A hydrophilized hollow polyvinylidene fluoride membrane, preparation method and application thereof

Abstract

The invention provides a hydrophilized hollow polyvinylidene fluoride membrane, a preparation method and an application thereof. On the basis of a co-irradiation method, a hollow polyvinylidene fluoride based membrane is encapsulated in a membrane assembly so that cavities capable of adding liquid are formed on both sides of a base membrane; a first solution is added to the cavity on the inner side of the membrane, and a second solution is added to the cavity on the outer side of the membrane; driven by a concentration difference on both sides of the membrane, the hydrophilic monomer in the first solution gradually diffuses from large pores on the inner side of the membrane to small pores on the outer side of the membrane, so that the membrane forms a gradient distribution of hydrophilic monomer concentration from large to small from the inside to the outside, and further initiates graft polymerization by means of irradiation. The invention further effectively controls the density and polymerization degree of grafting reaction between the monomer and each part of the membrane by adjusting the monomer mass concentration, diffusion time, irradiation intensity, number of irradiations, solvent concentration and solvent type, thereby realizing accurate control of hydrophilic modification of different regions of the base membrane, so that the base membrane can be used as a virus removal membrane and better used in the biopharmaceutical separation process.

Description

Technical Field

[0001] The invention relates to the technical field of polymer membrane materials, and in particular to a hydrophilized hollow polyvinylidene fluoride membrane, a preparation method and application thereof. Background Art

[0002] There is a great risk of contamination by endogenous or exogenous viruses in the production process of biological products. Therefore, at least two different virus removal processes are required in the biopharmaceutical process to ensure the safety of biological products. Membrane separation technology based on pore size screening mechanism is highly favored because it has the advantages of high virus removal efficiency and no damage to the structural properties of the target protein.

[0003] At present, common membrane materials for virus removal membranes include cellulose, polyethersulfone (PES) and polyvinylidene fluoride (PVDF). PVDF is a semi-crystalline polymer with good mechanical properties, weather resistance and chemical stability, and is therefore one of the mainstream membrane materials for ultrafiltration membranes and microfiltration membranes. The hydrophilic-modified PVDF membrane has a lower adsorption rate for proteins, which is a very important advantage for biopharmaceutical companies.

[0004] Common hydrophilic modification methods mainly include: physical coating, blending, chemical grafting and irradiation modification. Among them, the irradiation grafting method is a more convenient, higher overall modification efficiency, safer and cleaner hydrophilic method. Patent No. CN200610154892.6 announced the use of pre-irradiation method to achieve membrane hydrophilization, specifically, the polymer membrane is pre-irradiated first, and then placed in a monomer solution, and the free radicals remaining on the polymer membrane are used to initiate monomer polymerization to achieve grafting reaction and complete hydrophilization. However, in order to reduce the annihilation of free radicals after pre-irradiation, the irradiated and irradiated polymer membrane is required to be stored in a low temperature (<20°C) environment, the operating conditions are relatively high, and the hydrophilization effect is poor under the same irradiation dose; co-irradiation is to immerse the membrane to be modified in the modified monomer solution, irradiate the membrane and the monomer at the same time, initiate grafting polymerization, and achieve hydrophilization. The dose utilization rate of co-irradiation modification is high, and the modification can be achieved under relatively low conditions. However, the co-irradiation modification methods reported so far all involve completely immersing the membrane to be modified in a monomer solution for irradiation. Therefore, the amount of monomer grafting at different positions of the membrane is substantially the same, which results in the method being used in the modification process of a virus removal membrane with a gradient pore structure. It is easy for the method to be used in the modification process of a virus removal membrane with a gradient pore structure. This method may result in insufficient hydrophilization of the larger pore size due to a low amount of grafting, or a high grafting rate, which may result in the smaller pore size being completely blocked by the hydrophilized chain segments. For example, the pure water flux of the polyvinylidene fluoride membrane disclosed in patent CN116617876A decreased by about 30% after co-irradiation grafting modification. Since the virus removal membrane separation process requires the minimum pore size of the membrane to be around 20 nm, it is more likely to cause clogging of the membrane pores during the hydrophilization process.

[0005] Therefore, it is urgent to develop a hydrophilic modification method for gradient pore structure virus removal membranes. Summary of the invention

[0006] In view of the above problems existing in the prior art, the present invention provides a hydrophilic hollow polyvinylidene fluoride membrane, a preparation method and an application thereof, and adopts a co-irradiation method to achieve precise control of the hydrophilic modification of different regions of the hollow polyvinylidene fluoride membrane.

[0007] The specific content of the invention is as follows:

[0008] In a first aspect, the present invention provides a method for preparing a hydrophilized hollow polyvinylidene fluoride membrane, the method comprising:

[0009] Step 1, encapsulating a hollow polyvinylidene fluoride based membrane in a membrane assembly so that cavities capable of adding liquid are formed on both sides of the hollow base membrane;

[0010] Step 2, adding a first solution containing a hydrophilic monomer into the inner cavity of the base membrane, and adding a second solution not containing a hydrophilic monomer into the outer cavity of the base membrane, the hydrophilic monomer in the first solution diffuses to the outside of the base membrane driven by the concentration difference on both sides of the base membrane, and after a period of diffusion, the membrane assembly is placed in an irradiation device for irradiation to perform atom transfer radical polymerization modification;

[0011] Step 3: After the irradiation is completed, pour out the solution in the membrane assembly and wash with pure water to remove the residual hydrophilic monomer and self-polymer in the membrane;

[0012] Step 4, repeating steps 2-3 several times, increasing the concentration of the hydrophilic monomer in the first solution and reducing the diffusion time each time, removing the membrane assembly after completion, soaking the membrane fibers in pure water for 8-24 hours, and drying to obtain a hydrophilized hollow polyvinylidene fluoride membrane;

[0013] The hydrophilic monomer is a compound containing a hydroxyl group, an ester group, a carboxylic acid group, an epoxy group, and a double bond capable of free radical polymerization.

[0014] Optionally, the hydrophilic monomer is one or a mixture of more than one of hydroxybutyl acrylate, hydroxypropyl acrylate, hydroxyethyl acrylate, glycidyl acrylate, 2-methoxyethyl acrylate, hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate and glycidyl methacrylate.

