JPH0448063B2 - - Google Patents

Description

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

[Conventional technology]

Artificial organs such as artificial kidneys have undergone rapid development in recent years, and artificial lungs, artificial livers using activated carbon adsorbents, ascites 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 (Japanese Patent Application Laid-Open Nos. 57-75141, 58-27559,
(See Publications No. 58-10055, No. 58-12656, and the specification of Japanese Patent Application No. 71913/1983).

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

In recent years, high-pressure steam sterilization using an autoclave has been commonly used as a sterilization method.

Other methods include filling the container with formaldehyde aqueous solution or ethylene oxide gas, and irradiating with gamma rays, but these methods have concerns that the sterilizer may remain in the container during use, and that the sterilizing agent may be exposed to gamma rays. There are safety issues, such as the possibility that the contents or container may deteriorate and produce harmful substances inside, and their adoption in practice is often discouraged.

However, when employing the high-pressure steam sterilization method using an autoclave, the internal filling ( If the artificial organ is stored as a filling material (including filling materials, the same shall apply hereinafter), 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, the inside of the artificial organ may be When raising the temperature of the internal filling near the center to a predetermined temperature required for sterilization, or after sterilization, it is preferably cooled from the outside to a temperature below which the contents are difficult to deteriorate even if kept for a long time. When removing the contents from the autoclave, it takes a long time to bring the contents down to a temperature that can be handled with bare hands without the operator feeling too hot. In other words, when heating an artificial organ, the part near the outer wall of the artificial organ is heated to a temperature higher than the sterilization temperature in order to raise the temperature of the filling at the center of the artificial organ to the temperature required for sterilization. Due to long exposure to high temperatures required for sterilization, the quality of the containers and internal fillings used in artificial organs deteriorates, resulting in fatal defects such as the removal of active ingredients added to adsorbents. arise.

Therefore, when sterilizing an artificial organ using high-pressure steam in an autoclave, a liquid (usually water, physiological saline, or After passing an aqueous solution (containing some stabilizers, etc.) into the artificial organ and bringing its internal temperature almost to the sterilization temperature, external heating with high-pressure steam is used to maintain the temperature required for sterilization for a predetermined period of time. Sterilize the artificial organ for a period of time that allows grade sterilization (for example, 20 minutes when 10 ^-8 grade sterilization is performed by high-pressure steam sterilization at 121 ° C.),
Next, the sterilized high-temperature liquid that has not yet been passed through the artificial organ is cooled by a cooling device, and the liquid is passed through the artificial organ to cool the inside, thereby completing a series of sterilization operations. A method for sterilizing artificial organs by rapid heating and cooling has been reported (Japanese Patent Application No. 58-245761 and the same).
59-12462). In other words, this method uses rapid heating and cooling to prevent unnecessary desorption of a large amount of active ingredients and a decrease in the medicinal efficacy of the product. However, with this method, when passing a sterilized high-temperature liquid into an artificial organ, the sterilized high-temperature liquid passes through the device that allows the liquid to pass through the artificial organ. It is difficult to maintain the temperature of the liquid immediately before the artificial organ at the temperature required for sterilization because heat is taken away by the artificial organ. Therefore, there is a problem in that it takes a long time to bring the temperature inside the artificial organ almost to the sterilization temperature.

In addition, when cooling, if the temperature of the liquid flowing into the artificial organ is not sufficiently cooled, there will be a slight delay in the time for the artificial organ to start cooling from the inside, and it will take a long time to lower the temperature to the set temperature. It will take a while.

[Problem that the invention seeks to solve]

In view of this situation, the inventors of the present invention have conducted intensive research and have found that, when sterilizing an artificial organ, the artificial organ is not exposed to high temperatures for a long period of time, thereby preventing quality deterioration and performance deterioration of the internal filling material of the artificial organ. We have discovered a method to sterilize artificial organs without causing damage.

