Preparation method and application of high-flux blood-compatible polyimide separation membrane

Abstract

The invention provides a preparation method and application of a high-flux blood-compatible polyimide separation membrane, polyimide polymer powder is added into a solvent B, a quaternization reagent is added to obtain quaternization polyimide polymer powder, the quaternization polyimide polymer powder is added into a solvent C, and the high-flux blood-compatible polyimide separation membrane is obtained. And scraping the membrane casting solution by using a scraper to prepare an asymmetric separation membrane, and washing to obtain the high-flux blood-compatible polyimide separation membrane. The separation membrane applied to the field of biological water treatment is prepared through chemical imidization condensation reaction and quaternization reaction. The high-flux blood-compatible polyimide separation membrane obtained by the invention has excellent thermal stability, good mechanical properties, protein adsorption resistance, bacterial adhesion resistance, blood compatibility and anticoagulation capability. The method has wide application prospects in the fields of ultrafiltration, hemodialysis, purification, biological sewage treatment and the like.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic polymers, and particularly relates to a preparation method and application of a high-throughput blood-compatible polyimide separation membrane. Background Art

[0002] With the advancement of biomedical technology, blood compatibility has become a key criterion for evaluating the suitability of polymer materials for applications in biomaterials and medical devices. As a biopolymer with a unique chemical structure, internal salt polymers have excellent blood compatibility and antifouling properties, thereby improving the efficiency of blood separation and purification and enhancing therapeutic effects, and have attracted widespread attention in the field of bioclinical medicine. Among them, the long-term anticoagulant performance and blood compatibility of blood-contact materials are two important issues for their application in bio-contact materials in medical devices. It is necessary to improve the hydrophilicity and blood compatibility of polymer materials to make them stable and functionalized, and then solve this problem to achieve long-lasting antifouling and anticoagulant effects. Functionalized polymers exhibit excellent blood compatibility due to their strong hydrophilicity, charge neutrality and high solubility. When in contact with biological fluids, they can significantly reduce protein adsorption and bacterial adhesion, thereby minimizing biocompatibility issues and reducing the risk of thrombosis.

[0003] Polyimide (PI) materials are a class of biomedical organic polymers that have attracted widespread attention. Due to their excellent chemical stability, mechanical properties, thermal stability, and biocompatibility, they are widely used in implantable medical devices, medical catheters, bioelectronic devices, drug delivery, and other fields. They can also withstand various sterilization processes. Due to their rigid structure and inherent hydrophobicity, PI membrane surfaces are susceptible to bacterial and protein adsorption, which can easily lead to biofilm contamination, inflammation, coagulation, and thrombosis, limiting their application. Therefore, the development of novel polymer materials with durable anti-contamination properties and improved blood compatibility is of great significance.

[0004] Existing phosphate polymers employ a configuration where phosphate groups anchor the polymer chain and choline groups are free, resulting in limited surface charge distribution and dynamic hydration capacity, significantly weakening antifouling properties (such as protein adsorption resistance) and long-term stability. This is because the free choline groups cannot effectively cooperate with the phosphate groups to form a stable hydration layer, thereby reducing biomimetic affinity with biomembrane components. Through innovative molecular structure design and functional modification, we have successfully enhanced the material's functional properties by bonding the choline groups to the polymer backbone and distributing the phosphate groups in a free state.

[0005] Therefore, it is of great significance to construct a high-throughput blood-compatible polyimide separation membrane with structural biomimetic, anti-fouling, stability and high blood compatibility. Summary of the Invention

[0006] The present invention provides a preparation method and application of a high-throughput blood-compatible polyimide separation membrane, which can significantly improve the hydrophilicity, stability, antifouling property and blood compatibility of the polymer.

[0007] The technical solution adopted in the present invention is as follows:

[0008] On one hand, the present invention provides a method for preparing a high-throughput blood-compatible polyimide separation membrane, comprising the following steps: 1) adding a polyimide polymer powder to a solvent B, then adding a quaternizing agent, reacting at a temperature of 80-100° C. for 48-72 hours, finally pouring the reacted solution into deionized water for precipitation, filtering to obtain a solid powder, washing with ethanol 3-5 times, and vacuum drying at 90° C. for 24 hours to obtain a quaternized polyimide polymer powder; 2) adding the quaternized polyimide polymer powder to a solvent C and stirring at room temperature for 6-8 hours to prepare a casting solution, scraping the solution with a scraper having a thickness of 200 μm to form an asymmetric separation membrane, performing phase inversion exfoliation in deionized water, and washing to obtain a high-throughput blood-compatible polyimide separation membrane;

