Composite membrane, and preparation method therefor and use thereof

Abstract

The present application provides a composite membrane, and a preparation method therefor and the use thereof. The composite membrane comprises a continuous phase having a pore structure and a dispersion medium dispersed in the continuous phase, wherein a component of the continuous phase comprises a polymer, and the dispersion medium comprises a porous material. Further functionalization of the composite membrane can also provide more functional group loading areas, thereby enabling the introduction of a greater number of functional groups and further increasing the loading capacity of target molecules by a functionalized chromatography membrane.

Description

Composite membrane material and its preparation method and application Technical Field

[0001] The present invention relates to the technical field of functional materials, and in particular to a composite film material and a preparation method and application thereof. Background Art

[0002] Chromatographic separation is a new and efficient separation technology that often uses porous chromatographic membranes as separation and purification media. Porous chromatographic membranes are materials with a microporous structure. Their pore size can be adjusted as needed. By controlling the pore size of the chromatographic membrane, it can be used for the separation and purification of biomolecules of different sizes. It is widely used in the separation and purification of biomacromolecules such as proteins, and has significant advantages such as fast purification speed and high efficiency.

[0003] Normally, the pore size of chromatographic membranes is mostly between 0.5μm and 3μm, and they are mainly composed of a porous base membrane and a surface functional modification layer. The presence of the surface functional modification layer enables the chromatographic membrane to achieve targeted separation and purification of different substances. A commonly used preparation method for porous base membranes is the phase inversion method, in which the homogeneous polymer solution undergoes phase inversion and is transformed into a three-dimensional macromolecular network gel structure, which is finally solidified into a membrane; the functional modification layer is obtained by functional modification on the basis of the porous base membrane, including physical or chemical modification, to introduce specific functional groups into the internal pores and surface cortex of the membrane, thereby achieving separation and purification of different substances. However, because the pore size of traditional chromatographic base membranes is large, the specific surface area is low, resulting in a limited number of functional groups that can be introduced, which leads to a low loading capacity of the chromatographic membrane for target biological molecules.

[0004] Therefore, chromatography membrane technology still needs to be improved.

[0005] Summary of the Invention

[0006] Based on this, the present application provides a composite membrane material and its preparation method and application, aiming to increase the loading capacity of the medium used for separation and purification.

[0007] The technical solution of this application is as follows.

[0008] In a first aspect of the present application, a composite membrane material is provided, comprising a continuous phase having a pore structure and a dispersion medium dispersed in the continuous phase, wherein a component of the continuous phase comprises a polymer, and the dispersion medium comprises a porous material.

[0009] In the above-mentioned composite membrane material, porous materials are dispersed in a continuous phase with a pore structure. The porous materials have a large specific surface area and are dispersed in the continuous phase containing a pore structure, forming a secondary pore structure of the membrane, further increasing the specific surface area of ​​the composite membrane material. When used to prepare separation and purification media, due to the large specific surface area of ​​the composite membrane material itself, the number of functional groups that can be introduced during functionalization is increased, thereby increasing the loading capacity of the functionalized chromatographic membrane for the target molecules.

[0010] In some embodiments, the mass ratio of the continuous phase to the dispersion medium is 1:(0.1-2).

[0011] Further regulating the mass ratio of the continuous phase to the dispersion medium is beneficial to further increase the specific surface area.

[0012] In some embodiments, the pore size of the porous material is 20 nm to 500 nm.

[0013] In some embodiments, the pore size of the porous material is 100 nm to 500 nm.

[0014] Further regulating the pore size of porous materials is conducive to further functional modification so that the modified substances can enter the inner surface of the porous materials more smoothly, which can further increase the loading capacity of functional groups.

[0015] In some embodiments, the diameter of the porous material is 100 nm to 50 μm; and / or

[0016] The porosity of the porous material is 20% to 80%.

[0017] In some embodiments, the porous material comprises at least one of silicon dioxide, titanium dioxide, an organic polymer and an organometallic framework material; and / or

[0018] The surface of the porous material contains at least one of hydroxyl, carboxyl, amino, nitro, thiol and methyl groups; and / or

[0019] The polymer includes at least one of polyethersulfone, polysulfone, cellulose acetate, polynylon, polyvinylidene fluoride, polyimide, polyvinylidene chloride, polystyrene, polyethylene, polypropylene and acrylic polymers.

