Flat plate separation membrane for improving biocompatibility and preparation method of flat plate separation membrane

Abstract

The invention provides a flat separation membrane for improving biocompatibility and a preparation method thereof, and belongs to the field of separation membranes. The preparation method comprises the following steps: coating and casting a membrane casting solution on a base material, and sequentially carrying out air bath, coagulating bath, flowing water washing and drying shaping to prepare a flat plate separation membrane; the membrane casting solution comprises 5-20% of a first polymer; 1%-6% of polyarylester; 1%-6% of a hydrophilic pore-foaming agent; 0.1%-5% of vitamin E; the balance is an organic solvent; the first polymer is selected from any one of polyether sulfone, polysulfone, polyamide, cellulose acetate and polyacrylonitrile; cooling the film casting solution to 0-15 DEG C before coating and casting; the air bath adopts an over-wet environment. According to the invention, the vitamin E is added into the raw materials, and the blended membrane is prepared by combining a low-temperature membrane casting solution and an over-wet air bath forming process, so that the compatibility of membrane components is optimized, the biocompatibility of a membrane product is improved, the anti-oxidation effect is improved, the adhesion and activation of platelets are reduced, and the requirements of the blood separation membrane are met.

Description

Technical Field

[0001] This invention belongs to the field of separation membrane technology, and specifically relates to a flat sheet separation membrane with improved biocompatibility and its preparation method. Background Technology

[0002] Flat-sheet separation membranes (such as microfiltration, ultrafiltration, or nanofiltration) are widely used in water treatment, biopharmaceuticals, and food industries, especially in the field of blood separation, due to their compact structure and ease of modularization.

[0003] Polymers are the main raw materials for film formation, and materials used in the synthesis of membranes include polyethersulfone, polysulfone, polyamide, cellulose acetate, and polyacrylonitrile. To meet the requirements of blood separation membranes in terms of blood compatibility, precise separation, chemical stability, and high-strength mechanical properties, the film-forming materials are currently shifting from single polymers to composite materials of multiple polymers. For example, adding polyarylates to conventional synthetic membrane materials can significantly improve mechanical strength and toughness, enhance thermal stability, and improve processability and film-forming properties.

[0004] However, phase separation occurs due to the mismatch in solubility parameters of different materials in organic solvents, leading to poor compatibility of membrane components. In addition, existing membrane materials generally suffer from strong hydrophobicity, low surface energy, and easy adsorption of proteins or biomolecules, resulting in rapid flux decay, frequent cleaning, shortened service life, and the potential to trigger immune or inflammatory responses. This means that the safety of the membrane in contact with the biological system is reduced, and the biocompatibility of the membrane material is insufficient. Summary of the Invention

[0005] Therefore, the present invention aims to provide a flat-plate separation membrane with improved biocompatibility and a method for preparing the same, in order to solve at least one technical problem in the prior art.

[0006] This invention is implemented as follows: The first aspect of the present invention provides a method for preparing a flat sheet separation membrane with improved biocompatibility. The preparation method includes: coating and casting a casting solution on a substrate, and then sequentially subjecting the membrane to an air bath, a coagulation bath, a flowing water wash, and a drying and shaping process to obtain a flat sheet separation membrane. The casting solution comprises the following components by weight percentage: First polymer 5%~20%; Second polymer 1%~6%; Hydrophilic porogen 1%~6%; Vitamin E 0.1%~5%; The remainder is organic solvent; The first polymer is selected from any one of polyethersulfone, polysulfone, polyamide, cellulose acetate, and polyacrylonitrile; the second polymer is polyarylate. Before coating and casting, the casting solution is cooled down to 0℃~15℃; The air bath uses an excessively humid environment.

[0007] Furthermore, the hydrophilic porogen is selected from at least one of polyvinylpyrrolidone, polyethylene glycol, and polyvinyl alcohol; The organic solvent is selected from at least one of N-methylpyrrolidone and N,N-dimethylacetamide.

[0008] Furthermore, the casting solution comprises the following components by weight percentage: The first polymer is 10% to 16%; Second polymer 2%~5%; Hydrophilic porogen 2%~5%; Vitamin E 0.5%~2%; The remainder is organic solvent; The vitamin E used is α-tocopherol.

