JP2901669B2 - Manufacturing method of radiation sterilized medical device - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for producing a radiation-sterilized medical device. In particular, the present invention relates to a method for producing a radiation-sterilized medical device, preferably using a vacuum packaging method.

<Prior art> Radiation sterilization is now widely adopted as a reliable sterilization method, which does not require high pressure and high temperature in high-pressure steam sterilization, does not involve the problem of residual gas in gas sterilization, and has excellent features. However, on the other hand, there is a problem that the radiation sterilization causes deterioration of the polymer material and a decrease in strength and function over time after the sterilization, which hinders its spread. In order to solve such a problem, many proposals have been made and some of them have been implemented.

For example, JP-A-59-192373 discloses a method of irradiating radiation in an inert gas atmosphere, and JP-A-62-186866 discloses a method of vacuum-packaging and then sterilizing with radiation.
JP-A-204754 discloses a method of radiation sterilization by removing oxygen with an oxygen scavenger, and JP-A-63-111878 discloses a method of γ-ray sterilization in a substantially oxygen-free dry atmosphere. I have. According to these methods, since the medical device is shielded from oxygen, irradiation with the same amount of radiation as in the air surely suppresses a decrease in strength and a decrease in function. However, the resistance of the bacteria attached to the medical device to radiation also increases, and the D value, that is, the irradiation dose required to kill the number of bacteria in 10 minutes, increases. Law and Disinfection Law Vol.4 (Bunkodo) pages 163-16
This is a fact known from FIG. Therefore, in order to guarantee the same level of sterilization, it is necessary to increase the irradiation dose, and it can be said that the actual effect is that a sufficient effect on the strength deterioration and the function deterioration of the material described above has not been obtained.

Therefore, JP-A-58-134839 and JP-A-62-74364 disclose that a medical device is placed in an air-permeable bag, sterilized by radiation in air, and then the air inside is replaced with an inert gas. Alternatively, a method is disclosed in which an oxygen scavenger is enclosed in the inside and packaged with an oxygen impermeable material. According to this method, since the sterilization is performed in the air, there is no increase in the D value, and since oxygen is removed after the sterilization, deterioration over time can be prevented.

However, in these methods, when the sealing portion of the packaging bag is not complete and partially sealed, or when the bag is pinholed or damaged, oxygen in the outside air comes into contact with the sterilized medical device. As a result, the intended effect may not be obtained.

Japanese Patent Application Laid-Open No. 58-134840 discloses that an object to be sterilized is stored in a container which is open on one side, closed on the other side by a gas permeable material, and has a side surface made of a material having low oxygen permeability. ,
After sealing, radiation sterilization is carried out. After the sterilization, an inert gas is introduced through a gas permeable material, or a gas oxidizing agent is sealed in the container with a gas permeable material separated between the gas permeable materials. A radiation-sterilized packaging method is disclosed in which the inside of a container free of material is sealed. This method does not increase the D value of sterilization, and can prevent deterioration of the material over time. However, there is a gas permeable material on the opposite side of the opening, and when storing an object to be sterilized, gas permeable is used. Material damage is likely to occur. In particular, when the material to be sterilized has a pointed shape portion or uses gravity to store in a container and is dropped from above, the gas-permeable material is generally made of a porous material such as a nonwoven fabric. Therefore, the mechanical strength is weak and breakage easily occurs.

If such a container is damaged or if there is a pinhole in the container for any reason, and if the hermetically sealed part of the container is incomplete, the sterilized medical device will come into contact with the external air, Not only can the initial objectives not be fulfilled, but also sufficient assurance of sterility cannot be obtained.

<Problems to be Solved by the Invention> An object of the present invention is to solve the problems in the conventional method for producing a radiation-sterilized medical device. That is, the present invention provides an improved method for producing a radiation-sterilized medical device, in which the sterilization effect is more completely maintained, and oxygen is more completely prevented from being in contact with the medical device after radiation sterilization. It is intended to do so. In other words, the present invention provides a method for manufacturing a sterilized medical device with improved reliability and reliability when the medical device after radiation sterilization is placed in a deoxygenated state.

<Means for Solving the Problems> The inventors of the present invention have conducted intensive studies in order to achieve the object, and as a result, it has been found that it is advantageous to seal each of the double packaging bags airtightly, and furthermore, it is also possible to use vacuum packaging. Have been found to be preferable, and have reached the present invention.

That is, the present invention provides a medical device which is mainly made of a non-permeable material, is partially impermeable to bacteria, and contains a medical device through an opening of a packaging bag using a breathable material. Radiation sterilization is performed below, the oxygen inside the packaging bag is substantially removed, and then the packaging bag is hermetically sealed, and then the packaging bag is covered with an outer bag made of a material having low oxygen permeability. A method for producing a radiation-sterilized medical device, wherein oxygen in a gap between the packaging bag and the outer bag is substantially removed, and the outer bag is hermetically sealed in that state. .

