JPH0318371A - Radiation sterilization method for medical appliance - Google Patents

Abstract

PURPOSE:To allow the sterilization at a low dose and to suppress the deterioration of the medical appliance with age by hermetically sealing the medical appliance by using an oxygen impermeable material in such a manner that an oxygen concn. attains a specific range, then irradiating the appliance with radiations. CONSTITUTION:The medical appliance formed of a high-polymer material is hermetically sealed by using the oxygen impermeable material in such a manner that the oxygen concn. attains a >=0.5% and <4% range and is then irradiated with the radiations at the time of sterilizing the medical appliance by irradiating the same with the radiations. A synthetic resin film or sheet laminated with aluminum foil or deposited with aluminum by evaporation is adequate as the oxygen impermeable material for hermetic sealing of the medical appliance. The synthetic resin film or sheet laminated with an oxygen barrier type resin, such as ethylene/vinyl alcohol unit copolymer of polyvinylidene chloride, is adequate for the applications where transparency is required. Gamma rays are most generally used for the radiations and the dose of the radiations is preferably in a 1.5 to 2.5Mrad range.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for sterilizing medical devices. More particularly, it relates to a method for radiation sterilization of medical devices formed from polymeric materials.

[Conventional technology]

A radiation sterilization method has been known as one of the methods for sterilizing medical tools. In particular, in recent years, as residual ethylene oxide in gas-sterilized medical instruments has become a problem, the importance of radiation sterilization has increased, and its application to various products is being considered.

[Problem that the invention seeks to solve]

By the way, when medical devices are made of polymeric materials, there is a problem that their strength and functionality deteriorate over time when they are irradiated with radiation, which has hindered their widespread use. Therefore, in order to solve such problems, many proposals have been made and some of them have been implemented.

For example, Japanese Patent Publication No. 55-23620 discloses a method of irradiating radiation in a wet state with a saturated moisture content or higher, and Japanese Patent Publication No. 59-192373 discloses a method of irradiating in an inert gas atmosphere. Disclosed. According to these methods, the medical device is cut off from oxygen, so if the same amount of radiation is irradiated as in the air, the decrease in strength and functionality will certainly be suppressed. However, the resistance of bacteria attached to medical devices to radiation increases, and the D value (the dose of radiation required to kill 1/10% of bacteria) increases, so it is not possible to guarantee the same level of sterilization. In order to do this, it was necessary to increase the irradiation dose, and the reality was that sufficient effects could not be obtained.

Therefore, Japanese Patent Application Laid-Open No. 62-74364 discloses a method in which medical devices are placed in a gas-permeable bag, radiation sterilized in the air, and then sealed together with an oxygen absorber in an oxygen-impermeable packaging material. There is. According to this method, since sterilization is performed in air, there is no increase in the D value, and since oxygen is removed by an oxygen scavenger after sterilization, deterioration over time can be prevented.

However, enclosing an oxygen absorber after sterilization is not only extremely complicated, as the product cannot be sterilized in its final packaging, but also deterioration of the polymeric material may progress if the oxygen absorber is delayed. This poses a major problem in terms of practicality.

[Means for solving problems]

In order to solve these problems, the present inventors have developed medical devices with an oxygen concentration of 4 to 12 by using oxygen-impermeable materials.
% atmosphere and then irradiation with radiation, and filed a patent application in Japanese Patent Application No. 62-318405.

As a result of further investigation, we found that when the oxygen concentration is less than 4%, the D value is slightly affected, but when it is 0.5% or more, the D value can be suppressed to a much lower value than when it is 0%. It has been found that such conditions may be preferable depending on the purpose and use, since deterioration of the polymeric material constituting the tool can be suppressed to a lower level. That is, in the present invention, when sterilizing a medical device made of a polymeric material by irradiating it with radiation, the medical device is made of an oxygen-impermeable material to create an atmosphere with an oxygen concentration of 0.5% or more and less than 4%. This is a radiation sterilization method for medical devices, which is characterized by sealing the devices as described above and then irradiating them with radiation.

[For production]

In the present invention, by setting the oxygen concentration before sterilization to 0.5% or more, an increase in the D value during sterilization can be suppressed, and sterilization at a low dose becomes possible. Oxygen is consumed by radiation irradiation, and an oxygen-free atmosphere can be created after sterilization, so deterioration of medical tools over time can be suppressed.

〔Example〕

Although the medical device to which the present invention can be applied is made of a polymeric material, it may not only be made entirely of a polymeric material, but may also be partially made of a polymeric material. Any known polymer material can be used, including polyethylene polypropylene, polystyrene, polyvinyl chloride, ethylene-vinyl acetate copolymer, and ethylene-vinyl alcohol copolymer. polyvinyl alcohol,
Polymethyl methacrylate. Polyacrylonitrile, polyester, polyamide, polycarbonate, polyurethane, cellulose, cellulose acetate, ABS resin, AS resin, silicone rubber, polybutadiene. Examples include polychloroprene, polyisoprene, styrene-butadiene copolymers, and natural rubber.

Further, as the oxygen-impermeable material for sealing the medical device, it is preferable to use a synthetic resin film or sheet laminated with aluminum foil or aluminum bonded. Such materials are opaque, but for applications requiring transparency, synthetic resin films or sheets laminated with oxygen barrier resins such as ethylene-vinyl alcohol copolymers and vinylidene chloride are suitable. In addition, other resin sheets than these may be usable in some cases because their oxygen permeability will be reduced if they are made thicker.

