JP2003245529A - Method for manufacturing hollow fiber membrane - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for manufacturing a hollow fiber membrane reducing the fluctuation of performance not only in a fiber bundle but also between fiber bundles in drying a plurality of fiber bundles and irradiating wet membranes bundled into a fiber bundle state with microwaves. <P>SOLUTION: In the method for manufacturing the hollow fiber membrane, the angle of radiation of microwaves emitted from a wave guide pipe is set to 30-120° and the distance from the wave guide pipe to the wet membranes is 50-500 mm in drying a plurality of the fiber bundles and in irradiating the wet membranes bundled into the fiber bundle state with microwaves. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for simultaneously drying a plurality of bundles of wet films bundled in a yarn bundle by microwave irradiation to eliminate variations in performance within the yarn bundles and at the same time to improve performance between yarn bundles. The present invention relates to a method for manufacturing a hollow fiber membrane that eliminates the variation of

[0002]

2. Description of the Related Art In recent years, the technology of utilizing a membrane having selective permeability has been remarkably advanced, and gas / liquid separation filters, hemodialyzers, blood filters, and blood component selective separation filters in the medical field have been developed so far. Practical application is progressing in a wide range of fields. As the material of the membrane, a polymer such as cellulose type (regenerated cellulose type, cellulose acetate type, chemically modified cellulose type), polyacrylonitrile type, polymethylmethacrylate type, polysulfone type, polyethylene vinyl alcohol type, polyamide type or the like is used. Came. Of these, polysulfone-based polymers are heat-stable, acid-resistant, and alkali-resistant, and by adding a hydrophilizing agent to the membrane-forming stock solution to form a membrane, the blood compatibility is improved. Attention has been paid to research.

On the other hand, it is necessary to dry the membrane in order to manufacture the module by adhering the membrane, but a porous membrane made of an organic polymer, especially a dialysis membrane made of a hydrophobic polymer such as polysulfone is used. It is known that when the filtration membrane is dried after the membrane formation, the water permeation amount is remarkably reduced as compared with before drying. Therefore, the membrane must always be handled in a wet state or immersed in water.

As a conventional measure against this, a low volatility organic liquid such as glycerin is filled in the pores in the porous film after film formation and before drying. However, low-volatile organic liquids generally have high viscosity,
It takes a long time to wash and remove, and even after the membrane is molded into a module and washed, a small amount of eluate derived from a low-volatile organic liquid (various derivatives produced by a chemical reaction with the low-volatile organic liquid) is enclosed in the module. There was a problem with what was seen in the liquid.

As a method of drying without using a low-volatile organic liquid, Japanese Patent Laid-Open No. 277470/1994 discloses a method of using an inorganic salt such as calcium chloride instead of the low-volatile organic liquid. There is no change in the need for cleaning and removal. Moreover, even if the amount is very small, there is concern that the residual inorganic salts may adversely affect the dialysis patient.

Further, as a method for drying a film, Japanese Patent Laid-Open No. 11-
Japanese Patent No. 332980 discloses a method for producing a hollow fiber membrane in which the hollow fiber membrane is irradiated with microwaves while being subjected to wet heat treatment with steam. However, there is a drawback that the drying time is lengthened because it is subjected to steam treatment to prevent deformation of the film even though it is dried, and further, since it is the drying after the low volatile organic liquid such as glycerin is attached,
The goal of reducing elution from the membrane is not achieved.

Japanese Unexamined Patent Publication No. 8-52331 and Japanese Patent Publication No. 8
No. 9668 discloses a hydrophilizing film containing polyvinylpyrrolidone that has been dried without using a low-volatile organic liquid. These documents describe the ability to separate plasma components from blood, but it is clear that they are not effective as dialysis membranes because they permeate plasma proteins. Also,
Since it is dried at a temperature at which polyvinylpyrrolidone is decomposed / denatured, it is an extremely unfavorable production method for the purpose of reducing the eluate from the membrane.

Further, Japanese Unexamined Patent Publication (Kokai) No. 6-296686 discloses a hollow fiber membrane in which the abundance of polyvinylpyrrolidone on the inner surface of the membrane, which is in direct contact with blood, is about 20 to 50%. This mainly indicates a wet film for reducing adhered substances such as blood proteins and platelets. Therefore, it has been shown that blood proteins do not easily adhere to the filtrate, so that the change in the filtrate rate with time does not easily occur, but there is no description about dialysis performance such as low albumin permeability.

The present inventor proposed and patented a method for producing a high-performance blood purification membrane by drying a wet membrane having a specific performance without impregnating a low-volatile organic liquid such as glycerin ( Japanese Patent Application No. 2001-22246). However, as a result of subsequent studies, it became clear that when the yarn bundle was dried and then dried, a slight difference in performance occurred between the film in the central portion of the yarn bundle and the film in the outer peripheral portion. Therefore, the present inventor proposed a method for producing a blood purification membrane with improved performance difference in the yarn bundle and applied for a patent (Japanese Patent Application Nos. 2001-309673 and 2001-30).
9674, Japanese Patent Application No. 2001-309675). However, as a result of further studies conducted by the present inventors, it was found that when a plurality of yarn bundles were dried at the same time, a slight difference in performance occurred between the yarn bundles even with these methods. .

[0010]

SUMMARY OF THE INVENTION An object of the present invention is to eliminate a variation in performance within a yarn bundle in a method for simultaneously drying a plurality of wet films bundled into a yarn bundle by microwave irradiation. It is an object of the present invention to provide a method for manufacturing a hollow fiber membrane, which eliminates variations in performance between the two.