[0009] Furthermore, the casting solution comprises the following components by weight percentage: The first polymer is 12%~15%; Second polymer 3%~4%; 3%~4% hydrophilic porogen; Vitamin E 1%; The remainder is organic solvent.

[0010] Furthermore, the preparation steps of the casting solution are as follows: At 45℃~55℃ and under mechanical stirring, first mix a portion of the organic solvent with the second polymer, then add the first polymer, vitamin E, hydrophilic porogen and the remaining organic solvent, keep warm and stir continuously until completely dissolved.

[0011] Furthermore, before coating and casting, the temperature of the casting solution is reduced to 0°C to 5°C.

[0012] Furthermore, before coating and casting, the temperature of the casting solution is reduced to 4°C.

[0013] Furthermore, in the coating and casting stage, the doctor blade gap is 400μm~700μm, the coating speed is 50cm / min~300cm / min, and the substrate used for coating and casting is PET film or glass; During the air bath phase, the ambient humidity should be 80%~100%, and the air bath time should be 2min~10min. During the coagulation bath stage, a combination solvent of N-methylpyrrolidone and water is used, wherein the content of N-methylpyrrolidone is 40wt%~60wt%, the temperature of the coagulation bath is 40℃~60℃, and the residence time is 5min~20min. During the flowing water washing stage, the temperature of the flowing purified water is 20℃~50℃, and the washing time is 5min~20min; During the drying and shaping stage, the drying temperature is 40℃~80℃ and the time is 10min~60min.

[0014] Furthermore, in the coating and casting stage, the doctor blade gap is 600 μm, the coating speed is 100 cm / min, and the substrate used for coating and casting is PET film; During the air bath phase, the ambient humidity is required to be 90%, and the air bath time is 5 minutes. During the coagulation bath stage, the content of N-methylpyrrolidone was 50 wt%, the temperature of the coagulation bath was 50 °C, and the residence time was 10 min. During the flowing water washing stage, the temperature of the flowing purified water is 25℃, and the washing time is 10 minutes. During the drying and shaping stage, the drying temperature is 50℃ and the time is 20 minutes.

[0015] The second aspect of the present invention provides a method for preparing a biocompatible flat plate separation membrane as described above, resulting in a biocompatible flat plate separation membrane.

[0016] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention adds vitamin E to the film-forming raw materials and combines it with a molding process of low-temperature casting solution (0℃~15℃) and superhumid air bath to prepare an amphiphilic blend membrane, which optimizes the compatibility of membrane components, improves the biocompatibility of membrane products, enhances antioxidant activity, reduces platelet adhesion and activation, and meets the requirements of blood separation membranes.

[0017] 2. This invention achieves a synergistic effect of biocompatibility and vitamin antioxidant activity in the blended film by adding vitamin E, which has lipophilic antioxidant and free radical scavenger properties, to the casting solution for co-coating and optimizing the film-forming process.

[0018] 3. Before the casting solution of this invention comes into contact with the outside world, it is cooled to 0℃~15℃ in advance, and then undergoes coating, air bath and other steps to improve the stability of the system in the production process.

[0019] 4. The air bath stage of this invention provides an overhumidified environment with a humidity of ≥80%, which promotes the formation of pore morphology inside the membrane and controls and reduces the surface thickness to obtain a porous structure of the filtration section in the middle of the membrane. Attached Figure Description

[0020] Figure 1 This is an electron microscope cross-sectional view of the flat separation membrane prepared in Example 1 of this invention; Figure 2 This is an electron microscope cross-sectional view of the flat separation membrane prepared in Example 3 of this invention; Figure 3 This is an electron microscope cross-sectional view of the flat separation membrane obtained in Example 5 of this invention; Figure 4 This is an electron microscope cross-sectional view of the flat separation membrane prepared in Comparative Example 1 of this invention; Figure 5 This is an electron microscope cross-section of the substrate surface of the flat separation membrane prepared in Example 7 of this invention; Figure 6 This is an electron microscope cross-section of the substrate surface of the flat separation membrane prepared in Example 8 of this invention; Figure 7 This is an electron microscope cross-sectional view of the substrate surface of the flat separation membrane prepared in Comparative Example 3 of the present invention; Figure 8 This is an electron microscope cross-sectional view of the air surface and substrate surface of the flat separation membrane prepared in Comparative Example 4 of this invention. Figure 9 This is an electron microscope cross-sectional view of the air surface and substrate surface of the flat separation membrane prepared in Comparative Example 5 of this invention. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0022] A method for preparing a biocompatible flat-sheet separation membrane includes steps S1 to S6.

