Anion exchange resin membrane applied to blood purification and a preparation method thereof

Abstract

The application relates to the field of blood purification materials, and particularly discloses an anion exchange resin membrane applied to blood purification and a preparation method thereof. The anion exchange resin membrane applied to blood purification is prepared by blending a zwitterion-anion exchange copolymer and a hydrophobic film-forming polymer; the zwitterion-anion exchange copolymer is copolymerized by an anion exchange monomer and a zwitterion monomer, so that the resin membrane has anion exchange function and anti-protein adsorption function; the preparation method is as follows: the anion exchange monomer and the zwitterion monomer are subjected to free radical copolymerization under the action of an initiator; the copolymer and polyether sulfone are dissolved in a polar aprotic solvent to prepare a casting solution, and after casting film formation, phase inversion is completed by immersing in a coagulation bath; the obtained membrane is cleaned and subjected to alkalization treatment. The application solves the problems that traditional anion exchange resins easily cause non-specific protein adsorption, platelet adhesion and complement system activation.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of blood purification materials, more particularly, it relates to a kind of anion exchange resin membrane applied to blood purification and preparation method thereof. BACKGROUND

[0002] Blood purification is a key technology in modern medicine for treating end-stage renal disease, autoimmune diseases, drug poisoning and various metabolic disorders. Its core principle is to selectively remove pathogenic toxins, metabolic waste or abnormal antibodies from the patient's blood through extracorporeal circulation using specific separation membranes or adsorbents. Among them, the medium-sized negatively charged toxins (such as heparin, low-density lipoprotein, some inflammatory factors and autoantibodies) play an important role in the pathogenic process. Due to the fixed quaternary ammonium salt and other positive groups on its skeleton, anion exchange resin can efficiently adsorb these negatively charged substances through electrostatic interaction, so it has great application potential in purification devices such as blood perfusion and becomes an important supplement to existing blood purification technology.

[0003] However, when traditional anion exchange materials are directly applied to blood purification scenarios, they face serious biocompatibility challenges. This is mainly due to two inherent properties of the material itself: first, the polymer skeleton usually has strong hydrophobicity; second, the surface is densely distributed with a large number of positive charge sites. When blood comes into contact with this material, proteins in the plasma (such as albumin, fibrinogen, immunoglobulin, etc.) will be adsorbed by a large number of non-specific adsorption through hydrophobic interaction and strong electrostatic interaction. This adsorption will immediately trigger a series of adverse biological reactions: first, the adsorbed proteins undergo conformational changes, activating the coagulation and complement systems, leading to platelet aggregation and adhesion, and forming a thrombosis risk; second, it triggers a chain of inflammatory reactions, which can cause a decrease in white blood cells, an increase in body temperature and other allergic reactions in patients. These problems seriously limit the widespread application of traditional anion exchange resins in blood purification treatments that require long-term and high safety. SUMMARY

[0004] In order to solve the problem of non-specific protein adsorption, platelet adhesion and complement system activation caused by traditional anion exchange resin membranes, the present application provides an anion exchange resin membrane applied to blood purification and a preparation method thereof.

[0005] Firstly, the anion exchange resin membrane applied to blood purification provided by the present application adopts the following technical solution:

[0006] An anion exchange resin membrane applied to blood purification is prepared by blending a zwitterion-anion exchange copolymer and a hydrophobic film-forming polymer;

[0007] The amphoteric ion-anion exchange copolymer is copolymerized by an anion exchange monomer and an amphoteric ion monomer, so that the resin film has both anion exchange function and anti-protein adsorption function.

[0008] By adopting the technical scheme, the anion exchange functional group and the amphoteric ion structure are integrated in a single copolymer molecular chain by chemical bonding, and are further formed into a stable three-dimensional network structure with the membrane matrix by a phase inversion method. This design ensures that the anti-fouling amphoteric ion component cannot be dissolved or peeled off from the membrane even under complex fluid shear force and long-term use conditions during blood purification, thereby providing persistent and stable biocompatibility. Meanwhile, the anion exchange group is firmly fixed inside and on the surface of the whole porous membrane, realizing efficient and uniform adsorption of negative toxins. This structure fundamentally solves the technical contradiction between instability of the functional layer and mutual restriction of adsorption capacity and biocompatibility in the conventional physical blending or surface coating method.

