JP5952159B2 - Separation membrane and manufacturing method thereof - Google Patents

Description

  The present invention relates to a separation membrane containing a hydrophobic polymer and a hydrophilic polymer. More specifically, the present invention relates to a separation membrane that is resistant to chemical washing and can maintain the hydrophilicity and fractionation performance of the separation membrane over a long period of time in the use of concentrating enzymes and proteins.

  Conventionally, permselective separation membranes have been widely used for the concentration of enzymes and proteins. When the enzyme or protein is adsorbed on the membrane, not only will clogging result in a decrease in filtration performance, but also a problem that the product recovery rate is lowered. For this reason, it is known that among the selectively permeable separation membranes, membranes made of a hydrophilic material such as cellulose or polyacrylonitrile are suitable because they are difficult to adsorb on the membrane surface.

  However, these hydrophilic materials generally have a drawback of low chemical resistance and mechanical strength. In order to remove enzymes and proteins from the membrane after use, it is known that it is effective to wash at high temperature with an alkaline cleaning solution such as an aqueous sodium hydroxide solution or an aqueous sodium hypochlorite solution. However, since these hydrophilic materials have low resistance to high temperatures and alkaline solutions, it was not possible to use optimum cleaning conditions. For this reason, cleaning is performed under conditions where the temperature and pH are gentle, but the film deteriorates as the chemical exposure is repeated, and the fractionation performance gradually deteriorates. there were.

  In order to solve this problem, hydrophilicity is improved by blending or coating hydrophilic polymers and additives with hydrophobic materials such as polysulfone and polyvinylidene fluoride, which have excellent mechanical and chemical strength. Membranes that have been added have been developed.

  As a method for imparting hydrophilicity to a hydrophobic material, for example, as disclosed in Patent Documents 1 and 2, a method of blending polyethylene glycol, which is a hydrophilic polymer, in a film forming stock solution, or Patent Document 3 And 4 discloses methods of adding polyvinylpyrrolidone.

  However, since polyethylene glycol and polyvinyl pyrrolidone are water-soluble, there is a problem that even when initially showing good performance, they are gradually dissolved in the treatment liquid during use and the hydrophilicity is lost. At the same time, the part where the hydrophilic polymer is dropped becomes voids, and the fractionation performance decreases.

  Patent Document 5 proposes a method of retaining polyethylene glycol having a molecular weight of 35000 in a membrane as a hydrophilized polysulfone-based membrane resistant to strong oxidizing agents. Here, since polyethylene glycol is more hydrophilic than the base polysulfone, there is some effect as a separation membrane, but from the viewpoint of fouling resistance, a more hydrophilic and uniform hydrated layer can be formed. Polyvinylpyrrolidone is superior.

  In order to prevent the elution of polyvinyl pyrrolidone, as disclosed in Patent Document 6, a technique for cross-linking polyvinyl pyrrolidone with an alkali or the like to insolubilize has been developed. By performing such insolubilization treatment, elution of polyvinylpyrrolidone into water can be prevented, and it is now widely used in medical fields such as dialysis membranes.

JP-A-61-232860 JP 58-114702 A JP 2008-6327 A Japanese Patent No. 3117575 JP 2007-307463 A International Publication No. 04/018085

  However, since these are mainly assumed to be used for single use, such as for blood treatment, the problem of repeated use is not considered. Even if the hydrophilic polymer is cross-linked and insolubilized in water, it is difficult to maintain the hydrophilicity and fractionation performance over a long period of time because the decomposition of the hydrophilic polymer by chemicals cannot be suppressed. Thus, the hydrophilicity of the membrane and the membrane life are in a trade-off relationship, and since it was not clear how much hydrophilicity would provide satisfactory filtration performance, an attempt was made to make both sufficiently high after all. It has been continued but has not been achieved so far.

  An object of the present invention is to provide a separation membrane having hydrophilicity, high chemical resistance, a high water permeability retention rate when an enzyme solution is filtered, and a high enzyme removal rate, and a method for producing the same. . Another object of the present invention is to provide a module including the separation membrane, and an enzyme concentration method and a filtration method using the separation membrane.

  As a result of intensive studies to solve the above problems, the present inventors have found that a certain type of separation membrane containing a hydrophilic polymer and a hydrophobic polymer has hydrophilicity, high chemical resistance, and an enzyme solution. It was found that the retention rate of water permeability when filtered was high and the enzyme removal rate was also high.

That is, the present invention provides the following [1] to [16].
[1] A separation membrane comprising a hydrophobic polymer and a hydrophilic polymer, wherein the hydrophilic polymer contains polyvinyl pyrrolidone having a weight average molecular weight of 2000 or more and less than 50000, and is formed on one surface of the separation membrane. A separation membrane, wherein the difference between the contact angle and the contact angle of the other surface is 6 degrees or more.
[2] The separation membrane according to [1], wherein the polyvinyl pyrrolidone has a weight average molecular weight of 2500 or more and 32000 or less.
[3] The separation membrane according to [1] or [2], wherein a difference between a contact angle on one surface of the separation membrane and a contact angle on the other surface is 10 degrees or more.
[4] The hydrophobic polymer contains polyether sulfone or polysulfone, and the proportion of the polyvinyl pyrrolidone is 2% by mass or more and 8% by mass based on the total amount of the polyvinyl pyrrolidone and the polyether sulfone or the polysulfone. % Of the separation membrane according to any one of [1] to [3].
[5] The separation membrane according to [4], wherein a ratio of the polyvinyl pyrrolidone is 2% by mass or more and 4.1% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyether sulfone or the polysulfone.
[6] The hydrophobic polymer contains polyvinylidene fluoride, and the ratio of the polyvinyl pyrrolidone is 0.2% by mass or more and 2% by mass or less based on the total amount of the polyvinyl pyrrolidone and the polyvinylidene fluoride. The separation membrane according to any one of [1] to [3].
[7] The separation membrane according to [6], wherein a ratio of the polyvinyl pyrrolidone is 1.5% by mass or more and 2% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyvinylidene fluoride.
[8] The separation membrane according to any one of [1] to [7], which is a hollow fiber membrane.
[9] A module comprising the separation membrane according to any one of [1] to [8].
[10] An enzyme concentration method using the separation membrane according to any one of [1] to [8].
[11] A filtration method using the separation membrane according to any one of [1] to [8].
[12] A film-forming stock solution containing at least a hydrophobic polymer, a hydrophilic polymer, and a common solvent for dissolving the hydrophobic polymer and the hydrophilic polymer is coagulated in a solution containing water as a main component. And a process for producing a separation membrane, wherein the hydrophilic polymer contains polyvinylpyrrolidone having a weight average molecular weight of 2,000 or more and less than 50,000.
[13] The method for producing a separation membrane according to [12], wherein the membrane-forming stock solution is a poor solvent for the hydrophobic polymer and further contains a poor solvent having a molecular weight of 300 or less.
[14] The method for producing a separation membrane according to [12] or [13], wherein the membrane-forming stock solution is discharged into a hollow fiber shape.
[15] The method for producing a separation membrane according to [14], wherein the main component of the hollow agent used when the membrane-forming stock solution is discharged into a hollow fiber is water.
[16] The method for producing a separation membrane according to any one of [12] to [15], wherein the idle running time is 0.1 second or more and less than 10 seconds.

