JPS61143070A - Heat sterilization of artificial kidney - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

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 system is known per se, and it replaces the function of a living kidney by removing waste products from the blood into a dialysate through dialysis and by ultrafiltrating excess water in the blood. Hollow fiber artificial kidneys are becoming increasingly important because of their advantages of being small and easy to use relative to their effective membrane area. The artificial kidney is
It is necessary to sterilize the artificial kidney at the manufacturing stage to prevent bacterial contamination before supplying it to the user. Available for use.

Conventionally, artificial kidneys have been sterilized using the following two methods.

The first method is that the manufacturer uses relatively concentrated
The artificial kidney is usually sterilized and shipped by filling it with an aqueous formaldehyde solution with a concentration of 1 to 5%, and the user washes and removes the formaldehyde inside the artificial kidney, warms the artificial kidney to body temperature, and uses heparin-containing saline on the blood side. In this method, the tube is subjected to necessary treatments such as filling with saline and then subjected to dialysis. This method is an effective method for sterilization, but since the formaldehyde used as a sterilizing agent is toxic to the human body, it must be thoroughly washed and removed so that formaldehyde does not remain in the artificial kidney. To do this, large amounts of water must be flushed for a long period of time. Although this kind of cleaning is a complicated operation,
The drawback is that it requires considerable effort and time from the user. Furthermore, even after the formaldehyde concentration in the cleaning wastewater has decreased and formaldehyde is virtually undetectable, if cleaning is stopped and left as it is, the formaldehyde remaining in the hollow fiber membrane will gradually ooze out. be.

In the second method, the manufacturer supplies the dry hollow fiber artificial kidney with a sterilizing gas, for example, ethylene oxide or propylene oxide at a concentration of 10 to 30% as sterilizing components, and the remaining percentage of Freon or carbon dioxide. mixed gas,
The artificial kidney is sterilized by passing through the artificial kidney before being shipped, and the user then performs necessary treatments such as filling the dry sterile artificial kidney with dialysate, physiological saline, etc., and then uses it for dialysis. be. 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 such as rohydrin. There are also problems such as the formation of compounds. and,
To clean these residual gases, it is necessary to pass a large amount of physiological saline about twice or more.

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 system, 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 tends to change because the dry artificial kidney is brought into a wet 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 is 0.
A method of sterilizing an artificial kidney by irradiating it with gamma rays of 5 to 5 M rad has been proposed.

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.

In general, sterilization methods include, in addition to the above-mentioned methods, heat sterilization, which is widely used for sterilizing syringes and surgical instruments. For example, the 9th revised Japanese Pharmacopoeia states that high-pressure steam sterilization is performed at 115°C and 30°C.
It stipulates a method of killing microorganisms by heating in saturated steam for either 20 minutes at 121°C or 15 minutes at 126°C. Furthermore, the Japanese Pharmacopoeia also permits an intermittent sterilization method in which heating is performed 3 to 5 times for 30 to 60 minutes every 24 hours in water or flowing steam at 80 to 100°C.

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 could not be applied basolaterally to 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 is deformed, cracked, or destroyed due to the thermal expansion of the filling fluid and air contained within the artificial kidney and the self-generating pressure of water vapor, resulting in leakage of the filling fluid. This is due to the fact that it is difficult to aseptically seal 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, there is provided a container containing a hollow fiber bundle 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 an artificial kidney, comprising: (a) filling the artificial kidney with a filling liquid consisting of water or an aqueous solution; (b) connecting a pressure buffer bag to at least one of the openings; (c) (d) heat sterilize the artificial kidney by heating the artificial kidney to a temperature within the range of 80 to 130°C; (e) cooling the artificial kidney after sterilization, thereby recovering the filling liquid that had been transferred to the pressure buffer bag into the artificial kidney; and (f) aseptically sealing the opening connected to the pressure buffer bag, if necessary.

FIG. 1 is a diagram schematically showing how the heat sterilization method of the present invention is carried out. Figure 2 (a) or (b+
This is the fruit of the heat sterilization method of the present invention! +1! It is a figure showing an aspect. 3 to 5 show typical examples of buffer bags used in the embodiment shown in FIG. 2(a). 6 and 7 show connecting tubes suitable for use in the present invention, 6(a) and 7(b) are longitudinal cross-sectional views, respectively, and 6(b) and 7(b) are longitudinal sectional views. ) are cross-sectional views taken along line A-A'.