[0015] Optionally, the first solution is a mixed solution of the hydrophilic monomer, a first alcohol solution and water, the first alcohol solution is a methanol and / or ethanol solution; the mass concentration of the first alcohol solution is 10-50%; when used for the first time, the mass concentration of the hydrophilic monomer in the first solution is 0.5-20wt%; when used repeatedly, the mass concentration of the hydrophilic monomer in the first solution is 10-20% higher than that of the last use;

[0016] The second solution is a second alcohol solution, or a mixed solution of the second alcohol solution and water. The second alcohol solution is one or more of ethanol, n-propanol, isopropanol, and isobutanol solutions. The mass concentration of the second alcohol solution is 50-100%.

[0017] Optionally, when performing the first diffusion, the diffusion time is 1 to 20 minutes; when performing repeated diffusion, the diffusion time is 20 to 30% shorter than the previous diffusion time.

[0018] Optionally, the radiation emitted by the irradiation device is an electron beam, a gamma ray, a beta ray or a neutron ray;

[0019] The dose of a single irradiation is 1-50 kGy.

[0020] Optionally, the hollow polyvinylidene fluoride-based membrane has a gradient porous structure, the pore size decreases from the inside to the outside, the pore size of the inner macropore is 80 to 250 nm, and the pore size of the outer micropore is 15 to 30 nm;

[0021] The logarithmic removal rate of colloidal gold by the hollow polyvinylidene fluoride-based membrane is greater than 4LRV;

[0022] The pure water flux of the hollow polyvinylidene fluoride based membrane is 160-200LMH / 0.3MPa;

[0023] The wall thickness of the hollow polyvinylidene fluoride based membrane is 50-100 μm.

[0024] Optionally, the hollow polyvinylidene fluoride-based membrane is obtained by the following preparation method:

[0025] After uniformly mixing 30%-60% of polyvinylidene fluoride and 40%-70% of a diluent by mass, adding the mixture into a screw extruder at 200°C-270°C, and fully mixing the mixture to obtain a homogeneous film casting solution;

[0026] The homogeneous casting liquid is extruded through an annular spinneret, and a core liquid at 170-270° C. is injected into the spinneret to maintain a hollow inner cavity; the extruded fiber containing the core liquid is stretched at a speed of 40-100 m / min, and after passing through a room temperature air section for 10-100 ms, enters a cooling bath at a temperature of 0-50° C., and then solidifies into a membrane material;

[0027] The membrane material is immersed in an extractant, and after removing the diluent in the membrane, it is dried to obtain a hollow polyvinylidene fluoride-based membrane with a gradient pore structure.

[0028] Optionally, the diluent is one or a mixture of more than one of diethyl phthalate, dibutyl phthalate, dihexyl phthalate, dioctyl phthalate, tributyl citrate, triethyl citrate, dioctyl acetyl citrate, tributyl acetyl citrate, γ-butyrolactone, dioctyl adipate and dihexyl adipate;

[0029] The core liquid is one or a mixture of dihexyl phthalate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate and γ-butyrolactone;

[0030] The extractant is ethanol.

[0031] In a second aspect, the present invention provides a hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method described in the first aspect.

[0032] In a third aspect, the present invention provides an application of a hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method described in the first aspect, characterized in that the hydrophilized hollow polyvinylidene fluoride membrane is used for separation of proteins and viruses in the field of biopharmaceuticals.

[0033] Compared with the prior art, the present invention has the following advantages:

[0034] The invention provides a preparation method of a hydrophilized hollow polyvinylidene fluoride membrane. On the basis of a co-irradiation method, a hollow polyvinylidene fluoride membrane is encapsulated in a membrane assembly so that cavities capable of adding liquid are formed on both sides of the hollow base membrane; a first solution containing a hydrophilic monomer is added to the cavity on the inner side of the membrane, and a second solution not containing a hydrophilic monomer is added to the cavity on the outer side of the membrane; driven by a concentration difference on both sides of the membrane, the hydrophilic monomer in the first solution gradually diffuses from large pores on the inner side of the base membrane to small pores on the outer side of the base membrane, so that the base membrane forms a gradient distribution of hydrophilic monomer concentration from large to small from the inside to the outside, and further irradiation is used to initiate graft polymerization to realize hydrophilic modification of the hollow polyvinylidene fluoride membrane; and the invention further effectively controls the density and polymerization degree of grafting reaction between the monomer and each part of the membrane by adjusting the monomer mass concentration, diffusion time, irradiation intensity, irradiation times, solvent concentration and solvent type, so as to realize that the grafting quantity is in direct proportion to the size of the membrane pores, so as to obtain a gradient hydrophilized hollow polyvinylidene fluoride membrane.

[0035] The hydrophilized hollow polyvinylidene fluoride membrane provided by the present invention has a gradient distribution of the number of grafted hydrophilic groups inside the membrane structure, is firmly bonded to the base membrane, and has very little effect on the permeability of the membrane pores, thereby achieving a significant increase in the protein permeability without affecting the base membrane flux; the irradiation is performed multiple times in stages, and the required irradiation dose is small, and compared with alkali treatment and conventional irradiation, the damage to the mechanical properties of the membrane fibers is greatly reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0037] Figure 1 A flow chart of a method for preparing a hydrophilized hollow polyvinylidene fluoride membrane provided by an embodiment of the present invention is shown;

[0038] Figure 2 The cross-sectional SEM image of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown;

[0039] Figure 3 The macropore side SEM image of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown;

[0040] Figure 4 The SEM image of the pore side of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown;

[0041] Figure 5 The infrared images of the hydrophilized hollow polyvinylidene fluoride membranes provided in Example 1 and Comparative Examples 1 and 3 of the present invention are shown.

[0042] Figure 6 A schematic diagram of the structure of a membrane assembly provided in an embodiment of the present invention is shown.

[0043] Description of reference numerals:

[0044] 1. Tubular material with openings at both ends; 2. Sealant; 3. Liquid inlet of the outer cavity; 4. Hollow polyvinylidene fluoride based membrane; 5. The outer cavity of the basement membrane; 6. The inner cavity of the basement membrane. DETAILED DESCRIPTION

[0045] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means a limitation on the present invention and its application or use. Based on the embodiments of the present invention, any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts falls within the scope of protection of the present invention. In addition, all other embodiments obtained by ordinary technicians in this field without carrying out creative work belong to the scope of protection of the present invention.

[0046] In the embodiment, no specific experimental steps or conditions are indicated, and the operation or conditions of the conventional experimental steps described in the prior art in this field can be carried out. The reagents used and other instruments that do not indicate the manufacturer are conventional reagent products that can be obtained commercially. In addition, the accompanying drawings are only schematic diagrams of the embodiments of the present invention and are not necessarily drawn to scale. The same reference numerals in the figures represent the same or similar parts, and thus their repeated description will be omitted. Some block diagrams shown in the accompanying drawings are functional entities and do not necessarily correspond to physically or logically independent entities.

