JP4855414B2 - Skinless porous membrane and manufacturing method thereof - Google Patents

Description

  The present invention relates to a porous membrane useful as a separation membrane having a high permeation rate of a liquid and the like and a high fine particle blocking performance in a separation membrane for removing fine particles contained in a liquid, and a method for producing the same.

  Conventionally, gel filtration methods, centrifugal separation methods, adsorption separation methods, precipitation methods, and membrane filtration methods have been used as methods for removing submicron particles, particularly microbial particles, from a liquid. Among these removal methods, the membrane filtration method is superior in that it can be removed by the fractionation ability of fine particles of a specific size or more regardless of the type of fine particles, and can be processed in large quantities. It has been broken. In addition, the filtration method using a membrane is greatly expected for use in removing unnecessary substances from a useful protein-containing solution which is an intermediate raw material for pharmaceutical production or food production.

  Furthermore, human or animal plasma is used for various raw materials in the field of plasma preparation production, the field of plasma fractionation preparation production, the biotechnology field such as antibody drugs, etc., but pathogenic substances such as bacteria and viruses are potentially used. The danger of being mixed is pointed out. In recent years, since virus-mixed plasma is used as a transfusion preparation, there has been a problem that a transfused patient is infected with the virus.

  For filtration membranes used in such applications, especially for membranes that filter solutions with high solids concentrations such as plasma, there is always a need to devise a higher filtration rate without reducing the virus removal ability. . This is because if the filtration rate of the membrane to be used is increased, the required amount can be processed in a shorter time and the production efficiency of the target product can be increased.

  For this reason, various methods for inactivating or removing these viruses have been proposed. As a method for inactivating viruses, there are a sterilization method by heat treatment and a chemical treatment by chemicals represented by the Solvent / Detergent (S / D) method. However, these inactivation methods do not act equally on all viruses, and the inactivation effect is limited depending on the type of virus. For example, heat-resistant hepatitis A virus cannot be expected to be inactivated by heat treatment. In addition, poliovirus that causes paralysis of children and adenovirus that causes cold symptoms do not have an envelope composed of a lipid bilayer membrane and an envelope protein, so the envelope protein is lost by destroying the lipid bilayer membrane. The S / D method for losing infectivity is ineffective in principle. Furthermore, when the chemical used for the chemical treatment is harmful to the human body, a chemical removal step is essential.

  On the other hand, one method for physically removing viruses is a method for separating and removing viruses by membrane filtration. The advantage of this method compared to the inactivation method described above is that the separation function can be controlled according to the size of the particles, so that the possibility of a virus accidentally passing through the filtration membrane is suppressed, It is effective in removing all viruses regardless of the thermal or chemical properties of the virus.

  The smallest types of viruses are parvoviruses with a diameter of about 18 to 24 nm and polioviruses with a diameter of 25 to 30 nm, and relatively large types include HIV (human immunodeficiency virus) with a diameter of 80 to 100 nm. . In order to physically remove such viruses by membrane filtration, a microporous membrane having at least a maximum pore size of 100 nm or less is required.

  On the other hand, virus removal membranes used for the purification of blood transfusion plasma, plasma fractionation products, biopharmaceuticals and the like are required to have not only virus removal performance but also high permeability of physiologically active substances such as albumin and globulin. For this reason, an ultrafiltration membrane having a pore diameter of several nanometers or a reverse osmosis membrane having a smaller pore diameter is not suitable as a virus removal membrane.

  Even if the microporous membrane has a pore size suitable for virus removal, the microporous membrane having a skin layer with a low surface pore-opening property has a low flux. This is considered to be caused by the presence of a skin layer having a low pore-opening property that the holes on the inner side in the film thickness direction are not fully utilized or the skin layer itself has a large filtration resistance. Therefore, it is desirable not to have a skin layer on the surface, but it is generally composed of a polymer and a plasticizer, etc., particularly when obtaining a membrane having a pore size suitable for virus removal by a melt film-forming method using thermally induced phase separation. Since the composition is melted and rapidly cooled, a skin layer is easily formed on the surface. Also in the wet film formation method using concentration-induced phase separation, it becomes easy to form a skin layer on the surface by rapidly depositing the polymer.

  In Patent Document 1, a polyolefin resin having specific physical properties, an organic liquid, and an inorganic fine powder are mixed and then melt-molded by T-die extrusion molding or injection molding, and the organic liquid and inorganic fine powder are obtained from the obtained molded product. A method for producing a microporous polyolefin porous material by extracting selenium is disclosed. As shown in FIG. 13, the porous membrane produced by this method has poor pore opening on the outermost surface of the membrane, and a high filtration rate can be obtained for use as a separation membrane for removing fine particles contained in the liquid. There wasn't.

  Patent Document 2 discloses a microporous film containing a thermoplastic resin having a coarse structure layer having a large porosity and a dense structure layer having a low porosity, and the coarse structure layer and the dense structure layer are integrated. A multilayer microporous membrane and a method for producing the same are disclosed. As a method for forming the coarse structure layer, at least one surface of an uncured film formed from a composition containing a thermoplastic resin and a plasticizer is nonvolatile with partial solubility in the thermoplastic resin. A method of contacting a liquid is disclosed. When a film is formed into a flat film, the composition extruded into the flat film is sandwiched by a cooling roll and cooled to cause phase separation of the polymer and the plasticizer, and further cooled to fix the pore structure. At the same time, it is generally performed to adjust the film thickness that can occur during extrusion, but in the method for forming the coarse structure layer, the film thickness is due to the presence of a plasticizer between the cooling roll and the composition. In addition, it is difficult to arrange the plasticizer, and the plasticizer flows along the roll to the side of the roll. In addition, the porous membrane produced by hydrophilizing the surface of the porous membrane produced by the method has a reduced filtration rate over time when a 3% bovine immunoglobulin solution is filtered, but it is as high as plasma. In applications where a solution having a solid content concentration is filtered, it is necessary to further improve the filtration performance.

  Patent Documents 3 and 4 disclose a filtration method and system using a regenerated cellulose filter membrane. All of these have proposed methods for separating viruses according to their size. However, any of these methods uses an expensive filtration membrane such as a hollow fiber membrane or requires a special apparatus for filtration.

  Patent Document 5 discloses a microporous filtration membrane in which membrane elements composed of a prefilter region having a large pore diameter and an appropriate region having a small pore diameter are stacked after phase separation so that the suitable regions are aligned with each other. In order to reduce the pore size of the membrane thus prepared until virus removal is possible, there is a high possibility that a skin layer having a low porosity is formed on the surface of the appropriate layer during rapid cooling during phase separation. If suitable layers having skin layers are bonded together, the probability that a hole communicates from one membrane element to the other membrane element in the bonded region corresponds to the probability that the openings of the skin layers overlap each other. From this, it is clear that the flux is greatly reduced. In addition, even when one membrane element without a skin layer and having a slightly larger pore diameter is used, the flux is also inhibited by the skin layer present in the other membrane element.

  In Patent Document 6, a polymer solution in which a polymer is dissolved in a solvent is applied to a support material, and after spraying with humid air, the pore diameter is minimized on the inner side in the film thickness direction by dipping in a non-solvent. A method for manufacturing a membrane is disclosed. In this method, a device for blowing air and a device for controlling the humidity in the air are required, and an exhaust fan and a duct for exhausting the evaporated solvent are required, so that the manufacturing equipment becomes complicated. In addition, there is a possibility that the operator may injure health by sucking the evaporated solvent.

  Patent Document 7 discloses a method for producing a laminated film in which a multi-layer polymer solution is coated on a smooth continuous web by co-casting. When performing melt film formation by this method, cooling is hindered by the web, and when adjusting the film thickness with a cooling roll, if the roll gap and the web thickness are not uniform, unevenness will occur in the film thickness. Control is difficult. In addition, in film formation at a high temperature, the solvent evaporates from the surface of the polymer solution opposite to the side in contact with the web, the stability of the film is deteriorated, phase separation occurs before contact with the cooling roll, There is a possibility that problems such as an increase in the hole diameter may occur.

  Patent Document 8 discloses a method for producing a laminated film in which a plurality of polymer solutions are co-cast, phase-separated and then cooled. When using a web or film on the coat surface, cooling is inhibited by the web or the like as in Patent Document 7, and when the film thickness is adjusted with a cooling roll, both the roll gap and the thickness of the web are not uniform. Strict control is difficult because the film thickness is uneven. Also, in film formation at high temperature, the solvent evaporates from the surface of the polymer solution opposite to the side in contact with the web etc., resulting in poor film stability, and phase separation occurs before contact with the cooling roll. There is a possibility that problems such as an increase in the hole diameter may occur. Also, when using a drum on the surface of the coat, a separate cooling roll must be prepared after coating, which complicates the equipment, and in the case of thermally induced phase separation, the drum side on the coat drum There is a possibility that the plasticizer evaporates from the surface of the polymer solution on the opposite side and the film formation stability is deteriorated, phase separation occurs before contact with the cooling roll, and the pore diameter increases.

  In Patent Document 9, a composition comprising a polymer concentration of 40 to 80 parts by weight, a solvent of 20 to 60 parts by weight, and a fluorine compound of at least 05 parts by weight or more is melted and coextruded using a feed block or a multi-manifold die. Thus, a method for producing a laminated film in which a porous or non-porous layer is laminated on a microporous layer is disclosed. However, there is no description of conditions for realizing virus removal ability and achieving a high filtration rate. Moreover, since water repellency is expressed by containing a fluorine compound, it is not suitable for liquid filtration.

