JPH0422585B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for heat sterilization of an artificial kidney and an artificial kidney suitable for use in the heat sterilization. An artificial kidney comprising a container containing a hollow fiber bundle made of a selectively permeable membrane, the container having openings consisting of an inlet and an outlet for blood and an inlet and an outlet for dialysate. This is known per se, and is performed by removing waste products from the blood into the dialysate through dialysis and by ultrafiltration of excess water in the blood.
It replaces the function of a living kidney. Hollow fiber artificial kidneys are becoming increasingly important due to their advantages of being small and easy to use relative to their effective membrane area. Artificial kidneys must be sterilized to prevent bacterial contamination during the manufacturing process before being supplied to users. Until now, users have had to perform the necessary pretreatment on sterilized artificial kidneys. After it has aged, it is put to use. Conventionally, artificial kidneys have been sterilized using the following two methods. In the first method, the manufacturer fills the artificial kidney with a relatively concentrated aqueous formaldehyde solution, usually 1 to 5%, and then ships the artificial kidney after sterilizing it, and the user then washes and removes the formaldehyde inside the artificial kidney. Thereafter, the artificial kidney is heated to body temperature, the blood side is filled with heparin-containing physiological saline, and other necessary treatments are performed, followed by dialysis. Although this method is an effective method for sterilization, the formaldehyde used as a sterilizing agent is toxic to the human body, so it is necessary to completely wash and remove formaldehyde so that it does not remain in the artificial kidney. It is necessary, and for this purpose, large amounts of water must be flushed for a long period of time. However, such cleaning is a complicated operation and has the drawback of consuming considerable effort and time on the part of the user. Furthermore, even after the formaldehyde concentration in the cleaning waste water has decreased and formaldehyde is virtually undetectable, if cleaning is stopped and left as it is, the formaldehyde remaining in the hollow fiber membrane etc. will gradually ooze out. There is also. The second method involves the manufacturer adding a sterilizing gas to the dry hollow fiber artificial kidney, e.g.
The product is sterilized by passing through a mixed gas containing ~30% concentration of ethylene oxide or propylene oxide and the remaining percentage of Freon or carbon dioxide before shipping, and the user can then use the sterilized dry state supplied in this way. This is a method in which the artificial kidney is subjected to necessary treatments such as filling with dialysate, physiological saline, etc., and then subjected to dialysis. This method has the problem that gases such as ethylene oxide and propylene oxide are adsorbed and remain on the hollow fiber membrane of the artificial kidney, and these residual gases react with chlorine ions in the dialysate and physiological saline, causing harmful effects. There are also problems such as generation of chlorohydrin compounds. To clean these residual gases, it is necessary to pass about two or more large amounts of physiological saline. Furthermore, when passing liquid through the hollow fibers of a hollow fiber artificial kidney, since the hollow fibers are capillary tubes, in order to completely remove air bubbles, the liquid must be passed for a long time or the air inside the hollow fibers must be replaced with sterile carbon dioxide gas. Afterwards, it will be necessary to take measures such as passing fluid through, and in the latter case, the user will need to prepare equipment such as a carbon dioxide cylinder, a sterilizing filter, a pressure regulator, and a flow regulator. If air bubbles remain inside the hollow fiber,
There is a risk of microbubbles flowing into the body during dialysis, and there is also a risk of causing blood clots within the hollow fibers, increasing the amount of blood remaining in the dialyzer after dialysis, and increasing blood loss. Furthermore, this gas sterilization method has the disadvantage that the performance of the artificial kidney is likely to change because the dry artificial kidney is brought into a moist state during pretreatment, and the reproducibility of the performance of the artificial kidney is unstable. In addition to the above two types of sterilization methods, a third method has been proposed in which the artificial kidney is sterilized by irradiating it with gamma rays of 0.5 to 5 Mrad. This radiation sterilization method does not use a sterilizing agent, so there is no problem of residual toxicity. However, in the pretreatment of filling the dry artificial kidney with physiological saline, dialysate, etc., this method tends to cause changes in the performance of the artificial kidney, similar to the second method. Moreover, the materials constituting the artificial kidney are easily degraded by radiation, and there are still unresolved problems in improving the materials and selecting suitable materials. Generally speaking, in addition to the methods mentioned above, sterilization methods include:
There is a heat sterilization method, which is widely used to sterilize syringes and surgical instruments. For example, the 9th revised Japanese Pharmacopoeia states that the high-pressure steam sterilization method involves sterilizing microorganisms by heating in saturated steam under the following conditions: 115°C for 30 minutes, 121°C for 20 minutes, or 126°C for 15 minutes. stipulated. Furthermore, in the Japanese Pharmacopoeia mentioned above, 80 to 100℃
