JPH11178919A - Production method of artificial organs - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a production method of artificial organs which coats a fat-soluble modifier on a desired part. SOLUTION: This method is to coat a fat-soluble modifier on coated body fluid processing membrane of an artificial organ, the processing membrane is a microporous body fluid processing membrane made from a material with solution parameter σ being less than 13 (cal/cm<3> ), and this method consists of a filling process in which the microporous body fluid processing membrane is filled with filling fluid which is not compatible/less compatible with the fat- soluble modifier solution, and a coating process in which the fat-soluble modifier solution is brought into contact with the coated body fluid processing membrane.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an artificial organ having a microporous body fluid permeable membrane made of a hydrophobic material, wherein a part of the body fluid treatment membrane is coated with a fat-soluble modifier. The present invention also relates to a method for producing an artificial organ such as an artificial kidney, an artificial lung, and a plasma separation device which suppresses activation of leukocytes or platelets and has excellent biocompatibility.

[0002]

2. Description of the Related Art Synthetic polymer membranes have been widely used in dialysis membranes, blood component separation membranes and the like used for artificial organs such as artificial kidneys and plasma separators. However, for example, in the artificial kidney used for hemodialysis treatment, since extracorporeal circulation using the artificial kidney is frequently performed, a complication considered to be caused by activation of leukocytes or platelets occurs, and the dialysis patient has It is a serious problem. In particular, a decrease in antioxidant activity in blood and a high level of lipid peroxide have been confirmed in patients undergoing long-term hemodialysis, and as a result, arteriosclerotic diseases in long-term dialysis patients have increased.

[0003] In order to solve such problems of artificial organs, the surface of a dialysis membrane is coated with a vitamin E film having various physiological actions such as an antioxidant action in vivo, a stabilizing action on a biological membrane, and an inhibitory action on platelet aggregation. (Japanese Patent Publication No. 62-41738). In addition, polyunsaturated fatty acids such as eicosapentaenoic acid have antithrombotic properties,
Improvement of hyperlipidemia is expected.

Also, apart from the portion of the hollow fiber membrane that contacts the body fluid, the hydrophobicity of the portion that does not come into contact with the body fluid is enhanced, so that the hydrophobic substance can be effectively adsorbed and the like, and penetration into the body fluid can be prevented. it can.

[0005] However, when such a fat-soluble substance is used as a modifier for an artificial organ material, when the artificial organ material is hydrophilic, the fat-soluble modifier and the artificial organ material bind to each other. And there is a concern about problems such as peeling and elution. The higher the solubility parameter δ, which is an index of the hydrophilicity of the material, the stronger the hydrophilicity, but the regenerated cellulose (δ = 15.6)
When 5 (cal / cm ³ ) ^1/2 ) is coated with vitamin E, vitamin E is eluted into the blood when blood is introduced into the artificial organ and blood circulation is performed. It was confirmed that about 90% of vitamin E was eluted into the blood per minute.

On the other hand, when the solubility parameter δ is 13 (cal
/ Cm ³ ) In order to coat a dialysis membrane composed of a hydrophobic material of ^1/2 or less with vitamin E, a method of flowing a vitamin E solution described in JP-B-62-41738 is used.
The entire dialysis membrane is non-selectively coated. The solvent of the vitamin E solution used at this time is inactive to the dialysis membrane and dissolves vitamin E, such as Freon, hexane,
Alcohol and the like are selected, but since such a solvent often penetrates into the pores of the hydrophobic porous membrane, the solvent containing vitamin E easily passes through the micropores of the membrane. Are dispersed throughout the inner layer, intermediate layer, and outer layer, and are fixed non-selectively. In the above case, it is also immobilized on the non-contact surface with blood, and it is difficult to control the amount of immobilization. Further, when the entire membrane is immobilized with vitamin E, the hydrophobicity of the membrane becomes strong, and the ability to treat water such as body fluids may be reduced.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an artificial organ having a microporous body fluid permeable membrane made of a hydrophobic material which has solved the above-mentioned problems, and to coat a part of the body fluid treatment membrane with a fat-soluble modifier. To provide a method for producing an artificial organ. Another object of the present invention is to provide a method for producing an artificial organ such as an artificial kidney, an artificial lung, and a plasma separation apparatus which suppresses activation of leukocytes or platelets and has excellent biocompatibility.

[0008]

Means for Solving the Problems In order to solve the above problems, a method for producing an artificial organ according to the present invention has the following arrangement.

