JPH0970524A - Permselective separation membrane and method for producing the same - Google Patents

Abstract

(57) Abstract: [PROBLEMS] To provide a permselective separation membrane that suppresses the permeability of useful protein albumin and enhances the removal performance of medium and high molecular weight uremic proteins, and a method for producing the same. SOLUTION: In a permselective separation membrane containing a hydrophobic polymer and a hydrophilic polymer as main components, the hydrophilic polymer having a molecular weight of less than 100,000 is 10% by weight or more, based on the total weight of the hydrophilic polymer, 50% or more. A permselective separation membrane characterized by being contained in an amount of 50% by weight or more and 100% or more of a hydrophilic polymer in an amount of 50% by weight or more and 90% by weight or less based on the total weight of the hydrophilic polymer.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a permselective separation membrane and a method for producing the same. More specifically, when it is used for blood treatment by controlling the molecular weight distribution of the hydrophilic polymer present in the membrane, it maintains a high hemofiltration flow rate and low albumin permeability over a long period of time, and is a uremic substance composed of a medium polymer protein. The present invention relates to a membrane having a high selective permeation rate with respect to, and a method for producing these membranes.

[0002]

2. Description of the Related Art As a semipermeable membrane for blood treatment, natural materials such as cellulose, synthetic polymer membrane materials such as polysulfone, PMMA, and polyacrylonitrile have been widely used until today. Various technological developments have been made to bring humans closer to the human kidney. Among these membrane materials, polysulfone having high water permeability has attracted attention in recent years as one that meets the progress of dialysis technology. Originally, polysulfone is widely used as a thermoplastic heat-resistant engineering plastic in the fields of automobiles, electricity, and medical devices, but when a semipermeable membrane is made of polysulfone alone, the intermolecular cohesive force is strong, Further, since it is hydrophobic, it has a poor affinity with blood and cannot be used as it is for blood treatment. Therefore, by mixing hydrophilic polymer, inorganic salt, etc. as a pore-forming material and leaching to form a pore, at the same time, the surface of the polymer is made hydrophilic.
A method of using this as a semipermeable membrane and a reverse osmosis membrane was devised,
Filed

As a method of manufacturing a semipermeable membrane for blood treatment,
A method of forming a film by adding a metal salt, a method of forming a film by adding a hydrophilic polymer, a method of forming a film by adding a polyhydric alcohol, and the like are disclosed. However, JP-A-61-2286
0, when a polyhydric alcohol such as polyethylene glycol is added to form a film as in JP-A-58-114702,
With insufficient cleaning, residual alcohol on the membrane causes abnormalities in the patient's eye during dialysis. Japanese Patent Fair 6-75
667 also discloses a film forming method using polyvinylpyrrolidone, but although it has high water permeability, it has a problem of high albumin permeability for blood treatment (dialysis). The method using a metal salt disclosed in JP-A-62-121608 is also the same. JP-A-6-233921 proposes a method for producing a hollow fiber membrane in which a hydrophilic polymer having a high molecular weight is added to increase the viscosity so that a good solvent of the stock solution can be used as 100% core liquid. , This method cannot control the albumin permeability of the membrane.
Moreover, there is no knowledge about the molecular weight distribution of the hydrophilic polymer in the film. In Japanese Examined Patent Publication No. 2-18695, the content of high molecular weight polyvinylpyrrolidone is specified to be higher than that of polysulfone.
A film in which a large amount of polyvinylpyrrolidone is left in the film to improve the stain resistance and the cleaning property of the film is disclosed, but the high diffusion performance intended by the present invention has not been obtained. Further, Japanese Patent Publication No. 5-54373 discloses a membrane in which most of polyvinylpyrrolidone is washed and removed using a low-viscosity stock solution of polysulfone and polyvinylpyrrolidone having a relatively low molecular weight, but remains in the membrane as in the present invention. It is not specified that the molecular weight distribution of the hydrophilic polymer exhibits a high diffusion performance. Especially in recent years, dialysis started 20
Since several years have passed, many complications due to long-term dialysis have been reported, and a protein having a molecular weight of 20,000 to 40,000 has been attracting attention as a causative agent of carpal tunnel syndrome and other dialysis syndromes. No selective separation membrane that substitutes or mimics the high human renal function capable of actively removing the protein of the above has not been disclosed.