[0047] Technologies, methods, and equipment known to ordinary technicians in the relevant field may not be discussed in detail, but where appropriate, the technologies, methods, and equipment should be considered as part of the description of the present invention.

[0048] In the description of the present invention, it should be understood that the use of terms such as "first" and "second" to limit components is only for the convenience of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore cannot be understood as limiting the scope of protection of the present invention.

[0049] In addition, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0050] Virus removal membrane filtration mostly uses a pore structure with a gradient distribution of pore sizes. The small pore side of the gradient pore structure is used to ensure a high virus removal rate, while the large pore side is used to intercept pollutants such as protein aggregates of different sizes to ensure high flux, high virus removal rate and large load requirements. In addition, in order to minimize the adsorption of drug proteins on the virus removal membrane to ensure separation efficiency and reduce losses, hydrophilization of the virus removal membrane is the key to preparing high-performance virus removal membranes.

[0051] Among the commonly used modification methods, the co-irradiation modification method is to completely immerse the membrane to be modified in a monomer solution and irradiate it, so that the hydrophilic chain segments of the hydrophilic monomers are grafted onto the surface and pores of the membrane, thereby improving the hydrophilicity of the membrane material. However, the problem with this method is that the amount of hydrophilic monomer grafted at different positions of the membrane is basically the same, which results in the method being used in the modification process of a virus removal membrane with a gradient pore structure. It is easy for the method to be used in the modification process of a virus removal membrane with a gradient pore structure. This may result in insufficient hydrophilization of the larger pore size due to a low grafting amount, or a high grafting rate, resulting in the smaller pore size being completely blocked by the hydrophilic chain segments. The key to the virus removal membrane filtration process lies in the pore structure of the virus removal membrane.

[0052] Therefore, the present invention improves the existing co-irradiation modification method to prepare a hydrophilic hollow polyvinylidene fluoride membrane with a gradient distribution of the number of grafted hydrophilic groups inside the membrane structure, which is firmly bonded to the base membrane and has very little effect on the permeability of the membrane pores, thereby achieving precise control of the hydrophilic modification of different regions of the hollow polyvinylidene fluoride membrane. The specific implementation content is as follows:

[0053] In a first aspect, the present invention provides a method for preparing a hydrophilic hollow polyvinylidene fluoride membrane. Figure 1 The flow chart of the preparation method of the hydrophilized hollow polyvinylidene fluoride membrane shown in the embodiment of the present invention is shown as follows: Figure 1 As shown, the method includes:

[0054] S1, encapsulating the hollow polyvinylidene fluoride based membrane in a membrane assembly so that cavities capable of adding liquid are formed on both sides of the hollow base membrane;

[0055] When this step is implemented, the selected hollow polyvinylidene fluoride based membrane has a gradient porous structure to ensure high flux and high load. The pore size decreases from the inside to the outside. The pore size of the large pores on the inside is 80-250nm, and the pore size of the small pores on the outside is 15-30nm. The logarithmic removal rate of colloidal gold of the hollow polyvinylidene fluoride based membrane is greater than 4LRV, and the pure water flux of the hollow polyvinylidene fluoride based membrane is 160-200LMH / 0.3MPa; the hollow polyvinylidene fluoride based membrane provided in this step can be prepared by thermally induced phase separation, and the gradient pore structure can be constructed and regulated by changing the core liquid temperature and composition, air gap residence time and other factors. The method is simple and highly controllable; the gradient pore structure formed can simultaneously achieve the performance requirements of high virus removal rate and high flux and high load. The specific preparation process refers to the following method:

[0056] After uniformly mixing 30%-60% of polyvinylidene fluoride by mass and 40%-70% of diluent by mass, the mixture is added into a screw extruder at 200℃-270℃ and fully kneaded to obtain a homogeneous casting liquid; the homogeneous casting liquid is extruded through an annular spinneret, and a core liquid at 170-270℃ is injected into the inside to maintain a hollow inner cavity; the extruded fiber containing the core liquid is stretched at a speed of 40-100m / min, and after passing through a room temperature air section for 10-100ms, it enters a cooling bath at a temperature of 0-50℃, and then solidifies into a membrane material; the membrane material is immersed in an extractant, and after removing the diluent in the membrane, it is dried to obtain a hollow polyvinylidene fluoride based membrane with a gradient pore structure. Among them, the diluent can be selected from one or a mixture of diethyl phthalate, dibutyl phthalate, dihexyl phthalate, dioctyl phthalate, tributyl citrate, triethyl citrate, acetyl dioctyl citrate, acetyl tributyl citrate, γ-butyrolactone, dioctyl adipate and dihexyl adipate; the core liquid is selected from one or a mixture of dihexyl phthalate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate and γ-butyrolactone; and the extractant is ethanol.

[0057] The structural diagram of the membrane module is shown in Figure 6 The membrane assembly is formed by assembling a tubular material 1 with openings at both ends, a sealant 2, and a hollow polyvinylidene fluoride based membrane 4. The sealant 2 is used to seal the openings at both ends of the tubular material 1, and to fix the hollow polyvinylidene fluoride based membrane 4 in the tubular material 1 with openings at both ends; an outer cavity liquid inlet 3 for liquid inlet is provided on the outer wall of the tubular material 1 with openings at both ends. When in use, a plurality of hollow polyvinylidene fluoride based membranes 4 are placed in the tubular material 1 with openings at both ends, and the sealant 2 is used to fill only the gap between the hollow polyvinylidene fluoride based membrane 4 and the tubular material 1 at both ends, so as to achieve the sealing of the open ends ( The hollow part of the hollow polyvinylidene fluoride vinyl-based membrane 4 is not filled with sealant) and the hollow polyvinylidene fluoride vinyl-based membrane is fixed, and the hollow polyvinylidene fluoride vinyl-based membrane 4 and the membrane assembly are combined to form a base membrane outer cavity 5 and a base membrane inner cavity 6. The outer wall of the tubular material and the outer surface of the hollow polyvinylidene fluoride vinyl-based membrane 4, as well as the sealant at both ends together form the base membrane outer cavity 5, and the inner surface of the hollow polyvinylidene fluoride vinyl-based membrane forms the base membrane inner cavity 6; the first solution enters the base membrane inner cavity through the hollow part of the hollow polyvinylidene fluoride vinyl-based membrane 4, and the second solution enters the base membrane outer cavity 5 through the outer cavity liquid inlet 3.