  In Patent Document 10, a structure in which the in-plane average pore diameter is a minimum, a portion in which the in-plane average pore diameter is larger than the minimum portion, and a structure arranged in the minimum portion is a film thickness from the inner wall surface to the outer wall surface of the hollow fiber. A hollow fiber membrane having at least one pair in the direction is disclosed. However, from the scanning electron micrographs disclosed in the examples and the measurement results of the in-plane porosity, the in-plane average pore diameter is larger than the minimum portion existing between the two minimum portions in the film structure. It is clear that the porosity of the part is very large. The presence of such a layer with a high porosity inside the film may be crushed by external pressure. In addition, this patent document discloses a method for inducing microphase separation from the inside and outside of a hollow fibrous material by contacting the solidifying liquid from the inside and outside of the hollow fibrous material as a method for producing a membrane having the above structure. ing. When producing a flat membrane-like porous membrane using such a method, there will be a solvent on both surfaces of the polymer solution, and when it is sandwiched between rolls and cooled, the solidifying liquid flows. The polymer solution cannot be pressed firmly and it is difficult to make the film thickness uniform. Also, for example, in the case of dropping into a solidifying liquid and causing phase separation, in the case of a flat film, since it is molded in an unstable state depending on the discharge conditions, it is also difficult to make the film thickness uniform. . Furthermore, since a facility for recovering the contactable solidifying liquid is required, the manufacturing facility is complicated and expensive.

Therefore, a technique for stably producing a membrane having a pore size suitable for virus removal but having sufficient pore opening properties and a high permeation rate has not been known so far.
Japanese Patent Publication No. 60-23130 WO03 / 026679A1 brochure JP-A-1-192368 JP-A-1-254205 JP-T-2006-503687 GB2199786A brochure Japanese Patent Application Laid-Open No. 2006-7211 US2002 / 0113006A1 brochure WO03 / 104310A2 brochure JP-A-62-184108

  The present invention relates to a porous membrane useful as a separation membrane, which has a high permeation rate of liquid and the like, and a high fine particle blocking performance in a separation membrane for removing fine particles contained in a liquid, and a method for producing the same. The issue is to provide.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have determined that a composition having at least two types of high and low polymer concentrations containing at least a polymer and a plasticizer is a composition having a low polymer concentration. A film having a high hole opening rate and a high permeation rate can be obtained by a melt film-forming method in which layers made of are laminated so as to be positioned on both sides of a layer having a high polymer concentration, while having a pore size having fine particle blocking performance. As a result, the present invention has been completed.

That is, the present invention is as follows.
(1) A step of heating at least two kinds of compositions having high and low two polymer concentrations containing a polymer and a plasticizer above the melting point of the polymer to uniformly melt them independently, from the inlet side to the outlet side The layers made of the composition having a low polymer concentration are positioned on both sides of the layer having a high polymer concentration by extruding the composition together in contact with each other in a mold having an internal structure divided into at least three layers. A step of obtaining a molten laminate of the high-concentration composition and the low-concentration composition by the step of laminating, and directly contacting both surfaces of the molten laminate with a cooling surface at least 80 ° C. lower than the temperature at the time of melting A method for producing a skinless porous membrane, comprising: a step of obtaining a molded product by removing the plasticizer, and then a step of removing substantially all the plasticizer from the molded product.
(2) A step of preparing at least two kinds of compositions having high and low two polymer concentrations including a polymer and a plasticizer, a step of independently molding into a sheet, and a sheet comprising a composition having a low polymer concentration A step of obtaining a laminated body that is laminated so as to be positioned on both surfaces of a sheet having a high polymer concentration, a step of heating the laminated body to obtain a molten laminate of the high concentration composition and the low concentration composition, Obtaining a molding by directly contacting both sides of the molten laminate with a cooling surface at least 80 ° C. lower than the melting temperature, and then removing substantially all of the plasticizer from the molding. A method for producing a skinless porous membrane.
(3) The method for producing a skinless porous film according to (1) or (2), wherein the cooling surface at least 80 ° C. lower than the melting temperature is a cooled metal roll.
(4) After irradiating the skinless porous membrane according to any one of (1) to (3) with ionizing radiation, the method further comprises a step of hydrophilizing the pore surface by contacting 2-hydroxypropyl acrylate. A method for producing a skinless porous membrane.
(5) A polymer porous film having a multi-layer structure in which a high porosity layer is laminated on both sides of a low porosity layer, having no skin layer on both surfaces, and a maximum pore diameter determined by the bubble point method of 10 nm A skinless porous membrane characterized by having an average pore size of 100 nm or less determined from a water permeability measurement method larger than the maximum pore size, and having at least two minimum pore size layers in the low porosity layer.
(6) The skinless porous membrane according to (5), wherein the minimum pore diameter layer is located in the vicinity of the boundary between the low porosity layer and the high porosity layer.
(7) The skinless porous membrane according to (5) or (6), wherein the pore diameter at the center in the film thickness direction of the low porosity layer is larger than the pore diameter at the peripheral portion.
(8) The skin according to any one of (5) to (7), wherein the cross-sectional open area ratio of the high open area layer is at least 10% higher than that of the low open area layer. Less porous membrane.
(9) The skinless porous membrane according to any one of (5) to (8), wherein the ratio of the thickness of the high porosity layer to the low porosity layer is 1/5 or more.
(10) The skinless porous film according to any one of (5) to (9), which has a porous structure obtained by a melt film forming method.
(11) The skinless porous membrane according to any one of (5) to (10), wherein the porosity of both surfaces is 10% or more.
(12) Any one of (5) to (11), wherein the polymer is any of polyolefin, polyester, polyamide, fluorinated hydrocarbon polymer, polyphenylene ether, polyacetal, polyurethane, and polyethersulfone. The skinless porous membrane described.
(13) The skinless porous membrane according to any one of (5) to (12), wherein the pore surface is coated with a hydrophilic polymer.
(14) The skinless porous membrane according to (13), wherein the hydrophilic polymer has at least a hydroxyl group.
(15) A method of filtering a specific component from a liquid containing at least two components using the porous membrane according to any one of (5) to (17).
(16) Permeating only a physiologically active substance from a liquid containing at least one component selected from the group consisting of bacteria, fungi, viruses, pathogenic prions, leukocytes, and cell-derived particles and a physiologically active substance. (15) The liquid processing method according to (15).

According to the present invention, a membrane having a high permeation rate of a liquid and the like, and a membrane useful as a separation membrane for blocking fine particles contained in the liquid, such as colloids, insoluble polymers, bacteria, viruses, pathogenic prions and the like, and production thereof A method can be provided.
Furthermore, according to the present invention, it is possible to provide a separation membrane having a high filtration rate and a high virus removal performance in plasma filtration using a membrane in consideration of virus removal from plasma. It can be obtained with high production efficiency.
In addition, according to the present invention, in the production process of biopharmaceuticals such as antibody drugs, it is possible to provide a separation membrane capable of processing a large amount of high concentration pharmaceuticals with high filtration rate and high virus removal performance, and safety. Can be obtained with higher production efficiency.

2 is a scanning electron micrograph of the surface of the porous film obtained in Example 1 observed at 15000 times. 2 is a scanning electron micrograph obtained by observing a cross section of the porous film obtained in Example 1 at a magnification of 150 times. 2 is a scanning electron micrograph obtained by observing the vicinity of the surface of the cross section of the porous film obtained in Example 1 at a magnification of 15000 times. In the porous film obtained in Example 1, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs in 3000 times. In the porous film obtained in Example 1, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs in 15000 times. In the porous film obtained in Example 1, it is the scanning electron micrograph which observed the cross section near the center of a film | membrane by 15000 times. 4 is a scanning electron micrograph of the surface of the porous film obtained in Example 2 observed at 15000 times. 4 is a scanning electron micrograph obtained by observing a cross section of the porous film obtained in Example 2 at 150 times. 4 is a scanning electron micrograph of the surface vicinity of the cross section of the porous film obtained in Example 2 observed at 15000 times. In the porous film obtained in Example 2, it is the scanning electron microscope photograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs by 3000 time. In the porous film obtained in Example 2, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs in 15000 times. In the porous film obtained in Example 2, it is the scanning electron micrograph which observed the cross section of the center vicinity of a film | membrane by 15000 times. 4 is a scanning electron micrograph obtained by observing the surface of a porous film obtained in Comparative Example 2 at a magnification of 15000 times. 4 is a scanning electron micrograph obtained by observing the surface of the porous film obtained in Example 4 at a magnification of 15000 times. 4 is a scanning electron micrograph obtained by observing the cross section of the porous film obtained in Example 4 at 100 times. 4 is a scanning electron micrograph of the surface vicinity of the cross section of the porous film obtained in Example 4 observed at a magnification of 5000 times. In the porous film obtained in Example 4, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs in 3000 times. In the porous film obtained in Example 4, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs by 10000 times. In the porous film obtained in Example 4, it is the scanning electron micrograph which observed the cross section near the center of a film | membrane by 10000 time. 4 is a scanning electron micrograph of the surface of the porous film obtained in Example 6 observed at 15000 times. It is the scanning electron micrograph which observed the cross section of the porous film obtained in Example 6 by 200 time. 6 is a scanning electron micrograph of the surface vicinity of the cross section of the porous film obtained in Example 6 observed at a magnification of 5000 times. In the porous film obtained in Example 6, it is the scanning electron micrograph which observed the cross section of the boundary vicinity of the layer from which a hole diameter differs in 5000 times.

The present invention is described in detail below.
The skinless porous membrane of the present invention is a polymer porous membrane having a three-layer structure in which a high porosity layer is laminated on both sides of a low porosity layer, and there is no skin layer on both surfaces. The maximum pore diameter determined in (10) is 10 nm or more and 100 nm or less, the average pore diameter determined from the water permeability measurement method is larger than the maximum pore diameter, and the low porosity layer has at least two or more small pore diameter layers. And

  The skinless porous membrane of the present invention is prepared by preparing at least two kinds of compositions having at least two kinds of high and low polymer concentrations containing at least a polymer and a plasticizer, and the layer of the low concentration composition comprises the high concentration composition. It can be obtained by laminating so as to be positioned on both sides of the layer and using a melt film formation method. The melt film-forming method is a step of heating the composition above the melting point of the polymer to uniformly melt it, a step of forming the molten composition into a film, a plasticizer in the film, and possibly inorganic particles Therefore, the process further comprises a step of removing the plasticizer and inorganic particles from the film.

  Depending on the type and state of the polymer, a clear melting point may not be observed. However, when such a polymer is used, it is uniformly melted with a plasticizer and has sufficient fluidity to be molded. It is sufficient that a person having ordinary skill in the art can easily make this determination.