[0020] The second aspect of the present application further provides a method for preparing the composite film material of the first aspect, comprising the following steps:

[0021] mixing a porogen, the polymer, the porous material and a solvent to prepare a mixed solution;

[0022] The mixed solution is placed in water for film-forming treatment to prepare the composite membrane material.

[0023] During the film-forming process, the polymer forms a continuous phase, and the porous material is dispersed in the continuous phase. At the same time, under the action of the porogen, the continuous phase will form a pore structure, thereby obtaining a composite membrane material with a larger specific surface area.

[0024] In some embodiments, the porogen comprises at least one of polyvinyl pyrrolidone, glycerol and polyethylene glycol; and / or

[0025] The mass ratio of the porogen to the polymer is (0.5-0.8):1; and / or

[0026] The solvents include water and dimethylacetamide.

[0027] The third aspect of the present application provides use of the composite membrane material of the first aspect or the composite membrane material prepared by the preparation method of the composite membrane material of the second aspect in preparing a medium for separation and purification.

[0028] The fourth aspect of the present application provides a medium for separation and purification, which includes a basement membrane and a functional layer loaded on the surface of the basement membrane; the basement membrane includes the composite membrane material of the first aspect or the composite membrane material prepared by the preparation method of the composite membrane material of the second aspect, and the functional layer contains functional groups that can specifically bind to proteins.

[0029] The composite membrane material has a high specific surface area, which can increase the area of ​​the functional layer loaded on its surface, thereby increasing the number of introduced functional groups and significantly improving the protein loading capacity.

[0030] It should be noted that the functional groups capable of specifically binding to proteins can be functional groups that have been demonstrated in the art to specifically bind to various proteins. Specific binding can be achieved through the formation of ionic bonds, hydrogen bonds, or intermolecular forces such as electrostatic interactions between positive and negative charges, dipole interactions, and dispersion forces. For example, when the functional layer comprises polyethyleneimine, when using bovine serum albumin as the target molecule for a loading test, under neutral conditions, polyethyleneimine carries a positive charge and bovine serum albumin carries a negative charge. The electrostatic interaction between the two allows the bovine serum albumin to be loaded onto the membrane layer, achieving the purpose of targeted separation and purification of the bovine serum albumin. Furthermore, the basement membrane in the separation and purification medium can carry more functional groups, thereby increasing the loading capacity for the bovine serum albumin.

[0031] In some embodiments, the functional group includes at least one of an amine group, an imine group, a quaternary ammonium salt, a carboxyl group, a sulfonic acid group, a hydrophobic functional group, and an affinity functional group.

[0032] In some embodiments, the component of the functional layer includes at least one of polyethyleneimine, quaternary ammonium salt, polyallylamine and Protein A.

[0033] In some embodiments, the polyethyleneimine comprises cross-linked polyethyleneimine, wherein the cross-linked polyethyleneimine is formed by cross-linking polyethyleneimine with an epoxy-containing cross-linking agent, wherein the reaction sites of the cross-linking reaction include an amine group in the polyethyleneimine and an epoxy group in the cross-linking agent; and / or

[0034] The mass ratio of the functional layer to the base film is (0.09-0.42):1.

[0035] In a fifth aspect, the present application provides use of the separation and purification medium according to the fourth aspect in separating and purifying proteins.

[0036] In a sixth aspect of the present application, a separation and purification device is provided, wherein the separation and purification device comprises the composite membrane material of the first aspect or the composite membrane material prepared by the preparation method of the composite membrane material of the second aspect or the separation and purification medium of the third aspect.