An important feature of the heat sterilization method of the present invention is that a pressure buffer bag that exhibits a special function is made up of the blood inlet, blood outlet, dialysate inlet, and dialysate outlet of the artificial kidney filled with filling fluid. At least 10 of the openings are connected, the remaining openings are sealed with sealing means, and in this state the artificial kidney is heated to a temperature within the range of 80 to 130°C to sterilize it. When heating under these conditions, the filling fluid expanded due to the increase in temperature moves into the pressure buffer bag, and as a result, the internal pressure of the artificial kidney caused by the thermal expansion of the fluid and the increase in water vapor pressure increases. This effectively avoids deformation, cracking or destruction of the artificial kidney, which would otherwise occur if such a buffering effect were not present. That is, the pressure ml bag used in the present invention, the Ili! inside the artificial kidney. ! The artificial kidney has the function of storing tense fluid and the function of buffering the pressure increase inside the artificial kidney that occurs during heating.

The pressure buffer bag used in the method of the present invention is one that is sealed from the outside both in terms of pressure and bacteria, and includes, for example, a sealed bag. However, when using a sealed bag, pressure! In order to facilitate the manufacturing process, the bag is preferably such that it is capable of expanding itself in response to movement of expanded fluid into its interior.

In the method of the invention, it may be necessary to seal the opening connected to the pressure buffer bag with means for preventing leakage of the filling liquid.

In the present invention, heat sterilization is preferably carried out based on the 9th revised Japanese Pharmacopoeia, and the above-mentioned high-pressure sterilization method (115-16℃
) and Tj. In order to apply the intermittent sterilization method (80 to 100°C), it is carried out within the range of 80 to 130°C.

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 containing a number of hollow fibers 3 having selectively permeable membranes. 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 is provided with a blood inlet 6 and a blood outlet 6' which are usually thin side pipes with openings, and a dialysate inflow lower and a dialysate outflow lower' which are usually thick side pipes with openings. ing. Both ends of the container 2 are a blood distribution section 4 and a blood collection section 4', which are separated by a partition wall 5 from a dialysis room in the center of the container 2 where dialysis is performed. Container 2, hollow fiber 3. Bulkhead 5. Side pipes 6.6', 7 and 7' are all J heat sterilized 80
It is made of a material that does not substantially undergo thermal deformation in the temperature range of ~130°C.

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, that is, the spaces in the hollow fibers which are the blood passages, the spaces in the hollow fiber tubes which are the dialysate passages, the blood origin 4 and the blood collection part 4'. space.

and filling all the spaces in the side tubes 6.6', 7 and 7'. At least one of the side pipes 6.6', 7 and 7'
One (conduit 6' in FIG. 1) is connected to the pressure buffer bag 10 via a conduit 9, and the other side conduit is provided with means 8 (such as a stopper or a seal) to prevent leakage of the filling liquid. It has been subjected. 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 bag 10 may be heated together with the artificial kidney 1, or the pressure buffer bag 10 may be heated together with the artificial kidney 1. 10 may be placed outside the heater and only the artificial kidney li1 may be heated. When the artificial kidney 1 is heat sterilized, the filling liquid and air in the artificial kidney expand due to the rise in temperature, and the self-generating pressure of water vapor causes
These expanded portions of fluid exit the artificial kidney 1 and pass into the pressure buffer bag 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 the water or aqueous solution that has been retained in the pressure buffer bag 10 enters the artificial kidney 1 through the conduit 9.

FIG. 2 shows an example of an embodiment of the method of the invention, in which a pressure buffer bag 10, such as a balloon bag, is connected to the side tube 7' of the artificial kidney. In this method, the pressure buffer bag itself expands to absorb the fluid inside the artificial kidney expanded by heat sterilization, buffering the pressure, and thereby reducing the load on the container and blood distribution and collection parts of the artificial kidney. Become. In the embodiment shown in FIG. 2, there is no particular need to disconnect the artificial kidney from the pressure buffer bag after heat sterilization of the artificial kidney. However, if the artificial kidney is connected to the pressure buffer bag via the connecting conduit in the manner shown in Figure 1, it is necessary to disconnect the connection after sterilization, and in that case, the same procedure as described above must be performed. It is necessary to provide a seal with means to prevent leakage of the filling liquid.