30 ~ once every 24 hours under water or flowing steam
Intermittent sterilization, which involves heating three to five times for 60 minutes each, is also permitted. Since heat sterilization has the advantages of no residual toxicity and easy cleaning, it would be extremely convenient if heat sterilization could be applied to artificial kidneys. However, heat sterilization methods have not been applied to artificial kidneys to date, and it was thought that heat sterilization methods would be completely impossible to implement, especially for artificial kidneys filled with filling liquid. It had not been attempted at all. The reason for this is that when an artificial kidney is heated, the artificial kidney may be deformed, cracked, or destroyed due to the thermal expansion of the filling fluid and air contained in the artificial kidney and the self-generating pressure of water vapor, resulting in leakage of the filling fluid. This is due to the difficulty in aseptically sealing the artificial kidney after sterilization. The present invention has successfully solved the above problems, and an object of the present invention is to provide a method for heat sterilization of an artificial kidney filled with a filling liquid. Another object of the present invention is to provide a user with an artificial kidney that requires substantially no pretreatment prior to use. According to the present invention, an artificial artificial body has a container containing hollow fibers made of a selectively permeable membrane, and the container is provided with openings consisting of a blood inlet, a blood outlet, a dialysate inlet, and a dialysis outlet. A method for heat sterilization of kidneys, comprising: (a) filling each of a plurality of artificial kidneys with a filling fluid consisting of water or an aqueous solution; and (b) filling at least one of the openings in each artificial kidney through conduit means. (c) sealing the remaining opening not connected to the pressure buffer tank with a sealing means; (d) keeping the artificial kidney at a temperature within the range of 80 to 130°C; heat sterilize each artificial kidney by heating to a temperature of (f) aseptically sealing each opening connected to the pressure buffer; A heat sterilization method consisting of each step is provided. FIG. 1 is a diagram schematically showing how the heat sterilization method of the present invention is carried out. FIG. 2 is a diagram schematically showing an embodiment of the heat sterilization method of the present invention as one artificial kidney for convenience, and FIG. 3 is a diagram schematically showing the aseptic sealing in the method of the present invention as one artificial kidney for convenience. FIG. 3 is a diagram showing one method for doing so. Figures 4 and 5 show connecting tubes suitable for use in the method shown in Figure 3, with 4a and 5a being longitudinal cross-sectional views respectively, and 4b and 5b being respectively A-A'. FIG. An important feature of the heat sterilization method of the present invention is that a pressure buffer tank that performs a special function is installed at a blood inlet, a blood outlet, a dialysate inlet, and a dialysate inlet for each of the plurality of artificial kidneys filled with a filling liquid. The artificial kidney is connected to at least one of the openings consisting of the outflow port, the remaining openings are tightly plugged, and in this state the artificial kidney is heated to a temperature within the range of 80 to 130°C. When heating is performed under these conditions, the filling fluid and gas components such as air that were present in the artificial kidney, which expanded due to the rise in temperature, move into the pressure buffer tank, and as a result, the fluid (filling fluid and The internal pressure of the artificial kidney caused by the thermal expansion of the gaseous components and the increase in water vapor pressure will be buffered, which would otherwise occur if such a buffering effect were not present. It becomes possible to effectively avoid deformation, cracking or destruction of the waxy artificial kidney. That is, the pressure buffer tank used in the present invention has the function of storing the expanded fluid (filling liquid and gas components) in the artificial kidney and the function of buffering the increase in pressure within the artificial kidney that occurs during heating. . The pressure buffer tank used in the method of the present invention is a tank that communicates with the outside (atmosphere) in terms of pressure but is isolated from the outside (atmosphere) in terms of bacteria so that it can exert a pressure buffering effect. Alternatively, it may be a tank that is isolated from the outside in terms of pressure and bacteria. In the method of the present invention, when disconnecting the artificial kidney from the pressure buffer tank after heat sterilization of the artificial kidney, for the opening that was connected to the pressure buffer tank,
It is necessary to provide a seal with means to prevent leakage of the filling liquid. Another important feature of the present invention is that, according to the method of the present invention, this sealing can be easily performed aseptically. In the present invention, heat sterilization is preferably performed based on the 9th revised Japanese Pharmacopoeia, including high-pressure steam sterilization (115-126°C) and intermittent sterilization (80-100°C).