  In the present invention, a polymer is a material for forming a film, and a polymer that is usually used as a film material can be used. Polyolefin such as polyethylene, polypropylene, poly-4-methyl 1-pentene, polyethylene Polyesters such as terephthalate and polybutylene terephthalate, polyamides such as nylon 6 and nylon 66, fluorinated hydrocarbon polymers such as polyvinylidene fluoride, ethylene / tetrafluoroethylene, and polychlorotrifluoroethylene, polyphenylene ether, polyacetal, polyurethane, polyether Means sulfone or a mixture thereof. Among these, it is preferable to use polyethylene, polypropylene, or polyvinylidene fluoride as a material because a film having excellent film formability and high strength can be obtained. These polymers may be copolymers with other polymers, and other polymers may be graft polymerized on the side chain. Further, a polymer having a hydrophilic surface such as an ethylene vinyl alcohol copolymer or polyvinyl alcohol can be used, and the hydrophilic step can be omitted.

  The plasticizer used in the present invention can be uniformly melted at a temperature equal to or higher than the crystal melting point of the polymer when mixed with the polymer used as a film material and heated. In addition, a material having a thermally induced phase separation point at a temperature equal to or higher than normal temperature is used. Such plasticizers include bis (2-ethylhexyl) phthalate (hereinafter abbreviated as “DOP”), diisononyl phthalate (hereinafter abbreviated as “DINP”), diisodecyl phthalate (hereinafter abbreviated as “DIDP”). ), Di (n-octyl) phthalate (hereinafter abbreviated as “DnOP”), di (n-butyl) phthalate (hereinafter abbreviated as “DBP”), dicyclohexyl phthalate (hereinafter abbreviated as “DCHP”) Phthalates such as trimellitic acid tris (2-ethylhexyl), sebacic acid esters such as dibutyl sebacate, adipic acid esters such as dibutyl adipate, tri (2- Long-chain alkyl esters such as ethyl hexyl), tallow amines, stearic acid esters, stearyl alcohol, etc. Higher fatty alcohols such as Le, and the like are preferable hydrocarbon-based plasticizer such as liquid paraffin or paraffin wax. In particular, when the above-mentioned polyethylene, polypropylene, or polyvinylidene fluoride is used as a polymer material, it is more preferable to use bis (2-ethylhexyl) phthalate or bis (n-butyl) phthalate having high compatibility with them. Moreover, these plasticizers may be used in combination in order to adjust the pore size of the film obtained, not alone.

  In the present invention, the mixing ratio of the polymer and the plasticizer is preferably selected so that the ratio of the polymer is 10 to 80%, more preferably 15 to 70%, as the weight ratio. 20 to 60% is particularly preferable. When the ratio of the polymer is less than 10% by weight, the film formability is deteriorated, and practical strength cannot be obtained. On the other hand, when the proportion of the polymer exceeds 80% by weight, the porosity decreases, and the pure water permeation rate decreases.

  In the composition necessary for molding the porous film of the present invention, the composition may contain inorganic particles having a fine particle diameter in addition to the polymer and the plasticizer. If inorganic particles are included in the composition, the inorganic particles become a plasticizer carrier, improve the dispersibility of the polymer and plasticizer in the composition, improve the uniformity during heating and melting, and during cooling. This contributes to the improvement of the uniformity of thermally induced phase separation. Examples of inorganic particles include particles composed of metal oxides, metal hydroxides, metal carbonates, and derivatives thereof, such as calcium carbonate, titanium dioxide, amorphous silicon dioxide (hereinafter referred to as “silica particles”). Is preferred). In particular, silica particles are more preferable because they can be easily extracted with an alkaline solution after film formation. The particle size of the inorganic particles is preferably 1 nm to 1 mm, more preferably 1 nm to 1 μm, and particularly preferably 1 nm to 0.1 μm as the primary particle size. In addition, in order to increase the compatibility of the inorganic particles with the polymer, the particle surface may be chemically modified. For example, in the case of silica particles, the type generally referred to as hydrophobic silica particles corresponds to this, and examples include aerosil hydrophobic products (product grade example: R972), reolosil hydrophobic products (product grade example: DM-10), and the like. Further, the method for producing these silica particles is not particularly limited, such as a wet method or a dry method.

  The weight ratio of the inorganic particles to the plasticizer is preferably selected so as to be 1 to 10 to 10: 1, more preferably 1 to 5 to 5 to 1, and 1 to 3 to 3: 1. Is particularly preferred. By selecting the weight ratio within this range, it is possible to obtain a membrane having the necessary opening property in order to have a practical permeation rate.

  In the present invention, in addition to the polymer, plasticizer, and inorganic particles, other additives such as an antioxidant, an antistatic agent, a flame retardant, and an ultraviolet absorber may be mixed. In particular, it is preferable to add an antioxidant for suppressing thermal degradation of the polymer, particularly a hindered phenol-based antioxidant. For example, Irganox (manufactured by Ciba Specialty Chemicals Co., Ltd.) is added to the polymer by weight. The addition of 0.01 to 10% in a ratio is recommended for maintaining the strength of the resulting film.

  The first method for uniformly melting the composition is to charge the polymer and, if necessary, a continuous resin kneading apparatus such as a screw extruder heated to heat the polymer. It is a method of melting uniformly by introducing a plasticizer at an arbitrary ratio while melting and heating and kneading. The polymer may be charged in any form of powder, granules, and pellets. In the case of uniform melting by this method, the plasticizer is preferably liquid at room temperature. As an extruder, a single screw type extruder, a biaxial different direction screw type extruder, a biaxial same direction screw type extruder, etc. can be used.

  The second method for uniformly melting is to mix a polymer, a plasticizer, or, if necessary, an additive in advance using a stirring device such as a Henschel mixer, and disperse each raw material. It is a method in which it is introduced into a heated screw extruder and melted uniformly while heating and kneading. The composition is charged in a slurry form when the plasticizer is liquid at room temperature, and in a granular form when the plasticizer is liquid at room temperature and contains inorganic particles such as silica in the composition. When the plasticizer is solid at room temperature, it may be powdered or granular.

  The third method for uniform melting is a method using a simple resin kneading apparatus such as a Brabender or a mill, or a method of melting and kneading in a batch kneading vessel such as a mixer. According to this method, since it is a batch type process, the productivity is not good, but there is an advantage that a wide variety of compositions can be easily formed and the degree of freedom is high.

  The composition uniformly melted as described above is subsequently formed into a film in a laminated state by the following method.

  As a first method of film formation, at least two types of high and low polymer concentration compositions are put into separate heated screw extruders, uniformly melted while heating and kneading, and then flattened. Extruded separately through a film-forming die into a sheet, and then introduced into a cast roll while contacting a sheet with a higher polymer concentration on both surfaces of the sheet with a higher polymer concentration. This is a method of winding with a machine.

  As a second method of forming a film, at least two types of high and low polymer concentrations are put into separate heated screw extruders, melted uniformly while heating and kneading, and then gold It is a method of extruding together while making contact in a mold and winding up with a winder. At this time, as a mold for molding the composition melted by separate extruders, a mold having an internal structure in which at least three layers are divided from the inlet side to the outlet side is used. However, the point where the respective compositions merge can be arbitrarily provided between the inlet and the outlet of the mold.

  As a third method for forming a film, at least two types of high and low polymer compositions are prepared, put into separately heated screw extruders, and uniformly melted while heating and kneading. A compression molding machine that extrudes each sheet separately using flat film forming dies, and then superimposes a sheet having a higher polymer concentration on both surfaces of the sheet having a higher polymer concentration. It is the method of cooling after remelting by heating in etc. In either method, the composition that melts may further contain inorganic particles.

  In any of the above methods, when extruding into a sheet form through a flat film-forming die, the sheet-like film extruded from the die is usually melted in a roll unit of a cooling and rolling apparatus called a casting apparatus. It winds with the winder which adjusted winding speed so that it might become moderate winding tension, adjusting cooling and thickness by pinching and extruding a laminate. In order to obtain a pore diameter that allows virus removal, it is preferable to rapidly cool at the roll portion of the casting apparatus. Therefore, the surface temperature of the roll is preferably 80 ° C. or more lower than the melting temperature.

  Since the film obtained by the above film forming method contains a plasticizer and, in some cases, inorganic particles in the film, the plasticizer and inorganic particles are subsequently removed from the film. Then, the removal method will be described next.

  The extraction solvent for extracting the plasticizer is a poor solvent for the polymer used as the membrane material and a good solvent for the plasticizer, and the boiling point is lower than the melting point of the polymer used as the membrane material. Is desirable. For example, if the plasticizer is a phthalate ester, hydrocarbons such as n-hexane and cyclohexane, halogenated hydrocarbons such as methylene chloride and 1,1,1-trichloroethane, alcohols such as ethanol and isopropanol, diethyl Ethers such as ether and tetrahydrofuran, and ketones such as acetone and methyl ethyl ketone are suitable, and methylene chloride is particularly preferred because of its excellent extractability. When extracting a plasticizer, it can extract more effectively if it immerses at a temperature higher than room temperature. By the above extraction process, a porous membrane from which the plasticizer has been removed is obtained.

  In order to extract inorganic particles contained in the film, a method of immersing the film in a solution capable of dissolving the inorganic particles is recommended. In the case of extracting the inorganic particles, the extraction can be performed more effectively if the immersion treatment is performed at a temperature higher than room temperature, as in the case of extracting the plasticizer. In particular, when the inorganic particles are silica particles, a method of immersing the membrane in an aqueous sodium hydroxide solution of about 20 to 60% by mass for about 30 to 60 minutes is effective.

  In the present invention, when both the plasticizer and the inorganic particles are contained in the film, the extraction order is not particularly limited, but the plasticizer may be extracted before the inorganic particles because of its workability. preferable. By the above removal method, the plasticizer, and in some cases, both the plasticizer and the inorganic particles can be removed from the membrane to obtain a porous membrane. The film from which the plasticizer, and in some cases both the plasticizer and the inorganic particles are extracted, may be further surface treated with a hydrophilic polymer.