[0009] Optionally, the anion exchange monomer is methacryloyloxyethyl trimethyl ammonium chloride or (3-acrylamidopropyl) trimethyl ammonium chloride.

[0010] By adopting the technical scheme, the quaternary ammonium salt groups provided by the two monomers can always maintain strong positive electricity under physiological environment, and have strong and stable electrostatic adsorption capacity for negative target toxins such as heparin and inflammatory factors. In addition, the molecular chain segment length is moderate, which ensures that the ion exchange group has good spatial accessibility, and avoids the problem of loose membrane structure or decreased mechanical properties caused by excessively long chain segments.

[0011] Optionally, the amphoteric ion monomer is sulfobetaine methacrylate or carboxybetaine methacrylate.

[0012] By adopting the technical scheme, the positive and negative charge centers in the molecular structure form electrical neutrality in the form of internal salt, can strongly bind surrounding water molecules through ionic solvation, and form a dense “hydration layer” on the membrane surface. This layer of hydration layer can effectively block the direct contact of biological macromolecules such as plasma proteins and platelets with the membrane material, like a physical barrier, significantly reducing non-specific adsorption and subsequent coagulation and complement activation cascade reactions. By selecting these two monomers, the blood compatibility core problem mentioned in the background art is directly and effectively solved.

[0013] Optionally, in the amphoteric ion-anion exchange copolymer, the molar ratio of the structural units of the two monomers is 3:7 to 7:3.

[0014] By adopting the technical scheme, when the proportion is biased towards the anion exchange monomer, the adsorption capacity of the membrane is improved, but the anti-fouling effect may be weakened; on the contrary, the anti-fouling property is excellent but the adsorption efficiency may be insufficient. The proportion is limited in the narrow range of 3:7 to 7:3, which is the optimal interval verified through a large number of experiments. The resin membrane prepared in the interval can still exhibit excellent blood compatibility while ensuring a high enough adsorption clearance rate on the target toxin, successfully realizing the synergy and optimization of the two seemingly contradictory functional properties, and ensuring that the application has high efficiency and safety in clinical application.

[0015] In a second aspect, the application provides a preparation method of an anion exchange resin membrane.

[0016] The preparation method of the anion exchange resin membrane for blood purification comprises the following steps:

[0017] a. Synthesis of copolymer: free radical copolymerization of anion exchange monomer and zwitterionic monomer under the action of initiator to obtain zwitterionic-anion exchange copolymer;

[0018] b. Casting and molding: dissolving the copolymer and polyether sulfone in a polar aprotic solvent to prepare a casting solution, and then immersing the cast film in a coagulation bath to complete the phase inversion after casting;

[0019] c. Post-treatment: washing and alkalization treatment of the obtained membrane to convert the anion exchange group into hydroxyl type.

[0020] By adopting the technical scheme, first, a polymer with both hydrophilic and hydrophobic functions is "customized" through free radical copolymerization, and then it is introduced into the casting solution system as a key additive. During the phase inversion process, the copolymer will spontaneously migrate and enrich on the membrane pore surface and interface with the exchange of solvent and non-solvent, thereby constructing a functional blood contact surface in situ while the membrane is formed. This method is one-step, avoids complicated and unstable post-modification steps, is simple in process, is very suitable for large-scale production, and ensures the uniformity and reproducibility of the performance of the final product.

[0021] Optionally, in step b, the polar aprotic solvent is N-methylpyrrolidone or N,N-dimethylacetamide.

