A hemodialysis membrane based on in-situ construction of an anticoagulation protective layer by an interfacial polymerization method, and a preparation method and application thereof

Abstract

This invention relates to a hemodialysis membrane with an in-situ anticoagulant protective layer constructed using interfacial polymerization, its preparation method, and its applications, belonging to the field of medical membrane materials technology. The method involves a wet spinning process, in which a grafting agent is added to the spinning solution, and an anticoagulant is added to the core solution and coagulation bath. An interfacial polymerization reaction is then used to simultaneously form an anticoagulant protective layer on both the inner and outer surfaces of the membrane in situ. The hemodialysis membrane prepared by this invention exhibits excellent anticoagulant properties and biocompatibility, making it suitable for medical applications such as hemodialysis and hemofiltration. The process is simple, controllable, and easily scalable.

Description

Technical Field

[0001] This invention belongs to the field of medical membrane material technology, specifically a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization, its preparation method, and its application. Background Technology

[0002] Hemodialysis is the primary treatment for end-stage renal disease, and its core component is the hemodialysis membrane. An ideal hemodialysis membrane should possess excellent solute clearance capacity, superior biocompatibility, and anticoagulant properties. However, existing hemodialysis membrane materials (such as polysulfone, polyethersulfone, and cellulose acetate) often lack effective anticoagulant modifications on their surfaces, easily leading to platelet adhesion, activation of the coagulation system, and thrombosis, severely impacting dialysis safety and long-term efficacy.

[0003] Currently, methods to improve the anticoagulant properties of hemodialysis membranes mainly include surface coating, physical blending, and chemical grafting. Surface coating is simple to operate, but the coating is prone to peeling off; physical blending may affect the stability of the membrane structure; chemical grafting usually requires complex pretreatment and grafting steps, which is cumbersome and may damage the membrane structure. Therefore, developing a simple, robust, and durable method for preparing hemodialysis membranes is of great significance. Summary of the Invention

[0004] To address the aforementioned problems in the existing technology, the present invention aims to design and provide a technical solution for a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization, as well as its preparation method and application. This solution achieves in-situ interfacial polymerization of anticoagulants on both the inner and outer surfaces of the membrane simultaneously during wet spinning, forming a stable and uniform anticoagulant protective layer, which significantly improves the biocompatibility and anticoagulant performance of the hemodialysis membrane.

[0005] The method for preparing a hemodialysis membrane with an in-situ anticoagulant protective layer based on interfacial polymerization is characterized by the following steps: 1) Preparation of spinning solution: Dissolve the polymer material in an organic solvent at a concentration of 15-25 wt%, add a highly reactive grafting agent, and mix thoroughly to obtain a spinning solution containing the grafting agent, wherein the content of the grafting agent is 0.1-5 wt%. If the content of the grafting agent is too low, there will be insufficient reaction sites, and a complete and dense anticoagulant protective layer cannot be formed, resulting in limited performance improvement; if the content is too high, the reaction may be too vigorous, resulting in an excessively thick or defective protective layer, or even clogging the membrane pores, affecting the solute clearance rate, and potentially causing biocompatibility problems due to residual unreacted grafting agent.

[0006] 2) Preparation of core solution: Prepare an aqueous solution or a mixture of water and solvent containing an anticoagulant as the core solution, wherein the content of the anticoagulant is 0.2-5 wt%, and the core solution temperature is controlled at 15-60℃.

[0007] 3) Preparation of coagulation bath: Prepare an aqueous solution or mixed aqueous solution containing an anticoagulant as a coagulation bath, wherein the content of the anticoagulant is 0.2-5 wt%, and the temperature of the coagulation bath is controlled at 15-60℃.