The method for producing an artificial organ according to the present invention is directed to an artificial organ having a microporous body fluid treatment film made of a material having a solubility parameter δ of 13 (cal / cm ³ ) ^1/2 or less. A method of coating a coated portion with a fat-soluble modifier, comprising: filling a microporous surface of the body fluid treatment film with a filler liquid that is not compatible or has low compatibility with a fat-soluble modifier solution; A coating step of bringing the solubility modifier solution into contact with the coated portion of the body fluid treatment film.

[0010] In the method for producing an artificial organ according to the present invention, the coated portion is a surface portion of the body fluid treatment film which can come into contact with body fluid.

[0011] In the method for producing an artificial organ according to the present invention, the coated portion is a surface portion of the body fluid-treated film which cannot contact body fluid.

[0012] The method for producing an artificial organ according to the present invention includes a liquid removing step of removing a filler liquid on the surface of the coated portion of the body fluid treatment film between the filling step and the coating step.

[0013] In the method for producing an artificial organ according to the present invention, the coating step passes the fat-soluble modifier solution over the body fluid treatment membrane.

In the method for producing an artificial organ according to the present invention, the fat-soluble modifier is vitamin E.

In the method for producing an artificial organ according to the present invention, the filling liquid is water.

The solubility parameter δ in the present invention is:
It indicates the degree of hydrophilicity of the material. When the solubility parameter δ is high, the hydrophilicity is strong, and when the solubility parameter δ is low, the hydrophobicity is strong. The calculation method of the solubility parameter δ and the like are described in many documents such as, for example, Polymer Handbook (Basic Edition, pages 591 to 593).

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Artificial organs produced according to the present invention are, for example, artificial kidneys, artificial lungs, plasma separation devices and the like.

The artificial kidney has a function of moving waste products out of the blood and removing them by the action of dialysis or filtration through a body fluid treatment membrane such as a dialysis membrane or a blood filtration membrane.
It has microporosity of m to several μm. The body fluid treatment membrane for an artificial kidney includes a hydrophilic membrane typified by regenerated cellulose and a hydrophobic membrane typified by polysulfone.

FIG. 1 shows an example of a hollow fiber membrane type dialyzer which is a kind of artificial kidney. In this dialyzer 1, after inserting a hollow fiber bundle 5 composed of a large number of hollow fibers into a cylindrical main body 4 provided with an inlet pipe 2 and an outlet pipe 3 for dialysis fluid near both ends thereof, both ends thereof are made of polyurethane. The cylindrical body 4 is sealed together with the potting agents 6 and 7 at both ends. Headers 10 and 11 having an inflow port 8 and a discharge port 9 for bodily fluids are respectively in contact with both ends of the cylindrical main body 4, and caps 12 and 11 are provided.
13, the headers 10, 11 and the tubular main body 4 are fixed to each other. Further, tubes 14 and 15 connected to the human body are connected to the body fluid inlet 8 and the body fluid outlet 9 at both ends of the cylindrical main body 4. The hollow fiber membrane has a hollow fiber lumen communicating with the body fluid inlet 8 and the outlet 9, and an outside of the hollow fiber membrane communicating with the inlet pipe 2 and the outlet pipe 3.

The artificial lung has a function of releasing carbon dioxide in blood by diffusion of gas through a body fluid treatment membrane such as a hydrophobic gas permeable membrane and supplying oxygen. Several nm to several hundred nm
The present invention can be applied to an artificial lung having a hydrophobic gas permeable membrane having fine pores. For such a hydrophobic gas permeable membrane, polyethylene, polypropylene, or the like is used.

The plasma separation device has a function of separating blood plasma containing protein such as albumin from blood by filtration through a body fluid treatment membrane permeable to plasma proteins having microporosity of several tens nm to several μm. Various materials have been used.

When the solubility parameter δ representing the degree of hydrophilicity of the material is 13 (cal / cm ³ ) ^1/2 or less, the hydrophobic property becomes strong, and a fat-soluble modifier such as vitamin E is used. Of the fat-soluble modifier is less likely to come off, and the effect of the fat-soluble modifier can be effectively exhibited.

When such a body fluid treatment film is coated with a fat-soluble modifier, an organic solvent solution of the fat-soluble modifier is brought into contact with the body fluid treatment film and dried. However, when the body fluid treatment film having the microporous material is made of a hydrophobic material, the organic solvent solution intrudes into the inside of the microporous material by contacting the organic solvent solution of the fat-soluble modifier, and the oil is applied to the entire body fluid treatment film. The solubility modifier is coated.