[0037] In some embodiments, the separation and purification device includes at least one of a chromatography membrane, a chromatography column, and a solid phase extraction device. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Various other advantages and benefits will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiment below. The accompanying drawings are for illustration purposes only and are not to be considered as limiting the present application. The same reference numerals are used throughout the drawings to represent the same components. In the drawings:

[0039] FIG1 is an electron scanning microscope image of the composite film material prepared in Example 1, wherein (a1), (a2) and (a3) ​​are electron scanning microscope images of the front, back and side surfaces of the composite film material, respectively;

[0040] FIG2 is an electron scanning microscope image of the composite film material prepared in Example 2, wherein (b1), (b2) and (b3) are electron scanning microscope images of the front, back and side surfaces of the composite film material, respectively;

[0041] FIG3 is an electron scanning microscope image of the composite film material prepared in Comparative Example 1, wherein (c1), (c2) and (c3) are electron scanning microscope images of the front, back and side surfaces of the composite film material, respectively. DETAILED DESCRIPTION

[0042] To facilitate understanding of the present application, the present application will be described in more detail below, along with preferred embodiments thereof. However, the present application may be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and comprehensive understanding of the disclosure herein.

[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0044] In the description of the embodiments of this application, the technical terms "first" and "second" are used only to distinguish different objects and should not be understood to indicate or imply relative importance or implicitly indicate the quantity, specific order, or primary and secondary relationship of the indicated technical features. In the description of the embodiments of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0045] The "ranges" disclosed in this application can be defined in the form of lower limits and upper limits. A given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundaries of the particular range. Ranges defined in this way can be inclusive or exclusive of the end values, any end value can be included or excluded independently, and can be arbitrarily combined, that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60 to 120 and 80 to 110 are listed for a particular parameter, it is understood that ranges of 60 to 110 and 80 to 120 are also expected. In addition, if the minimum range values ​​1 and 2 are listed, and if the maximum range values ​​3, 4, and 5 are also listed, the following ranges are all expected: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, and 2 to 5. In this application, unless otherwise specified, the numerical range "a to b" is an abbreviation for any combination of real numbers between a and b, where a and b are both real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" are listed herein, and "0-5" is simply an abbreviation for these numerical combinations. Furthermore, when a parameter is expressed as an integer ≥ 2, this is equivalent to listing the parameter as, for example, the integers 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and so on. For example, when a parameter is expressed as an integer selected from "2-10," this is equivalent to listing the integers 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0046] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0047] In this application, unless otherwise specified, "room temperature" generally refers to 4°C to 30°C, preferably 20±5°C.

[0048] In one embodiment of the present application, a composite membrane material is provided, comprising: a continuous phase containing a pore structure and a dispersion medium dispersed in the continuous phase, wherein the components of the continuous phase include a polymer, and the dispersion medium includes a porous material.

[0049] In the above-mentioned composite membrane material, porous materials are dispersed in a continuous phase with a pore structure. The porous materials have a large specific surface area and are dispersed in the continuous phase containing a pore structure, forming a secondary pore structure of the membrane, further increasing the specific surface area of ​​the composite membrane material. When used to prepare separation and purification media, due to the large specific surface area of ​​the composite membrane material itself, the number of functional groups that can be introduced during functionalization is increased, thereby increasing the loading capacity of the functionalized chromatographic membrane for the target molecules.

[0050] In some embodiments, the mass ratio of the continuous phase to the dispersion medium is 1:(0.1-2).

[0051] Further regulating the mass ratio of the continuous phase to the dispersion medium is beneficial to further increase the specific surface area.

[0052] In the above “1:(0.1~2)”, the values ​​include the minimum and maximum values ​​of the range, and every value between the minimum and maximum values. Specific examples include but are not limited to the point values ​​in the embodiments and the following point values: 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2; or a range consisting of any two values.

[0053] In some embodiments, the pore size of the porous material is 20 nm to 500 nm.

[0054] In some embodiments, the pore size of the porous material is 100 nm to 500 nm.

[0055] In some embodiments, the pore size of the porous material is 200 nm to 500 nm.

[0056] Further regulating the pore size of porous materials is conducive to further functional modification so that the modified substances can enter the inner surface of the porous materials more smoothly, which can further increase the loading capacity of functional groups.

[0057] In the above “20nm~500nm”, the values ​​include the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Specific examples include but are not limited to the point values ​​in the embodiments and the following point values: 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 110nm, 120nm, 130nm, 140nm, 150nm, 160nm, 170nm, 180nm, 190nm, 200nm, 210nm, or a range consisting of any two values.

[0058] It can be understood that in the technical solution of the present application, the shape of the porous material can be any shape, including but not limited to: spherical, spherical, square and irregular shapes.