[0008] In steps 2 and 3) of this invention, a higher anticoagulant content results in more molecules forming an anticoagulant protective layer on the membrane surface. However, excessively high concentrations may lead to an overly thick or dense protective layer, potentially clogging membrane pores and affecting solute exchange efficiency. Excessively high core solution temperature and coagulation bath temperature can cause excessively rapid interfacial polymerization, resulting in an uneven or defective protective layer on the inner surface of the membrane, affecting performance uniformity. It may also cause premature solidification of the nascent fiber cortex, affecting membrane structure formation. Conversely, excessively low temperatures and slow reaction rates may lead to insufficient grafting of the anticoagulant, preventing the formation of a complete and continuous protective layer and impacting anticoagulant efficacy. In this invention, the polar groups (such as amide bonds and carboxyl groups) introduced by the grafting agent in reaction with the anticoagulant improve the hydrophilicity of the membrane surface. Increased hydrophilicity helps reduce non-specific protein adsorption, further enhancing blood compatibility.

[0009] 4) Wet spinning: The spinning solution and core solution are co-extruded through a hollow fiber spinneret. After forming nascent fibers in the air section, they are solidified in a coagulation bath. The residence time of the nascent fibers in the coagulation bath is 5-15 seconds. 5) Interfacial polymerization reaction: At the interface between the core solution and the spinning solution, the anticoagulant and the grafting agent undergo an interfacial polymerization reaction, forming an inner anticoagulant protective layer in situ on the inner surface of the membrane; at the interface between the coagulation bath and the spinning solution, the anticoagulant and the grafting agent undergo an interfacial polymerization reaction, forming an outer anticoagulant protective layer in situ on the outer surface of the membrane. 6) Post-processing: The formed membrane fibers are rinsed, soaked, and dried to obtain a hemodialysis membrane with inner and outer anticoagulant protective layers.

[0010] The method for preparing a hemodialysis membrane with an in-situ anticoagulant protective layer based on interfacial polymerization is characterized in that, in step 1), the content of the grafting agent is 0.5-4wt%, preferably 2-3wt%.

[0011] The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization is characterized in that, in step 1), the polymer material is at least one selected from polylactic acid, polysulfone, polyethersulfone, cellulose acetate, polyacrylonitrile, polyvinylidene fluoride, and polymethyl methacrylate. The organic solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and N-methylpyrrolidone; The grafting agent is at least one of the following: trimesoyl chloride, isophthaloyl chloride, terephthaloyl chloride, toluene diisocyanate, sebacate chloride, adipicoyl chloride, diphenylmethane diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

[0012] The method for preparing a hemodialysis membrane with an in-situ anticoagulant protective layer based on interfacial polymerization is characterized in that, in step 2), the content of the anticoagulant is 0.8-4 wt%, preferably 1.5-2.5 wt%; the core fluid temperature is controlled at 20-50℃, preferably 30-40℃; and the anticoagulant is at least one of ethylenediaminetetraacetic acid or its salt, citrate, vitamin K antagonist, acetylsalicylic acid, hirudin, and cysteine.

[0013] The method for preparing a hemodialysis membrane with an in-situ anticoagulant protective layer based on interfacial polymerization is characterized in that, in step 3), the content of the anticoagulant is 0.8-4 wt%, preferably 1.5-2.5 wt%; and the core fluid temperature is controlled at 20-50℃, preferably 30-40℃.

[0014] The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization is characterized in that, in step 4), the air section distance is 4-10 cm and the winding speed is 6-15 m / min.

[0015] The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization is characterized in that, in step 6), the rinsing time is 24-60 hours, the soaking time is 6-24 hours, and the drying temperature is room temperature to 23-27℃.

[0016] The hemodialysis membrane prepared by the method is characterized in that: the hemodialysis membrane is a hollow fiber membrane having an anticoagulant protective layer formed in situ on the inner and outer surfaces.

[0017] The hemodialysis membrane is characterized in that the thickness of the anticoagulant protective layer is 10-200 nm, preferably 50-100 nm.