[Means for solving problems]

That is, when sterilizing an artificial organ using high-pressure steam in an autoclave, the present invention uses a liquid that is previously sterilized and kept at a high temperature close to the steam sterilization temperature of the artificial organ (hereinafter referred to as a high-temperature liquid for a sterilized predetermined temperature liquid). When passing liquid into an artificial organ using a liquid passing device, the liquid that has lost heat in the device and has dropped to a temperature lower than a predetermined temperature is discharged just before the artificial organ and Only the liquid at the specified temperature (hereinafter referred to as sterilized predetermined temperature liquid) is passed into the artificial organ, and after the internal temperature reaches almost the steam sterilization temperature, the internal temperature is heated to a predetermined temperature by external heating with high pressure steam while the liquid is being filled. Sterilization is performed by maintaining the sterilization temperature for an hour, and then cooling the liquid (hereinafter referred to as sterilized high-temperature liquid) that has been previously sterilized and maintained at a high temperature with a cooling device while passing through the artificial organ. The present invention relates to a method for sterilizing an artificial organ, which comprises passing a sterilized low-temperature liquid (hereinafter referred to as sterilized low-temperature liquid) into the artificial organ using a liquid passing device to cool the inside of the artificial organ.

〔Example〕

The present invention provides that when a liquid passing device is used to pass a sterilized high-temperature liquid at a predetermined temperature close to the steam sterilization temperature of the artificial organ, the liquid from which heat has been removed in the device is passed immediately before the artificial organ. Then, the device is discharged from the outlet, and only the sterilized liquid at a predetermined temperature is allowed to flow through the device, until its internal temperature reaches almost the steam sterilization temperature, and while the liquid is being filled,
Sterilization is performed by maintaining the steam sterilization temperature for a predetermined period of time by external heating using high-pressure steam.

The types of artificial organs and their fillings used in the present invention are not particularly limited.

In the present invention, a sterilized predetermined temperature liquid close to the steam sterilization temperature of an artificial organ refers to a liquid that has been sterilized in advance by a method such as steam sterilization and is in a state where it cannot function as a cooling device, such as when a refrigerant is passed through it. These aqueous solutions, usually containing water, saline, or some stabilizer, are passed through the artificial organ through a non-condensed cooling device.

The predetermined temperature is 0 to 0 higher than the temperature employed as the sterilization condition when externally steam sterilizing the artificial organ.
The temperature is 3°C higher. For example, since steam sterilization temperatures are often in the range of 115-134°C, the predetermined temperature will be 115-137°C.

In the present invention, a device for passing a liquid used for sterilizing an artificial organ into an artificial organ includes a sterilizing liquid storage tank for heating and storing the sterilized high-temperature liquid for predetermined temperature liquid, and piping connecting the storage tank and the artificial organ. In addition, the pipe is equipped with a valve installed immediately after the storage tank, a cooling device, and a pipe switching valve connected to the pipe leading to the discharge port in order to discharge the liquid whose temperature has dropped below a predetermined temperature. A thermometer is provided immediately before the discharge port to check whether the temperature of the liquid inside the pipe is lower than a predetermined temperature.

If an artificial organ is exposed to high temperatures for a long period of time, the quality and performance of internal fillings etc. will deteriorate. Therefore, in the method of the present invention, the device for supplying liquid to the artificial organ is heated immediately before the connection with the artificial organ. Using the discharge port, among the high temperature liquid for sterilized predetermined temperature liquid, which is close to the steam sterilization temperature of the artificial organ, the liquid whose temperature is lower than the predetermined temperature from which heat has been removed in the device is discharged, and the sterilized predetermined temperature liquid is discharged. By passing the liquid through the artificial organ and replacing the internal filling liquid, the internal temperature of the artificial organ reaches almost the steam sterilization temperature in a short time. The number of times the internal filling liquid is replaced is 1 or more times, preferably 2 to 5 times.