According to the present invention, there is provided a method for producing a radiation-sterilized medical device, wherein oxygen in the packaging bag is substantially removed by removing gas in the packaging bag under reduced pressure; A method for producing a radiation-sterilized medical device in which oxygen in the void is substantially removed by removing the gas in the void under reduced pressure; wherein the packaging bag has the open port at an end provided with the bacteria-impermeable gas-permeable material. A method for producing a radiation-sterilized medical device, comprising: sealing the hermetic seal of the packaging bag with the inside portion of the packaging bag of the bacteria-impermeable breathable material, and then cutting the outer portion of the sealing portion; It includes a method for producing a radiation-sterilized medical device that is performed by removing.

 Hereinafter, the present invention will be described in more detail.

The medical device to which the present invention can be applied is effective when it is formed from a polymer material. However, the medical device may not only be formed entirely of a polymer material but also partially formed of a polymer material. Any known polymer material can be applied, and cellulose, cellulose acetate,
Polyvinyl alcohol, polymethyl-methacrylate,
Examples include polyacrylonitrile, polycarbonate, polyester, polyamide, ethylene-vinyl alcohol copolymer, silicone rubber, polyethylene, polystyrene, polyvinyl chloride, polyurethane, ABS resin, polybutadiene, and polypropylene.

The medical device of the present invention has at least a part of such a polymer material, and specific examples thereof include a hollow fiber type hemodialyzer, a blood filter, a plasma separator, and an adsorption type blood processing device. Body fluid treatment devices such as vessels. In addition, these may be manufactured by a commonly used method.

Further, a packaging bag (hereinafter also referred to as an interior bag) which is partially made of a non-breathable material using a bacteria-impermeable breathable material used in the present invention is mainly made of a non-breathable material. There is no particular limitation as long as a medical device as an object to be sterilized can be stored therein.
Any shape such as a box shape or a bag shape may be used. The material may be a material through which nitrogen and oxygen can permeate to some extent, but if possible, a material having a relatively low oxygen permeability is desirable.

Furthermore, the bacteria-impermeable, air-permeable material used in the present invention includes, for example, paper, nonwoven fabric, film, sheet, filter, membrane, porous body, etc., which allow gas to pass through but not microorganisms. It preferably has a hole or void having a diameter of 0.5 μm or less, and has a surface which can be sealed with heat or an adhesive.

The material having a low oxygen permeability used for the outer bag according to the present invention has an oxygen permeability coefficient of 50 NCC / m ² · Hr · atm or less, preferably 10 NCC / m ² · Hr · atm or less, and more preferably 5 NCC / m ² · Hr · atm or less.
For example, a film, a sheet, or the like having an m ² · Hr · atm or less. Examples of a material constituting such a material having a low oxygen permeability include metal foil, polyvinylidene chloride-based resin, polyvinyl alcohol-based resin, polyamide-based resin, polyester-based resin, polyolefin-based resin, and a combination of two or more of these. can give. The thickness of the material having a low oxygen permeability may be any thickness depending on the application, and may be any shape as long as it can cover the interior bag.

A preferred specific example of the step of substantially removing oxygen inside the inner bag in the production method of the present invention includes a method in which the gas inside the inner bag is removed under reduced pressure. As the gas, air which is an oxygen-containing gas is usually used. In such a case, the upper limit of the internal pressure after the decompression is sufficient as long as oxygen in the internal gas does not adversely affect the medical device after sterilization so that a problem does not occur. (Torr) degree is preferable,
Further, about 200 Torr is preferable. In addition, the lower limit of the internal pressure after the decompression, for example, when the inner bag is made of a soft plastic film or sheet, it is necessary that the inner bag is in a range that does not cause damage to the inner bag due to the reduced pressure, and is more preferably 50 Torr. Is 100 torr as a specific example.

Before performing the decompression process in the inner bag, oxygen may be removed by substituting the gas in the inner bag with an inert gas, in which case the preferable range of the pressure during the decompression process is Usually between 600 torr and 200 torr. Here, examples of the inert gas include nitrogen, helium, argon, carbon dioxide and the like.

By performing the decompression treatment in this manner, oxygen in the inner bag is substantially removed, and oxygen in the void between the inner bag and the outer bag is substantially removed by decompression to reduce the inner bag. This makes it possible to prevent damage due to expansion.

Further, as a preferred method for substantially removing oxygen in an oxygen-containing gas such as air existing in a gap between the inner bag and the outer bag in the production method of the present invention, a method of sealing after decompression treatment, that is, a method of vacuum packaging. Is raised. In this case, the pressure at the time of decompression is not particularly limited as long as it is in a range that can easily prevent adverse effects on the medical device, but is preferably about 400 Torr or less, more preferably 200 Torr or less. By evacuating this part, the volume of the form in which the object to be sterilized is packed is reduced, and an effect that is advantageous for subsequent packing and transportation can be obtained.

As the radiation in the production method of the present invention, γ-rays are usually used, and the irradiation conditions are usually about 2.0 to 5.0 Mrad.
It is appropriately selected within the range of the degree.

Further, the interior bag in the production method of the present invention is a bag mainly composed of a sheet using a non-permeable material,
At the end, a bacterium-impermeable breathable sheet is provided, and the other portion is sealed with an opening at the end provided with the bacterium-impermeable breathable sheet for storing a medical device. It is preferred to use By using the interior bag of such a form, it becomes easy to prevent the bacteria-impermeable air-permeable sheet from being damaged due to storage of the medical device.