  When the film obtained by the melt film formation method as described above is produced from only one kind of composition, when the pore diameter of the film obtained by using only the composition having a high polymer concentration of the present invention is reduced, As shown in FIG. 13, a skin layer having a low porosity is formed on the surface, and the permeation rate of liquid or the like is greatly reduced. On the other hand, the film obtained by using only the composition having a low polymer concentration of the present invention has a high porosity and can prevent the formation of a skin layer, but cannot reduce the pore diameter. By forming a film in the laminated state as in the above production method, a film having a pore size capable of blocking particles such as viruses can be obtained while preventing the formation of a skin layer.

  The maximum pore diameter determined by the bubble point method of the porous film of the present invention is preferably 10 nm or more and 100 nm or less. The bubble point method is a method of measuring the gas permeation behavior in a state where the membrane is filled with a liquid and evaluating the size of the largest hole in the membrane. The maximum pore diameter in the present invention is a value measured by a bubble point method based on ASTM F316-86. Specifically, the evaluation membrane set in the filter holder is dipped in the test solution and wetted, and one side of the filter is slowly pressurized with air. The lowest pressure at which the flow meter installed on the gas permeation side of the filter detects the rising of a stable flow bubble is recorded as the bubble point, and converted to the maximum pore size using the formula described later.

  By setting the maximum pore size of the membrane to 100 nm or less, when filtering particles to be removed, for example, a solution containing viruses, the concentration of a virus having a relatively large size such as AIDS virus can be reduced. Further, the maximum pore size can be designed to be smaller depending on the size of the particles to be removed, and the maximum pore size is preferably 75 nm or less, more preferably 55 nm or less, if a larger range of viruses is to be removed. 45 nm or less is particularly preferable.

  The average pore diameter determined from the water permeability measurement method of the porous membrane of the present invention is preferably larger than the maximum pore diameter determined by the bubble point method. The water permeation measurement method is a method of calculating the average pore diameter of the membrane from the amount of water permeation of pure water when the pressure is applied to the membrane, the porosity, and the film thickness, and the measurement method will be described in detail later.

  The smaller the maximum pore size, the higher the ability to prevent fine particles such as viruses. The larger the average pore diameter determined from the water permeation measurement method, the higher the processing amount per unit time when removing the fine particles from the liquid containing the fine particles by filtration. Separation membrane that combines high filtration rate and high blocking performance when removing particles from liquids containing sub-micron particles or less because the average pore size obtained from the water permeability measurement method is larger than the maximum pore size obtained by the bubble point method As useful.

  The membrane described in Patent Document 9 is common to the present invention in that the maximum pore diameter determined by the bubble point method is 10 nm or more and 100 nm or less, but the average pore diameter determined from the water permeability measurement method. Does not have the feature of the present invention that is larger than the maximum pore size determined by the bubble point method, and in order to filter a solution with a high solid content concentration such as plasma, the desired performance may not be obtained. It is possible to get.

  In the present invention, it is desired that the average pore diameter determined from the water permeability measurement method is at least larger than the maximum pore diameter determined by the bubble point method, but preferably 1.1 times or more, more preferably 1.5 times or more than the maximum pore diameter. Preferably it is 2.0 times or more. In the present invention, the maximum pore diameter and the average pore diameter are used to characterize the membrane, but these values do not necessarily reflect the characteristics of the pore distribution of the membrane.

  In the porous membrane of the present invention, it is preferable that the average pore diameter determined by the water permeation measurement method satisfies the above-mentioned conditions and is in a certain range depending on the application. In the present invention, the average pore diameter is in the range of 10 to 200 nm, preferably 15 to 180 nm, more preferably 20 to 160 nm. By setting the average pore diameter within this range, it is possible to achieve a practical filtration rate while maintaining the removal performance of particles to be removed, such as viruses.

The water permeability of the porous membrane of the present invention varies depending on the pore diameter, but is preferably in the range of 1 to 3000, preferably 10 to 2000, and more preferably 100 to 1000. The water permeability is a value obtained by converting the film thickness to 100 μm, and the unit is L / m ² /hr/(0.1 MPa) / 100 μm. In the unit, “hr” means “one hour” as a unit time. By setting the water permeation amount within this range, it is possible to achieve a practical filtration rate while maintaining the removal performance of particles to be removed, such as viruses.

  The porous membrane of the present invention preferably has a porosity of 10% or more on the membrane surface. In the present invention, the porosity of the film surface is an area ratio occupied by voids on the surface of the film, and is obtained from image analysis of a scanning electron micrograph of the film surface. When the porosity of the membrane surface is less than 10%, resistance to the solution to be filtered is caused, and the filtration rate becomes insufficient.

  The porous membrane of the present invention also includes a membrane composed of at least three layers having different open area ratios. In the present invention, the layer is a region in which the area ratio occupied by the void portion measured at every constant thickness in the film thickness direction is in a certain range in the film cross section, and is an image of a scanning electron micrograph of the film cross section. Obtained from analysis. In the present invention, the region where the difference in the area ratio of the void portion measured for every 1 μm thickness is within 5% or less is the same layer from the measurement accuracy. In addition, when there is a region where the difference in the area ratio of the void portion exceeds 5% with respect to one layer in the cross section of the membrane, the membrane is assumed to be composed of two layers having different open area ratios. The presence of a low porosity layer between two high porosity layers means that the polymer occupies a high proportion of the space in the low porosity layer, so the strength of the membrane is increased and the membrane is crushed by external force. It is preferable because it can be prevented. In order to provide appropriate strength, it is preferable that the cross-sectional area ratio of the high-permeability layer is at least 10% or more larger than that of the low-permeability area.

  In general, a layer having a small pore diameter appears in a portion having a low porosity. However, in the low porosity layer having the three-layer structure of the present invention as described above, it is assumed that two or more such small pore layers exist. Even if a defect is produced on one side and sufficient particle removability is not expressed, the leakage of particles can be prevented by the further small pore diameter layer expressing further particle removability. When forming the porous film used in the present invention, especially when the thickness of the sheet-like composition is adjusted to 200 μm or more, the cooling rate is slower in the central part of the sheet-like composition than in the peripheral part of the central part. For this reason, the hole diameter at the center of the membrane is larger than the hole diameter at the periphery of the center. In addition, the hole diameter continuously increases from the peripheral part of the central part toward the central part. Such pore size distribution characteristics are obtained from a composition having a high polymer concentration, particularly when a film having a high polymer concentration and a composition having a low polymer concentration are coextruded. Found in the low porosity layer.

  For example, the film has a high polymer concentration of 32% by mass, a low polymer concentration of 10% by mass, and a molded product having a thickness of 300 to 550 μm. When the cooling rate is 30 to 170 ° C./min, the layer composed of the composition having a high polymer concentration is already separated from one boundary with the layer composed of the composition composed of the composition having a low polymer concentration on one side. A porous film having an internal structure in which a layer having a small pore size, a layer having a large pore size, and a layer having a small pore size is divided into three layers in this order toward the boundary is obtained.

  As described above, since the pore diameter at the center of the membrane is larger than the pore diameter at the periphery of the center, clogging inside the membrane is suppressed when removing the particles from a liquid containing sub-micron particles or less. However, it is useful as a separation membrane that can maintain a high filtration rate.

  The porous membrane of the present invention preferably has a porosity in a certain range, and its value is 20 to 80%, preferably 30 to 80%, more preferably 40 to 80%. By setting the porosity within this range, it is possible to achieve a practical filtration rate while maintaining the mechanical strength necessary for filtration. In the present invention, the porosity is a numerical value obtained from the thickness and mass of a membrane cut out by 10 cm square, and the density value of a polymer as a membrane material, and will be described in detail later.

  The porous film of the present invention has a film thickness in the range of 10 to 1000 μm, preferably 20 to 500 μm, more preferably 30 to 300 μm. By setting the film thickness within this range, a practical filtration rate can be realized while maintaining the mechanical strength necessary for filtration as well as the porosity. In addition, in this invention, a film thickness is an average value of the numerical value which measured the thickness of 10 different locations of a porous film using the film thickness meter.

  In addition, from the structure observation result of the scanning electron microscope, the ratio of the thickness of the high porosity layer to the low porosity layer can be easily calculated. In order to protect the region, it is preferable that the thickness ratio is 1/5 or more because it provides sufficient surface openness and is useful for protecting the internal dense layer.

  The pore surface of the porous membrane of the present invention may be coated with a hydrophilic polymer, but in the present invention, the pore surface means that the porous membrane is immersed in a liquid and all the pores of the membrane are liquid. It means the part in contact with the liquid in the filled state.

  And the hydrophilic polymer which coat | covers the said pore surface means the polymer which contains a hydrophilic group in this molecular structure. Examples of the hydrophilic group include a hydroxyl group, an amide group, a carboxyl group, a sulfonic acid group, a polyoxyethylene group having about 1 to 4 repeating units, and among them, a polymer containing a hydroxyl group is particularly preferable. This is because the polymer containing a hydroxyl group is present on the surface of the pores and has sufficient hydrophilicity to allow spontaneous penetration of water, thereby preventing clogging of the membrane and solid content such as plasma. This is because the permeation rate when filtering a high-concentration solution can be kept high.

  Examples of the polymer containing a hydroxyl group include poly (ethylene oxide) derivatives such as polyvinyl alcohol, ethylene vinyl alcohol copolymer, cellulose, cellulose acetate, cellulose butyrate, poly (1-hydroxyethylene oxide), and poly (2-hydroxyethylene oxide). A polymer obtained by polymerizing an ester of acrylic acid or methacrylic acid such as 2-hydroxypropyl acrylate, 2-hydroxyethyl acrylate, 4-hydroxybutyl acrylate, and 2-hydroxyethyl methacrylate with a polyhydric alcohol; Or a mixture thereof. Particularly, a polymer obtained by polymerizing 2-hydroxypropyl acrylate is suitable because it has sufficient hydrophilicity and has a large effect of maintaining a high permeation rate when filtering a solution having a high solid content concentration such as plasma. Used for.

  The amount of the hydrophilic polymer that covers the pore surface of the porous membrane used in the present invention is such that the mass of the hydrophilic polymer that coats the pore surface of the porous membrane is 3 with respect to the porous membrane before coating. It is preferable that it exists in the range of -200 mass%, 5-100 mass% is more preferable, It is especially preferable to set it as 10-70 mass%. By setting the amount of the hydrophilic polymer to be coated within this range, it is possible to keep a high permeation rate when filtering a solution having a high solid content concentration such as plasma. The mass ratio of the hydrophilic polymer is a value obtained by measuring the mass of the dried membrane before and after hydrophilization. In the following description, the mass ratio of the mass of the hydrophilic polymer to the mass of the porous membrane before hydrophilization may be referred to as “hydrophilization rate”.