In order to apply this, it is carried out within the range of 80 to 130℃. The present invention will be described below with reference to the drawings. FIG. 1 is a diagram schematically showing how heat sterilization of an artificial kidney is performed according to the method of the present invention. In FIG. 1, an artificial kidney 1 consists of a container 2 in which a number of hollow fibers 3 having selectively permeable membranes are housed. A pair of partition walls 5 are installed inside the container 2, and the hollow fibers 3 are supported by the partition walls 5. The container 2 has a blood inlet 6 and a blood outlet 6', which are usually thin side pipes with an opening, and a dialysate inlet 7 and a dialysate outlet 7', which are usually thick side pipes with an opening. It is provided. Both ends of the container 2 are connected to a blood distribution section 4.
and a blood collecting section 4', which are separated by a partition wall 5 from a dialysis room located at the center of the container 2 where dialysis is performed. Container 2 Hollow fiber 3, partition wall 5, side pipes 6, 6',
7, and 7' are all heat sterilized 80-130
It is made from a material that does not substantially undergo thermal deformation in the temperature range of 30°F. In heat sterilizing the artificial kidney 1 according to the method of the present invention, the artificial kidney 1 is first filled with a filling liquid of water or an aqueous solution. Thereby, the filling liquid fills all the spaces in the container 2, i.e. the spaces within the hollow fibers which are the passages for the blood, the spaces between the hollow fibers which are the passages for the dialysate, the blood distribution section 4 and the blood collection section 4'. , and all the spaces within the side tubes 6, 6', 7 and 7'. At least one of the side pipes 6, 6', 7 and 7' (conduit 6' in FIG. 1) is connected to a pressure buffer tank 10 via a conduit 9, and the other side pipes are filled with liquid. Leakage prevention means 8 (such as plugs or seals) are provided. In this state, the artificial kidney 1 is heated to a temperature of 80 to 130°C to perform heat sterilization. At this time, the pressure buffer tank 10 may be heated together with the artificial kidney 1, or the pressure buffer tank 10 may be heated together with the artificial kidney 1. Place the artificial kidney 1 outside the heater.
You can just heat it. When the artificial kidney 1 is heat sterilized, the expanded portion of these fluids is removed from the artificial kidney 1 due to the expansion of the filling fluid and air inside the artificial kidney due to the rise in temperature, and the self-generating pressure of water vapor. It exits and passes into the pressure buffer tank 10, thereby buffering the pressure within the artificial kidney. If the artificial kidney is cooled after completing the specified sterilization, the fluid remaining in the artificial kidney will contract and the water vapor pressure will also decrease, resulting in a reduced pressure state inside the artificial kidney. As a result, the artificial kidney attempts to return from this reduced pressure state to a normal pressure state, and water or aqueous solution that has been stagnant in the pressure buffer tank 10 enters the artificial kidney 1 through the conduit 9. The heat sterilization method of the present invention can be carried out by either of the two embodiments described below. The first embodiment uses a pressure buffer tank containing a filling liquid in advance, and connects the filling liquid in the artificial kidney and the filling liquid in the pressure buffer tank so that they communicate with each other. This method involves heat sterilization.
FIG. 2 schematically shows an example of this first embodiment, and does not necessarily accurately show the actual embodiment. That is, a case where the pressure buffer tank has a buffer bellows 14 as described later and a case where it has a sterilization filter 15 are shown, and in order to show three types of connection formats with the artificial kidney, they are summarized into one for convenience. This is what is illustrated. Here, a plurality of artificial kidneys are each connected to one pressure buffer tank 10, and the filling liquid in each artificial kidney is connected to the filling liquid phase 12 in the pressure buffer tank 10, and this liquid phase A gas phase 13 exists above 12. In Figure 2, 1
4 is a bellows for pressure buffering, and 15 is a sterilization filter for passing gas. It is preferable to use either or both of such a bellows and a sterilization filter to buffer the pressure. In this first embodiment, during heat sterilization,
The expanded fluid (filling liquid and air) moves from the artificial kidney 1 to the pressure buffer tank 10, but during cooling, only the filling liquid returns to the artificial kidney 1, and the air enters the gas phase 13.
It remains in the artificial kidney 1 and does not return to artificial kidney 1. Therefore, after heat sterilization, the amount of gaseous components such as air that existed in the artificial kidney decreases by that amount.