[0004]

DISCLOSURE OF THE INVENTION As a result of intensive studies conducted by the present inventors to overcome the above drawbacks, the present invention has been accomplished. That is, it is an object of the present invention to provide a permselective separation membrane that suppresses the permeability of albumin, which is a useful protein, and enhances the removal performance of medium and high molecular weight uremic proteins, and a method for producing the same.

[0005]

In order to achieve the above object, the present invention has the following constitution.

[(1) In a permselective separation membrane composed mainly of a hydrophobic polymer and a hydrophilic polymer, the hydrophilic polymer having a molecular weight of less than 100,000 is 10% by weight based on the total weight of the hydrophilic polymer. As described above, 50% by weight or less is contained, and 100,000 or more hydrophilic polymers are 50% by weight or more based on the total weight of the hydrophilic polymers.
A permselective separation membrane comprising 90% by weight or less.

(2) In a permselective separation membrane mainly composed of a hydrophobic polymer and a hydrophilic polymer, the hydrophilic polymer having a molecular weight of less than 100,000 is 10% by weight or more based on the total weight of the hydrophilic polymer. , 50% by weight or less, and 100,000 or more of the hydrophilic polymer is 50% by weight or more based on the total weight of the hydrophilic polymer, 9
A permselective separation membrane, which is obtained by insolubilizing a composition containing 0% by weight or less.

(3) Hydrophobic polymer and hydrophilic polymer, solvent,
A film-forming undiluted solution containing at least an additive is used, and the content ratio of the hydrophilic polymer having a molecular weight of 100,000 or more is 1.8% by weight or more and 20% by weight or less with respect to the entire film-forming undiluted solution. Method for producing permselective separation membrane.

(4) A permselective separation membrane having a total mass transfer coefficient of 0.0025 cm / min or more at a Stokes radius of at least 3 nm in a diffusion performance test with dextran and an albumin permeability of 4% or less. "

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, the stock solution used for forming a selective separation membrane contains at least a hydrophobic polymer, a hydrophilic polymer, a solvent, and an additive.

As the hydrophobic polymer, most engineering plastics such as polysulfone, polyamide, polyimide, polyphenyl ether and polyphenylene sulfide can be used, but polysulfone having the following basic skeleton is particularly preferable. Among the following basic skeletons, those having a modified benzene ring portion can also be preferably used.

[0012]

Embedded image The hydrophilic polymer is not particularly limited, but those which form a microphase-separated structure, which is invisible to the eyes in a solution with the hydrophobic polymer, are preferably used. Specific examples thereof include polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose, and polyvinylpyrrolidone. These may be used alone or in combination. Among them, polyvinylpyrrolidone is preferably used because it is industrially relatively easy to obtain. Here, as the hydrophilic polymer, two or more kinds having different molecular weights are used in the present invention. With respect to the molecular weight distribution, it is particularly preferable to use one having a weight-average molecular weight that differs by 5 times or more in the ratio.

As the solvent, an amphoteric solvent that dissolves well the hydrophobic polymer, the hydrophilic polymer and the additive is used. Specifically, dimethylacetamide, dimethylformamide, dimethylsulfoxide, acetone, acetaldehyde, 2-methylpyrrolidone, etc.
Dimethylacetamide is preferable in terms of stability and toxicity. As the additive, those which are compatible with the hydrophilic polymer in the poor solvent of the hydrophobic polymer are used, and specific examples thereof include alcohol, glycerin, water and esters.
From the viewpoint of process suitability, water is particularly preferable.

In the permselective separation membrane of the present invention, the hydrophilic polymer having a molecular weight of less than 100,000 is contained in the hydrophilic polymer in an amount of 10 or less.
50% by weight or more, and 100,000 or more of hydrophilic polymer is 50% by weight based on the total weight of the hydrophilic polymer.
As described above, the content is 90% by weight or less. That is, in the present invention, in the hydrophilic polymer, in the high molecular weight hydrophilic polymer, the presence of the low molecular weight hydrophilic polymer, while suppressing the permeation of albumin, which is a useful protein, has a diffusion performance in the middle molecular region or higher. It has been found that it is particularly improved. This is probably because a low molecular weight polymer can be incorporated into a large high molecular weight polymer to form an appropriate network structure for permeating a medium molecular weight protein. However, when the high molecular weight hydrophilic polymer is used alone, it is not possible to achieve the low albumin permeability required for artificial kidneys and the like while maintaining high water permeability. Further, when the low molecular weight hydrophilic polymer alone is used, it is difficult to control the pore size by appropriate film forming conditions, and the process becomes unstable due to changes in the film forming conditions, which not only deteriorates the quality of the film but also improves the water permeability. In that case, albumin suddenly leaks at a certain point and cannot be used as a blood treatment membrane for dialysis.