[0011]

As described above, a dry membrane for blood purification having a dialysis performance, which is dried without using a membrane pore-holding agent that causes eluate from a module, is a patented invention of the present inventors. No. 2001-22246). The cause was that when dried without using a pore-holding agent, a low-performance membrane completely different from the wet state was obtained. Therefore, the inventors of the present invention previously prepared a wet membrane having a higher water permeation rate and a larger pore size than the target performance and drying and shrinking the wet membrane to obtain a membrane having a target dialysis performance. As a result of intensive research based on the idea that no one has ever thought of manufacturing it, as a result, there is very little eluate, little adhesion of blood proteins and platelets, and a membrane with excellent dialysis performance with selective permeability is obtained. Provided a way. However, after further research,
When manufacturing a blood purification membrane by the method of Japanese Patent Application No. 2001-22246, the inventors of the present invention dry the wet membrane in the form of a bundle of yarns, and if the membrane of the central portion of the bundle of yarns and the membrane of the outer peripheral portion have a water permeability or It was discovered that the transmission performance varies. Therefore,
As a result of diligent research to eliminate the variation, it was found that the variation can be suppressed by devising the drying process, and new patent applications were filed (Japanese Patent Application Nos. 2001-309673, 2001-309674, and 2001-3096).
75). However, when manufacturing a blood purification membrane according to these inventions, the microwave irradiation device is scaled up in order to simultaneously dry a plurality of wet membranes bundled in a yarn bundle in a specific amount (50 bundles) or more. As a result, we have newly discovered that the amount of water permeation and the permeation performance vary among yarn bundles. Then, as a result of earnest research for eliminating the variation, the inventors have found that the variation can be suppressed by further devising the drying process, and the present invention has been completed.

That is, the present invention is (1) a method for producing a hollow fiber membrane in which a wet membrane bundled into a yarn bundle is irradiated with microwaves and a plurality of bundles are simultaneously dried. A method for producing a hollow fiber membrane, characterized in that the radiation angle of the wave is 30 to 120 degrees, and the distance from the waveguide to the wet membrane is 50 to 500 mm. A method for producing a hollow fiber blood purification membrane in which a wet membrane containing no membrane pore-holding agent is microwave-irradiated to dry a plurality of bundles at the same time, and the microwave irradiation angle of the microwave is 30 to 120 degrees. And a distance from the waveguide to the wet membrane is 50 to 500 mm, a method for producing a hollow fiber blood purification membrane, comprising: (3) a membrane pore-holding agent bundled in a yarn bundle. Heat and dry the wet film at a temperature of 40 ℃ to 120 ℃. A method of manufacturing a hollow fiber blood purification membrane to dry more beams simultaneously irradiated microwave with,
The microwave radiation angle from the waveguide is 30 to 1
20 ° and the distance from the waveguide to the wet film is 50
To 500 mm, a method for producing a hollow fiber blood purification membrane, (4) A method according to any one of (1) to (3), characterized in that a plurality of waveguides are used.
(5) A method of manufacturing according to any one of (1) to (4), characterized in that a dehumidifying body is ventilated in the yarn bundle, (6) a film in the central portion and the outer peripheral portion of the yarn bundle at the start of drying. The difference in the water content of is within 10% (1) to (5)
(7) The irradiation output of microwaves is reduced when the average water content of the yarn bundle after the start of drying reaches 20 to 70% (1) to (6). )
(8) The difference in the water content of the membrane between the central portion and the outer peripheral portion of the yarn bundle at the time when the average water content of the yarn bundle after the start of drying is 8 to 70% is (8). % Or less, the production method according to any one of (1) to (7), (9) the membrane is composed of a polysulfone-based polymer and polyvinylpyrrolidone (1) to
The manufacturing method according to any one of (8). (10) The film-forming stock solution comprises a polysulfone-based polymer, polyvinylpyrrolidone, and a solvent, and the ratio of polyvinylpyrrolidone to the polysulfone-based polymer is 18 to 27% by weight. (1) to (9) And (11) the production method according to any one of (1) to (10), characterized in that after drying, a part of the polyvinylpyrrolidone in the film is further insolubilized in water. Is.

According to the present invention, the irradiation angle of microwave is 30 to 120 degrees, and the distance from the waveguide to the wet film is 50 to 500 mm. It is possible to improve not only the variation in the internal performance but also the variation in the performance between the yarn bundles, and it is possible to improve the production efficiency.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION Although the present invention is not limited to blood purification membranes, the method for producing hollow fiber blood purification membranes (hereinafter sometimes simply referred to as "membranes" or "hollow fiber membranes") is described below. The details will be described. The method for producing a hollow fiber blood purification membrane of the present invention is characterized in that a wet membrane having a high water permeability and a large pore diameter is produced in advance and dried after solvent removal without impregnation with a membrane pore retaining agent.

Usually, the membrane pore retaining agent used in the production of the hollow fiber blood purification membrane is classified into a viscous organic substance and an inorganic substance which may be toxic to the human body. Membrane pore retainers made of viscous organic substances are difficult to completely wash and remove due to their high viscosity, so they remain in the membrane and increase the amount of elution from the membrane. It may cause chemical reaction with the retentive agent to produce harmful substances. On the other hand, even a membrane pore-holding agent made of an inorganic substance remains in a very small amount, which may adversely affect dialysis patients.

The term "membrane pore-holding agent" as used in the present invention is a substance that is filled in the pores in the membrane during the production process before drying in order to prevent performance deterioration during drying. It is possible to fill the pores in the membrane with the retaining agent by immersing the wet membrane in a solution containing the membrane pore retaining agent. Even after drying, if the membrane pore retaining agent is only washed and removed, it is possible to maintain the same performance as the wet membrane such as water permeability and blocking rate due to the effect of the membrane pore retaining agent.

Membrane pore retaining agents include ethylene glycol, propylene glycol, trimethylene glycol,
1,2-butylene glycol, 1,3-butylene glycol, 2-butyne-1,4-diol, 2-methyl-
2,4-pentadiol, 2-ethyl-1,3-hexanediol, glycerin, tetraethylene glycol,
Glycol- or glycerol-based compounds such as polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400 and organic compounds such as sucrose fatty acid ester, and inorganic salts such as calcium chloride, sodium carbonate, sodium acetate, magnesium sulfate, sodium sulfate and zinc chloride Can be mentioned.

In the present invention, a wet membrane having a high water permeability and a large pore size means a water permeability of 100 mL / (m ² · hr).
-MmHg) or more and a weight average molecular weight of 40,000
0 means a polyvinylpyrrolidone permeability of more than 75% and an albumin permeability of 0.3% or more in bovine plasma system.

