JPS6229060B2 - - Google Patents

Description

[Detailed description of the invention] The present invention relates to a method for sterilizing artificial organs.

Artificial organs such as artificial kidneys have undergone rapid development in recent years, and artificial lungs, artificial livers using activated carbon adsorbents, condensate treatment devices, plasma separation devices, etc. have been put into practical use. Furthermore, various treatment devices using adsorbents (including adsorbents and adsorbents, hereinafter the same) have been developed (for example, Japanese Patent Application Laid-open Nos. 57-75141 and 58-75).
No. 27559, No. 58-10055, No. 58-12656, and specification of Japanese Patent Application No. 1982-71913).

Generally, these artificial organs and treatment devices are sterilized in the final manufacturing process to prevent contamination during the manufacturing process, and then sealed in an aseptic condition before being provided to the user.

As the sterilization method used, high-pressure steam sterilization using an autoclave has become common in recent years.

Other methods include filling formaldehyde aqueous solution or ethylene oxide gas, and γ
There are methods of irradiating with radiation, but these methods have safety issues such as sterilizing agent remaining during use and deterioration of the container, so they are not very common.

However, internal fillings (including fillers, fillers, , hereinafter the same), if only the conventional method of heat sterilization by adding high-pressure steam or high-temperature water from the outside of the artificial organ is used, internal filling of the part near the center of the artificial organ can be avoided. It takes a long time to raise an object to a predetermined temperature, or to sterilize this part and then cool it from the outside to bring it down to a predetermined temperature. Moreover, in this case, the internal filling near the outer wall of the artificial organ is heated to a temperature higher than the sterilization temperature in order to raise the filling near the center of the artificial organ to a predetermined temperature. The long exposure to high temperatures required for artificial organs can lead to problems such as deterioration of the quality of the containers and internal fillings used in artificial organs.

The present inventor has completed the present invention as a result of extensive research aimed at developing a method for sterilizing artificial organs that eliminates the above-mentioned problems.

That is, the present invention provides a method for sterilizing artificial organs using high-pressure steam in an autoclave using a liquid that has been previously sterilized and kept at a high temperature (hereinafter referred to as sterilized high-temperature liquid) close to the steam sterilization temperature of the artificial organ. ) is passed into the artificial organ, its internal temperature is rapidly brought to almost the sterilization temperature, and while the liquid is being filled,
After sterilizing by maintaining the sterilization temperature for a predetermined period of time by external heating with high-pressure steam, the liquid that has been previously sterilized and held on the high temperature side (hereinafter referred to as the sterilized liquid on the high temperature side) is delivered to the artificial organ. Sterilization of artificial organs characterized by passing a sterilized low-temperature liquid obtained by cooling with a cooling device midway through the artificial organ, rapidly cooling the internal temperature, and completing the sterilization operation. Regarding the method.

In one embodiment of the present invention, the interior of the artificial organ and the solid or liquid internal filling filled therein are sterilized in advance by a method such as steam sterilization at a temperature close to the steam sterilization temperature of bacteria that have adhered to or become mixed in. Liquids held at high temperatures (usually water, physiological saline, or their aqueous solutions containing some stabilizers) are kept in a state where they cannot function as a cooling device, for example, when no refrigerant is flowing through them. A liquid is passed through the inside of the artificial organ via a cooling device to rapidly raise the temperature of the inside of the artificial organ and the internal filling to approximately the sterilization temperature, and in the presence of the liquid, heating is performed from the outside of the artificial organ using high pressure steam. After maintaining the temperature required for sterilization and performing the sterilization operation for the required time, the sterilized high-temperature liquid is transferred to the artificial organ in a state where it can function as a cooling device, for example, by using a refrigerant. The artificial organ is cooled to a cold liquid (sterilized low-temperature liquid) of approximately 50° C. or lower through the cooling device that has been converted to a state in which liquid is being passed through the artificial organ, and the liquid is passed through the artificial organ. This is a sterilization method that rapidly cools the

The method of the present invention has the drawback of conventional methods which sterilize by heating and sterilizing only by adding high pressure steam or high temperature water from outside the artificial organ. The advantage is that there is no quality deterioration or performance deterioration of the internal filling material due to the long time it takes to raise the temperature, or there is no quality deterioration or performance deterioration of the internal filling material etc. due to prolonged heating at a temperature higher than the sterilization temperature. It has the advantage of not being Furthermore, it has the advantage that the quality and performance of the internal fillings do not deteriorate due to prolonged cooling, which is a disadvantage of natural cooling or forced cooling using cold water from outside the artificial organ. Furthermore, the sterilized low temperature liquid used in the present invention is guaranteed to be sterile, since it has just been prepared by cooling the sterilized high temperature liquid. Another effect is the simplification of sterilization operations. Furthermore, the sterilized low-temperature liquid can be used as it is as the internal filling liquid for sterilized artificial organs, and there is no need to take measures against thermal expansion of the filling liquid during heat sterilization and shrinkage during cooling. You can get the effect. It is also clear that at the same time the external surface of the artificial organ is steam sterilized.