  According to the present invention, it is possible to provide a separation membrane having a hydrophilic property, high chemical resistance, a high water permeability retention rate when an enzyme solution is filtered, and a high enzyme removal rate, and a method for producing the same. . In addition, according to the present invention, it is possible to provide a module including the separation membrane, and an enzyme concentration method and a filtration method using the separation membrane. More specifically, by using the separation membrane of the present invention, the hydrophilicity of the membrane can be maintained even under harsh washing conditions using a high-temperature alkaline solution unique to the filtration of proteins and enzymes. Can hardly adhere to the membrane surface and can maintain good filterability. That is, it is possible to provide a separation membrane that is more suitable for repeated use than in the past.

Hereinafter, preferred embodiments of the present invention will be described in detail.
The separation membrane of this embodiment includes a hydrophobic polymer and a hydrophilic polymer. Since the hydrophobic polymer has high mechanical and chemical strength, it has a role of ensuring the strength of the separation membrane. On the other hand, the hydrophilic polymer keeps the surface of the separation membrane hydrophilic and makes it difficult for proteins and enzymes to adhere to it, thus contributing to good filtration performance.

  Here, the separation membrane means a membrane used in a separation process such as microfiltration or ultrafiltration, and is preferably a porous membrane. The pore diameter is preferably from 0.1 nm to 5 μm, and more preferably from 1 nm to 0.5 μm. Further, the shape of the separation membrane is not particularly limited. Examples of the shape of the separation membrane include a flat membrane, a hollow fiber membrane, a multilayered composite membrane, etc. Among them, the hollow fiber membrane can increase the degree of integration per unit installation area and can increase the membrane area. Therefore, it is particularly preferable.

  The hydrophobic polymer preferably includes a hydrophobic resin component having excellent heat resistance, chemical resistance, and the like. Examples of the resin component include polysulfone, polyethersulfone, polyethylene, polypropylene, polytetrafluoroethylene, and polyfluoride. And vinylidene chloride. Of these, polysulfone such as polysulfone and polyethersulfone is particularly preferred because of its excellent resistance to alkaline aqueous solutions used in enzyme and protein washing and good compatibility with hydrophilic polymers. Polymers of the type are preferred.

  The separation membrane of this embodiment contains polyvinylpyrrolidone (hereinafter also referred to as “PVP”) having a weight average molecular weight of 2000 or more and less than 50000 as a hydrophilic polymer. By using PVP having a weight average molecular weight of 2,000 or more and less than 50,000, it is possible to produce a film having excellent hydrophilicity and strength to withstand repeated use at a high level. Moreover, it is preferable to use PVP having a weight average molecular weight of 2500 or more and 32000 or less. By using PVP having a weight average molecular weight of 2500 or more and 32000 or less, it is possible to produce a film having a higher level of superior hydrophilicity and strength to withstand repeated use. PVP is also preferred as a hydrophilic polymer from the viewpoint of safety and high compatibility with hydrophobic polymers.

  Other hydrophilic polymers include, for example, polyethylene glycol, polyvinyl alcohol, polyhydroxymethacrylate, polyacrylonitrile, polyacrylamine, polyethyleneimine, surfactants (for example, alkyl sulfate salts, polyoxyethylene alkyl ether sulfate salts) Anionic surfactants such as alkylbenzene sulfonates and fatty acid salts; polyoxyethylene alkyl ethers, polyoxyalkylene derivatives, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitol fatty acid esters, glycerin fatty acid esters, Contains nonionic surfactants such as polyoxyethylene fatty acid esters; cationic surfactants such as alkylamine salts and quaternary ammonium salts) It may be.

  Conventionally, high molecular weight PVP having a weight average molecular weight of 50,000 or more has been used in many separation membranes. For example, those having a K value (viscosity characteristic value) of 30 (weight average molecular weight of about 50000) or 90 (weight average molecular weight of about 1600000), which are indicators of the molecular weight of PVP, are widely used. This is because the high molecular weight PVP tends to remain in the membrane, so that the membrane can easily have a hydrophilic effect. However, these membranes show high hydrophilicity immediately after production, but when post-treatment such as cross-linking is not performed, the membrane gradually elutes into the processing solution during use, and the hydrophilicity is lowered. . When PVP is insolubilized by crosslinking or the like, a decrease due to elution can be suppressed, but decomposition by chemicals such as sodium hypochlorite used as a cleaning agent cannot be prevented. Therefore, in applications where the separation membrane is repeatedly used while being chemically cleaned, the loss of PVP is unavoidable.

  When the PVP in the separation membrane decreases, not only the hydrophilicity is lost, but also the pore size becomes large and the initial fractionation performance cannot be maintained. This is presumably because, immediately after the film formation, the molecular chain of PVP extends and spreads into the micropores formed by the hydrophobic polymer serving as the membrane substrate, and the pore diameter appears to be small. When an oxidizing agent such as sodium hypochlorite used as a cleaning agent comes into contact therewith, the molecular chain of PVP is cut and the PVP filling the micropores is dropped, so that the apparent blocking rate is considered to decrease. . As described above, the conventional techniques have a problem in terms of the lifetime of the film under severe cleaning conditions. However, these problems can be solved by using a low molecular weight PVP having a molecular weight of less than 50000 (corresponding to a K value of 30). In addition, when PVP having a molecular weight of less than 2000 is used, it is difficult to impart hydrophilicity to the separation membrane.