When only one surface of a body fluid treatment membrane having a microporous material made of a hydrophobic material or a hollow fiber membrane is used,
The present invention has the following filling step and coating step in order to selectively coat the inner surface portion or the outer surface portion with the fat-soluble modifier.

<Filling Step> In the filling step, a liquid which is not compatible or has low compatibility with the organic solvent solution of the fat-soluble modifier and which does not deteriorate the body fluid treatment film is placed inside the microporous body of the body fluid treatment film. Used. Usually, water is used. Water is safe for living organisms, wastewater treatment is easy, and it is easy to select an organic solvent having no compatibility.

As an example, as a method for filling water into the microporosity of the hollow fiber membrane, any method may be used as long as the water is filled. Is contained, the hollow fiber membrane may be brought into contact with water or may be subjected to moderate pressure. In addition, an organic solvent (eg, ethanol or methanol) or an aqueous solution thereof that is compatible with water is brought into contact with the hollow fiber membrane or filled into the microporous layer by moderate pressure, and then the organic solvent or the organic solvent aqueous solution is replaced with water. There are methods. Appropriate pressurization is at most about 2 kg / cm ² .

<Coating Step> When the inner surface of the hollow fiber is coated as a body fluid treatment membrane, a fat-soluble modifier is used as an organic solvent solution, and the body fluid treatment membrane of an artificial organ (in the case of the artificial kidney shown in FIGS. 1 and 2). The lipophilic modifier adheres to the inner surface of the hollow fiber membrane by flowing into the hollow fiber cavity of the dialysis membrane.
At this time, when water is used as the filling liquid, the water is filled in the microporous portion of the hollow fiber membrane middle part and the outer surface part, and the fat-soluble modifier which is insoluble or hardly soluble in water, and The organic solvent does not penetrate into the hollow fiber membrane middle part and the outer surface part, and the fat-soluble modifier is not coated. An organic solvent solution of this fat-soluble modifier is left for a predetermined time, for example, 30 minutes.
It is preferable that the fat-soluble modifier is sufficiently blended into the inner surface of the hollow fiber membrane by contacting for 2 to 60 minutes, preferably 1 to 10 minutes.

Further, the coated surface is dried by introducing an inert gas into the hollow fiber cavity or the like to form a film of the fat-soluble modifier. After discharging the organic solvent solution, 10 to 80 ° C,
Preferably, a gas inert to the fat-soluble modifier used at a temperature of 15 to 30 ° C., for example, air, nitrogen, carbon dioxide or the like is introduced to evaporate and remove the organic solvent.

By performing the liquid removing step between the filling step and the coating step, coating can be performed more efficiently.

<Liquid Removal Step> After the filling step, if the filling liquid remains in the vicinity of the portion to be coated with the fat-soluble modifier such as the hollow fiber membrane cavity as a body fluid treatment membrane, the oil When the organic solvent solution of the solubility modifier flows into the hollow fiber cavity, time and the organic solvent solution are wasted until the solution is replaced with the organic solvent solution. Therefore, before entering the coating step, it is preferable to remove the filling liquid at the site to be coated with the fat-soluble modifier.

The filling liquid can be removed by blowing a gas such as air or nitrogen onto the surface to be coated. It is preferable to use a dried gas.

Although the description has been made mainly on the coating of the inner surface of the hollow fiber membrane, in the case of coating the outer surface of the hollow fiber membrane, an organic solvent solution of a fat-soluble modifier is allowed to flow outside the hollow fiber membrane. Good.

The body fluid treatment membrane used in the present invention has a microporosity and is made of a material having a solubility parameter δ of 13 (cal).
/ Cm ³ ) Any film may be used as long as it is ^1/2 or less. Preferably, polyethylene (δ = 7.70), polymethyl methacrylate (δ = 9.10), polystyrene (δ = 9.70).
15), polypropylene (δ = 9.40), polysulfone (δ = 9.90), polyhydroxyethyl methacrylate (δ = 10.00), nylon 66 (δ = 11.1)
8), selected from cellulose diacetate (δ = 11.35), polyacrylonitrile (δ = 12.35), polyvinyl alcohol (δ = 12.60), cellulose triacetate, ethylene-vinyl alcohol copolymer, and polycarbonate At least one polymer material can be used.