[0059] In some embodiments, the porous material is spherical.

[0060] In some embodiments, the porous material has a diameter of 100 nm to 50 μm.

[0061] In the above “100nm~50μm”, the values ​​include the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Specific examples include but are not limited to the point values ​​in the embodiments and the following point values: 100nm, 200nm, 300nm, 400nm, 500nm, 1μm, 1.5μm, 2μm, 2.5μm, 3μm, 3.5μm, 4μm, 4.5μm, 5μm, 6μm, 7μm, 8μm, 9μm, 10μm, 11μm, 12μm, 13μm, 14μm, 15μm, 16μm, 17μm, 18μm, 19μm, 20μm, 11μm, 12μm, 13μm, 14μm, 15μm, 16μm, 17μm, 18μm, 19μm, 20μm, 21μm, 22μm, 23μm, 24μm, 25μm, 26μm, 27μm, 28μm, 29μm, 30μm, 31μm, 32μm, 33μm, 34μm, 35μm, 36μm, 37μm, 38μm, 39μm, 40μm; or a range consisting of any two values.

[0062] In some embodiments, the porosity of the porous material is 20% to 80%.

[0063] In the above "20% to 80%", the values ​​include the minimum and maximum values ​​of the range, and every value between the minimum and maximum values. Specific examples include but are not limited to the point values ​​in the embodiments and the following point values: 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%; or a range consisting of any two values.

[0064] The porous material may be a commonly used porous material in the art; further, the components of the porous material include at least one of silicon dioxide, titanium dioxide, an organic polymer and an organic metal framework material.

[0065] In some embodiments, the organic polymer includes at least one of polymethyl methacrylate aerogel microspheres, polystyrene aerogel microspheres, or polyimide aerogel microspheres.

[0066] In some embodiments, the organic metal framework material includes at least one of a zeolite imidazole framework, cobalt dimethyl imidazole, an organic metal framework material containing iron, an organic metal framework material containing zinc, or an organic metal framework material containing chromium.

[0067] In some embodiments, the surface of the porous material contains at least one of hydroxyl, carboxyl, amino, nitro, thiol and methyl groups.

[0068] When the surface of the porous material contains some functional groups, the porous material can further have good interactions with other materials. For example, the presence of hydrophilic groups such as hydroxyl and amine makes silica have good hydrophilicity, which can form hydrogen bonds with water molecules, making the porous material have good dispersibility and solubility in water. In addition, groups such as hydroxyl and amine can also form hydrogen bonds with similar groups in other molecules to achieve the purpose of adsorption and purification.

[0069] It can be understood that the above-mentioned groups on the surface of the porous material can be inherent in the porous material itself, or can be obtained through further chemical modification. For example, the porous silica material itself has hydroxyl groups, and can be further modified with amino groups, nitro groups, sulfhydryl groups or methyl groups on the surface. These surface-modified porous materials can be prepared using commonly used methods in the art and can also be purchased commercially.

[0070] In some embodiments, the polymer includes at least one of polyethersulfone, polysulfone, cellulose acetate, polynylon, polyvinylidene fluoride, polyimide, polyvinylidene chloride, polystyrene, polyethylene, polypropylene, and acrylic polymers.

[0071] In one embodiment of the present application, a method for preparing the composite film material is further provided, comprising the following steps S10 to S20.

[0072] Step S10: mixing the porogen, polymer, porous material and solvent to prepare a mixed solution.

[0073] Step S20: placing the mixed solution in water for film-forming treatment to prepare a composite film material.

[0074] During the film-forming process, the polymer forms a continuous phase, and the porous material is dispersed in the continuous phase. At the same time, under the action of the porogen, the continuous phase will form a pore structure, thereby obtaining a composite membrane material with a larger specific surface area.

[0075] In some embodiments, the polymer is a water-insoluble polymer.

[0076] In some embodiments, the porogen is a water-soluble porogen.

[0077] In some embodiments, the porogen includes at least one of polyvinyl pyrrolidone, glycerol, and polyethylene glycol.

[0078] In some embodiments, the mass ratio of the porogen to the polymer is (0.5-0.8):1.

[0079] In some embodiments, the solvent is miscible with water.

