Porous polyethersulfone membrane for removing viruses and preparation method of porous polyethersulfone membrane

Abstract

The invention provides a polyethersulfone porous membrane for virus removal and a preparation method thereof.The polyethersulfone porous membrane for virus removal sequentially comprises an outer layer area and an inner layer area in the thickness direction, the average pore size of the outer layer area is 10-20 nm, the thickness of the outer layer area is 20-50 microns, the average pore size of the inner layer area is 5-10 microns, and the thickness of the inner layer area is 20-50 microns. The thickness of the inner layer area is 60 to 150 [mu] m; the polyethersulfone porous membrane for removing viruses is prepared by a method which at least comprises the following steps: taking polyethersulfone as a raw material, and obtaining the polyethersulfone porous membrane for removing viruses under the action of a water-soluble diluent and a hydrophilic additive, wherein the water-soluble diluent comprises ethylene carbonate and polyethylene glycol. The polyethersulfone porous membrane for virus removal has high virus removal rate and protein transmittance.

Description

Technical Field

[0001] The invention belongs to the technical field of membrane materials, and in particular relates to a polyethersulfone porous membrane for removing viruses and a preparation method thereof. Background Art

[0002] In recent years, biological pharmaceutical products have been widely used due to their high therapeutic effects and few side effects. In the manufacturing process, it is necessary to separate and purify the fluid containing biological macromolecules such as antibodies to remove various viruses contained in the fluid. At present, membrane separation is the most commonly used method to remove viruses from fluids. This is because membrane separation technology has high separation efficiency, low energy consumption, and can be carried out at room temperature. It can not only efficiently intercept various viruses, but also will not inactivate proteins, so that various biological macromolecules can be efficiently recovered. Polyethersulfone has become the first choice for virus removal membrane materials due to its excellent biocompatibility, good mechanical properties and good hydrophilicity. At present, more than 60% of virus removal membrane products on the market use polyethersulfone as membrane material. In order to obtain greater economic benefits, it is necessary to make biopharmaceutical products (membranes) remove viruses to the maximum extent while allowing as much protein as possible to pass through during the separation and purification process of filtering and removing viruses. The smallest virus particles are parvoviruses, which are only 18-24nm in size, while the size of proteins such as antibodies is about 10nm. Therefore, the pore size of the membrane used to separate proteins and viruses needs to be evenly distributed between 10-20nm to maximize the removal of viruses while allowing as much protein as possible to pass through.

[0003] U.S. Patent US20200238221A1 prepares a membrane mainly used for filtering viruses, proteins or macromolecules. The membrane has a high protein flux and a long service life, but the average pore size is large and can only intercept large particles with a particle size of several hundred nanometers, but cannot intercept small viruses with a particle size of 20 nm.

[0004] Chinese patent CN202310435896.5 uses volatile poor solvents and multiphase induced phase separation to prepare a high-throughput, high-retention asymmetric polyethersulfone ultrafiltration membrane with a dense cortex, which can ensure the removal of viruses, but the retention rate of bovine serum albumin (BSA) is more than 96%, and it is difficult to guarantee the protein yield.

[0005] In order to simultaneously meet the requirements of high virus retention and high protein permeability, Chinese patent CN1759924B discloses a multi-layer composite ultrafiltration membrane co-cast by different polymer solutions. The composite membrane structure can simultaneously meet the requirements of high virus retention and high protein permeability. However, since the membrane is a composite membrane, different polymers have poor compatibility, which makes the two layers easy to peel off and be damaged, which easily reduces the life of the filter membrane.

[0006] Chinese patent CN202211637916.9 performs pre-phase separation in a low temperature and high humidity environment to form a small pore surface, and then solidifies in a solidifying liquid containing a permeation additive (preferably hexafluoroisopropanol or trifluoroethanol) to form an asymmetric porous membrane structure with a small gradient and continuous change. The structure does not require compounding and is made of a casting liquid. However, the membrane structure formed has a small gradient change, and is easily contaminated and blocked by aggregated protein groups during the actual filtration process, reducing the protein permeation flux and the life of the filter membrane. In addition, the fluorine-containing permeation additive contained in the solidifying liquid used in the preparation process is harmful to the human body and the environment.

[0007] Therefore, how to simply and practically prepare a polyethersulfone membrane that can simultaneously improve virus removal rate and protein permeability is an urgent problem to be solved. Summary of the invention

[0008] The invention provides a polyethersulfone porous membrane for virus removal and a preparation method thereof. The polyethersulfone porous membrane for virus removal has high virus removal rate and protein permeability.