Further, the body fluid treatment membrane of the present invention may contain a hydrophilic polymer such as polyvinylpyrrolidone and polyethylene glycol.

The fat-soluble modifier used in the present invention includes fat-soluble vitamins and highly unsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Further, it can also be used in the case where a portion which cannot contact with the body fluid is coated, and the hydrophobicity of the body fluid treatment film is adjusted so that a hydrophobic substance is adsorbed. Vitamin E is typical as a fat-soluble vitamin. And tocopherol derivatives such as tocotrienol acetate, tocopherol acetate, and tocopherol nicotinate.

The thickness of the vitamin E film is 0.0
It is from 0.01 to 1.0 μm, preferably from 0.01 to 0.3 μm. When the film thickness is 0.001 μm or less, the effect of biocompatibility obtained by coating with vitamin E hardly appears, and when the film thickness is 1.0 μm or more, dialysis performance may be reduced.

Further, the coating amount of vitamin E is 1 to 10
00 mg / m ² , preferably 10 to 300 mg / m ² . When the coating amount of vitamin E is 1 mg / m ² or less, the coating of vitamin E is likely to be uneven, and the effect of biocompatibility is reduced. On the other hand, when the concentration is 1000 mg / m ² or more, the film thickness of vitamin E becomes thick, and the elution of vitamin E and the dialysis performance may decrease.

[0038] Such vitamin E is used in an amount of 0.01 to 20 w
/ V%, preferably 0.1 to 10 w / v%, as an organic solvent solution, is preferably introduced into a body fluid permeable membrane of an artificial organ (dialysis membrane in the case of the artificial kidney shown in FIGS. 1 and 2). The coating amount of vitamin E depends on the vitamin E concentration of the processed vitamin E solution, so that the coating amount can be easily controlled.

The preferred range for vitamin E is:
The same applies to other fat-soluble modifiers.

The organic solvent used in the present invention may be any one which is insoluble in the synthetic polymer film and incompatible with the filling liquid. When water is used as the filling liquid, water-insoluble solvents include alcohols such as n-butanol, isobutanol, sec-butanol, 2-ethylhexanol, diethyl ether and the like, and hydrocarbons such as n-hexane and the like. Or, for example, 1, 2, 2
Chlorofluorohydrocarbons such as trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, 1,1,2,2-tetrachloro-1,2-difluoroethane or, for example, methyl fluoride, tetrafluoride Perfluorocycloalkanes such as carbon, tetrafluoroethane, tetrafluoroethylene, perfluoromethylpropylcyclohexane, and perfluorobutylcyclohexane; and fluorinated hydrocarbons such as perfluorodecane, perfluoromethyldecalin, and perfluoroalkyltetrahydropyran. .
In the case where the organic solvent is removed by evaporation with a gas, those which are volatile and have a low boiling point are more preferable.

Although the above description has been made mainly of the hollow fiber membrane type artificial kidney which is a dialyzer, it goes without saying that the present invention can be used for artificial organs having other body fluid treatment membranes. When the solubility parameter δ is 13 (cal
/ Cm ³ ) ^1/2 or less, and is not limited to a hollow fiber membrane, and may be a flat membrane or the like.

Next, embodiments of the present invention will be described in more detail with reference to the accompanying drawings.

[0043]

Example 1 Inner diameter: about 200 μm, outer diameter: about 280 μm, pore diameter (inner surface: 3 nm, outer surface: 500 nm), length: about 2
4 cm, solubility parameter δ 9.90 (cal / c
m ³ ) Using 10300 ^1/2 polysulfone hollow fiber membranes,
As shown in FIG. 1, it is inserted into the cylindrical main body 1, and both ends are fixed with polyurethane potting agents 6, 7, and headers 10, 11 are attached to both ends.
To form a dialyzer (artificial kidney) 1. Note that the film area of the dialyzer 1 was 1.5 m ² .

Next, 500 ml / min from the dialysate inlet.
, Water was introduced for 1 minute, and water was filled in the micropores of the hollow fiber membrane. Then, after the water outside the hollow fiber membrane was removed by a head, air was introduced from the header for 10 minutes to remove the water in the hollow fiber membrane inner cavity.