  In general, when PVP having a low molecular weight is used, since the PVP is almost completely removed from the membrane during spinning or washing with water, the effect of hydrophilizing the membrane is small. Further, when the amount added is increased in order to increase the effect, the amount of elution during use becomes large as in Comparative Example 2 of JP-A-6-296686, although it temporarily remains in the membrane. .

  However, by leaving a large amount of low molecular weight PVP in the hydrophobic polymer, while maintaining high hydrophilicity, more surprisingly, even when the membrane is subjected to chemical cleaning, the change in the blocking rate is low. It was found that the molecular weight PVP was clearly smaller than when the high molecular weight PVP was used. This is thought to be because the size of the micropores formed by the original hydrophobic polymer almost matches the apparent pore size because the molecular chain of PVP is short. For this reason, even if PVP decomposes and falls off in contact with an oxidizing agent, it is considered that the change in pore size is small and the influence on the fractionation performance is small.

  The preferable range of the proportion of PVP present in the separation membrane varies depending on the type of the hydrophobic polymer that coexists. When the hydrophobic polymer contains polyethersulfone or polysulfone, the proportion of polyvinylpyrrolidone is preferably 2% by mass or more and 8% by mass or less based on the total amount of polyvinylpyrrolidone and polyethersulfone or polysulfone. More preferably, the content is 2% by mass or more and 4.1% by mass or less. On the other hand, when the hydrophobic polymer contains polyvinylidene fluoride, the proportion of polyvinylpyrrolidone is preferably 0.2% by mass or more and 2% by mass or less based on the total amount of polyvinylpyrrolidone and polyvinylidene fluoride. More preferably, it is 5 mass% or more and 2 mass% or less. In each case, if the content ratio of PVP is not less than the above lower limit value, hydrophilicity can be further imparted to the membrane, and good filterability can be obtained. Moreover, if the content rate of PVP is below the said upper limit, the elution at the time of filtration will be suppressed more, and the change of the hole diameter by the drop-out of PVP will also be small.

  In the separation membrane of this embodiment, the contact angle of one surface (secondary side surface) is 6 degrees or more larger than the other surface (primary side surface). Here, the primary side surface refers to the side of the membrane in direct contact with the liquid to be treated, and the secondary side surface refers to the side in contact with the filtrate. That the contact angle of the secondary surface is larger than the primary surface indicates that the secondary surface is more hydrophobic. That is, the contact angle of the secondary side surface is larger than the primary side surface, which means that there is a distribution in the amount of hydrophilic polymer in the separation membrane, and more hydrophilic polymer is present on the side closer to the primary side surface. It means that it exists.

  In addition to proteins and enzymes, which are target concentrates, the liquid to be treated contains trace amounts of low-molecular-weight impurity components, which are generally smaller than the pore size of the primary surface, so that the membrane And pass through the filtrate. However, by making the secondary side surface more hydrophobic than the primary side surface, these impurities are adsorbed on the membrane, so that the impurities that have passed through the primary side surface can be captured and the filtrate becomes more clarified. Can do. Therefore, the rejection rate including impurities can be further increased.

  The contact angle of the surface of the separation membrane is preferably 75 degrees or less with respect to the contact angle of at least one of the primary side surface and the secondary side surface. The contact angle of water in the air is an index representing the degree of hydrophilicity of the film surface, and the smaller the value, the more hydrophilic it is. For example, the contact angle of a membrane made of a single hydrophobic material such as polysulfone or polyvinylidene fluoride is 80 degrees or more, while the contact angle of a membrane of a single hydrophilic material such as polyacrylonitrile is 80 Less than degrees. In the filtration of proteins and enzymes, the present inventors have obtained a good filterability equivalent to a membrane made of a hydrophilic material when the contact angle of the surface directly in contact with the liquid to be treated is 75 degrees or less. I found it easy to be. If the contact angle is 75 degrees or less, the adsorption of enzymes and proteins to the membrane surface can be suppressed sufficiently small, and the decrease in filtration performance can be sufficiently suppressed. Further, the lower limit of the contact angle is preferably 55 ° or more because deterioration on the film surface due to chemicals can be suppressed and the change in pore diameter can be suppressed sufficiently small in practice. The lower limit of the contact angle is more preferably 60 degrees or more and 70 degrees or less.

  The separation membrane of the present embodiment was again immersed in 500 ppm sodium hypochlorite aqueous solution at 60 ° C. for 3 hours using dextran having an initial rejection rate value (A) of 50% or more and less than 95%. It is preferable that the separation membrane satisfy the B ≧ A × 0.5 value (B) when the rejection rate is measured. This means that the retention rate of the dextran blocking rate of the separation membrane before and after immersion in an aqueous sodium hypochlorite solution is used as an indicator of the resistance of the separation membrane to the cleaning agent (chemical resistance). ing.

  A sodium hypochlorite aqueous solution is generally used as a cleaning agent when a liquid containing protein or enzyme is filtered, and further has an action of oxidatively decomposing PVP in the membrane, and thus is suitable. As an index of chemical resistance, B ≧ A × 0.6 is more preferable, and B ≧ A × 0.7 is more preferable.

  As described above, dextran having a separation membrane having an initial rejection rate value A of 50% or more and less than 95% is used. This is because when dextran having A of 50% or more and less than 95% is used, a change can be clearly detected when the pore size of the membrane changes. If the initial blocking rate is less than 50% or 95% or more, the pore size of the original membrane is sufficiently larger or smaller than dextran, so even if the pore size of the membrane changes slightly due to chemical immersion, the blocking rate changes. It is difficult to detect with. When the retention ratio B / A of the dextran blocking ratio before and after chemical immersion is 0.5 or more, the change in pore diameter is small, and stable performance can be maintained for a long time in the filtration of proteins and enzymes.

  In this embodiment, it is preferable that the UV absorbance of the extract when the separation membrane is extracted with pure water is less than 0.10. When the UV absorbance of the extract is less than 0.10, the amount of elution of the hydrophilic polymer is sufficiently small, and the hydrophilic polymer remaining in the separation membrane is strongly entangled with the hydrophobic polymer chain. It shows that. When the UV absorbance of the extract is less than 0.10, stable filtration performance can be obtained over a longer period. The extraction method can be carried out in accordance with the dissolution test of the artificial kidney device approval standard (specified by the Ministry of Health and Welfare in 1983) used in the medical field.