[0009] The present invention provides a polyethersulfone porous membrane for virus removal, which comprises an outer layer region and an inner layer region in sequence along the thickness direction, wherein the average pore size of the outer layer region is 10-20 nm, the thickness of the outer layer region is 20-50 μm, the average pore size of the inner layer region is 5-10 μm, and the thickness of the inner layer region is 60-150 μm; the polyethersulfone porous membrane for virus removal is prepared by a method comprising at least the following processes: using polyethersulfone as a raw material, under the action of a water-soluble diluent and a hydrophilic additive, the polyethersulfone porous membrane for virus removal is obtained; wherein the water-soluble diluent comprises ethylene carbonate and polyethylene glycol 400.

[0010] Optionally, the tensile strength of the polyethersulfone porous membrane for virus removal is 3 to 8 MPa.

[0011] Optionally, the bovine serum albumin permeability of the polyethersulfone porous membrane for virus removal is not less than 95%.

[0012] Optionally, the polyethersulfone porous membrane for virus removal has a removal rate of colloidal gold particles of not less than 4, wherein the particle size of the colloidal gold ions is 18 to 22 nm.

[0013] The present invention provides a method for preparing the polyethersulfone porous membrane for virus removal as described above, comprising: step 1: melting a mixture comprising polyethersulfone powder, a water-soluble diluent and a hydrophilic additive at 180-200°C to obtain a casting solution; the water-soluble diluent comprises ethylene carbonate and polyethylene glycol 400; step 2: applying the casting solution on the surface of a steel plate to obtain a primary ecological membrane located on the surface of the steel plate; the temperature of the steel plate is 160-200°C; step 3: immersing the primary ecological membrane and the steel plate in ice water at 0-10°C for curing, so that the primary ecological membrane is peeled off from the steel plate to obtain an initial membrane; step 4: washing the initial membrane with water, then placing it in an aqueous solution containing Na2S2O8, and then immersing it at 80-100°C for 4-8h to obtain an intermediate membrane; step 5: washing the intermediate membrane with water to obtain the polyethersulfone porous membrane for virus removal.

[0014] Optionally, based on 100 parts by mass of the mixed material, the mass parts of the polyethersulfone powder are 12 to 18, preferably 13 to 16; the mass parts of the water-soluble diluent are 70 to 82, preferably 74 to 79; and the mass parts of the hydrophilic additive are 6 to 12, preferably 8 to 10.

[0015] Optionally, based on 100 parts by mass of the water-soluble diluent, the mass fraction of the acetic carbonate is 70 to 90, preferably 75 to 85.

[0016] Optionally, the hydrophilic additive includes one or more of polyvinylpyrrolidone K17, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K90; preferably polyvinylpyrrolidone K17.

[0017] Optionally, before step 2, the method further includes: degassing the casting solution.

[0018] Optionally, in step 2, the casting liquid is scraped onto the surface of the steel plate to obtain a primary ecological film located on the surface of the steel plate; the temperature of the steel plate is 160-200°C, comprising: at 160-200°C, the casting liquid is scraped onto the surface of the steel plate to form a scraped casting liquid layer with a thickness of 80-200μm, preferably 100-150μm, to obtain a primary ecological film located on the surface of the steel plate.

[0019] The implementation of the present invention has at least the following beneficial effects:

[0020] The invention provides a polyethersulfone porous membrane for virus removal and a preparation method thereof. The polyethersulfone porous membrane for virus removal comprises an outer region (tightly packed dendritic nanopore structure or dendritic pore structure) and an inner region (loose ant-hole-like pore structure or ant-hole-like pore structure) in sequence along the thickness direction. The average pore size of the outer region is 10-20 nm, and the average pore size of the inner region is 5-10 μm. Since the pore size of the outer region is nanometer-level pore size, and the pore size of the inner region is micrometer-level pore size, the pore size difference between the two regions is relatively small. At the transition between the inner and outer layers of the inner and outer regions, the pore size changes rapidly from large to small, and the change is obvious, forming a mutation structure at the transition between the inner and outer layers, wherein the outer region (dendritic pore structure) has high permeability, and the inner region (ant-hole-like pore structure) has the characteristics of high porosity and high permeability. Such a mutation structure can not only ensure that the porous membrane has a higher flux, but also improve its virus retention rate, ensure efficient virus removal, and have a higher protein permeability. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a cross-sectional SEM image of the polyethersulfone porous membrane for virus removal in Example 1;

[0022] Figure 2 is a cross-sectional SEM enlarged image of the outer layer region (dense layer) of the virus removal polyethersulfone porous membrane in Example 1;

[0023] Figure 3 This is a cross-sectional SEM enlarged image of the inner layer region (support layer) of the polyethersulfone porous membrane for virus removal in Example 1;

[0024] Figure 4 is a SEM image of the outer surface layer of the outer layer region of the virus removal polyethersulfone porous membrane in Example 1;