Further, the content of the hydrophilic polymer in the selective separation membrane is preferably 3% by weight or more and 15% by weight or less with respect to the hydrophobic polymer. This is because if it is less than 3% by weight, the wettability tends to be insufficient and coagulation may be caused when contacting blood. On the other hand, if it exceeds 15% by weight, a large amount of the hydrophilic polymer in the membrane tends to reduce the permeation performance and insufficient control of albumin leak.

In the present invention, the above-mentioned molecular weight of 10
Less than 10,000 hydrophilic macromolecules is 1 based on the total weight of hydrophilic macromolecules
A selective separation membrane containing 0% by weight or more and 50% by weight or less and 100,000 or more hydrophilic polymers contained in an amount of 50% by weight or more and 90% by weight or less based on the total weight of the hydrophilic polymer,
For example, when used in an artificial kidney or the like, insolubilization treatment is preferable in order to reduce the elution of the hydrophilic polymer as much as possible. The insolubilization means that the polymer is not dissolved in a good solvent for each polymer before the crosslinking due to the crosslinking. In addition, the film after the insolubilization treatment preferably contains 2% by weight or more and 15% by weight or less of the insoluble matter with respect to the total weight of the film. If it is less than 2% by weight, the active layer in the vicinity of the inner surface of the membrane becomes thin, and when it is used for blood treatment, for example, it tends to cause aggregation of blood components. Also, 15% by weight
If it exceeds, the active layer may become too thick and the water permeability may deteriorate.

Further, the ratio of the derived polymer in the insolubilized product is such that the hydrophobic polymer is 15% by weight or more and 40% by weight or less,
The hydrophilic polymer content is preferably 60% by weight or more and 85% by weight or less. If the hydrophobic polymer is less than 15% by weight,
The proportion of hydrophobic groups becomes small, and the structure of the entire membrane tends to change easily due to external pressure. On the other hand, if it exceeds 40% by weight, on the other hand, the flexibility is reduced, which may be disadvantageous when performing thread shape processing (crimping etc.) of the film.

The insolubilization method is not limited, but it is preferable to carry out the crosslinking by, for example, γ-ray, electron beam, heat, chemical method or the like. In particular, γ-ray irradiation in the presence of water is preferable, and the irradiation amount is preferably 10 to 50 KGy, more preferably 20 to 40 KGy. By the insolubilization bridge treatment, the hydrophobic polymer and the hydrophilic polymer are bound to each other, and the elution of the hydrophilic polymer is reduced. In addition, although it is considered that such treatment causes changes in performance and structure, the network structure that positively permeates medium- and high-molecular-weight proteins shows some deterioration in performance because the structure is retained and reinforced by the crosslinking treatment. However, it hardly changes.

In the present invention, the fact that a hydrophobic polymer or a hydrophilic polymer is contained in the selective separation membrane means that it is a solid 13C.
-It can be analyzed by NMR spectrum analysis. The content of the hydrophobic polymer and the hydrophilic polymer can be analyzed by elemental analysis.

In the present invention, a film-forming stock solution containing at least a hydrophobic polymer, a hydrophilic polymer, a solvent and an additive is used, and two or more hydrophilic polymers having different molecular weights are contained,
Further, the selective separation membrane of the present invention can be obtained by setting the content ratio of the hydrophilic polymer having a molecular weight of 100,000 or more to 1.8% by weight or more and 20% by weight or less with respect to the entire membrane forming solution. . If it exceeds 20% by weight, the viscosity of the stock solution increases,
It becomes difficult to form a film, and the water permeability and the diffusion performance are deteriorated. On the other hand, if the amount is less than 1.8% by weight, an appropriate network structure for permeating the medium and high molecular weight uremic protein cannot be constructed.