[0009] The molecules of the polyimide polymer powder include the following structure:

[0010]

[0011] The molecular structure of the quaternary ammonium reagent is shown below:

[0012]

[0013] wherein R is independently selected from one or a combination of a chain alkoxy group having 1 to 10 carbon atoms, a chain alkenyloxy group having 2 to 10 carbon atoms, a chain alkynyloxy group having 2 to 10 carbon atoms, a cyclic alkoxy group having 3 to 10 carbon atoms, a cyclic alkenyloxy group having 3 to 10 carbon atoms, a trimethylsilyl group, a trimethylsilyloxy group, a halogen-containing alkyl group, a phenyl group, a biphenyl group, a naphthyl group, a pyridyl group, a thienyl group, a halophenyl group, a halobiphenyl group, a phenol group, a phenol group containing an alkyl group, a phenol group containing an alkenyl group, a phenol group containing an alkynyl group, a phenol group containing a nitrile group, a monohalogenated phenol group, and a polyhalogenated phenol group;

[0014] The high-throughput blood-compatible polyimide separation membrane molecule comprises the following structure:

[0015]

[0016] Preferably, the raw materials of the polyimide polymer powder include, by mole fraction, 1 part of diamine monomer, 1 part of dianhydride monomer, 0.3 part of dehydrating agent, 0.01 part of catalyst, and 20 parts of non-aqueous solvent A.

[0017] Preferably, the diamine monomer is any one or a combination of the compounds represented by the following structural formulas:

[0018]

[0019] The dianhydride monomer is any one or a combination of the following structural formulas:

[0020]

[0021] The dehydrating agent is any one of toluene, xylene, cyclohexane, n-hexane, and petroleum ether; the catalyst is any one of isoquinoline, quinoline, 4-hydroxyquinoline, and 8-hydroxyquinoline; and the non-aqueous solvent A is any one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, m-cresol, sulfolane, and dimethyl sulfoxide, or a combination thereof.

[0022] Preferably, the synthesis steps of the polyimide polymer powder are as follows: S1. Under a nitrogen atmosphere, a diamine monomer and a non-aqueous solvent A are mixed and dissolved in a round-bottom flask, and stirred at 90°C for complete dissolution to form a mixed solution; S2. A dianhydride monomer in an amount equimolar to the diamine monomer is added to the mixed solution in step S1, and 80-100 mL of a dehydrating agent and 0.05 mL of a catalyst are added dropwise, and the mixture is reacted and mixed at 90°C for 12 hours to obtain a polyamic acid solution; S3. The polyamic acid solution in step S2 is heated to 135°C and the reaction is maintained for 4 hours to remove moisture, and then heated to 180°C and maintained for 12 hours to finally obtain a viscous polycondensation solution; S4. The viscous polycondensation solution in step S3 is added to ice methanol to obtain a crude product of polyimide polymer powder, the precipitated crude product powder is washed with hot ethanol, and vacuum dried at 80°C for 48 hours to obtain a pure polyimide polymer powder.

[0023] Preferably, the chain group in the group R includes a straight chain group and a branched chain group, and the straight chain group or the branched chain group includes one or more of a halogen atom, an oxygen atom or an unsaturated bond functional group; the unsaturated bond functional group includes one or more of a carbon-carbon double bond, a carbon-carbon triple bond, a carbon-nitrogen double bond, a carbon-nitrogen triple bond, a carbon-oxygen double bond, a sulfur-oxygen double bond, a phosphorus-oxygen double bond, an amide, a carboxylate, a sulfonate and a phosphate; the unsaturated bond functional group is located at the end group or inside; the halogen atom is a fluorine, chlorine, bromine or iodine atom, and the halogenated group includes partial substitution and full substitution.

[0024] Preferably, in step S2, the solid content of the total amount of the diamine monomer and the dianhydride monomer in the entire reaction mixed solution system is controlled to be 15% to 20%.

[0025] Preferably, the stirring speed of the mixed solution system in step S1 is 100 rpm; the heating rate of the reaction system in step S3 is: heating to 135°C at a heating rate of 5°C / min and maintaining at 135°C for 4 hours, then heating from 135°C to 180°C at a heating rate of 10°C / min and maintaining for 12 hours.

[0026] Preferably, the solid content of the polyimide polymer powder in solvent B is 15 to 20 wt %, and the solvent B is one or more of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and sulfolane; the solid content of the quaternized polyimide polymer powder in solvent C is 15 to 20 wt %; and the solvent C is any one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, and sulfolane.

[0027] Another aspect of the present invention provides a high-throughput blood-compatible polyimide separation membrane prepared by the above method.