  As a method of coating the pore surface of the porous membrane used in the present invention with a hydrophilic polymer, the membrane surface to be a porous membrane is coated with a monomer of a hydrophilic polymer raw material and then crosslinked with heat, radiation, a crosslinking agent, etc. A method in which a hydrophilic polymer is dissolved in a suitable solvent to coat the surface of the film, and radicals are generated by irradiating the film with ionizing radiation such as electron beams and gamma rays at a low temperature, and then in a liquid or gaseous state. Known methods (hereinafter referred to as pre-irradiation method), methods of polymerizing monomers by irradiating ionizing radiation in a state where the film is previously contacted with the monomer (hereinafter referred to as simultaneous irradiation method), etc. Among them, the method of contacting the monomer after irradiating the porous film with ionizing radiation is particularly preferable because the surface of the pores can be uniformly coated.

  As a method of irradiating the porous film used in the present invention with ionizing radiation, it is recommended to irradiate the radiation with the oxygen concentration around the film kept as low as possible. The irradiation dose is preferably 10 to 500 kGy, more preferably 50 to 300 kGy in the porous film used in the present invention. As a method for bringing the monomer into contact with the porous film after irradiation, a method in which the monomer is dissolved in a solvent to form a solution and the porous film is immersed in the solution for a predetermined time is recommended. As the solvent for dissolving the monomer, for example, when the monomer is an ester of acrylic acid or methacrylic acid such as 2-hydroxypropyl acrylate and a polyhydric alcohol, alcohols such as methanol, ethanol, propanol and butanol, water Or mixtures thereof are suitable.

As a method of coating the amount of the hydrophilic polymer to be coated in the above-described range (3 to 200% by mass with respect to the porous film before coating), the time and temperature at which the porous film and the monomer are brought into contact with each other are changed. Alternatively, it can be adjusted by changing the monomer concentration when the monomer is dissolved in the solvent. In the present invention, a reaction may be performed after adding a diacrylate compound such as polyethylene glycol diacrylate to the monomer, and the polymer chain resulting from the polymerization of the monomer may be crosslinked. This method is effective for keeping the water permeability high when the amount of the hydrophilic polymer covering the pore surface increases.
It becomes possible to manufacture the hydrophilic porous membrane of the present invention by the above manufacturing conditions.

  A typical application using the hydrophilized porous membrane of the present invention will be described in detail below.

  The hydrophilized porous membrane of the present invention includes a conventional microfiltration membrane or a part of the ultrafiltration membrane including purification of a useful product by removing the unnecessary product from a liquid containing at least a useful product and an unnecessary product. Filtration membranes can be used in a wide range of applications where they are currently used. Examples of such applications include purification of water from sludge or oil / water mixtures, purification of intermediate raw materials in the field of pharmaceutical production or food production, etc. The hydrophilized porous membrane of the present invention is a solution with a high solid content concentration. Is particularly useful for the purification of bioactive substances that may potentially be contaminated by the high filtration rate and high blocking performance against viruses and similar size particles. It is. Examples of the physiologically active substance include proteins in plasma that are useful as raw materials for plasma fractionated preparations. Examples of such proteins include albumin, immunoglobulin, fibrinogen, blood coagulation factor, antithrombin III, fibrin glue, haptoglobin. , Activated protein C, C1-inactivator and the like, but are not limited to those exemplified. Unwanted substances that may potentially be mixed in the physiologically active substance include bacteria, fungi, viruses, pathogenic prions, leukocytes, and cell-derived particles. Therefore, if the hydrophilized porous membrane of the present invention is used, it is possible to provide a useful product-containing liquid purified by removing unnecessary products by filtering a liquid containing at least useful products and unnecessary products. . Furthermore, the present invention also provides a liquid processing method for removing unnecessary substances by filtering a liquid containing at least useful substances and unnecessary substances through the hydrophilic porous membrane of the present invention. As an application from the opposite viewpoint, it is also possible to collect and concentrate viruses from a fluid using the hydrophilic porous membrane of the present invention for virus identification or testing.

  The hydrophilized porous membrane of the present invention can be used alone or in combination with a suitable support structure. Examples of suitable support structures include porous supports such as woven or non-woven fabrics.

  Further, the present invention includes taking the form of a filter for filtration containing at least one membrane for the purpose of easily carrying out filtration using the hydrophilized porous membrane of the present invention. The filter for filtration of the present invention includes those in which the hydrophilic porous membrane of the present invention contained in the filter is formed into a pleated shape. When the membrane is formed in a pleated shape, it is preferable because it can provide a larger membrane surface with respect to the filter capacity than a flat membrane-like membrane.

  Furthermore, the present invention communicates a housing (a) having at least one inlet and at least one outlet, and an inner space of the housing (a) with the first space (c) communicating with the inlet and the outlet. A filtration cartridge including a diaphragm (b) divided into a second space (d), wherein at least a part of the diaphragm (b) is constituted by the hydrophilic porous membrane of the present invention. A filtration cartridge is also provided.

  In addition, in the filter for filtration and the cartridge for filtration of this invention, components other than the hydrophilized porous membrane of this invention can be used without being specifically limited if it is a material normally used as a housing formation raw material.

  In the following examples and comparative examples, each value was measured based on the following definition.

[Hydrophilicity]
Before irradiating with ionizing radiation, the mass of the porous membrane was previously weighed with an electronic balance. Radiation was generated by irradiation with ionizing radiation, and then contacted with a liquid or gaseous monomer to obtain a hydrophilic porous film. The mass of the obtained hydrophilized porous membrane was weighed with the aforementioned electronic balance, and the mass change rate calculated by the equation (1) was defined as the hydrophilization rate (wt%).
Hydrophilization rate (wt%) = (mass of hydrophilized porous membrane−mass of porous membrane before hydrophilization) / (mass of porous membrane before hydrophilization) × 100 (1)

[Film thickness]
The thickness of the porous film was measured using a film thickness meter (Digital Indicator IDF-130, manufactured by Mitutoyo). The average value of the numerical values measured at 10 different points was taken as the film thickness of the porous membrane.

[Porosity]
The mass and volume of the porous membrane were measured, and the porosity (%) was calculated by the equation (2).
Porosity (%) = {1- (mass of porous membrane) / (specific gravity of porous membrane) / (volume of porous membrane)} × 100 (2)

[Water permeability]
A film arbitrarily cut into a circular shape with a diameter of 25 mm from the porous film was used as an evaluation film, and this mass was weighed with an electronic balance. The film thickness was measured with the above-mentioned film thickness meter. The evaluation membrane was set in a filter holder (PP-25 trade name, manufactured by Advantech Co., Ltd.), pure water at a temperature of 25 ° C. was pressurized with an air pressure of 0.1 MPa and allowed to permeate for a certain time, and the permeation amount was measured. From the film area and film thickness of the evaluation film, the amount of water permeation was calculated by equation (3).
Water permeability (L / m ² /hr/(0.1 MPa) / 100 μm)
= (Pure water permeation [L]) / (Membrane area [m ² ]) / (Pure water permeation time [hr]) / (Transmembrane differential pressure [0.1 MPa]) / {100 / (Film thickness) [Μm])} (3)

[Average pore size]
Considering each flow path when a fluid flows through the pores of the porous membrane as a cylindrical tube, and using the Hagen-Poiseillele law that holds when the fluid flows in a steady flow in the cylindrical tube, The flow rate of pure water flowing through the holes is expressed by equation (4).
Flow rate of one hole [m ³ / second] = π × (radius of cylindrical tube [m]) ⁴ / {8 × (pure water viscosity [Pa · second])} × (transmembrane pressure difference [Pa]) / (Film thickness [m]) (4)
On the other hand, the number of pores present per unit area of the porous membrane is expressed by equation (5).
Number of pores [− / m ² ] = (porosity) / {π × (radius [m] of cylindrical tube) ² } (5)
When the equations (4) and (5) are used, the flow rate of pure water per unit area flowing in the porous film is expressed by the equation (6).
Flow rate of porous membrane [m ³ / m ² / second] = (radius of cylindrical tube [m]) ² × (porosity) / {8 × (viscosity of pure water [Pa · second])} × (intermembrane difference Pressure [Pa]) / (film thickness [m]) (6)
The average pore size of the porous membrane was set to be twice the radius of the cylindrical tube calculated using the equation (5) and each measurement value in the calculation of the water permeation amount described above, and the average pore size was calculated by equation (7).
Average pore diameter (nm) = 2 × (radius of cylindrical tube [m]) × 10 ⁹ = 2 × √ {(permeation amount of pure water [m ³ ]) / (membrane area [m ² ]) / (pure water Permeation time [second]) × 8 × (viscosity of pure water [Pa · second]) × (film thickness [m]) / (transmembrane differential pressure [Pa]) / (porosity)} × 10 ^9. (7)

[Maximum hole diameter]
The bubble point (MPa) calculated | required from the bubble point method based on ASTM F316-86 was converted as a largest hole diameter (nm) by following Formula (9) based on following Formula (8) as described in ASTM F316-86. As a test solution for immersing the porous membrane, a fluorocarbon liquid having a surface tension of 12 mN / m (perfluorocarbon coolant FX-3250 trade name, manufactured by Sumitomo 3M) was used.
Maximum pore diameter (μm) = 2860 × (surface tension) / (bubble point, Pa) (8)
Therefore, maximum pore diameter (nm) = maximum pore diameter (μm) × 1000
= {2860 × (surface tension) / (bubble point, Pa)} × 1000
= 2.86 × (surface tension) / (bubble point, MPa) (9)

[Structural observation of porous film]
A film arbitrarily cut to a suitable size from a 10 cm square porous film was fixed to a sample stage with a conductive double-sided tape, and an osmium coating of about 3 to 5 nm was applied to obtain a sample for inspection. Using a high-resolution scanning electron microscope apparatus (S-4700, manufactured by Hitachi, Ltd.), the structure of the surface and cross section of the porous film was observed at an acceleration voltage of 1.0 kV and a predetermined magnification.