[0080] In one embodiment, the solvent includes water and dimethylacetamide; further, the mass ratio of water to dimethylacetamide is (0.02-0.26):1.

[0081] The types of polymers and porous materials and their mass ratios are the same as those described above and will not be repeated here.

[0082] In some embodiments, the solid content of the mixed solution is 10% to 16%.

[0083] In some embodiments, the mixing step in step S10 is performed under stirring conditions.

[0084] In some embodiments, before the film forming step, the method further includes a step of degassing the mixed solution.

[0085] In some embodiments, the film forming step in step S20 may adopt a film forming method commonly used in the art, including but not limited to scraping film forming, and the specific steps are as follows:

[0086] The mixed liquid is poured onto a glass plate, scraped with a scraper to form a wet film, then immersed in deionized water to obtain a formed film, and then washed with deionized water to remove residual solvent to obtain a composite membrane material.

[0087] It can be understood that in the mixed liquid, the polymer and the porogen are dissolved in the solvent. When a wet film is scraped into a wet film with a scraper and then immersed in deionized water, the solvent and the water-soluble porogen (such as polyvinyl pyrrolidone, glycerol or polyethylene glycol) are released from the wet film, so that the water-insoluble polymer forms a continuous phase with a porous structure. The dispersion medium is also insoluble in water and is dispersed in the continuous phase to form a composite membrane material.

[0088] One embodiment of the present application further provides the use of the above-mentioned composite membrane material or the composite membrane material prepared by the above-mentioned composite membrane material preparation method in the preparation of a medium for separation and purification.

[0089] The above-mentioned composite membrane material itself has a large specific surface area. When used to prepare separation and purification media, due to the large specific surface area of ​​the composite membrane material itself, the number of functional groups that can be introduced during functionalization is increased, thereby increasing the loading capacity of the functionalized chromatographic membrane for target molecules.

[0090] One embodiment of the present application further provides a separation and purification medium, comprising a basement membrane and a functional layer supported on the surface of the basement membrane; the basement membrane comprises the above-mentioned composite membrane material or a composite membrane material prepared by the above-mentioned composite membrane material preparation method, and the functional layer contains functional groups that can specifically bind to proteins.

[0091] The composite membrane material has a high specific surface area, which can increase the area of ​​the functional layer loaded on its surface, thereby increasing the number of introduced functional groups and significantly improving the protein loading capacity.

[0092] It should be noted that the functional groups capable of specifically binding to proteins can be functional groups that have been demonstrated in the art to specifically bind to various proteins. Specific binding can be achieved through the formation of ionic bonds, hydrogen bonds, or intermolecular forces such as electrostatic interactions between positive and negative charges, dipole interactions, and dispersion forces. For example, when the functional layer comprises polyethyleneimine, when using bovine serum albumin as the target molecule for a loading test, under neutral conditions, polyethyleneimine carries a positive charge and bovine serum albumin carries a negative charge. The electrostatic interaction between the two allows the bovine serum albumin to be loaded onto the membrane layer, achieving the purpose of targeted separation and purification of the bovine serum albumin. Furthermore, the basement membrane in the separation and purification medium can carry more functional groups, thereby increasing the loading capacity for the bovine serum albumin.

[0093] It is understood that the functional groups capable of specifically binding to proteins may be any of various groups known in the art capable of specifically binding to proteins, including hydrophilic functional groups, hydrophobic functional groups and affinity functional groups.

[0094] In some embodiments, the functional group includes at least one of a hydrophilic functional group such as an amine group, an imine group, a quaternary ammonium salt, a carboxyl group, a sulfonic acid group, a hydrophobic functional group, and an affinity functional group.

[0095] In some embodiments, the polyethyleneimine includes cross-linked polyethyleneimine, which is formed by cross-linking polyethyleneimine with a cross-linking agent containing an epoxy group, and the reaction sites of the cross-linking reaction include an amine group in the polyethyleneimine and an epoxy group in the cross-linking agent.

[0096] It can be understood that the number of epoxy groups contained in one molecule of the epoxy-containing cross-linking agent is greater than or equal to 2.

[0097] In some embodiments, the mass ratio of the functional layer to the base film is (0.09-0.42):1.