[0023] S1. Prepare the casting solution; The casting solution comprises the following components by weight percentage: 5%~20% of the first polymer, preferably 10%~16%, most preferably 12%~15%; 1%~6% of the second polymer, preferably 2%~5%, most preferably 3%~4%; 1%~6% of the hydrophilic porogen, preferably 2%~5%, most preferably 3%~4%; 0.1%~5% of vitamin E, preferably 0.5%~2%, more preferably 0.75%~1%, most preferably 1%; and the balance is an organic solvent.

[0024] Wherein, the first polymer is selected from any one of polyethersulfone, polysulfone, polyamide, cellulose acetate, and polyacrylonitrile, preferably polyethersulfone (PES); the second polymer is polyarylate (PAR); the hydrophilic porogen is selected from at least one of polyvinylpyrrolidone (PVP), polyethylene glycol, and polyvinyl alcohol; vitamin E is selected from α-tocopherol; and the organic solvent is selected from at least one of N-methylpyrrolidone (NMP) and N,N-dimethylacetamide (DMAC).

[0025] The preparation steps of the casting solution are as follows: at 45℃~55℃ and under mechanical stirring, first take a portion of the organic solvent and mix it with the second polymer polyarylate PAR, then add the first polymer, vitamin E, hydrophilic porogen and the remaining organic solvent, keep warm and stir continuously until completely dissolved.

[0026] S2, coating casting; PAR materials exhibit slightly lower solubility than the primary polymer (such as PES). PAR solubility is better at low temperatures, but when the temperature rises above 80°C, dissolved PAR is more likely to precipitate from the organic solvent. Furthermore, the casting solution temperature directly affects the adhesion of vitamin E to the flat-sheet membrane. To improve system stability and membrane quality during production, the casting solution is cooled before contact with the external environment. Specifically, before coating and casting, the casting solution is cooled to 0°C–15°C, preferably 0°C–5°C, and most preferably 4°C.

[0027] The specific steps of coating casting are as follows: a doctor blade coater is used to coat the substrate with the cooled casting liquid. The doctor blade gap during coating casting is 400μm~700μm, with 600μm being optimal. The coating speed is 50cm / min~300cm / min, with 100cm / min being optimal. The substrate can be PET film, glass, etc., with PET film being preferred.

[0028] S3, air bath; The ambient humidity requirement is 80%~100%, preferably 90%, and the air bath time is 2min~10min, preferably 5min.

[0029] To promote the formation of pore morphology inside the membrane and to control and reduce the surface thickness to obtain a porous structure of the filtration section in the middle of the membrane, the air bath provides an overhumidified environment with a humidity of ≥80%.

[0030] S4, coagulation bath; The solvent used is a combination of N-methylpyrrolidone and water, wherein the content of N-methylpyrrolidone is 40wt%~60wt%, preferably 50wt%, the temperature of the coagulation bath is 40℃~60℃, preferably 50℃, and the residence time is 5min~20min, preferably 10min.

[0031] S5. Running water washing; Select flowing purified water at a temperature of 20℃~50℃, preferably 25℃; the washing time is 5min~20min, preferably 10min.

[0032] S6. Drying and shaping; The drying temperature is 40℃~80℃, with 50℃ being optimal, and the drying time is 10min~60min, with 20min being preferred.