[0028] Another aspect of the present invention provides the use of the high-throughput hemocompatible polyimide separation membrane produced by the above method in ultrafiltration, microfiltration, nanofiltration, wastewater treatment, hemodialysis, and purification. The high-throughput hemocompatible polyimide separation membrane is used in ultrafiltration, biological wastewater treatment, and hemodialysis to achieve optimized mechanical properties, high-efficiency antifouling properties, and enhanced hemocompatibility.

[0029] The present invention has the following advantages:

[0030] (1) The present invention introduces a zwitterionic phosphate structure into the polyimide side chain through molecular structure design and construction, and prepares a high-throughput blood-compatible polyimide separation membrane from a casting liquid prepared by a phase inversion method. The prepared high-throughput blood-compatible polyimide separation membrane has good thermal stability and mechanical properties.

[0031] (2) The present invention breaks through the bottleneck of anti-fouling technology: through structural design, it achieves high-efficiency anti-protein adsorption and anti-bacterial adhesion properties, thereby improving the recyclability and easy cleaning of the separation membrane in biological sewage treatment and blood filtration.

[0032] (3) The present invention solves the problem of blood compatibility and develops a polyimide material with a cell membrane-mimicking structure, which can be used in medical scenarios such as hemodialysis and purification to reduce thrombosis and inflammatory reactions and promote the anti-coagulation process. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The high-throughput blood-compatible polyimide FPI and ZFPI-Me / Et / i Pr NMR 1H-NMR spectrum (a), nuclear magnetic 31 P-NMR spectra (b-d) and FT-IR spectra (e);

[0034] Figure 2 The high-throughput blood-compatible polyimide FPI and ZFPI-Me / Et / i TGA graph (a) and stress-strain diagram (b) of Pr;

[0035] Figure 3 The high-throughput blood-compatible polyimide FPI and ZFPI-Me / Et / i Anti-nonspecific protein adsorption image of Pr (a) and anti-protein immunoadsorption fluorescence staining image (b);

[0036] Figure 4 The high-throughput blood-compatible polyimide FPI and ZFPI-Me / Et / i Antibacterial adhesion plate image of Pr;

[0037] Figure 5 The high-throughput blood-compatible polyimide FPI and ZFPI-Me / Et / i Pr hemolysis rate graph (a), C3a and C5a protein complement activation graph (b), blood coagulation index graph (c), plasma recalcification time (d) and anti-platelet adhesion SEM graph (e). DETAILED DESCRIPTION

[0038] The present invention will be further described below with reference to specific examples, but the present invention is not limited to the following examples.

[0039] To further illustrate the present invention, the preparation method and application of a high-throughput blood-compatible polyimide separation membrane provided by the present invention are described in detail below with reference to examples.

[0040] Synthetic polyimide polymer powder: The raw materials of polyimide powder FPI are composed of the following components:

[0041]

[0042] The diamine monomer is 2-(4-aminophenyl)-5-aminobenzimidazole in the following structural formula, the dianhydride monomer is 4,4'-(hexafluoroisopropylidene)diphthalic anhydride, the dehydrating agent is toluene, the non-aqueous solvent A is N-methylpyrrolidone, and the catalyst is isoquinoline. The synthetic route is:

[0043]

[0044] Furthermore, the molecular structure of the polyimide FPI is shown below:

[0045]

[0046] Further, the synthesis steps are as follows:

[0047] Under a nitrogen atmosphere, the diamine monomer and non-aqueous solvent A were mixed and dissolved in a round-bottom flask to form a mixed solution, which was stirred at 90°C until completely dissolved. The dianhydride monomer was slowly added to the reaction mixture and mixed for 12 hours, and toluene dehydrating agent and isoquinoline catalyst were added. The temperature was heated to 135°C and maintained for 4 hours, and then maintained at 180°C for 12 hours. The water produced during the polycondensation process was removed to a water separator via an azeotropic water system. The viscous polycondensation solution was added to ice methanol to obtain a polyimide powder. The precipitated powder was washed with hot ethanol and vacuum dried at 80°C for 48 hours to obtain a polyimide powder FPI.