[0098] It should be noted that since the continuous phase in the composite membrane material in the base membrane also has a pore structure and is dispersed with a dispersion medium, when the functional layer is loaded on the surface of the base membrane, the functional layer includes but is not limited to: the surface of the continuous phase loaded in the composite membrane material, the outer surface and inner surface of the pore structure of the continuous phase.

[0099] The method for preparing the separation and purification medium includes the following step S30:

[0100] S30: The base membrane is immersed in an aqueous solution of polyethyleneimine and dried to prepare a medium for separation and purification.

[0101] Furthermore, when the polyethyleneimine comprises cross-linked polyethyleneimine, the preparation step comprises the following steps S31 to S32:

[0102] Step S31: placing the base film in an aqueous solution of a cross-linking agent containing an epoxy group to perform a cross-linking reaction;

[0103] Step S32: placing the product obtained in step S31 in an aqueous solution of polyethyleneimine to continue the cross-linking reaction and prepare a medium for separation and purification.

[0104] In some embodiments, the epoxy-containing crosslinking agent is an organic small molecule crosslinking agent, including but not limited to at least one of epichlorohydrin, 1,4-butanediol diglycidyl ether, and polyethylene glycol diglycidyl ether.

[0105] Another embodiment of the present application further provides use of the above separation and purification medium in separating and purifying proteins.

[0106] The functional layer of the separation and purification medium contains functional groups that can specifically bind to proteins, thereby being able to bind to proteins in a targeted manner and increasing the protein loading capacity.

[0107] In some embodiments, the protein is bovine serum albumin. Another embodiment of the present application further provides a separation and purification device, which contains the composite membrane material or the composite membrane material prepared by the method for preparing the composite membrane material or the separation and purification medium.

[0108] In some embodiments, the separation and purification device includes at least one of a chromatography membrane, a chromatography column, and a solid phase extraction device.

[0109] The present application will be described below in conjunction with specific embodiments, but the present application is not limited to the following embodiments. It should be understood that the attached claims summarize the scope of the present application. Under the guidance of the concept of the present application, those skilled in the art should realize that certain changes made to the various embodiments of the present application will be covered by the spirit and scope of the claims of the present application.

[0110] The following are specific examples.

[0111] Example 1

[0112] (1) Preparation of composite membrane materials

[0113] First, add 1.8 g of dispersion medium (porous silica spheres with a diameter of 3 μm, a pore size of 100 nm, and a porosity of 75%) to a mixed solution of 25.65 g of N,N-dimethylacetamide and 0.52 g of deionized water. After stirring evenly, add 3.58 g of porogen (polyvinylpyrrolidone PVP) and continue stirring until completely dissolved. Then add 4.97 g of polymer (polyethersulfone PES, with a number average molecular weight of 6w) and stir to form a mixed solution. Let it stand for more than 12 hours to degas for use.

[0114] Pour the degassed mixture evenly onto a clean, dry glass plate, scrape it at a constant speed with a scraper to form a film, place it in a constant temperature and humidity chamber for 5 seconds, and then soak it in deionized water at 25°C for 5 minutes. After the film is formed and falls off the glass plate, wash it with deionized water to remove the residual solvent to obtain a composite membrane material, which is then stored in deionized water for use.

[0115] The mass ratio of the polymer to the dispersion medium in the mixed solution is the mass ratio of the continuous phase to the dispersion medium in the formed composite film material, which is Y, as shown in Table 1.

[0116] The front, back and side surfaces of the prepared composite membrane were observed under an electron scanning microscope. The electron scanning microscope images are shown in Figure 1, where (a1), (a2) and (a3) ​​are the electron scanning microscope images of the front, back and side surfaces of the composite membrane, respectively. From the electron scanning microscope images, the continuous phase containing the porous structure and the dispersion medium dispersed in the continuous phase can be clearly observed.

[0117] The specific surface area of ​​the composite membrane was measured by mercury intrusion testing (fully automatic mercury intrusion instrument, Micromeritics Atuo Pore V). The specific results are shown in Table 1.

[0118] (2) Preparation of separation and purification medium

[0119] 1: The composite membrane material prepared in step (1) was immersed in a 30 wt% aqueous solution of 1,4-butanediol diglycidyl ether at room temperature for 30 min, then placed in a sealed container at room temperature for 3 h, and finally immersed in water for 3 times, each time for 10 min. The product was marked as M-1.