The material of the buffer bag is required to have physical properties such as not bursting upon expansion. Any material may be used as long as it has heat and humidity resistance at 80 to 130°C, is medically safe, and has zero toxicity. For example, there are buffer bags made of rubber-like elastic materials such as natural rubber, synthetic rubber such as polyisoprene rubber and polybutadiene rubber, silicone rubber, polyurethane elastomer, etc.
0 of buffer bags made of materials that do not have rubber-like elasticity, such as nylon, polyester polyester, nylon, polyester laminate film, etc.
Either can be used as the pressure buffer bag of this embodiment. Regarding the volume of the II shock bag, it is necessary that the maximum expansion volume within the pressure limit is at least larger than the increase in the volume of the fluid (filling liquid and air) due to expansion due to heating.

The shape of the buffer bag used in the embodiment of the present invention can be in various shapes such as a bag shape, a balloon shape, or a tube shape. It is a bag in which a thick part 21 and a thin part 22 are integrated, the thick part is a neck that engages with the side tube of the artificial kidney, the thin part is an inflatable part, and the thick part is a neck part that engages with a side tube of an artificial kidney. The thickness T(#lI) of the thin part and the thickness t(s) of the thin part are expressed by the following formula (1
) to 3).

0.05 tea≦t≦2.04Il --(
110,25M≦T≦5.0#lIR...(al<
(T/t)≦30 (3) The volume of the buffer bag at zero pressure (normal pressure) is 2 to 100 d, preferably 4 to 50 d. The maximum inflation volume differs depending on the artificial kidney and its filling state, but in humans, the artificial organ and its filling state are 4001d and residual, air 1
In the case of 0-20d, 20-70all is expected.

Therefore, the buffer bag must be able to expand when the zero pressurized volume does not reach the maximum inflation volume, and the buffer bag must be stretched flat to prevent gas from entering the bag during use. or fill it with a small amount of water or an aqueous solution. However, in order to allow the thin portion to expand and flatten, the thickness 1) should be 0.05 to 2.0. ．． Preferably it is 0.10 to 1.0. Moreover, when it is necessary to expand, it is preferable that the elongation at break is in the range of 100 to 1500%. More preferably 300 to 1000
% range.

On the other hand, the neck, which is attached to the side tube of the artificial kidney, is the fixing part of the bag, and is thick so as to have a sealing effect to prevent leakage of filling liquid, etc. and secondary contamination after heat sterilization.

This thickness T) is 0.25-5.0ms+, preferably 0.4-3.0M. Although the thin part and the thick part are molded into one piece, they can also be molded into two or more pieces and integrated by adhesive or the like. The relationship between their thicknesses satisfies equation (3).

FIG. 3 shows a buffer bag suitable for a narrow side tube of an artificial kidney, such as a blood port. The inner diameter and length of the neck 21 that engages with the side tube may be dimensioned to provide a sealing engagement with the side tube. FIG. 4 shows a buffer bag suitable for a large side tube, such as a dialysate inlet. In FIG. 5, the inner surface 23 of the neck matches the outer shape of the side tube, and the thickness T in this case is defined as the average of the minimum dimension T+ and the maximum dimension T2. In addition, the expansion part 22
The shape of is substantially cylindrical, second ellipsoidal or fifth
It may have an overall oval shape as shown in the figure.

As described above, in the heat sterilization method of the present invention, after the heat treatment is completed, the opening connected to the pressure buffer bag may be aseptically sealed before disconnecting the artificial kidney from the pressure buffer bag. It may be necessary.

As shown in FIGS. 6 and 7, the main method for performing this aseptic seal is to connect the side tube of the artificial kidney to the pressure buffer via a connecting tube 30 having a welded part 31. This method achieves aseptic sealing by melt-sealing the melt-sealed portion 31 after the heat sterilization process is completed and before disconnecting the side pipe and the pipe.

Any material can be used for the connecting tube 30 as long as the melt-sealing portion 31 can be melt-sealed by heat, high frequency, or ultrasonic waves, and can be sterilized by high-pressure steam. Examples include polyvinyl chloride, polyolefin, polyurethane, and the like.

In addition to the methods described above, if the side tube or conduit of the artificial kidney can be melt-sealed, it may be melt-sealed.

