JPH0452149B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for sterilizing artificial organs through equal volume passage of fluid and an apparatus used therefor.

[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, and the like 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 an aqueous formaldehyde solution or ethylene oxide gas, and irradiating with gamma rays. There are safety issues, such as concerns that objects and containers may deteriorate and produce harmful substances inside, and their adoption is often discouraged in practice.

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 filler inside the artificial organ. (including fillers and fillers, the same shall apply hereinafter), if only the conventional method of heat sterilization by adding high-pressure steam or high-temperature water from outside the artificial organ is used, When raising the temperature of the internal filling near the center to the predetermined temperature required for sterilization, or 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. Preferably, when the contents are removed from the autoclave, a long period of time is required to ensure that the temperature has dropped to a temperature that can be handled with bare hands without the operator feeling that the contents are 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 prolonged exposure to the high temperatures required for sterilization, the quality of the internal filling of containers used for artificial organs deteriorates, resulting in fatal defects such as removal of active ingredients added to the adsorbent. 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).

However, when using this method to pass high-temperature sterilization liquid through multiple artificial organs, if multiple internal circuits such as pipes and valves are connected in parallel to each artificial organ, It is not necessarily guaranteed that the flow rate of the flowing sterile hot fluid is the same for each artificial organ. If the flow rate of the sterilized high-temperature liquid flowing into each artificial organ is significantly different, the rate of temperature rise of the internal filling of each artificial organ will be different due to the sterilized high-temperature liquid, and as a result, the internal filling of each artificial organ will be The time required for the object to reach a predetermined temperature close to the steam sterilization temperature of the artificial organ will vary greatly. Therefore, when the internal temperature of an artificial organ, which has a small flow rate and a slow temperature rise, reaches the predetermined temperature, the internal filling of the artificial organ, which has a larger flow rate and a shorter temperature rise time, will take a longer time than necessary. The problem is that exposure to high temperatures results in deterioration of the performance and quality of the artificial organ.

[Problem that the invention seeks to solve]

The inventors of the present invention have conducted extensive research in view of the above circumstances, and have found that when sterilizing multiple artificial organs using high-pressure steam in an autoclave, each artificial organ is sterilized in advance, and then the steam sterilization temperature of the artificial organ is We learned that differences in the time required to reach the predetermined temperature by passing a liquid maintained at a high temperature close to that between each artificial organ cause deterioration in the performance and quality of the artificial organ. In order to eliminate the difference in required time, it is necessary to equalize the flow rate of the sterilized liquid that flows to each artificial organ and has a predetermined temperature close to the steam sterilization temperature of the artificial organ. The present inventors have discovered a method for sterilizing an artificial organ and an apparatus used therein, in which a flow meter is installed in series with the flow meter, and the flow rate of the liquid at a predetermined temperature is detected by the flow meter and the flow rate can be adjusted. .

[Means for solving problems]

That is, in sterilizing a plurality of artificial organs using high-pressure steam in an autoclave, the present invention provides that the 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 heated to a high temperature. (hereinafter referred to as sterilized high temperature liquid for predetermined temperature liquid) is passed through a wake device having a flow meter installed in the conduit in series with each artificial organ, and the liquid is passed through the flow meter. Therefore, by detecting the flow rate of each artificial organ and adjusting it to a predetermined amount, the internal temperature of each artificial organ can be made to reach a predetermined temperature almost simultaneously, and the liquid at a predetermined temperature (hereinafter referred to as a plated predetermined temperature liquid) can be heated. During filling, the liquid is 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 that has been previously sterilized and kept at a high temperature (hereinafter referred to as sterilized high-temperature liquid) is passed through the artificial organ. Equal volume flow sterilization of artificial organs characterized by passing a sterilized low-temperature liquid cooled using a cooling device (hereinafter referred to as sterilized low-temperature liquid) into the artificial organ to cool the inside thereof. A method and apparatus for sterilizing a plurality of artificial organs using high-pressure steam in an autoclave, wherein a sterilizing liquid storage tank for storing a liquid that has been sterilized in advance and kept at a high temperature and a sterilizing liquid outlet are connected to each other through the artificial organ. The present invention relates to an apparatus for sterilizing an artificial organ by passing an equal amount of liquid therethrough, in which a flow meter is provided in series with the artificial organ in a conduit connected to the artificial organ.