[Porosity of membrane surface and cross section]
From the surface structure observation results described above, the area ratio occupied by the voids on the surface of the film was measured by image analysis processing. The electron microscope photography at this time was implemented at 15000 times magnification.
Judgment of Layers with Different Pore Diameters in the Cross Section of the Membrane From the structure observation results of the cross section described above, the area ratio occupied by voids in the cross section of the membrane was measured by image analysis processing. The electron micrographs at this time were performed at a magnification of 3000 times, 5000 times, 10000 times, and 15000 times.

[Determination of layers with different pore diameters in membrane cross section]
From the structure observation results of the cross section described above, the area ratio occupied by the voids in the cross section of the film was measured by image analysis processing. The electron micrographs at this time were performed at a magnification of 3000 times, 5000 times, 10000 times, and 15000 times.

[Filtration rate of fresh human plasma]
A membrane cut arbitrarily from a hydrophilic porous membrane into a circular shape with a diameter of 25 mm was used as an evaluation membrane, and this mass was weighed with an electronic balance. Fresh human plasma used as a test solution is a filtered CPD solution (26.3 g of trisodium citrate dihydrate, 3.27 g of citric acid monohydrate, glucose, 100 mL of blood collected from a donor as an anticoagulant. 23.2 g and 2.51 g of sodium dihydrogen phosphate dihydrate dissolved in 1 L of distilled water for injection and filtered through a filter with a pore size of 0.2 μm) were added and mixed with 14 ml of blood at 3000 rpm. It was obtained by centrifuging for 5 minutes and collecting the supernatant. In order to remove suspended matters mixed in the test solution, hydrophilic Durapore membrane filter (product code: VVLP manufactured by Millipore, nominal pore size: 100 nm), and then a regenerated cellulose hollow fiber membrane filter (Planova manufactured by Asahi Kasei Pharma Co., Ltd.) A 75N filter (product name) was prefiltered to remove impurities and used as a stock solution for filtration. The temperature of the filtrate solution was adjusted to 25 ° C., pressurized with an air pressure of 0.1 MPa, and filtered for 30 minutes. The amount of filtrate accumulated for 30 minutes was measured, and the filtration rate (L / m ² ) of human fresh plasma was calculated by the equation (10).
Plasma filtration rate (L / m ² ) = (Total amount of filtrate in plasma for 30 minutes) / (Membrane area × Plasma filtration time × Transmembrane pressure difference) (10)

[Solid fraction in filtered plasma]
About 1 g of filtered plasma after measuring the filtration rate was collected, and its mass was weighed with an electronic balance. The collected filtered plasma was dried in a vacuum dryer at 60 ° C. for about 6 hours until a constant weight was obtained, and a solid content in the filtered plasma was obtained as a residue. The residue was weighed with the electronic balance described above, and the solid content rate (wt%) in the filtered plasma was calculated by the equation (11).
Solid content ratio (wt%) in filtered plasma = (mass of residue after drying) / (mass of filtered plasma before drying) × 100 (11)
[Removal rate of colloidal gold particles]
A film arbitrarily cut into a circular shape having a diameter of 25 mm from the hydrophilic porous film was used as an evaluation film. The gold colloid stock solution used for the preparation of the test solution was prepared as follows. Tetrachlorogold (III) acid tetrahydrate (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in water for injection (Japan Pharmacopoeia) to prepare a 6.0 mM chloroauric acid aqueous solution. Was added and heated to 80 ° C. while stirring with a stirrer. After the aqueous solution was heated to 80 ° C., 14 g of 4% sodium citrate aqueous solution prepared by dissolving sodium citrate dihydrate (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) in water for injection was added within 20 minutes. The mixture was stirred for 30 minutes while being kept at 80 ° C. After cooling this with cold water for 15 minutes, 18 mL of 30% polyvinylpyrrolidone aqueous solution prepared by dissolving polyvinylpyrrolidone K15 (manufactured by Tokyo Chemical Industry Co., Ltd.) in water for injection was added and stirred for 1 minute to obtain a gold colloid stock solution. . The average particle size of the gold colloid obtained by TEM observation was 34.5 nm. The colloidal gold solution used as the test solution was a solution in which the stock solution was diluted about 10 times with water for injection and the absorbance at 535 nm of the diluted solution was in the range of 1.0 to 1.2. In addition, the light absorbency was measured using the ultraviolet visible spectrophotometer (Shimadzu Corporation UV-1700). The temperature of the test solution was adjusted to 25 ° C., pressurized with an air pressure of 0.1 MPa, and allowed to pass through 3 mL. The absorbance of the obtained permeate was measured, and the removal rate of the gold colloid particles was calculated by the equation (12).
Removal rate of colloidal gold particles (−Log) = − Log [(absorbance of permeate) / (absorbance of test solution)] (12)

[Bovine diarrhea virus removal performance]
A membrane cut arbitrarily from a hydrophilic porous membrane into a circular shape with a diameter of 25 mm was used as an evaluation membrane, and this mass was weighed with an electronic balance. A stock solution of bovine diarrhea virus (hereinafter referred to as “BVDV”) used for the preparation of the test solution was obtained by adding BVDV to 0.5% horse serum. In order to remove the suspended solids mixed in the BVDV stock solution, a sample obtained by pre-filtering with the aforementioned Planova 75N filter to remove impurities was used as a test solution. The temperature of the test solution was adjusted to 25 ° C., pressurized with an air pressure of 0.0272 MPa, and allowed to pass through about 2 mL. The BVDV concentration in the obtained filtrate and test solution was measured by adding each solution to the cells and culturing for 3 to 4 days. Then, using the aggregation reaction, the BVDV concentration was determined by the TCID ₅₀ measurement method according to the equation (13). Removal performance was calculated.
Removal performance of BVDV (-Log) =-Log [(BVDV concentration in filtrate) / (BVDV concentration in test solution)] (13)

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.

[Production Example 1]
Polyethylene resin (Asahi Kasei Chemicals Co., Ltd. Sun Fine, product name) 32% by weight, plasticizer (CGI Esther Co., Ltd. DOP, industrial product) 37% by weight, silica particles (Tokuyama Co., Ltd. Leoroseal DM-10, product name) 31% by weight and 0.32% by weight of antioxidant (Irganox 1010FP, product name, manufactured by Ciba Specialty Chemicals Co., Ltd.) are mixed and stirred and mixed at room temperature for 10 minutes using a mixer (Kawata Super Mixer capacity 100 L). did. The obtained mixed raw material is put into an extruder (BT-40-S-30-L type twin screw extruder manufactured by Plastic Engineering Laboratory Co., Ltd., special order product), and is formed into a sheet form from a flat film extrusion die at 200 ° C. The temperature of the cast roll is set to 120 ° C. with a casting apparatus (custom machine manufactured by Daiki Kogyo Co., Ltd.), and the gap of the cast roll is adjusted so that the thickness of the sheet is about 100 μm. It wound up with the winder at the speed. The production conditions of the sheet are shown in Table 1.

[Production Example 2]
The same raw materials and equipment as in Production Example 1 were used below. 40% by weight of a polyethylene resin, 37% by weight of a plasticizer, 23% by weight of silica particles, and 0.40% by weight of an antioxidant were mixed and stirred and mixed at room temperature for 5 minutes using a mixer. The obtained mixed raw material is put into an extruder, extruded from a flat film extrusion die at 200 ° C. into a sheet shape, the temperature of the cast roll is set to 140 ° C. with a casting apparatus, and the gap between the cast rolls is about 100 μm thick. While being adjusted so as to become, it was wound up by a winder at a speed of 4.2 m / min. The production conditions of the sheet are shown in Table 1.

[Production Example 3]
The same raw materials and equipment as in Production Example 1 were used below. 32% by weight of a polyethylene resin, 42% by weight of a plasticizer, 26% by weight of silica particles, and 0.32% by weight of an antioxidant were mixed and stirred and mixed at room temperature for 5 minutes using a mixer. The obtained mixed raw material is put into an extruder, extruded from a flat film extrusion die at 200 ° C. into a sheet shape, the temperature of the cast roll is set to 120 ° C. with a casting apparatus, and the gap between the cast rolls is about 100 μm thick. While being adjusted so as to become, it was wound up by a winder at a speed of 4.2 m / min. The production conditions of the sheet are shown in Table 1.

[Production Example 4]
The same raw materials as in Production Example 1 were used below. 10% by weight of a polyethylene resin, 43.5% by weight of a plasticizer, 26.5% by weight of silica particles, and 0.10% by weight of an antioxidant were mixed and stirred and mixed at room temperature for 5 minutes using a mixer. The obtained mixed raw material was put into an extruder (ZSK40MC same direction meshing type twin screw extruder manufactured by Werner), and the remaining 20% by weight of plasticizer was used using a feeder (KUBOTA loss-in-weight feeder plunger pump double-line type). Then, while being introduced into the extruder, it was heated and kneaded with a screw and extruded from a strand die for molding a pellet at 200 ° C. The extruded product was passed through a cooling bath at 25 ° C. and molded into a pellet using a fan cutter (made of star plastic). The same equipment as in Production Example 1 was used below. The obtained pellet raw material is put into an extruder, extruded into a sheet form from a flat film extrusion die at 200 ° C., the temperature of the cast roll is set to 120 ° C. with a casting apparatus, and the thickness of the sheet is about 100 μm at the gap of the cast roll. While being adjusted so as to become, it was wound up with a winder at a speed of 3.2 m per minute. The production conditions of the sheet are shown in Table 1.