Furthermore, when using the above-mentioned pressure 1 bag as an alternative method,
The pressure buffer bag may be left on without being removed and used as a seal.

A suitable connecting tube for use in the method described above includes a cylindrical engagement portion 32. as shown in FIGS. 6 and 7. Melting part 31 and cylindrical conduit part 33
The engaging portion 32 is capable of engaging with a side tube of an artificial organ, and the welding portion 31 is shaped like a thin neck and has a maximum external dimension of 2 to 15 mm in cross section. ．． The connecting tube 30 is made of a material that can be melt-sealed and has a maximum internal dimension of 1 to 14 #I in its cross section. Melting part 31
is located at the center of the connecting tube 30, and the coupling portion 32 and the conduit portion 33 are located at both ends of the connecting tube 30.

Further, the shapes and dimensions of the engaging portion 32 and the conduit portion 33 may be determined in consideration of the shape and sealing properties of the respective mating tubes. From the viewpoint of practicality as a conduit, the melt-sealed portion 31 preferably has an internal dimension of 1jIII or more in its cross section, and a cross-sectional dimension of 14 m or less in consideration of the dimensions of the side tube of the artificial kidney and the melt-sealed area. . Further, the maximum outer dimension of the welded portion 31 is preferably 2 to 15IIIR depending on the inner diameter, taking into consideration the aqueous solution retention and the welded area. More preferable melted part 3
The maximum external dimension of the cross-sectional view of No. 1 is 3 to 8 m, and the internal dimension of the cross section is 2 to 7 m.

The cross-sectional shapes are circular, oval, oval, and quadrilateral.
This is preferable because the melt-sealing operation is easy to perform, but it is not limited thereto.

FIG. 6 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 engage and seal (they have a cylindrical shape).

The AA' cross section of the melt-sealed portion 31 is circular. FIG. 7 shows a connecting tube 30 suitable for engagement with a thick side tube (dialysate port) of an artificial kidney.The shape of the engagement portion 32 is cylindrical with a conical top 34, and the shape of the engagement portion 32 is cylindrical with a conical top portion 34, which engages and seals the side tube. In addition, a collar 35 is attached to facilitate the work of attaching and detaching the connecting tube when using this artificial kidney on a patient. 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 can be destroyed by heat sterilization heating. This has the advantage that deformation and seal failure do not occur, the blood flow path can be maintained, and in addition, it is heat sterilized and sealed, and secondary bacterial contamination can be prevented.

Furthermore, the artificial kidney heat sterilized by the method of the present invention 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.

Furthermore, according to the present invention, an artificial kidney suitable for heat sterilization is a hollow fiber type artificial kidney composed of a hollow fiber, a partition wall, and a container.

The partition wall and the container have substantially heat resistance in the range of 40 to 130°C, and the partition wall member has a linear expansion coefficient a [1/”C)
is 40 to 130°C, the coefficient b[1/
°C] and temperature t [''C], the relationship of the following formula is established, (4,13x 10-5) e'-08769t≦
Provided is an artificial kidney characterized in that a≦2b and the partition member does not undergo secondary metastasis in 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 and by a method known per se.

That is, the hollow fiber materials include cellulose, cellulose ester, polyacrylonitrile, polyvinyl alcohol, polyaromatic acid amide (for example, polyamide benzhydrazide isophthalamide), polycarbonate, polyether polysulfone, polyacrylonitrile, and polycarbonate.

Polysulfone is a preferred material.

An example of the material for the container is 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 the urethane resins, poly(ester type urethane) is preferable, which is obtained by addition polymerizing a prepolymer whose terminal end is an isocyanate, a polyol (III! forming 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 Cellulose hollow fibers io, o with an inner diameter of 250μ and a membrane thickness of 30μ
oo books are collected and stored in a polycarbonate container,
Both ends were gripped and fixed with urethane resin to form a partition, and a polypropylene blood distribution plate was tightened and fixed with a polycarbonate bag cap to assemble a hollow fiber artificial kidney.

Next, the blood side and dialysate side of the artificial kidney were filled with distilled water at 20°C, and one place at the dialysate port was filled so that the thickness of the thin part was 0.
．． A buffer bag made of 5JII silicone rubber and having a volume of 50 d as shown in FIG. 5 was attached so as not to allow gas to enter the buffer bag. The amount of fluid filled in the artificial kidney was 422
m, and the residual air amount was measured after heat sterilization.
It was 7m. The other two blood ports and one dialysate port were fitted with silicone rubber plugs to prevent leakage of the filled fluid.

