JPH0467869B2 - - Google Patents

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a method for initiating sterilization of an artificial organ.

[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 the temperature of the internal filling near the center is raised to a predetermined temperature necessary for sterilization, and after sterilization, it is cooled from the outside to a temperature below which the contents are difficult to deteriorate even if kept for a long time, more preferably. When taking out 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 being felt as hot by the operator. 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. The artificial organ is sterilized for a time that allows for high-grade sterilization (for example, 20 minutes when 10 ^-8 grade sterilization is performed by high-pressure steam sterilization at 121°C), and then the artificial organ is still passed through the artificial organ. A rapid temperature rise characterized by completing a series of sterilization operations by passing a high-temperature liquid that has not been sterilized and cooled by a cooling device into the artificial organ and cooling the inside of the artificial organ. A method of sterilizing artificial organs by rapid cooling has been reported (Patent Application No. 58-245761 and No. 59)
-Refer to each specification of No. 12462).

When a sterilized, high-temperature liquid is passed through an artificial organ, the temperature inside the artificial organ is rapidly raised to a predetermined temperature by the sterilized, high-temperature liquid, which may cause unnecessary desorption of a large amount of active ingredients. It is possible to prevent a decline in the medicinal efficacy of the product. However, a so-called heat exchange phenomenon occurs inside the artificial organ, and at the same time the temperature of the filling inside the artificial organ increases, the high temperature liquid decreases to a temperature lower than its initial temperature. Therefore, even if the temperature near the liquid inlet of the artificial organ reaches a predetermined temperature, the temperature near the exit becomes lower than the predetermined temperature, creating a temperature difference inside the artificial organ. Therefore, even if sterilization is carried out for the time required for sterilization near the entrance after the temperature near the entrance of the artificial organ circuit reaches a predetermined temperature, the sterilization time near the exit of the artificial organ circuit will not be enough, and the predetermined sterilization under these temperature and time conditions is not complete. If this is anticipated and the sterilization time is set long in advance, there is a problem in that the time required to sterilize a part of the artificial organ becomes unnecessarily long, resulting in thermal deterioration of the performance and quality of the artificial organ. Furthermore, when a plurality of artificial organs are sterilized at once, the problem of internal temperature differences becomes even more serious.

[Problem that the invention seeks to solve]

In view of the above circumstances, the present inventors have conducted intensive research and found that when sterilizing artificial organs using high-pressure steam in an autoclave, long-term high-pressure steam heating causes deterioration of the performance and quality of the artificial organ. We have discovered a method for sterilizing artificial organs that does not require sterilization and that can sterilize multiple artificial organs at once.

[Means for solving problems]

That is, in sterilizing artificial organs using high-pressure steam in an autoclave, the present invention provides a solution that has been sterilized in advance and maintained at a high temperature close to the steam sterilization temperature of the artificial organs to a plurality of artificial organs installed in the autoclave. (hereinafter referred to as sterilized high temperature liquid for predetermined temperature liquid) using a liquid passing device,
A thermometer installed downstream of an artificial organ that detects (1) one or more artificial organs that have been previously recognized to have a slower internal temperature rise than other artificial organs, or (2) all artificial organs placed in an autoclave. The internal temperature of the organ is detected, and valves are installed in the conduits connected to each artificial organ placed in the autoclave, and the degree of restriction of these valves is adjusted so that the time required for internal heating of each artificial organ is almost the same. After the internal temperature of the artificial organ reaches a predetermined temperature by adjusting the liquid at a predetermined temperature (hereinafter referred to as sterilized predetermined temperature liquid), the internal temperature of the artificial organ is maintained at the sterilization temperature for a predetermined period of time by external heating using high-pressure steam. A sterilized low-temperature liquid (hereinafter referred to as sterilized high-temperature liquid) that is sterilized and then cooled using a cooling device while passing through the artificial organ. (referred to as sterile low temperature liquid)
The present invention relates to a method for starting sterilization of an artificial organ, which comprises passing liquid into the artificial organ to cool the inside thereof.