The stability of the stock solution by adding a high molecular weight hydrophilic polymer can be explained as follows. The additive is clathrated by the intermolecular force with the coexisting hydrophilic polymer and does not come into direct contact with the hydrophobic polymer. But,
Due to the high temperature during the dissolution, a part is detached, which promotes the recrystallization of oligomers such as a dimer of the hydrophobic polymer, which causes the stock solution to become cloudy. As the molecular weight of the hydrophilic polymer increases, the inclusion effect increases, so that the stability of the stock solution is improved. The stock solution viscosity is
Although it depends on the molecular weight of the hydrophilic polymer, naturally, the decrease in the viscosity of the stock solution causes yarn breakage, yarn sway, and the like at the time of forming the hollow fiber to deteriorate the stability. Also in this respect, it is important to increase the average molecular weight in the mixed system of hydrophilic polymers.

Next, the polymer concentration of the stock solution for film formation will be described. From the above-mentioned point, as the polymer concentration is increased, the film-forming property is improved, but on the contrary, the porosity is reduced and the water permeability is reduced, so that an optimum range exists. Therefore, the concentration of the hydrophobic polymer is 10 to 30% by weight, preferably 15 to 25% by weight, and the concentration of the hydrophilic polymer is 2 to 20% by weight, preferably 3 to 1%.
5% by weight.

As the method for producing the selective separation membrane of the present invention,
An example will be described below.

[0024] The above-mentioned stock solution for film formation was used at the same time as the core liquid.
The hollow fiber membrane is formed by discharging simultaneously from the die of the heavy slit tube structure. Then, after undergoing a predetermined water washing and moisturizing process,
Being rolled up. Furthermore, for example, when it is used for an artificial kidney or the like, it is preferably modularized, filled with water, and crosslinked.

Furthermore, the permselective separation membrane of the present invention has an overall mass transfer coefficient of 0.0 at least 3 nm in the diffusion performance test described in the examples with dextran.
025 cm / min or more and albumin permeability of 4
% Or less. Albumin permeability is 3% or less,
It is preferably 2% or less.

In the present invention, the form of the permselective separation membrane is not particularly limited, such as a flat membrane and a hollow fiber membrane.

The permselective separation membrane obtained by the present invention is an artificial kidney, an artificial liver, an endotoxin filter,
It can be used for various applications such as medical applications such as bioreactors and water treatment.

[0028]

EXAMPLES The present invention will now be described based on examples.

The measuring method used is as follows.

(1) Measurement of water permeability Performance of the module (area: 1.6 m ² ) in which both ends of the hollow fiber are sealed is applied with a water pressure of 100 mmHg on the inside of the hollow fiber, and the amount of filtration per unit time flowing out to the outside is measured. did. The water permeability was calculated by the following equation.

UFR (ml / hr / m ² / mmHg) = Q _W / (P × T × A) where Q _W : filtration amount (ml), T: outflow time (hr),
P: pressure (mmHg), A: membrane area (m ² ) (in terms of hollow fiber inner surface area).

(2) Measurement of diffusion performance with dextran Basically, the measurement was performed in the same manner as the dialysis performance measurement method. The outline is shown below. Dextran with different molecular weight distribution (average molecular weight manufactured by FULKA ~ 1200, ~ 6000,15000 ~
20000, 40000, 56000, 222000)
Was dissolved in ultrafiltered water to a concentration of 0.5 mg / ml. This solution is heated to 37 ° C and kept warm, pumped to the blood side (inside the hollow fiber) at a flow rate of 200 ml / min, and the ultrafiltrated water is kept at 37 ° C so that the dialysate side is countercurrent to the blood side. Was sent at 500 ml / min. Here, it should be noted that the filtration pressure should be adjusted to zero. That is, the diffusion performance of the membrane is measured under the condition that ultrafiltration does not occur. The feeding was continued for 20 minutes until the equilibrium state was reached, and then the blood side inlet, outlet, and dialysis side were sampled. The sampled solution was filtered with a filter having a pore size of 0.5 micron. The solution was used as a column for gel permeation chromatography (Tosoh TSKge
G3000PW), column temperature 40 ° C., mobile phase pure water for liquid chromatography, 1 ml / min, sample injection amount 50
Analysis was carried out in μl, and the overall mass transfer coefficient of the module was determined by the concentration changes at the inlet and outlet on the blood side. In addition,
Prior to the measurement, the column was calibrated using 5 kinds of monodisperse dextran. The overall mass transfer coefficient was calculated using the following formula.