In this way, the artificial kidney with one sieve bag attached was heated to 115°C under a pressure of 2.0K97cd using a high-pressure steam sterilizer.
Heat sterilize for 0 minutes, and reduce the internal pressure of the sterilizer to 2. by introducing sterilized air. After being maintained at OKs/d and gradually cooled to room temperature, it was taken out from the high-pressure steam sterilizer.

There was no change in weight of this artificial kidney before and after heat sterilization, and there was no leakage of the filling fluid. In addition, as a result of conducting a sterility test,
Both bacteria and fungi were negative. Furthermore, when the hollow fibers were tested for leaks, there were no leaks, and an artificial kidney could be manufactured.

Examples 2 to 8 and Comparative Examples 1 to 3 The blood side and dialysate side of a hollow fiber artificial kidney assembled under the same conditions as Example 1 were filled with distilled water at 20°C, and one place at the dialysate port was filled with distilled water. A buffer bag as shown in the following embodiment was attached so as not to allow air to enter therein, and heat sterilization was performed using a high-pressure steam sterilizer under various conditions shown in Table 1 below.

The results are shown in Table 1 below.

In addition, when sterility tests were conducted on the artificial kidneys shown in Examples 2 to 8, all results were negative. That is, very good results were obtained in the present invention. The silicone rubber buffer bag used was an inflatable balloon type and had the shape shown in FIGS. 4 and 5. A bag-shaped polypropylene buffer bag was made from polypropylene film.

In Comparative Examples 1 to 3 in Table 1, the reason why the buffer bags were damaged by heat sterilization was that the volume of the tube bag was smaller than the increase in volume of water and residual air in the artificial kidney due to expansion due to heating. This is thought to be because.

(Margin below)

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram showing an embodiment of the present invention, and FIG.
a) or (b) is a perspective view showing another embodiment of the present invention. 3 to 5 are vertical sectional views showing typical examples of buffer bags used in the practical embodiment of the present invention. Figures 6 and 7 show a connecting tube for use in the present invention. The vertical cross-sectional view (a) and the cross-sectional view +b+ are in the relationship of the A-A' arrow view of the ζω diagram, respectively. In the drawing, 1 is an artificial kidney, 2 is a container, 3 is a hollow fiber,
8 is a filling leak prevention means, 9 is a conduit, 10 is a pressure buffer bag, and 30 is a connecting tube. Patent applicant Teijin Co., Ltd. 2nd trouble (b> 3rd country chapter 4th country 45th trouble θ (dn $7

Claims (1)

[Scope of Claims] 1. It has a container containing hollow fibers made of a selectively permeable membrane, and the container has openings consisting of a blood inlet, a blood outlet, a dialysate inlet, and a dialysate outlet. A method for heat sterilizing an artificial kidney provided, comprising: (a) filling the artificial kidney with a filling liquid consisting of water or an aqueous solution; (b) connecting a pressure buffer bag to at least one of the openings; (c) (d) heat sterilizing the artificial kidney by heating the artificial kidney to a temperature within the range of 80 to 130°C; (e) cooling the artificial kidney after sterilization, thereby transferring the filling liquid that had been transferred to the pressure buffer bag to the artificial kidney; (f) aseptically sealing the opening connected to the pressure buffer bag as needed. 2. The method of claim 1, wherein the pressure buffer bag is a sealed bag made of rubber elastic material so as to be inflatable by increasing internal pressure. 3. The bag is a bag in which a thick part and a thin part are integrated, the thick part is a neck that engages with the opening of the artificial kidney, and the thin part is an inflatable part, Claim 2, wherein the thickness T (mm) of the thick portion and the thickness (mm) of the thin portion satisfy the relationships of the following formulas (1) to (3):
The method described in section. 0.05mm≦t≦2mm...(1) 0.25mm≦T≦5mm...(2) 1<T/t≦30...(3) 4. After the step (f), the step (b) 2. The method according to claim 1, wherein the connection made in . 5. In the step (b), by interposing a conduit between the opening and the pressure buffer bag, and connecting one end of the conduit to the opening and the other end of the conduit to the pressure buffer bag. 2. The method of claim 1, further comprising connecting the opening and the pressure buffer bag.