[0022] By adopting the technical scheme, the two polar aprotic solvents of N-methylpyrrolidone and N,N-dimethylacetamide have excellent solubility, and can fully dissolve the hydrophobic polyether sulfone matrix and the hydrophilic zwitterion-anion exchange copolymer at the same time, forming a thermodynamically stable homogeneous casting solution. This is the prerequisite for preparing a structure-uniform and defect-free separation membrane. In addition, the boiling points of the two solvents are moderate, and the water exchange speed is suitable, which can effectively regulate the kinetics of the phase inversion process, and is beneficial to the formation of a porous structure with ideal pore size, distribution and porosity, which is crucial for the mass transfer and diffusion of toxin molecules and blood flow resistance.

[0023] Optionally, in step b, the coagulation bath is water or a mixture of water and a solvent.

[0024] By adopting the technical scheme, using water or a mixture of water and a solvent as the coagulation bath is a classic and efficient means to induce liquid-liquid phase separation of a thermodynamically unstable system, thereby realizing polymer solidification molding. The strong non-solvent property of water ensures that the membrane structure can be quickly solidified and shaped to form a stable three-dimensional network. By adjusting the content of the solvent in the coagulation bath, the speed of phase separation can be accurately controlled: slower phase separation helps to form more open and uniform finger-like pore structures, while fast phase separation tends to form a dense skin layer. This makes the method have good adjustability, and can be customized to optimize the micro-morphology of the membrane according to different toxin removal needs.

[0025] Optionally, in step c, the alkali treatment uses a 0.1-1.0 mol / L sodium hydroxide solution.

[0026] By adopting the technical scheme, using a 0.1-1.0 mol / L sodium hydroxide solution for post-treatment realizes complete and thorough conversion of the anion exchange group from chloride type (or other halogen ion type) to hydroxide type. Hydroxide type is the most active form of anion exchange resin in blood purification applications, and has the fastest exchange kinetics for target toxins. The alkali solution in this concentration range can ensure that the conversion reaction proceeds sufficiently, and also avoids chemical degradation or hydrolysis damage to the polymer membrane skeleton (especially polyether sulfone) that may be caused by high alkali concentration, thereby activating the highest adsorption performance of the resin membrane while ensuring its long-term chemical stability and mechanical integrity.

[0027] In summary, the present application has the following beneficial effects:

[0028] 1. The application successfully realizes the synergistic and stable combination of antifouling function and adsorption function at the molecular level by adopting the technical scheme of preparing functional copolymer by chemical copolymerization of zwitterionic monomer and anion exchange monomer, and then blending the functional copolymer with a membrane matrix material to form a membrane. The resin membrane can significantly reduce non-specific protein adsorption and platelet adhesion in the blood purification process, effectively reduce the risk of blood coagulation and inflammatory response, and at the same time maintain the high adsorption and removal capacity of negative electrically charged toxins such as heparin, thereby fundamentally solving the technical problem that the biocompatibility and adsorption efficiency of traditional materials are difficult to balance.

[0029] 2. In the application, sulfobetaine methacrylate is preferably used as the zwitterionic monomer, and methacryloyloxyethyl trimethyl ammonium chloride is preferably used as the anion exchange monomer, and the molar ratio of the two is controlled in the optimized interval of 3:7 to 7:3. This preferred scheme ensures that the zwitterionic chain segment in the final product can form a dense and stable hydration layer to provide excellent blood compatibility, and at the same time, the anion exchange group has sufficient steric hindrance and charge density, thereby achieving the best balance between antifouling performance and ion exchange capacity, and making the comprehensive performance of the product meet the stringent requirements of clinical application.

[0030] 3. The method of the application realizes one-step in-situ forming of functional materials by organically combining the synthesis of functional copolymer and phase inversion film forming process. The method has a simple and efficient process route, avoids complex post-modification or surface coating steps, improves the stability and reproducibility of production, and more importantly, ensures the uniform and stable existence of functional components in the membrane and on the surface, avoids the risk of functional layer falling off during use, and provides a reliable and economically beneficial technical path for large-scale production of high-performance blood purification materials. DETAILED DESCRIPTION

[0031] The application will be further described in detail below in conjunction with examples. It is particularly pointed out that: in the following examples, the specific conditions are not specified, and the conventional conditions or the conditions recommended by the manufacturer are used. In the following examples, the raw materials used can be obtained from ordinary commercial sources unless otherwise specified.