  The separation membrane of the present embodiment preferably has a dextran rejection rate of 20% or more, which can be measured by the measurement method described in the Examples described later. The molecular weight of the target concentrate protein or enzyme is about several thousand to several tens of thousands, and if the inhibition rate of dextran having a weight average molecular weight of 10,000 is 20% or more, higher fractionation performance can be obtained. The blocking rate is more preferably 30% or more, and further preferably 40% or more.

Separation membrane of the present embodiment, pure water permeation amount measured by the measuring method described in Examples is preferably less than 100L ^{/ m} 2 ^/ h or more 10000L ^{/ m} 2 ^/ h. When the pure water permeation amount is 100 L / m ² / h or more, a sufficient treatment capacity can be obtained with a low transmembrane pressure (hereinafter also referred to as “TMP”). Moreover, if it is less than 10000 L / m < ² > / h, it is not necessary to worry about the capability of incidental facilities, such as a pump, and it can be used universally.

In this embodiment, if the pure water permeation amount of the separation membrane is C (L / m ² / h) and the water permeation amount when the enzyme solution is filtered is D (L / m ² / h), D / C ≧ 0 And the enzyme blocking rate when the enzyme solution is filtered is preferably 99.0% or more.

  In the separation membrane of this embodiment, the filtration ability of the enzyme solution is evaluated by the retention rate of the water permeability when the enzyme solution is filtered and the inhibition rate of the enzyme. If the enzyme blocking rate is 99.0% or more and the water permeability retention ratio D / C is 0.05 or more, the enzyme is not allowed to pass to the filtrate side, and the adsorption to the membrane surface is small. Enzyme can be concentrated and recovered with high efficiency. In addition, the high retention rate of the water permeability means that the original water permeability of the membrane is well reflected even when the enzyme solution is filtered, and it is easy to determine the membrane area required for introduction into the facility. become. More preferably, D / C ≧ 0.10, and further preferably D / C ≧ 0.12.

  The separation membrane of the present invention is preferably a hollow fiber membrane. By being a hollow fiber membrane, it is possible to increase the membrane area per module unit volume as compared to a planar membrane.

Hereinafter, the manufacturing method of the separation membrane of this embodiment is demonstrated.
The separation membrane according to the present embodiment secures a predetermined idle running section after discharging the film-forming stock solution, or so-called wet film-forming method, in which the film-forming stock solution is discharged and coagulated in a coagulation solution having a coagulation power. It can be produced by a so-called non-solvent induced phase separation method.

  The film-forming stock solution in this embodiment contains at least a hydrophobic polymer, a hydrophilic polymer, and a common solvent that dissolves the hydrophobic and hydrophilic polymer components. The common solvent is not particularly limited as long as it can dissolve the hydrophobic and hydrophilic polymer components described above, and a known solvent can be appropriately selected and used. From the viewpoint of improving the stability of the film-forming stock solution, the common solvent is at least one selected from the group consisting of N-methylpyrrolidone (NMP), dimethylformamide (DMF), dimethylacetamide (DMAC), and dimethylsulfoxide (DMSO). It is preferred to use a seed solvent. From the viewpoint of easy handling and higher water permeability, it is particularly preferable to use N-methylpyrrolidone. Moreover, you may use the mixed solvent of the at least 1 sort (s) of common solvent selected from said group, and another solvent. In this case, it is preferable to use a mixed solvent in which the total amount of the common solvent selected from the above group is preferably 80% by mass or more, more preferably 90% by mass or more based on the total amount of the mixed solvent.

  Examples of the above-mentioned “coagulating solution having coagulation ability with respect to the film-forming stock solution” include water, alcohols such as ethanol, aqueous solutions of solvents, and the like. It is preferable to use a solution to be used. Here, “including as a main component” means including 50 mass% or more. The ratio of water in the coagulation solution is more preferably 70% by mass or more, and still more preferably 80% by mass or more.

  As one of the problems when using low molecular weight PVP for the separation membrane, the spinnability is very poor due to low viscosity, and it is difficult to form a membrane as shown in Comparative Example 2 of Japanese Patent No. 4724914. There was a thing. However, in the method for producing a separation membrane of the present embodiment, the spinnability can be greatly improved by using a solution containing water as a main component for the coagulation solution.

  The film forming raw material preferably contains a poor solvent. As the poor solvent, a poor solvent having a molecular weight of 300 or less is particularly preferable. The poor solvent here means a solvent in which insoluble components are observed when 5 g of the hydrophobic polymer is dissolved in 100 g of a solvent at 25 ° C.

  When a poor solvent is added to the membrane-forming raw material, the content efficiency of the hydrophilic polymer that remains in the separation membrane increases, so that low molecular weight PVP can be efficiently contained in the hydrophobic polymer. This is because when a phase separation occurs in film formation by a non-solvent induced phase separation method, these poor solvents are dilute phases of a hydrophobic polymer (that is, a phase mainly composed of a solvent, and finally a void portion). The hydrophilic polymer tends to remain in the concentrated layer of the hydrophobic polymer (the phase that finally forms the column part of the separation membrane). As a result, it is considered that a large amount of hydrophilic polymer remains in the structure made of the hydrophobic polymer of the separation membrane finally produced. When the molecular weight of the poor solvent is increased, the molecular chain of the poor solvent is entangled with the molecular chains of the hydrophilic and hydrophobic polymers, making it difficult to escape from the film-forming stock solution and the effect is reduced, but the molecular weight is 300 or less. And, since the poor solvent quickly escapes to the lean phase side, an excellent effect can be obtained. Accordingly, the hydrophilic polymer can be efficiently left even with a small addition amount, which is advantageous in terms of cost.

  Examples of poor solvents include water, alcohols such as glycerin and ethanol, ethylene glycols, etc., but they are relatively poorly compatible with hydrophilic polymers and easy to handle. Low molecular weight ethylene glycol-based substances such as ethylene glycol (hereinafter referred to as “TEG”), triethylene glycol, and ethylene glycol are particularly preferable.

  In the separation membrane manufacturing method of the present embodiment, it is preferable to form the separation membrane into a hollow shape.