[Example 1]

Two sheets are cut out from each of the sheets obtained in Production Example 1 and Production Example 4 in a 12 cm square, and two sheets of Production Example 1 are stacked, and the sheets of Production Example 4 are arranged on top and bottom, and a total of four sheets are stacked. A laminated body was obtained. A metal frame having a thickness of 200 μm is arranged around the laminated body, and sandwiched between compression plates (iron 30 cm square, weight 8 kg) and introduced into a 200 ° C. compression molding machine (hydraulic molding machine TD-37 manufactured by Toho Machinery Co., Ltd.). Then, after preheating for 1 minute, a pressure of 5 kg / cm ² was applied and held for 5 minutes. Subsequently, it was introduced into a compression molding machine at 25 ° C. (hydraulic molding machine manufactured by Oji Co., Ltd.) and cooled to room temperature by applying a pressure of 5 kg / cm ² to obtain a laminated integrated sheet. The sheet was cut into 11 cm squares and fixed to a metal frame, and the operation of immersing in methyl ethyl ketone (manufactured by Wako Pure Chemical Industries, Ltd.) for 30 minutes at room temperature was repeated 4 times. The operation of immersing in an aqueous solution of sodium (manufactured by Wako Pure Chemical Industries, Ltd.) for 30 minutes is repeated twice to extract the plasticizer and silica particles, followed by drying overnight at room temperature to obtain a flat membrane-like porous membrane. It was. The average pore size, maximum pore size, film thickness, and porosity of the obtained porous membrane were measured by the methods described above. The measurement results are shown in Table 2 together with the film production conditions and the basic physical properties of the film. Further, as a result of observing the surface structure of the porous film using the above-described scanning electron microscope, it was found from FIG. 1 that the porosity of the film surface was 22%, and 3 in the film thickness direction of the film cross section as shown in FIG. Layers with different layer open areas were observed. Further, as apparent from the comparison between FIG. 5 and FIG. 6, in the inner layer, the hole diameter was small near the boundary with the outer layer, and the hole diameter was large in the central portion. According to FIG. 3, the area ratio of the void portion in the outer layer was 43%, and according to FIG. 5, the area ratio of the void portion in the inner layer was 20%. Furthermore, according to FIG. 6, the area ratio of the void portion at the center of the inner layer was 27%.
[Example 2]

Two sheets are cut out from each of the sheets obtained in Production Example 2 and Production Example 4 in a 12 cm square, and two sheets of Production Example 2 are stacked, and the sheets of Production Example 4 are arranged on top and bottom, and a total of four sheets are stacked. A flat porous membrane was obtained according to Example 1 except that the laminate was used. Table 2 shows the basic physical properties of the obtained porous film. Further, as a result of observing the surface structure of the porous film using the above-described scanning electron microscope, it was found from FIG. 7 that the porosity of the film surface was 20%, and 3 in the film thickness direction of the film cross section as shown in FIG. Layers with different layer open areas were observed. Further, as apparent from the comparison between FIG. 11 and FIG. 12, in the inner layer, the hole diameter is small near the boundary with the outer layer, and the hole diameter is large in the center. According to FIG. 9, the area ratio of the void portion in the outer layer was 40%, and according to FIG. 11, the area ratio of the void portion in the inner layer was 24%. Furthermore, according to FIG. 12, the area ratio of the void portion at the center of the inner layer was 26%.
[Example 3]

  Cut out 2 sheets each in a 12 cm square from the sheets obtained in Production Example 3 and Production Example 4, place the sheets of Production Example 4 on top and bottom of each other, and stack the 4 sheets in total. A flat porous membrane was obtained according to Example 1 except that the laminate was used. Table 2 shows the basic physical properties of the obtained porous film. Moreover, as a result of observing the surface structure of the porous film using the above-mentioned scanning electron microscope, the porosity of the film surface was 20%, and three layers having different porosity in the film thickness direction of the film cross section were observed. It was done. In the inner layer, the hole diameter was small near the boundary with the outer layer, and the hole diameter was large in the center. The area ratio of the void portion in the outer layer was 47%, and the area ratio of the void portion in the inner layer was 29%. Furthermore, the area ratio of the void portion at the center of the inner layer was 35%.

[Comparative Example 1]
The sheet obtained in Production Example 3 was subjected to the extraction step alone as in Example 1 to obtain a flat membrane-like porous film. Table 3 shows the basic physical properties of the obtained porous film. Moreover, as a result of observing the surface structure of the porous film using the scanning electron microscope described above, the porosity of the film surface was 8%. This comparative example shows an example that is not suitable for filtration of a liquid having a high solid content concentration because the water permeability decreases and the average pore size decreases when the porosity of the membrane surface decreases in the present invention. .

[Comparative Example 2]
A porous membrane was produced according to Example 1 of Patent Document 1. That is, except that the silica particles used are Nippon Sil LP (hydrophilic silica) manufactured by Tosoh Silica Co., Ltd., using the same raw materials and equipment as in Production Example 1, 32% by weight of polyethylene resin, 48% by weight of plasticizer, silica A mixed raw material obtained by mixing 20% by weight of particles and 0.32% by weight of an antioxidant at room temperature for 30 minutes is put into an extruder, and extruded at 200 ° C. from a flat film extrusion die into a sheet shape and molded. Then, the extraction process was performed in the same manner as in Example 1 from the obtained sheet. An electron micrograph of the obtained film is shown in FIG. As can be seen from FIG. 13, the porous film produced according to Example 1 of Patent Document 1 had poor pore opening on the outermost surface of the film.
[Example 4]

Polyethylene resin (Sunfine product name, manufactured by Asahi Kasei Chemicals Co., Ltd.) 32.0% by mass, plasticizer (DOP industrial product, manufactured by CG Esther Co., Ltd.) 37.1% by mass, silica particles (Leoro Seal DM-10, manufactured by Tokuyama Corporation) ) 30.9% by mass, 0.32% by mass of antioxidant (Irganox 1010FP product name, manufactured by Ciba Specialty Chemicals Co., Ltd.) and mixed for 10 minutes at room temperature using a mixer (Kawata Supermixer capacity 100 L) Stir and mix. Let the obtained mixed raw material be A-1. On the other hand, 15.0% by mass of a polyethylene resin, 52.3% by mass of a plasticizer, 32.7% by mass of silica particles, and 0.15% by mass of an antioxidant are mixed, and similarly stirred and mixed at room temperature for 5 minutes using a mixer. did. Let the obtained mixed raw material be B-1. The mixed raw material B-1 was added to the first extruder (BTN-25-S2-45-L, the same direction twin screw extruder manufactured by Plastics Engineering Laboratory Co., Ltd.) which was heated to 220 ° C. Was extruded into a second extruder (equipment name is the same as the first extruder) heated to 200 ° C., extruded from a 220 ° C. flat film coextrusion type 2 / 3-layer die into a sheet shape, and the temperature of the cast roll Adjusting the gap between the cast rolls so that the thickness of the sheet is about 600 μm by a casting apparatus (custom machine manufactured by Daiki Kogyo Co., Ltd.) at 100 ° C., the speed of the winder is 1.3 m / min. The tension was set at 4.7 kgf / cm ² and winding was performed. The obtained sheet was cut into a 30 cm square and fixed to a metal frame, and the operation of immersing in methylene chloride (industrial product manufactured by Wako Pure Chemical Industries, Ltd.) at 38 ° C. for 1 hour was repeated 4 times, and further 20% by mass at 80 ° C. The operation of immersing in an aqueous solution of sodium hydroxide (industrial product manufactured by Wako Pure Chemical Industries, Ltd.) for 1 hour is repeated twice to extract the plasticizer and silica particles, and dry overnight at room temperature. Obtained.

The obtained porous film was put in an aluminum bag filled with nitrogen, and irradiated with gamma rays at a temperature of −80 ° C. to a dose of 100 kg. The membrane is taken out of the bag, and 5.5% by mass of 2-hydroxypropyl acrylate (manufactured by Wako Pure Chemical Industries, Ltd.) in a t-butanol (special grade manufactured by Wako Pure Chemical Industries, Ltd.) / Water (1: 3) solution at 40 ° C. After soaking for 20 minutes, it was thoroughly washed with an isopropyl alcohol (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) / Water (1: 1) solution to obtain a hydrophilic porous membrane. The hydrophilicity ratio, film thickness, porosity, water permeability, average pore diameter, and maximum pore diameter of the obtained hydrophilic porous membrane were measured by the methods described above. The measurement results are shown in Table 4 together with the film production conditions.
Further, as a result of observing the surface structure of the hydrophilized porous membrane using the above-mentioned scanning electron microscope, as shown in FIG. 14, the porosity of the membrane surface is 22%, as shown in FIG. Three layers with different hole area ratios were observed. Further, as apparent from comparing FIG. 18 and FIG. 19, in the inner layer, the hole diameter was small near the boundary with the outer layer, and the hole diameter was large in the center. According to FIG. 16, the area ratio of the void portion in the outer layer was 43%, and according to FIG. 18, the area ratio of the void portion in the inner layer was 20%. Further, according to FIG. 19, the area ratio of the void portion at the center of the inner layer was 27%.
[Example 5]

The same materials and equipment as in Example 4 were used below. 32% by mass of a polyethylene resin, 41.8% by mass of a plasticizer, 26.2% by mass of silica particles, and 0.32% by mass of an antioxidant were mixed and stirred and mixed at room temperature for 5 minutes using a mixer. Let the obtained mixed raw material be A-2. On the other hand, a raw material having the same composition as B-1 of Example 5 was also prepared. The mixed raw material A-2 was charged into the first extruder whose temperature was raised to 220 ° C, and the mixed raw material B-1 was charged into the second extruder whose temperature was raised to 200 ° C. Winding at a speed of 1.0 m / min while adjusting the gap between the cast rolls to a sheet thickness of about 550 μm using a casting machine that extrudes from the layer die into a sheet and the cast roll temperature is 100 ° C. The machine was wound with the tension set at 5.1 kgf / cm ² . An extraction step and then a hydrophilization treatment were performed from the obtained sheet in the same manner as in Example 1 to obtain a flat membrane-like hydrophilized porous membrane. Table 4 shows the basic physical properties of the obtained hydrophilic porous membrane.

[Production Example 5]
A mixed raw material having the same composition as A-1 in Example 5 was prepared. The mixed raw material is put into an extruder (a BT-40-S-30-L type twin screw extruder manufactured by Plastic Engineering Laboratory Co., Ltd.), and extruded from a flat membrane extrusion die into a sheet at 200 ° C. The cast roll temperature was set to 120 ° C. with a casting machine (made by Daiki Kogyo Co., Ltd.), and the gap of the cast roll was adjusted so that the thickness of the sheet was about 100 μm, at a speed of 3.5 m / min. It wound up with the winder. The conditions for producing the sheet are shown in Table 5.

