阅读说明：本技术 多孔膜 (Porous membrane ) 是由 高园康隼 小室雅廉 于 2020-03-27 设计创作，主要内容包括：本发明的课题在于,提供在制造多孔膜时膜彼此粘着的现象(膜粘连)得以降低的多孔膜。前述课题可通过下述多孔膜来解决,所述多孔膜包含疏水性高分子和亲水性高分子,利用飞行时间型二次离子质谱分析法(TOF-SIMS)对前述多孔膜的表面进行测定时的、源自前述亲水性高分子的离子的计数相对于源自前述疏水性高分子的离子的计数之比的平均值T为1.0≤T。(The present invention addresses the problem of providing a porous film in which the phenomenon of sticking of films to each other (film blocking) is reduced during production of the porous film. The above object can be achieved by a porous membrane comprising a hydrophobic polymer and a hydrophilic polymer, wherein an average value T of a ratio of a count of ions derived from the hydrophilic polymer to a count of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time of flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq.T.)

1. A porous membrane comprising a hydrophobic polymer and a hydrophilic polymer,

an average value T of a ratio of a count of ions derived from the hydrophilic polymer to a count of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq.T.

2. The porous membrane according to claim 1, wherein the ion derived from the hydrophobic macromolecule is C₆H₄O(m/z＝92)。

3. The porous membrane according to claim 1 or 2, wherein the ion derived from the hydrophilic polymer is C₄H₅O₂(m/z＝85)。

4. A porous membrane according to any one of claims 1 to 3, wherein the hydrophilic polymer is a water-insoluble hydrophilic polymer.

5. The porous membrane according to any one of claims 1 to 4, wherein the hydrophilic polymer is electrically neutral.

6. The porous membrane according to any one of claims 1 to 5, wherein the hydrophilic polymer is a methacrylate-based polymer.

7. The porous membrane of claim 6, wherein the methacrylate-based polymer is polyhydroxyethyl methacrylate.

8. The porous membrane according to any one of claims 1 to 7, wherein the hydrophobic polymer is a polysulfone-based polymer.

9. The porous membrane according to claim 8, wherein the polysulfone-based polymer is polyether sulfone.

10. A porous film according to any one of claims 1 to 9, which has a bubble point of 1.4 to 2.0 MPa.

11. The porous film according to any one of claims 1 to 10, wherein the water permeability of pure water is 150 to 500L/hr-m²·bar。

12. A porous membrane according to any one of claims 1 to 11 for use in the removal of viruses.

13. The porous membrane according to any one of claims 1 to 12, wherein a log-elimination ratio (LRV) of a virus is 4 or more.

14. The porous membrane according to any one of claims 1 to 13, wherein the hydrophilic polymer is coated on a substrate membrane comprising the hydrophobic polymer.

15. The porous membrane according to any one of claims 1 to 14, wherein the content of the hydrophilic polymer is 5 to 20% by weight based on the hydrophobic polymer.

16. A method for producing a porous membrane comprising a hydrophobic polymer and a hydrophilic polymer, comprising the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

an average value T of a ratio of a count of ions derived from the hydrophilic polymer to a count of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq.T.

17. A method for reducing blocking of a base material film comprising a hydrophobic polymer after hydrophilization, which comprises the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

an average value T of a ratio of a count of ions derived from the hydrophilic polymer to a count of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq.T.

18. The method of claim 16 or 17, wherein the adjusting procedure comprises: the hydrophilized porous film is subjected to washing and/or high-pressure hot water treatment.

19. The method according to any one of claims 16 to 18, wherein the hydrophilization process comprises: and a step of bundling the base material films and performing hydrophilization treatment.

Technical Field

The present invention relates to a porous film, a method for producing the porous film, and a method for reducing film blocking.

Background

In recent years, treatments using plasma fractionation agents and biopharmaceuticals as drugs have become widespread because of their low side effects and high therapeutic effects. However, since the plasma fractionation preparation is derived from human blood and the biopharmaceutical is derived from animal cells, there is a risk that pathogenic substances such as viruses are mixed into the pharmaceutical.

In order to prevent the virus from being mixed into the pharmaceutical product, it is necessary to remove or inactivate the virus. Examples of the method for removing or inactivating viruses include heat treatment, optical treatment, and chemical treatment. Membrane filtration methods that are effective for all viruses, not only for their thermal properties and chemical properties, have attracted attention in view of problems such as denaturation of proteins, inactivation efficiency of viruses, and contamination of chemicals.

Examples of viruses to be removed or inactivated include polioviruses having a diameter of 25 to 30nm, parvoviruses having a diameter of 18 to 24nm, which are minimal viruses, and HIV viruses having a diameter of 80 to 100nm, which are larger viruses. In recent years, there has been an increasing demand for removal of small viruses such as parvovirus.

The first property required for virus removal membranes is safety. Safety includes safety against contamination with pathogenic substances such as viruses, and safety against contamination with foreign substances such as eluates from virus-removal membranes, in plasma fractionation preparations and biopharmaceuticals.

As safety against contamination with pathogenic substances such as viruses, it is important to remove viruses sufficiently by using a virus-removing membrane. In non-patent document 1, the target clearance (LRV) of mouse parvovirus and porcine parvovirus is 4.

Further, as safety against mixing of foreign matters such as the eluted matter, it is important not to generate the eluted matter from the virus removal membrane.

The second property required for virus removal membranes is productivity. The productivity means that proteins such as albumin having a size of 5nm and globulin having a size of 10nm can be efficiently recovered.

Patent document 1 discloses a virus removal method using a porous membrane containing a hydrophobic polymer and a water-insoluble polymer.

Patent document 2 discloses a virus-removing membrane in which a polyvinylidene fluoride (PVDF) -containing membrane formed by a thermally-excited phase separation method is hydrophilized on the surface by a graft polymerization method.

Documents of the prior art

Patent document

Patent document 1: international publication No. 2016/031834

Patent document 2: international publication No. 2004/035180

Non-patent document 1: PDA Journal of GMP and differentiation in Japan, Vol.7, No.1, p.44(2005)

Disclosure of Invention

Problems to be solved by the invention

The problem to be solved by the present invention is to provide a porous film in which a phenomenon of sticking of films to each other (referred to as "film blocking" in the present specification) is reduced when the porous film is manufactured. Another object of the present invention is to provide a method for reducing blocking of a porous film during production thereof. Further, as another object of the present invention, there is provided a porous hollow fiber membrane in which the membrane blocking (hereinafter, the membrane blocking in the porous hollow fiber membrane may be referred to as "fiber blocking") generated in the production of the porous hollow fiber membrane is reduced, and a method for reducing the membrane blocking generated in the production of the porous hollow fiber membrane.

Means for solving the problems

The present inventors found the following problems: when a porous film is produced by the method disclosed in patent document 1, film blocking occurs in which the films adhere to each other particularly after the porous film is hydrophilized by coating. The inventor takes the first notice that: when membrane sticking occurs between membranes in the production of a membrane module using the membranes, an operation of tearing the membranes from each other occurs in the production process, and as a result, there is a risk that the membrane module production efficiency is deteriorated and the membranes are damaged by the tearing operation, resulting in a reduction in performance thereof. In particular, it was found that: when the porous membrane is a hollow fiber membrane, membrane sticking occurs in which the porous hollow fiber membranes adhere to each other after hydrophilization by coating of the porous hollow fiber membranes performed by bundling the porous hollow fiber membranes, and this problem becomes remarkable. As described above, the present inventors have found a new problem of reducing the occurrence of blocking after hydrophilization, which has not been known in the past, in a porous film, and have conducted intensive studies to solve the problem, and as a result, have found: the present inventors have completed the present invention by adopting a specific configuration as described below, and thus have obtained a porous film with reduced film blocking.

That is, the present invention includes the following embodiments.

[ 1] A porous membrane comprising a hydrophobic polymer and a hydrophilic polymer,

an average value T of a ratio of a count of ions derived from the hydrophilic polymer to a count of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time of flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq.T.

[ 2 ] the porous film according to the above [ 1], wherein the ion derived from the hydrophobic polymer is C₆H₄O(m/z＝92)。

[ 3 ] the porous film according to the above [ 1] or [ 2 ], wherein the ion derived from the hydrophilic polymer is C₄H₅O₂(m/z＝85)。

The porous film according to any one of [ 1] to [ 3 ], wherein the hydrophilic polymer is a water-insoluble hydrophilic polymer.

The porous film according to any one of [ 1] to [ 4 ], wherein the hydrophilic polymer is electrically neutral.

The porous membrane according to any one of [ 1] to [ 5 ], wherein the hydrophilic polymer is a methacrylate-based polymer.

The porous film according to the above [ 6 ], wherein the methacrylate-based polymer is polyhydroxyethyl methacrylate.

The porous membrane according to any one of [ 1] to [ 7 ], wherein the hydrophobic polymer is a polysulfone-based polymer.

The porous membrane according to the above [ 9 ] or [ 8 ], wherein the polysulfone-based polymer is polyether sulfone.

The porous film according to any one of [ 1] to [ 9 ] above, wherein the porous film has a bubble point of 1.4 to 2.0 MPa.

The porous film according to any one of [ 1] to [ 10 ] above, wherein the water permeability of pure water is 150 to 500L/hr · m²·bar。

The porous membrane according to any one of [ 1] to [ 11 ] above, which is used for removing a virus.

The porous membrane according to any one of [ 1] to [ 12 ] above, wherein a log-elimination ratio (LRV) of the virus is 4 or more.