[0025] Figure 5 This is a cross-sectional SEM image of the polyethersulfone porous membrane for virus removal in Comparative Example 1;

[0026] Figure 6 This is a cross-sectional SEM image of the polyethersulfone porous membrane used for virus removal in Comparative Example 2. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] An embodiment of the present invention provides a polyethersulfone porous membrane for virus removal, which includes an outer layer region and an inner layer region in sequence along the thickness direction, wherein the average pore size of the outer layer region is 10 to 20 nm, the thickness of the outer layer region is 20 to 50 μm, the average pore size of the inner layer region is 5 to 10 μm, and the thickness of the inner layer region is 60 to 150 μm; the polyethersulfone porous membrane for virus removal is prepared by a method including at least the following processes: using polyethersulfone as a raw material, and obtaining a polyethersulfone porous membrane for virus removal under the action of a water-soluble diluent and a hydrophilic additive; wherein the water-soluble diluent includes ethylene carbonate and polyethylene glycol 400.

[0029] According to the research and analysis of the inventors: the polyethersulfone porous membrane for virus removal has a porous structure, which is an asymmetric structure with one side dense and the other side loose. Specifically, the polyethersulfone porous membrane for virus removal includes an outer layer region (dense layer) and an inner layer region (support layer) in the thickness direction. The average pore size of the outer layer region is 10-20nm, the thickness of the outer layer region is 20-50μm, and the outer layer region is a tightly packed dendritic nanopore structure. The average pore size of the inner layer region is 5-10μm, the thickness of the inner layer region is 60-150μm, and the inner layer region is a loose ant nest-like pore structure. The outer layer region is helpful for separating viruses due to its smaller average pore size and porosity, and the inner layer region is helpful for passing fluid due to its larger average pore size and porosity. Therefore, the polyethersulfone porous membrane for virus removal has both good virus separation performance and water permeability. In the process of applying the virus removal polyethersulfone porous membrane to remove viruses from fluids, the fluid can flow in from the inner region (loose ant-hole-like pore structure) side and out from the outer region (dense dendritic pore structure) side. The virus enters the membrane with the fluid, passes through the inner region (loose ant-hole-like pore structure), and is then retained in the outer region (dense dendritic pore structure), thereby completing the separation of the virus without affecting the permeability of the protein. Therefore, the virus removal polyethersulfone porous membrane provided by the embodiment of the present invention has a high virus retention rate and a high protein permeability, and can separate biological components at low pressure in a short time, especially the separation of proteins such as antibodies and viruses.

[0030] In some embodiments, the virus-removing polyethersulfone porous membrane has a bovine serum albumin permeability of not less than 95%.

[0031] In some embodiments, the virus removal polyethersulfone porous membrane has a colloidal gold particle removal rate of no less than 4, wherein the particle size of the colloidal gold ions is 18 to 22 nm.

[0032] The virus-removing polyethersulfone porous membrane also has relatively high tensile strength. Specifically, the tensile strength of the polyethersulfone porous membrane may be 3 to 8 MPa.

[0033] The embodiment of the present invention also provides a method for preparing the above-mentioned polyethersulfone porous membrane for virus removal, comprising: step 1: melt-treating a mixture comprising polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive at 180-200°C to obtain a casting liquid; the water-soluble diluent comprises ethylene carbonate and polyethylene glycol 400; step 2: scraping the casting liquid on the surface of a steel plate to obtain a primary ecological membrane located on the surface of the steel plate; the temperature of the steel plate is 160-200°C; step 3: immersing the primary ecological membrane and the steel plate in ice water at 0-10°C for curing treatment, so that the primary ecological membrane is peeled off from the steel plate to obtain an initial membrane; step 4: washing the initial membrane with water, then placing it in an aqueous solution containing Na2S2O8, and then soaking it at 80-100°C for 4-8 hours to obtain an intermediate membrane; step 5: washing the intermediate membrane with water to obtain a polyethersulfone porous membrane for virus removal.