[0018] The application of the hemodialysis membrane in hemodialysis, hemofiltration, and extracorporeal circulation therapy.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. In-situ construction: The anticoagulant protective layer is constructed simultaneously during the spinning process, which is simple and requires no post-processing grafting; 2. Dual protection: An anticoagulant layer is formed simultaneously on the inner and outer surfaces, comprehensively enhancing the membrane's anticoagulant performance; 3. Strong bonding: The protective layer formed by interfacial polymerization is chemically bonded to the base film and is not easily detached; 4. High biocompatibility: The anticoagulant is evenly distributed, significantly reducing the risk of thrombosis; 5. Wide range of applications: Applicable to a variety of membrane materials and anticoagulants, with flexible and adjustable processes. Attached Figure Description

[0020] Figure 1 This is a diagram showing the physicochemical properties of the nanofiltration membrane of this invention; In the image: a - optical image of the membrane filaments; b - cross-sectional scanning electron microscope image of the hollow fiber membrane; c - surface scanning electron microscope image of the hollow fiber membrane. Detailed Implementation

[0021] The present invention will be clearly and completely described below with reference to the accompanying drawings and specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally determined according to national standards; if there is no corresponding national standard, they are performed according to general standard requirements or general methods. Example 1

[0022] 1) Dissolve dried polysulfone in N,N-dimethylformamide to prepare a 20 wt% solution, add 1 wt% trimesoyl chloride, and ultrasonically degas for 2 hours to obtain the spinning solution; 2) Prepare an aqueous solution containing 1 wt% ethylenediaminetetraacetic acid as the core fluid, and control the temperature at 30℃; 3) Prepare an aqueous solution containing 1 wt% ethylenediaminetetraacetic acid as a coagulation bath, and control the temperature at 25℃; 4) A wet spinning device is used to co-extrude the spinning solution and the core solution, with an air section distance of 5cm, and then solidify it in a coagulation bath. The winding speed is 10m / min. 5) Rinse the formed membrane fibers with ultrapure water for 24 hours, soak them in a glycerol aqueous solution for 12 hours, and dry them at room temperature; 6) A polysulfone hollow fiber hemodialysis membrane with anticoagulation protective layers on both the inner and outer surfaces was obtained. Example 2

[0023] 1) Dissolve 18.0 g of dried polyethersulfone (PES, MW=58,000) particles in 82.0 g of ultra-dry N,N-dimethylacetamide (DMAc) and mechanically stir in a 60°C water bath for 8 h until completely transparent, preparing a solution of approximately 18 wt%. Then add 0.72 g of toluene diisocyanate (TDI, purity >98%) and continue stirring for 3 h to ensure thorough dispersion, obtaining a spinning solution containing the grafting agent (TDI content approximately 0.8 wt%). Place the solution in a vacuum dryer and ultrasonically degas for 2.5 h for later use.

[0024] 2) Prepare a core solution containing 2.5wt% sodium citrate (analytical grade): Weigh 2.50 g of sodium citrate and dissolve it in 97.50 g of deionized water. Stir magnetically until completely dissolved. Precisely control the core solution temperature at 35±0.5℃ using a constant temperature water bath and continuously purge with nitrogen to prevent oxidation.

[0025] 3) Preparation of a coagulation bath containing 2.0 wt% sodium citrate: Weigh 20.0 g of sodium citrate and dissolve it in 980.0 g of deionized water. After thorough stirring, add 200.0 g of N-methylpyrrolidone (NMP) and mix thoroughly to obtain a water / NMP mixed coagulation bath (water:NMP=83:17, v / v). Maintain a constant temperature of 30±0.5℃ in the coagulation bath and use a circulating pump to maintain a slight flow of fluid within the bath to avoid concentration gradients.

[0026] 4) Wet spinning equipment is used: the spinneret adopts an annular orifice structure (inner diameter 0.9 mm, outer diameter 1.4 mm). The feeding rate of the spinning solution metering pump is set to 6.0 mL / min, corresponding to a feeding pressure of approximately 0.18 MPa; the core solution is controlled by a precision injection pump at a flow rate of 3.5 mL / min. The vertical distance (air section) between the spinneret and the surface of the coagulation bath is adjusted to 6 cm. After the formed nascent fibers enter the coagulation bath, the residence time is 6 ± 1 s. The winding device speed is set to 15 m / min, and the draw ratio is approximately 1.5.