The porous membrane according to any one of [ 1] to [ 13 ], wherein the hydrophilic polymer is applied to a base film comprising the hydrophobic polymer.

The porous film according to any one of [ 1] to [ 14 ], wherein a content of the hydrophilic polymer is 5 to 20% by weight based on the hydrophobic polymer.

A method for producing a porous membrane comprising a hydrophobic polymer and a hydrophilic polymer, comprising the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS), the average value T of the ratio of the count of ions derived from the hydrophilic polymer to the count of ions derived from the hydrophobic polymer is 1.0. ltoreq.T.

[ 17 ] A method for reducing blocking of a base film comprising a hydrophobic polymer after hydrophilization, which comprises the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS), the average value T of the ratio of the count of ions derived from the hydrophilic polymer to the count of ions derived from the hydrophobic polymer is 1.0. ltoreq.T.

The method according to the above [ 16 ] or [ 17 ], wherein the adjusting step comprises: the hydrophilized porous film is subjected to washing and/or high-pressure hot water treatment.

The method according to any one of [ 16 ] to [ 18 ], wherein the hydrophilization step includes: and a step of bundling the substrate films and performing hydrophilization treatment.

The porous membrane according to any one of [ 1] to [ 15 ] above, which has a dense layer at least in a filtration downstream portion of the membrane,

the porous membrane has a slant-type asymmetric structure in which the average pore diameter of the fine pores becomes larger from a filtration downstream portion toward a filtration upstream portion, and

the inclination index of the average pore diameter inclined from the dense layer to the coarse layer is 0.5 to 12.0.

The porous film according to [ 20 ] above, wherein the dense layer has pores of 10nm or less in an amount of 8.0% or less.

The porous membrane according to the above [ 20 ] or [ 21 ], wherein a value of standard deviation/average pore diameter of the pore diameter in the dense layer is 0.85 or less.

The porous film according to any one of [ 20 ] to [ 22 ], wherein the dense layer has a ratio of pores having a size of more than 10nm and 20nm or less of 20.0% to 35.0%.

The porous membrane according to any one of [ 20 ] to [ 23 ] above, wherein a porosity in the dense layer is 30.0% or more and 45.0% or less.

The porous film according to any one of [ 20 ] to [ 24 ], wherein the dense layer has a thickness of 1 to 8 μm.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, a porous film in which film blocking is reduced in the production of the porous film can be provided. This enables not only the membrane module to be efficiently manufactured, but also the performance of the porous membrane to be prevented from being degraded.

Detailed Description

The present embodiment (hereinafter, may be referred to as "embodiment") will be described below. The present invention is not limited to the following embodiments, and various modifications can be made within the scope of the present invention. The embodiments described below are illustrative of methods for refining the technical idea of the present invention, and the like, but are not limited to these illustrations.

< porous film >

In one embodiment, the porous membrane contains a hydrophobic polymer and a hydrophilic polymer, and the average value T of the ratio of the number of ions derived from the hydrophilic polymer to the number of ions derived from the hydrophobic polymer when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq. T.

In one embodiment, the porous film is not particularly limited as long as the average value T of the porous film is set to an appropriate value, thereby improving the blocking of the film, and a flat film or a hollow fiber film can be exemplified. From the viewpoint of the degree of improvement in membrane blocking, a hollow fiber membrane is preferred. In the case of a hollow fiber membrane, as the surface of the membrane, there are an inner surface and an outer surface as long as the average value T of the outer surface satisfies 1.0. ltoreq. T. In the case of a flat film, as long as the average value T of either one of the two surfaces present shows the value of the present invention, it is preferable that both surfaces of the flat film show the value of the present invention.

The porous film of the present embodiment has reduced film blocking during production. This enables not only the membrane module to be efficiently manufactured, but also the performance of the porous membrane to be prevented from being degraded. In one embodiment, the porous membrane suppresses the decrease in Flux over time due to adsorption of proteins during filtration. Further, in one embodiment, the porous membrane has high virus removal performance.

The porous membrane of the present embodiment contains a hydrophobic polymer and a hydrophilic polymer. The porous membrane is not particularly limited as long as it contains a hydrophobic polymer and a hydrophilic polymer, and the hydrophobic polymer and the hydrophilic polymer may be blended to form a membrane, and the membrane obtained by the blend membrane formation (blended membrane) may be further covered with a hydrophilic polymer. In addition, a membrane in which a substrate membrane formed of a hydrophobic polymer is hydrophilized with a hydrophilic polymer by, for example, coating or grafting is also included in the porous membrane.

In the present specification, the hydrophobic polymer refers to a polymer having a contact angle of more than 90 degrees when PBS (a product obtained by dissolving 9.6g of Dulbecco PBS (-) powder "NISSUI" sold by Nikkiso pharmaceutical Co., Ltd. in water and making the total amount to be 1L) is brought into contact with a film of the polymer.

In one embodiment, the hydrophobic polymer is not particularly limited as long as it is a hydrophobic polymer, and examples thereof include polyolefin, polyamide, polyimide, polyester, polyketone, polyvinylidene fluoride (PVDF), polymethyl methacrylate, polyacrylonitrile, and polysulfone-based polymers. From the viewpoint of high film-forming properties and control of the film structure, polysulfone-based polymers are preferred.

The hydrophobic polymers may be used alone or in combination of two or more.

Examples of the polysulfone-based polymer include polysulfone (PSf) having a repeating unit represented by the following formula 1 and Polyethersulfone (PES) having a repeating unit represented by the following formula 2, and polyethersulfone is preferable from the viewpoint of film-forming properties.

Formula 1:

formula 2:

the polysulfone-based polymer may contain a substituent such as a functional group or an alkyl group in the structure of formula 1 or 2, and a hydrogen atom of the hydrocarbon skeleton may be substituted with another atom or substituent such as a halogen atom.

The polysulfone-based polymer may be used alone or in combination of two or more.

In one embodiment, the porous membrane contains a hydrophilic polymer.

In one embodiment, the porous membrane can be hydrophilized by the presence of a hydrophilic polymer on the pore surface of the base membrane containing a hydrophobic polymer, from the viewpoint of preventing a rapid decrease in filtration rate due to membrane clogging caused by protein adsorption. The substrate film is a film containing a hydrophobic polymer and to be coated, grafted, or crosslinked. The substrate film may contain a hydrophilic polymer. For example, the blend film is sometimes also a substrate film.

Examples of the method for hydrophilizing the substrate film include coating, grafting reaction, and crosslinking reaction of the substrate film formed of a hydrophobic polymer after film formation. Further, after the blend film of the hydrophobic polymer and the hydrophilic polymer is formed into a film, the blend film may be covered with the hydrophilic polymer by coating, a graft reaction, a crosslinking reaction, or the like.

In the present specification, the hydrophilic polymer refers to a polymer having a contact angle of 90 degrees or less when PBS (a product obtained by dissolving 9.6g of Dulbecco PBS (-) powder "NISSUI" sold by Nikkiso pharmaceutical Co., Ltd. in water and making the total amount of the powder 1L) is brought into contact with a film of the polymer.

The contact angle is preferably 60 degrees or less, and more preferably 40 degrees or less. When the hydrophilic polymer having a contact angle of 60 degrees or less is contained, the porous membrane is easily wetted with water, and when the hydrophilic polymer having a contact angle of 40 degrees or less is contained, the tendency to be easily wetted with water is more remarkable.

The contact angle is an angle formed between the film and the surface of the water droplet when the water droplet is dropped on the surface of the film, and is defined in JIS R3257.

In one embodiment, the hydrophilic polymer may be a water-insoluble hydrophilic polymer. Water insoluble means: the effective membrane area reaches 3cm²The membrane module assembled in the above manner, when 100mL of 25 ℃ pure water was filtered by dead-end filtration at a constant pressure of 2.0bar, the dissolution rate was 0.1% or less.

The dissolution rate was calculated by the following method.

The filtrate obtained by filtering 100mL of 25 ℃ pure water was collected and concentrated. The amount of carbon was measured using the obtained concentrated solution with a total organic carbon instrument TOC-L (manufactured by Shimadzu corporation), and the dissolution rate from the membrane was calculated.

In the present specification, the water-insoluble hydrophilic polymer refers to a substance satisfying the contact angle and the dissolution rate. The water-insoluble hydrophilic polymer includes not only a hydrophilic polymer whose substance itself is water-insoluble but also a hydrophilic polymer which is water-soluble but is water-insoluble in the production process. That is, even a water-soluble hydrophilic polymer is included in the water-insoluble hydrophilic polymer of the present embodiment as long as the water-soluble hydrophilic polymer satisfies the contact angle and the dissolution rate is satisfied in the constant-pressure dead-end filtration after the membrane module is assembled by water-insolubilization in the production process. The water-insoluble hydrophilic polymer obtained by making a water-soluble hydrophilic polymer water-insoluble in the film production process may be, for example, the following: a substance obtained by coating a water-soluble hydrophilic polymer obtained by copolymerizing a monomer having an azide group in the side chain with a hydrophilic monomer such as 2-methacryloyloxyethyl phosphorylcholine onto a base film of a hydrophobic polymer and then covalently bonding the water-soluble hydrophilic polymer to the base film by heat treatment, thereby insolubilizing the water-soluble hydrophilic polymer. In addition, a hydrophilic monomer such as 2-hydroxyalkyl acrylate may be graft-polymerized to the base film of the hydrophobic polymer.

The hydrophilic polymer is preferably electrically neutral from the viewpoint of preventing adsorption of protein as a solute.

In the present embodiment, the term "charge neutrality" means that no charge is present in a molecule or that the amount of cations and anions in a molecule is equal.