This will decrease compared to before heat sterilization. Since it is desirable that the amount of gaseous components present in the artificial kidney be as small as possible, the above-mentioned reduction in the content of gaseous components brought about by heat sterilization is advantageous, and herein such gaseous component content is A decrease in the filling state of the artificial kidney is sometimes referred to as an improvement. If the filling state of the artificial kidney is insufficient, air bubbles existing in the blood flow path may cause blood clots, etc., and air bubbles existing in the dialysate flow path may reduce the effective membrane area of the hollow fibers, causing dialysis to fail. This is not preferable because it reduces efficiency. The first method of the invention described above
This embodiment is a highly preferred embodiment, since it allows an improvement in the filling state of the artificial kidney.
In a second embodiment, the pressure buffer tank 10
is made of materials such as metal, glass, and heat-resistant resin.
The conduit 9 is preferably made of a material such as silicone rubber or heat-resistant synthetic rubber. In the heat sterilization method of the present invention, after the heat treatment is completed, it is necessary to aseptically seal the opening connected to the pressure buffer tank before disconnecting the artificial kidney from the pressure buffer tank. There are two main methods for achieving this aseptic seal. The first method, as shown in the artificial kidney 1 at the left end of FIG. There is a plug 1 inside to prevent filling liquid from leaking.
1 is suspended, and after the heat sterilization process is completed, before disconnecting the side pipe 6' and the conduit 9,
This is a method of installing the stopper 11 in the side pipe 6'. After heat sterilization, the inside of the artificial kidney and the inside of the pressure buffer tank are in a sterile state, so by the above operation, the side tube 6'
A sterile seal can be achieved. The second method is also exemplified in the artificial kidney at the right end of FIG. 2, but as shown in FIG. After the side pipe 7' and the conduit 9 are connected, and after the heat sterilization process is completed, the melt-sealed part 31 is melt-sealed before the connection between the side pipe 7' and the conduit 9 is disconnected, so that a sterile state is maintained. This is how sealing is achieved. Any material can be used for the connecting tube 30 as long as the melt-sealing portion 31 can be melt-sealed with heat, high frequency, or ultrasonic waves, and can be sterilized with high-pressure steam. Examples include polyvinyl chloride, polyolefin, polyurethane, and the like. In addition to the above two methods, if the side tube or conduit 9 of the artificial kidney can be melt-sealed, it may be melt-sealed, as exemplified by the artificial kidney in the center of FIG. Connecting tubes suitable for use in the second method described above include a cylindrical engagement portion 32, a melt seal portion 31 and a cylindrical engagement tube as shown in FIGS. 4 and 5. It is a cylindrical tube consisting of a conduit portion 33, and the engaging portion 32 can be engaged with a side tube of an artificial kidney, and the melt-sealed portion 31 has a narrow neck shape and has a maximum external dimension of its cross section. The connecting tube 30 is made of a sealable material and has a maximum internal dimension of 2 to 15 mm and a cross section of 1 to 14 mm. The melting part 31 is located in the center of the connecting tube 30, and the connecting part 32 and the conduit part 33 are located in the connecting tube 30.
at both ends. In addition, the engaging portion 32 and the conduit portion 33
The shape and dimensions of each tube may be determined by taking into consideration the shape and sealing properties of the mating tubes to be engaged. Melting part 3
From the viewpoint of practicality as a conduit, it is preferable that No. 1 has an internal cross-sectional dimension of 1 mm or more, and a cross-sectional dimension of 14 mm or less considering the size of the side tube of the artificial kidney and the sealed area. Further, the maximum outer dimension of the melt-sealed portion 31 is preferably 2 to 15 mm depending on the inner diameter, considering the aqueous solution retention and sealing area. More preferably, the maximum outer dimension of the sectional view of the welded portion 31 is 3 to 8 mm, and the inner dimension of the cross section is 2 to 7 mm. The cross-sectional shape may be circular, oval, oval, quadrilateral, or the like. Melting part 31
If the cross section is small, a circular cross section is preferable, and if the cross section is relatively large, a flat oval, oval, or quadrilateral cross section is preferable because it facilitates the melting operation, but the cross section is not limited to these. FIG. 4 shows a connecting tube 30 suitable for engagement with a narrow side tube (blood port) of an artificial kidney. The engaging portion 32 and the conduit portion 33 have a cylindrical shape so as to form a sealing engagement. The A-A' cross section of the welded portion 31 is circular. FIG. 5 shows a connecting tube 30 suitable for engagement with a thick side tube (dialysate port) of an artificial kidney. The shape of the engaging part 32 is cylindrical with a conical top part 34, and it engages and seals with the side tube, and also has a flange to facilitate the work of attaching and detaching the connecting tube when using this artificial kidney on a patient. 35 is attached. In this connecting tube, the A-A' cross section of the melt-sealed portion 31 is shaped like a flat oval. According to the method of the present invention, heat sterilization of an artificial kidney can be easily carried out. Moreover, during this process, the artificial kidney filled with water or an aqueous solution will not be destroyed, deformed, or have poor sealing due to heat sterilization heating.