These materials are generally used to seal the medical device in the form of a bag or tray, but other forms are also possible.

Methods of sealing in an atmosphere with an oxygen concentration of 0.5% or more and less than 4% include a method of sealing in a gas atmosphere adjusted to an oxygen concentration in this range, and a method of packaging medical devices under vacuum. At the same time or after that, a gas having an oxygen concentration within the range specified by L is blown into the container to seal it, or at the same time or after the medical device is packaged under an appropriate reduced pressure, nitrogen gas is blown into the container to seal it, and the oxygen contained in the remaining air is used to seal the device. 6. There are methods to obtain the oxygen concentration described in (h), and methods to seal in air with an appropriate amount of oxygen scavenger. Such methods have been conventionally used for long-term preservation of foods, and are well known to those skilled in the art.

In addition, known devices can be used as they are.

Further, as the gas other than oxygen contained in the gas, nitrogen, carbon dioxide, an inert gas, etc. are preferable, and nitrogen is particularly preferable from the point of view of economical efficiency.

The radiation used in the present invention includes gamma rays,
X-rays, electron beams, and the like can be used, but gamma rays are most commonly used. In addition, the radiation dose is preferably in the range of 1.5 to 5.0 Mrad, and in particular in the present invention, a dose as high as that in irradiation in an oxygen-free atmosphere is not required, so it is in the range of 1.5 to 2.5 Mrad. is preferred.

According to the method of the present invention, the strength deterioration of medical devices due to sterilization can be reduced to a small extent, so it can be preferably applied to the sterilization of various medical devices, but especially when applied to highly functional medical devices. This is preferable because it is less likely to cause functional decline. Examples of such medical devices include hemodialyzers,
Examples include devices that use semipermeable membranes, such as blood filters, plasma separators, and artificial lungs. In particular, when the membrane is made of cellulose acetate, the D value tends to increase more easily than when radiation sterilizing ordinary polymeric materials because the membrane contains a large amount of glycerin. This is preferable because the D value is maintained at a low value.

The present invention will be explained in more detail with reference to specific examples below, but the present invention is not limited thereto.

Example 1 Approximately 100 hollow fiber membranes made of cellulose acetate containing glycerin are bundled and tied at the center with thread, and a bacterial solution (water suspension of Bacillus pumilus) is placed in the center.
0.1 d was added dropwise and air-dried. This is packed into aluminum laminated films under various degrees of vacuum using a vacuum packaging machine.
(polyethylene terephthalate/polyethylene/aluminum/polyethylene laminated film), and by blowing nitrogen gas into the package and sealing it, several samples with different internal oxygen concentrations were prepared. The obtained sample was then irradiated with gamma rays, and the D value at each oxygen concentration was measured. The results are shown in Table 1.

Sterilization is possible at absorbed doses below 2.5 Mrad, as shown in Table 18, but at concentrations below 0.1%, sterilization is possible at absorbed doses below 2.5 Mrad.
Requires a dose higher than d.

Example 2 Using a vacuum packaging machine and an aluminum laminated film, hemodialyzers containing cellulose acetate hollow fiber membranes were packaged to have various oxygen concentrations.2. Gamma rays were irradiated to give an absorbed dose of OMrad. After the irradiation, the oxygen flux inside the package was measured, and the results shown in Table 2 were obtained.

Table 2 As is clear from the above results, the D value indicates that the oxygen concentration is 0.
In the case of 0% and 0.1%, it shows a very high value,
When it exceeds 0.5%, it shows a considerably low value,
It can be seen that sterilization is possible at low doses. And 8D
As is clear from Table 2, if the oxygen concentration before packaging is less than 4%, the inside of the package after radiation irradiation is generally widely used to guarantee sterilization. 0 parts can be in a state where no oxygen exists. Therefore, subsequent deterioration over time can be suppressed, and a decrease in strength and function can be prevented when stored for a long period of time.

Example 3 Hollow fiber hemodialyzers were packaged in the same manner as in Example 2 to produce packages with different internal oxygen concentrations.

Then, these were irradiated with gamma rays so that the absorbed dose was 2.0 Mrad. Next, we conducted a dialysis membrane eluate test on the membrane immediately after irradiation in accordance with the Medical Plastics Association's proposed standards for artificial kidney devices, and the membrane based on the present invention passed all items.
For comparison, a sample sealed in air failed the ΔpH. The measurement results of ΔpH are shown in Table 3 (passing basis! 1S
The value is 1.5 or less).

(Margin below C) Table 3 From the results of Table 3, it can be seen that in order to keep the Δp l-1 value low, it is necessary to lower the oxygen concentration before light 1.1.

As is clear from the results of Examples 1 to 3, in order to keep the [■] value low and also to reduce the deterioration of the polymer material due to radiation irradiation, the oxygen concentration should be set to 0.5% or more and less than 4%. is found to be appropriate.

〔Effect of the invention〕

According to the present invention, since the D value in radiation sterilization can be kept low, absorption line 1
Sterilization is possible at 2.5 Mrad or less. Moreover, since the inside of the package can be kept in an oxygen-free state after sterilization, deterioration of the medical device over time can be prevented. Furthermore, since there is no need for troublesome operations such as enclosing an oxygen absorber after sterilization, it is also excellent in practicality.

Claims (1)

[Claims] When sterilizing a medical device made of a polymeric material by irradiating it with radiation, the medical device is sealed using an oxygen-impermeable material in an atmosphere with an oxygen concentration of 0.5% or more and less than 4%, A radiation sterilization method for medical tools, which comprises then irradiating radiation.