On the other hand, 2.0 g of vitamin E (dl-α-tocopherol) was dissolved in 100 ml of hexane to adjust the concentration of the hexane solution of vitamin E to 2 w / v%. Then, a 50 ml syringe is connected to the tube 15 communicating with the bodily fluid outlet 9 of the dialyzer 1, the tube 14 communicating with the bodily fluid inlet is inserted into the vitamin E solution, and the plunger of the syringe is operated to hollow the dialyzer. The lumen of the fibrous membrane was filled with a solution of vitamin E. In this state, it was left at room temperature for 2 minutes. Next, after discharging the vitamin E solution from the dialyzer, nitrogen gas at 60 ° C. was blown to dry the inner surface of the hollow fiber membrane to remove hexane. Vitamin E coverage in the dialyzer thus obtained is 2
It was 3.8mg / ^{m 2.}

[0046]

Example 2 A dialyzer was manufactured in the same manner as in Example 1 using the same polysulfone hollow fiber as in Example 1 and adjusting the concentration of vitamin E in the hexane solution of vitamin E to 5 w / v%. Vitamin E coverage in this dialyzer was 55.2 mg / m ² .

Comparative Example 1 For comparison, Example 1 was used.
Vitamin E coating treatment was performed using the same polysulfone hollow fiber as in Example 1 and using a hexane solution having a vitamin E concentration of 2 w / v% without a water filling step. The phenomenon that the solution was filtered out of the hollow fiber membrane was observed. The amount of vitamin E in the dialyzer thus obtained was 115.7 mg / m
It was ² .

(Comparative Example 2) For comparison, Example 1 was used.
Vitamin E coating treatment was performed using the same polysulfone hollow fiber as in Example 1 and using a hexane solution having a vitamin E concentration of 5 w / v% in the same manner as in Example 2 without a water filling step. The phenomenon that the solution was filtered out of the hollow fiber membrane was observed. Vitamin E coverage in the dialyzer thus obtained was 298.6 mg / m
It was ² .

(Experimental Example 1) Using the dialyzer of Example 1 and Comparative Example 1, the clearance of vitamin B12 was measured. 2 mg / dl of vitamin B12 / on the blood side
After waiting for 5 minutes at a flow rate of 200 ml / min using acetic acid dialysate and at a flow rate of 500 ml / min and a filtration flow rate of 15 ml / min using acetic acid dialysate for 5 minutes, the blood-side inlet flow rate (Q _Bi ) The blood-side inlet concentration (C _Bi ), the blood-side outlet flow rate (Q _Bo ), and the blood-side outlet concentration (C _Bo ) were determined, and the clearance was calculated by the following equation.

Clearance (C _L ) = (CBi × QBi)
−CBo × QBo) / CBi The measurement temperature was 37 ° C. and the concentration was determined from the absorbance at 360 nm.

As a result of the measurement, the clearance of vitamin B12 was 132 ml / min in Example 1 and 93 ml / min in Comparative Example 1.

[0052]

As described above, an artificial organ having a microporous body fluid treatment film made of a material having a solubility parameter δ of 13 (cal / cm ³ ) ^1/2 or less is applied to a portion covered with the body fluid treatment film. A method of coating a fat-soluble modifier with a filling liquid that is not compatible or has low compatibility with a fat-soluble modifier solution in the microporosity of the body fluid treatment membrane; By having a coating step of bringing the liquid agent solution into contact with the coated part of the body fluid treatment film, if the coating treatment of the fat-soluble modifier is performed without performing the filling step, the fat-soluble modifier organic solvent solution will The fat-soluble modifier can be coated only on the necessary parts, compared to the entire film being coated not only on the inner surface of the film but also on the inner and outer surfaces of the film, and the fat-soluble used The modifier can be reduced.

In addition, when the fat-soluble modifier treatment is performed without performing the filling step, the concentration of the fat-soluble modifier organic solvent solution,
The present invention can improve the difficulty of controlling the coating amount due to the fluctuation factor of the coating amount due to the pressure at the time of treatment, the affinity of the body fluid treatment film for the organic solvent used, and the permeability.

Further, as shown in Table 1, if the whole membrane is coated with vitamin E, which is hydrophobic, the hydrophobicity of the whole membrane becomes high, and the dialysis due to a decrease in the amount of filtration with respect to water and a decrease in the affinity with the dialysate. In the present invention, the problem that the performance is deteriorated can be limited to a portion requiring a fat-soluble modifier (for example, only the inner surface of a hollow fiber membrane), so that the original dialysis performance is impaired. This makes it possible to obtain the effect of the fat-soluble modifier without using it.