[0034] According to the research and analysis of the inventors: In the preparation system provided by the embodiment of the present invention, polyethylene glycol (water-soluble non-solvent) and hydrophilic additives are used as pore formers to improve the pore interconnectivity of the polyethersulfone porous membrane for virus removal, increase the porosity of the polyethersulfone porous membrane for virus removal, and make the pores on the surface of the polyethersulfone porous membrane for virus removal more uniform; ethylene carbonate (water-soluble high-temperature solvent) dissolves the polyethersulfone powder at high temperature to form a casting liquid, and ethylene carbonate (water-soluble high-temperature solvent) and polyethylene glycol (water-soluble non-solvent) and polyvinyl pyrrolidone (hydrophilic additive) can undergo mass transfer with ice water during subsequent curing and film formation, thereby promoting the curing and film formation of polyethersulfone and promoting A relatively dense dendritic pore structure is formed on the surface of the nascent membrane close to the ice water, that is, a tight outer layer area is formed. At the same time, a heat transfer reaction occurs on the surface of the nascent membrane close to the steel plate, forming a relatively loose ant-hole-like pore structure, that is, a loose inner layer area is formed. At the same time, polyethylene glycol, as a non-solvent, can regulate the compatibility of the reaction system to form a macroporous structure. The additive polyvinyl pyrrolidone can undergo a self-crosslinking reaction under the catalysis of Na2S2O8 to form an interpenetrating network structure in the membrane pores, which can slightly reduce the membrane pores and increase the interception rate without affecting the flux. At the same time, the interpenetrating network structure allows polyvinyl pyrrolidone to remain permanently in the membrane pores to achieve permanent hydrophilicity. Therefore, the preparation method of the embodiment of the present invention can produce a polyethersulfone porous membrane for virus removal with a high virus removal rate and protein permeability.

[0035] The embodiments of the present invention do not limit the specific process of melt treatment. For example, a mixture containing polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive can be placed in a three-necked flask and stirred for melt treatment at 180-200° C. for 2-6 hours to obtain a clear and transparent casting solution.

[0036] The embodiment of the present invention does not limit the mass ratio of each substance in the mixture.

[0037] In some embodiments, based on 100 parts by mass of the mixed material, the mass parts of the polyethersulfone powder are 12 to 18, preferably 13 to 16; the mass parts of the water-soluble diluent are 76 to 86, preferably 78 to 84; the mass parts of the hydrophilic additive are 1 to 6, preferably 2 to 4.

[0038] The mass parts of acetic carbonate may be 70 to 90, preferably 75 to 85, based on 100 mass parts of the water-soluble diluent.

[0039] In the mixed material, the mass ratio of polyethersulfone powder, hydrophilic additive and water-soluble diluent can be (12-18): (1-6): (76-86); preferably (13-16): (2-4): (78-84).

[0040] The weight average molecular weight of the polyethylene glycol may be 360 ​​to 440, for example, 360, 400, 440 or any two thereof. In a specific implementation, the polyethylene glycol may include polyethylene glycol 400, that is, the weight average molecular weight of the polyethylene glycol is 400, which helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal, and avoids the problem of poor compatibility of the reaction system and difficulty in melting due to the high molecular weight of the polyethylene glycol, thereby deteriorating the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal.

[0041] The above-mentioned hydrophilic additive may include polyvinyl pyrrolidone, and the weight-average molecular weight of the polyvinyl pyrrolidone may be 1700 to 1100000, for example, 1700, 49000, 1100000 or a range consisting of any two of them. In a specific implementation, the above-mentioned polyvinyl pyrrolidone includes one or more of polyvinyl pyrrolidone K17, polyvinyl pyrrolidone K30, and polyvinyl pyrrolidone K90; polyvinyl pyrrolidone K17 is preferred, which helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal, and avoid the situation where the molecular weight of polyvinyl pyrrolidone is too high, which will make the hydrophilicity of the membrane after cross-linking poor, thereby deteriorating the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal.

[0042] In the preparation system provided by the embodiment of the present invention, polyethylene glycol (water-soluble non-solvent) and polyvinyl pyrrolidone (hydrophilic additive) are used as pore formers to improve the pore interconnectivity of the polyethersulfone porous membrane for virus removal, increase the porosity of the polyethersulfone porous membrane for virus removal, and make the pores on the surface of the polyethersulfone porous membrane for virus removal more uniform; ethylene carbonate (water-soluble high-temperature solvent) dissolves the polyethersulfone powder at high temperature to form a casting liquid, and ethylene carbonate (water-soluble high-temperature solvent) and polyethylene glycol (water-soluble non-solvent) and polyvinyl pyrrolidone (hydrophilic additive) can undergo mass transfer with ice water during subsequent solidification and film formation, thereby promoting the solidification and film formation of polyethersulfone and promoting the initial A dense dendritic pore structure is formed on the surface of the eco-membrane close to the ice water, that is, a tight outer layer area is formed. At the same time, a heat transfer reaction occurs on the surface of the primary eco-membrane close to the steel plate, forming a loose ant-hole-like pore structure, that is, a loose inner layer area is formed. At the same time, polyethylene glycol, as a non-solvent, can regulate the compatibility of the reaction system to form a macroporous structure. The additive polyvinyl pyrrolidone can undergo self-cross-linking reaction under the catalysis of Na2S2O8 to form an interpenetrating network structure in the membrane pores, which can slightly reduce the membrane pores and increase the retention rate without affecting the flux. At the same time, the interpenetrating network structure allows polyvinyl pyrrolidone to remain permanently in the membrane pores to achieve permanent hydrophilicity.