[0033] Example 1 A method for preparing a flat-plate separation membrane with improved biocompatibility, comprising the following steps: According to the formula of polyethersulfone (PES) 12%, PAR 3%, PVP 3%, vitamin E 1%, and the remainder NMP, weigh the raw materials, first add all of the PAR and 1 / 2 of the NMP solvent to the stirred tank, and stir at 50℃ and 100r / min until completely dissolved, then add PES, PVP and the remaining 1 / 2 of the NMP, and continue stirring until completely dissolved to obtain the casting solution. The casting solution was cooled to 4°C and then coated and cast on a substrate (PET film). The casting solution was then subjected to air bath, coagulation bath, flowing water washing and drying in sequence. The specific conditions for each stage were as follows: (1) Coating and casting stage: doctor blade gap = 550μm, coating speed = 100cm / min; (2) Air bath stage: air bath humidity = 90%, time = 3min; (3) Coagulation bath stage: coagulation bath solvent is 50%NMP + 50% water, temperature = 50°C, time = 10min; (4) Flowing water washing stage: water washing temperature = 25°C, time = 10min; (5) Drying and shaping stage: drying at 50°C for 20min; a flat sheet separation membrane was obtained.

[0034] The electron microscope cross-sectional image of the flat plate separation membrane prepared in this embodiment is shown below. Figure 1 As shown, by Figure 1 It can be seen that the flat sheet separation membrane has an asymmetric pore structure, and its main body is a relatively uniform sponge pore structure, which plays the role of support and filtration.

[0035] Example 2 A method for preparing a flat-plate separation membrane with improved biocompatibility, comprising the following steps: Weigh the raw materials according to the following formula: 12% polyethersulfone (PES), 3% PAR, 3% PVP, 2% vitamin E, and the remainder is DMAC. First, add all of the PAR and 1 / 2 of the DMAC solvent to a stirred tank and stir at 50°C and 100 r / min until completely dissolved. Then add PES, PVP and the remaining 1 / 2 of the DMAC and continue stirring until completely dissolved to obtain the casting solution. The casting solution was cooled to 4°C and then coated and cast onto a substrate (PET film). The casting solution was then subjected to an air bath, a coagulation bath, a flowing water wash, and a drying and shaping process. The specific conditions for each stage were as follows: (1) Coating and casting stage: doctor blade gap = 600 μm, coating speed = 100 cm / min; (2) Air bath stage: air bath humidity = 85%, time = 5 min; (3) Coagulation bath stage: coagulation bath solvent is 45% NMP + 55% water, temperature = 50°C, time = 15 min; (4) Flowing water wash stage: water wash temperature = 25°C, time = 15 min; (5) Drying and shaping stage: drying at 50°C for 20 min; a flat sheet separation membrane was obtained.

[0036] Example 3 A method for preparing a flat-plate separation membrane with improved biocompatibility, comprising the following steps: According to the formula of polyethersulfone (PES) 12%, PAR 3%, PVP 3%, vitamin E 2.5%, and the remainder NMP, weigh the raw materials, first add all of the PAR and 1 / 2 of the NMP solvent to the stirred tank, and stir at 50℃ and 100r / min until completely dissolved, then add PES, PVP and the remaining 1 / 2 of the NMP, and continue stirring until completely dissolved to obtain the casting solution. The casting solution was cooled to 4°C and then coated and cast on a substrate (PET film). The casting solution was then subjected to air bath, coagulation bath, flowing water washing and drying and shaping in sequence. The specific conditions for each stage were as follows: (1) Coating and casting stage: doctor blade gap = 550μm, coating speed = 100cm / min; (2) Air bath stage: air bath humidity = 80%, time = 5min; (3) Coagulation bath stage: coagulation bath solvent is 50%NMP + 50% water, temperature = 50°C, time = 10min; (4) Flowing water washing stage: water washing temperature = 25°C, time = 10min; (5) Drying and shaping stage: drying at 75°C for 10min; a flat sheet separation membrane was obtained.

[0037] Example 4 A method for preparing a flat-plate separation membrane with improved biocompatibility, comprising the following steps: According to the formula of polyethersulfone (PES) 15%, PAR 3%, PVP 3%, vitamin E 1%, and the remainder NMP, weigh the raw materials, first add all of the PAR and 1 / 2 of the NMP solvent to the stirred tank, and stir at 50℃ and 100r / min until completely dissolved, then add PES, PVP and the remaining 1 / 2 of the NMP, and continue stirring until completely dissolved to obtain the casting solution. The casting solution was cooled to 4°C and then coated and cast on a substrate (PET film). The casting solution was then subjected to air bath, coagulation bath, flowing water washing and drying and shaping in sequence. The specific conditions for each stage were as follows: (1) Coating and casting stage: doctor blade gap = 500μm, coating speed = 100cm / min; (2) Air bath stage: air bath humidity = 90%, time = 3min; (3) Coagulation bath stage: coagulation bath solvent is 50%NMP + 50% water, temperature = 50°C, time = 10min; (4) Flowing water washing stage: water washing temperature = 25°C, time = 10min; (5) Drying and shaping stage: drying at 50°C for 20min; a flat sheet separation membrane was obtained.