  As a method of forming into a hollow shape, a double tubular nozzle is used as a forming nozzle at the time of film formation, and a film-forming stock solution is extruded from the double tubular nozzle together with a hollow agent, into a solution containing water as a main component. A discharging method can be used. Thereby, the membrane-forming stock solution is solidified to produce a hollow fiber membrane. The hollow agent is a liquid that flows in the hollow portion. As the hollow agent, water, alcohol, an aqueous solution containing a solvent, or the like is used. In this embodiment, it is preferable that the main component of the hollow agent is water. Moreover, it is more preferable that the ratio of water is 70 mass% or more, and it is still more preferable that it is 80 mass% or more.

  By using pure water with strong coagulation power for the hollow agent, even when a film-forming stock solution with poor spinnability is used, yarn breakage can be prevented by solidifying the inner surface side quickly, and good productivity can be obtained. Can do. Thereby, even when low molecular weight PVP, which is difficult to form a film, is used, good spinnability can be maintained.

  In the separation membrane manufacturing method of the present embodiment, the idle running time is preferably 0.1 seconds or more and less than 10 seconds, and more preferably 0.3 seconds or more and less than 3 seconds. If the idling time is 0.1 seconds or more, the inner surface can be sufficiently solidified before entering the coagulation water bath, and the membrane can be flattened even when a sudden force is applied from the outer surface side when it reaches the water. Can be prevented. Further, if the idle running time is less than 10 seconds, it is possible to prevent the film from stretching during idle running and causing yarn breakage. Here, the idle running time refers to the time during which the separation membrane passes through the air from dry spinning from the spinneret to landing in the water bath for coagulation in dry and wet spinning.

  The separation membrane described above can be used as a module containing a large number of membranes. Here, the separation membrane module is roughly classified into an immersion membrane module and a pressure membrane module. The submerged membrane module includes a separation membrane and an end fixing portion that fixes at least one end of the separation membrane, and the separation membrane is exposed. The separation membrane is the treated separation membrane. Examples include a separation membrane module. The pressure membrane module has a casing around the separation membrane, and is an integral type in which the separation membrane is fixed in the casing, and the casing and the separation membrane are independent of each other. There are cartridge types that are inserted and used, and in both types, the separation membrane can be applied as a separation membrane. In concentrating enzymes and proteins, since they dislike contamination, a pressurized membrane module that can be used in a closed system and can be easily replaced is preferred.

  As the filtration method using the separation membrane described above, either dead-end filtration or crossflow filtration can be used. However, crossflow filtration suppresses fouling by the shear force applied in the horizontal direction with the membrane surface. This is particularly preferable because it can be performed.

  The preferred embodiment of the present invention has been described above, but the present invention is not limited to the above embodiment.

  Hereinafter, the contents of the present invention will be described more specifically with reference to examples and comparative examples. In addition, this invention is not limited to the following Example. Moreover, when there was no description in particular, the measurement was performed at 25 degreeC.

(Measurement method of contact angle of separation membrane)
The surface of the separation membrane was flattened, and the surface to be measured was fixed on the slide glass with double-sided tape with the surface to be measured facing up. A water droplet was dropped on the surface of the membrane, and the contact angle was obtained by the θ / 2 method using a contact angle measuring device (FACE CONACT-ANGULEYYER, manufactured by Kyowa Interface Science). The θ / 2 method is a method of obtaining the contact angle θ from the angle (θ / 2) of the straight line connecting the left or right end point and the apex of the water droplet to the film surface.

  The measurement was performed 5 times for each of the primary side and the secondary side, and the average value was obtained. In the case of a hollow fiber membrane, a flat surface was obtained by the following method. When measuring the contact angle of the outer surface, the membrane surface was crushed and flattened using a glass round bar. When measuring the contact angle of the inner surface, the hollow fiber was cut in the length direction, and the membrane surface was flattened with a glass round bar with the inner surface side of the hollow fiber exposed.

(Dextran blocking rate measurement method)
A plurality of unused separation membranes were prepared, and half of them were used to measure the dextran blocking rate (A). The remaining half of the separation membranes were treated as described in (Chemical immersion method) below, and then the dextran blocking rate (B) was measured.

  A commercially available dextran was diluted to 0.1% by mass with water to prepare an aqueous dextran solution. An injection needle was inserted into both ends of a wet hollow fiber membrane having a length of about 20 cm, and the injection needle at one end was connected to a pump via a tube so that an aqueous dextran solution could be fed. A tube was attached to the other end of the injection needle, the tip of the tube was placed in a container containing a dextran aqueous solution, and a circuit was constructed so that the dextran aqueous solution that passed through the hollow portion returned to the container. A dextran aqueous solution container was placed under the separation membrane so that the filtrate filtered from the inner surface to the outer surface side of the separation membrane could be recovered. In addition, the outflow pressure from the separation membrane can be measured. The hollow part of the separation membrane was fed so that it flowed at a flow rate of 1.0 m / sec dextran aqueous solution. At this time, the outflow pressure was adjusted to be 0.05 MPa. In this state, cross flow filtration was performed in which a dextran aqueous solution was refluxed in the hollow portion of the separation membrane and a part thereof was filtered.

When 30 minutes passed from the start of filtration, the dextran aqueous solution and the filtrate were sampled, and the integrated value of the signal was measured with an RI measuring instrument (RI-8021, manufactured by Tosoh Corporation). The dextran inhibition rate was calculated by the following formula.
Dextran rejection [%] = 100− (integral value of filtrate signal / integral value of signal of dextran aqueous solution × 100)

(Chemical immersion method)
The wet separation membrane was immersed in a 500 ppm sodium hypochlorite aqueous solution at 60 ° C. for 3 hours, and then thoroughly washed with water.

(Measurement method of molecular weight of PVP contained in separation membrane)
The separation membrane was dissolved in a solvent, and then water was added to precipitate a hydrophobic polymer serving as a membrane substrate. The hydrophobic polymer was removed, the liquid from which PVP was eluted was evaporated, and solid PVP was precipitated. The molecular weight of PVP obtained under the following conditions was measured using GPC.

[Measurement condition]
Column: Suprema linear M (diameter 8 mm, length 30 cm)
Column temperature: 40 degrees Solvent: Water / acetonitrile (80/20) +0.15 mol / L NaCl + 0.03 mol / L NaH ₂ PO ₄ , pH = 9
Detector: UV-Photometer GAT-LCD (wavelength 254 nm)
Indicator substance: The molecular weight of Kollidon 90, Kollidon 30, Sokalan HP165 was measured by a light scattering method (described in MJR Cantow, J. Polym. Sci., A-1, 5 (1967)), Used as an indicator substance.