The permeability of bovine plasma albumin can be measured by the following method. First, length 20c
A small module is manufactured by bundling 100 hollow fiber membranes of m. Heparin-added bovine plasma (heparin 5000 IU / I, protein concentration 6.
0 g / dL (deciliter)) at a linear velocity of 1.
The mixture is passed through at 0 cm / sec, and ultrafiltration is performed for 30 minutes at an average pressure of 50 mmHg of inlet pressure and outlet pressure of the module. The concentrations of the obtained filtrate and the original solution are measured with an ultraviolet spectrophotometer at a wavelength of 280 nm, and the transmittance is calculated by substituting it in the following formula (1). Transmittance (%) = (absorbance of filtrate) × 100 / (absorbance of original solution) (1)

The transmittance of polyvinylpyrrolidone is 3% by weight of the aqueous solution to be filtered.
K30, weight average molecular weight 40,000 phosphate buffer (0.15 mol / liter, pH 7.4)
It can be determined by performing the same operation as the measurement of the transmissivity of bovine plasma albumin, except that the aqueous solution was used and the average pressure of the inlet pressure and the outlet pressure of the module was set to 200 mmHg.

A wet membrane having a high water permeability and a large pore size is formed of a polysulfone-based polymer (hereinafter also simply referred to as "polymer"),
Polyvinylpyrrolidone, a film-forming stock solution consisting of a solvent,
It can be produced by using an aqueous solution of a polymer solvent as the internal liquid in a production method in which the internal liquid is discharged from a double annular nozzle, passed through an air gap, and then solidified in a coagulation bath. The internal liquid forms the hollow part and the inner surface of the membrane, and it has been known that the pore size of the inner surface increases in proportion to the concentration of the solvent in the internal liquid. In the present invention, since the dialysis membrane having the target performance is obtained by drying and shrinking the wet membrane, the solvent concentration in the internal liquid is
It is necessary to make the concentration higher than when producing a wet membrane having a target dialysis performance.

Examples of the polysulfone polymer used in the present invention include those having a repeating unit represented by the following formula (2) or formula (3). In the formula, Ar represents a 2-substituted phenyl group at the para position, and the degree of polymerization and the molecular weight are not particularly limited. _{-O-Ar-C (CH 3} ) 2 -Ar-O-Ar-SO 2 -Ar- (2) -O-Ar-SO 2 -Ar- (3)

Since the higher the molecular weight of polyvinylpyrrolidone is, the higher the hydrophilicity of the membrane is, the smaller the molecular weight of polyvinylpyrrolidone is, the smaller the amount of polyvinylpyrrolidone is. Is used. A large amount of polyvinylpyrrolidone must be left in the membrane in order to impart a hydrophilic effect to the membrane by using polyvinylpyrrolidone having a weight average molecular weight of less than 900,000. Will increase. On the contrary, if the residual amount of polyvinylpyrrolidone having a weight average molecular weight of less than 900,000 in the membrane is reduced in order to reduce the eluate, the hydrophilic effect becomes insufficient, and as a result, when hemodialysis is performed. The filtration rate is lowered with time and the sufficient effect cannot be exhibited.

The solvent used for dissolving the polysulfone-based polymer and polyvinylpyrrolidone dissolves both of them, and includes N-methyl-2-pyrrolidone, N, N-dimethylformamide and N, N-dimethylacetamide. Etc.

The concentration of the polymer in the stock solution for film formation is not particularly limited as long as it is within the concentration range in which the film can be formed and the obtained film has the performance as a film, and is preferably 5 to 35% by weight, preferably It is 10 to 30% by weight. In order to achieve high water permeability, the polymer concentration should be low,
5% by weight is preferred.

What is more important is the amount of polyvinylpyrrolidone added, and the mixing ratio of polyvinylpyrrolidone to the polymer is 27% by weight or less, preferably 10 to 27.
%, And more preferably 20 to 27% by weight. The mixing ratio of polyvinylpyrrolidone to polymer is 27.
If the amount exceeds 10% by weight, the amount of elution tends to increase.
If it is less than 10% by weight, it is difficult to obtain a sponge-structured film because the viscosity of the stock solution is low. Further, a fourth component such as water or a poor solvent may be added for the purpose of controlling the viscosity of the stock solution and the dissolved state, and the kind and the addition amount thereof may be arbitrarily selected depending on the combination.

As the coagulation bath, for example, water; methanol,
Liquids such as alcohols such as ethanol; ethers; aliphatic hydrocarbons such as n-hexane and n-heptane that do not dissolve the polymer are used, and water is preferable. Also,
It is also possible to control the coagulation rate by adding a small amount of a solvent that dissolves the polymer to the coagulation bath. The temperature of the coagulation bath is −30 to 90 ° C., preferably 0 to 90.
C., more preferably 0 to 80.degree. When the temperature of the coagulation bath is higher than 90 ° C or lower than -30 ° C, it is difficult to stabilize the surface state of the hollow fiber membrane in the coagulation bath.

For drying after washing with a solvent, a sufficiently wet yarn bundle is irradiated with microwaves in the form of a yarn bundle in which a large number of hollow fiber membranes are bundled (hereinafter, simply referred to as "thread bundle"). However, it is more preferable to perform microwave irradiation at the same time as heating and drying at a temperature of 40 ° C. or higher and 120 ° C. or lower. By performing the heat drying and the microwave irradiation at the same time, it is possible not only to suppress the variation in the performance within the yarn bundle, but also to shorten the drying time as compared with the microwave irradiation alone.

Further, in order to eliminate the difference in drying speed between the central portion and the outer peripheral portion of the yarn bundle, it is preferable to ventilate the dehumidifying body having a temperature of less than 40 ° C. Ventilation in the yarn bundle means flowing air between the hollow fiber membranes. In the present invention, 40
Ventilation of the dehumidifying body having a temperature of not less than 120 ° C and not more than 120 ° C into the yarn bundle means that the yarn bundle is heated and dried at the same time as being ventilated into the yarn bundle.

Since the microwave irradiation is suitable for drying the yarn bundle having a low moisture content more uniformly, the average moisture content of the yarn bundle is 20 to 20 in order to prevent the deformation and melting of the film due to overheating.
It is preferable to reduce the output of microwave irradiation at the time of 70%, preferably 50 to 70%.

Further, the average water content of the yarn bundle is 20 to 70.
%, Preferably 50 to 70%, it is preferable that the difference in water content of the membrane between the central portion and the outer peripheral portion of the yarn bundle is within 5% in order to suppress variations in performance. When the yarn bundle is dried, air is blown into the yarn bundle so that the average water content of the yarn bundle becomes 20 to 70%, preferably 50 to 70%. It is possible to keep the difference in rate within 5%. Here, the central portion of the yarn bundle refers to a range of 1/6 of the diameter from the center point in the circular cross section of the yarn bundle. Further, the outer peripheral portion of the yarn bundle refers to a range of 1/6 of the diameter from the outer periphery in the circular cross section of the yarn bundle.