〔Example〕

The present invention passes a sterilized high-temperature liquid at a predetermined temperature through a plurality of artificial organs installed in an autoclave using a liquid passing device having a flow meter that can be installed in series in a conduit to each artificial organ. , by detecting the flow rate of each artificial organ with the flowmeter and adjusting it to a predetermined amount, the internal temperature of each artificial organ is made to reach the predetermined temperature almost simultaneously, and while being filled with a sterilized predetermined temperature liquid,
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 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 is 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, for example, 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, the predetermined temperature is 115-137°C since steam sterilization temperatures are often in the range of 115-134°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 sterilizing liquid storage tank that connects the storage tank with a plurality of artificial organs. The pipe consists of a pipe that connects the artificial organ and a sterile liquid outlet, and the pipe further has a valve and a cooling device installed immediately after the storage tank, and the pipe is connected in series with the artificial organ in the pipe line. A flow meter is provided and constitutes the apparatus of the present invention.

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, a device that supplies fluid to the artificial organ is provided with a device that is installed in series with each artificial organ. The flow rate of liquid at a predetermined temperature in multiple artificial organs is detected using a flow meter, and the flow rate of the liquid flowing through each artificial organ is controlled by a sterilizing liquid such as a valve installed just before or after each artificial organ. After the internal temperature of any artificial organ reaches a predetermined temperature close to the steam sterilization temperature of the artificial temperature, by adjusting the flow rate to the same amount using a device that can adjust the flow rate, the liquid can be used for a longer period of time. A predetermined temperature close to the steam sterilization temperature of the artificial organ can be reached almost simultaneously so as not to be exposed to high temperatures for a long time.

The flowmeter used in the present invention includes a positive displacement flowmeter (oval type, Roots type, Bronny type, etc.), a vane wheel type flowmeter, which indicates the accumulated value of the flow rate until the internal temperature of the artificial organ reaches the predetermined temperature. It may be an integrated value measuring flow meter such as a flow rate meter with an instantaneous value time integration function added, a rotor meter, an ultrasonic flow meter,
The flowmeter may be a flowmeter that measures a flow rate (instantaneous flow rate) that indicates the flow rate per unit time, such as a differential pressure flowmeter or an electromagnetic flowmeter. In addition, such a flow meter may be installed upstream or downstream of the artificial organ, but
It is more preferable to install it on the downstream side, taking into account the contamination of the liquid flowing into the flowmeter, which has a complicated structure.

The method of sterilization, in which the temperature is maintained at 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 a normal high-pressure steam sterilization method using an autoclave. The sterilization begins after the internal temperatures of all of the artificial organs reach a predetermined temperature close to the autoclaving temperature at the same time by adjusting the flow rate of the sterilized predetermined temperature liquid to each artificial organ. Further, the number of times the internal filling liquid 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.

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.

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. At this time, a flow meter may be used for operation in the same manner as when increasing the internal temperature of the artificial 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 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. 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 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 the predetermined temperature liquid in the cooling device and the sterilized high-temperature liquid to be cooled pass through to the artificial organ, but also the refrigerant pipe for example, the sterilized high-temperature liquid for the 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 predetermined temperature liquid or the sterilized high-temperature liquid for preparing 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 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 example of the present invention in which high-pressure steam sterilization is performed at 121° C. for 20 minutes will be described based on FIGS. 1 and 2. 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 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 of an embodiment of the apparatus of the present invention shown in FIG. 1, an embodiment of the equal volume liquid flow sterilization method of the present invention will be described in terms of high-pressure steam sterilization 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 sterile 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. Cooling device 7
and the artificial organ circuit inlets 11-1 to 11-n are connected by pressure-resistant stainless steel piping, and a rotameter 15 is installed as a flow meter in the autoclave 1 downstream from each artificial organ outlet 12-1 to 12-n.
-1 to 15-n and valves 14-1 to 14-n
is installed. Furthermore, outside the autoclave 1, a thermometer 13 is installed in the pressure-resistant stainless steel piping downstream from the collection point of the pressure-resistant stainless steel piping downstream of the valves 14-1 to 14-n.

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℃ is heated to 123 to 127, which is close to the steam sterilization temperature of artificial organs 2-1 to 2-n.
It was maintained in a sterile liquid storage tank 6 at .degree. 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.
As a device for passing a sterilized predetermined temperature liquid close to the steam sterilization temperature of n, detecting the flow rate with rotameters 15-1 to 15-n, and adjusting the flow rate of the liquid,
The flow rate was adjusted using the valves 14-1 to 14-n, so that the flow rate flowing to each of the artificial organs 2-1 to 2-n was the same.

By passing liquid and replacing the internal filling liquid, the internal temperature of the artificial organs 2-1 to 2-n was rapidly raised to the heat sterilization temperature. At this time, no refrigerant was allowed to flow through the cooling device 7.