The sterilized high-temperature liquid is usually sterilized under the conditions described in the Japanese Pharmacopoeia, such as steam sterilization using a temperature of 105°C or higher, often 115 to 130°C or higher, and usually at 115°C. Conditions such as 30 minutes at 121℃, 20 minutes at 126℃, and 5 minutes at 126℃ are adopted.

In addition, the sterilized high-temperature liquid is a liquid that is once sterilized at a high temperature and then cooled to convert into a sterilized low-temperature liquid, and is not necessarily a sterilized liquid for heating artificial organs. It does not need to be at the same high temperature as the high-temperature liquid that was used, but it can be made by lowering the temperature of a sterilized high-temperature liquid tank.
It may be normal pressure high temperature water of ~95°C, physiological saline or an aqueous solution thereof containing some stabilizers.

Sterilized high temperature liquid and sterilized low temperature liquid The sterilized high temperature side liquid for preparation may be freshly sterilized, or once sterilized, it may be properly sterilized to prevent bacterial growth. temperature (e.g. 70
℃ or higher, preferably 80℃ or higher) for a relatively short period of time (for example, within 24 hours) in an appropriate container. Moreover, as already mentioned, they may be prepared by simply cooling the former supplied from the same storage tank to obtain the latter, or prepared separately under different conditions or in a device within the range that satisfies the above sterilization conditions. The liquids may be supplied separately, for example, one from a 121°C storage tank and the other from an 80°C storage tank.

The filling inside the artificial organ includes a solid material such as an adsorbent or a membrane, and an aqueous solution coexisting therewith (such as a stabilizer solution for maintaining the effectiveness and shape of the solid material).

As the cooling device, a known liquid-liquid or gas-liquid heat exchanger such as a coiled tube type, double tube type, or plate type may be used.

In addition, in the embodiment shown in FIG. 1, the sterilized high-temperature liquid and the sterilized low-temperature liquid for liquid production are respectively passed through this cooling device. Passing a sterile, hot liquid through the artificial organ may also sterilize the cooling device.

According to another embodiment of the invention, the sterilized hot liquid is passed directly into the artificial organ without passing through the cooling device, and after the artificial organ is sterilized, the sterilized hot liquid is However, the liquid may be cooled by passing through a separately provided conduit that leads to the artificial organ via a cooling device, for example, and then flowing into the artificial organ.

The refrigerant used may be a liquid refrigerant, such as cold tap water, industrial water or other cooling water, or cold air or other gas.

As described above, the method of the present invention shortens unnecessary thermal history, which is different from sterilization itself by heating and cooling in artificial organ sterilization methods using high-pressure steam,
This is a very useful sterilization method that can minimize the problem of thermal deterioration of the walls and internal fillings of artificial organs.

Hereinafter, one embodiment of the present invention will be described based on the drawings, but the present invention is not limited to this embodiment.

Note that FIG. 1 is a schematic system diagram showing an apparatus for carrying out the sterilization method of the present invention.

An artificial organ 2 is installed in a high temperature steam sterilizer 1. The device 1 is provided with a heater 3, a high-temperature distilled liquid 4, and a discharge valve 5. A high temperature liquid tank 6 and a cooling device 7 are installed outside the device 1. A jacket 8 is installed in the high temperature liquid tank 6 to heat the tank 6, and a breathing filter 9 is provided above the tank 6. The high temperature liquid tank 6 and the cooling device 7 are connected via a valve 10 with pressure-resistant stainless steel piping. Cooling device 7
and the artificial organ circuit inlet 11 are connected by pressure-resistant stainless steel piping and, inside the high-pressure steam sterilizer 1, by a heat-resistant tube.

First, the same water, physiological saline, or an aqueous solution containing some stabilizer as the filling liquid for the artificial organ 2 is placed in the high-temperature liquid tank 6, and heated to a high temperature using the jacket 8 to sterilize it. liquid.
Sterilization conditions are preferably carried out in accordance with the Japanese Pharmacopoeia. i.e. 30 minutes at 115℃, 20 minutes at 121℃
It is preferable to choose sterilization conditions of either 15 minutes at 126° C. or 15 minutes at 126°C.