Examples of the hydrophilic polymer include vinyl polymers.

Examples of the vinyl polymer include homopolymers such as hydroxyethyl methacrylate, hydroxypropyl methacrylate, dihydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, polyethylene glycol methacrylate, vinylpyrrolidone, acrylamide, dimethylacrylamide, gluconoxyethyl methacrylate, 3-sulfopropylmethacryloyloxyethyl dimethyl ammonium betaine, 2-methacryloyloxyethyl phosphorylcholine, and 1-carboxydimethylmethacryloyloxyethyl methyl ammonium; random copolymers, graft copolymers and block copolymers of styrene, ethylene, propylene, propyl methacrylate, butyl methacrylate, ethylhexyl methacrylate, octadecyl methacrylate, benzyl methacrylate, methoxyethyl methacrylate and other hydrophobic monomers with hydroxyethyl methacrylate, hydroxypropyl methacrylate, dihydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, polyethylene glycol methacrylate, vinyl pyrrolidone, acrylamide, dimethylacrylamide, gluconoxyethyl methacrylate, 3-sulfopropylmethacryloyloxyethyl dimethylammonium betaine, 2-methacryloyloxyethyl phosphorylcholine, 1-carboxydimethylmethacryloyloxyethyl methyl ammonium and other hydrophilic monomers, the methacrylate-based polymer is preferred, and polyhydroxyethyl methacrylate is more preferred.

Examples of the vinyl polymer include copolymers of a cationic monomer such as dimethylaminoethyl methacrylate or diethylaminoethyl methacrylate with an anionic monomer such as acrylic acid, methacrylic acid, vinylsulfonic acid, sulfopropyl methacrylate or phosphoryloxyethyl methacrylate and the above hydrophobic monomer, and polymers containing the anionic monomer and the cationic monomer in such an amount as to exhibit electroneutrality may be used.

Examples of the hydrophilic polymer include cellulose as a polysaccharide and cellulose triacetate as a derivative thereof. The polysaccharide or a derivative thereof may be obtained by crosslinking hydroxyalkyl cellulose or the like.

The hydrophilic polymer may be polyethylene glycol or a derivative thereof, or a block copolymer of ethylene glycol and the hydrophobic monomer; random copolymers and block copolymers of ethylene glycol and propylene glycol, ethylbenzyl glycol, and the like. In addition, the polyethylene glycol and the copolymer may be non-water-soluble by substituting a hydrophobic group for one end or both ends thereof.

Examples of the compound in which a single terminal or both terminals of polyethylene glycol are substituted with a hydrophobic group include α, ω -dibenzylpolyethylene glycol, α, ω -didodecyl polyethylene glycol, and the like, and a copolymer of polyethylene glycol and a hydrophobic monomer such as dichlorodiphenyl sulfone having a halogen group at both terminals in the molecule, and the like can be used.

Examples of the hydrophilic polymer include polyethylene terephthalate, polyether sulfone, and the like obtained by polycondensation, in which a hydrogen atom in the main chain of polyethylene terephthalate, polyether sulfone, and the like is substituted with a hydrophilic group, and hydrophilization is performed. As the hydrophilized polyethylene terephthalate, polyether sulfone, or the like, a hydrogen atom in the main chain may be substituted with an anionic group or a cationic group, and the anionic group and the cationic group may be in the same amount.

The hydrophilic polymer may be a polymer obtained by ring-opening an epoxy group of a bisphenol a type or a novolac type epoxy resin; a polymer obtained by introducing a vinyl polymer, polyethylene glycol, or the like into an epoxy group.

Further, silane coupling may be performed.

The hydrophilic polymer may be used alone or in combination of two or more.

As the hydrophilic polymer, homopolymers of hydroxyethyl methacrylate, hydroxypropyl methacrylate, and dihydroxyethyl methacrylate are preferable from the viewpoint of ease of production; a random copolymer of a hydrophilic monomer such as 3-sulfopropylmethacryloyloxyethyldimethylammonium betaine, 2-methacryloyloxyethylphosphorylcholine, and 1-carboxydimethylmethacryloyloxyethylmethanammonium, and a hydrophobic monomer such as butyl methacrylate or ethylhexyl methacrylate, and is more preferably a homopolymer of hydroxyethyl methacrylate or hydroxypropyl methacrylate from the viewpoints of ease of solvent selection of a coating solution when a hydrophilic polymer is coated, dispersibility in the coating solution, and handling; random copolymers of hydrophilic monomers such as 3-sulfopropylmethacryloyloxyethyldimethylammonium betaine and 2-methacryloyloxyethylphosphorylcholine and hydrophobic monomers such as butyl methacrylate and ethylhexyl methacrylate.

The content of the hydrophilic polymer is not particularly limited as long as the film blocking does not occur at the time of producing the porous film, and from the viewpoint of water permeability and virus removal performance, the content is 5 wt% or more as a lower limit value, 6 wt% or more as another embodiment, 7 wt% or more as another embodiment, 8 wt% or more as another embodiment, 9 wt% or more as another embodiment, and 10 wt% or more as another embodiment, with respect to the hydrophobic polymer. The upper limit of the amount of the hydrophobic polymer is 20 wt% or less, and the other is 19 wt% or less. Still another embodiment may be 18 wt% or less, still another embodiment may be 17 wt% or less, still another embodiment may be 16 wt% or less, still another embodiment may be 15 wt% or less, and still another embodiment may be 14 wt% or less. The ratio of the hydrophilic polymer to the hydrophobic polymer in the porous film hydrophilized by coating (i.e., the weight of the hydrophilic polymer/the weight of the hydrophobic polymer × 100) is sometimes referred to as a coating rate. The "weight of the hydrophilic polymer" in the calculation formula of the coating rate means the weight of the hydrophilic polymer applied to the base film, and does not include the weight of the hydrophilic polymer mixed into the base film when the hydrophobic polymer and the hydrophilic polymer are blended to form a film.

The porous film or the base film of the present embodiment may be formed by blending a hydrophilic polymer and a hydrophobic polymer.

The hydrophilic polymer used for blend film formation is not particularly limited as long as it is compatible with the hydrophobic polymer in a good solvent, and polyvinylpyrrolidone or a copolymer containing vinylpyrrolidone is preferable as the hydrophilic polymer.

Specific examples of the polyvinylpyrrolidone include LUVITEC (trade name) K60, K80, K85, K90 and the like sold by BASF corporation, and LUVITEC (trade name) K80, K85, K90 are preferable.

The copolymer containing vinylpyrrolidone is preferably a copolymer of vinylpyrrolidone and vinyl acetate from the viewpoint of compatibility with a hydrophobic polymer and suppression of interaction between a protein and a membrane surface.

The copolymerization ratio of vinylpyrrolidone to vinyl acetate is preferably 6:4 to 9:1 from the viewpoint of adsorption of a protein to the surface of a membrane and interaction with a polysulfone-based polymer in the membrane.

Specific examples of the copolymer of vinylpyrrolidone and vinyl acetate include LUVISKOL (trade name) VA64 and VA73 sold by BASF corporation.

The hydrophilic polymer may be used alone or in combination of two or more.

In one embodiment, in the case where a water-soluble hydrophilic polymer is used in the blend film formation, it is preferable to wash the blend film with hot water after the blend film formation from the viewpoint of suppressing elution of foreign matter from the film during filtration. By washing, the hydrophilic polymer insufficiently entangled with the hydrophobic polymer is removed from the membrane, and elution during filtration is suppressed.

As the hot water washing, high-pressure hot water treatment or warm water treatment after coating may be performed.

In one embodiment, the average value T of the ratio of the count of ions derived from a hydrophilic polymer to the count of ions derived from a hydrophobic polymer when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS) is 1.0. ltoreq. T.

If the average value T is 1.0 or more, film blocking is reduced. As a mechanism of reducing the film blocking, the following can be exemplified: for example, when the hydrophobic polymer is a polysulfone-based polymer and the hydrophilic polymer is a methacrylate-based polymer, if the average value T is 1.0 or more, the hydroxyl groups of the methacrylate-based polymer are disposed on the surface side of the membrane more than when the average value T is less than 1.0, and the hydroxyl groups facing the surface side are bonded to water molecules in the air to form a layer of water molecules on the surface, thereby preventing the adhesion between the membranes and the entanglement of the polymers.

The average value T is measured by the method described in examples as "measurement of the ion count ratio".

As ions derived from the hydrophobic polymer to be counted, ions most suitable for expressing the hydrophobic polymer are selected, and spectra are detected using the selected ions as detection ions. For example, in the case of polyethersulfones, C may be₆H₄O(m/z 92) is used as the detector ion, in the case of PVDF, C may be used₃F(m/z＝55)、C₄F (m/z 67) was used as the detection ion. As criteria for selecting the focused ion, there are: ions that do not overlap with other components constituting the membrane, ions that reflect the characteristics of the substance.

As the ions derived from the hydrophilic polymer to be counted, ions most suitable for expressing the hydrophilic polymer are selected and detected as detection ions. For example, in the case of polyhydroxyethylmethacrylate, C may be added₄H₅O₂(m/z 85) as the detector ion, in the case of polyvinylpyrrolidone, C may be used₄H₆NO (m/z 84) is used as the detector ion, in the case of polyvinylacetate, C may be used₂H₃O₂(m/z 59) was used as the detection ion.