[0120] 2: Soak the product M-1 in a 20wt% aqueous solution of polyethyleneimine (number average molecular weight 5w) at room temperature for 1 hour, then soak it in a 5wt% sulfuric acid solution at room temperature for 5 minutes, and then soak it in water for 3 times, each time for 10 minutes. The product is labeled M-2 and can be used as a medium for separation and purification;

[0121] During the preparation process, the amount of polyethyleneimine aqueous solution and cross-linking agent aqueous solution used is much greater than the mass of the base film, and the mass ratio of polyethyleneimine to the base film is 85:1.

[0122] (3) Performance test, as follows:

[0123] Water flux test: Water flux refers to the amount of water that can flow through a separation and purification medium per unit time and per unit area under a certain pressure. Use a water flux tester to test the water flux of a separation and purification medium: Place the separation and purification medium membrane in a membrane tank, set the pressure of the water flux tester at 0.5 bar, and record the time required for 100 mL of water to flow out.

[0124] BSA (bovine serum albumin) loading test:

[0125] Adsorption: First, clean the separation and purification medium membrane with deionized water, then rinse the membrane with Tris buffer (tromethamine), then soak the membrane of fixed mass and volume in BSA solution and shake for 30 minutes, and then clean the membrane with Tris.

[0126] Desorption: Soak the cleaned membrane in a mixture of Tris and NaCl and shake for 30 minutes. Finally, test the amount of BSA in the mixture. The amount of BSA in the mixture represents the amount of BSA loaded by the medium for separation and purification.

[0127] Please see Table 1 for specific test results.

[0128] Example 2

[0129] Example 2 is basically the same as Example 1, except that the dispersion medium used in step (1) of Example 2 is porous silica spheres with a diameter of 3 μm and a pore size of 200 nm.

[0130] The other steps and conditions were the same as those in Example 1. Please see Table 1 for the specific results.

[0131] Among them, the front, back and side of the composite membrane material prepared in Example 2 were placed under an electron scanning microscope for observation. The electron scanning microscope image is shown in Figure 2, wherein (b1), (b2) and (b3) are electron scanning microscope images of the front, back and side of the composite membrane material, respectively. From the electron scanning microscope image, the continuous phase containing the porous structure and the dispersion medium dispersed in the continuous phase can be clearly observed.

[0132] Example 3

[0133] Example 3 is basically the same as Example 2, except that the composite membrane material in step (2) of Example 3 is immersed in an aqueous solution of 1,4-butanediol diglycidyl ether with a mass concentration of 15 wt%.

[0134] The other steps and conditions are the same as those in Example 2. Please see Table 1 for the specific results.

[0135] Example 4

[0136] Example 4 is basically the same as Example 2, except that the dispersion medium used in step (1) of Example 4 is porous polystyrene microspheres with a diameter of 3 μm and a pore size of 200 nm.

[0137] The other steps and conditions are the same as those in Example 2. Please see Table 1 for the specific results.

[0138] Example 5

[0139] Example 5 is basically the same as Example 2, except that: in step (1) of Example 5, the mass ratio of the polymer to the dispersion medium in the mixed solution is different from that in Example 2, that is, the value of Y is controlled differently from that in Example 2.

[0140] The other steps and conditions are the same as those in Example 2. Please see Table 1 for the specific results.

[0141] Comparative Example 1

[0142] Comparative Example 1 is substantially the same as Example 1, except that no dispersion medium is added in step (1) of Comparative Example 1.

[0143] The other steps and conditions are the same as those in Example 2. Please see Table 1 for the specific results.

[0144] The front, back and side surfaces of the composite membrane material prepared in Comparative Example 1 were observed under an electron scanning microscope. The electron scanning microscope images are shown in FIG3 , wherein (c1), (c2) and (c3) are electron scanning microscope images of the front, back and side surfaces of the composite membrane material, respectively. Only a continuous phase containing a porous structure can be observed from the electron scanning microscope images.

[0145] The relevant parameters and test results in each embodiment and comparative example are shown in Table 1.

[0146] Table 1

[0147] “ / ” means that the substance or parameter does not exist.