〔Example〕

The present invention uses a liquid passing device to pass a sterilized high-temperature liquid at a predetermined temperature close to the steam sterilization temperature of the artificial organs through a plurality of artificial organs installed in an autoclave. After the internal temperature of a predetermined number of artificial organs set at a predetermined position reaches a predetermined temperature using a sterilized predetermined temperature liquid, the internal temperature of the artificial organs is detected by a meter, and then the internal temperature of a predetermined number of artificial organs set at a predetermined position reaches a predetermined temperature using a sterilized predetermined temperature liquid. Sterilize by maintaining at sterile temperature.

A predetermined number of artificial organs placed in a predetermined location are:
One or more artificial organs for which the internal temperature rise due to passage of sterilized liquid at a specified temperature is slower than that of other artificial organs, and if such recognition is not possible, autoclaving is required. means any artificial organ placed inside.

The types of artificial organs and their fillings used in the present invention are not particularly limited;
In particular, any adsorbent may be used as long as it forms a compatible solution with a specific solution and maintains adsorption performance.

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. Typically, water, saline, or an aqueous solution thereof containing some stabilizer, etc., is passed through the artificial organ through a non-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.

A device for passing a liquid used for sterilizing an artificial organ into an artificial organ according to the present invention includes a sterilizing liquid storage tank that heats and stores the sterilized high-temperature liquid for predetermined temperature liquid, and a sterilization liquid storage tank that connects the storage tank with a plurality of artificial organs. The pipe further has a valve and a cooling device provided immediately after the storage tank, branches immediately before each artificial organ, and each branch pipe is connected to a different artificial organ. Furthermore, thermometers are installed in predetermined downstream pipes of the artificial organ.

In the present invention, the thermometer installed downstream of each artificial organ is preferably installed outside the autoclave in order to be less susceptible to the influence of the temperature inside the autoclave. Further, the liquid used for sterilization after passing through each artificial organ is discharged through a pipe connected to each artificial organ and having each valve.

The method of sterilizing by maintaining the steam sterilization temperature for a predetermined period of time by external heating with high-pressure steam is carried out in the same way as the normal high-pressure steam sterilization method using an autoclave, but the high-temperature liquid for sterilized predetermined temperature liquid is extracted from the sterilization liquid storage tank. By passing liquid through a predetermined number of artificial organs installed in an autoclave, for example, all of the artificial organs installed, the internal temperature of each artificial organ can be measured using a thermometer installed downstream of each artificial organ. The internal temperature of the artificial organ is detected, and the sterilization is started after reaching a predetermined temperature close to the high-pressure steam sterilization temperature. Further, the number of times the internal filling effect is replaced when the internal temperature of the artificial organ reaches approximately the steam sterilization temperature is 1 or more times, preferably 2 to 5 times.

In addition, we confirmed that the time required for internal heating of each artificial organ was almost the same by making the amount of sterilized liquid at a predetermined temperature almost equal flowing through the pipes connected to each artificial organ installed in the autoclave. If possible, instead of using a thermometer downstream of each artificial organ, the downstream pipes of each artificial organ should be combined into one, and one thermometer installed in the pipe downstream of the combined part. Instead of the above method, a method may be used in which it is estimated that the internal temperature of each artificial organ has reached a predetermined temperature when the predetermined temperature has been reached. In other words, a thermometer installed downstream of the convergence part of the pipes downstream of the artificial organ,
The internal temperature of the artificial organ may also be detected.

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. Normally 121℃,
A 20 minute sterilization method is employed.

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.

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, but it does not necessarily have to be the same high-temperature liquid 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 refrigerant 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 addition, in the case of the embodiments shown in FIGS. 1 and 2, the sterilized high-temperature liquid for predetermined temperature liquid preparation and the sterilized high-temperature liquid for adjusting sterilized low-temperature liquid are passed through cooling devices into the artificial organ, respectively. be done. Therefore, when passing a high temperature liquid for a sterilized predetermined temperature liquid,
The cooling device can thereby also be sterilized. 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 tank, such as through a sterile liquid storage tank, and a cooling device is present in the sterilized high-temperature liquid for preparing the sterilized predetermined temperature liquid or the sterilized low-temperature liquid. It may be something that does.

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, examples of high-pressure steam sterilization at 121°C for 20 minutes according to the present invention are shown in Figures 1 and 2.
This will be explained based on the diagram. The present invention is not limited to these 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 container and adsorbent for the artificial organ. In other words, the conditions are 115℃ according to the Japanese Pharmacopoeia.
30 minutes, 126°C for 15 minutes, etc. can be selected, but in these cases, it is desirable to change the temperature setting value and time in parallel as appropriate according to the explanation below.