[0048] Example 1:

[0049] Quaternization of polyimide polymer powder: Polyimide FPI (12.97 g) was mixed with 60 mL of dimethyl sulfoxide and added to a round-bottom flask. 2-methoxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide (4.14 g, 30 mmol) was slowly added to the round-bottom flask at a rate of 0.5 to 1 drop / second through a constant pressure titration funnel. The molar ratio of the polymer to 2-methoxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide was 0.5 to 1 drop / second. The reaction mixture was stirred at a ratio of 1:1.5 to 2, the dripping rate was controlled at 0.5-1.5 drops / second, the reaction temperature was controlled at 85-100°C, the reaction was stirred throughout, and the reaction was completed after 70-72 hours. The cooled reaction solution was poured into deionized water, washed with deionized water several times, and dried at 60°C for 24 hours to obtain a light yellow powdery solid product (i.e., a quaternized polyimide polymer powder) with a yield of 95%. The structure of the product zwitterionic polyimide ZFPI-Me is as follows:

[0050]

[0051] Furthermore, the preparation method of ZFPI-Me high-throughput blood-compatible polyimide separation membrane is as follows: the prepared quaternized polyimide polymer powder is added to dimethyl sulfoxide, stirred at room temperature for 6 to 8 hours to prepare a casting liquid; the casting liquid is then dropped onto a casting glass plate, and at room temperature, a scraper with a thickness of 200 μm is used to scrape an asymmetric separation membrane and a phase inversion process is carried out in deionized water. The polyimide separation membrane is gently peeled off from the casting glass plate and washed with deionized water for 3 to 5 times. Before use, the polyimide separation membrane is fully immersed in deionized water to remove residual solvent, and finally a high-throughput blood-compatible polyimide separation membrane is obtained, and named as zwitterionic polyimide ZFPI-Me separation membrane.

[0052] Example 2:

[0053] Quaternization of polyimide polymer powder: Polyimide FPI (12.97 g) was mixed with 60 mL of dimethyl sulfoxide and added to a round-bottom flask. 2-Ethoxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide (4.56 g, 30 mmol) was slowly added to the round-bottom flask at a rate of 0.5 to 1 drop / second through a constant pressure titration funnel. The molar ratio of the polymer to 2-Ethoxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide was 0.5 to 1 drop / second. The reaction mixture was stirred at a ratio of 1:1.5 to 2, the dripping rate was controlled at 0.5-1.5 drops / second, the reaction temperature was controlled at 85-100°C, the reaction was stirred throughout, and the reaction was completed after 70-72 hours. The cooled reaction solution was poured into deionized water, washed with deionized water several times, and dried at 60°C for 24 hours to obtain a light yellow powdery solid product (i.e., a quaternized polyimide polymer powder) with a yield of 95%. The structure of the product zwitterionic polyimide ZFPI-Et is as follows:

[0054]

[0055] Furthermore, the preparation method of ZFPI-Et high-throughput blood-compatible polyimide separation membrane is as follows: the prepared quaternized polyimide polymer powder is added to dimethyl sulfoxide and stirred at room temperature for 6 to 8 hours to prepare a casting liquid; the casting liquid is then dropped onto a casting glass plate, and at room temperature, a scraper with a thickness of 200 μm is used to scrape an asymmetric separation membrane and a phase inversion process is carried out in deionized water. The polyimide separation membrane is gently peeled off from the casting glass plate and washed with deionized water for 3 to 5 times. Before use, the polyimide separation membrane is fully immersed in deionized water to remove residual solvent, and finally a high-throughput blood-compatible polyimide separation membrane is obtained, and named as zwitterionic polyimide ZFPI-Et separation membrane.

[0056] Example 3:

[0057] Quaternization of polyimide polymer powder: Polyimide FPI (12.97 g) was mixed with 60 mL of dimethyl sulfoxide and added to a round-bottom flask. 2-isopropyloxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide (4.98 g, 30 mmol) was slowly added to the round-bottom flask at a rate of 0.5 to 1 drop / second through a constant pressure titration funnel. The polymer and 2-isopropyloxy-1,3,2-dioxyphosphoric acid 2-oxide heterocyclopentane oxide were added. The molar ratio of addition is 1: (1.5-2), the dripping rate is controlled to be 0.5-1.5 drops / second, the reaction temperature is controlled at 85-100°C, the reaction is stirred throughout the process, and the reaction time is 70-72 hours. The cooled reaction solution is poured into deionized water, washed with deionized water several times, and dried at 60°C for 24 hours to obtain a dark yellow powdery solid product (i.e., quaternized polyimide polymer powder) with a yield of 95%. The product zwitterionic polyimide ZFPI- i The Pr structure is as follows:

[0058]

[0059] Furthermore, ZFPI- i The preparation method of a Pr high-throughput blood-compatible polyimide separation membrane comprises the following steps: adding the prepared quaternized polyimide polymer powder to dimethyl sulfoxide, stirring at room temperature for 6 to 8 hours, and preparing a casting solution; then dripping the casting solution onto a casting glass plate, scraping an asymmetric separation membrane at room temperature using a 200 μm-thick scraper, and performing a phase inversion process in deionized water; gently peeling the polyimide separation membrane from the casting glass plate, washing it with deionized water for 3 to 5 times, and fully soaking the polyimide separation membrane in deionized water before use to remove residual solvent, thereby obtaining a high-throughput blood-compatible polyimide separation membrane named zwitterionic polyimide ZFPI- i Pr separation membrane.