In one embodiment, the average value T is not particularly limited as long as it is a value at which film blocking is reduced in the production of a film, and the upper limit may be 7.0 or less, 6.0 or less, 5.0 or less, 4.0 or less, 3.0 or less, or 2.0 or less, and the lower limit may be 1.0 or more, 1.5 or more, 2.0 or more, or 2.5 or more.

In one embodiment, the porous film has reduced film blocking during manufacture. In particular, the film blocking of the porous film after the hydrophilization treatment is reduced. The degree of reduction of the film blocking is not particularly limited, and for example, in the production of a film assembly, the film blocking is not particularly limited as long as the film blocking is reduced to such a degree that a step of tearing the film is not necessary. For example, if 4% of the films constituting a bundle of films can be collected without resistance from the bundle of films bundled and hydrophilized, it can be judged that the blocking of the films is reduced.

In one embodiment, the porous membrane has a tilted asymmetric structure. The inclined asymmetric structure means that: the average pore diameter of the fine pores may be configured to increase from the filtration downstream portion to the filtration upstream portion of the membrane, and may be configured to have a local slight inversion of the average pore diameter due to structural unevenness or measurement error, as long as the average pore diameter tends to increase from the filtration downstream portion to the filtration upstream portion in the film thickness direction. The inclination index of the average pore diameter inclined from the dense layer to the coarse layer is 0.5 to 12.0.

In this specification, when the liquid is passed through the inner surface side of the porous membrane, the region from the inner surface to 10% of the membrane thickness is the upstream region of filtration, and the region from the outer surface to 10% of the membrane thickness is the downstream region of filtration.

In the present specification, a porous membrane is defined as a dense layer in a visual field having an average pore diameter of 50nm or less, and a coarse layer in a visual field having an average pore diameter of more than 50 nm.

In the present specification, the dense layer and the coarse layer of the porous membrane are determined by imaging the cross section of the membrane with a Scanning Electron Microscope (SEM). For example, the imaging magnification is set to 50,000 times, and the field of view is set horizontally with respect to the film thickness direction at an arbitrary portion of the film cross section. After the set one field of view is photographed, the photographing field of view is horizontally moved with respect to the film thickness direction, and the next field of view is photographed. This photographing operation is repeated to photograph the cross section of the film without a gap, and the obtained photographs are combined to obtain one photograph of the cross section of the film. In the sectional photograph, the average pore diameter per 1 μm (2 μm in the direction perpendicular to the film thickness direction) x (1 μm from the filter downstream surface toward the filter upstream surface side in the film thickness direction) range was calculated from the filter downstream surface toward the filter upstream surface side.

In the present specification, the average pore diameter is calculated by a method using image analysis. Specifically, the binarization processing of the hole portion and the solid portion is performed using an Image-pro plus manufactured by Media Cybernetics. The hole and the solid are recognized based on the brightness, and the unrecognizable part and noise are corrected by a drawing tool. The porous structure observed at the depth of the pore portion, which is an edge portion of the outline of the pore portion, is identified as the pore portion. After the binarization processing, the aperture was calculated assuming that the area value of empty hole/1 is a true circle. All the pores were treated, and the average pore diameter was calculated for each range of 1. mu. m.times.2. mu.m. The number of the holes cut at the end of the visual field is also counted.

In the present specification, the inclination index of the average pore diameter inclined from the dense layer to the coarse layer is calculated from a first visual field defined as the dense layer and a second visual field defined as the coarse layer adjacent thereto. The region where the average pore diameter is 50nm or less is shifted from the visual field defined as a dense layer to the visual field defined as a coarse layer having an average pore diameter of more than 50 nm. The field of view of the adjacent dense and coarse layers was used to calculate the tilt index. Specifically, the inclination index of the average pore diameter inclined from the dense layer to the coarse layer can be calculated by the following formula.

The gradient index (nm/μm) of the average pore diameter from the dense layer to the coarse layer is (average pore diameter (nm) of the coarse layer (second field) — average pore diameter (nm) of the dense layer (first field))/1 (μm)

In one embodiment, the porous membrane has a dense layer and a coarse layer. In one embodiment, the porous membrane has a coarse layer on the filtration upstream face side relative to the dense layer, and the dense layer is adjacent to the coarse layer.

In one embodiment, the porous membrane has a coarse layer on the inner surface portion and a dense layer on the outer surface portion. In this case, the inner surface portion is a filtration upstream portion, and the outer surface portion is a filtration downstream portion.

In one embodiment, the dense layer is not particularly limited as long as it is present at least in a portion downstream of filtration. For example, the starting point of the dense layer may be present at the downstream portion of filtration, and the end point of the dense layer may be present at a position beyond the downstream portion of filtration on the upstream face side of filtration.

In one embodiment, the thickness of the dense layer is not particularly limited as long as it is a thickness capable of removing viruses, and examples thereof include 1 to 10 μm, 1 to 8 μm as another embodiment, and 2 to 8 μm as another embodiment.

In one embodiment, the proportion (%) of pores having a size of 10nm or less in the dense layer of the porous membrane is preferably 8.0% or less, and more preferably 5.0% or less.

The presence ratio (%) of the fine pores of 10nm or less in the dense layer means: the value calculated by the following formula based on the analysis of the SEM image is defined as the average of all the visual fields of the dense layer.

(defined as the total number of pores having a pore diameter of 10nm or less in one visual field of the dense layer/the total number of pores in the same visual field) × 100

In one embodiment, the proportion (%) of pores having a size of more than 10nm and 20nm or less in the dense layer of the porous membrane is preferably 20.0% or more and 35.0% or less.

The proportion (%) of pores having a size of more than 10nm and 20nm or less in the dense layer is: the value calculated by the following formula based on the analysis of the SEM image is defined as the average of all the visual fields of the dense layer.

(defined as the total number of pores having a pore diameter of more than 10nm and not more than 20nm in one visual field of the dense layer/the total number of pores in the same visual field) × 100

In one embodiment, the porosity (%) in the dense layer of the porous membrane is preferably 30.0% or more and 45.0% or less.

The porosity (%) in the dense layer means: analysis of the SEM images described above defined as the average of all the fields of view of the dense layer of the values calculated as follows.

(defined as the total area of the pores in one field of view/the area of the same field of view of the dense layer) × 100

It is also important that the standard deviation/mean pore size of the pore size in the dense layer is small in order to maintain virus removal performance and achieve high efficiency protein recovery. A small standard deviation/average pore diameter of the pore diameter in the dense layer means that too large pores and too small pores are present in a small amount. According to the studies of the present inventors, in order to suppress clogging of protein monomers in the dense layer and achieve efficient protein recovery while maintaining virus removal performance, the standard deviation/average pore diameter of the pore diameter in the dense layer is preferably 0.85 or less, more preferably 0.70 or less.

In one embodiment, a porous membrane may be used to filter the protein solution. Specifically, for example, viruses contained in the protein solution can be removed by filtration. At this time, the water permeation amount of pure water is the standard of the filtration rate Flux of the protein solution. The protein solution has a lower water permeability than pure water because of a higher viscosity than pure water, but the higher the water permeability of pure water, the higher the filtration rate of the protein solution. Therefore, in one embodiment, the porous membrane can be a membrane for protein treatment that can achieve more efficient protein recovery by increasing the water permeability of pure water.

The mechanism of virus removal by the virus removal membrane is considered as follows. The solution containing the virus passes through a virus removal layer formed by overlapping a plurality of virus capturing surfaces perpendicular to the direction of the passage. The size of the wells in this plane must be distributed, and the virus is captured by the portion of the wells that is smaller than the size of the virus. In this case, although the virus trapping rate of one surface is low, since the surfaces are laminated in multiple layers, high virus removal performance can be achieved. For example, even if the virus trapping rate of one surface is 20%, the total virus trapping rate is 99.999% by overlapping 50 layers of the surface. In the region with an average pore diameter of 50nm or less, most viruses can be trapped.

In one embodiment, the water permeability of pure water in the membrane for protein treatment is preferably 150 to 500L/hr · m²·bar。

The water permeability of pure water is 150L/hr m²And bar or more, thereby enabling efficient recovery of proteins. Further, the water permeability of pure water was adjusted to 500L/hr · m²Bar or less, thereby enabling the sustained virus removal performance to be exhibited.

In the present specification, the water permeability of pure water is measured by the method described in the examples as "water permeability measurement".

In one embodiment, the porous membrane is made of a hydrophobic polymer hydrophilized with a hydrophilic polymer by the above method.

In the present embodiment, the Bubble Point (BP) is: when pressure is applied with air from the upstream side of filtration of a membrane impregnated with hydrofluoroether, pressure is generated when bubbles are generated from the downstream side of filtration. When air is permeated through the film impregnated with the solvent, the smaller the diameter of the pores, the higher the applied pressure is. The maximum pore size of the membrane can be evaluated by evaluating the pressure at which air first permeates through.

The bubble point is shown below in relation to the maximum pore size.

D_BP＝4γ·cosθ/BP

Here, D_BPRepresents the maximum pore diameter, γ represents the surface tension (N/m) of the solvent, cos θ represents the contact angle (-) of the solvent with the membrane, and BP represents the bubble point (MPa).

When used as a virus-removing membrane, the rate of parvovirus clearance of the porous membrane is preferably 4 or more, more preferably 5 or more, as LRV. The parvovirus is preferably a virus close to the virus mixed in the actual purification step, and is preferably Porcine Parvovirus (PPV) in view of ease of operation.

The maximum pore diameter of the membrane is related to LRV, and the higher the bubble point, the higher the virus removal performance, and in order to maintain the permeability of the protein as a useful component and exert the virus removal performance, and from the viewpoint of controlling the water permeability of pure water, the bubble point is preferably 1.40 to 2.00MPa, more preferably 1.40 to 1.80MPa, further preferably 1.50 to 1.80MPa, and further preferably 1.60 to 1.80 MPa.