Clearance

Embedded image Here, CBi: module inlet side concentration, CBo: module outlet side concentration, QB: module supply liquid amount (ml / m
in) is shown.

[0034]

Embedded image Here, A represents an area (m ² ).

The Stokes radius is described in the literature {J. Brandr
up, E .; H. Imergut "Polymer H
and book "(1989), pp. 112-113, John Wiley & Sons, inc}, {Artificial Organ 13: 6 (1984) 23-30}. Stokes radius (nm) = 0. 04
456 x (dextran molecular weight) ^0.43821 (3) Measurement of albumin permeability Hematocrit 30% kept at 37 ° C in a blood tank,
Bovine blood (heparin-treated blood) having a total protein amount of 6.5 g / dl was used to pump the inside of the hollow fiber at a rate of 200 ml / min using a pump. At that time, the pressure at the module outlet side was adjusted so that the filtration amount was 20 ml / min per 1 m ^{2 of the} module area (that is, 32 ml / min at 1.6 m ² ), and the filtrate and the outlet blood were returned to the blood tank. One hour after the start of the reflux, blood and filtrate at the inlet and outlet of the hollow fiber were sampled, and the blood side was analyzed by a BCG method and the filtrate side was analyzed by a CBB method kit (Wako Pure Chemical Industries), and albumin transmittance (%) was determined from the concentration. Was calculated.

[0036]

Embedded image Here, CF: in the filtrate, CBi: module inlet, C
Bi: The albumin concentration at the module outlet is shown.

(4) Measurement of Polyvinylpyrrolidone Molecular Weight Distribution by Gel Permeation Chromatography 100 mg of the hollow fiber which has undergone a predetermined coagulation and water washing step is dissolved in 5 mg of methylene chloride before γ-irradiation, and water extraction is carried out in the presence of salt to obtain The resulting aqueous solution is ultracentrifuged (20,000 rpm x
After separation for 10 min), the aqueous layer was filtered with a filter having a pore size of 0.5 micron to obtain a sample liquid. Tosoh TSK-gel-GMPWx1 2
A column having the theoretical plate number (8900 plates) connected in series was used, and 0.08 M Tris buffer (pH 7.
9), the flow rate was 1.0 ml / min, and the sample injection amount was 0.3 ml. The molecular weight distribution was determined using 5 kinds of monodisperse polyethylene glycol as reference substances.

(5) Weight average molecular weight of polyvinylpyrrolidone in spinning dope The weight average molecular weight of polyvinylpyrrolidone in the spinning dope was calculated from the correlation curve between the K value and the weight average molecular weight determined by the light scattering method. BASF's technical information document "Koll
idon: Polyvinylpyrrolidone
e for Pharmaceutical indu
The weight average molecular weight and the K value were calculated using the following formula from “Stry” FIG. ^15. Weight average molecular weight (Mw) = exp ^1.055495 × K ^2.871682 (6) Content of polyvinylpyrrolidone by elemental analysis Measurement of the sample after γ-ray irradiation is dried at room temperature with a vacuum pump,
10 mg thereof was analyzed with a CHN coder, and the content of polyvinylpyrrolidone was calculated from the nitrogen content. The insoluble matter obtained in the item (7) was also measured in the same manner, and the composition content derived from polyvinylpyrrolidone and polysulfone was calculated.

(7) Measurement of insoluble matter amount 10 g of the hollow fiber membrane after γ-ray irradiation was taken and dissolved in 100 ml of dimethylformamide. 1500r with centrifuge
Insoluble matter is separated at pm for 10 minutes, and the supernatant is discarded. This operation was repeated 3 times, the remaining solid matter was evaporated to dryness, and the content of the insoluble matter was determined from its weight.