The temperature for steam sterilization of artificial organs is not particularly limited as long as it can be sterilized without deteriorating the quality of the container or internal filling used in the artificial organ.
Usually the conditions listed in the Japanese Pharmacopoeia, e.g.
A temperature of 105°C or higher, often 115 to 134°C, is used.
The predetermined time is usually 30 minutes at 115℃, and 30 minutes at 121℃.
Conditions such as 20 minutes at 126 degrees Celsius, 15 minutes at 126 degrees Celsius, and 3 minutes at 134 degrees Celsius are used.

The method of sterilizing by maintaining at the steam sterilization temperature for a predetermined period of time by external heating with high-pressure steam is carried out in the same manner as a normal high-pressure steam sterilization method using an autoclave.

Next, the present invention cools the inside of the artificial organ by passing a sterilized low-temperature liquid that has been cooled by a cooling device during the passage of the sterilized high-temperature liquid into the artificial organ and replacing the internal filling liquid. urge The number of times the internal filling liquid is replaced is 1 or more times, preferably 2 to 5 times. In addition, when cooling an artificial organ, a sterilized high-temperature liquid, or in some cases a sterilized high-temperature liquid for a predetermined temperature, is cooled by passing it through a cooling device and then discharged from the system just before the artificial organ. The temperature of the artificial organ may be lowered by the cooling device, and the lowered temperature of the liquid may be used to cool and lower the temperature of the high-temperature conduit leading directly to the artificial organ. In this case, the fluid in the fluid passage device, that is, the pipe leading to the artificial organ, is not sufficiently cooled and the fluid, which remains at a high temperature, is discharged just before the artificial organ, and only the fluid that has cooled to the set temperature is discharged. Since the liquid is passed through the artificial organ, the inside of the artificial organ can be cooled in a shorter time.

In other words, after confirming that the temperature has sufficiently fallen to the set temperature (for example, less than 60℃, preferably 20 to 40℃) using a thermometer installed just before the artificial organ, By waiting for a predetermined period of time (for example, 20 minutes) to pass, and then switching the flow of the liquid from the outside discharge side to the flow side to the artificial organ just before the artificial organ, the sterilized low-temperature liquid is immediately transferred to the artificial organ. Passes fluid into the organ.

Here, the sterilized high-temperature liquid is a liquid used for the purpose of being sterilized at a high temperature and then being cooled and converted into a sterilized low-temperature liquid. It may be a high-temperature liquid for temperature liquids, but it does not necessarily have to be the same high-temperature liquid as this.
It may be normal pressure high temperature water of ~95°C, physiological saline or an aqueous solution thereof containing some stabilizers.

The sterilized low-temperature liquid refers to the sterilized high-temperature liquid passed through the cooling device in a state where it can function as a cooling device, for example, in a state where a refrigerant is passed through the cooling device to a temperature lower than 60°C, preferably 20 to 40°C. refers to something that is cooled to

Examples of the cooling device include known liquid-liquid or gas-liquid heat exchangers such as a spiral tube type, double tube type, and plate type.

Further, as the refrigerant used in the cooling device, a refrigerant such as low-temperature tap water, industrial water, or other cooling water, or low-temperature air or other gas may be used.

The sterilized high-temperature liquid for predetermined temperature liquid close to the steam sterilization temperature of artificial organs and the sterilized high-temperature liquid for adjusting sterilized low-temperature liquid may be immediately sterilized, or once sterilized, the sterilized high-temperature liquid may be used to prevent bacterial growth. (e.g. 70℃ or higher, preferably 80℃ or higher)
may be kept in a suitable container for a relatively short period of time (e.g. within 24 hours). Also, they are
They may be supplied from the same storage tank, or may be supplied separately under different conditions or within different devices within the range that satisfies the sterilization conditions.