[0043] In step 2, the casting solution can be applied by scraping on the surface of the steel plate at a temperature of 160 to 200° C. to obtain a primary film on the surface of the steel plate. One side of the primary film faces outward (the side away from the steel plate), and the other side (the side close to the steel plate) is in contact with the steel plate at a temperature of 160 to 200° C.

[0044] In a specific implementation, the casting liquid is scraped onto the surface of the steel plate at 160-200°C to obtain a primary ecological film on the surface of the steel plate, including: at 160-200°C, the casting liquid is scraped onto the surface of the steel plate to form a scraped casting liquid layer with a thickness of 80-200μm, preferably 100-150μm, to obtain a primary ecological film on the surface of the steel plate.

[0045] In step 3, the steel plate (the nascent eco-membrane and the steel plate) bonded with the nascent eco-membrane is immersed in ice water at 0-10°C for curing treatment. The outward surface of the nascent eco-membrane first contacts the ice water and undergoes a mass transfer reaction with the ice water. The rapid mass transfer between ethylene carbonate (a water-soluble high-temperature solvent), polyethylene glycol (a water-soluble non-solvent), and polyvinyl pyrrolidone (a hydrophilic additive) and water will promote the formation of a dense cortex. This is because: first, reducing the mass transfer rate will increase the porosity of the surface and reduce the formation of a dense cortex. Second, the viscosity of the casting liquid will have a greater impact on the structure and performance of the filter membrane finally formed. The higher the viscosity of the casting liquid, the greater the mass transfer resistance and the slower the mass transfer rate. Thirdly, the solid content of the casting liquid plays a decisive role in the viscosity of the casting liquid. When the solid content is low, the viscosity of the casting liquid decreases, and the pore size of the surface pores increases. Ethylene carbonate is a water-soluble high-temperature solvent, and its mass transfer rate is lower than that of N,N-dimethylacetamide (DMAc) used in the conventional non-solvent induced phase separation method, resulting in delayed phase separation. When the solid content is low, the viscosity of the casting liquid decreases, and the pore size of the surface pores increases. Therefore, under the above-mentioned combined effect, an outer layer region (first outer surface) with a large number of uniform small pores is formed.

[0046] At the same time, the other side of the initial ecological membrane that is attached to the steel plate surface is close to the steel plate with a higher temperature. During the heat transfer reaction with ice water, the ethylene carbonate-polyethersulfone system shows a phenomenon of high-temperature compatibility and low-temperature phase separation, which is a typical thermally induced phase separation process. It will promote the formation of a cross-sectional ant-hole-like pore structure and form a relatively loose porous structure, that is, the formation of an inner layer area. At the same time, polyethylene glycol is added to the system as a non-solvent additive, which makes the system compatibility worse and makes it easier to cool and separate the phases to form an inner layer area with a macroporous structure. Under the joint action of the two, a loose ant-hole-like pore structure is formed, that is, the formation of an inner layer area (second outer surface). In this way, as heat and mass transfer continue to occur on both sides of the surface, an initial membrane is gradually formed with a porosity and average pore size that increases (e.g., a gradient increasing trend) from the outer layer area (first outer surface) to the inner layer area (second outer surface).

[0047] As the curing process proceeds, the initial film is gradually peeled off from the steel plate to obtain the initial film.

[0048] In addition, the embodiments of the present invention do not limit the specific operations of step 2 (film forming treatment) and step 3 (curing treatment). For example, in some embodiments, the casting liquid is allowed to stand at 160-200°C for 0.5-4.5 hours for degassing, and then poured onto a steel plate at 160-200°C, and coated on the steel plate with a stainless steel scraper for film forming treatment to obtain a primary eco-film, which helps to improve the film forming effect. This is because if the temperature of the film forming treatment is too low, the casting liquid system will solidify and it will be difficult to scrape and form a film; if the temperature of the film forming treatment is too high, the water-soluble diluent will volatilize, which is not conducive to the subsequent mass transfer process.

[0049] In addition, if the temperature of the ice water used for the curing treatment is too high or too low, it is difficult to form a sudden asymmetric structure and a double continuous structure. The embodiment of the present invention is conducive to the formation of a polyethersulfone porous membrane with the above structure by limiting the temperature of the film forming treatment and the curing treatment.