Further, the blood flow path can be maintained, and in addition, it can be heat sterilized and sealed, and secondary contamination by bacteria can be prevented. Furthermore, the artificial kidney heat sterilized by the method of the present invention has an improved filling state and can exhibit excellent mass exchange performance and blood compatibility.
Artificial kidneys heat sterilized by the method of the invention have an overall high degree of sterility guarantee, there is no risk of residual toxicity and are easy to prepare for cleaning. Further, according to the present invention, in a hollow fiber type artificial kidney comprising a hollow fiber, a partition wall, and a container, the hollow fiber artificial kidney is suitable for heat sterilization.
The partition wall and the container have substantially heat resistance in the range of 40 to 130°C, and the linear expansion coefficient a of the partition member is
[1/°C] is in the range of 40 to 130°C, and the coefficient b [1/°C] of the container member and the temperature t [°C] have the following relationship: (4.13×10 ^-5 ) An artificial kidney is provided, characterized in that e ^0.00769t ≦a≦2b and the partition member does not undergo secondary metastasis within a temperature range of 50 to 120°C. The artificial kidney configured as described above does not cause deformation or destruction of members or seal failures due to heat sterilization and heating, and can maintain the blood flow path and treatment liquid flow path. As a result, combined with the heat resistance of the hollow fibers, excellent performance can be achieved. In order to create an artificial kidney that satisfies the above conditions, it is generally necessary to assemble the artificial kidney using the following materials by a method known per se. That is, the materials for the hollow fibers include cellulose, cellulose ester, polyacrylonitrile, polyvinyl alcohol, polyaromatic acid amide (for example, polyamide benzhydrazide isophthalamide),
Polycarbonate, polyether polysulfone, etc. can be used. Particularly preferred materials are cellulose and polyacrylonitrile, polycarbonate and polysulfone. Examples of container materials include polycarbonate,
polysulfone, poly-4-methylpentene-1,
Polyvinylidene fluoride and polyacetals can be used, especially highly transparent polycarbonates, polysulfones, poly-4-
Methylpentene-1 is the preferred material. The material for the partition walls is preferably a high molecular weight polymer. Among high-molecular polymers, preferred are polymers that are polymerized and crosslinked by addition polymerization from two or more components, ie, one or more prepolymers, a curing agent, etc., and whose total mass does not substantially change. Such polymers include urethane resins and epoxy resins. Among urethane resins, poly(ester type urethane) is preferred, which is produced by addition polymerization of a prepolymer whose terminal end is an isocyanate and a polyol (curing agent) consisting of a fatty acid having a hydroxyl group and an ester of glycerin. Embodiments of the present invention will be explained in detail below using examples. Example 1 and Comparative Example 1 Cellulose hollow fiber 10000 with inner diameter 250μ and membrane thickness 30μ
The books are bundled and stored in a polycarbonate container, both ends are gripped and fixed with urethane resin to form a septum, a polypropylene blood distribution plate is tightened and fixed with a polycarbonate bag cap, and a hollow fiber artificial kidney is constructed. Assembled. The blood and dialysate sides of the hollow fiber artificial kidney assembled in this way are filled with distilled water, a silicone rubber tube is connected to one of the dialysate ports, and the other port of this tube is connected to a glass pressure tube. Connected to 200ml of distilled water in a buffer tank, heat sterilized at 115℃ for 30 minutes using a high-pressure steam sterilizer, and then
It was slowly cooled to room temperature and taken out from the high pressure steamer. The weight (a) of the artificial kidney obtained in this way before filling, the weight (b) after filling, and the weight (c) of the artificial kidney after heat sterilization were measured, and from these measured values,
The amount of filling liquid before and after heat sterilization was determined by calculation. The results are shown in Table 1 below. In addition, as Comparative Example 1, the results of replacing the air on the blood side and the dialysate side with carbon dioxide gas before filling with distilled water for the purpose of improving the filling condition are also shown, but the results are also shown. It can be seen that the heat-sterilized artificial kidney thus obtained is improved in both the substantial filling amount and the appearance.