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.

Based on the schematic system diagram shown in FIG. 1, an embodiment of the sterilization initiation method of the present invention will be described with respect to implementation of a high-pressure steam sterilization method at 121° C. for 20 minutes.

n artificial organs 2-1 in autoclave 1
~2-n will be installed. 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, and the jacket 8 is installed in the sterilization liquid storage tank 6.
A breathing filter 9 is provided at the top of the tank 6. 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 inlets 11-1 to 11-n are connected with pressure-resistant stainless steel piping in the autoclave 1, and a thermometer 13 is installed downstream from each artificial organ circuit outlet 12-1 to 12-n outside the autoclave 1. -1～
13-n and valves 14-1 to 14-n are connected by pressure-resistant stainless steel piping.

First, with the valve 10 closed, the same water, physiological saline, or an aqueous solution containing some stabilizer as the filling liquid for the artificial organs 2-1 to 2-n is poured into the sterile liquid storage tank 6, and the jacket 8 is placed in the tank. The liquid was sterilized by heating it to a high temperature of 127° C. and holding it for 30 minutes or more to produce a sterilized high-temperature liquid, which 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 gas phase within the sterilization liquid storage tank 6 was almost pressurized, and the pressure reached approximately 2.3 atm.

Next, the valves 10 and 14-1 to 14-n
Open the artificial organs 2-1 to 2- in the sterile liquid storage tank 6.
A sterilized predetermined temperature liquid close to the steam sterilization temperature of 2-n was passed through the installed artificial organs 2-1 to 2-n. The internal filling liquid is replaced by liquid passage, and the artificial organ 2-1
The internal temperature of ~2-n was rapidly raised to near the predetermined temperature. At this time, no refrigerant was allowed to flow through the cooling device 7.

At this time, a thermometer 1 was installed outside the autoclave 1 near the artificial organ circuit exits 12-1 to 12-n.
3-1 to 13-n, the temperature of the liquid discharged from the artificial organs 2-1 to 2-n was observed, and changes in the temperature readings of all the thermometers 13-1 to 13-n were ascertained. Then, the relationship between the internal temperature of the artificial organs 2-1 to 2-n and the temperature of the thermometer installation location is investigated in advance, and a predetermined number of artificial organs 2-1 to 2-n, for example, all artificial organs 2-1 to 2-n installed in the autoclave 1, are checked. When it was detected that the temperature measured by the thermometers 13-1 to 13-n corresponding to the internal temperature of 121° C. reached the predetermined temperature of 121° C., the valves 14-1 to 14-n were closed to stop the substitution. This time point was taken as the starting point for measuring the predetermined sterilization time, and from this point on, the artificial organs 2-1 to 2-n were sterilized using high-pressure steam at the steam sterilization temperature for a predetermined time period, that is, 121° C. for 20 minutes.

In addition, the time required to raise the temperature of the autoclave 1 is measured in advance, and the artificial organs 2-1 to 2-
It is preferable that the time when the temperature inside the autoclave 1 reaches 121°C coincides with the time when the temperature rise of the autoclave 1 is completed and the temperature reaches 121°C.

By the end of sterilization after a predetermined period of time has elapsed, refrigerant is flowed into the cooling device 7 so that it can function as a cooling device, and after sterilization is completed, the valve 14-
1 to 14-n are opened and the physiological saline as a stabilizer liquid in the sterilized liquid storage tank 6 is cooled by the cooling device 7 while being passed through the artificial organs 2-1 to 2-n, as a sterilized low-temperature liquid. By passing liquid into the artificial organs 2-1 to 2-n and replacing them in the same manner as in the above method, the artificial organs 2-
The inside of 1-2-n was rapidly lowered to below 40°C.