Next, the obtained sterilized high-temperature liquid is transferred to a high-temperature liquid tank 6 at a temperature equal to or higher than the sterilization temperature of the artificial organ.
keep it inside. The sterilization temperature for such an artificial organ is also preferably selected from temperatures in accordance with the Japanese Pharmacopoeia.

Next, after heating the heating water in the high-pressure steam sterilizer 1 under pressure, the valve 10 is opened, and the sterilized high-temperature liquid in the high-temperature liquid tank 6 is supplied into the artificial organ 2 through the circuit inlet 11. do. At this time,
No refrigerant is allowed to flow through the cooling device 7. That is, without heat exchange, the sterilized high-temperature liquid in the high-temperature bath 6 is supplied to the artificial organ 2 at high temperature, and is passed through the inside of the artificial organ 2 to replace the internal filling liquid. The internal temperature of organ 2 is rapidly raised to approximately the heat sterilization temperature. The amount of the sterilized high temperature liquid passed through the artificial organ is at least 1 times, preferably 2 to 5 times, the internal volume of the artificial organ. In addition,
It is preferable to measure the time required to raise the temperature of the high-pressure steam sterilizer 1 in advance, and to make the time when the replacement inside the artificial organ 2 ends and the time when the temperature rise of the device 1 ends coincide with each other.

After the replacement and the temperature increase of the device 1 are completed, the valve 10 is closed and the artificial organ 2 is sterilized for a predetermined period of time. When sterilization is completed, the refrigerant is flowed into the cooling device 7, the valve 10 is opened, and the water, physiological saline, or an aqueous solution containing a stabilizer, etc. in the high temperature liquid tank 6 is cooled and passed through the artificial organ. Replace. This replacement is also 1 times or more, preferably 2 to 5 times the internal volume of the artificial organ.

Note that sterilization refers to a state in which the inside of an artificial organ reaches a sterilization temperature, and sterilization does not include heating or cooling.

By performing these operations, the time required to raise and cool the temperature inside the artificial organ is shortened. In the case of the conventional method of heating only from the outside, it takes a considerable amount of time from the time the inside of the heat sterilization can reaches a predetermined temperature until the center of the artificial organ reaches a predetermined temperature. For example, for an artificial organ with an internal diameter of 65 mm and filled with adsorbent and filling fluid, the time can be as long as 120 minutes. However, using the method of the present invention, that time is reduced to 5-10 minutes. The same thing can be said in the case of cooling. Therefore, when conventional methods heat sterilize the center of an artificial organ, the artificial organ is exposed to high temperatures for a long period of time, resulting in material deterioration, but with the method of the present invention, the artificial organ is exposed to high temperatures for a long time. Such problems do not arise because the exposure time is shortened. In addition, when performing replacement for cleaning and cooling after sterilization, ensuring sterility becomes a problem, but in the method of the present invention, the sterilizing liquid maintained at sterile conditions is cooled in a sealed circuit and supplied. This ensures complete sterility.

Furthermore, when heat sterilizing an artificial organ whose interior is filled with a filling liquid, damage to the artificial organ due to thermal expansion of the filling liquid becomes a problem, but with the method of the present invention, thermal expansion is absorbed outside the artificial organ, so this is a problem. do not become.

The method of the present invention can be applied to artificial organs in general, and it goes without saying that it can be applied not only to sterilization at the final stage of the manufacturing process, but also to sterilization of artificial organs during use.

As described above, the sterilization method of the present invention is a useful method that can solve the process problems of conventional sterilization methods and provide highly stable artificial organs.

[Brief explanation of the drawing]

FIG. 1 is a schematic system diagram showing an embodiment of an apparatus for carrying out the sterilization method of the present invention. (Main symbols in the drawing) 1: High pressure steam sterilizer,
2: Artificial organ, 6: High temperature liquid bath, 7: Cooling device, 1
0: Valve.

Claims (1)

[Claims] 1. When sterilizing an artificial organ using high-pressure steam in an autoclave, a pre-sterilized liquid that is kept at a high temperature close to the steam sterilization temperature of the artificial organ is passed through the artificial organ to rapidly raise its internal temperature. After filling the liquid with the liquid, the liquid is maintained at the sterilization temperature for a predetermined period of time by external heating using high-pressure steam, and then the liquid, which has been previously sterilized and kept at the high temperature side, is delivered to the artificial organ. A method for sterilizing an artificial organ, characterized by passing a sterilized, low-temperature liquid obtained by cooling it with a cooling device into the artificial organ during the process, and rapidly cooling the internal temperature of the artificial organ.