[Brief description of the drawings]

FIG. 1 is a perspective view of a dialyzer according to an embodiment of the present invention, which has a partially cut-out portion.

FIG. 2 is a longitudinal sectional view of a hollow fiber membrane showing an example of the present invention.

[Explanation of symbols]

 Reference Signs List 1 dialyzer 2 dialysate inlet pipe 3 dialysate outlet pipe 4 cylindrical main body 5 hollow fiber membrane 6,7 potting agent 8 body fluid inlet 9 body fluid outlet 10,11 header 12,13 cap 14,15 tube 16 hollow fiber membrane 17 Coating

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[Procedure amendment]

[Submission date] February 17, 1998

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0027

[Correction method] Change

[Correction contents]

<Coating Step> When the inner surface of the hollow fiber is coated as a body fluid treatment membrane, a fat-soluble modifier is used as an organic solvent solution, and a body fluid treatment membrane of an artificial organ (dialysis membrane in the case of the artificial kidney shown in FIG. 1) is used. ) By flowing into the hollow fiber lumen
The fat-soluble modifier adheres to the inner surface of the hollow fiber membrane. At this time, when water is used as the filling liquid, the water is filled in the microporous portion of the hollow fiber membrane middle part and the outer surface part, and the fat-soluble modifier which is insoluble or hardly soluble in water, and The organic solvent does not penetrate into the hollow fiber membrane middle part and the outer surface part, and the fat-soluble modifier is not coated. It is preferable to allow the organic solvent solution of the fat-soluble modifier to come into contact with the inner surface of the hollow fiber membrane sufficiently for a predetermined time, for example, 30 seconds to 60 minutes, and preferably 1 to 10 minutes, to allow the fat-soluble modifier to adapt sufficiently.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0038

[Correction method] Change

[Correction contents]

[0038] Such vitamin E is used in an amount of 0.01 to 20 w
/ V%, preferably 0.1 to 10 w / v%, in an organic solvent solution is preferably introduced into a body fluid permeable membrane of an artificial organ (dialysis membrane in the case of the artificial kidney shown in FIG. 1). The coating amount of vitamin E depends on the vitamin E concentration of the processed vitamin E solution, so that the coating amount can be easily controlled.

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0054

[Correction method] Change

[Correction contents]

Furthermore, vitamin E which is hydrophobic throughout the membrane
Is coated, the hydrophobicity of the entire membrane becomes high, the problem that dialysis performance is reduced due to a decrease in the amount of filtration with respect to water and a decrease in affinity with the dialysate, the present invention,
It is possible to coat only the part requiring the fat-soluble modifier (for example, only the inner surface of the hollow fiber membrane), so that the effect of the fat-soluble modifier can be obtained without impairing the original dialysis performance. It is possible.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] Brief description of drawings

[Correction method] Change

[Correction contents]

[Brief description of the drawings]

FIG. 1 is a perspective view of a dialyzer according to an embodiment of the present invention, which has a partially cut-out portion.

Claims (7)

[Claims] 1. The method according to claim 1, wherein the solubility parameter δ is 13 (cal / c).
m ³ ) A method of coating a fat-soluble modifier on an artificial organ having a microporous body fluid treatment film made of a material having a thickness of ^1/2 or less, wherein the body fluid treatment film is coated with a fat-soluble modifier. A filling step of filling the microporous with a filling liquid having no or low compatibility with the fat-soluble modifier solution, and a coating step of bringing the fat-soluble modifier solution into contact with the covering portion of the body fluid treatment film. A method for producing an artificial organ, comprising: 2. The method for producing an artificial organ according to claim 1, wherein the covering portion is a surface portion of the body fluid treatment film that can come into contact with a body fluid. 3. The method for producing an artificial organ according to claim 1, wherein the coating portion is a surface portion of the body fluid treatment film that cannot contact body fluid. 4. The method according to claim 1, further comprising, between the filling step and the coating step, a liquid removing step of removing a filler liquid on a surface of the coated portion of the body fluid treatment film. A method for producing an artificial organ. 5. The method for producing an artificial organ according to claim 1, wherein the coating step comprises passing the fat-soluble modifier solution over the body fluid treatment film. 6. The method for producing an artificial organ according to claim 1, wherein the fat-soluble modifier is vitamin E. 7. The method for producing an artificial organ according to claim 1, wherein the filling liquid is water.