[0058] Specifically, the sealant 2 can be selected from epoxy glue or polyurethane glue; the tubular material 1 with openings at both ends can be integral or spliced ​​by pipe joints, and its material is a plastic that can withstand modified solutions, radiation resistance and has no shielding effect on rays; preferably polycarbonate, polysulfone, polyethersulfone, polyethylene terephthalate, polypropylene or polyethylene.

[0059] S2, adding a first solution containing a hydrophilic monomer into the cavity inside the base membrane, and adding a second solution not containing a hydrophilic monomer into the cavity outside the base membrane, the hydrophilic monomer in the first solution diffuses to the outside of the base membrane driven by the concentration difference on both sides of the base membrane, and after a period of diffusion, the membrane assembly is placed in an irradiation device for irradiation to perform atom transfer radical polymerization modification;

[0060] When this step is implemented, the hydrophilic monomer is a compound containing hydrophilic groups such as hydroxyl, ester, carboxylic acid, and epoxy groups and double bonds capable of free radical polymerization; specifically, it can be selected from one or a mixture of more than one of hydroxybutyl acrylate, hydroxypropyl acrylate, hydroxyethyl acrylate, glycidyl acrylate, 2-methoxyethyl acrylate, hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, and glycidyl methacrylate; the first solution is a mixed solution of the hydrophilic monomer, a first alcohol solution, and water, the first alcohol solution being selected from methanol and / or ethanol solution, with a mass concentration of 10 to 50%; the second solution is a second alcohol solution, or a mixed solution of the second alcohol solution and water, the second alcohol solution being selected from one or more of ethanol, n-propanol, isopropanol, and isobutanol solution, with a mass concentration of 50 to 100%. Since the first solution contains hydrophilic monomers, while the second solution does not contain hydrophilic monomers, the concentration difference between the first solution and the second solution causes the hydrophilic monomers to diffuse from the inner side of the basement membrane to the outer side of the basement membrane under the drive of the concentration difference, thereby entering the basement membrane pores to form a gradient concentration distribution. During the first diffusion, the mass concentration of the hydrophilic monomer in the first solution is 0.5-20wt%, and the diffusion time is 1-20min; after the first diffusion is completed, the membrane assembly is placed in an irradiation device for irradiation, so that the hydrophilic monomer undergoes a grafting reaction and is firmly bonded to the basement membrane; the radiation emitted by the irradiation device is an electron beam, a gamma ray, a beta ray or a neutron ray; the dose of a single irradiation is 1-50kGy.

[0061] In specific implementation, in order to avoid the problem that the amount of monomer grafting at different positions of the base membrane is basically the same, which leads to the problem that the smaller pore size is completely blocked by the hydrophilic chain segment, this step adds the first solution to the cavity formed by the inner side of the base membrane and the membrane assembly, and adds the second solution to the cavity formed by the outer side of the base membrane and the membrane assembly, and forms a concentration difference inside and outside the base membrane to implement gradient diffusion, so that after irradiation, the amount of hydrophilic monomer grafting is proportional to the size of the membrane pore size. That is, the amount of hydrophilic monomer grafting is distributed in a decreasing manner from the large pore side to the small pore side in the base membrane.

[0062] S3, after the irradiation is completed, pour out the solution in the membrane assembly and wash it with pure water to remove the hydrophilic monomers and self-polymers remaining in the membrane;

[0063] S4, repeating steps 2-3 several times, increasing the concentration of the hydrophilic monomer in the first solution and reducing the diffusion time each time, removing the membrane assembly after completion, soaking the membrane fibers in pure water for 8-24 hours, and drying to obtain a hydrophilized hollow polyvinylidene fluoride membrane;

[0064] In specific implementation, the present invention controls the density and polymerization degree of the grafting reaction between the monomer and each part of the base film by controlling the monomer mass concentration and diffusion time. Each time it is repeated, the concentration of the hydrophilic monomer in the first solution is increased and the diffusion time is reduced. The mass concentration of the hydrophilic monomer in the first solution is 10-20% higher than that of the last use; the diffusion time is 20-30% shorter than that of the last diffusion time.

[0065] In a second aspect, the present invention provides a hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method described in the first aspect.

[0066] The preparation method provided by the present invention comprises the following steps: on the basis of a co-irradiation method, a hollow polyvinylidene fluoride based membrane is encapsulated in a membrane assembly, so that cavities capable of adding liquid are formed on both sides of the hollow base membrane; a first solution containing a hydrophilic monomer is added to the cavity on the inner side of the membrane, and a second solution not containing a hydrophilic monomer is added to the cavity on the outer side of the membrane; driven by the concentration difference on both sides of the membrane, the hydrophilic monomer in the first solution gradually diffuses from the large pores on the inner side of the base membrane to the small pores on the outer side of the base membrane, so that the base membrane forms a gradient distribution of the hydrophilic monomer concentration from large to small from the inside to the outside, and further irradiation is used to induce graft polymerization to realize hydrophilic modification of the hollow polyvinylidene fluoride based membrane; and the present invention further effectively controls the density and polymerization degree of the grafting reaction between the monomer and each part of the membrane by adjusting the monomer mass concentration, diffusion time, irradiation intensity, irradiation times, solvent concentration and solvent type, so as to realize that the grafting quantity is in direct proportion to the size of the membrane pores, so as to obtain a gradient hydrophilic hollow polyvinylidene fluoride membrane.

[0067] In a third aspect, the present invention provides an application of a hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method described in the first aspect, characterized in that the hydrophilized hollow polyvinylidene fluoride membrane is used for separation of proteins and viruses in the field of biopharmaceuticals.

[0068] The hydrophilized hollow polyvinylidene fluoride membrane provided by the present invention has a gradient distribution of the number of grafted hydrophilic groups inside the membrane structure, is firmly bonded to the base membrane, and has very little effect on the permeability of the membrane pores, thereby achieving a significant increase in the protein permeability without affecting the base membrane flux; the irradiation is performed multiple times in stages, and the required irradiation dose is small, and compared with alkali treatment and conventional irradiation, the damage to the mechanical properties of the membrane fibers is greatly reduced.

[0069] In order to enable those skilled in the art to more clearly understand the present invention, the hydrophilized hollow polyvinylidene fluoride membrane, preparation method and application of the present invention are now described in detail through the following examples.