[0032] Example 1

[0033] The present embodiment provides an anion exchange resin membrane for blood purification and a preparation method thereof.

[0034] Step 1: In a 250 mL three-necked flask equipped with a stirrer, a condenser and a nitrogen inlet tube, 100 mL of deionized water was added as a solvent. After purging with nitrogen to remove air, the following were sequentially added:

[0035] Anion exchange monomer: (3-acrylamidopropyl) trimethylammonium chloride (ATAC) aqueous solution (75 wt%), 10.67 g (about 0.05 mol).

[0036] Zwitterionic monomer: sulfobetaine methacrylate (SBMA), 14.93 g (about 0.05 mol).

[0037] The total moles of the two monomers were controlled to be 0.1 mol, and the structural unit mole ratio of ATAC to SBMA was 1:1.

[0038] Subsequently, 0.16 g (about 1 mmol) of azobisdimethylamidin hydrochloride (AIBA) was added as a water-soluble initiator. Under continuous nitrogen and stirring, the reaction system was warmed to 70°C, and reacted at this temperature for 8 hours. After the reaction was completed, the obtained viscous reaction liquid was poured into a large amount of acetone for precipitation. The white precipitate was collected by filtration and washed with acetone three times. Finally, the product was dried in a vacuum drying oven at 50°C for 24 hours to obtain a white zwitterionic-anion exchange copolymer (P(ATAC-co-SBMA)).

[0039] Step 2, 2.0 g of the copolymer P(ATAC-co-SBMA) synthesized above and 18.0 g of a hydrophobic film-forming polymer polyether sulfone (PES) (i.e., the mass ratio of the copolymer to PES was 1:9) were weighed and added together into 80 g of a polar aprotic solvent N-methyl pyrrolidone (NMP). Under continuous mechanical stirring at 80°C for 12 hours, until all the polymers were completely dissolved, a uniform and transparent casting solution was obtained. The casting solution was left to stand for defoaming for standby use.

[0040] The defoamed casting solution was cast into a film on a clean glass plate using a doctor blade with a gap setting of 200 μm. Subsequently, the glass plate with the liquid film was immediately immersed horizontally into a coagulation bath (deionized water at a temperature of 25°C). The casting solution underwent phase separation in water and solidified into a nascent film.

[0041] Step 3: The nascent film was peeled off from the glass plate, immersed in a large amount of deionized water and washed repeatedly to completely remove the residual NMP solvent. Subsequently, the film was immersed in a 0.5 mol / L sodium hydroxide aqueous solution for 24 hours for alkalization treatment, so that the anion exchange groups in the film were completely converted from chloride type to hydroxide type. Finally, the film was washed with deionized water to neutral.

[0042] Example 2

[0043] The difference between this example and Example 1 is only that in Step 1, the structural unit mole ratio of the anion exchange monomer ATAC to the zwitterionic monomer SBMA was adjusted to be 3:7.

[0044] That is, the amount of ATAC was about 0.03 mol, and the amount of SBMA was about 0.07 mol. The remaining preparation steps and parameters were exactly the same as those of Example 1.

[0045] Example 3

[0046] The difference between this example and Example 1 is that the molar ratio of the structural units of the anion exchange monomer ATAC and the zwitterionic monomer SBMA is adjusted to 7:3 in Step 1.

[0047] That is, the amount of ATAC is about 0.07 mol, and the amount of SBMA is about 0.03 mol. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0048] Example 4

[0049] The difference between this example and Example 1 is that the anion exchange monomer is replaced by equimolar methacryloyloxyethyl trimethyl ammonium chloride (DMC) in Step 1.