[0027] 5) The spun hollow fiber membrane fibers were immediately introduced into a deionized water overflow tank and continuously rinsed for 36 hours, with fresh ultrapure water replaced every 12 hours during this period to thoroughly replace residual organic solvents and unreacted small molecules. Subsequently, the membrane fibers were transferred to a 15% (v / v) glycerol aqueous solution and allowed to stand and soak at 4°C for 24 hours as a pore-preserving treatment.

[0028] 6) The membrane fibers were evenly laid on a clean polytetrafluoroethylene mesh and naturally dried in a clean environment at 25±2℃ and 50±5% relative humidity for 48 h. The final product was a polyethersulfone hollow fiber hemodialysis membrane with sodium citrate anticoagulant molecules grafted onto both the inner and outer surfaces by chemical bonding, labeled as PES-CA.

[0029] Example 3: Preparation of cellulose acetate-based anticoagulant hemodialysis membrane

[0030] 1) 15.0 g of cellulose acetate (CA, acetyl content 39.5%) granules were dried in an oven at 80℃ for 12 h, then dissolved in 85.0 g of ultra-dry dimethyl sulfoxide (DMSO). The solution was vigorously stirred in an oil bath at 75℃ for 10 h to obtain a clear solution. After cooling to room temperature, 0.45 g of adipic acid chloride (purity >99%) was added, and stirring was continued for 4 h under nitrogen protection to obtain a homogeneous spinning solution (adipic acid chloride content approximately 0.45 wt%). The solution was filtered through a 0.45 μm PTFE membrane and then degassed under vacuum for 3 h.

[0031] 2) Prepare the core solution containing 0.8 wt% recombinant hirudin (activity >15000 ATU / mg): Accurately weigh 80.0 mg of hirudin lyophilized powder and slowly dissolve it in 9.92 g of phosphate-buffered saline (PBS, pH 7.4) at 4°C, avoiding vigorous stirring to prevent air bubbles. After complete dissolution, stabilize the core solution temperature at 20±0.5°C using a water bath, and operate in the dark throughout the process.

[0032] 3) Preparation of the coagulation bath: Using an ion-additive system, dissolve 5.0 g of lithium chloride (LiCl) and 10.0 g of polyvinylpyrrolidone (PVP K30) in 985.0 g of deionized water and mix thoroughly. The temperature of the coagulation bath is controlled at 18±0.5℃.

[0033] 4) Wet spinning: A spinneret with an inner diameter of 1.0 mm and an outer diameter of 1.6 mm is used. The spinning solution feed pressure is set to 0.12 MPa, and the core solution flow rate is 2.8 mL / min. The air section distance is extended to 10 cm to promote partial solvent evaporation and skin pre-formation. After the nascent fibers enter the low-temperature coagulation bath, the curing time is approximately 8 seconds. The winding speed is set to 8 m / min.

[0034] 5) The membrane fibers were first rapidly rinsed with cold deionized water at 4°C for 5 min, and then continuously dialyzed and rinsed in a large volume of flowing ultrapure water (4°C) for 60 h. Subsequently, they were immersed in PBS protective solution containing 5% sorbitol and refrigerated at 4°C for 12 h.

[0035] 6) Final drying was performed using freeze-drying: The membrane fibers were placed in a freeze dryer and pre-frozen at -50℃ for 4 h, and then sublimated and dried at -30℃ and <10 Pa vacuum for 24 h. A cellulose acetate anticoagulant hollow fiber membrane with a porous structure grafted with hirudin was obtained, labeled CA-HIR. Example 4

[0036] 1) The polymer solution was prepared in the same way as in step 1 of Example 1, but the amount of grafting agent trimethylbenzene chloride (TMC) was increased to 1.5 wt% (i.e., 1.5 g TMC was added to 100 g 20 wt% PSF / DMF solution), and the ultrasonic degassing time was extended to 3 h.