[0070] Example 1

[0071] (1) preparing a casting solution: 49% by mass of polyvinylidene fluoride, 45% by mass of tributyl citrate and 6% by mass of dioctyl adipate were mixed evenly, and then added into a screw extruder at 230° C. and fully kneaded to obtain a uniform casting solution;

[0072] (2) The casting solution is squeezed through a ring-shaped die under pressure to form a hollow fiber, and 180° C. acetyl citrate triethyl is injected into the inside as a core liquid.

[0073] (3) Phase separation and solidification: The hollow fiber described in step (2) is pulled out from the die mouth at a speed of 60 m / min, and after a 15 ms room temperature air section for 10-100 ms, it enters a cooling bath at a temperature of 10° C. to solidify into a film.

[0074] (4) Extraction diluent: The prepared hollow fiber membrane was immersed in ethanol at 60°C to remove tributyl citrate and dioctyl adipate. After drying, a hollow polyvinylidene fluoride-based membrane with a gradient pore structure was obtained. The pore size on the large pore side was 196 nm, the pore size on the small pore side was 18 nm, the wall thickness was 97 μm, and the logarithmic removal rate of colloidal gold was 4.2LRV.

[0075] (5) The hollow polyvinylidene fluoride to be modified is encapsulated in a membrane module and a cavity into which liquid can be added is formed on both sides of the membrane; the schematic diagram of the structure of the membrane module is shown in Figure 6 The membrane assembly is formed by assembling a tubular material 1 with openings at both ends, a sealant 2, and a hollow polyvinylidene fluoride based membrane 4. The sealant 2 is used to seal the openings at both ends of the tubular material 1, and the hollow polyvinylidene fluoride based membrane 4 is fixed in the tubular material 1 with openings at both ends; an outer cavity liquid inlet 3 for liquid inlet is opened on the outer wall of the tubular material 1 with openings at both ends. When in use, a plurality of hollow polyvinylidene fluoride based membranes 4 are placed in the tubular material 1 with openings at both ends, and the sealant 2 is used to fill only the hollow polyvinylidene fluoride based membranes 4 at both ends. The gap between the polyvinyl fluoride vinyl based film 4 and the tubular material 1 realizes the sealing of the open end (the hollow part of the hollow polyvinyl fluoride vinyl based film is not filled with sealant) and the fixation of the hollow polyvinyl fluoride vinyl based film 4, and the combination of the hollow polyvinyl fluoride vinyl based film and the membrane assembly jointly forms the base membrane outer cavity 5 and the base membrane inner cavity 6, the outer wall of the tubular material and the outer surface of the hollow polyvinyl fluoride vinyl based film, as well as the sealant at both ends jointly form the base membrane outer cavity 5, and the inner surface of the hollow polyvinyl fluoride vinyl based film forms the base membrane inner cavity 6.

[0076] (6) preparing a 60 wt % ethanol / water solution and using it as the second solution, and adding the second solution into the cavity on the small pore side (outer cavity) of the membrane through the outer cavity inlet 3, preparing a modified solution (first solution) with 2 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution, and adding the first solution into the cavity on the large pore side (inner cavity) of the membrane in the module through the hollow part of the hollow polyvinylidene fluoride membrane;

[0077] (7) After the monomers diffused for 5 minutes driven by the concentration difference on both sides of the membrane, the membrane assembly was placed in an irradiation device for irradiation modification; the irradiation ray was an electron beam, and the irradiation dose was 3 kGy, to obtain a membrane after the first irradiation modification;

[0078] (8) Pour out the solution in the membrane assembly and add pure water into the cavities on both sides of the membrane. Pour out the pure water after 5 minutes and repeat this process 5 times to remove the remaining monomers and self-polymers.

[0079] (9) Repeat steps (6), (7), and (8) 4 times, gradually increase the concentration of the modified solution in step (6) to 10% higher than the last modified concentration; gradually shorten the diffusion time in step (7) to 20% shorter than the last diffusion time, and obtain a membrane after 5 irradiations. Dismantle the membrane assembly, and finally obtain a hydrophilized hollow polyvinylidene fluoride membrane with a gradient pore structure.

[0080] Example 2

[0081] The modified solution prepared by mixing 2 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution in step (6) of Example 1 was replaced by 2 wt % hydroxyethyl methacrylate and 30 wt % ethanol / water solution, while other conditions remained unchanged.

[0082] Example 3

[0083] The modified solution prepared by mixing 2 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution in step (6) of Example 1 was changed to 0.5 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution, while other conditions remained unchanged.

[0084] Example 4

[0085] The modified solution prepared by mixing 2 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution in step (6) of Example 1 was changed to 8 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution, while other conditions remained unchanged.

[0086] Example 5

[0087] The monomer diffusion for 5 min driven by the concentration difference on both sides of the membrane in step (7) of Example 1 was changed to the monomer diffusion for 10 min driven by the concentration difference on both sides of the membrane, and other conditions remained unchanged.

[0088] Example 6

[0089] The single irradiation dose of 3 kGy in step (7) of Example 1 was changed to a single irradiation dose of 10 kGy, and other conditions remained unchanged.

[0090] Example 7

[0091] The wall thickness of the polyvinylidene fluoride hollow fiber membrane in Example 1 was changed from 97 μm to 50 μm, while other conditions remained unchanged.

[0092] Example 8

[0093] The step (6) in Example 1 in which a 60 wt % ethanol / water solution is prepared and added as the second solution into the cavity on the pore side of the membrane (outer cavity) is changed to a 90 wt % ethanol / water solution is prepared and added as the second solution into the cavity on the pore side of the membrane (outer cavity), while other conditions remain unchanged.

[0094] Example 9

[0095] The step (6) in Example 1 in which a 60 wt % ethanol / water solution is prepared and added as the second solution into the cavity on the pore side (outside) of the membrane is replaced by a 60 wt % isopropanol / water solution being prepared and added as the second solution into the cavity on the pore side (outside) of the membrane, while other conditions remain unchanged.

[0096] Comparative Example 1

[0097] The 60 wt % ethanol / water solution prepared in step (6) of Example 1 is prepared and added as the second solution to the cavity on the small pore side (outer cavity) of the membrane, 2 wt % hydroxypropyl acrylate and 30 wt % ethanol / water solution are prepared into a modified solution (first solution), and added to the cavity on the large pore side (inner cavity) of the membrane in the component, and the 60 wt % ethanol / water solution is prepared and added as the second solution to the cavity on the small pore side (outer cavity) of the membrane, 30 wt % ethanol / water solution is used as the modified solution (first solution), and added to the large pore side (inner cavity) of the membrane in the component, while other conditions remain unchanged.