Also for the same reason, it is preferable that the difference in water content of the membrane between the central portion and the outer peripheral portion of the yarn bundle at the start of drying is within 10%. If the yarn bundle is left unsolved after solvent removal, there will be a difference in water content between the central portion and the outer peripheral portion of the yarn bundle.Therefore, immersing the yarn bundle in water immediately before entering the drying process It is possible to keep the difference in water content between the outer part and the outer part within 10%. Here, the water content means the weight (A) of the yarn bundle (or film) before drying.
(G)) and the weight (B (g)) of the dried yarn bundle (or film), which is calculated by the equation (4). Moisture content (%) = (A−B) × 100 / B (4)

In the present invention, the microwave irradiation to the yarn bundle is performed simultaneously in a plurality of bundles in a closed irradiation furnace. In order to suppress variations in performance among yarn bundles, the irradiation angle of microwaves emitted from the waveguide and the distance from the waveguide to the wet film (yarn bundle) are extremely important. In the present invention, the waveguide means a microwave irradiation source. It is preferable to use a plurality of waveguides in proportion to the number of yarn bundles.

In the present invention, the radiation angle (radiation half-value angle) is preferably 30 to 120 degrees, more preferably 50 to 110 degrees. If the radiation angle is less than 30 degrees, the yarn bundles located inside the irradiation furnace will dry quickly, and the variation among the yarn bundles will increase, which is not preferable. Further, when the radiation angle exceeds 120 degrees, a large amount of microwaves are reflected on the inner wall of the irradiation furnace, and the yarn bundles located outside in the irradiation furnace are irradiated with the microwaves, so that the yarn bundle is dried quickly. Similarly, the variation in performance between yarn bundles becomes large, which is not preferable. Here, the radiation angle means that the radiation energy is halved with respect to the point (A) having the strongest radiation energy on a curve equidistant from the center point (O) of the irradiation surface of the waveguide (see FIG. 1). Angle BOC (angle AOB = angle AO) formed by the point (B and C)
It means the size of C).

Under the microwave irradiation conditions of the present invention,
Besides the radiation angle, the distance from the waveguide to the wetting film (thread bundle) is very important. The range of distance is 50 to 500
mm is preferable, and more preferably 100 to 400 mm. If the distance is less than 50 mm, only the upper part of the yarn bundle will dry quickly, which is not preferable, and if it exceeds 500 mm, the production efficiency tends to be poor. Here, the distance from the waveguide to the wet film means the shortest distance from the center point of the irradiation surface of the waveguide to the closest yarn bundle. The microwave output is preferably high, but the optimum value varies depending on the amount of the film to be dried.

By irradiating the dried film with radiation such as electron rays and γ rays, a part of PVP in the film can be insolubilized in water, so that the amount eluted from the film can be further reduced. . Irradiation may be performed before or after modularization. Further, if all the PVP in the membrane is insolubilized, the elution amount can be reduced, but leukopenia symptoms are observed during dialysis, which is not preferable.

The water-insoluble PVP referred to in the present invention is
It is obtained by subtracting the amount of PVP soluble in water from the total amount of PVP in the membrane. The total amount of PVP in the film can be easily calculated by elemental analysis of nitrogen and sulfur. Also,
The amount of PVP soluble in water can be determined by the following method. After completely dissolving the membrane with N-methyl-2-pyrrolidone, water is added to the obtained polymer solution to completely precipitate the polysulfone-based polymer. After allowing the polymer solution to stand still, the amount of PVP in the supernatant can be quantified by liquid chromatography to quantify the PVP soluble in water.

The production method of the present invention is a method of simultaneously drying a plurality of wet films bundled in a yarn bundle and containing no membrane pore-holding agent, wherein the wet film is dried by microwave irradiation or is dried.
Alternatively, it is a method in which the wet film is dried by heating at a temperature of 40 ° C. or higher and 120 ° C. or lower and is irradiated with microwaves to be dried.
˜120 degrees, and the distance from the waveguide to the wet film is 50 to 500 mm, and the film obtained by using the present manufacturing method is a dry film containing no pore-holding agent. The pure water permeation rate is 10 to 1,000 mL / (m ² ·
hr · mmHg), the transmittance of polyvinylpyrrolidone having a weight average molecular weight of 40,000 is 75% or less, and the transmittance of albumin in the bovine plasma system is less than 0.3%,
Further, the hollow fiber blood purification membrane is characterized in that the variations in the respective performances are small.

In the recent hemodialysis therapy, β2-microglobulin (molecular weight: 11,800), which is a causative substance for improving dialysis amyloid pathology, is sufficiently permeated, but albumin (molecular weight: 67,000) is used. There is a demand for a membrane having a fractional property that almost does not allow permeation, and the membrane of the present invention has an albumin permeability of 0.
It is 3% or less. An albumin permeability of more than 0.3% means a large loss of effective albumin in the body, and is not preferable as a hemodialysis membrane.

Further, the permeation amount of pure water is 10 mL / (m ² ·
In the case of a membrane having a thickness of at least hr · mmHg), the permeability (A (%)) of polyvinylpyrrolidone and the clearance (B (mL / min)) of β2-microglobulin are expressed by the following linear function (5). There is a strong correlation. For clearance evaluation, it is necessary to mold and process into a dialysis-specification module with an effective membrane area of 1.5 m ² .
With this evaluation method, it is possible to easily measure, and it is possible to easily estimate the clearance. B (mL / min) = 0.636A + 29.99 (5) Here, the clearance of β2-microglobulin is
A module with an effective membrane area of 1.5 m ² has a blood flow rate of 20
Dialysis measurement was carried out under the conditions of 0 mL / min (inner side of the membrane) and a flow rate of dialysate of 500 mL / min (outer side of the membrane) according to the performance evaluation standard of the Japan Society for Artificial Organs. The clearance of β2-microglobulin is required to be various according to the physical strength of the dialysis patient and the medical condition and the progress of the medical condition.
When the transmittance of polyvinylpyrrolidone exceeds 75%, the transmittance of albumin exceeds 0.3%. Therefore, the transmittance of polyvinylpyrrolidone needs to be 75% or less.

