JPH0448064B2 - - 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 No. 57-75141), JP-A No. 58-27559,
No. 58-10055, No. 58-12656 and patent application
58-71913).

Generally, these artificial organs and treatment devices are sterilized in the final manufacturing process to prevent contamination during the manufacturing process, and then sealed 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 above-mentioned high-pressure steam sterilization method using an autoclave, an aqueous solution containing water with a large heat capacity, physiological saline, or some stabilizer, or a solid filler with low thermal conductivity is used as an internal filling material. If the conventional method of heating sterilization by adding high-pressure steam or high-temperature water from the outside of the artificial organ is used, the internal parts near the center of the artificial organ When the temperature of the filling is raised to a predetermined temperature required for sterilization, or after sterilization, the contents are cooled from the outside to a temperature below which the contents will not deteriorate easily even if kept for a long time, and more preferably the contents are removed from the autoclave. It takes a long time to lower the product to the point where the worker can handle it with bare hands without worrying that the product is too hot. In other words, when heating an artificial organ, in order to raise the temperature of the filling at the center of the artificial organ to the temperature required for sterilization, the part near the outer wall of the artificial organ is heated to a temperature higher than the sterilization temperature. The long exposure to the high temperatures required for sterilization can lead to deterioration of the quality of containers and internal fillings used in artificial organs, such as the removal of active ingredients added to adsorbents.

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-temperature steam is used to maintain the temperature necessary 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 (see the specifications of Japanese Patent Application No. 58-245761 and No. 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, if this method continues, sterilized, high-temperature fluid will be pumped into the artificial organ using a hydraulic head or a pump. When fluid is passed through the water head, it is not possible to adjust the flow rate by increasing the flow rate, and it takes a long time to fill the artificial organ with sterilized high-temperature fluid. The fluid easily loses heat to the fluid passing device, and it takes a long time to bring the temperature inside the artificial organ to the sterilization temperature. Therefore, artificial organs are exposed to high temperatures close to sterilization temperatures for an unnecessary long period of time, resulting in problems such as deterioration of the performance and quality of the internal fillings of the artificial organs. In addition, when cooling, it takes a long time to fill the artificial organ with sterilized low-temperature liquid, so the sterilized low-temperature liquid is easily warmed by the liquid passing device, which sets the temperature inside the artificial organ. It takes a long time to bring the temperature down. In addition, when a pump is used to pass liquid, there are problems in that the installation of the pump complicates the device and makes it difficult to ensure the sterility of the device. Furthermore, in this method, since the artificial organ is placed in an autoclave, the artificial organ is affected by the external conditions such as the temperature and pressure inside the autoclave. In other words, if the temperature inside the autoclave around the artificial organ is high, and the inside of the artificial organ is at a lower temperature and under saturated vapor pressure at that temperature, the artificial organ will receive heat from the surroundings and increase its temperature, and the inside of the artificial organ will be heated. This causes a bumping phenomenon. As a result, the filling status of medicinal ingredients within the artificial organ changes, and parts with weak mechanical strength, such as the filter part, are damaged or deformed, resulting in phenomena that significantly reduce the performance of the artificial organ.

[Problem that the invention seeks to solve]

In view of the above circumstances, the present inventors have conducted intensive research and found that if the pressure in the sterilization liquid storage tank exceeds the water saturated vapor pressure at the temperature inside the autoclave, high-pressure steam is used in the autoclave. When sterilizing an artificial organ, by using a simple device with only a pipe from a high-temperature sterilizing liquid storage tank, the high-temperature sterilizing liquid can be quickly passed into the artificial organ, and in this case, the artificial organ can be They discovered that heat is received from an autoclave to reach a higher temperature and does not cause boiling inside the artificial organ.The artificial organ is not exposed to high temperatures for a long time, and the quality and performance of the internal fillings of the artificial organ are reduced. We have completed a method for sterilizing artificial organs that does not cause 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). ) is stored in a sterile liquid storage tank whose internal pressure exceeds the saturated vapor pressure of water at the temperature inside the autoclave, and then the liquid at a predetermined temperature (hereinafter referred to as sterilized predetermined temperature liquid) is placed inside an artificial organ. A liquid passage device is used to pass liquid through the autoclave, and after sterilization by maintaining the sterilization temperature for a predetermined period of time by external heating with high-pressure steam while filling the liquid, a pressure exceeding the saturated steam pressure of water at the temperature inside the autoclave is applied inside the autoclave. A liquid that has been sterilized in advance and is kept at a high temperature (hereinafter referred to as sterilized high temperature liquid) stored in a sterile liquid storage tank.
A sterilized low-temperature liquid (hereinafter referred to as sterilized low-temperature liquid) that is cooled by a cooling device while passing through the artificial organ is passed through the artificial organ, and after cooling the inside, it is discharged into the atmosphere. The present invention relates to a method for sterilizing an artificial organ, characterized by:

〔Example〕

The present invention stores a sterilized high-temperature liquid at a predetermined temperature close to the steam sterilization temperature of artificial organs in a sterilization liquid storage tank having a pressure higher than the saturated vapor pressure of water at the temperature inside an autoclave, and then stores the sterilized high-temperature liquid at a predetermined temperature in A liquid is passed into the artificial organ using a liquid passing device, the internal temperature of which is brought to approximately the steam sterilization temperature, and while the liquid is being filled, the temperature is maintained at the steam sterilization temperature for a predetermined period of time by external heating using high pressure steam. Sterilize.

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 that is 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 the liquid. Typically, water, saline, or an aqueous solution thereof containing some stabilizer, etc., is passed through the artificial organ through a cold 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, the device for passing the liquid used for sterilizing the artificial organ through the artificial organ heats and stores the sterilized high-temperature liquid for a predetermined temperature liquid, and adjusts the internal pressure to the saturated vapor pressure of water at the temperature inside the autoclave. It consists of a sterile liquid storage tank connected to a pressurizing device that generates a pressure exceeding 100 mL, and piping connecting the storage tank and the artificial organ, and the piping further has a valve and a cooling device installed immediately after the storage tank.

If an artificial organ is sterilized only by external heating, it must be exposed to high temperatures for a long period of time in order to sterilize the inside of the artificial organ, resulting in quality and performance deterioration of the internal fillings, etc. By keeping the pressure in the sterilized liquid storage tank at a pressure higher than the saturated vapor pressure of water at the temperature inside the autoclave, the sterilized liquid at a specified temperature is immediately passed through the artificial organ, 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 or more times.
Five times.

A pressurizing device such as a compressor is used to increase the pressure in the sterilizing liquid storage tank to a pressure that exceeds the saturated vapor pressure of water at the temperature inside the autoclave. Connecting the sterile liquid storage tank, the pressurizing device, and/or the sterile liquid storage tank to the pressurizing device in order to detect the pressure in the sterile liquid storage tank when the device is used when the pressurizing device is connected to the sterile liquid storage tank. A pressure gauge may be attached to the piping.

The pressure in the sterilizing liquid storage tank must be higher than the saturated steam pressure of water at the upper limit of temperature fluctuation within the autoclave. The normal sterilization temperature is 121℃, so this is the saturated steam pressure of water at this temperature.
It is preferably 1.2 atm or higher.

Here, if the pressure inside the artificial organ communicating with the sterilization liquid storage tank is 1.2 atm or less, the temperature of the autoclave reaches the required sterilization temperature of 121°C (therefore, its saturated steam pressure is 1.2 atm). In some cases, a bumping phenomenon occurs within the artificial organ, generating bubbles that can seriously damage the filling state of the adsorbent inside.

In addition, in practice, instead of setting the critical pressure as mentioned above, the pressure should be set at an additional 0.3 to 0.3 degrees, taking into account the temperature fluctuations inside the autoclave (usually ±1 degree) and a slight margin.
It is more desirable to have a pressure 1.0 atm higher (therefore 1.5 to 2.3 atm). Note that the pressure inside the artificial organ can be set not only by the pressure inside the sterilizing liquid storage tank described above, but also by taking into account the head pressure depending on the level of the sterilizing liquid in the tank. For example, if the liquid level in the sterilization liquid storage tank is about 3 m higher than the position in the autoclave where the artificial organ is installed, the internal pressure of the storage tank should be increased to 1.2 atm in anticipation of the head pressure of 0.3 atm being added to the artificial organ. Even when set to
This means that there is a margin of 0.3 amtm.

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.