[0098] Comparative Example 2

[0099] In this comparative example, the polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure to be modified in Example 1 is hydrophilized by a pre-irradiation method, and the specific steps are as follows:

[0100] (1) The dried polyvinylidene fluoride hollow fiber virus removal base membrane with a gradient pore structure is placed in a sealed bag and filled with nitrogen for 20 minutes to remove the air inside.

[0101] (2) placing the sealed bag in step (1) in an irradiation device for irradiation modification, wherein the irradiation device is an electron beam and the irradiation dose is 15 kGy.

[0102] (3) The irradiated polyvinylidene fluoride hollow fiber virus removal membrane in step (2) is taken out and stored in an environment of -0°C.

[0103] (4) Preparing a modified solution: Preparing a 12.2 wt % hydroxypropyl acrylate solution, the solvent being a 30 wt % ethanol / water solution.

[0104] (5) The membrane in step (3) was taken out and immersed in the modified solution in step (4) for 17 minutes. After the reaction was completed, the membrane fibers were taken out and immersed in pure water for 8 hours. The water was changed four times to obtain a hydrophilized polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure.

[0105] Comparative Example 3

[0106] In this comparative example, the polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure to be modified in Example 1 is hydrophilized by co-irradiation method, and the specific steps are as follows:

[0107] (1) Preparation of modified solution: Prepare a 12.2 wt % hydroxypropyl acrylate solution, the solvent is a 30 wt % ethanol / water solution.

[0108] (2) The modified solution is placed in a sealed bag and filled with nitrogen for 20 minutes to remove the air inside. The dried polyvinylidene fluoride hollow fiber membrane with a gradient pore structure is placed in a sealed bag and sealed.

[0109] (3) After standing for 17 minutes, the sealed bag in step (2) is placed in an irradiation device for irradiation modification, wherein the irradiation ray is an electron beam and the irradiation dose is 15 kGy, to obtain an irradiation-modified polyvinylidene fluoride hollow fiber virus removal membrane.

[0110] (4) Cleaning: Soak the modified polyvinylidene fluoride hollow fiber virus removal membrane in the sealed bag in pure water for 8 hours, and repeat 4 times to obtain a hydrophilized polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure.

[0111] Comparative Example 4

[0112] The preparation method is basically the same as that of Comparative Example 3, except that the 12.2 wt % hydroxypropyl acrylate solution in step (1) of Comparative Example 3 is replaced by a 3.05 wt % hydroxypropyl acrylate solution, and other conditions remain unchanged.

[0113] Comparative Example 5

[0114] The preparation method is basically the same as that of Comparative Example 3, except that the 17 min of standing still in step (3) of Comparative Example 3 is changed to 1 h of standing still, and other conditions remain unchanged.

[0115] Comparative Example 6

[0116] The preparation method is basically the same as that of Comparative Example 3, except that the irradiation dose of 15 kGy in step (3) of Comparative Example 3 is changed to 50 kGy, and other conditions remain unchanged.

[0117] Comparative Example 7

[0118] The preparation method is basically the same as that of Comparative Example 3, except that the polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure to be modified is replaced by the virus removal membrane in Example 7, and other conditions remain unchanged.

[0119] The performance of the polyvinylidene fluoride hollow fiber virus removal membrane with a gradient pore structure in the examples and comparative examples was characterized by the following test method:

[0120] 1. Scanning electron microscope image

[0121] The virus removal membrane samples before and after modification were sampled multiple times, and the membrane surface and cross-sectional structure as well as the pore size and wall thickness on both sides were directly observed using a scanning electron microscope. The arithmetic mean values ​​of the pore size and wall thickness were calculated, with the number of samplings being 5; as an example, Figure 2 The cross-sectional SEM image of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown. Figure 3 The macroporous side SEM image of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown. Figure 4 The SEM image of the pore side of the hydrophilized hollow polyvinylidene fluoride membrane provided in Example 1 of the present invention is shown.

[0122] 2. Infrared spectrum

[0123] The virus removal membrane samples before and after modification were subjected to ATR-FTIR scanning analysis, and 64 scans were performed to obtain 4 cm -1 The resolution is 600-4000cm -1 ; As an example, Figure 5 The infrared images of the hydrophilized hollow polyvinylidene fluoride membranes provided in Example 1 and Comparative Examples 1 and 3 of the present invention are shown.

[0124] 3. Determination of pore size

[0125] At room temperature of 25°C, a pore size analyzer (full-function membrane pore size analyzer, BSD-PBL, Beijing Best Instruments) was used to analyze the pore size.

[0126] 4. Determination of grafting rate

[0127] Take 100cm 2 The virus-removing base membrane was placed in a 60°C oven for 4 hours to fully dry the internal moisture and weigh it. The weight of the virus-removing base membrane was obtained by taking the average value three times. 2 The modified virus removal membrane was placed in a 60°C oven for 4 hours to fully dry the internal moisture and then weighed. The weight of the modified virus removal membrane was obtained by taking the average value after repeating the process three times.

[0128] The grafting rate of the virus removal membrane was calculated according to grafting rate = (M2-M1) / M1×100%.

[0129] 5. Determination of mechanical strength

[0130] The upper and lower ends of the virus removal membrane with a length of 50 mm were clamped on a tensile testing machine and tested using an AGS-J electronic universal testing machine. The tensile speed used was 250 mm / min, and the tensile strength and elongation at break were measured.

[0131] 6. Determination of water contact angle

[0132] Select a virus removal membrane with a uniform inner and outer diameter of about 2 cm and put it into a 60℃ oven to dry for 1 hour. Use double-sided tape to stick the dried membrane flat on the surface of a glass slide. Then put the glass slide on the platform of the contact angle tester, drop about 0.1μL of pure water on the membrane by the drop method, and measure the static contact angle on the contact angle tester. Each membrane is measured at 3 different positions, and the arithmetic average of the static contact angles is taken to obtain the water contact angle of the membrane.

[0133] 7. Determination of pure water flux

[0134] The virus removal membrane and the membrane shell are packaged into a component, and the membrane component is used as a filter membrane. The pure water with a pressure of 0.3MPa and a water temperature of 25°C is passed through the filter membrane. After stabilization for 30 minutes, the water output (V) of a certain time (t) is collected and measured. The effective area of ​​the filter membrane through which the pure water passes is A. The pure water flux corresponding to the virus removal membrane is calculated according to Jw=Vt / A, L·m -2 ·h -1 .