[0050] That is, DMC 7.86 g (about 0.05 mol) and SBMA 14.93 g (about 0.05 mol) are used for copolymerization. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0051] Example 5

[0052] The difference between this example and Example 1 is that the zwitterionic monomer is replaced by equimolar carboxybetaine methacrylate (CBMA) in Step 1.

[0053] That is, ATAC 10.67 g (about 0.05 mol) and CBMA 13.36 g (about 0.05 mol) are used for copolymerization. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0054] Example 6

[0055] The difference between this example and Example 1 is that the concentration of the sodium hydroxide solution used for alkalization treatment is changed to 0.1 mol / L in Step 2. The soaking time is also 24 hours. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0056] Example 7

[0057] The difference between this example and Example 1 is that the mass ratio of the zwitterionic-anion exchange copolymer and polyether sulfone (PES) is adjusted to 1:19 in Step 2.

[0058] That is, 1.0 g of copolymer P(ATAC-co-SBMA) and 19.0 g of PES are weighed and dissolved in 80 g of NMP. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0059] Example 8

[0060] The difference between this example and Example 1 is only that the mass ratio of zwitterionic-anionic exchange copolymer to polyethersulfone (PES) is adjusted to 3:7 in Step 2.

[0061] That is, 6.0 g of copolymer P(ATAC-co-SBMA) and 14.0 g of PES are weighed and dissolved in 80 g of NMP. The remaining preparation steps and parameters are exactly the same as in Example 1.

[0062] Example 9

[0063] The difference between this example and Example 1 is only that the polar aprotic solvent is replaced by an equal amount of N,N-dimethylacetamide (DMAC) in Step 2.

[0064] The remaining preparation steps and parameters are exactly the same as in Example 1.

[0065] Example 10

[0066] The difference between this example and Example 1 is only that the coagulation bath is replaced by an NMP / water mixture (volume ratio 1:9) in Step 2.

[0067] The remaining preparation steps and parameters are exactly the same as in Example 1.

[0068] Comparative Example 1

[0069] This comparative example uses physical blending of two single-function polymers to replace the core copolymer of the present application.

[0070] Preparation method: No copolymer is synthesized. Directly weigh 1.0 g of poly(3-acrylamidopropyl) trimethylammonium chloride (homopolymer, as an anion exchanger) and 1.0 g of polysulfobetaine methacrylate (homopolymer, as a antifouling agent) and dissolve them together with 18.0 g of polyethersulfone (PES) in 80 g of N-methyl pyrrolidone (NMP). The subsequent film forming, phase inversion and post-treatment steps are exactly the same as in Example 1.

[0071] Comparative Example 2

[0072] This comparative example only uses an anion exchange homopolymer, completely missing the zwitterionic antifouling component.

[0073] Preparation method: No copolymer is synthesized, and no antifouling polymer is added. Directly weigh 2.0 g of poly(3-acrylamidopropyl) trimethylammonium chloride and dissolve it together with 18.0 g of PES in 80 g of NMP. The subsequent steps are the same as in Example 1.

[0074] Comparative Example 3

[0075] This comparative example only uses a zwitterionic homopolymer, completely missing the anion exchange function.

[0076] Preparation method: No synthetic copolymer. Directly weigh 2.0 g of polysulfobetaine methacrylate and 18.0 g of PES together and dissolve in 80 g of NMP. The subsequent steps are the same as Example 1.

[0077] Ion exchange capacity: According to the standard of ASTM D2187, the acid-base titration method is used for determination. Accurately weigh 0.1 g of dry film sample, convert it into chloride type with 1 mol / L NaCl solution, and then titrate with 0.01 mol / L NaOH standard solution to calculate the ion exchange capacity per unit mass of dry film.

[0078] Human serum albumin adsorption capacity: According to the standard of ISO / TS10993-4, immerse a 1 cm x 1 cm film piece in 1 mL of human serum (37°C) for 2 hours. Use the BCA protein quantification kit to determine the difference in protein concentration before and after adsorption, and calculate the protein adsorption capacity per unit area.