In the case of the embodiments shown in FIGS. 1 to 3, the sterilized high temperature liquid for predetermined temperature liquid and the sterilized high temperature liquid for adjusting the sterilized low temperature liquid are respectively passed into the artificial organ through a cooling device. . Therefore, passing the hot fluid for the sterilized temperature fluid may also sterilize the cooling device. On the other hand, not only the sterilized high-temperature liquid for a predetermined temperature liquid and the sterilized high-temperature liquid to be cooled pass through the cooling device and reach the artificial organ, but also, for example, the refrigerant pipe is a sterilized high-temperature liquid for a predetermined temperature liquid. A cooling device is placed in the high temperature liquid tank, such as through a sterile liquid storage tank, and the cooling device is used to store high temperature liquid for sterilized predetermined temperature liquid and sterilized high temperature liquid for preparing sterilized low temperature liquid. It may be something that exists inside.

In addition, after the sterilized high-temperature liquid is directly introduced into the artificial organ without passing through a cooling device, and the artificial organ is sterilized, the sterilized high-temperature liquid is then passed through the cooling device, for example, into the artificial organ. After passing through a separately provided conduit and being cooled, the fluid may flow into the artificial organ.

Below, an embodiment of the present invention in which high-pressure steam sterilization at 121° C. for 20 minutes is performed will be described based on FIGS. 1 to 3. The present invention is not limited to such embodiments. That is, the sterilization conditions for high-pressure steam sterilization referred to in this specification are not limited to 121° C. for 20 minutes, and can be selected according to the characteristics of the artificial organ container and adsorbent. In other words, the conditions can be selected as 115°C for 30 minutes, 126°C for 15 minutes, etc. according to the Japanese Pharmacopoeia.
In these cases, it is desirable to change the temperature setting value and time in parallel as appropriate according to the following explanation.

In addition, although physiological saline is used as the sterilized high-temperature solution, sterilized high-temperature solution, and sterilized low-temperature solution in this example, it is also possible to use water or an aqueous solution of other stabilizers. Of course.

An embodiment of the sterilization method of the present invention will be described using an apparatus for carrying out high-pressure steam sterilization at 121° C. for 20 minutes based on the schematic system diagram shown in FIG.

An artificial organ 2 is placed in an autoclave 1. The autoclave 1 is provided with a heater 3, a high-temperature distillate 4, and a discharge valve 5. A sterilizing liquid storage tank 6 and a cooling device 7 are installed outside the autoclave 1. A jacket 8 is installed in the sterilizing liquid storage tank 6 so that the tank 6 can be heated, and a breathing filter 9 is provided above the tank 6. Sterile liquid storage tank 6 and cooling device 7
and are connected to each other via a valve 10 with pressure-resistant stainless steel piping. Cooling device 7 and artificial organ circuit inlet 1
1 through pressure-resistant stainless steel piping, and the artificial organ circuit outlet 16 and valve 14 are connected through pressure-resistant stainless steel piping. A three-way valve 13 is provided as a pipe switching valve in the pressure-resistant stainless steel pipe just before the artificial organ circuit inlet 11, and this valve is linked so that the opening and closing of each downstream pipe are reversed, or both are open or closed. and work. The pipe on the downstream side of the three-way valve 13, which is different from the artificial organ 2 side, serves as a discharge port. Further, a thermometer 15 is provided outside the autoclave 1 and upstream of the three-way valve 13.

First, with the valve 10 closed, the same water as the filling liquid for the artificial organ 2, physiological saline, or an aqueous solution thereof containing some stabilizer is poured into the sterile liquid storage tank 6, and heated to a high temperature of 127°C using the jacket 8. Heat to
The liquid was sterilized by holding it for 30 minutes or more, resulting in a sterilized high-temperature liquid that became a sterilized high-temperature liquid for a predetermined temperature liquid and a sterilized high-temperature liquid.

The obtained sterilized liquid at a high temperature of 127°C was maintained in a sterilizing liquid storage tank 6 at a temperature of 123 to 127°C, which is close to the steam sterilization temperature of the artificial organ 2. At this time, the gas phase inside the sterilization liquid storage tank 6 was almost pressurized, and the pressure reached about 2.3 atm.