In the present embodiment, the bubble point can be measured by the method described in the examples as "bubble point measurement".

Parvovirus clearance can be measured by the method described in the examples as "porcine parvovirus clearance measurement".

< method for producing porous film and method for reducing film blocking >

One embodiment relates to a method for producing a porous membrane containing a hydrophobic polymer and a hydrophilic polymer, including the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS), the average value T of the ratio of the count of ions derived from the hydrophilic polymer to the count of ions derived from the hydrophobic polymer is 1.0. ltoreq.T.

One embodiment relates to a method for reducing blocking of a base material film comprising a hydrophobic polymer after hydrophilization, the method comprising the steps of:

a hydrophilization step of hydrophilizing a base film comprising a hydrophobic polymer with a hydrophilic polymer to obtain a hydrophilized porous film; and

a conditioning step of treating the hydrophilized porous film in such a manner that,

when the surface of the porous membrane is measured by time-of-flight secondary ion mass spectrometry (TOF-SIMS), the average value T of the ratio of the count of ions derived from the hydrophilic polymer to the count of ions derived from the hydrophobic polymer is 1.0. ltoreq.T.

In one embodiment, the hydrophilization step is a coating step of a substrate film described below. In one embodiment, the conditioning step is a cleaning step and/or a high-pressure hot water treatment step of the coated substrate film described below. Either or both of the cleaning step and the high-pressure hot water treatment step may be performed.

Specific examples of the method for producing a porous film and the method for reducing blocking of the film will be described below.

In one embodiment, the porous film is not particularly limited, and may be produced, for example, in the following manner, or may be produced while reducing blocking of the film. The case of using a polysulfone-based polymer as the hydrophobic polymer will be described below.

For example, in the case of a hollow fiber membrane, a polysulfone-based polymer, a solvent, and a non-solvent are mixed, dissolved, and deaerated to obtain a liquid as a membrane-forming stock solution, and the liquid is ejected simultaneously with a core liquid from an annular portion and a central portion of a double-tube nozzle (spinneret), and introduced into a coagulation bath through an air-forwarding portion to form a membrane. The obtained film was washed with water, wound, and the liquid in the hollow portion was removed, followed by heat treatment and drying. Thereafter, hydrophilization treatment is performed.

In the case of flat membrane, for example, a polysulfone-based polymer, a solvent, and a non-solvent are mixed and dissolved to prepare a solution, which is then deaerated to prepare a membrane-forming stock solution, and the solution is formed into a membrane by a typical process known in the art. In a typical process, a film-forming dope is cast on a support, and the cast film is introduced into a non-solvent to cause phase separation. Next, the film is put in a substance (for example, water, alcohol, or a mixture thereof) which is a non-solvent for the polymer, and the solvent is removed to dry the film, whereby a porous film can be obtained. Thereafter, the resulting film is subjected to hydrophilization treatment.

The solvent used in the film-forming solution can be widely used as long as it is a good solvent for polysulfone-based polymers such as N-methyl-2-pyrrolidone (NMP), N-Dimethylformamide (DMF), N-dimethylacetamide (DMAc), dimethyl sulfoxide, and ∈ -caprolactam, and preferably an amide-based solvent such as NMP, DMF, and DMAc, and more preferably NMP.

The non-solvent is preferably added to the film-forming dope. Examples of the non-solvent used in the film-forming solution include glycerin, water, and a diol compound is preferable.

The diol compound is a compound having hydroxyl groups at both ends of the molecule, and is preferably a compound represented by formula 3 below and having an ethylene glycol structure in which the repeating unit n is 1 or more.

Examples of the diol compound include diethylene glycol (DEG), triethylene glycol (treg), tetraethylene glycol (TetraEG), and polyethylene glycol (PEG), and DEG, treg, and TetraEG are preferable, and treg is more preferable.

Formula 3:

although the detailed mechanism is not clear, the addition of the non-solvent to the film-forming dope increases the viscosity of the film-forming dope, and suppresses the diffusion rate of the solvent and the non-solvent in the coagulation liquid, thereby facilitating the control of coagulation, facilitating the control of the structure preferable as a porous film, and being suitable for forming a desired structure.

The ratio of the solvent/non-solvent in the film-forming solution is preferably 20/80-80/20 in terms of mass ratio.

The concentration of the polysulfone-based polymer in the membrane-forming solution is preferably 15 to 35% by mass, more preferably 20 to 30% by mass, from the viewpoint of the membrane strength and the permeability.

The film-forming dope is obtained by dissolving a polysulfone-based polymer, a good solvent and a non-solvent at a certain temperature while stirring. The compound containing nitrogen of tertiary nitrogen or less (NMP, DMF, DMAc) is oxidized in air, and further oxidation is likely to occur when the compound is heated, and therefore the temperature at the time of dissolution is preferably 80 ℃. The film-forming dope is preferably prepared in an inert gas atmosphere or under vacuum. The inert gas includes nitrogen gas, argon gas, and the like, and nitrogen gas is preferable from the viewpoint of production cost.

The film-forming dope is preferably deaerated from the viewpoint of suppressing formation of defects after film formation and from the viewpoint of preventing yarn breakage during spinning in the case of a hollow fiber film.

The defoaming step can be performed as follows. The pot containing the completely dissolved film-forming stock solution was depressurized to 2kPa, and left to stand for 1 hour or more. This operation was repeated 7 times or more. In order to improve the defoaming efficiency, the solution may be stirred during defoaming.

(method for producing hollow fiber Membrane)

The hollow fiber membrane is produced by using the membrane-forming dope through the following steps.

The film-forming dope is preferably removed from the foreign matter until it is discharged from the nozzle. By removing foreign matter, yarn breakage during spinning can be prevented, and the structure of the film can be controlled. In order to prevent the contamination of foreign matter such as a seal from the film-forming stock solution tank, it is also preferable to provide a filter before the film-forming stock solution is discharged from the nozzle. The filter having different pore diameters may be provided in multiple stages, and is not particularly limited, and for example, a mesh filter having a pore diameter of 30 μm and a mesh filter having a pore diameter of 10 μm are preferably provided in this order from the side close to the membrane-forming raw liquid tank.

The composition of the core solution used for film formation is preferably the same as that of the good solvent used for the film-forming dope and the solidification solution.

For example, if NMP is used as a solvent of the membrane-forming dope and NMP/water is used as a good solvent/non-solvent of the coagulating liquid, the core liquid is preferably composed of NMP and water.

If the amount of the solvent in the core liquid is increased, the solidification is delayed and the film structure is formed slowly, and if the amount of water is increased, the solidification is accelerated. In order to obtain a preferable membrane structure of the porous hollow fiber membrane by appropriately performing solidification and controlling the membrane structure, the ratio of the good solvent/water in the core liquid is preferably 60/40 to 80/20 in terms of a mass ratio.

In order to form a suitable pore diameter, the spinneret temperature is preferably 25 to 50 ℃.

The film-forming dope is ejected from the nozzle and introduced into the coagulation bath through the air-moving section. The residence time of the air traveling section is preferably 0.02 to 1.0 second. By setting the retention time to 0.02 seconds or more, sufficient coagulation can be achieved until the coagulation bath is introduced, and an appropriate pore diameter can be formed. By setting the residence time to 1 second or less, excessive progress of coagulation can be prevented, and precise control of the membrane structure in the coagulation bath can be performed.

Further, the air-traveling portion is preferably sealed. Although the detailed mechanism is not clear, it is considered that: by sealing the air moving part, a vapor atmosphere of water and a good solvent is formed in the air moving part, and the phase separation is gradually performed before the film-forming raw liquid is introduced into the coagulation bath, so that the formation of excessively small pores is suppressed, and the CV value of the pore diameter is also decreased.

The spinning speed is not particularly limited as long as a defect-free film can be obtained, and is preferably as slow as possible in order to slow down the liquid exchange between the film and the coagulation bath in the coagulation bath and to control the film structure. Therefore, from the viewpoint of productivity and solvent exchange, it is preferably 4 to 15 m/min.

The draft ratio is a ratio of a drawing speed to a linear speed of a film forming dope discharged from a spinneret. The draft ratio is a ratio of the draw ratio after being ejected from the spinneret.

In general, when the film formation is performed by the wet phase separation method, a rough film structure is determined when the film formation raw liquid passes through the air-moving section and leaves the coagulation bath. The membrane interior is composed of a solid portion formed by intertwining polymer chains and a void portion where no polymer exists. Although the detailed mechanism is not clear, when the film is excessively stretched before the completion of solidification, in other words, when the film is excessively stretched before the polymer chains are entangled with each other, the polymer chains are entangled with each other and are torn, and the pores are excessively formed due to the connection of the pores, or the pores are excessively formed due to the division of the pores. Too large pores may cause leakage of virus, and too small pores may cause clogging.

From the viewpoint of structural control, the draft ratio is preferably as small as possible, and the draft ratio is preferably 1.1 to 6, more preferably 1.1 to 4.

The film-forming dope is appropriately coagulated in the air-jet part through the filter and the spinneret, and then introduced into the coagulating liquid. Although the detailed mechanism is not clear, it is considered that: as the spinning speed is reduced, a boundary film formed at the interface between the outer surface of the film and the coagulation liquid becomes thick, and liquid exchange is performed slowly at the interface, whereby coagulation proceeds slowly as compared with the case where the spinning speed is high, and therefore, the inclination of the average pore diameter from the dense layer to the coarse layer becomes slow.