At this time, this operation causes the artificial organ 2-
It was found that the temperature increases of 1 to 2-n were almost the same, and that the time required for all artificial organs 2-1 to 2-n to reach the predetermined temperature (121° C.) varied within 1 minute. And artificial organs 2-1 to 2 by the above-mentioned replacement
Thermometer 13 detects that the temperature rise of autoclave 1 is completed, and 121
The artificial organs 2-1 to 2-n were sterilized for 20 minutes, which was a predetermined time set as a condition for high-pressure steam sterilization at .degree. At this time, in order to prevent the sterilizing liquid in the artificial organs 2-1 to 2-n from boiling, each artificial organ circuit outlet 12-1 to 12-n and the valve 14-1 to
14-n may be provided to detect changes in pressure so that the pressure within the system does not fall below the saturated vapor pressure.

After a predetermined period of time has elapsed and the sterilization is completed, the refrigerant is poured into the cooling device 7 so that it can function as a cooling device, and after the 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 the internal filling liquid in the same manner as in the above method, the inside of the artificial organs 2-1 to 2-n was rapidly lowered to 40° C. or lower.

FIG. 2 is a schematic system diagram showing an embodiment of the apparatus of the present invention for carrying out another embodiment of the equal volume flow sterilization method of the present invention, and the apparatus includes a rotameter 15-1. ~15-n and valve 14-1~
The apparatus has the same configuration as the apparatus shown in FIG. 1, except that the apparatus 14-n is provided outside the autoclave 1 on the downstream side of each of the artificial organs 2-1 to 2-n.

Therefore, according to the present invention, the flow rate of each artificial organ can be adjusted so that the internal temperature of each artificial organ can reach a predetermined temperature at the same time.

〔Effect of the invention〕

The method of sterilizing an artificial organ by passing an equal amount of liquid therein and the device used therefor of the present invention, when sterilizing a plurality of artificial organs, pours approximately the same amount of high-temperature liquid into each artificial organ and heats it from the inside. At the same time, it is possible to reach a predetermined temperature close to the steam sterilization temperature of the artificial organ, so there is no deterioration in the quality and performance of the artificial organ at this time, and all artificial organs installed in the autoclave can be submitted to high-pressure steam sterilization. can. Moreover, since each artificial organ is made to reach a predetermined temperature close to the steam sterilization temperature, the time required for high-pressure steam sterilization can be shortened.

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

[Brief explanation of the drawing]

FIGS. 1 and 2 are schematic system diagrams showing an embodiment of the apparatus of the present invention for carrying out an embodiment of the equal volume flow sterilization method of the present invention. (Main symbols in the drawing), 1: Autoclave, 2
-1 to 2-n: Artificial organ, 6: Sterile liquid storage tank, 7:
Cooling device, 15-1-15-n: rotameter.

Claims (1)

[Claims] 1. When sterilizing a plurality of artificial organs using high-pressure steam in an autoclave, the plurality of artificial organs placed in the autoclave are sterilized in advance at a temperature close to the steam sterilization temperature of the artificial organs. A liquid maintained at a high temperature is passed through each artificial organ using a liquid passing device having a flow meter installed in series in the pipe, and the flow rate of each artificial organ is detected by the flow meter. By controlling the amount, the internal temperature of each artificial organ is made to reach a predetermined temperature almost simultaneously, and while being filled with the liquid at a predetermined temperature, it is maintained at the sterilization temperature for a predetermined period of time by external heating with high-pressure steam, and then sterilized. A liquid that has been sterilized in advance and kept at a high temperature is passed through the artificial organ, and a sterilized low-temperature liquid that is cooled using a cooling device is passed into the artificial organ.
A method for sterilizing an artificial organ by passing an equal volume of fluid through it, characterized by cooling the inside of the organ. 2. The method for sterilizing an artificial organ by passing an equal amount of liquid according to claim 1, wherein the flow meter is installed downstream of the artificial organ. 3. A device that sterilizes multiple artificial organs using high-pressure steam in an autoclave, which connects a sterilizing liquid storage tank that stores a liquid that has been previously sterilized and is kept at a high temperature and a sterilizing liquid outlet through the artificial organ. A device for sterilizing artificial organs by passing an equal amount of liquid through them, in which a flow meter is installed in series with the artificial organ in a connecting pipe. 4. An equal volume sterilization device for an artificial organ according to claim 3, wherein a flow meter is installed on the downstream side of the artificial organ.