[0038] Example 5 The only difference between this embodiment and Example 1 is that the amount of vitamin E in the raw materials is 0.5%, and the organic solvent NMP is adjusted accordingly. Other conditions and steps are the same as in Example 1.

[0039] Example 6 The only difference between this embodiment and Example 1 is that the amount of vitamin E in the raw materials is 0.75%, and the organic solvent NMP is adjusted accordingly. Other conditions and steps are the same as in Example 1.

[0040] Example 7 The only difference between this embodiment and Embodiment 1 is that the casting solution is cooled to 0°C, while the other conditions and steps are the same as in Embodiment 1.

[0041] Example 8 The only difference between this embodiment and Embodiment 1 is that the casting solution is cooled to 10°C, while the other conditions and steps are the same as in Embodiment 1.

[0042] Comparative Example 1 The only difference between this comparative example and Example 1 is that: vitamin E was not included in the raw materials, and the organic solvent NMP was adjusted simultaneously; other conditions and steps were the same as in Example 1.

[0043] Comparative Example 2 The only difference between this comparative example and Example 1 is that the casting solution is not cooled down, i.e., its temperature is room temperature. Other conditions and steps are the same as in Example 1.

[0044] Comparative Example 3 The only difference between this embodiment and Embodiment 1 is that the casting solution is heated to 40°C, while the other conditions and steps are the same as in Embodiment 1.

[0045] Comparative Example 4 The only difference between this comparative example and Example 1 is that the humidity during the air bath stage is 50%, while the other conditions and steps are the same as in Example 1.

[0046] Comparative Example 5 The only difference between this comparative example and Example 1 is that the humidity during the air bath stage is 70%, while the other conditions and steps are the same as in Example 1.

[0047] The performance of the flat sheet separation membranes prepared in Examples 1 to 8 and Comparative Examples 1 to 5 was tested.

[0048] 1. Aperture distribution test The pore size distribution of the flat-plate separation membrane was measured using a BSD-PB bubble pressure membrane pore size analyzer from Best Instruments Technology Co., Ltd. Test samples were cut to standard sizes, vacuum-lubricated with anhydrous ethanol, and then pressurized with high-purity nitrogen gas to pass through the flat-plate separation membrane. The membrane pore size was calculated as shown in Table 1 below.

[0049] Table 1

[0050] The average pore size of the flat plate separation membrane prepared in the embodiments of the present invention is mainly in the range of 0.2μm~0.6μm, which meets the medical use requirements of separating plasma from whole blood through a specific membrane pore size while retaining blood cells such as red blood cells, white blood cells, and platelets. It can be used for plasma separation.

[0051] Table 1 shows that the range between the smallest and largest pores increases with increasing vitamin E addition. Electron micrographs of the flat separation membranes prepared in Examples 3, 5, and Comparative Example 1 are shown below. Figures 2 to 4 As shown. By Figure 1 Combination Figures 2 to 4 The comparison shows that when no vitamin E is added in Comparative Example 1, the pore structure of the flat separation membrane tends to be finger-like. The addition of vitamin E helps to regulate the structure of the main filtration layer from finger-like to sponge-like. When the amount of vitamin E increases, it is more conducive to the formation of a loose macroporous structure in the membrane. However, with the excessive increase of vitamin E, the membrane material will be difficult to maintain a dense and uniform state. Therefore, the excessive addition of vitamin E in Example 3 will reduce the membrane's support strength.

[0052] Furthermore, compared with Example 1, Comparative Examples 4 and 5 show that reducing air humidity during air bath operation leads to a decrease in membrane pore size and an increase in range of the flat sheet separation membrane. When the ambient air humidity is low, a dense skin layer is more easily formed on the surface under the same operating time. When preparing the polyethersulfone / polyarylate mixed flat sheet separation membrane in this invention, the residence time under conventional air bath operation is short, resulting in the inability to form a stable pore structure. Therefore, the excessively humid environment is artificially controlled.