The good solvent has an effect of slowing down the solidification and the water has an effect of speeding up the solidification, and therefore, in order to perform solidification at an appropriate speed, to form a film having an appropriate thickness of a dense layer and to obtain a film having an appropriate pore diameter, the ratio of the good solvent/water is preferably 50/50 to 5/95 in terms of mass ratio as a solidification liquid composition.

From the viewpoint of controlling the pore diameter, the temperature of the coagulation bath is preferably 10 to 40 ℃.

The membrane lifted from the coagulation bath was washed with warm water.

In the water washing step, it is preferable to reliably remove the good solvent and the non-solvent. When the membrane is dried under a condition including a solvent, the solvent is concentrated in the membrane during the drying, and the polysulfone-based polymer is dissolved or swelled, thereby possibly changing the membrane structure.

The temperature of the warm water is preferably 50 ℃ or higher in order to increase the diffusion rate of the solvent and the non-solvent to be removed and to improve the washing efficiency.

The residence time of the membrane in the water bath is preferably 10 to 300 seconds for sufficient washing with water.

The film lifted from the water bath was wound on a frame by a winder. At this time, when the film is wound in the air, the film is gradually dried, but the film may shrink although slightly. In order to produce the same film structure and produce a uniform film, it is preferable to roll the film in water.

The film wound around the frame is cut at both ends and bundled, and is held on the support so as not to be loosened. The held film is subjected to liquid-passing cleaning in the particle removal step.

The cloudy liquid remains in the hollow portion of the film wound around the frame. The liquid contains particles of a polysulfone-based polymer having a size of from nanometer to micrometer. If the membrane is dried without removing the cloudy liquid, the fine particles may block the pores of the membrane and degrade the membrane performance, and therefore, it is preferable to remove the liquid in the hollow portion in the particle removal step.

In the water immersion step, the good solvent and the non-solvent contained in the film are removed by diffusion.

The water temperature in the water soaking process is preferably 10-30 ℃, and the soaking time is preferably 30-120 minutes.

The water used for impregnation is preferably replaced several times.

The wound film is preferably subjected to a high-pressure hot water treatment. Specifically, it is preferable that: the membrane is placed in a high-pressure steam sterilizer in a state of being completely immersed in water, and is treated at 120 ℃ or higher for 2 to 6 hours. Although the detailed mechanism is not clear, not only the solvent and the non-solvent remaining in a small amount in the film are completely removed by the high-pressure hot water treatment, but also the winding and existence state of the polysulfone-based polymer in the dense layer region are optimized.

The membrane treated with high-pressure hot water is dried to complete a base membrane made of a polysulfone-based polymer. The drying method is not particularly limited, and is air drying, drying under reduced pressure, hot air drying, or the like, and it is preferable to dry the film in a state where both ends of the film are fixed so that the film does not shrink during drying.

In one embodiment, the substrate membrane is subjected to a coating process to form a porous hollow fiber membrane.

For example, when the hydrophilization treatment is performed by coating, the coating process includes: a step of immersing the substrate film in the coating liquid, a step of removing the excess coating liquid from the immersed substrate film, and a step of drying the removed substrate film. In addition, a step of cleaning the film may be provided before and after the drying step.

In the dipping step, the substrate film is dipped in the hydrophilic polymer solution in a bundle state. The solvent of the coating liquid is not particularly limited as long as it is a good solvent for the hydrophilic polymer and a poor solvent for the polysulfone-based polymer, and is preferably an alcohol.

The concentration of the hydrophilic polymer in the coating liquid is preferably 0.5 mass% or more as the lower limit value from the viewpoint of sufficiently covering the pore surface of the base material membrane with the hydrophilic polymer and suppressing the decrease in Flux with time due to protein adsorption during filtration, is not particularly limited as long as the membrane blocking is reduced as the upper limit value, is preferably 20.0 mass% or less, and is preferably 10.0 mass% or less from the viewpoint of covering with an appropriate thickness and preventing the decrease in Flux due to too small a pore diameter.

The immersion time of the substrate film in the coating liquid may be, for example, 1 to 72 hours, and preferably 1 to 24 hours.

The substrate film immersed in the coating liquid for a predetermined time is subjected to a liquid removal step to remove excess coating liquid adhering to the hollow portion and the outer periphery of the film. The liquid removal method may be any liquid removal method such as a centrifugal separation method or a suction liquid removal method, and in order to efficiently remove the remaining coating liquid, it is preferable to set the centrifugal force at the time of the centrifugal operation to 10G or more and the centrifugal operation time to 10 minutes or more, and in the case of a method other than the centrifugal separation, it is preferable to set the liquid removal conditions so that the removal efficiency can be obtained to the same degree as that of the centrifugal separation method.

In order to remove the coating liquid that cannot be removed in the liquid removal step, a cleaning step may be added after the liquid removal step. By performing the cleaning step, the average value T can be adjusted, specifically, the average value T can be increased.

The cleaning liquid is not particularly limited as long as it is a poor solvent for the polysulfone-based polymer, and is preferably an alcohol aqueous solution, and more preferably a methanol aqueous solution. The alcohol concentration of the aqueous solution is preferably 0 to 25% from the viewpoint of peeling of the hydrophilic polymer attached to the membrane.

The time for the cleaning step may be appropriately adjusted to achieve the desired average value T. Furthermore, the cleaning process may be carried out several times until the desired average value T is reached.

The hollow fiber membrane cleaned with the cleaning liquid is subjected to a liquid removal step to remove excess cleaning liquid adhering to the hollow portion and the outer periphery of the membrane. The liquid removal method may be any liquid removal method such as a centrifugal separation method or a suction liquid removal method, and in order to efficiently remove the remaining hydrophilic polymer, it is preferable to set the centrifugal force at the time of the centrifugal operation to 10G or more and the centrifugal operation time to 10 minutes or more, and in the case of a method other than the centrifugal separation, it is preferable to set the liquid removal conditions so that the removal efficiency can be obtained to the same degree as that of the centrifugal separation method.

The porous hollow fiber membrane of the present embodiment can be obtained by drying the membrane subjected to liquid removal. The drying method is not particularly limited, and vacuum drying is preferable because of the most efficient method.

The inner diameter of the porous hollow fiber membrane is preferably 200 to 400 μm from the viewpoint of ease of processing into a membrane module, and the membrane thickness is, for example, 200 μm or less as an upper limit, 150 μm or less as another aspect, 100 μm or less as another aspect, 80 μm or less as another aspect, 20 μm or more as a lower limit, 30 μm or more as another aspect, 40 μm or more as another aspect, and 50 μm or more as another aspect.

The dried hollow fiber membrane is preferably subjected to a high-pressure hot water treatment process. By performing the high-pressure hot water treatment step, the average value T can be adjusted, specifically, the average value T can be increased.

The conditions in the high-pressure hot water treatment step may be appropriately adjusted so as to achieve the desired average value T, and for example, the membrane is preferably placed in an autoclave in a state of being completely immersed in water and treated at 120 ℃ or higher for 1 hour or longer. The high-pressure hot-water treatment step is a high-pressure hot-water treatment step performed after the coating of the base material film, and is clearly different from the high-pressure hot-water treatment step performed at a stage before the coating of the base material film, which is performed at 120 ℃ or higher for 2 to 6 hours. The high pressure hot water treatment process may be carried out a plurality of times until the desired average value T is reached. The high-pressure hot water treatment step removes low-molecular components in the hydrophilic polymer applied to the membrane, and also reduces the amount of dissolved substances from the membrane, thereby opening pores in the membrane.

The porous hollow fiber membrane of the present embodiment can be obtained by drying the membrane subjected to the high-pressure hot water treatment. The drying method is not particularly limited, and vacuum drying is preferable because of the most efficient method.

Either or both of the cleaning step and the high-pressure hot water treatment step may be performed.

(method for producing Flat film)

A flat film was produced by using the film-forming dope through the following steps.

The film-forming dope can be cast on the support using various casting apparatuses known in the art. The support is not particularly limited as long as it is a material that does not pose a problem in film formation, and in one embodiment, a nonwoven fabric is exemplified.

The cast film is passed through a dry part having a predetermined length as necessary, and then introduced into a coagulation bath to be dipped and coagulated. The film-forming stock solution temperature during casting may be, for example, in the range of 25 ℃ to 50 ℃. The thickness of the porous film is, for example, 20 μm or more and 100 μm or less.

The film-forming dope cast on the support is brought into contact with a solidifying liquid and solidified to form a porous film. The solidification liquid used may use a non-solvent or a mixed solution containing a non-solvent and a solvent. Here, water is preferably used as the non-solvent, and a solvent used in the preparation of the stock solution is preferably used as the solvent. For example, if NMP is used as a solvent of the membrane formation dope and NMP/water is used as a good solvent/non-solvent of the coagulation liquid, the coagulation liquid is preferably composed of NMP and water. The non-solvent in the coagulating liquid may be, for example, in a range of 50 wt% or more and 95 wt% or less. The temperature of the solidification liquid may be, for example, 10 ℃ or higher and 40 ℃ or lower.

The form of contact with the solidification liquid is not particularly limited as long as the solidification liquid can be sufficiently contacted with the film-forming dope cast onto the support to be solidified, and may be a liquid tank form in which the solidification liquid is stored, and the liquid whose temperature and composition have been adjusted may be circulated or renewed in the liquid tank as necessary. The liquid tank is most suitable, but in some cases, the liquid may be in a form in which the liquid flows in the pipe, or in a form in which the solidified liquid is sprayed by spraying or the like.