Further, since the membrane prepared by the production method of the present invention does not use the membrane pore retaining agent in the production process, there is no eluate derived from the membrane pore retaining agent. Therefore, the absorbance of the eluate test solution for the membrane of the present invention is less than 0.04, and the test solution does not contain a membrane pore retaining agent. Here, the eluate test liquid was prepared based on the approval criteria of the artificial kidney device, and 1.5 g of the dry hollow fiber membrane cut into 2 cm and 150 mL of distilled water for injection were tested in a glass container for injection in the Japanese Pharmacopoeia. Put it in a glass container compatible with the alkaline elution test of
It means that the mixture was heated at 70 ± 5 ° C. for 1 hour, and after cooling, the membrane was removed and distilled water was added to make 150 mL. The absorbance is measured by an ultraviolet absorption spectrum at a wavelength showing a maximum absorption wavelength at 220 to 350 nm. The artificial kidney device approval standard stipulates that the absorbance should be 0.1 or less, but since the membrane of the present invention does not retain the membrane pore retaining agent, it is 0.
It is possible to achieve less than 04. Further, with respect to the presence or absence of a membrane pore-holding agent, gas chromatographic, liquid chromatography, differential refraction system, ultraviolet spectrophotometer, infrared absorption spectrophotometric method in which the test solution is concentrated or water is removed,
It can be detected by measuring by a known method such as nuclear magnetic resonance spectroscopy and elemental analysis. Further, it is possible to detect whether or not the membrane pore retaining agent is contained in the membrane by these measuring methods.

The membrane produced by the production method of the present invention comprises a polysulfone-based polymer and polyvinylpyrrolidone, and the concentration of polyvinylpyrrolidone on the inner surface of the membrane is 3
It is 0 to 45% by weight. An important factor for the blood compatibility of the membrane is the hydrophilicity of the inner surface of the membrane that is in contact with blood. In a polysulfone-based membrane containing polyvinylpyrrolidone (hereinafter also simply referred to as “PVP”), the PVP concentration on the inner surface of the membrane is important. Is. When the PVP concentration on the inner surface of the membrane is too low, the inner surface of the membrane exhibits hydrophobicity, plasma proteins are easily adsorbed, and blood coagulation easily occurs. That is, the blood compatibility of the membrane is poor. On the other hand, if the PVP concentration on the inner surface of the membrane is too high, the amount of PVP eluted into the blood system increases, which is not desirable for the purpose and application of the present invention. Therefore, the concentration of PVP on the inner surface of the membrane in the present invention is in the range of 30-40%, preferably 33-40%.

The PVP concentration on the inner surface of the film was determined by X-ray photoelectron spectroscopy (X-ray Photoelectron spectroscopy).
n spectroscopy, hereinafter XPS). That is, the XPS of the inner surface of the film is measured by arranging the samples on the double-sided tape, incising in the fiber axis direction with a cutter, expanding the inside of the film so that it is on the front side, and then measuring by an ordinary method. . That is, C1s, O1s, N1
It means the concentration obtained from the surface intensity of s, S2p spectrum and the surface concentration of nitrogen (nitrogen atom concentration) and the surface concentration of sulfur (sulfur atom concentration) using the relative sensitivity coefficient attached to the device. When is the structure of equation (2), it can be calculated by equation (6). PVP concentration (% by weight) = C ₁ M ₁ × 100 / (C ₁ M ₁ + C ₂ M ₂ ) (6) where C ₁ : nitrogen atom concentration (%) C ₂ : sulfur atom concentration (%) M ₁ : Molecular weight of repeating unit of PVP (111) M ₂ : Molecular weight of repeating unit of polysulfone polymer (442)

[0044]

EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto. (Measurement of Platelet Adhesion Amount)
The procedure was as follows. A small module was prepared by bundling 10 hollow fiber membranes having a length of 15 cm, and heparin-added human fresh blood was added to the module at a linear velocity of 1.0 cm / sec.
It was passed for 1 minute, followed by saline for 1 minute.
Next, the hollow fiber membrane was shredded at intervals of about 5 mm, and the membrane surface was irradiated with ultrasonic waves in physiological saline containing 0.5% polyethylene glycol alkylphenyl ether (trade name Triton X-100 manufactured by Wako Pure Chemical Industries, Ltd.). The lactate dehydrogenase (hereinafter referred to as “LDH”) released from the adhered platelets was quantified to calculate the LDH activity per membrane area (inner surface conversion). The LDH monotest kit (Boehringer Mannheim, Yamanouchi) was used to measure the enzyme activity. As a positive control, a film containing no PVP (the film of Example 1 before γ-ray irradiation was used, the effective chlorine concentration was 1,500
It was soaked in ppm sodium hypochlorite for 2 days, and then soaked in ethanol for 1 day).

(Amount of adsorbed plasma protein) The amount of adsorbed plasma protein on the membrane was the same as that for measuring the transmittance of albumin except that the ultrafiltration time was 240 minutes, followed by washing with physiological saline for 1 minute. did. Next, the hollow fiber membrane was shredded at intervals of about 5 mm, and the plasma protein extracted by stirring in physiological saline containing 1.0% sodium laurate was quantified to calculate the protein adsorption amount per membrane weight. For the protein concentration, BCA protein assay (Pierce) was used. As a positive control, P
A film containing no VP (the film of Example 1 before γ-irradiation was added to sodium hypochlorite having an effective chlorine concentration of 1,500 ppm to 2%).
After being dipped for one day, it was dipped in ethanol for one day), and compared with the test product at the same time.