[0037] 2) Preparation of the compound anticoagulant core solution: Weigh 0.5 g of disodium ethylenediaminetetraacetate (EDTA-2Na) and 0.5 g of acetylsalicylic acid (aspirin), and dissolve them together in 99.0 g of deoxygenated deionized water. Stir in a 40°C water bath until completely dissolved and a clear solution is formed. The core solution temperature is controlled at 32±0.5°C, and the solution is wrapped in aluminum foil to protect it from light.

[0038] 3) The coagulation bath is prepared in the same way as step 3 of Example 1, which is an aqueous solution containing 1 wt% EDTA-2Na at a temperature of 25°C.

[0039] 4) The spinning process parameters are basically the same as in Example 1, but the winding speed is increased to 14 m / min to obtain a thinner membrane wall and a higher water flux potential.

[0040] 5) The post-processing procedure is the same as step 5 in Example 1.

[0041] 6) Finally, a polysulfone hollow fiber hemodialysis membrane with EDTA and aspirin molecules grafted onto the inner surface and EDTA molecules grafted onto the outer surface was obtained, labeled as PSF-EDTA / ASA. Example 5

[0042] 1) 22.0 g of polyvinylidene fluoride (PVDF, Mw=400,000) powder and 4.4 g of polyvinylpyrrolidone (PVPK90, as a pore-forming agent) were dissolved together in 73.6 g of ultra-dry N-methylpyrrolidone (NMP). The solution was stirred in an oil bath at 85°C for 24 h to form a homogeneous viscous solution. After cooling to 50°C, 0.66 g of sebacate chloride and 0.44 g of isophorone diisocyanate (IPDI) were added sequentially. The mixture was stirred for another 6 h under a nitrogen atmosphere to obtain a double-grafting agent spinning solution (total grafting agent content approximately 1.0 wt%). The solution was allowed to stand overnight to remove bubbles.

[0043] 2) Preparation of core solution containing 3.0 wt% L-Cysteine: Weigh 3.00 g of cysteine ​​and dissolve it in 97.00 g of deionized water that has been bubbled with nitrogen for 30 min to remove oxygen. Adjust the pH to 6.5 using dilute hydrochloric acid. The core solution temperature is strictly controlled at 25±0.5℃, and nitrogen gas is continuously introduced for protection.

[0044] 3) Prepare a mixed coagulation bath containing 2.0 wt% polyethylene glycol (PEG 6000) and 1.0 wt% cysteine. Set the temperature to 20°C.

[0045] 4) Wet spinning: A large-aperture spinneret (inner diameter 1.2 mm, outer diameter 2.0 mm) is used. The spinning solution is extruded at a pressure of 0.20 MPa, and the core solution flow rate is 5.0 mL / min. The air section distance is 4 cm. The coagulation bath is two-stage: the first stage is the above-mentioned mixed bath, and the second stage is a pure water bath. The total coagulation time is approximately 12 s. The winding speed is 6 m / min to obtain high mechanical strength.

[0046] 5) The membrane fibers were rinsed in a 50°C water bath and then in deionized water at room temperature for 24 h each to completely remove PVP and solvent. They were then soaked in a 10% ethanol aqueous solution for 6 h and finally dried at room temperature.

[0047] 6) A PVDF hollow fiber membrane with cysteine ​​grafted on both the inner and outer surfaces and excellent antioxidant and anticoagulant properties was obtained and labeled as PVDF-CYS.

[0048] Comparative Example 1: Ordinary polysulfone hollow fiber membranes were prepared by conventional wet spinning using only PVDF / DMF solution without the addition of grafting agents and anticoagulants.

[0049] The following performance test data demonstrates the beneficial effects of the present invention. Platelet adhesion experiment: The adhesion of platelets on the surface was observed using scanning electron microscopy. Using the number of platelets adhered in the comparative example as a reference, the platelet adhesion rate = (number of platelets adhered in the example / number of platelets adhered in the comparative example) * 100%. Static coagulation time test: An equal volume of fresh pig blood was contacted with the membrane sample, and the time for complete blood coagulation was recorded. Solute clearance rate test: The clearance performance was tested using a urea-simulated solution. The test results are shown in Table 1.