[0050] In step 4, the initial membrane is washed with water, then placed in an aqueous solution containing Na2S2O8, and then soaked at 80-100°C for 4-8 hours to allow the hydrophilic additive to undergo a self-crosslinking reaction to obtain an intermediate membrane. Exemplarily, the soaking temperature may be 80°C, 90°C, 100°C, or a range consisting of any two thereof, preferably 90°C, and the soaking time may be 4h, 6h, 8h, or a range consisting of any two thereof, preferably 6h. It helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal. The reason for the analysis is that if the soaking temperature is too low and the cross-linking reaction time is too short, the cross-linking reaction will be incomplete, and it will be difficult to achieve the effect of increasing hydrophilicity and shrinking the pores; if the soaking temperature is too high and the cross-linking reaction time is too long, it will lead to excessive cross-linking, blocking the pores and reducing the flux. Therefore, the embodiments of the present invention help ensure sufficient cross-linking and improve the pore structure and surface hydrophilicity of the polyethersulfone porous membrane by limiting the above-mentioned immersion temperature and time, which helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal.

[0051] The present invention is further described below by specific examples and comparative examples. Unless otherwise specified, the reagents, materials and instruments used below are all conventional reagents, conventional materials and conventional instruments, which can be commercially available, and the reagents and materials involved can also be synthesized by conventional synthesis methods.

[0052] Example 1

[0053] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0054] 12 g of polyethersulfone powder (Solvay 3000MP), 10.75g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 75.25g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0055] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a steel plate at 180°C, and coated on the surface of the steel plate with a stainless steel scraper to form a uniform primary eco-film, wherein the distance between the stainless steel scraper and the steel plate was 150 μm;

[0056] The nascent eco-film and the steel plate are immersed in a 0°C ice water coagulation bath to solidify them into a film, thereby obtaining an initial film;

[0057] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0058] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0059] Example 2

[0060] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0061] 14 g of polyethersulfone powder (Solvay 3000MP), 10.5g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 73.5g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0062] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with the distance between the stainless steel scraper and the steel plate being 150 μm;

[0063] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0064] The initial film was placed in a 0.4% Na2S2O8 aqueous solution at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film.

[0065] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0066] Example 3

[0067] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0068] 18 g of polyethersulfone powder (Solvay 3000MP), 10g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 70g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0069] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0070] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0071] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0072] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0073] Example 4

[0074] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0075] 14 g of polyethersulfone powder (Solvay 3000MP), 8.4g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 75.6g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0076] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0077] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0078] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0079] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0080] Example 5

[0081] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0082] 14 g of polyethersulfone powder (Solvay 3000MP), 5.6g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 78.4g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0083] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0084] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0085] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0086] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0087] Example 6

[0088] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0089] 14 g of polyethersulfone powder (Solvay 3000MP), 16.8g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 67.2g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0090] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0091] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0092] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0093] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0094] Example 7

[0095] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0096] 14 g of polyethersulfone powder (Solvay 3000MP), 10g polyethylene glycol 400, 6g polyvinyl pyrrolidone (K17, molecular weight 8000), and 70g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0097] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0098] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0099] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0100] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0101] Example 8

[0102] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0103] 14 g of polyethersulfone powder (Solvay 3000MP), 10.625g polyethylene glycol 400, 1g polyvinyl pyrrolidone (K17, molecular weight 8000), and 74.375g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0104] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0105] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0106] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0107] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0108] Example 9

[0109] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0110] 14 g of polyethersulfone powder (Solvay 3000MP), 10.5g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 73.5g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0111] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 80 μm between the stainless steel scraper and the steel plate;

[0112] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0113] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0114] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0115] Example 10

[0116] The preparation process of the virus removal polyethersulfone porous membrane of this embodiment includes the following steps:

[0117] 14 g of polyethersulfone powder (Solvay 3000MP), 10.5g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 73.5g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0118] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 200 μm between the stainless steel scraper and the steel plate;

[0119] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0120] The initial film was placed in a 0.4% mass concentration Na2S2O8 aqueous solution and immersed at 90°C for 6 hours to allow the polyvinyl pyrrolidone to self-crosslink and obtain an intermediate film;

[0121] The intermediate membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a polyethersulfone porous membrane for virus removal.

[0122] Comparative Example 1

[0123] The preparation process of the virus removal polyethersulfone porous membrane of this comparative example comprises the following steps:

[0124] 14 g of polyethersulfone powder (Solvay 3000MP), 10g polyethylene glycol 400, 2g polyvinyl pyrrolidone (K17, molecular weight 8000), and 74g N,N-dimethylacetamide were stirred and dissolved in a three-necked flask at 50°C for 6h to prepare a clear and transparent casting solution;

[0125] The casting solution was placed at 25°C for 12 hours for degassing, then poured onto a 25°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with a distance of 150 μm between the stainless steel scraper and the steel plate;

[0126] The nascent eco-film is immersed in a 0°C ice-water coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0127] The initial membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a porous membrane.