Furthermore, in the manufacturing method of the present invention, when performing the hermetic sealing of the inner bag, the heat-sealing seal or the adhesive seal between the non-breathable sheets on the storage part side of the medical device that does not include the bacteria-impermeable breathable sheet part. It is practically advantageous to cut and remove the bacteria-impermeable and air-permeable sheet portion because the entire interior bag can be made compact. Alternatively, a method may be used in which the bacteria-impermeable and air-permeable sheet portion is covered with a sheet or the like made of an air-impermeable material so as to be hermetically sealed. Note that the hermetic seal in the present invention refers to hermetic sealing without air permeability.

Hereinafter, the present invention will be described more specifically with reference to examples.

<Examples> Example 1, Comparative Example 1 A cellulose acetate hollow fiber bundle containing glycerin or the like, which was previously immersed in a glycerin aqueous solution containing a buffer and then dried, was loaded into a cylindrical container, and tube sheets were provided at both ends. The hemodialyzer created by forming is stored in a polyethylene terephthalate and polypropylene laminate packaging bag having a bacteria-impermeable and air-permeable portion made of a polypropylene nonwoven fabric near the opening, and after completely sealing the opening, Irradiated with 2.5 Mrad of gamma rays. Then, under vacuum of about 100 Torr, air and other gases in the packaging bag are removed through the part of the breathable material and then completely sealed with the part of polyethylene terephthalate and polypropylene laminate,
Parts of the breathable material were cut off.

Then, the whole was covered with an outer bag made of a laminated film of aluminum and polypropylene, and vacuum-packed with a vacuum packing machine in a state where the pressure between the packaging bag and the outer bag was reduced by about 10 Torr. As a comparative example, a hemodialyzer was sealed in a packaging bag consisting of only aluminum and a polyethylene laminate film and irradiated with 2.5 Mrad of γ-ray. According to the dialysis type artificial kidney device approval criteria for these things,
A dialysis membrane eluate test was performed on the dialysis membrane immediately after irradiation and after storage for one month. As a result, both of the samples according to the present invention and the comparative examples passed the test immediately after γ-ray irradiation. Of course, the sterility test passed. On the other hand, after storage for one month after γ-irradiation, the sample according to the present invention passed all the items of the dialysis membrane elution test, but in the comparative example, ΔpH was 1.7, which was 1.5 times the reference value.
This was a rejection.

Example 2 A hemodialyzer was stored in a packaging bag in the same manner as in Example 1,
After completely sealing the opening, irradiate 2.5 Mrad of gamma rays,
Next, after the inside was replaced with nitrogen gas through the permeable portion, the pressure was reduced to about 400 Torr, and the packaging bag was hermetically sealed in that state, and the portion of the permeable material was cut off. Further, when the same operation as in Example 1 was performed, all items of the sterility test and the dialysis membrane eluate test after one month passed.

<Effects of the Invention> According to the production method of the present invention, an excellent effect of more completely maintaining the sterilization effect and ensuring and facilitating placing the medical device after radiation sterilization in a state not affected by oxygen. Is obtained.

In particular, vacuum packaging by a reduced pressure operation for removing oxygen to a concentration that does not adversely affect the present invention can be easily performed, and is practically advantageous.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Shuji Tanaka 2-1 Hinode-machi, Iwakuni-shi, Yamaguchi Prefecture Teijin Limited Medical Iwakuni Factory (56) References JP-A-62-186866 (JP, A) JP-A-62-74364 (JP, A) JP-A-59-105808 (JP, A) JP-A-58-134840 (JP, A) Japanese Utility Model Showa 56-125248 (JP, U) (58) Fields investigated (Int) .Cl. ⁶ , DB name) A61L 2/00-2/26

Claims (5)

(57) [Claims] 1. A medical device is stored through an opening of a packaging bag mainly made of a non-breathable material and partially made of a non-bacterium-impermeable and breathable material. Radiation sterilization is performed below, the oxygen inside the packaging bag is substantially removed, and then the packaging bag is hermetically sealed, and then the packaging bag is covered with an outer bag made of a material having low oxygen permeability. A method for producing a radiation-sterilized medical device, wherein oxygen in a gap between the packaging bag and the outer bag is substantially removed, and the outer bag is hermetically sealed in that state. 2. The method for producing a radiation-sterilized medical device according to claim 1, wherein the oxygen inside the packaging bag is substantially removed by removing the gas inside the packaging bag under reduced pressure. 3. The method for producing a radiation-sterilized medical device according to claim 1, wherein the oxygen in the space between the packaging bag and the outer bag is substantially removed by removing the gas in the space under reduced pressure. 4. The method for producing a radiation-sterilized medical device according to claim 1, wherein the packaging bag has the opening at an end provided with the bacteria-impermeable and breathable material. 5. The hermetic sealing of the packaging bag is performed by sealing the inside portion of the packaging bag with the bacteria-impermeable permeable material and then cutting and removing the outer portion of the sealing portion. Item 10. A method for producing a radiation-sterilized medical device according to Item 1.