[0046]

[Example 1] (Film formation and removal of residual solvent) Polysulfone (Amoco Engineering Polymer)
rs P-1700) 18.0 wt%, polyvinylpyrrolidone (BASF K90, weight average molecular weight 1,
(200,000) 4.3% by weight was dissolved in 77.7% by weight of N, N-dimethylacetamide to obtain a uniform solution. Here, the mixing ratio of polyvinylpyrrolidone to polysulfone in the film-forming stock solution was 23.9% by weight.
This film-forming stock solution was kept at 60 ° C., and an inner solution composed of a mixed solution of 30% by weight of N, N-dimethylacetamide and 70% by weight of water was used together with a spinneret (double annular nozzle 0.1 mm-
0.2 mm-0.3 mm), the mixture was passed through an air gap of 0.96 m and immersed in a coagulation bath made of water at 75 ° C. At this time, from the spinneret to the coagulation bath is surrounded by a cylindrical tube, while flowing nitrogen gas containing water vapor into the tube,
The humidity inside the cylinder was controlled at 54.5% and the temperature was controlled at 51 ° C. The spinning speed was fixed at 80 m / min. Here, the ratio of the air gap to the spinning speed is 0.012 m / (m /
Minutes). After cutting the wound yarn bundle, the yarn bundle (length 3
The residual solvent in the film was removed by washing with a hot water shower at 80 ° C. for 2 hours from above the cut surface (0 cm, number of films 9400).

(Drying of wet film and insolubilization treatment of PVP)
Yarn bundle after removing the residual solvent (water content is 300%, water content of the membrane at the center of the yarn bundle is 300%, water content of the membrane at the outer periphery of the yarn bundle is 300%, center portion and outer periphery of the yarn bundle 90 bundles having a water content difference of 0% in Example 2) were uniformly arranged at equal intervals in a microwave irradiation furnace (wind speed in the irradiation furnace was 3 m / sec) in which the temperature was set to 90 ° C. At this time, the yarn bundle was fixed with a jig so that the cut surface of the yarn bundle was always above or below. Furthermore, in order to uniformly irradiate each yarn bundle with microwaves in the irradiation furnace,
The respective waveguides were evenly fixed at equal intervals. Microwave irradiation was performed for 13 minutes at a microwave radiation angle of 52 degrees, a distance from the waveguide to the yarn bundle (wet film) of 280 ± 5 mm, and a microwave output of 30 kW (kilowatt). At this point, the water content of the yarn bundle located in the center of the irradiation furnace was 50% (the water content of the membrane at the center of the yarn bundle was 52%, and the water content of the membrane at the outer periphery of the yarn bundle was 48%). . The moisture content of the yarn bundle located at the outermost position in the irradiation furnace is 54% (the moisture content of the membrane at the center of the yarn bundle is 55%, and the moisture content of the membrane at the outer periphery of the yarn bundle is 53%).
%)Met. Then only the microwave output is 21
The dried film (yarn bundle) having a water content of less than 1% was obtained by lowering the power to kW and then performing microwave irradiation for 5 minutes. From the start of drying to the end of drying, dehumidified air (humidity of 10% or less) was blown from the lower part of each yarn bundle to the upper part at a wind speed of 4 m / sec. At this time, an average wind speed of 0.4 m / sec was measured from the top of the yarn bundle at the start of drying. Furthermore, by irradiating the obtained dry film (yarn bundle) with 2.5 Mrad γ-rays, PV in the film
Part of P was insolubilized.

(Results of Performance Evaluation) The performance of this film is shown in Table 1. The performance shows the average value of the results of measuring 10 times each of the yarn bundle located in the central part of the irradiation furnace and the yarn bundle located in the outermost part of the irradiation furnace. When this membrane was used as a module with an effective filtration area of 1.5 m ² and the clearance of β2-microglobulin was measured, it was found to be 32 mL / min.
It became clear that it was equivalent to the clearance of 32.5 mL / min calculated by substituting the transmittance of P into the equation (5).
Further, when permeation of urea and vitamin B12 was measured in the module, the clearance and permeation rate of urea were 185 mL / min and 83%, respectively. Similarly, for vitamin B12, it was 95 mL / min and 48%. The measurement is

The same procedure as in the above was carried out. In addition, the total P in the film
62% of the VP amount was insoluble in water. As a result of the eluate test of the membrane, the absorbance of the eluate test solution was 0.04 or less. Further, since the membrane pore retaining agent was not used, the eluate test solution did not contain the membrane pore retaining agent. Further, it was revealed that this membrane had a lower platelet adhesion amount (positive control membrane 43.4 Unit / m ² ) and a lower plasma protein adhesion amount (positive control membrane 6) than the positive control membrane.
2.5 mg / g). From the performance mentioned above, this membrane
It was revealed that the amount of elution from the membrane was extremely small and the adhesion of blood proteins and platelets was small. In addition, it was found that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus has excellent dialysis performance. Furthermore, since the difference in the performance of the film between the central portion and the outer peripheral portion of the yarn bundle is smaller than that of the conventional drying method (Comparative Example 1), it is clear that there is little variation in performance. In addition, the performance difference between the yarn bundle located at the center of the irradiation furnace and the yarn bundle located at the outermost portion of the irradiation furnace is also comparative examples 8 to 1.
It became clear that it was less than 1.

[0049]

Example 2 The same operation as in Example 1 was performed except that polyvinylpyrrolidone was 4% by weight and N, N-dimethylacetamide was 78% by weight in the stock solution for film formation. At this time, the mixing ratio of polyvinylpyrrolidone to polysulfone in the film-forming stock solution was 22.2% by weight. The performance of this membrane is shown in Table 1. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, since the difference in the performance of the film between the central portion and the outer peripheral portion of the yarn bundle is smaller than that of the conventional drying method (Comparative Example 1), it is clear that there is little variation in performance. Further, it was revealed that the difference in performance between the yarn bundle located in the central part of the irradiation furnace and the yarn bundle located at the outermost part in the irradiation furnace was smaller than in Comparative Examples 8 to 11.

[0050]

[Example 3] The polyvinylpyrrolidone in the stock solution for film formation was changed to 4.
The same operation as in Example 1 was performed except that 8% by weight and 77.2% by weight of N, N-dimethylacetamide were used. At this time, the mixing ratio of polyvinylpyrrolidone to polysulfone in the film-forming stock solution was 26.7% by weight. The performance of this membrane is shown in Table 2. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, the difference in the film performance between the central portion and the outer peripheral portion of the yarn bundle is due to the conventional drying method (Comparative Example 1).
It is clear that there is less variation in performance because it is smaller than In addition, the performance difference between the yarn bundle located at the center of the irradiation furnace and the yarn bundle located at the outermost portion of the irradiation furnace is also shown in Comparative Example 8.
It became clear that it was less than that of ~ 11.