[0128] Comparative Example 2

[0129] The preparation process of the virus removal polyethersulfone porous membrane of this comparative example comprises the following steps:

[0130] 14 g of polyethersulfone powder (Solvay 3000MP), 86g of ethylene carbonate was stirred and melted in a three-necked flask at 180°C for 4h to prepare a clear and transparent casting solution;

[0131] The casting solution was placed at 180°C for 2.5 hours for degassing, then poured onto a 180°C steel plate, and coated on the steel plate with a stainless steel scraper to form a uniform primary eco-film, with the distance between the stainless steel scraper and the steel plate being 150 μm;

[0132] The nascent eco-film is immersed in a liquid nitrogen coagulation bath to solidify it into a film, thereby obtaining an initial film;

[0133] The initial membrane was immersed in pure water for 48 hours to remove polyethylene glycol 400 and polyvinyl pyrrolidone (to extract the diluent and unreacted additives) to obtain a porous membrane.

[0134] Test example

[0135] 1. Scanning electron microscope image

[0136] The polyethersulfone porous membrane for virus removal (membrane product) was sampled multiple times and directly observed using a scanning electron microscope;

[0137] 2. Determination of porosity and average pore size

[0138] Porosity: Image J image analysis software was used to characterize and analyze the SEM electron microscope images to obtain the porosity of different areas of the membrane cross section.

[0139] Average pore size: The membrane product is sampled multiple times and measured using a scanning electron microscope;

[0140] Thickness of the support layer (inner region), thickness of the separation layer (outer region): The membrane product was sampled multiple times and observed and measured using a scanning electron microscope.

[0141] 3. Mechanical strength test

[0142] The upper and lower ends of a film product with a length of 30 mm were clamped on a tensile testing machine and tested using an AGS-J electronic universal testing machine, wherein the tensile speed used was 250 mm / min, and the tensile strength was measured.

[0143] 4. Determination of pure water flux

[0144] The membrane product and the membrane shell are packaged into a membrane assembly, and the membrane assembly is used as a filter membrane. Pure water with a certain pressure P (in bar) and a water temperature of 25°C is passed through the filter membrane. After stabilization for 30 minutes, samples are taken at intervals (T) and the water production (V) is measured for a certain period of time. The average value is calculated three times, and the effective area of ​​the filter membrane through which pure water passes is A (in m 2 ). According to J = V / (A×T×P), the pure water flux J corresponding to the membrane product is calculated in units of L / (m 2 ·h·bar).

[0145] 5. Determination of removal rate and permeability

[0146] The determination process of the removal rate of 20nm colloidal gold particles (logarithmic removal rate (LRV) of 20nm colloidal gold) is as follows:

[0147] (1) Preparation of colloidal gold solution: A colloidal gold solution with a particle size of 20 nm (Nanopartz) was purchased at a concentration of 0.05 mg / ml. 0.2 wt % sodium dodecyl sulfate (SDS) was added to the solution to prepare a raw material solution.

[0148] (2) Filtration of colloidal gold solution: Pure water at a pressure of 0.1 MPa and a water temperature of 25°C was passed through the filter membrane. After stabilization for 30 min, a 0.2 wt% SDS solution was passed through the membrane assembly for 5 min to wet the membrane and reduce the adsorption of gold nanoparticles. The prepared colloidal gold raw material solution was then passed through the membrane assembly. The filtration area of ​​the membrane for removing viruses was 0.001 m 2 .

[0149] (3) Removal rate of colloidal gold particles: The raw material solution and the permeate of the prepared 20 nm colloidal gold solution were collected, and the absorbance of the raw material solution (A) and the permeate (B) at the maximum absorption wavelength was measured using an ultraviolet spectrophotometer. According to LRV=log 10 (A / B) Calculation of the logarithmic removal value (LRV) of 20 nm colloidal gold.

[0150] (4) BSA protein particle permeability:

[0151] A 600ppm bovine serum albumin (BSA) solution was prepared in PBS buffer as the raw material solution, and pure water at a pressure of 0.1MPa and a water temperature of 25°C was passed through the filter membrane. After stabilization for 30 minutes, the PBS buffer was passed through the membrane assembly for 5 minutes to wet the membrane, and then the BSA raw material solution was passed through the membrane assembly. The BSA raw material solution and the permeate were collected and measured using an ultraviolet spectrophotometer. The BSA raw material solution concentration (C0) and the permeate concentration (C1) were converted to obtain the permeability S (%) of the membrane product to BSA protein particles according to S = C1 / C0 × 100%.