[0050]

[0051] Table 1 shows that the hemodialysis membrane prepared by the present invention has a significantly prolonged clotting time, a significantly reduced platelet adhesion, and a good solute clearance rate, and its overall performance is better than that of the control example.

[0052] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a hemodialysis membrane with an in-situ anticoagulant protective layer based on interfacial polymerization, characterized in that... Includes the following steps: 1) Preparation of spinning solution: Dissolve the polymer material in an organic solvent, the concentration of the polymer material is 15-25 wt%, add a highly reactive grafting agent, mix evenly to obtain a spinning solution containing the grafting agent, wherein the content of the grafting agent is 0.1-5 wt%; 2) Preparation of core solution: Prepare an aqueous solution or a mixture of water and solvent containing an anticoagulant as the core solution, wherein the content of the anticoagulant is 0.2-5 wt%, and the core solution temperature is controlled at 15-60℃; 3) Preparation of coagulation bath: Prepare an aqueous solution or mixed aqueous solution containing an anticoagulant as a coagulation bath, wherein the content of the anticoagulant is 0.2-5 wt%, and the temperature of the coagulation bath is controlled at 15-60℃; 4) Wet spinning: The spinning solution and core solution are co-extruded through a hollow fiber spinneret. After forming nascent fibers in the air section, they are solidified in a coagulation bath. The residence time of the nascent fibers in the coagulation bath is 5-15 seconds. 5) Interfacial polymerization reaction: At the interface between the core solution and the spinning solution, the anticoagulant and the grafting agent undergo an interfacial polymerization reaction, forming an inner anticoagulant protective layer in situ on the inner surface of the membrane; at the interface between the coagulation bath and the spinning solution, the anticoagulant and the grafting agent undergo an interfacial polymerization reaction, forming an outer anticoagulant protective layer in situ on the outer surface of the membrane. 6) Post-processing: The formed membrane fibers are rinsed, soaked, and dried to obtain a hemodialysis membrane with inner and outer anticoagulant protective layers.

2. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 1), the content of grafting agent is 0.5-4wt%, preferably 2-3wt%.

3. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 1): the polymer material is at least one of polylactic acid, polysulfone, polyethersulfone, cellulose acetate, polyacrylonitrile, polyvinylidene fluoride, and polymethyl methacrylate; The organic solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and N-methylpyrrolidone; The grafting agent is at least one of the following: trimesoyl chloride, isophthaloyl chloride, terephthaloyl chloride, toluene diisocyanate, sebacate chloride, adipicoyl chloride, diphenylmethane diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

4. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 2): the content of the anticoagulant is 0.8-4 wt%, preferably 1.5-2.5 wt%; the core fluid temperature is controlled at 20-50℃, preferably 30-40℃; the anticoagulant is at least one of ethylenediaminetetraacetic acid or its salt, citrate, vitamin K antagonist, acetylsalicylic acid, hirudin, and cysteine.

5. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 3): the content of anticoagulant is 0.8-4wt%, preferably 1.5-2.5wt%; the core fluid temperature is controlled at 20-50℃, preferably 30-40℃.

6. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 4): the air section distance is 4-10cm, and the winding speed is 6-15m / min.

7. The method for preparing a hemodialysis membrane based on in-situ construction of an anticoagulant protective layer using interfacial polymerization as described in claim 1, characterized in that... In step 6): the rinsing time is 24-60 hours, the soaking time is 6-24 hours, and the drying temperature is room temperature to 23-27℃.

8. A hemodialysis membrane prepared by the method according to any one of claims 1-7, characterized in that: The hemodialysis membrane is a hollow fiber membrane with an anticoagulant protective layer formed in situ on the inner and outer surfaces.

9. The hemodialysis membrane as described in claim 8, characterized in that: The thickness of the anticoagulant protective layer is 10-200 nm, preferably 50-100 nm.

10. The application of the hemodialysis membrane as described in claim 1 in hemodialysis, hemofiltration, and extracorporeal circulation therapy.

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