Example 1 Polysulfone (Udel-P3500, Amoco) 18
Parts, polyvinylpyrrolidone (BASF K90) 3 parts,
Add 6 parts of polyvinylpyrrolidone (BASF K30) to 72 parts of dimethylacetamide and 1 part of water, heat and dissolve,
It was used as a film forming stock solution. The stock viscosity was 70 poise at 30 ° C. This stock solution was sent to a spinneret part at a temperature of 50 ° C., and a solution consisting of 65 parts of dimethylacetamide as a core liquid and 35 parts of water was discharged as a core liquid from a double slit tube having an outer diameter of 0.3 mm and an inner diameter of 0.2 mm to form a hollow fiber membrane. After forming, temperature 30 ℃,
It was obtained by passing through a coagulation bath of 20 wt% dimethylacetamide and 80 wt% of water at a temperature of 40 ° C. through a dry zone atmosphere with a dew point of 28 ° C. and a humidity of 250 mm, followed by a washing process at 20 ° C. for 20 seconds and a moisturizing process with glycerin. The hollow fiber membranes were wound into a bundle. 1.6 m ^{2 of} this hollow fiber membrane
Was filled into a case and potted to obtain a module. Next, as a result of examining the molecular weight distribution of the hollow fiber residual polyvinylpyrrolidone by gel permeation chromatography before γ-irradiation, a molecular weight of less than 100,000 was 27%, 1
73% was over 100,000. The overall mass transfer coefficient (Ko) of the module before γ-ray irradiation was measured, and as a result, it was 0.0025 cm / m at a Stokes radius of 4.5 nm.
in, water permeability 980 ml / hr / m ² / mmHg,
The albumin transmittance was 1.4%. After γ-ray irradiation, the overall mass transfer coefficient (Ko), water filtration performance, and albumin permeability were measured in the same manner, and Ko was found to have a Stokes radius of 4 nm.
0.0025cm / min, water permeability 1000ml
/ Hr / m ² / mmHg, albumin permeability was 1.5%. Furthermore, the amount of polyvinylpyrrolidone in the hollow fiber membrane was 8% when measured by an elemental analysis method. In addition, when the amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured, it was 1
It was 1%. When the composition of the insoluble matter was examined, it was 26% derived from polysulfone and 74% derived from polyvinylpyrrolidone.

Example 2 Polysulfone (Amoco Udel-P3500) 18
Parts, polyvinylpyrrolidone (BASF K90) 4 parts,
5 parts of polyvinylpyrrolidone (BASF K30) was added to 72 parts of dimethylacetamide and 1 part of water, and dissolved by heating to obtain a film forming stock solution. The stock viscosity was 120 poise at 30 ° C. The module was formed through the same steps as in Example 1. Next, as a result of examining the molecular weight distribution of the polyvinylpyrrolidone remaining in the hollow fiber by the gel permeation chromatography method before γ-irradiation, the molecular weight of less than 100,000 was 35% and 100,000 or more was 65%.
Met.

After γ-irradiation, the overall mass transfer coefficient (Ko), water filtration performance and albumin permeability were measured and found to be Ko.
Is 0.0025 cm / mi with a Stokes radius of 3.3 nm
n, water permeability 800 ml / hr / m ² / mmHg, albumin permeability 2.0%. Further, the amount of polyvinylpyrrolidone in the hollow fiber membrane was measured by elemental analysis, and was found to be 9%. The amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured and found to be 12%. When the composition of the insoluble matter was examined, it was 20% derived from polysulfone and 80% derived from polyvinylpyrrolidone.

Example 3 Polysulfone (Amoco Udel-P3500) 18
And 9 parts of polyvinylpyrrolidone (BASF K60) were added to 72 parts of dimethylacetamide and 1 part of water, and dissolved by heating to prepare a stock solution for film formation. The stock viscosity was 100 poise at 30 ° C. The module was formed through the same steps as in Example 1. Next, as a result of examining the molecular weight distribution of the polyvinylpyrrolidone remaining in the hollow fibers by gel permeation chromatography before γ-irradiation, the molecular weight was 40% for less than 100,000 and 60% for 100,000 or more.

After γ-irradiation, the overall mass transfer coefficient (Ko), water filtration performance and albumin permeability were measured and found to be Ko.
Is 0.0025 cm / mi with a Stokes radius of 3.5 nm
n, water permeability 500 ml / hr / m ² / mmHg, albumin permeability 1.8%. Further, the amount of polyvinylpyrrolidone in the hollow fiber membrane was measured by elemental analysis and found to be 5%. Further, the amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured and found to be 10%. When the composition of the insoluble matter was examined, it was 15% derived from polysulfone and 85% derived from polyvinylpyrrolidone.