Next, the artificial organ 2 side of the three-way valve 13 is closed, the discharge port side is opened, the valve 10 is opened, and the sterile liquid storage tank 6 is opened.
A sterilized high-temperature liquid close to the steam sterilization temperature of the artificial organ 2 inside was passed through as a sterilized high-temperature liquid for a predetermined temperature, and was discharged through the three-way valve 13.

A predetermined temperature in which the liquid passing device is heated to 121° C. or higher, the amount of heat removed from the liquid is reduced, the amount thereof is approximately constant, and the temperature of the discharged liquid is close to the steam sterilization temperature of the artificial organ; In other words, 121℃ or higher (121~
When it is confirmed by the thermometer 15 that the temperature is almost constant (123°C), the outlet side of the three-way valve 13 is closed,
The side of the artificial organ 2 was opened and a sterilized liquid at a predetermined temperature of 121° C. or higher was supplied into the artificial organ 2 through the circuit inlet 11. At this time, no refrigerant was allowed to flow through the cooling device 7. In other words, without heat exchange,
The predetermined temperature of the sterilized liquid in the sterile liquid storage tank 6
By supplying a liquid with a temperature of 121°C or higher (121 to 123°C) to the artificial organ 2 and passing it through the interior of the artificial organ 2 to replace the internal filling liquid, the internal temperature of the artificial organ 2 is rapidly brought to the heat sterilization temperature. After raising the valve to
4 closed.

Note that the time required for heating up the autoclave 1 is measured in advance, and the time when the temperature inside the artificial organ 2 reaches 121°C coincides with the time when the heating of the autoclave 1 ends and reaches 121°C. preferable.

Both the temperature raised by the substitution and the temperature raised in the autoclave 1 reached 121°C or higher. Thereafter, the artificial organ 2 was sterilized for 20 minutes, which was the predetermined time set as the conditions for high-pressure steam sterilization at 121°C. By the time sterilization is completed, a refrigerant is poured into the cooling device 7 so that it can function as a cooling device 7, and by passing through the valve 10 and the cooling device 7, the effluent from the sterilization liquid storage tank 6 whose temperature has decreased is removed. Three-way valve 1 opened in three directions
It is discharged to the outside of the system through the outlet side of
The pipe line between the pipe and the three-way valve 13 was also cooled with this liquid. Check with thermometer 15 that the temperature of the liquid in the pipe and the pipe has fallen below 60℃, and then close the three-way valve 1.
The outlet side of No. 3 was closed.

After that, when sterilization for a predetermined period of 20 minutes is completed, the valve 14 is opened and while the cooling device 7 is kept operating, physiological saline as a stabilizer solution is passed into the artificial organ 2 as a sterilized low-temperature solution. By replacing the artificial organ 2 in the same manner as in the above method, the inside of the artificial organ 2 was rapidly lowered to 80°C or lower, and after about 2 minutes, the temperature was lowered to 40°C.

FIG. 2 is a schematic system diagram showing another embodiment for implementing the sterilization method of the present invention, in which the device includes a valve in the conduit leading to the artificial organ circuit inlet 11 instead of the three-way valve 13. 17, and a cooling device 7
The autoclave 1 is equipped with a pressure-resistant stainless steel pipe that branches as a discharge port between the autoclave 1 and the valve 17, and has the valve 12 installed outside the autoclave 1.
It has the same configuration as the device shown in the figure.

Moreover, FIG. 3 is a schematic system diagram showing yet another embodiment for carrying out the sterilization method of the present invention,
In this device, a valve 17 is provided in the piping instead of the three-way valve 13, and a discharge port is branched between the cooling device 7 and the valve 17, and the pressure-resistant stainless steel piping having the valve 12 is connected to the inside of the autoclave 1. The configuration is the same as that of the device shown in FIG. 1 except that the device is provided at

In the apparatus shown in FIGS. 2 and 3,
The function of the three-way valve 13 shown in FIG.
This can be achieved by combining the operations of and 17.