The membrane after contact with the solidifying liquid removes the solvent by contact with a liquid that is non-solvent with respect to the membrane material. When the membrane is dried in a state including a solvent, the solvent is concentrated in the membrane during the drying, and the polysulfone-based polymer is dissolved or swollen, thereby possibly changing the membrane structure.

Examples of the non-solvent used include water, alcohol, and a mixed liquid thereof, and the temperature of the non-solvent is 50 ℃ or higher for the purpose of improving the cleaning efficiency.

In order to sufficiently perform the cleaning, the residence time of the membrane in the cleaning bath may be, for example, 10 to 300 seconds.

The washed membrane is dried to complete a base material membrane made of a polysulfone-based polymer. The drying method is not particularly limited, and air drying, vacuum drying, hot air drying, or the like may be used.

In one embodiment, the base material film is made hydrophilic by bundling the base material film and contacting the bundle with a liquid (sometimes referred to as a coating liquid) in which a hydrophilic polymer is dissolved. The form of contact with the coating liquid is not particularly limited as long as the substrate film is provided with desired hydrophilicity, and may be a liquid tank form in which the coating liquid is stored, and further, the liquid whose temperature and composition have been adjusted may be circulated or renewed in the liquid tank as necessary. The liquid tank is most suitable, but may be a liquid flowing in the pipe.

The film after contact with the coating liquid can be cleaned by a cleaning process. By performing the cleaning step, the average value T can be adjusted, specifically, the average value T can be increased.

The cleaning liquid is not particularly limited as long as it is a poor solvent for the polysulfone-based polymer, and is preferably an alcohol aqueous solution, and more preferably a methanol aqueous solution. The alcohol concentration of the aqueous solution is preferably 0 to 25% from the viewpoint of peeling of the hydrophilic polymer attached to the membrane.

The time for the cleaning step may be appropriately adjusted until the desired average value T is reached. The cleaning process may be carried out several times until the desired average value T is reached.

The film after the cleaning step is dried by air drying, vacuum drying, hot air drying, or the like.

The dried film is preferably subjected to a high-pressure hot water treatment step. By performing the high-pressure hot water treatment step, the average value T can be adjusted, specifically, the average value T can be increased.

The conditions in the high-pressure hot water treatment step may be appropriately adjusted so as to achieve the desired average value T, and for example, the membrane is preferably placed in an autoclave in a state completely immersed in water and treated at 120 ℃ or higher for 1 hour or longer. The high pressure hot water treatment process may be carried out a plurality of times until the desired average value T is reached. The high-pressure hot water treatment step removes low-molecular components in the hydrophilic polymer applied to the membrane, and also reduces the amount of dissolved substances from the membrane, thereby making it possible to open pores in the membrane.

Either or both of the cleaning step and the high-pressure hot water treatment step may be performed.

The porous film of the present embodiment can be obtained by drying the film subjected to the high-pressure hot water treatment by a drying method such as air drying, vacuum drying, or hot air drying.

Examples

The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following examples. The test methods shown in the examples are as follows.

(1) Inner diameter and film thickness measurement

The inner diameter and the film thickness of the porous hollow fiber membrane were determined by imaging the vertical cut surface of the porous hollow fiber membrane with a solid microscope. The film thickness was defined as (outer diameter-inner diameter)/2.

Further, the membrane area is calculated from the inner diameter and the effective length of the membrane.

The film thickness of the flat film is obtained by photographing the vertical cut surface of the flat film with a solid microscope.

(2) Determination of the ion count ratio

The count of ions derived from the hydrophobic macromolecule on the outer surface of the porous hollow fiber membrane was determined as follows: the hollow fiber membrane was wrapped with a wrapping paper, and was held between glass slides to be flat, and then measurement was performed using a TOF-SIMS apparatus (nano-TOF, ULVAC-PHI corporation) with one outer surface of the flat hollow fiber membrane as a measurement surface. As a region to be analyzed in the hollow fiber membrane, about 1cm was cut out along the fiber length direction from the second portion obtained by trisecting the hollow fiber membrane formed into a bundle along the fiber length direction, and analysis was performed. As for the measurement conditions, the primary ion is set to Bi₃ ⁺⁺An ion (C in examples and comparative examples described below) most suitably expressing the hydrophobic polymer was detected by a detector, with an acceleration voltage of 30kV, a current of about 0.1nA (in terms of DC), an analysis area of 600. mu. m.times.600. mu.m, and an accumulation time of 30 minutes₆H₄O (m/z 92)) as a detection ion to detect a spectrum. In terms of the characteristics of the measuring apparatus, the measuring depth corresponds to 1 to 2nm from the surface. The number of ions derived from the hydrophilic polymer was also measured under the same measurement conditions, and the ions of the hydrophilic polymer were most suitably expressed (in the following examples and comparative examples, C is used)₄H₅O₂(m/z 85)) as a detection ion. The resolution of the analysis area at the time of measurement was set to 256 × 256 pixels. What is needed isThe measured data were processed using the device plus software WincadenceN. The resolution of the analysis area at the time of data processing is set to 256 × 256 pixels. The ratio (T) of the count (Ti) of the ions derived from the hydrophilic polymer To the count (To) of the ions derived from the hydrophobic polymer detected in a rectangular region consisting of 1 pixel in the circumferential direction of the hollow fiber membrane and 400 μm in the fiber length direction of the hollow fiber membrane was determined¹Ti/To). Calculate T¹Average value (T) of values from the end to the other end of the hollow fiber in the circumferential direction in the analysis area by TOF-SIMS^A). In addition, T is also obtained for the other external surface on the back side of the one external surface by the same method¹Average value of (T)^B). In this case, the measurement site may be a site about 1 to 2cm away from the measurement site on the one outer surface in the fiber length direction. By taking T^AAnd T^BTo obtain T. Here, the end of the hollow fiber within the analysis area is specified as: the average intensity of the ions derived from the hydrophobic polymer on the outer surface of the hollow fiber is less than 80% of the average intensity of the ions derived from the hydrophobic polymer of 50 pixels in the center of the outer surface of the hollow fiber.

The calculation method of the average value T is explained more specifically. First, the count (Ti) of the ions derived from the hydrophilic polymer detected in a rectangular region consisting of 1 pixel in the circumferential direction of the hollow fiber membrane and 400 μm in the fiber length direction of the hollow fiber membrane was obtainedⁿ) Relative To the count of ions originating from the hydrophobic macromolecule (To)ⁿ) Ratio of (T)ⁿ＝Tiⁿ/Toⁿ). Here, n is the number of rectangular regions, and the end in the direction orthogonal to the advancing direction of the membrane in the production of the hollow fiber membrane in the analysis area by TOF-SIMS is referred to as the 1 st and the end on the other side is referred to as the nth. In the determination of T¹～TⁿAfter all the values of (2), T is calculated¹～TⁿAverage value (T) of values of^A). In addition, T is also obtained for the other external surface on the back side of the one external surface by the same method¹～TⁿAverage value of (T)^B). In this case, the measurement site may be a site about 1 to 2cm away from the measurement site on the one outer surface in the fiber length direction. By taking T^AAnd T^BTo obtain T.

The length of one side of the analysis area may be set as appropriate so as to be 1 time or more and less than 1.5 times the length between both ends in the circumferential direction of the flat hollow fiber membrane, and 1.2 times is preferable. In addition, to find TⁿThe length of the rectangular region in the fiber longitudinal direction is preferably equal to or greater than 2/3 in the analysis visual field, and 2/3 is preferably exemplified.

The number of ions derived from the hydrophobic polymer on the flat membrane surface may be measured as in the case of the hollow fiber membrane, and there is no need to wrap the flat membrane surface with a wrapping paper and flatten the flat membrane surface with a slide glass. In the flat membrane, an arbitrary site of the produced flat membrane is selected as an analysis site. The measurement conditions, the analysis area and the accumulation time were the same as those of the hollow fiber membrane. In the case of a flat film, the count of ions derived from the hydrophilic polymer (Ti) detected in a rectangular region consisting of 1 pixel in the direction perpendicular to the advancing direction in the production of the flat film and 400 μm in the advancing direction in the production of the flat film was obtainedⁿ) Relative To the count of ions originating from the hydrophobic macromolecule (To)ⁿ) Ratio of (T)ⁿ＝Tiⁿ/Toⁿ). Here, n is the number of rectangular regions, and the end in the direction orthogonal to the film advancing direction in the production of a flat film in the analysis area by TOF-SIMS is referred to as the 1 st and the end on the other side is referred to as the nth. For example, when a film is present in the entire analysis area, n is 256. In the determination of T¹～TⁿAfter all the values of (2), T is calculated¹～TⁿAverage value (T) of values of^A). In addition, T is also obtained for another surface by the same method¹～TⁿAverage value of (T)^B). In this case, the measurement site may be a position about 1 to 2cm from the measurement site on the one surface in the advancing direction in the production of the flat film. By taking T^AAnd T^BTo obtain T.

(3) Determination of water permeation amount

The effective membrane area reaches 3cm²The membrane module assembled in the above manner was subjected to constant pressure dead-end filtration at 1.0bar to measure the filtration amount of pure water at 25 ℃ and the permeated water amount was calculated from the filtration time.

(4) Bubble point determination

The effective membrane area reaches 0.7cm²The filtration downstream side of the membrane module assembled in the above-described manner was filled with hydrofluoroether, and the pressure was increased from the filtration upstream side by the compressed air via the dead end, and the pressure at which the generation of bubbles from the filtration downstream side was confirmed (when the flow rate of air reached 2.4 mL/min) was defined as the bubble point.