[0060] Test picture Figure 1 As shown in (a), through 1 H-NMR spectroscopy identified the FPI and ZFPI-Me / Et / i Chemical structure of Pr polymer.

[0061] All signals can be readily assigned to individual proton H groups, and the integrated ratios of the proton H groups are consistent with the expected polymer structure. The aromatic hydrogens of the benzene ring exhibit multiple peaks in the 7.23–8.32 ppm range. Furthermore, new proton H peaks at 2.60–4.90 ppm are attributed to alkyl hydrogens with distinct zwitterionic structures.

[0062] like Figure 1 As shown in (b~d), 31P-NMR also showed significant chemical shift values, indicating that FPI and ZFPI-Me / Et / i Pr polymers have been successfully synthesized.

[0063] like Figure 1 As shown in (e), ZFPI-Me / Et / i Chemical structure spectra of Pr polymers. FPI and ZFPI-Me / Et / i Pr polymers were respectively -1 、1373cm -1 (irregular vibration absorption peak of CN bond), 1780cm -1 and 1722cm -1 The same imide ring absorption peaks are shown at 1050 cm (absorption peaks of asymmetric and symmetric vibrations of imide bonds). -1 The obvious stretching vibration absorption peak at ZFPI-Me / Et / i Pr polymer was successfully synthesized.

[0064] ZFPI-Me / Et / i Thermal properties of Pr polymer, test diagram as shown Figure 2 As shown in (a).

[0065] The FPI and ZFPI-Me / Et / i The heat resistance of Pr polymers. TGA results show that ZFPI-Me / Et / i Pr polymer has good thermal stability.

[0066] By observing the FPI and ZFPI-Me / Et / i The TGA curves of the Pr polymer were analyzed to study its thermal properties. i Pr polymers can meet the thermal performance indicators of biomedical and water treatment membranes.

[0067] FPI and ZFPI-Me / Et / i Mechanical properties testing of Pr polymer.

[0068] The mechanical properties of the material were evaluated by tensile test (GB / T 228.1-2010). 2 A film with a thickness of 200 μm is loaded onto the fixture, the frame is adjusted to a suitable position, and the tensile properties test is performed at a tensile rate of 3.0 mm / min.

[0069] Test picture Figure 2(b) As shown, FPI and ZFPI-Me / Et / i Pr separation membrane can meet the actual filtration requirements of frequent cleaning and operating pressure.

[0070] The test results are shown in Table 1:

[0071] Table 1 Mechanical properties test results

[0072]

[0073] Anti-nonspecific protein static adsorption experiment:

[0074] The static adsorption of protein on the membrane surface is a key indicator for evaluating the antifouling performance of separation membranes. A 30 mm diameter membrane was washed three times with phosphate-buffered saline (PBS, pH 7.4) and then immersed in 1 mg / mL BSA protein at room temperature. After 10 hours, the sample was removed from the solution. The sample was gently rinsed three times with PBS to remove any loosely bound surface BSA. The amount of BSA adsorbed on the membrane surface was calculated using Equation 1.

[0075] Test picture Figure 3 As shown in (a),

[0076]

[0077] Nonspecific protein adsorption (μg / cm 2 );

[0078] C a (g / L): concentration of BSA in the solution before adsorption, measured by UV-visible spectrophotometry (UV-1900i, Shimadzu, Japan) at 278 nm;

[0079] C b (g / L): concentration of BSA in the solution after adsorption, measured by UV-visible spectrophotometry (UV-1900i, Shimadzu, Japan) at 278 nm;

[0080] V solution is the volume of the solution (L),

[0081] S(cm 2 ) is the area of ​​the membrane sample.

[0082] The experimental results are as follows Figure 3 As shown in (a), the results showed that ZFPI-Me / Et / i Pr separation membrane has excellent anti-protein adsorption ability, which can significantly prevent non-specific protein deposition and dirt, and has the potential to be used as medical materials such as biological clinical medical devices, hemodialysis, and implant materials.