(Measurement method of PVP content ratio in membrane)
¹ H-NMR measurement of the porous membrane was carried out under the following conditions, and the content ratio of PVP was calculated from the obtained spectrum by the following method.

[Measurement condition]
Device: ECS400 (JEOL Ltd.)
Resonance frequency: 399.78 MHz
Solvent: d ₇ -DMF
Measurement temperature: 25 ° C
Sample concentration: about 5% by mass
Integration count: 256 times

(1) In the case of polyether sulfone In the obtained spectrum, the integral value (I _PvP ) of the signal derived from polyvinyl pyrrolidone (4H min) appearing in the vicinity of 2 ppm and the signal derived from the polyether sulfone (4H min) appearing in the vicinity of 8 ppm. It was calculated from the integral value (I _PES ) by the following formula.
PVP content ratio (mass%) = 111 (I _PVP / 4) / {232 (I _PES / 4) +111 (I _PVP / 4)} × 100

(2) In the case of polysulfone In the obtained spectrum, the integral value (I _PvP ) of the signal derived from polyvinyl pyrrolidone (4H min) appearing in the vicinity of 2 ppm and the integral value of the signal derived from polysulfone (4H min) appearing in the vicinity of 7.3 ppm It calculated from the following formula from (I _PSf ).
PVP content ratio (mass%) = 111 (I _PVP / 4) / {443 (I _PSf / 4) +111 (I _PVP / 4)} × 100

(Method for measuring absorbance of extract)
The extraction of the separation membrane was performed in accordance with the elution test of Japanese Pharmacopoeia artificial kidney device approval criteria. That is, the hollow fiber membrane is dried and cut to a length of 2 cm (2 cm square if it is a flat membrane), 1.5 g of the membrane and 150 mL of distilled water for injection are placed in a glass container and heated at 70 ± 5 ° C. for 1 hour. did. After cooling, the membrane was removed and distilled water was added to 150 mL. The absorbance of this solution was measured with a UV measuring instrument at a wavelength showing the maximum absorption wavelength at 220 or more and less than 350 nm, and the absorbance of the extract under that condition was determined.

(Measurement method of pure water permeability)
First, the hollow fiber membrane was thinly cut with a razor or the like in a direction perpendicular to the longitudinal direction of the membrane, and the inner diameter of the membrane was measured using a microscope. Thereafter, one end of a wet hollow fiber membrane having a length of about 10 cm is sealed, and an injection needle is inserted into the hollow portion at the other end, and pure water at 25 ° C. is applied at a pressure of 0.1 MPa from the injection needle in an environment at 25 ° C. Was injected into the hollow portion, the amount of water permeating from the outer surface was measured, and the pure water permeation amount was measured from the following formula. This measurement was performed four times, and the arithmetic average was defined as the pure water permeability of each membrane.

(Preparation of enzyme solution)
The following two types of enzyme solutions were used according to the pore size of the separation membrane.
(1) When the molecular weight of dextran used in the measurement of dextran blocking rate is less than 100,000 (assuming low molecular weight enzymes. Many enzymes are included here)
What diluted commercially available NOVAZYME Savinease 10 times with water was used as the enzyme solution.

(2) When the molecular weight of dextran used in the measurement of the dextran blocking rate is 100,000 or more (assuming a high molecular weight enzyme, proteasome (molecular weight about 2 million), etc.)
A high molecular weight polyethylene oxide aqueous solution is used as a simulated solution of the enzyme solution. A 0.1 mass% aqueous solution of polyethylene oxide (manufactured by Meisei Chemical Industry Co., Ltd., Alcox E-160) was prepared and used as the enzyme solution.

(Measurement method of water permeability during enzyme filtration)
Injection needles were placed at both ends of a wet hollow fiber membrane having a length of about 20 cm, and the injection needle at one end was connected to a pump via a tube so that the enzyme solution could be fed. A tube was attached to the other end of the injection needle, the tip of the tube was placed in a container containing the enzyme solution, and a circuit was constructed so that the enzyme solution that passed through the hollow portion returned to the container. The container for the enzyme solution was installed at the lower part of the separation membrane so that the filtrate filtered from the inner surface to the outer surface side of the separation membrane could be recovered. In addition, the outflow pressure of the enzyme solution from the separation membrane can be measured. The hollow part of the separation membrane was fed so as to flow at a flow rate of 1.0 m / sec of the enzyme solution. At this time, the outflow pressure was adjusted to be 0.05 MPa. Moreover, TMP was adjusted to be 0.1 MPa. In this state, cross-flow filtration was performed in which the enzyme solution was refluxed in the hollow part of the separation membrane and a part was filtered.
Water permeability during enzyme filtration [L / m ² / h] = Enzyme solution filtration per minute [L / min] × 60 [min / h] / A [m ² ]
However, A is the membrane area [m ² ] of the module, TMP = ((inflow pressure) + (outflow pressure)) / 2 [MPa].

(Measurement method of enzyme blocking rate)
The enzyme inhibition rate was determined from the amount of enzyme activity in the filtrate by the following method. In the above enzyme filtration, when 30 minutes passed from the start of filtration, the enzyme solution and the filtrate were sampled, and dimethylcasein and TNBS (2,4,6-trinitrobenzene sulphonic acid) were added, respectively. The absorbance at a wavelength of 425 nm was measured for this sample with an enzyme automatic analyzer (manufactured by Thermo Fisher Scientific). The enzyme inhibition rate was calculated by the following formula.
Enzyme inhibition rate [%] = 100− (filtrate absorbance / enzyme solution absorbance) × 100

(Measurement method of rejection rate including impurities)
The total rejection including impurities was determined from the ultraviolet absorbance of the filtrate by the following method. At the time of the above enzyme filtration, when 30 minutes passed from the start of filtration, the enzyme solution and the filtrate were sampled and each diluted 30 times. The diluted solution was measured for absorbance at a wavelength of 280 nm with a UV measuring instrument (manufactured by SHIMADZU, UVmini 1240). The enzyme inhibition rate was calculated by the following formula.
Blocking rate including impurities [%] = 100− (filtrate absorbance / enzyme solution absorbance) × 100

Example 1
Polyethersulfone (manufactured by BASF, EP6020) is 22% by mass, PVPK17 (manufactured by BASF, LuvitecK17, weight average molecular weight 9000) is 5% by mass, NMP is 43% by mass, and TEG (molecular weight 194) is 30% by mass as a poor solvent. The raw materials to be mixed were dissolved to obtain a film forming stock solution. This film-forming stock solution is extruded from the outside of the double-tube nozzle, and from the center, water is sent as an internal coagulation liquid, and after passing through an idle running time of 1.2 seconds, it is allowed to pass through water at a temperature of 50 ° C. to solidify, A hollow fiber membrane having an inner diameter of 0.75 mm and an outer diameter of 1.30 mm was obtained (thus, the evaluation of spinnability was “◯”).