[0148] By analyzing the data in Table 1 and comparing the data of Examples 1 to 5 with Comparative Example 1, it can be seen that the composite membrane material of the present application has a larger specific surface area. When further functionalized, it can also provide more functional group loading area, thereby introducing more functional groups, thereby increasing the loading capacity of the functionalized chromatography membrane for the target molecule.

[0149] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0150] The above embodiments merely illustrate several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of this patent shall be determined by the appended claims.

Claims

1. A composite membrane material, characterized in that: The composite membrane material includes a continuous phase with a pore structure and a dispersion medium dispersed in the continuous phase. The component of the continuous phase includes a polymer, and the dispersion medium includes a porous material.

2. The composite film material according to claim 1, wherein The mass ratio of the continuous phase to the dispersion medium is 1:(0.1-2).

3. The composite film material according to any one of claims 1 to 2, characterized in that: The pore size of the porous material is 20 nm to 500 nm.

4. The composite film material according to any one of claims 1 to 2, characterized in that: The pore size of the porous material is 100 nm to 500 nm.

5. The composite film material according to any one of claims 1 to 2, characterized in that: The diameter of the porous material is 100 nm to 50 μm; and / or The porosity of the porous material is 20% to 80%.

6. The composite film material according to any one of claims 1 to 2, characterized in that: The components of the porous material include at least one of silicon dioxide, titanium dioxide, an organic polymer and an organometallic framework material; and / or The surface of the porous material contains at least one of hydroxyl, carboxyl, amino, nitro, thiol and methyl groups; and / or The polymer includes at least one of polyethersulfone, polysulfone, cellulose acetate, polynylon, polyvinylidene fluoride, polyimide, polyvinylidene chloride, polystyrene, polyethylene, polypropylene and acrylic polymers.

7. The method for preparing a composite film material according to any one of claims 1 to 6, wherein: The steps include: mixing a porogen, the polymer, the porous material and a solvent to prepare a mixed solution; The mixed solution is placed in water for film-forming treatment to prepare the composite membrane material.

8. The method for preparing a composite film material according to claim 7, wherein: The porogen comprises at least one of polyvinyl pyrrolidone, glycerol and polyethylene glycol; and / or The mass ratio of the porogen to the polymer is (0.5-0.8):1; and / or The solvents include water and dimethylacetamide.

9. Use of the composite membrane material according to any one of claims 1 to 6 or the composite membrane material prepared by the method for preparing the composite membrane material according to any one of claims 7 to 8 in preparing a medium for separation and purification.

10. A medium for separation and purification, characterized in that: The separation and purification medium includes a base membrane and a functional layer loaded on the surface of the base membrane; the base membrane includes a composite membrane material as described in any one of claims 1 to 6 or a composite membrane material prepared by the preparation method of the composite membrane material as described in any one of claims 7 to 8, and the functional layer contains functional groups that can specifically bind to proteins.

11. The separation and purification medium according to claim 10, wherein The functional group includes at least one of an amine group, an imine group, a quaternary ammonium salt, a carboxyl group, a sulfonic acid group, a hydrophobic functional group and an affinity functional group.

12. The separation and purification medium according to claim 10, wherein The components of the functional layer include at least one of polyethyleneimine, quaternary ammonium salt, polyallylamine and Protein A.

13. The separation and purification medium according to claim 12, wherein: The polyethyleneimine includes cross-linked polyethyleneimine, which is formed by cross-linking polyethyleneimine with a cross-linking agent containing an epoxy group, and the reaction sites of the cross-linking reaction include an amine group in the polyethyleneimine and an epoxy group in the cross-linking agent; and / or The mass ratio of the functional layer to the base film is (0.09-0.42):

1.

14. Use of the separation and purification medium according to any one of claims 10 to 13 in separating and purifying proteins.

15. A separation and purification device, characterized in that: The separation and purification device contains the composite membrane material according to any one of claims 1 to 6, or the composite membrane material prepared by the method for preparing the composite membrane material according to any one of claims 7 to 8, or the separation and purification medium according to any one of claims 10 to 13.

16. The separation and purification device according to claim 15, characterized in that: The separation and purification device includes at least one of a chromatographic membrane, a chromatographic column and a solid phase extraction device.

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