By performing these operations, the time required to raise the temperature inside the artificial organ is shortened. In the case of conventional methods of heating only from the outside, it takes a considerable amount of time for the interior of the autoclave to reach a predetermined temperature and for the center of the artificial organ to reach a predetermined temperature. For example, in the case of an artificial organ with an internal diameter of 65 mm and filled with adsorbent and filling fluid, it can take up to 120 minutes.
In addition, if the liquid that has lost heat while passing through the device and reaches just before the artificial organ and has reached a temperature lower than the predetermined temperature is not discharged, the liquid that has reached a temperature lower than the predetermined temperature after passing through the artificial organ must be discharged. The time required for the internal temperature to reach the predetermined temperature is approximately 30 minutes when using the device of the embodiment, and if the liquid is discharged according to the method of the present invention, the artificial organ will be completely drained after the liquid has started flowing. The time required for the internal temperature to reach the specified temperature is approximately
It was hot in 15 seconds.

〔Effect of the invention〕

In conventional methods, when heat sterilizing the center of an artificial organ, the artificial organ is exposed to high temperatures for a long period of time, causing material deterioration, but the present invention allows the artificial organ to be exposed to high temperatures for a short period of time. Therefore, such problems are significantly alleviated. Furthermore, when performing replacement for cleaning and cooling after sterilization, ensuring sterility is generally an issue, but in the method of the present invention, the sterilizing liquid maintained under sterile conditions is cooled in a sealed circuit. Complete sterility is ensured as the product is supplied in a sealed container.

Furthermore, when heat sterilizing an artificial organ that is filled with a filling liquid, damage to the artificial organ due to thermal expansion of the filling liquid is a problem, but with the method of the present invention, thermal expansion is absorbed outside the artificial organ. It will not be a problem because it will be done.

The method of the present invention can be applied to all kinds of artificial organs, and can be applied not only to sterilization at the final stage of the manufacturing process but also to sterilization of artificial organs during use, and it simplifies the sterilization operation. It has the effect of transforming

[Brief explanation of drawings]

FIGS. 1 to 3 are schematic system diagrams each illustrating an embodiment using an apparatus for carrying out the sterilization method of the present invention. Main symbols in the drawings: 1...autoclave, 2...
...Artificial organ, 7...Cooling device, 12,17...Valve, 13...Three-way valve.

Claims (1)

[Scope of Claims] 1. When an artificial organ is sterilized using high-pressure steam in an autoclave, a liquid that has been previously sterilized and maintained at a high temperature close to the steam sterilization temperature of the artificial organ is passed through the artificial organ. When the liquid is passed through the device, the liquid, which loses heat in the device and drops to a temperature lower than a predetermined temperature, is discharged immediately before the artificial organ;
Only the liquid at a predetermined temperature is passed into the artificial organ to bring its internal temperature almost to the steam sterilization temperature, and then the artificial organ is sterilized by maintaining it at the sterilization temperature for a predetermined period of time by external heating with high-pressure steam while the liquid is being filled. Then, while passing the pre-sterilized liquid at a high temperature into the artificial organ, a sterilized low-temperature liquid cooled by a cooling device is passed through the artificial organ using a liquid passing device. A method for sterilizing an artificial organ, characterized by draining the liquid and cooling the inside of the organ. 2. When a liquid passing device is used to pass liquid into an artificial organ and the inside thereof is cooled, the liquid, which is still at a high temperature due to insufficient cooling within the liquid passing device, is discharged just before the artificial organ. The method for sterilizing an artificial organ according to claim 1, wherein only the liquid whose temperature has dropped to a set temperature is passed into the artificial organ to cool the inside thereof. 3. The method for sterilizing an artificial organ according to claim 1, wherein the predetermined temperature is 115 to 137°C. 4. The method for sterilizing an artificial organ according to claim 2, wherein the set temperature is 20 to 60°C.