  The amount of PVP in this hollow fiber membrane was 2.7% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary surface and the secondary surface were 65 degrees and 76 degrees, respectively. . In addition, this hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.057.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The unused hollow fiber membrane had a dextran rejection (A) of 60%. On the other hand, the rejection (B) of the hollow fiber membrane immersed in a 500 ppm sodium hypochlorite aqueous solution at 60 ° C. for 3 hours is 53%, and (A) × 0.5 = 30 <(B), That is, B> A × 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Moreover, the pure water permeation amount (C) of this hollow fiber membrane was 140 L / m ² / h. The water permeation amount (D) during enzyme filtration was 20 L / m ² / h, and D / C> 0.05. Moreover, the enzyme blocking rate was 99.9%, indicating good enzyme filterability.

(Example 2)
A hollow fiber membrane was produced in the same manner as in Example 1 except that K25 (manufactured by BASF, Kollidon K25, weight average molecular weight 31000) was used as the raw material PVP grade instead of K17.

  The amount of PVP in this hollow fiber membrane was 4.1% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary side surface and the secondary side surface were 60 ° and 72 °, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.08.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran rejection (A) of the unused hollow fiber membrane is 70%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 52%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{82L / m 2 / h, 12L} / m 2 / h, D / C> 0.05 It became. The enzyme inhibition rate was 99.9%.

Example 3
A hollow fiber membrane was produced in the same manner as in Example 1 except that K12 (BASF, Kollidon K12PF, weight average molecular weight 2500) was used as the raw material PVP grade instead of K17.

  The amount of PVP in the hollow fiber membrane was 2.0% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary surface and the secondary surface were 70 degrees and 80 degrees, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.02.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran rejection (A) of the unused hollow fiber membrane is 51%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 48%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Moreover, the pure water permeation amount (C) of this hollow fiber membrane and the water permeation amount (D) at the time of enzyme filtration are 185 L / m ² / h and 21 L / m ² / h, respectively, and D / C> 0.05 It became. The enzyme inhibition rate was 99.9%.

Example 4
Polysulfone (manufactured by Solvey, Udel P-3500) was 20% by mass, PVPK17 was 5% by mass, NMP was 45% by mass, and a raw material consisting of 30% by mass of TEG as a poor solvent was mixed and dissolved to obtain a film forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1.

  The amount of PVP in the hollow fiber membrane was 2.5% by mass based on the total amount of polysulfone and PVP, and the contact angles of the primary surface and the secondary surface were 70 degrees and 82 degrees, respectively. The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.03.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran rejection (A) of the unused hollow fiber membrane is 50%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 43%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{116L / m 2 / h, 13L} / m 2 / h, D / C> 0.05 It became. The enzyme inhibition rate was 99.0%.

(Example 5)
A raw material composed of 22% by mass of polyethersulfone, 25% by mass of PVPK17, 23% by mass of NMP, and 30% by mass of TEG as a poor solvent was mixed and dissolved to obtain a film forming stock solution. A hollow fiber membrane was obtained by film formation in the same manner as in Example 1.

  The amount of PVP in this hollow fiber membrane was 12.8% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary surface and the secondary surface were 55 ° and 65 °, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.25.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran rejection (A) of the unused hollow fiber membrane is 71%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 40%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{53L / m 2 / h, 8L} / m 2 / h, D / C> 0.05 It became. The enzyme inhibition rate was 99.9%.

(Example 6)
A raw material solution comprising 20% by mass of polyvinylidene fluoride (manufactured by Arkema, RC10231), 5% by mass of PVPK17, 45% by mass of NMP, and 30% by mass of TEG as a poor solvent was obtained by mixing and dissolving. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1. The amount of PVP in the hollow fiber membrane was 1.8% by mass based on the total amount of polyvinylidene fluoride and PVP, and the contact angles of the primary side surface and the secondary side surface were 65 ° and 77 °, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.06.

  Dextran having a molecular weight of 200,000 was used for measuring the rejection rate. The dextran rejection (A) of the unused hollow fiber membrane is 84%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 74%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{1500L / m 2 / h, 202L} / m 2 / h, D / C> 0.05 It became. The enzyme inhibition rate was 99.5%.

(Example 7)
A raw material composed of 20% by mass of polyvinylidene fluoride (manufactured by Arkema, RC10231), 5% by mass of PVPK17, and 75% by mass of NMP was mixed and dissolved to obtain a film forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1. The amount of PVP in this hollow fiber membrane was 0.5% by mass based on the total amount of polyvinylidene fluoride and PVP, and the contact angles of the primary surface and the secondary surface were 70 degrees and 80 degrees, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.02.

  Dextran having a molecular weight of 200,000 was used for measuring the rejection rate. The dextran rejection (A) of the unused hollow fiber membrane is 80%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 75%, and B> A × It was 0.5, and it was confirmed that there was no significant deterioration due to chemical immersion.

Moreover, the pure water permeation amount (C) of this hollow fiber membrane and the water permeation amount (D) at the time of enzyme filtration were 1750 L / m ² / h and 153 L / m ² / h, respectively, and D / C> 0.05 It became. The enzyme inhibition rate was 99.2%.

(Comparative Example 1)
A raw material consisting of 22% by mass of polyethersulfone, 5% by mass of PVPK30 (manufactured by BASF, LuvitecK30, weight average molecular weight 50000) and 73% by mass of NMP was mixed and dissolved to obtain a film forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1.