FIG. 2 is a schematic system diagram showing another embodiment for carrying out the sterilization initiation method of the present invention, in which the apparatus includes valves 14 downstream of the artificial organs 2-1 to 2-n.
In addition to -1 to 14-n, a collecting valve 15 and each artificial organ 2-1 to 2 are downstream of the collecting part of the downstream piping.
The apparatus has the same configuration as the apparatus shown in FIG. 1, except that a thermometer 13 for collectively measuring the temperature of the sterilizing liquid flowing out from the tube 13-n is provided in place of the thermometers 13-1 to 13-n. Using the valves 14-1 to 14-n and the valve 15, the amount of the sterilized predetermined temperature liquid flowing through the conduits connected to each of the artificial organs 2-1 to 2-n installed in the autoclave 1 is approximately equal. The time required for internal heating of each artificial organ 2-1 to 2-n is almost the same, and the degree of throttling of each valve is adjusted so that bumping does not occur within the artificial organs 2-1 to 2-n.

By performing these operations, it was possible to sterilize multiple artificial organs without exposing them to high temperatures for long periods of time.

[Effects of the Invention] The artificial organ sterilization method of the present invention provides a method for sterilizing a sterilized predetermined temperature liquid in a conduit connected to the artificial organ when the liquid is passed through a plurality of artificial organs installed in an autoclave. A valve is provided, and the degree of restriction of the valve is adjusted based on the detected internal temperature of the artificial organ. Therefore, it is possible to sterilize a plurality of artificial organs at once while keeping the internal temperature uniform in each artificial organ and preventing deterioration of performance and quality of the artificial organ due to sterilization.

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 drawings]

1 and 2 are schematic system diagrams showing an apparatus for carrying out an embodiment of the sterilization initiation method of the present invention. (Main symbols in the drawing), 1: Autoclave, 2
-1 to 2-n: artificial organ, 7: cooling device, 13,
13-1 to 13-n: Thermometer.

Claims (1)

[Claims] 1. When sterilizing artificial organs using high-pressure steam in an autoclave, a plurality of artificial organs installed in the autoclave are sterilized in advance at a temperature close to the steam sterilization temperature of the artificial organs and then kept at a high temperature. A thermometer installed downstream of the artificial organ is used to pass the liquid through the artificial organ, and a thermometer installed downstream of the artificial organ is used to test one or more artificial organs whose internal temperature has been recognized to rise more slowly than other artificial organs. The internal temperature is detected, and valves are installed in the conduits connected to each artificial organ installed in the autoclave, and the degree of restriction of these valves is adjusted so that the time required for internal heating of each artificial organ is almost the same. After the internal temperature of the artificial organ reaches a predetermined temperature using the liquid at a predetermined temperature, the artificial organ is sterilized by being maintained at the sterilization temperature for a predetermined period of time by external heating using high-pressure steam, and then, after being sterilized in advance, it is heated to a high temperature. Start of sterilization of an artificial organ, characterized by passing a sterilized low-temperature liquid that is cooled using a cooling device during passage of the retained liquid into the artificial organ to cool the inside thereof. Method. 2. The method for starting sterilization of an artificial organ according to claim 1, wherein the predetermined temperature is 115 to 137°C. 3. The method for starting sterilization of an artificial organ according to claim 1, wherein the predetermined time for sterilization by high-pressure steam is 3 to 30 minutes. 4. When sterilizing artificial organs 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 organs is passed through the multiple artificial organs installed in the autoclave. A device is used to pass fluid through, and a thermometer installed downstream of the artificial organ detects the internal temperature of all the artificial organs installed in the autoclave. By installing valves in the interior of the artificial organs and adjusting the degree of restriction of these valves so that the time required for internal heating of each artificial organ is almost the same, the internal temperature of the artificial organs is brought to a predetermined temperature by the liquid at a predetermined temperature. After reaching this temperature, the liquid was sterilized by being maintained at the sterilization temperature for a predetermined period of time by external heating using high-pressure steam, and then the liquid, which had been previously sterilized and maintained at a high temperature, was cooled using a cooling device while passing through the artificial organ. A method for starting sterilization of an artificial organ, characterized by passing a sterilized low-temperature liquid into the artificial organ to cool the inside thereof. 5. The method for starting sterilization of an artificial organ according to claim 4, wherein the predetermined temperature is 115 to 137°C. 6. The method for starting sterilization of an artificial organ according to claim 4, wherein the predetermined time for sterilization by high-pressure steam is 3 to 30 minutes. 7. The method for starting sterilization of an artificial organ according to claim 4, wherein the internal temperature of the artificial organ is detected by a thermometer installed downstream of a collection point of piping downstream of the artificial organ.