[0051]

[Example 4] N, N-dimethylacetamide 5 was added to the internal liquid.
The same operation as in Example 3 was performed except that a mixed solution containing 2% by weight and 48% by weight of water was used. The performance of this membrane is shown in Table 2. The amount of elution from this membrane is extremely small,
It became clear that blood proteins and platelets were less attached. In addition, albumin has low permeability and β2
-Since it was suggested that the clearance of microglobulin was also excellent, it was found that the membrane had excellent dialysis performance. Furthermore, since the difference in the performance of the film between the central portion and the outer peripheral portion of the yarn bundle is smaller than that of the conventional drying method (Comparative Example 1), it is clear that there is little variation in performance. Further, it was revealed that the difference in performance between the yarn bundle located in the central part of the irradiation furnace and the yarn bundle located at the outermost part in the irradiation furnace was smaller than in Comparative Examples 8 to 11.

[0052]

Fifth Embodiment A microwave radiation angle from the waveguide is set to 35.
The same operation as in Example 1 was performed except that the time was changed. The performance of this membrane is shown in Table 3. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, the difference in the film performance between the central portion and the outer peripheral portion of the yarn bundle is due to the conventional drying method (Comparative Example 1).
It is clear that there is less variation in performance because it is smaller than In addition, the performance difference between the yarn bundle located at the center of the irradiation furnace and the yarn bundle located at the outermost portion of the irradiation furnace is also shown in Comparative Example 8.
It became clear that it was less than that of ~ 11.

[0053]

[Sixth Embodiment] The microwave radiation angle from the waveguide is set to 11
The same operation as in Example 1 was performed except that the temperature was set to 5 degrees. The performance of this membrane is shown in Table 3. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, the difference in the film performance between the central portion and the outer peripheral portion of the yarn bundle is due to the conventional drying method (Comparative Example 1).
It is clear that there is less variation in performance because it is smaller than In addition, the performance difference between the yarn bundle located at the center of the irradiation furnace and the yarn bundle located at the outermost portion of the irradiation furnace is also shown in Comparative Example 8.
It became clear that it was less than that of ~ 11.

[0054]

Example 7 The same operation as in Example 1 was performed except that the distance from the waveguide to the wet film (yarn bundle) was set to 60 ± 5 mm. The performance of this membrane is shown in Table 4. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, since the difference in the performance of the film between the central portion and the outer peripheral portion of the yarn bundle is smaller than that of the conventional drying method (Comparative Example 1), it is clear that there is little variation in performance. Further, it was revealed that the difference in performance between the yarn bundle located in the central part of the irradiation furnace and the yarn bundle located at the outermost part in the irradiation furnace was smaller than in Comparative Examples 8 to 11.

[0055]

Example 8 The same operation as in Example 1 was performed except that the distance from the waveguide to the wet film (yarn bundle) was 480 ± 5 mm. The performance of this membrane is shown in Table 4. It was revealed that the amount of elution from the membrane was extremely small and that blood proteins and platelets were not attached to this membrane. Further, it was suggested that the membrane has a low albumin permeability and an excellent β2-microglobulin clearance, and thus it was found that the membrane has excellent dialysis performance. Furthermore, since the difference in the performance of the film between the central portion and the outer peripheral portion of the yarn bundle is smaller than that of the conventional drying method (Comparative Example 1), it is clear that there is little variation in performance. Further, it was revealed that the difference in performance between the yarn bundle located in the central part of the irradiation furnace and the yarn bundle located at the outermost part in the irradiation furnace was smaller than in Comparative Examples 8 to 11.

[0056]

[Comparative Example 1] Yarn bundle after removal of residual solvent (water content is 300%,
Example: 90 yarns having a water content of 300% in the central part of the yarn bundle, a water content of 300% in the outer peripheral part of the yarn bundle, and a water content difference of 0% between the central part and the outer peripheral part of the yarn bundle. Example 1 except that a yarn bundle having a water content of less than 1% was obtained by blasting and drying at a temperature of 87 ° C. for 7 hours (wind speed 10 m / sec) in the same arrangement of yarn bundles in the same irradiation furnace as in Example 1. The same operation as in 1 was performed. The results are shown in Table 5. It was clarified that there is a difference in the performance of the membrane between the central portion and the outer peripheral portion of the yarn bundle in the amount of water permeation and the transmittance of PVP, and as a result, there is variation in the performance within the yarn bundle.

[0057]

[Comparative Example 2] The same operation as in Example 1 was carried out except that no γ-ray irradiation was performed. The results are shown in Table 6. It was revealed that the absorbance of the dissolution test liquid exceeded 0.04 due to the dissolution of PVP. The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0058]

[Comparative Example 3] The polyvinylpyrrolidone in the stock solution for film formation was compared with 5.
The same operation as in Example 1 was performed except that 0% by weight and 77.0% by weight of N, N-dimethylacetamide were used. At this time, the mixing ratio of polyvinylpyrrolidone to polysulfone in the film-forming stock solution was 27.8% by weight. The performance of this membrane is shown in Table 6. Since the mixing ratio of polyvinylpyrrolidone to polysulfone in the stock solution for film formation exceeds 27% by weight, the amount of elution and the concentration of PVP on the inner surface of the film are increased. The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0059]

[Comparative Example 4] The polyvinylpyrrolidone in the stock solution for film formation was compared with 3.
The same operation as in Example 1 was performed, except that 6% by weight and 78.4% by weight of N, N-dimethylacetamide were used. At this time, the mixing ratio of polyvinylpyrrolidone to polysulfone in the film-forming stock solution was 20.0% by weight. The performance of this membrane is shown in Table 6. It was revealed that the PVP amount on the inner surface of the film was less than 30%. The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0060]

[Comparative Example 5] N, N-dimethylacetamide 6 was added to the inner liquid.
The same operation as in Example 3 was performed except that a mixed solution of 0% by weight and 40% by weight of water was used. The performance of this membrane is shown in Table 6. This membrane had an albumin transmittance of more than 0.3% and a PVP transmittance of more than 75%. The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0061]

[Comparative Example 6] N, N-dimethylacetamide 1 was added to the inner liquid.
The same operation as in Example 1 was performed except that a mixed solution of 0% by weight and 90% by weight of water was used. The performance of this membrane is shown in Table 6. Pure water permeability is 10mL / (m ² · hr · m
The performance was lower than mHg). The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0062]

Comparative Example 7 The same operation as in Example 1 was performed except that the drying temperature was 170 ° C. The performance of this membrane is shown in Table 6.
In this membrane, all PVP in the membrane was insoluble in water. Using this membrane as a module with an effective filtration area of 1.5 m ² and performing clinical blood evaluation according to the performance evaluation criteria of the Japanese Society for Artificial Organs under the condition of a blood flow rate of 500 mL / min (outer side of the membrane),
Leukopenia symptoms were observed in which the white blood cell count in dialysis patients was temporarily reduced. The performance evaluation was performed only on the outer peripheral portion of the yarn bundle located in the center of the irradiation furnace.