(5) Filtration assay for immunoglobulins

For the effective membrane area of 3cm²The membrane module assembled in the above manner was subjected to a high-pressure steam sterilization treatment at 122 ℃ for 60 minutes. A solution was prepared using Venoglobulin IH 5% intravenous injection (2.5g/50mL) from Mitsubishi pharmaceutical corporation in such a manner that the immunoglobulin concentration of the solution reached 15g/L and the sodium chloride concentration reached 0.1M, pH to 4.5. The prepared solution was filtered through the dead end for 180 minutes at a constant pressure of 2.0 bar.

The cumulative immunoglobulin permeation amount for 180 minutes was calculated from the filtrate recovery amount for 180 minutes, the immunoglobulin concentration of the filtrate, and the membrane area of the membrane module.

(6) Porcine parvovirus clearance assay

(6-1) preparation of filtered solution

A solution was prepared using Venoglobulin IH 5% intravenous injection (2.5g/50mL) from Mitsubishi pharmaceutical corporation in such a manner that the immunoglobulin concentration of the solution reached 15g/L and the sodium chloride concentration reached 0.1M, pH to 4.5. A solution obtained by injecting a solution of Porcine Parvovirus (PPV) of 0.5 vol% was used as a filtration solution.

(6-2) Sterilization of the Membrane

The effective membrane area is up to 3cm²The assembled membrane module was subjected to a high-pressure steam sterilization treatment at 122 ℃ for 60 minutes.

(6-3) filtration

The filtration solution prepared in (1) was filtered through the dead end for 180 minutes at a constant pressure of 2.0 bar.

(6-4) viral clearance

Titer (TCID) of the filtrate obtained by filtering the filtered solution by virus assay₅₀Value) was measured. Viral clearance of PPV is measured by LRV ═ Log (TCID)₅₀) Perml (filtered solution)) -Log (TCID)₅₀) /mL (filtrate)).

It was confirmed that a porous hollow fiber membrane according to an embodiment of the present invention having a coating rate of about 10% as shown in example 2 below exhibited an LRV > 5.

(example 1)

A solution obtained by mixing 24 parts by mass of PES (ULTRASON (registered trademark) E6020P, manufactured by BASF corporation), 31 parts by mass of NMP (manufactured by KISHIDA chemical corporation) and 45 parts by mass of treg (manufactured by kanto chemical corporation) under vacuum was used as a film-forming stock solution. The membrane-forming dope was discharged from the annular portion of the double-tube nozzle, and a mixed solution of 77 parts by mass of NMP and 23 parts by mass of water was discharged from the central portion as a core liquid. The ejected film-forming dope and core liquid were introduced into a coagulation bath containing 15 parts by mass of NMP and 85 parts by mass of water at 18.5 ℃ through a closed air-moving section.

The film drawn out of the coagulation bath was wound up in water using a frame. The spinning speed was set at 5m/min and the draft ratio was set at 1.79.

The wound film was cut at both ends of the frame and bundled, both ends were held by a support so as not to be loosened, and after high-pressure hot water treatment at 128 ℃ for 6 hours, a hollow fiber-shaped base film was obtained by vacuum drying.

The hollow fiber-shaped substrate films were bundled, immersed in 1.7 parts by mass of polyhydroxyethyl methacrylate (manufactured by 2-hydroxyethyl methacrylate (manufactured by kanto chemical corporation, hereinafter) having a weight average molecular weight of 120000) and 98.3 parts by mass of methanol (manufactured by wako pure chemical industries, hereinafter, the same) for 20 hours, and then centrifuged at 537G for 10 minutes. The deliquored fiber bundles were vacuum dried for 20 hours. The vacuum-dried fiber bundle was subjected to high-pressure hot water treatment at 128 ℃ for 60 minutes, and the treated fiber bundle was immersed in water at 20 ℃ for 20 hours. The above high-pressure hot water treatment and water immersion operations were again carried out to vacuum-dry the fiber bundle for 20 hours, to obtain a hollow fibrous porous membrane.

From the resultant fiber bundle, 4 fibers were easily pulled out, and it was confirmed that no film blocking occurred.

(example 2)

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 1, except that the fiber bundle after centrifugation was washed at a flow rate of 350ml/min for 60 minutes with a washing solution containing 15 parts by mass of methanol and 85 parts by mass of water, and the washed fiber bundle was centrifuged again at 537G for 10 minutes.

(example 3)

A porous membrane in a hollow fiber shape was obtained in the same manner as in example 2, except that the high-pressure hot water treatment and the water immersion treatment were not performed.

(example 4)

A porous membrane having a hollow fiber shape was obtained in the same manner as in example 1, except that the coating liquid composition was changed to 1.1 parts by mass of polyhydroxyethylacrylate and 98.9 parts by mass of methanol.

(example 5)

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 4, except that the fiber bundle after centrifugation was washed at a flow rate of 350ml/min for 60 minutes with a washing solution containing 15 parts by mass of methanol and 85 parts by mass of water, and the washed fiber bundle was centrifuged again at 537G for 10 minutes.

(example 6)

A porous membrane having a hollow fiber shape was obtained in the same manner as in example 1, except that the coating liquid composition was changed to 2.3 parts by mass of polyhydroxyethylacrylate and 97.7 parts by mass of methanol.

(example 7)

A hollow fiber-like porous membrane was obtained in the same manner as in example 6, except that the fiber bundle after centrifugation was washed at a flow rate of 350ml/min for 60 minutes with a washing solution containing 15 parts by mass of methanol and 85 parts by mass of water, and the washed fiber bundle was centrifuged again at 537G for 10 minutes.

(example 8)

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 1, except that the coating liquid composition was changed to 5.0 parts by mass of polyhydroxyethylmethacrylate and 95.0 parts by mass of methanol, the fiber bundle after centrifugal liquid removal was washed at a flow rate of 350ml/min for 60 minutes with a washing liquid containing 15 parts by mass of methanol and 85 parts by mass of water, and the washed fiber bundle was centrifuged again at 537G for 10 minutes.

(example 9)

A porous membrane having a hollow fiber shape was obtained in the same manner as in example 8, except that the coating liquid composition was changed to 10.0 parts by mass of polyhydroxyethylacrylate and 90.0 parts by mass of methanol.

(example 10)

A porous membrane having a hollow fiber shape was obtained in the same manner as in example 8, except that the coating liquid composition was changed to 15.0 parts by mass of polyhydroxyethylacrylate and 85.0 parts by mass of methanol.

(example 11)

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 2, except that the liquid removal operation was performed by a vacuum ejector, the supply pressure for pressurizing the vacuum ejector was 0.4MPa, the liquid removal time was 10 minutes, the liquid removal operation for cleaning liquid was performed by a vacuum ejector, the supply pressure for pressurizing the vacuum ejector was 0.4MPa, and the liquid removal time was 10 minutes.

(example 12)

The film-forming dope described in example 1 was applied to a polyester nonwoven fabric, and the coated fabric was introduced into a 18.5 ℃ coagulation bath containing a coagulation solution containing 15 parts by mass of NMP and 85 parts by mass of water, and after the film-forming dope was coagulated, the film-forming dope was continuously dried with hot air to obtain a base film. The flat film dried by hot air was bundled and introduced into a liquid tank containing 1.7 parts by mass of a coating liquid of polyhydroxyethyl methacrylate (manufactured by 2-hydroxyethyl methacrylate (manufactured by kanto chemical Co., Ltd.; hereinafter) having a weight average molecular weight of 120000 and 98.3 parts by mass of methanol (manufactured by Wako pure chemical industries, Ltd.; hereinafter) and the flat film taken out of the liquid tank was vacuum-dried, and the vacuum-dried bundle was subjected to a high-pressure hot water treatment at 128 ℃ for 60 minutes, and the high-pressure hot water-treated bundle was vacuum-dried, thereby obtaining a flat film.

Comparative example 1

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 1, except that the high-pressure hot water treatment and the water immersion were not performed after the removal of the coating solution. This is a porous film corresponding to example 1 of patent document 1.

The fiber bundles after vacuum drying are subjected to fiber blocking, and in an operation of extracting fibers from the fiber bundles in the production of a membrane module, a careful operation such as tearing is performed without damaging the fibers, and therefore, the operation efficiency is significantly reduced.

Comparative example 2

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 4, except that the high-pressure hot water treatment and the water immersion were not performed after the removal of the coating solution.

The fiber bundles after vacuum drying are subjected to fiber blocking, and in an operation of extracting fibers from the fiber bundles in the production of a membrane module, a careful operation such as tearing is performed without damaging the fibers, and therefore, the operation efficiency is significantly reduced.

Comparative example 3

A hollow fiber-shaped porous membrane was obtained in the same manner as in example 6, except that the high-pressure hot water treatment and the water immersion were not performed after the removal of the coating solution.

The fiber bundles after vacuum drying are subjected to fiber blocking, and in an operation of extracting fibers from the fiber bundles in the production of a membrane module, a careful operation such as tearing is performed without damaging the fibers, and therefore, the operation efficiency is significantly reduced.

The measurement results of (1) to (5) of the porous hollow fiber membranes obtained in examples 1 to 11 and comparative examples 1 to 3 are shown in table 1. In table 1, "-" indicates an unmeasured item.

[ Table 1]

Industrial applicability

The porous membrane of the present invention is suitable for use in purification of plasma fractionation preparations, biopharmaceuticals, and the like, and has industrial applicability in this point.