[0152] The test results are shown in Table 1

[0153] Table 1

[0154]

[0155]

[0156] Combination Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6As shown in Table 1, the porosity and average pore size of the virus removal polyethersulfone porous membrane of the embodiment of the present invention increase from the loose ant-shaped pore structure side to the densely packed dendrite pore structure side. Comparative Examples 1-10 and Comparative Examples 1-2 show that the polyethersulfone porous membrane provided by the present invention has a special structure with one side dense and the other side loose, and has excellent water flux and high colloidal gold retention rate and BSA permeability, and pollution resistance. Among them, it can be seen from Comparative Examples 1-10 and Comparative Examples 1-2 that the present invention can prepare a polyethersulfone porous membrane with excellent performance by selecting a specific hydrophilic additive and matching a specific preparation process, while the membrane structure prepared in Comparative Examples 1 and 2 does not meet the limitation of the average pore size, and Comparative Example 1 is a membrane prepared by pure NIPS, with poor mechanical strength, low BSA permeability, and poor anti-pollution ability; Comparative Example 2 is prepared by pure TIPS, and the colloidal gold retention rate is poor.

[0157] The preferred specific embodiments and experimental verification of the present invention are described in detail above. It should be understood that ordinary technicians in this field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in this technical field through logical analysis, reasoning or limited experiments based on the concept of the present invention on the basis of the prior art should be within the protection scope of the present invention.

Claims

1. A polyethersulfone porous membrane for virus removal, characterized in that: The virus-removing polyethersulfone porous membrane includes an outer layer region and an inner layer region in sequence along the thickness direction, wherein the average pore size of the outer layer region is 10 to 20 nm, the thickness of the outer layer region is 20 to 50 μm, the average pore size of the inner layer region is 5 to 10 μm, and the thickness of the inner layer region is 60 to 150 μm; The virus-removing polyethersulfone porous membrane is prepared by a method comprising at least the following steps: using polyethersulfone as a raw material, under the action of a water-soluble diluent and a hydrophilic additive, obtaining the virus-removing polyethersulfone porous membrane; Wherein, the water-soluble diluent includes ethylene carbonate and polyethylene glycol.

2. The polyethersulfone porous membrane for virus removal according to claim 1, characterized in that: The tensile strength of the polyethersulfone porous membrane for virus removal is 3 to 8 MPa.

3. The polyethersulfone porous membrane for virus removal according to claim 1 or 2, characterized in that: The bovine serum albumin permeability of the virus-removing polyethersulfone porous membrane is not less than 95%.

4. The polyethersulfone porous membrane for virus removal according to any one of claims 1 to 3, characterized in that: The virus removal polyethersulfone porous membrane has a colloidal gold particle removal rate of not less than 4, wherein the particle size of the colloidal gold ions is 18 to 22 nm.

5. A method for preparing a polyethersulfone porous membrane for virus removal according to any one of claims 1 to 4, characterized in that: include: Step 1: melt-treating a mixture of polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive at 180-200° C. to obtain a casting solution; The water-soluble diluent includes ethylene carbonate and polyethylene glycol; Step 2: applying the casting solution on the surface of the steel plate to obtain a primary ecological film on the surface of the steel plate; The temperature of the steel plate is 160-200°C; Step 3: immersing the nascent eco-film and the steel plate in ice water at 0-10° C. for curing, so that the nascent eco-film is peeled off from the steel plate to obtain an initial film; Step 4: washing the initial membrane with water, then placing it in an aqueous solution containing Na2S2O8, and then soaking it at 80-100°C for 4-8h to obtain an intermediate membrane; Step 5: After washing the intermediate membrane with water, the virus removal polyethersulfone porous membrane is obtained.

6. The preparation method according to claim 5, characterized in that: Based on 100 parts by mass of the mixed material, the mass parts of the polyethersulfone powder are 12 to 18, preferably 13 to 16; the mass parts of the water-soluble diluent are 76 to 86, preferably 78 to 84; the mass parts of the hydrophilic additive are 1 to 6, preferably 2 to 4.

7. The preparation method according to claim 5 or 6, characterized in that: Based on 100 parts by mass of the water-soluble diluent, the mass fraction of the acetic carbonate is 70 to 90, preferably 75 to 85.

8. The preparation method according to any one of claims 5 to 7, characterized in that: The hydrophilic additive includes one or more of polyvinyl pyrrolidone K17, polyvinyl pyrrolidone K30, and polyvinyl pyrrolidone K90; polyvinyl pyrrolidone K17 is preferred.

9. The preparation method according to any one of claims 5 to 8, characterized in that: The polyethylene glycol includes polyethylene glycol 400.

10. The preparation method according to any one of claims 5 to 9, characterized in that: In step 2, the casting solution is applied by scraping on the surface of the steel plate to obtain a primary ecological film on the surface of the steel plate; The temperature of the steel plate is 160-200°C, including: The casting liquid is coated on the surface of the steel plate by blade coating to form a blade coating casting liquid layer with a thickness of 80 to 200 μm, preferably 100 to 150 μm, to obtain a primary green film on the surface of the steel plate.

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