In addition, the present invention cools the inside of the artificial organ by passing a sterilized low-temperature liquid cooled by a cooling device into the artificial organ while passing the sterilized high-temperature liquid into the artificial organ, and replacing the internal filling liquid. It also applies when forcing someone.

In other words, when the temperature inside the autoclave has not yet cooled down and is close to the sterilization temperature, passing the sterilized low temperature inside the artificial organ will prevent bumping from occurring even if the internal temperature suddenly drops. is necessary. Therefore, if the temperature inside the autoclave is still close to 121℃, 1.2 atm inside the artificial organ is
The inside of the sterilizing liquid storage tank must be pressurized or the liquid level must be raised so that the above pressure is applied.

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 at the same high temperature as this.
It may be normal pressure high temperature water at 95°C, physiological saline, or an aqueous solution thereof containing some stabilizer.

The sterilized low-temperature liquid refers to the sterilized high-temperature liquid that is 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. It refers to something that has been 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, the refrigerant used in the cooling device may be a liquid refrigerant such as low-temperature tap water, industrial water or other cooling water, or low-temperature air or other gas.

The sterilized high-temperature liquid for predetermined temperature liquid and the sterilized high-temperature liquid for adjusting the sterilized low-temperature liquid, which are close to the steam sterilization temperature of artificial organs, may be freshly sterilized, or once sterilized, they can be used to remove bacteria. It may be kept in a suitable container for a relatively short period of time (for example, within 24 hours) at an appropriate temperature that does not allow reproduction (for example, 70°C or higher, preferably 80°C or higher). They may also be supplied from the same storage tank,
It may be supplied separately under different conditions or within a device within the range that satisfies the sterilization conditions.

In the case of the embodiment shown in FIG. 1, the sterilized high temperature liquid for predetermined temperature liquid and the sterilized high temperature liquid for adjusting the sterilized low temperature liquid are each passed through a cooling device into the artificial organ. 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 present in the high temperature liquid bath, such as through a bath of sterile liquid, i.e. a sterile liquid storage tank;
The cooling device may be present in a sterile temperature liquid or a sterile hot liquid for conversion to a sterile cold liquid.

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.

The present invention will be explained below based on FIG. 1 using an example in which high-pressure steam sterilization was performed at 121°C for 20 minutes, but the present invention is not limited to this example. . 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 container and adsorbent for the artificial organ. That is, the conditions were adjusted to 115°C and 30°C according to the Japanese Pharmacopoeia.
minutes, 126℃ for 15 minutes, etc.
In these cases, it is desirable to change the temperature setting value and time in parallel as appropriate according to the following explanation.

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

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 sterile liquid storage tank 6 so that the tank 6 can be heated, and a breathing filter 9 is provided above the tank 6 via a valve 19. The sterilizing liquid storage tank 6 and the cooling device 7 are connected via a valve 10 with pressure-resistant stainless steel piping. The cooling device 7 and the artificial organ circuit inlet 11 are connected by pressure-resistant stainless steel piping. Furthermore, the artificial organ circuit outlet 14 and the valve 12 are connected by pressure-resistant stainless steel piping. A compressor 15 as a pressurizing device is connected to the sterilizing liquid storage tank 6 through a pressure-resistant stainless steel piping via a valve 17, and a pressure-resistant stainless steel piping branches off in the middle of the piping from the sterilizing liquid storage tank 6 to the valve 17. A pressure gauge 16 is provided via a valve 18.

First, the same water as the filling liquid for the artificial organ 2, physiological saline, or an aqueous solution thereof containing some stabilizer is placed in the sterile liquid storage tank 6, and the jacket 8 is heated to a high temperature of 127°C with the valve 19 open. 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 the sterilizing liquid storage tank 6 at 123 to 127°C, which is close to the steam sterilization temperature of artificial organs. At this time, the pressure inside the sterilization liquid storage tank 6 was approximately 2.3 atm.