[0053] Therefore, the amount of vitamin E added as a processing aid needs to be limited to a specific range and a high humidity needs to be maintained to achieve a balance in membrane mechanical properties. In this invention, the amount of vitamin E added can be 0.1% to 5%, preferably 0.5% to 2%, and the air bath humidity is ≥80%.

[0054] 2. Contact Angle Test The contact angle is the angle θ formed at the solid-liquid-gas three-phase interface point on a solid horizontal plane, where a liquid droplet is placed, and the liquid phase is sandwiched between the two tangents of the gas-liquid interface and the solid-liquid interface. θ = 90° can be used as the boundary between wetting and non-wetting; θ < 90° indicates wetting, and θ > 90° indicates non-wetting. The JC2000D1 contact angle measuring instrument from Shanghai Zhongchen Digital Technology Equipment Co., Ltd. was used for testing. A 2μL droplet was placed on the surface of a flat separation membrane, and the contact angle test results are shown in Table 2 below.

[0055] Table 2

[0056] With the addition of the fat-soluble substance vitamin E, the hydrophilicity of the flat plate separation membrane surface gradually decreases. When the amount of vitamin E added in Examples 2 and 3 is excessive, the membrane surface will transition from hydrophilic to hydrophobic. Therefore, controlling the amount of vitamin E added to below 2% is more conducive to the wetting of the filter membrane. This experiment also indirectly proves that vitamin E effectively adheres to the flat plate separation membrane sample and forms a stable structure.

[0057] 3. Antioxidant capacity test—DPPH free radical scavenging rate Under simulated blood filtration conditions, the ability of the membrane to scavenge DPPH free radicals was measured to reflect the antioxidant capacity of the flat-plate separation membrane. The following experiment was conducted.

[0058] Prepare 1.0×10 -4 A 1.5 cm solution of 1 mol / L DPPH anhydrous ethanol was selected. 2 A flat-plate separation membrane sample was immersed in 3 mL of anhydrous DPPH ethanol solution. The solution without the membrane served as a blank control. The samples were allowed to stand at room temperature in the dark for 60 min. The absorbance of the solution was measured at 517 nm using UV light. The membrane-treated group was designated as the sample, and the blank group was designated as the control. The measurement process should also be conducted in the dark as much as possible. The DPPH free radical scavenging rate of the membrane was calculated below. The test results are shown in Table 3.

[0059] DPPH removal rate (%) = ×100%; where A control is the absorbance of the blank group without a plate separation membrane; and A sample is the absorbance of the group with a membrane.

[0060] Table 3

[0061] As can be seen from the comparison of Examples 1 to 6 and Comparative Example 1, the antioxidant capacity of the flat sheet separation membrane is significantly improved after the addition of vitamin E. The antioxidant capacity first increases and then tends to level off as the amount added increases, approaching the peak value at 0.75% to 1%. When the amount added is excessive, there is basically no improvement. Therefore, considering all factors, an addition amount of 1% is better. This experiment proves that the introduction of vitamin E effectively improves the biocompatibility of the membrane product and helps to reduce rejection reactions caused by in vitro blood filtration.

[0062] Furthermore, compared with Example 1, Examples 7 and 8, and Comparative Examples 2 and 3 show that the antioxidant properties of the flat sheet separation membrane are reduced when the casting solution temperature is increased. This is because the stability of vitamin E in the casting solution deteriorates and its function is weakened when the temperature is increased.

[0063] 4. Platelet adhesion test Bovine whole blood containing sodium citrate anticoagulated by Guangzhou Ruite Biotechnology Co., Ltd. was used, and 1cm of the blood was cut. 2 The platelet separation membrane samples were soaked in 2ml centrifuge tubes, and the changes in platelet content in the soaking solution were measured using a hematology analyzer. The changes in platelet content over time are shown in Table 4 below.