[Table] Furthermore, the results of a sterility test for the artificial kidney obtained according to the present invention were negative for both bacteria and fungi. Furthermore, a leak test of the hollow fiber was conducted to confirm that there was no leak, and then dialysis performance was evaluated. At this time, after measuring the filling condition of the present invention in order to confirm the effect of improving the filling condition, 10 g, 20 g, and 30 g of the filling liquid on the dialysate side were removed, and the artificial kidney was shaken well to reduce air bubbles. Measurement was performed after the distribution was made uniform. The results are shown in Table 2 below.

[Table] From the results in Table 2, it is clear that the filling state affects the dialysis performance. Examples 2 to 4 A hollow fiber type artificial kidney assembled under the same conditions as in Example 1 and filled with distilled water was heat sterilized using a high-pressure steam sterilizer in the same manner as in Example 1 while varying the temperature. did. Regarding the artificial kidney obtained in this way, as in Example 1, the weight of the artificial kidney before and after filling (a and b),
The weight (c) of the artificial kidney after heat sterilization was measured, and the amount of filling liquid after heat sterilization was calculated from these measured values. The results are shown in Table 3. Furthermore, the artificial kidney obtained in this way was tested for sterility, and the result was negative for both bacteria and fungi. That is, according to the present invention, an artificial kidney with an improved filling state could be obtained.

【table】

[Table] Example 5 A hollow fiber artificial kidney assembled in the same manner as in Example 1.
It was filled with 15 wt % saline solution, a connecting tube made of medical polyvinyl chloride and shaped as shown in FIG. 5 was attached to the dialysate port, and piping was connected as shown in FIG. 3. A sterilization filter is attached to the buffer tank, and 115
Heat sterilization was performed at ℃ for 30 minutes. After cooling, the melt-sealed portion of the connecting tube is melt-sealed using an ultrasonic welter to aseptically isolate the artificial kidney and the buffer means.
The conduit side of the connecting tube was then cut to produce a product. The results of a sterility test on the product showed negative results for both bacteria and fungi.

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing an embodiment of the present invention expressed as one artificial kidney for convenience, and FIG. 2 is also a schematic diagram showing an embodiment of the heat sterilization method of the present invention. FIG. 3 is a perspective view of a sterilely sealed embodiment of the present invention, represented for convenience as a single artificial kidney. 4 and 5 are a vertical sectional view a and a horizontal sectional view b, respectively, showing a connecting tube provided for the present invention.
The relationship is as shown in the A-A' arrow view in the figure. In the drawing, 1 is an artificial kidney, 2 is a container, 3 is a hollow fiber, 8 is a filling liquid leakage prevention means, 9 is a conduit, 1
0 is a pressure buffer tank, 14 is a bellows, 15 is a sterilization filter, and 30 is a connecting tube.

Claims (1)

[Scope of Claims] 1. A container containing hollow fibers made of a selectively permeable membrane, and the container is provided with openings consisting of a blood inlet, a blood outlet, a dialysate inlet, and a dialysate outlet. A method for heat sterilizing artificial kidneys comprising: (a) filling each of a plurality of artificial kidneys with a filling liquid comprising water or an aqueous solution; and (b) providing conduit means in at least one of the openings in each artificial kidney. (c) sealing the remaining opening not connected to the pressure buffer tank with a sealing means; (d) keeping the artificial kidney within the range of 80 to 130°C; heat sterilize each artificial kidney by heating it to a temperature of (f) cooling the kidneys, thereby allowing each artificial kidney to collect the filling fluid that had been transferred to the pressure buffer; (f) then aseptically sealing each opening connected to the pressure buffer; A heat sterilization method consisting of each step of 2. The method according to claim 1, wherein after the step (f), the connection made in the step (b) is unwound. 3. Before the step (b), the filling liquid is introduced into the pressure buffer tank, and two phases, a filling liquid phase and a gas phase, are introduced into the pressure buffer tank.
forming a phase and then carrying out the connection of step (b), thereby communicating the filling liquid in each artificial kidney with the filling liquid phase in the pressure buffer tank. Method described. 4. The method according to claim 3, wherein the pressure buffer tank is a tank that communicates with the outside in terms of pressure, but is isolated from the outside in terms of bacteria.