Next, valve 10 and valve 19 were closed, valve 17 was opened, and compressor 15 was operated. After opening the valve 18, it was confirmed by the pressure gauge 16 that the pressure in the sterilizing liquid storage tank 6 was 2.3 atm or more, which exceeded the saturated vapor pressure of water at the temperature in the autoclave 1. Valve 12
After opening, the valve 10 was opened and the liquid at a predetermined temperature was supplied into the artificial organ 2 through the artificial organ circuit inlet 11. At this time, no refrigerant was allowed to flow through the cooling device 7. That is, the predetermined temperature of the sterilized liquid in the sterilization liquid storage tank 6 is maintained without heat exchange.
Sterilized predetermined temperature liquid of 121°C or higher (cooling device for checking the temperature difference between the sterilized predetermined temperature high temperature liquid supplied from the sterile liquid storage tank 6 and the sterilized predetermined temperature liquid supplied to the artificial organ 2) 7 and artificial organ circuit entrance 11
A thermometer may be installed in the pressure-resistant stainless steel piping between the artificial organ 2 and the artificial organ 2. After the internal temperature was raised to approximately the heat sterilization temperature, the valve 12 was 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. is preferred.

As described above, when the temperature of the autoclave 1 reaches 121°C or higher while repeatedly replacing the liquid with a sterilized predetermined temperature liquid at a temperature of 121°C or higher, the valve 12 is closed and the high-temperature steam at 121°C is removed. The artificial organ 2 was sterilized for 20 minutes, which was the predetermined time set as the sterilization conditions. A refrigerant is passed through the cooling device 7 until the sterilization is completed, and when the sterilization is completed, the physiological saline as a stabilizer solution in the sterilization liquid storage tank 6 is cooled by the cooling device 7 while being passed through the artificial organ, and the sterilized low temperature is reached. By passing the liquid into the artificial organ 2 and replacing it 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. The pressure applied to the inside of the artificial organ 2 during this entire period was approximately 2.3 atm, and no bumping phenomenon occurred.

By performing these operations, the time required to raise the temperature inside the artificial organ can be shortened without causing a bumping phenomenon inside the artificial organ. 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 inner diameter of 65 mm and filled with adsorbent and filling liquid, the time is
It can be as long as 120 minutes.

〔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 time, resulting in material deterioration, but the present invention lowers the pressure in the sterilization liquid storage tank to below atmospheric pressure. By increasing the temperature, sterilized liquid at a predetermined temperature can be quickly passed from a high-temperature sterile liquid storage tank using a simple device with only a pipe line, and the time that the artificial organ is exposed to high temperature is shortened, thereby eliminating such problems. will be resolved. In addition, when performing replacement for cleaning and cooling after sterilization, ensuring sterility becomes a problem, but in the method according to the present invention, the sterilizing liquid maintained at sterile conditions is cooled in a sealed circuit and supplied. This ensures complete sterility.

Furthermore, since the sterilizing liquid storage tank has an internal pressure that exceeds the saturated vapor pressure of water at the temperature inside the autoclave, no bumping phenomenon occurs inside the artificial organ. Therefore, phenomena that degrade the performance of the artificial organ, such as changes in the filling status of medicinal ingredients within the artificial organ, do not occur.

The method of the present invention can be applied to artificial organs in general, 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, simplifying the sterilization operation. It has the effect of transforming

[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 drawings: 1...autoclave, 2...
...Artificial organ, 6... Sterile liquid storage tank, 7... Cooling device.

Claims (1)

[Claims] 1. When sterilizing an artificial organ using high-pressure steam in an autoclave, a liquid that has been sterilized in advance and kept at a high temperature close to the steam sterilization temperature of the artificial organ is heated to a temperature that is equal to or lower than the pressure inside the autoclave. After storing the liquid in a sterilized liquid storage tank with a pressure exceeding the saturated vapor pressure of water at a certain temperature, the liquid at a predetermined temperature is passed through the artificial organ using a liquid passing device, and while the liquid is being filled, external injection using high-pressure steam is carried out. After sterilization by maintaining the sterilization temperature for a predetermined period of time by heating, the liquid that has been previously sterilized and kept at a high temperature is stored in a sterilization liquid storage tank with a pressure that exceeds the saturated steam pressure of water at the temperature inside the autoclave. , a method of sterilizing an artificial organ characterized by passing a sterilized low-temperature liquid cooled by a cooling device into the artificial organ while the liquid is being passed through the artificial organ, cooling the inside of the organ, and then expelling it into the atmosphere. Method. 2. The method for sterilizing an artificial organ according to claim 1, wherein the pressure inside the sterilization liquid storage tank is 1.2 atm or more.