Comparative Example 1 Polysulfone (Amoco Udel-P3500) 18
Part, polyvinylpyrrolidone (BASF K90) 1.5
Parts, polyvinylpyrrolidone (BASF K30) 7.5
Parts to 72 parts of dimethylacetamide and 1 part of water, and dissolved by heating to obtain a film-forming stock solution. The stock solution viscosity was 60 poise at 30 ° C. A film was formed according to Example 1 and modularized. Next, the molecular weight distribution of the polyvinylpyrrolidone remaining in the hollow fiber was examined by gel permeation chromatography before γ-ray irradiation. As a result, the molecular weight was less than 100,000, 60%, and 100,000 or more, 40%.

After γ-irradiation, the overall mass transfer coefficient (Ko), water filtration performance and albumin permeability were measured and found to be Ko.
Has a Stokes radius of 2.5 nm and Ko of 0.0025 cm
/ Min, water permeability 600ml / hr / m ² / mmH
g, albumin transmittance was 0.5%. Furthermore, the amount of polyvinylpyrrolidone in the hollow fiber membrane was 4% when measured by an elemental analysis method. Further, the amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured and found to be 0.15%. When the composition of the insoluble matter was examined, it was 10% derived from polysulfone and 90% derived from polyvinylpyrrolidone.

Comparative Example 2 Polysulfone (Udel-P3500, Amoco) 18
Parts, and 7 parts of polyvinylpyrrolidone (BASF K90) were added to 74 parts of dimethylacetamide and 1 part of water and dissolved by heating to give a stock solution for film formation. The stock solution viscosity was 250 poise at 30 ° C. A film was formed according to Example 1 and modularized.
Next, as a result of examining the molecular weight distribution of the polyvinylpyrrolidone remaining in the hollow fiber by gel permeation chromatography before γ-irradiation, a molecular weight of less than 100,000 was 8% and 100,000 or more was 92%.
Met.

After γ-ray irradiation, the overall mass transfer coefficient (Ko), water filtration performance, and albumin permeability were measured and found to be Ko.
Is 0.0025 cm / mi with Stokes radius of 2.8 nm
n, water permeability of 120 ml / hr / m ² / mmHg, and albumin permeability of 4.5%. Furthermore, the amount of polyvinylpyrrolidone in the hollow fiber membrane was 16% when measured by an elemental analysis method. Further, the amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured and found to be 20%. When the composition of the insoluble matter was examined, it was 4% derived from polysulfone and 96% derived from polyvinylpyrrolidone.

Comparative Example 3 Polysulfone (Udel-P3500, Amoco) 18
And 9 parts of polyvinylpyrrolidone (BASF K30) were added to 72 parts of dimethylacetamide and 1 part of water, and dissolved by heating to obtain a film forming stock solution. The stock solution viscosity was 30 poise at 30 ° C. A film was formed according to Example 1 and modularized.
Next, the molecular weight distribution of the polyvinylpyrrolidone remaining in the hollow fiber was examined by gel permeation chromatography before γ-ray irradiation. As a result, a molecular weight of less than 100,000 was 80%, and 100,000 or more was 20.
%Met.

After γ-ray irradiation, the overall mass transfer coefficient (Ko), water filtration performance, and albumin permeability were measured and found to be Ko.
Is 0.0025 cm / mi with Stokes radius of 2.8 nm
n, water permeability 710 ml / hr / m ² / mmHg, albumin permeability 0.02%. Furthermore, the amount of polyvinylpyrrolidone in the hollow fiber membrane was 4% when measured by an elemental analysis method. Further, the amount of insoluble matter in the hollow fiber after γ-ray irradiation was measured and found to be 0.5%. When the composition of the insoluble matter was examined, it was 42% derived from polysulfone and 58% derived from polyvinylpyrrolidone.