[0135] 8. Determination of membrane protein flux and protein permeability

[0136] The virus removal membrane and the membrane shell are packaged into a membrane assembly, and the membrane assembly is used as a filter membrane. Immunoglobulin (IgG) is prepared into a 10 mg / ml solution with PBS buffer solution as the stock solution for testing. The pressure is 0.3 MPa, the operating temperature is 25°C, and the permeate is collected for 20 minutes and the volume of the permeate is measured. The protein flux of the virus removal membrane is calculated according to J=Vt / A. In the formula, J is the protein flux, L·m -2 ·h -1 ; V is the volume of permeate collected within the test time t, L; t is the test time, h; A is the effective virus removal membrane area, m 2 The IgG protein concentration in the stock solution and the collected permeate was tested by the Coomassie Brilliant Blue method, and the protein permeability was calculated by the following formula: Protein permeability (%) = C p / C f × 100%, where C p is the concentration of IgG in the permeate, C f is the concentration of IgG in the stock solution, in mg / ml.

[0137] 9. Determination of membrane protein adsorption properties

[0138] Place the virus-removing membrane to be tested in a 60°C oven and dry it to constant weight. The weight at this time is taken as its initial mass M3. Prepare a 1mg / ml bovine serum albumin (BSA) solution (isoelectric point 4.7, negatively charged), test its concentration with a UV spectrophotometer and record it as C1. The membrane to be tested is soaked and cleaned with ethanol and deionized water successively, then placed in a BSA solution and immersed at a constant temperature of 25°C for 24 hours to allow the membrane surface and pores to fully adsorb BSA. Use a UV spectrophotometer to test the concentration of the BSA solution after adsorption and record it as C2.

[0139] The protein adsorption amount was obtained according to Q = (C1-C2) × V / M3; where Q is the protein adsorption amount, mg / g; C1 and C2 are the protein concentrations before and after the membrane adsorbed protein, mg / ml; V is the volume of the protein solution, ml; and M3 is the initial mass of the membrane, g.

[0140] 10. Determination of Colloidal Gold Retention Rate

[0141] Prepare 0.27wt% sodium dodecyl sulfate (SDS) diluent, and prepare colloidal gold (AGP) and 0.27wt% SDS diluent in a ratio of 1:9 to obtain AGP solution. Test the absorbance of AGP solution at 530, 526 and 520nm, where the measured values ​​should be 0.9≤A526≤1.2; 0.985≤A530 / A520≤1.025. If the measurement results meet the above requirements, it means that the configured AGP solution can be used for filtration experiments. If it is not in the above range, it needs to be reconfigured. After the membrane filaments before and after modification are prepared into components, the pure water flux is tested under a pressure of 0.3MPa. After the test is completed, the pure water solution is replaced with AGP solution, and the test is continued under a pressure of 0.3MPa. 5ml of permeate is collected and the absorbance of the permeate is tested at 526nm. The logarithmic removal rate of colloidal gold is log(M526 / A526), ​​where M526 is the absorbance of the permeate at 526 nm and A526 is the absorbance of the AGP solution at 526 nm.

[0142] Table 1 Performance characterization results of examples and comparative examples

[0143]

[0144]

[0145] According to Table 1, we can see that:

[0146] 1. By comparing Examples 1-9 and Comparative Examples 1-7, it can be seen that the method of the present invention can achieve gradient hydrophilization of a gradient pore structure virus removal membrane. After modification, the water contact angle on the large pore side of the membrane can be reduced to 20°, and the water contact angle on the small pore side can be reduced to 60°. It has high pure water flux, high protein flux, high protein permeability and low protein adsorption.

[0147] 2. Comparison with Examples 1-9 shows that the present invention can achieve regulation of the grafting rate and thus the pore size of the gradient pores by controlling the type, concentration, diffusion time, irradiation dose, wall thickness, solvent concentration and solvent type of the monomers, and simultaneously achieve high pure water flux, protein flux, protein permeability and low protein adsorption.

[0148] 3. By comparing Examples 1-9 and Comparative Examples 1-7, it can be seen that the present invention introduces gradient diffusion and gradient monomer concentration processes on the basis of co-irradiation, and accurately controls the polymerization concentration and intensity in different areas of the membrane, thereby realizing controllable hydrophilic modification of the virus removal membrane with a gradient pore structure. Compared with the pre-irradiation method and the conventional co-irradiation method, the grafting rate and average pore size of the membrane have better controllability. It is possible to simultaneously improve the flux and hydrophilicity of the membrane at a lower irradiation dose, and the damage to the mechanical strength of the membrane is lower.

[0149] 4. Comparison of Examples 1, 5, 6, 7 and Comparative Examples 3-6 shows that the hydrophilic hollow polyvinylidene fluoride virus removal membrane prepared by the present invention has a lower impact on the pore size under the condition of ensuring hydrophilic precursor, so the flux of the membrane does not fluctuate greatly. However, when the wall thickness of the base membrane is reduced, the pore size and flux of the hydrophilic virus removal membrane prepared by the direct co-irradiation method are sharply reduced.

[0150] according to Figure 2 , 3 As shown in the SEM images of 4, the pore size and position distribution of the large pore side and small pore side of the hydrophilized hollow polyvinylidene fluoride membrane prepared by the present invention are extremely uniform. The present invention introduces a gradient diffusion process based on the co-irradiation method, and induces the monomer to gradually transfer from the large pore side to the small pore side within a certain period of time through factors such as the concentration difference and diffusion time on both sides of the membrane, so that the small pore side is grafted with an appropriate amount of monomer without blocking the pore size, while the large pore side is grafted with more monomers, so that the pore structure of the membrane is more controllable during the entire modification process.

[0151] according to Figure 4 It can be seen that the hydrophilic groups are grafted on both the large pore side and the small pore side of the hydrophilic hollow polyvinylidene fluoride membrane prepared by the present invention, and the number of hydrophilic groups grafted on the large pore side is greater. The number of hydrophilic groups grafted on the large pore side and the small pore side of the hydrophilic hollow polyvinylidene fluoride membrane prepared by the co-irradiation method is similar. After research, the inventor believes that since the monomers on the surface and in the pore size of the membrane are relatively uniform when the co-irradiation method is directly used for modification, the length of the grafted chain segments generated at each point is comparable. Therefore, the membrane with a gradient pore structure is prone to insufficient hydrophilization due to too low grafting amount or excessive grafting amount, resulting in decreased membrane pore blockage flux. The gradient diffusion process introduced by the present invention has a good control of the modification of the gradient pores, and maximizes the protein permeability and protein permeability of the membrane without blocking the membrane pores.