[0079] Platelet adsorption number: According to the standard of YY / T0616.5, immerse the film piece in fresh platelet-rich plasma (1 x 10 8 Platelets / mL) at 37°C for 1 hour. After glutaraldehyde fixation, dehydration, critical point drying and gold spraying, count the number of platelets under 5000 times by scanning electron microscopy (SEM, Hitachi SU8010) and take the average value.

[0080] Heparin clearance rate: Prepare a 100 μg / mL heparin sodium solution (pH 7.4 PBS buffer), immerse a 1 cm x 1 cm film piece in 10 mL of the solution, and shake at 37°C for 4 hours. Use the toluidine blue method to determine the heparin concentration before and after the reaction, and calculate the clearance rate.

[0081] Wet tensile strength: According to the standard of GB / T1040.3, cut the film sample into 10 mm x 50 mm strips, and use a universal material testing machine (Instron5967) to perform tensile testing at a speed of 10 mm / min in a wet state, and record the breaking strength.

[0082] Ion exchange capacity (mmol / g) Human serum albumin adsorption amount (μg / cm²) Platelet adsorption number (number / 1000 μm²) Heparin clearance rate (%) Wet tensile strength (MPa) Example 1 1.05 2.1 15 95.2 5.8 Example 2 0.78 1.8 12 88.5 5.9 Example 3 1.25 5.6 45 96.8 5.5 Example 4 1.02 2.3 16 94.7 5.7 Example 5 0.98 2.5 18 93.5 5.6 Example 6 0.92 2.2 16 90.1 5.7 Example 7 0.51 3.5 28 75.3 6.2 Example 8 1.32 2.5 17 96.5 4.1 Example 9 1.02 2.2 16 94.0 5.5 Example 10 1.04 2.1 15 94.8 5.7 Comparative Example 1 0.95 8.7 62 89.5 4.5 Comparative Example 2 1.10 25.4 >100 93.8 5.9 Comparative Example 3 0.02 1.9 11 3.5 5.4

[0083] It can be seen from the combination of Example 1 and Comparative Example 1 and Table 1 that, although the total amount of functional component elements of both is similar, the anion exchange resin membrane of Example 1 is significantly lower than Comparative Example 1 (8.7 μg / cm2and 62 / 1000 μm2) in human serum albumin adsorption amount (2.1 μg / cm2) and platelet adsorption amount (15 / 1000 μm2). This data difference clearly proves that the integration of the two functional groups in the same molecular chain by chemical copolymerization can achieve uniform distribution of the function at the molecular level, effectively avoiding the surface function "island" effect caused by phase separation during physical blending, thereby fundamentally improving the blood compatibility of the material.

[0084] It can be seen from the combination of Example 1 and Comparative Example 2 and Table 1 that, Comparative Example 2, which lacks the zwitterionic component, has an anion exchange capacity (1.10 mmol / g) and a heparin clearance rate (93.8%) comparable to Example 1 (1.05 mmol / g, 95.2%), but its human serum albumin adsorption amount (25.4 μg / cm2) and platelet adsorption amount (>100 / 1000 μm2) are sharply increased. This comparison strongly proves that relying solely on anion exchange function cannot solve the biocompatibility problem, and the introduction of the zwitterionic component to form a dense hydration layer is crucial for inhibiting non-specific protein adsorption and platelet activation, and is the key to the success of the present application.

[0085] It can be seen from the combination of Example 1 and Comparative Example 3 and Table 1 that, Comparative Example 3, which lacks the anion exchange component, although exhibits excellent antifouling performance (albumin adsorption amount 1.9 μg / cm2), has extremely low ion exchange capacity (0.02 mmol / g) and heparin clearance rate (3.5%). This result clearly shows that the zwitterionic component can only provide biocompatibility, while the core function of high-efficiency blood purification, adsorption and removal of toxins, must rely on the anion exchange component, and both are indispensable.