[0051]

By controlling the molecular weight distribution of the hydrophilic polymer present in the permselective separation membrane, for example, when used in the medical field, excellent uremic substance diffusion performance is maintained over a range of low to medium polymers. At the same time, since albumin permeability can be suppressed, when used for hemodialysis, hemofiltration, hemodiafiltration, etc., good therapeutic results can be expected for improving the morbidity of renal failure patients. Moreover, it can be applied to an endotoxin removal filter for purifying dialysate by utilizing its high water permeability.

[Brief description of drawings]

FIG. 1 shows a molecular weight distribution of hydrophilic polymer polyvinylpyrrolidone in a film before γ-ray irradiation.

FIG. 2 shows the relationship between the overall mass transfer coefficient (Ko) of a film after γ-ray irradiation and the Stokes radius.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Minoru Tanaka, 1-1-1, Sonoyama, Otsu City, Shiga Prefecture Toray Co., Ltd. Shiga Plant

Claims (18)

[Claims] 1. In a permselective separation membrane comprising a hydrophobic polymer and a hydrophilic polymer as main components, the hydrophilic polymer having a molecular weight of less than 100,000 is 10% by weight or more based on the total weight of the hydrophilic polymer. A permselective separation membrane comprising 50% by weight or less and 100,000 or more hydrophilic polymers in an amount of 50% by weight or more and 90% by weight or less based on the total weight of the hydrophilic polymers. 2. The permselective separation membrane according to claim 1, wherein the hydrophobic polymer is a polysulfone resin. 3. The permselective separation membrane according to claim 1, wherein the hydrophilic polymer is polyvinylpyrrolidone. 4. The hydrophilic polymer content is 3% by weight or more and 15% by weight or less with respect to the hydrophobic polymer.
3. The permselective separation membrane according to any one of 3 above. 5. The permselective separation membrane according to any one of claims 1 to 4, which is used as an artificial kidney. 6. A selective permeable separation membrane comprising a hydrophobic polymer and a hydrophilic polymer as main components, wherein the hydrophilic polymer having a molecular weight of less than 100,000 is 10% by weight or more based on the total weight of the hydrophilic polymer, A selection which is characterized in that a membrane containing 50% by weight or less and 100,000 or more hydrophilic polymers in an amount of 50% by weight or more and 90% by weight or less with respect to the total weight of the hydrophilic polymer is insolubilized. Permeable separation membrane. 7. The content of insoluble matter is 2 with respect to the total weight of the film.
The permselective separation membrane according to claim 6, wherein the content is not less than 15% by weight and not more than 15% by weight. 8. The composition of the insolubilized product is derived from the hydrophobic polymer before insolubilization of 15% by weight or more and 40% by weight or less and the hydrophilic polymer of 60% by weight or more and 85% by weight or less. The selectively permeable separation membrane described. 9. The permselective separation membrane according to claim 6, wherein the hydrophobic polymer is a polysulfone resin. 10. The permselective separation membrane according to claim 6, wherein the hydrophilic polymer is polyvinylpyrrolidone. 11. A hydrophilic membrane having a molecular weight of 100,000 or more and containing two or more hydrophilic polymers having different molecular weights, using a stock solution for film formation containing at least a hydrophobic polymer and a hydrophilic polymer, a solvent, and an additive. The method for producing a permselective separation membrane, wherein the content ratio of the permeable polymer is 1.8% by weight or more and 20% by weight or less with respect to the entire membrane forming solution. 12. The method for producing a permselective separation membrane according to claim 11, wherein the hydrophobic polymer is a polysulfone resin. 13. The method for producing a permselective separation membrane according to claim 11, wherein the hydrophilic polymer is polyvinylpyrrolidone. 14. A hydrophilic polymer containing two kinds of hydrophilic polymers different in weight average molecular weight by 5 times or more, and a low molecular weight component in the hydrophilic polymer is 20% by weight or more and 70% by weight or less. 11. The method for producing a permselective separation membrane according to any one of 11 to 13. 15. A permselective separation membrane having a Stokes radius of at least 3 nm, an overall mass transfer coefficient of 0.0025 cm / min or more, and an albumin permeability of 4% or less in a diffusion performance test with dextran. 16. The permselective separation membrane according to claim 15, wherein the albumin permeability is 3% or less. 17. The permselective separation membrane according to claim 15, wherein the albumin permeability is 2% or less. 18. The permselective separation membrane according to any one of claims 15 to 17, which is used as an artificial kidney.