[0064] Table 4

[0065] By dynamically monitoring changes in platelet content in the soaking solution, the adsorption effect of the platelet separation membrane sample on platelets can be indirectly reflected. The results show that the addition of vitamin E effectively inhibits platelet adhesion, and the biocompatibility optimization effect gradually becomes more pronounced with increasing addition amount in the early stages. Vitamin E also exhibits a certain degree of temperature responsiveness; the anticoagulant performance of the platelet separation membrane is relatively stable at lower casting solution temperatures, but decreases significantly with increasing temperature, and the anticoagulant effect time is shorter at higher temperatures. Therefore, this invention can effectively reduce blood loss during blood separation, lower the incidence of medical device coagulation accidents during blood filtration treatment, and improve the quality of patient treatment.

[0066] 5. Stability Test Because this invention uses two polymer materials as the membrane substrate, it requires a high degree of solubility in the organic solvent. NMP is typically used as the main solvent, but it is prone to hydrolysis at high temperatures, generating byproducts such as 4-(methylamino)butyric acid. These byproducts further polymerize, leading to discoloration, precipitation, or changes in viscosity of the casting solution. At low temperatures, the hydrolysis rate of NMP decreases significantly. Furthermore, long-term storage at high temperatures will cause the oxidative deactivation of vitamin E. PAR, under the combined action of highly polar organic solvents and high temperatures, is more prone to side reactions such as hydrogen bond stacking and transesterification, leading to irreversible gelation. Using the casting solutions prepared in Examples 1, 7, and 8, and Comparative Examples 2 and 3 as examples, the relationship between the storage time and temperature of the casting solution under a sealed, light-protected environment was studied and summarized, as shown in Table 5 below.

[0067] Table 5

[0068] As can be seen from Table 5, when the casting solution temperature is between 0℃ and 10℃, no gelation occurs after 21 days of storage, indicating that the membrane components have excellent compatibility. The effect is even better when the temperature is between 0℃ and 5℃. When the casting solution temperature is room temperature or heated to 40℃, gelation occurs in a short time, indicating that the membrane components have poor compatibility, which in turn reduces the biocompatibility of the prepared flat sheet separation membrane.

[0069] 6. Air bath time test Since the flat sheet separation membrane of this invention uses multi-component composite membrane material and uses fat-soluble vitamin E as an additive, molding under normal low humidity conditions will greatly prolong the air bath time, increase the processing difficulty and molding instability. Therefore, this invention uses artificially applied excessively humid environment as part of the air bath. Taking Example 1, Comparative Example 4 and Comparative Example 5 as examples for comparison, the corresponding relationship between molding time and ambient humidity is shown in Table 6 below.

[0070] Table 6

[0071] As can be seen from Table 6, the lower the humidity applied during air bath operation, the longer the time required.

[0072] The substrate surface and air surface of the flat sheet separation membrane are the surfaces in contact with the substrate and air, respectively. Electron micrographs of the substrate surfaces of the flat sheet separation membranes prepared in Examples 7, 8, and Comparative Example 3 are shown below. Figures 5 to 7 As shown, Figures 5 to 7The adhesion of vitamin E to the substrate surface after casting at 0℃, 10℃, and 40℃ was demonstrated. The comparison shows that increasing the temperature of the casting solution before coating and casting leads to uneven vitamin E adhesion, reduced adhesion effect, and even extremely sparse local content. The adhesion effect of vitamin E directly affects the biocompatibility of the flat plate separation membrane. Therefore, it reflects the phenomenon shown in Table 4 that the flat plate separation membrane is still effective in the short term, but the anticoagulation effect is weak in the later stage of dialysis treatment. In order to improve the reliability of the flat plate separation membrane and extend its service life, this invention reduces the temperature of the casting solution to make vitamin E adhere more evenly.

[0073] Figure 8 China A and Figure 9 In the middle section, A represents the electron microscope cross-sectional view of the air surface of the flat separation membrane prepared in Comparative Example 4 and Comparative Example 5, respectively. Figure 8 China B and Figure 9 Figure B shows electron microscope cross-sectional images of the substrate surfaces of the flat separation membranes prepared in Comparative Examples 4 and 5, respectively. Compared to the porous substrate surface, the hydrophilic porogen moves directionally from the substrate surface to the air surface during the air bath process. When the humidity is below 80%, insufficient air bath will result in a thicker skin layer on the air surface and potential problems such as incomplete elution of the hydrophilic porogen on the surface.

