claims 1 to 12, wherein a plurality of different medical products packaged individually are stored in the package. A packaged medical article manufactured by the manufacturing method according to any one of claims 1 to 14.

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