[0152] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification.

[0153] For the method embodiments, for the sake of simplicity, they are all described as a series of action combinations, but those skilled in the art should know that the present invention is not limited by the order of the actions described, because according to the present invention, some steps can be performed in other orders or simultaneously. Secondly, those skilled in the art should also know that the embodiments described in the specification are all preferred embodiments, and the actions and components involved are not necessarily required by the present invention.

[0154] The above is a detailed introduction to a hydrophilized hollow polyvinylidene fluoride membrane, a preparation method and an application provided by the present invention. Specific examples are used in this article to illustrate the principle and implementation mode of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea; at the same time, for a general technician in this field, according to the idea of ​​the present invention, there will be changes in the specific implementation mode and the scope of application. In summary, the content of this specification should not be understood as a limitation on the present invention.

Claims

1. A method for preparing a hydrophilic hollow polyvinylidene fluoride membrane, characterized in that: The method comprises: Step 1, encapsulating the hollow polyvinylidene fluoride based membrane in a membrane assembly, so that cavities capable of adding liquid are formed on both the inner and outer sides of the base membrane; Step 2, adding a first solution containing a hydrophilic monomer into the inner cavity of the base membrane, and adding a second solution not containing a hydrophilic monomer into the outer cavity of the base membrane, the hydrophilic monomer in the first solution diffuses to the outside of the base membrane driven by the concentration difference on both sides of the base membrane, and after a period of diffusion, the membrane assembly is placed in an irradiation device for irradiation to perform atom transfer radical polymerization modification; Step 3: After the irradiation is completed, pour out the solution in the membrane assembly and wash with pure water to remove the residual hydrophilic monomer and self-polymer in the membrane; Step 4, repeating steps 2-3 several times, increasing the concentration of the hydrophilic monomer in the first solution and reducing the diffusion time each time, removing the membrane assembly after completion, soaking the membrane fibers in pure water for 8-24 hours, and drying to obtain a hydrophilized hollow polyvinylidene fluoride membrane; Wherein, the hollow polyvinylidene fluoride based membrane is a polyvinylidene fluoride hollow fiber membrane with a gradient porous structure, and the pore size decreases from the inside to the outside; The hydrophilic monomer is one of hydroxybutyl acrylate, hydroxypropyl acrylate, hydroxyethyl acrylate, glycidyl acrylate, 2-methoxyethyl acrylate, hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate and glycidyl methacrylate, or a mixture of more than one of them.

2. The method for preparing a hydrophilized hollow polyvinylidene fluoride membrane according to claim 1, characterized in that: The first solution is a mixed solution of the hydrophilic monomer, the first alcohol solution and water, the first alcohol solution is a methanol and / or ethanol solution; the mass concentration of the first alcohol solution is 10-50%; when used for the first time, the mass concentration of the hydrophilic monomer in the first solution is 0.5-20wt%; when used repeatedly, the mass concentration of the hydrophilic monomer in the first solution is 10-20% higher than that of the last use; The second solution is a second alcohol solution, or a mixed solution of the second alcohol solution and water. The second alcohol solution is one or more of ethanol, n-propanol, isopropanol, and isobutanol solutions. The mass concentration of the second alcohol solution is 50-100%.

3. The method for preparing the hydrophilized hollow polyvinylidene fluoride membrane according to claim 1, characterized in that: When the diffusion is performed for the first time, the diffusion time is 1 to 20 minutes; when the diffusion is performed repeatedly, the diffusion time is 20 to 30% shorter than the previous diffusion time.

4. The method for preparing a hydrophilized hollow polyvinylidene fluoride membrane according to claim 1, characterized in that: The radiation emitted by the irradiation device is an electron beam, a gamma ray, a beta ray or a neutron ray; The dose of a single irradiation is 1-50 kGy.

5. The method for preparing a hydrophilized hollow polyvinylidene fluoride membrane according to claim 1, characterized in that: The diameter of the macropores on the inner side of the hollow polyvinylidene fluoride membrane is 80-250 nm, and the diameter of the small pores on the outer side is 15-30 nm; The logarithmic removal rate of colloidal gold by the hollow polyvinylidene fluoride-based membrane is greater than 4LRV; The pure water flux of the hollow polyvinylidene fluoride based membrane is 160~200LMH / 0.3MPa; The wall thickness of the hollow polyvinylidene fluoride based membrane is 50-100 μm.

6. The method for preparing a hydrophilized hollow polyvinylidene fluoride membrane according to claim 1, characterized in that: The hollow polyvinylidene fluoride film is obtained by the following preparation method: After uniformly mixing 30%-60% of polyvinylidene fluoride and 40%-70% of diluent by mass, adding the mixture into a screw extruder at 200°C-270°C, and fully mixing the mixture to obtain a homogeneous film casting solution; The homogeneous casting liquid is extruded through an annular spinneret, and a core liquid at 170-270° C. is injected into the spinneret to maintain a hollow inner cavity; the extruded fiber containing the core liquid is stretched at a speed of 40-100 m / min, and after passing through a room temperature air section for 10-100 ms, enters a cooling bath at a temperature of 0-50° C., and then solidifies into a membrane material; The membrane material is immersed in an extractant, and after removing the diluent in the membrane, it is dried to obtain a hollow polyvinylidene fluoride-based membrane with a gradient pore structure.

7. The method for preparing a hydrophilized hollow polyvinylidene fluoride membrane according to claim 6, characterized in that: The diluent is one or a mixture of diethyl phthalate, dibutyl phthalate, dihexyl phthalate, dioctyl phthalate, tributyl citrate, triethyl citrate, dioctyl acetyl citrate, tributyl acetyl citrate, γ-butyrolactone, dioctyl adipate and dihexyl adipate; The core liquid is one or a mixture of dihexyl phthalate, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate and γ-butyrolactone; The extractant is ethanol.

8. A hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method according to any one of claims 1 to 7.

9. An application of a hydrophilized hollow polyvinylidene fluoride membrane obtained by the preparation method according to any one of claims 1 to 7, characterized in that: The hydrophilized hollow polyvinylidene fluoride membrane is applied to the separation of proteins and viruses in the field of biopharmaceuticals.

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