[0074] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for preparing a flat sheet separation membrane with improved biocompatibility, the method comprising: A flat plate separation membrane is prepared by coating and casting a casting solution on a substrate, and then sequentially performing air bath, coagulation bath, flowing water washing and drying and setting, characterized in that the casting solution comprises the following components by weight percentage: The first polymer is selected from any one of polyether sulfone, polysulfone, polyamide, cellulose acetate, polyacrylonitrile; the second polymer is polyarylate; Before coating and casting, the temperature of the casting solution is reduced to 0-15°C by refrigeration; The air bath uses a humid environment. The hydrophilic pore-forming agent is selected from at least one of polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol; The organic solvent is selected from at least one of N-methylpyrrolidone and N,N-dimethylacetamide. The casting solution comprises the following components by weight percentage: The first polymer is selected from any one of polyether sulfone, polysulfone, polyamide, cellulose acetate, polyacrylonitrile; the second polymer is polyarylate; Before coating and casting, the temperature of the casting solution is reduced to 0-15°C by refrigeration; 2. The method for preparing a flat sheet separation membrane with improved biocompatibility according to claim 1, wherein The air bath uses a humid environment. The hydrophilic pore-forming agent is selected from at least one of polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol; 3. The method for preparing a biocompatible flat-sheet separation membrane according to claim 1, characterized in that, The organic solvent is selected from at least one of N-methylpyrrolidone and N,N-dimethylacetamide. The casting solution comprises the following components by weight percentage: The first polymer is selected from any one of polyether sulfone, polysulfone, polyamide, cellulose acetate, polyacrylonitrile; the second polymer is polyarylate; The casting solution comprises the following components by weight percentage: The first polymer is selected from any one of polyether sulfone, polysulfone, polyamide, cellulose acetate, polyacrylonitrile; the second polymer is polyarylate; The preparation steps of the casting solution are as follows: At 45-55°C and under mechanical stirring, first mix part of the organic solvent with the second polymer, then add the first polymer, vitamin E, the hydrophilic pore-forming agent and the remaining organic solvent, and continue to stir under heat until completely dissolved.

4. The method for preparing a biocompatible flat-sheet separation membrane according to claim 3, characterized in that, Before coating and casting, the temperature of the casting solution is reduced to 0-5°C. Before coating and casting, the temperature of the casting solution is reduced to 4°C.

8. The preparation method of the flat plate separation membrane with improved biocompatibility according to claim 1, characterized in that, During the coating and casting stage, the doctor blade gap is 400-700μm, the coating speed is 50-300cm / min, and the substrate used for coating and casting is PET film or glass; During the air bath stage, the environmental humidity is required to be 80-100%, and the air bath time is 2-10min; During the coagulation bath stage, a combined solvent of N-methylpyrrolidone and water is used, wherein the content of N-methylpyrrolidone is 40-60wt%, the temperature of the coagulation bath is 40-60°C, and the residence time is 5-20min; 5. The method for preparing a flat sheet separation membrane with improved biocompatibility according to any one of claims 1 to 4, characterized in that, During the flowing water washing stage, the temperature of the flowing purified water is 20-50°C, and the water washing time is 5-20min; During the drying and setting stage, the drying temperature is 40-80°C, and the time is 10-60min.

6. The method of claim 1, wherein the flat sheet membrane is a biocompatible flat sheet membrane.

9. The preparation method of the flat plate separation membrane with improved biocompatibility according to claim 8, characterized in that, 7. The method of claim 6, wherein the method is a method of preparing a flat sheet separation membrane with improved biocompatibility, characterized by, During the coating and casting stage, the doctor blade gap is 600μm, the coating speed is 100cm / min, and the substrate used for coating and casting is PET film; During the air bath stage, the environmental humidity is required to be 90%, and the air bath time is 5min; ​ ​ ​ ​ ​ ​ ​ ​ In the coagulation bath stage, the content of N-methyl pyrrolidone is 50wt%, the temperature of the coagulation bath is 50℃, and the residence time is 10min; In the flowing water washing stage, the temperature of the flowing purified water is 25℃, and the water washing time is 10min; In the drying and setting stage, the drying temperature is 50℃, and the time is 20min.

10. The improved biocompatible flat separation membrane prepared by the preparation method of the improved biocompatible flat separation membrane according to any one of claims 1 to 9.

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