[0083] Anti-protein immunosorbent fluorescent staining:

[0084] The experimental results are as follows Figure 3 As shown in (b), the results showed that ZFPI-Me / Et / i Pr separation membrane has excellent anti-protein adsorption ability, which can significantly prevent non-specific protein deposition and dirt, and has the potential to be used as medical materials such as biological clinical medical devices, hemodialysis, and implant materials.

[0085] Antibacterial performance when tested according to the oscillation method in GB / T 20944.3-2008 standard, Escherichia coli and Staphylococcus aureus.

[0086] The process is briefly described as follows:

[0087] All membrane samples were immersed in a bacterial suspension at 37°C (10 5 The membrane was then incubated at 4 °C (CFU / mL) for 4 hours, then gently rinsed with PBS to remove unattached bacteria. The membrane was then ultrasonicated for 5 minutes to collect strongly adherent bacteria. 10 μL of the collected suspension was spread on an agar plate and incubated at 37°C for 24 hours. The bacterial adhesion rate on the membrane was calculated using Equation 2.

[0088]

[0089] N1: bacterial colony count of control membrane;

[0090] N2:ZFPI-Me / Et / i The number of bacterial colonies on the Pr separation membrane.

[0091] The non-functionalized separation membrane was used as a control, and the experimental results were as follows: Figure 4 As shown: The results showed that ZFPI-Me / Et / i Pr membrane has strong antibacterial adhesion properties and is beneficial for preventing biofilm formation and facilitating cleaning.

[0092] Hemolysis rate test:

[0093] Whole blood was separated by centrifugation and red blood cell standard solution was prepared. 1×1 cm 2 The membrane was placed in a well plate, 2 mL of red blood cell suspension was added, and the cells were incubated at 37°C for 1 hour. The cells were centrifuged, and the supernatant was collected and the absorbance at 540 nm was measured. The positive control group was PBS buffer solution, and the negative control group was saline solution. The hemolysis rate was calculated using formula -3. The experimental results are shown in Figure 3. Figure 5 As shown in (a), ZFPI-Me / Et / i The hemolysis rate of the Pr membrane samples was less than 5%, indicating excellent biosafety. The hemolysis rate of the membrane was calculated using Formula 3.

[0094]

[0095] A s is the absorbance of the sample at 540 nm;

[0096] A N is the absorbance of the negative control at 540 nm;

[0097] A P is the absorbance value of the positive control at 540 nm.

[0098] Complement activation assay:

[0099] Complement activation of membrane samples was studied in vitro using a commercial enzyme-linked immunosorbent assay (ELISA) kit. The specific steps were as follows: wash 1 × 1 cm 2 After three incubations, the membrane samples were immersed in a 24-well plate at 37°C for 2 hours and 2 mL of saline was added. After equilibration, 1 mL of whole blood was added to each sample. Finally, the samples were incubated at 37°C for 2 hours. The whole blood was centrifuged at 2000 rpm for 20 minutes to obtain plasma. C3a and C5a concentrations were measured using an ELSA assay kit. A control group, without membrane addition, was measured using the same method.

[0100] The experimental results are as follows Figure 5 As shown in (b), the concentrations of anaphylatoxins C3a and C5a in the blood can indicate the extent of complement activation and can be quantified using an ELISA kit. i The concentrations of C3a and C5a on Pr membranes are low, thereby inhibiting complement activation.

[0101] Complete coagulation time test

[0102] The free hemoglobin method is used to evaluate the anticoagulant performance of the membrane by measuring the coagulation time of whole blood. The specific steps are as follows: 5 mL of fresh rabbit blood is activated with 500 μL of CaCl2 solution (0.1 mol / L), and then 100 μL of the activated blood is added to the membrane surface (1×1 cm 2 After incubation at 37°C for 5, 10, 20, and 30 minutes, 2.5 mL of deionized water was added to the 24-well plate to stop the reaction. The absorbance of free hemoglobin in deionized water was measured at 540 nm. The membrane coagulation index can be quantified using Equation 4:

[0103]

[0104] A 样品 is the absorbance of the sample solution;

[0105] A 血液 is the absorbance of fresh blood.

[0106] Fresh rabbit blood was used to study the complete coagulation time and evaluate the anticoagulant properties of the membrane. A higher coagulation index indicated that the material had excellent anticoagulant properties.

[0107] The experimental results are as follows Figure 5 As shown in (c), with the increase of clotting time, the coagulation index values ​​of all membranes gradually decreased. At 20 minutes, the coagulation index of the control FPI membrane dropped to 12.34%, while that of the ZFPI-Me / Et / i The coagulation index of the Pr membrane remained at about 53.29%, significantly exceeding that of the control membrane. i Pr membrane has significant anticoagulant properties.