[Production Example 6]
The same raw materials as in Example 5 were used for the following. 10% by mass of polyethylene resin, 43.5% by mass of plasticizer, 26.5% by mass of silica particles, and 0.10% by mass of antioxidant were mixed, and the mixture was stirred and mixed at room temperature for 5 minutes using the same mixer as in Example 5. . The obtained mixed raw material was put into an extruder (ZSK40MC same direction meshing type twin screw extruder manufactured by Werner), and the remaining 20% by mass of plasticizer was used using a feeder (KUBOTA loss-in-weight feeder plunger pump double-line type). Then, while being introduced into the extruder, it was heated and kneaded with a screw and extruded from a strand die for molding a pellet at 200 ° C. The extruded product was passed through a cooling bath at 25 ° C. and molded into a pellet using a fan cutter (made of star plastic). The same equipment as in Production Example 5 was used below. The obtained pellet raw material is put into an extruder, extruded into a sheet form from a flat film extrusion die at 200 ° C., the temperature of the cast roll is set to 120 ° C. with a casting apparatus, and the thickness of the sheet is about 100 μm at the gap of the cast roll. While being adjusted so as to become, it was wound up with a winder at a speed of 3.2 m per minute. The conditions for producing the sheet are shown in Table 5.

[Example 6]

Two sheets are cut out from each of the sheets obtained in Production Example 5 and Production Example 6 in a 12 cm square, 1 sheet of Production Example 5 and 2 sheets of Production Example 6 are prepared, and the sheet of Production Example 5 is produced. A laminated body in which a total of 3 sheets were stacked was sandwiched between 6 sheets. A metal frame having a thickness of 200 μm is arranged around the laminate, and is inserted into a compression molding machine (hydraulic molding machine TD-37 manufactured by Toho Machinery Co., Ltd.) sandwiched between compression plates (iron 30 cm square, mass 8 kg). Then, a pressure of 5 kg / cm ² was applied and held for 4 minutes. Subsequently, it was introduced into a compression molding machine at 25 ° C. (hydraulic molding machine manufactured by Oji Co., Ltd.) and cooled to room temperature by applying a pressure of 5 kg / cm ² to obtain a laminated integrated sheet. The sheet was cut into 11 cm squares and fixed to a metal frame, and a flat membrane-like hydrophilized porous membrane was obtained by carrying out an extraction step and then a hydrophilization treatment in the same manner as in Example 5. Table 6 shows the basic physical properties of the obtained hydrophilic porous membrane. Moreover, as a result of observing the surface structure of the hydrophilized porous membrane using the above-mentioned scanning electron microscope, the porosity of the membrane surface is 22% as shown in FIG. 20, and as shown in FIG. Three layers with different hole area ratios were observed. Further, FIG. 23 shows that the hole diameter gradually increases in the inner layer from the boundary with the outer layer toward the center. According to FIG. 22, the area ratio of the void portion in the outer layer was 43%, and according to FIG. 23, the area ratio of the void portion in the inner layer was 20%.

[Example 7]

The same raw materials as in Example 4 were used for the following. 20% by mass of a polyethylene resin, 46.7% by mass of a plasticizer, 33.3% by mass of silica particles, and 0.20% by mass of an antioxidant were mixed and stirred and mixed at room temperature for 5 minutes using the same mixer as in Example 5. . The obtained mixed raw material was put into an extruder (ZSK40MC same direction meshing twin screw extruder manufactured by Werner), heated and kneaded with a screw, and extruded from a strand die for pellet molding at 200 ° C. The extruded product was passed through a cooling bath at 25 ° C. and molded into a pellet using a fan cutter (made of star plastic). This is referred to as pellet B-2. On the other hand, the raw material of the same composition as A-1 of Example 5 was also prepared.
The same equipment as in Example 5 was used below. The mixed raw material A-1 is charged into the first extruder whose temperature is raised to 220 ° C., and the pellet B-2 is charged into the second extruder whose temperature is raised to 200 ° C., and the same amount of plasticizer as the B-2 is extruded. Is introduced into the second extruder using a feeder (a KUBOTA loss-in-weight feeder plunger pump dual type) (by this operation, the polyethylene resin concentration in the melt-kneaded product becomes 10% by mass), While extruding into a sheet form from a 220 ° C flat film co-extrusion two-layer / three-layer die, the cast roll temperature was adjusted to 100 ° C while adjusting the gap between the cast rolls to a sheet thickness of about 610 µm. The winder was wound at a speed of 1.3 m / min with the tension of the winder set to 4.6 kgf / cm ² . By performing an extraction step and then a hydrophilization treatment in the same manner as in Example 4 from the obtained sheet, a flat membrane-like hydrophilized porous membrane was obtained. Table 4 shows the basic physical properties of the obtained hydrophilic porous membrane.
[Example 8]

Using the hydrophilized porous membranes obtained by hydrophilizing the porous membranes obtained in Examples 4 to 6 and the porous membrane obtained in Comparative Example 2 in the same manner as in Example 4, The filtration rate of plasma and the removal rate of colloidal gold particles were measured by the methods described above. The measurement results are shown in Table 7 together with the basic physical properties of the film.
The filtered stock solution after filtration through a regenerated cellulose hollow fiber membrane filter had increased transparency and the suspended matter visible to the naked eye was removed. However, the solid content concentration was 8.5%, which is necessary for plasma. Ingredients were not lost.

[Example 9]

  Using the hydrophilized porous membranes obtained by hydrophilizing the hydrophilized porous membranes obtained in Examples 4 and 7 and the porous membrane obtained in Comparative Example 2 in the same manner as in Example 4, BVDV Removal performance was measured by the method described above. The measurement results are shown in Table 8 together with the basic physical properties of the film.

INDUSTRIAL APPLICABILITY The present invention is useful as a separation membrane for blocking sub-micron particles contained in a liquid, and is used in a field where a high permeation rate is required as a performance, particularly from a physiologically active solution such as plasma, virus, bacteria, pathogenic prion, etc. Can be used as a medical separation membrane that can be removed with high blocking performance. The plasma thus obtained can be used as various raw materials in the field of plasma preparation production, plasma fractionation preparation production, biotechnology, and the like.
Furthermore, the present invention provides an industrial process filter for removing fine particles from chemicals, treated water, etc., an oil / water separation membrane, a liquid gas separation membrane, a separation membrane for purification of water and sewage, a battery separator such as a lithium ion battery, and a polymer battery. The solid electrolyte support can be used for a wide range of applications.

Claims (16)

A step of heating at least two compositions having high and low two polymer concentrations including a polymer and a plasticizer to a temperature equal to or higher than the melting point of the polymer to uniformly melt each independently, at least from the inlet side to the outlet side; By extruding the composition in contact with each other in a mold having an internal structure divided into three layers, the layers made of the composition having a low polymer concentration are positioned on both sides of the layer having a high polymer concentration. A step of obtaining a molten laminate of the high-concentration composition and the low-concentration composition by a step of laminating, by bringing both surfaces of the molten laminate into direct contact with a cooling surface that is at least 80 ° C. lower than the melting temperature A method for producing a skinless porous membrane, comprising a step of obtaining a molded product, and then a step of removing substantially all the plasticizer from the molded product. A step of preparing at least two kinds of compositions having high and low two polymer concentrations including a polymer and a plasticizer, a step of independently forming into a sheet shape, and a sheet comprising a composition having a low polymer concentration is a polymer. A step of obtaining a laminated body superposed so as to be positioned on both surfaces of a high-concentration sheet, a step of heating the laminated body to obtain a molten laminate of the high-concentration composition and the low-concentration composition, A skinless pore having a step of obtaining a molding by directly contacting both sides of the molten laminate to a cooling surface at least 80 ° C. lower than the temperature, and then removing substantially all of the plasticizer from the molding A method for producing a membrane. The method for producing a skinless porous film according to claim 1 or 2, wherein the cooling surface is at least 80 ° C lower than the melting temperature and is a cooled metal roll. A skin further comprising the step of hydrophilizing the pore surface by contacting 2-hydroxypropyl acrylate after irradiating the skinless porous membrane according to any one of claims 1 to 3 with ionizing radiation. A method for producing a porous film. It is a polymer porous film having a multilayer structure in which a high porosity layer is laminated on both sides of a low porosity layer, and there is no skin layer on both surfaces, and the maximum pore size determined by the bubble point method is 10 nm or more and 100 nm. Hereinafter, a skinless porous membrane having an average pore size determined from a water permeability measurement method larger than the maximum pore size and having at least two or more minimum pore size layers in the low porosity layer. 6. The skinless porous membrane according to claim 5, wherein the minimum pore diameter layer is located in the vicinity of the boundary between the low porosity layer and the high porosity layer. The skinless porous membrane according to claim 5 or 6, wherein the pore size at the center in the film thickness direction of the low porosity layer is larger than the pore size at the peripheral portion. The skinless porous membrane according to any one of claims 5 to 7, wherein a cross-sectional open area ratio of the high open area layer is at least 10% higher than that of the low open area layer. The skinless porous film according to any one of claims 5 to 8, wherein the ratio of the thickness of the high porosity layer to the low porosity layer is 1/5 or more. The skinless porous film according to claim 5, which has a porous structure obtained by a melt film forming method. The skinless porous film according to any one of claims 5 to 10, wherein the porosity of both surfaces is 10% or more. The skinless porous material according to any one of claims 5 to 11, wherein the polymer is any of polyolefin, polyester, polyamide, fluorinated hydrocarbon polymer, polyphenylene ether, polyacetal, polyurethane, and polyethersulfone. film. The skinless porous membrane according to any one of claims 5 to 12, wherein the pore surface is coated with a hydrophilic polymer. The skinless porous membrane according to claim 13, wherein the hydrophilic polymer has at least a hydroxyl group. The method of filtering a specific component from the liquid containing at least 2 types of component using the porous film in any one of Claims 5-17. It is characterized by permeating only a physiologically active substance from a liquid containing at least one component selected from the group consisting of bacteria, fungi, viruses, pathogenic prions, leukocytes, and cell-derived particles and a physiologically active substance. The liquid processing method according to claim 15.