[0063]

[Comparative Example 8] The same operation as in Example 1 was performed except that the radiation angle of the microwave radiated from the waveguide was 20 degrees. The performance of this membrane is shown in Table 7. It was clarified that there was a difference in performance between the yarn bundle located in the center of the irradiation furnace and the yarn bundle located in the outermost portion of the irradiation furnace, and as a result there was variation among the yarn bundles.

[0064]

[Comparative Example 9] The same operation as in Example 1 was performed except that the radiation angle of the microwave radiated from the waveguide was set to 130 degrees. The performance of this membrane is shown in Table 7. It was clarified that there was a difference in performance between the yarn bundle located in the center of the irradiation furnace and the yarn bundle located in the outermost portion of the irradiation furnace, and as a result there was variation among the yarn bundles.

[0065]

Comparative Example 10 The same operation as in Example 1 was performed except that the distance from the waveguide to the wet film (yarn bundle) was set to 30 ± 5 mm. Only the upper side of the yarn bundle was dry and the lower side was undried.

[0066]

Comparative Example 11 The same operation as in Example 1 was performed except that the distance from the waveguide to the wet film (yarn bundle) was 520 ± 5 mm. The entire yarn bundle was undried.

[0067]

[Table 1]

[0068]

[Table 2]

[0069]

[Table 3]

[0070]

[Table 4]

[0071]

[Table 5]

[0072]

[Table 6]

[0073]

[Table 7]

[0074]

According to the method for producing a hollow fiber membrane of the present invention,
Even when a plurality of wet films bundled in a yarn bundle are dried at the same time, it is possible to eliminate variations in performance within the yarn bundle and at the same time eliminate variations in performance between yarn bundles.
The membrane produced according to the present invention has an extremely small amount of elution from the membrane and has excellent dialysis performance with little adhesion of blood proteins and platelets, and thus can be used for pharmaceutical applications, medical applications, and general industrial applications.

[Brief description of drawings]

FIG. 1 is a diagram for explaining the relationship between a waveguide and a radiation angle in the manufacturing method of the present invention.

[Explanation of symbols]

1 Waveguide O Center point of the irradiation surface of the waveguide A Point where the radiant energy is strongest on the curve equidistant from the center point of the irradiation surface of the waveguide B Equal distance from the center point of the irradiation surface of the waveguide Point at which the radiant energy is half of the strongest radiant energy on the curve of C. The radiant energy at the strongest radiant energy on the curve equidistant from the center point of the irradiation surface of the waveguide. The point at which

Front page continuation (51) Int.Cl. ⁷ Identification symbol FI theme code (reference) D01F 6/94 D01F 6/94 Z D06M 10/00 D06M 10/00 EJ F term (reference) 4C077 AA05 BB01 LL05 LL30 PP09 PP15 4D006 GA13 HA15 HA18 MA01 MA22 MB01 MC40 MC62 NA05 NA18 NA19 NA42 NA64 PA01 PB09 PC47 4L031 AA12 AA14 AB06 CA08 CB03 CB08 4L035 AA04 BB04 BB11 BB16 CC05 DD03 MF01

Claims (11)

[Claims] 1. A method for producing a hollow fiber membrane, wherein a wet film bundled into a bundle of yarns is irradiated with microwaves to dry a plurality of bundles at the same time, and the radiation angle of the microwaves irradiated from the waveguide is 3.
A method for producing a hollow fiber membrane, which is 0 to 120 degrees and the distance from the waveguide to the wet membrane is 50 to 500 mm. 2. A method for producing a hollow fiber blood purification membrane, which comprises microwave-irradiating a wet membrane, which does not contain a membrane pore-holding agent, bundled into a bundle of fibers to dry a plurality of bundles at the same time. The microwave radiation angle is 30 to 120 degrees,
A method for producing a hollow fiber blood purification membrane, characterized in that the distance from the waveguide to the wet membrane is 50 to 500 mm. 3. A hollow fiber blood purification wherein a wet membrane containing no membrane pore-holding agent bundled into a bundle of fibers is heated and dried at a temperature of 40 ° C. or higher and 120 ° C. or lower, and a plurality of bundles are simultaneously dried by microwave irradiation. A method of manufacturing a film, characterized in that the microwave emitted from the waveguide has an emission angle of 30 to 120 degrees, and the distance from the waveguide to the wet film is 50 to 500 mm. Method for producing filamentous blood purification membrane. 4. The manufacturing method according to claim 1, wherein a plurality of waveguides are used. 5. The manufacturing method according to claim 1, wherein a dehumidifying body is ventilated in the yarn bundle. 6. The method according to claim 1, wherein the difference in water content of the membrane between the central portion and the outer peripheral portion of the yarn bundle at the start of drying is within 10%. 7. The average water content of the yarn bundle after the start of drying is 20 to
The manufacturing method according to any one of claims 1 to 6, wherein the irradiation output of the microwave is reduced at the time of reaching 70%. 8. The average water content of the yarn bundle after the start of drying is 20 to
The manufacturing method according to any one of claims 1 to 7, wherein a difference in water content of the membrane between the central portion and the outer peripheral portion of the yarn bundle at the time of reaching 70% is within 5%. 9. The membrane comprises a polysulfone-based polymer and polyvinylpyrrolidone.
The manufacturing method according to any one of 1. 10. The film-forming stock solution comprises a polysulfone-based polymer, polyvinylpyrrolidone, and a solvent, and the ratio of polyvinylpyrrolidone to the polysulfone-based polymer is 18 to 27% by weight.
9. The manufacturing method according to any one of 9. 11. The method according to claim 1, wherein after drying, a part of polyvinylpyrrolidone in the film is further insolubilized in water.
10. The manufacturing method according to any one of 10 to 10.