  The amount of PVP in the hollow fiber membrane was 1.3% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary surface and the secondary surface were 73 ° and 77 °, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.13.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran blocking rate (A) of the unused hollow fiber membrane is 67%, the blocking rate (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 17%, and B <A × It was 0.5, and it was confirmed that the pore diameter of the membrane was greatly changed by chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{74L / m 2 / h, 8L} / m 2 / h, D / C> 0.05 It became. The enzyme blocking rate was 98.5%.

(Comparative Example 2)
A raw material consisting of 22% by mass of polyethersulfone, 5% by mass of PVPK90 (manufactured by BASF, Luvitec K90, weight average molecular weight 1600000) and 73% by mass of NMP was mixed and dissolved to obtain a membrane forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1.

  The amount of PVP in this hollow fiber membrane was 3.2% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary side surface and the secondary side surface were 65 ° and 70 °, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.15.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The unused hollow fiber membrane has a dextran rejection rate (A) of 87%, and the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 has a rejection rate (B) of 27%, and B <A × It was 0.5, and it was confirmed that the pore diameter of the membrane was greatly changed by chemical immersion.

Further, the pure water permeation amount (C) and the water permeation amount (D) during enzyme filtration of this hollow fiber membrane are 44 L / m ² / h and 6 L / m ² / h, respectively, and D / C> 0.05 It became. The enzyme inhibition rate was 98.6%.

(Comparative Example 3)
A raw material consisting of 22% by mass of polyethersulfone, 5% by mass of PVPK30, 43% by mass of NMP, and 30% by mass of TEG as a poor solvent was mixed and dissolved to obtain a film forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1.

  The amount of PVP in the hollow fiber membrane was 2.5% by mass based on the total amount of polyethersulfone and PVP, and the contact angles of the primary surface and the secondary surface were 70 degrees and 72 degrees, respectively. . The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.13.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The dextran rejection (A) of the unused hollow fiber membrane is 80%, the rejection (B) of the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 is 12%, and B <A × It was 0.5, and it was confirmed that the pore diameter of the membrane was greatly changed by chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{52L / m 2 / h, 7L} / m 2 / h, D / C> 0.05 It became. The enzyme inhibition rate was 97.3%.

(Comparative Example 4)
A raw material composed of 22% by mass of polyethersulfone and 78% by mass of NMP was mixed and dissolved to obtain a film forming stock solution. Using this membrane-forming stock solution, a hollow fiber membrane was produced in the same manner as in Example 1.

  The amount of the hydrophilic polymer in the hollow fiber membrane is 0% by mass with respect to the polyethersulfone, and the contact angles between the primary surface and the secondary surface are 84 degrees and 84 degrees, respectively. It was confirmed that the secondary side was hydrophobic. The hollow fiber membrane was extracted with pure water, and the absorbance of the extract was measured and found to be 0.005.

  Dextran with a molecular weight of 10,000 was used for the blocking rate measurement. The unused hollow fiber membrane has a dextran rejection rate (A) of 66%, and the hollow fiber membrane immersed in hypochlorous acid in the same manner as in Example 1 has a rejection rate (B) of 64%, and B> A × It was 0.5, and there was no influence by chemical immersion.

Further, pure water permeation amount of the hollow fiber membrane (C), water permeation amount at the time of the enzyme filtration (D) are each ^{131L / m 2 / h, 4L} / m 2 / h, D / C <0.05 Thus, the water permeability at the time of enzyme filtration was poor as compared with the system to which a hydrophilic polymer was added. The enzyme blocking rate was 93.5%.

The above results are summarized in Table 1 and Table 2 below.

Claims (16)

A separation membrane comprising a hydrophobic polymer and a hydrophilic polymer,
The hydrophilic polymer contains polyvinylpyrrolidone having a weight average molecular weight of 2000 or more and less than 50000,
A separation membrane, wherein a difference between a contact angle of one surface of the separation membrane and a contact angle of the other surface is 6 degrees or more.   The separation membrane according to claim 1, wherein the polyvinyl pyrrolidone has a weight average molecular weight of 2500 or more and 32000 or less.   The separation membrane according to claim 1 or 2, wherein a difference between a contact angle of one surface of the separation membrane and a contact angle of the other surface is 10 degrees or more. The hydrophobic polymer contains polyethersulfone or polysulfone;
The separation according to any one of claims 1 to 3, wherein a ratio of the polyvinyl pyrrolidone is 2% by mass or more and 8% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyether sulfone or the polysulfone. film.   The separation membrane according to claim 4, wherein a ratio of the polyvinyl pyrrolidone is 2% by mass or more and 4.1% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyether sulfone or the polysulfone. The hydrophobic polymer contains polyvinylidene fluoride;
The separation membrane according to any one of claims 1 to 3, wherein a ratio of the polyvinyl pyrrolidone is 0.2% by mass or more and 2% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyvinylidene fluoride. .   The separation membrane according to claim 6, wherein a ratio of the polyvinyl pyrrolidone is 1.5% by mass or more and 2% by mass or less based on a total amount of the polyvinyl pyrrolidone and the polyvinylidene fluoride.   The separation membrane according to any one of claims 1 to 7, which is a hollow fiber membrane.   A module comprising the separation membrane according to claim 1.   The enzyme concentration method using the separation membrane as described in any one of Claims 1-8.   The filtration method using the separation membrane as described in any one of Claims 1-8. A membrane-forming stock solution containing at least a hydrophobic polymer, a hydrophilic polymer, and a common solvent for dissolving the hydrophobic polymer and the hydrophilic polymer is coagulated in a solution containing water as a main component and separated. Comprising the step of producing a film,
The hydrophilic polymer has a weight average molecular weight of viewing contains polyvinylpyrrolidone less 50000 2000 or more,
A method for producing a separation membrane, wherein a difference between a contact angle of one surface of the separation membrane and a contact angle of the other surface is 6 degrees or more .   The method for producing a separation membrane according to claim 12, wherein the membrane-forming stock solution is a poor solvent for the hydrophobic polymer and further contains a poor solvent having a molecular weight of 300 or less.   The method for producing a separation membrane according to claim 12 or 13, wherein the membrane-forming stock solution is discharged in the form of a hollow fiber.   The manufacturing method of the separation membrane of Claim 14 whose main component of the hollow agent used when discharging the said membrane-forming stock solution in the shape of a hollow fiber is water.   The method for producing a separation membrane according to any one of claims 12 to 15, wherein the idle running time is 0.1 second or more and less than 10 seconds.