[0086] It can be seen from the combination of Example 1, Example 2 and Example 3 and Table 1 that the monomer molar ratio has a decisive influence on the performance of the membrane. When the molar ratio is 1:1 (Example 1), the membrane achieves the best balance between adsorption performance (clearance rate 95.2%) and biocompatibility (platelet adsorption 15). When the molar ratio is adjusted to 3:7 (Example 2), the clearance rate decreases to 88.5% due to insufficient anion exchange component; and when the molar ratio is adjusted to 7:3 (Example 3), the biocompatibility is significantly deteriorated (platelet adsorption 45) due to insufficient zwitterionic component. This proves that limiting the molar ratio to the range of 3:7 to 7:3 is necessary and optimal for obtaining a product with excellent comprehensive performance.

[0087] It can be seen from the combination of Example 1, Example 7 and Example 8 and Table 1 that the mass ratio of copolymer to PES directly affects the functionality and mechanical strength of the membrane. When the ratio is 1:19 (Example 7), insufficient functional groups result in a decline in all performance indicators. When the ratio is 3:7 (Example 8), although the exchange capacity (1.32 mmol / g) is the highest, the wet tensile strength of the membrane is significantly reduced to 4.1 MPa, which is difficult to meet the application requirements. This comparison confirms that the 1:9 ratio adopted in Example 1 achieves the best combination in terms of ensuring functionality and mechanical strength.

[0088] It can be seen from the combination of Example 1 and Example 6 and Table 1 that the concentration of alkali solution has a direct impact on the efficiency of activating anion exchange groups. The ion exchange capacity (0.92 mmol / g) and heparin clearance rate (90.1%) of the membrane treated with 0.1 mol / L NaOH (Example 6) are lower than those of the membrane treated with 0.5 mol / L NaOH (Example 1). This indicates that a lower alkali concentration is insufficient to complete the complete conversion of the groups, thereby affecting the final adsorption efficiency, proving the necessity of the preferred concentration range.

[0089] The specific embodiments are merely an explanation of the present application, which is not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, but as long as the modifications are within the scope of the claims of the present application, they are protected by the Patent Law.

Claims

1. An anion exchange resin membrane for blood purification, characterized by, The resin membrane is prepared by blending a zwitterionic-anion exchange copolymer and a hydrophobic film-forming polymer; The zwitterionic-anion exchange copolymer is copolymerized from an anion exchange monomer and a zwitterionic monomer, so that the resin membrane has both anion exchange function and anti-protein adsorption function; The anion exchange monomer is methacryloyloxyethyl trimethyl ammonium chloride or (3-acrylamidopropyl) trimethyl ammonium chloride, the zwitterionic monomer is sulfobetaine methacrylate or carboxybetaine methacrylate, and the molar ratio of the structural units of the two monomers in the zwitterionic-anion exchange copolymer is 3:7 to 7:

3.

2. A method for producing a membrane of an anion exchange resin for blood purification as claimed in claim 1, characterized by, The method comprises the following steps: a. Copolymer synthesis: free radical copolymerization of an anion exchange monomer and a zwitterionic monomer in the presence of azobisdimethylamidinum hydrochloride to obtain a zwitterionic-anion exchange copolymer; b. Casting and molding: co-dissolving the copolymer and polyether sulfone in a polar aprotic solvent to prepare a casting solution, and then casting a film and immersing it in a coagulation bath to complete phase inversion; c. Post-treatment: washing and alkalization treatment of the obtained membrane to convert the anion exchange groups into hydroxyl groups.

3. The method of claim 2, wherein, In step b, the polar aprotic solvent is N-methyl pyrrolidone or N,N-dimethylacetamide.

4. The method for producing a membrane of an anion exchange resin for blood purification according to claim 2, characterized by, In step b, the coagulation bath is water or a mixture of water and a polar aprotic solvent.

5. The method for producing a membrane of an anion exchange resin for blood purification according to claim 2, characterized by, In step c, the alkaline solution used in the alkalization treatment is a 0.1-1.0 mol / L sodium hydroxide solution.