[0108] Plasma recalcification time

[0109] Plasma recalcification time (PRT) is a technically valuable indicator for simulating the in vitro coagulation process. Membranes in contact with blood can activate the intrinsic coagulation cascade. A longer PRT indicates enhanced anticoagulant properties of the membrane. The specific experimental steps are as follows:

[0110] The membrane samples were washed multiple times with saline and immersed in a 24-well plate at 37°C for 1 hour. 2 mL of saline was then added. After equilibration, 500 μL of fresh plasma was dropped onto the sample surface. The samples were then incubated at 37°C for 2 hours. The incubated plasma and 100 μL of a CaCl₂ aqueous solution were then transferred to a 96-well plate for recalcification. The absorbance at 405 nm was measured at 30-second intervals at 37°C using a microplate reader to measure the time to reach this absorbance.

[0111] The experimental results are as follows Figure 5 As shown in (d), ZFPI-Me / Et / i The Pr membrane significantly improved the anticoagulant ability, with a PRT value of 25-28 minutes, compared to 15 minutes for the control membrane. The results showed that the improvement of hydrophilicity contributes to the excellent anticoagulant performance.

[0112] Antiplatelet adhesion test

[0113] Platelets were obtained by centrifuging whole blood at 1500rpm for 5 minutes. The membrane sample was placed in a 24-well plate, rinsed three times with PBS solution, and soaked for 2 hours. The sample was removed from the above solution, platelets were gradually dripped into it, and incubated at 37°C for 2 hours. The sample was removed and rinsed with PBS solution to remove the platelets adsorbed on the membrane surface. The platelets were fixed by treating the membrane with 2.5wt% glutaraldehyde at ambient temperature. Subsequently, the sample was dehydrated using gradient concentrations of ethanol. After freeze-drying, the adhesion of platelets to the PES membrane was observed using SEM.

[0114] Platelet adhesion is one of the key indicators for evaluating the anticoagulant performance of materials. Figure 5 As shown in (e), compared with the control group, ZFPI-Me / Et / i Only a small amount of platelets remained on the surface of the Pr membrane. i Pr membrane has excellent anti-platelet adhesion and anti-coagulation properties.

[0115] Based on the above embodiments and test data, through molecular structure innovation (such as Figure 1 As shown by NMR and IR characterization, the phosphorylcholine zwitterionic group was covalently bonded to the polyimide side chain, achieving the following breakthroughs:

[0116] 1) Thermal stability is significantly improved, and TGA shows that the 5% thermal decomposition temperature reaches 385℃ ( Figure 2 a) Meet the requirements of high temperature sterilization;

[0117] 2) The mechanical properties were optimized, and the elongation at break of the ZFPI-Me membrane reached 46.5% (Table 1), meeting the mechanical strength requirements for repeated cleaning of the separation membrane;

[0118] 3) Breakthrough in antifouling performance, BSA protein adsorption is lower than that of the control group ( Figure 3 a), the adhesion rate of E. coli decreased ( Figure 4 ), confirming its excellent anti-biofouling properties;

[0119] 4) Blood compatibility leaps, hemolysis rate <3% ( Figure 5 a), plasma recalcification time was extended to 28 minutes ( Figure 5 d), platelet adhesion decreased by 89% ( Figure 5 e), fully meeting the GB / T 16886 standard for blood-contact materials. These innovative achievements effectively address technical bottlenecks such as protein adsorption and thrombosis caused by the strong hydrophobicity of traditional polyimide membranes, demonstrating significant advantages in applications such as hemodialysis and biological wastewater treatment.

[0120] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A method for preparing a high-throughput blood-compatible polyimide separation membrane, characterized in that: 1) adding a polyimide polymer powder to solvent B, then adding a quaternizing agent, reacting at a temperature of 80-100° C. for a reaction time of 48-72 hours, finally pouring the reacted solution into deionized water for precipitation, filtering to obtain a solid powder, washing with ethanol 3-5 times, and vacuum drying at 90° C. for 24 hours to obtain a quaternized polyimide polymer powder; 2) adding the quaternized polyimide polymer powder to solvent C and stirring at room temperature for 6-8 hours to prepare a casting solution, scraping the solution into an asymmetric separation membrane using a scraper with a thickness of 200 μm, and performing phase inversion exfoliation in deionized water, followed by washing to obtain a high-throughput blood-compatible polyimide separation membrane; The molecules of the polyimide polymer powder include the following structure: The molecular structure of the quaternary ammonium reagent is shown below: wherein R is independently selected from one or a combination of a chain alkoxy group having 1 to 10 carbon atoms, a chain alkenyloxy group having 2 to 10 carbon atoms, a chain alkynyloxy group having 2 to 10 carbon atoms, a cyclic alkoxy group having 3 to 10 carbon atoms, a cyclic alkenyloxy group having 3 to 10 carbon atoms, a trimethylsilyl group, a trimethylsilyloxy group, a halogen-containing alkyl group, a phenyl group, a biphenyl group, a naphthyl group, a pyridyl group, a thienyl group, a halophenyl group, a halobiphenyl group, a phenol group, a phenol group containing an alkyl group, a phenol group containing an alkenyl group, a phenol group containing an alkynyl group, a phenol group containing a nitrile group, a monohalogenated phenol group, and a polyhalogenated phenol group; The high-throughput blood-compatible polyimide separation membrane molecule comprises the following structure:

2. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 1, wherein: Calculated by mole fraction, the raw materials of the polyimide polymer powder include: 1 part of diamine monomer, 1 part of dianhydride monomer, 0.3 parts of dehydrating agent, 0.01 parts of catalyst, and 20 parts of non-aqueous solvent A.

3. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 2, wherein: The diamine monomer is any one or combination of the compounds represented by the following structural formula: The dianhydride monomer is any one or a combination of the following structural formulas: The dehydrating agent is any one of toluene, xylene, cyclohexane, n-hexane, and petroleum ether; the catalyst is any one of isoquinoline, quinoline, 4-hydroxyquinoline, and 8-hydroxyquinoline; and the non-aqueous solvent A is any one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, m-cresol, sulfolane, and dimethyl sulfoxide, or a combination thereof.

4. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 1 or 2, wherein: The synthesis steps of the polyimide polymer powder are as follows: S1, under a nitrogen atmosphere, mixing and dissolving a diamine monomer and a non-aqueous solvent A in a round-bottom flask, and stirring at 90° C. to completely dissolve to form a mixed solution; S2, adding a dianhydride monomer in an amount equimolar to the diamine monomer to the mixed solution in step S1, and dropwise adding 80-100 mL of a dehydrating agent and 0.05 mL of a catalyst, and reacting and mixing at 90° C. for 12 hours to obtain a polyamic acid solution; S3, heating the polyamic acid solution in step S2 to 135° C. and maintaining the reaction for 4 hours to remove moisture, and then heating to 180° C. and maintaining the reaction for 12 hours to finally obtain a viscous polycondensation solution; S4, adding the viscous polycondensation solution in step S3 to icy methanol to obtain a crude polyimide polymer powder, washing the precipitated crude product powder with hot ethanol, and vacuum drying at 80° C. for 48 hours to obtain a pure polyimide polymer powder.

5. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 1, wherein: The chain group in the group R includes a straight chain group and a branched chain group, and the straight chain group or the branched chain group includes one or more of a halogen atom, an oxygen atom or an unsaturated bond functional group; the unsaturated bond functional group includes one or more of a carbon-carbon double bond, a carbon-carbon triple bond, a carbon-nitrogen double bond, a carbon-nitrogen triple bond, a carbon-oxygen double bond, a sulfur-oxygen double bond, a phosphorus-oxygen double bond, an amide, a carboxylate, a sulfonate and a phosphate; the unsaturated bond functional group is located at the end group or inside; the halogen atom is a fluorine, chlorine, bromine or iodine atom, and the halogenated group includes partial substitution and full substitution.

6. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 4, wherein: In step S2, the total amount of the diamine monomer and the dianhydride monomer in the entire reaction mixture solution system is controlled to have a solid content of 15% to 20%.

7. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 4, wherein: The stirring speed of the mixed solution system in step S1 is 100 rpm; the heating rate of the reaction system in step S3 is: heating to 135°C at a heating rate of 5°C / min and maintaining at 135°C for 4 hours, then heating from 135°C to 180°C at a heating rate of 10°C / min and maintaining for 12 hours.

8. The method for preparing a high-throughput blood-compatible polyimide separation membrane according to claim 1, wherein: The solid content of the polyimide polymer powder in solvent B is 15 to 20 wt %, and the solvent B is one or a mixture of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and sulfolane; the solid content of the quaternized polyimide polymer powder in solvent C is 15 to 20 wt %, and the solvent C is any one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, and sulfolane.

9. A high-flux blood-compatible polyimide separation membrane prepared by the preparation method according to any one of claims 1 to 8.

10. Use of a high-flux blood-compatible polyimide separation membrane prepared by the preparation method according to any one of claims 1 to 8 in ultrafiltration, microfiltration, nanofiltration, sewage treatment, hemodialysis and purification.

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