Hollow fiber hemodialysis membrane based on in-situ self-assembly and preparation method thereof

Abstract

The invention discloses a hollow fiber hemodialysis membrane based on in-situ self-assembly and a preparation method thereof. According to the membrane, PES is used as a matrix, PES, PVP and SF are co-dissolved in a N, N-dimethylacetamide DMAc solvent according to a specific proportion, and dry-wet spinning and an accurate non-solvent induced phase separation regulation technology are adopted, so that the silk fibroin and PVP have a synergistic effect in the phase inversion process, and the membrane is prepared. And multi-stage microphase separation and self-assembly are carried out, so that in-situ and lasting anchoring on the membrane substrate and the surface is realized. The dialysis membrane prepared by the method has excellent long-acting pollution resistance, excellent blood compatibility and a stable three-dimensional gradient structure. The invention further provides an intelligent response type expansion scheme of the membrane, and the membrane can dynamically adjust the performance according to the physiological state of a patient by introducing an environment response component, so that individualized precise dialysis is realized.

Description

Technical Field

[0001] This invention relates to the field of biomedical polymer separation membrane technology, specifically to a self-assembled and physically locked polyethersulfone hollow fiber membrane with a three-dimensional gradient pore structure and its preparation method. Background Technology

[0002] Polyethersulfone (PES) has become one of the mainstream materials for hemodialysis membranes due to its excellent mechanical strength, thermal stability, and chemical stability. However, the inherent hydrophobicity of PES makes it easy to adsorb biomolecules such as plasma proteins and platelets during hemodialysis, leading to membrane fouling and thrombosis, thereby reducing dialysis efficiency, increasing patient risks, and shortening membrane lifespan.

[0003] In order to improve the hydrophilicity and blood compatibility of PES membranes, conventional methods include: (1) physical blending of hydrophilic polymers (such as polyvinylpyrrolidone PVP), but PVP is easily washed off during long-term use; (2) hydrophilic modification or coating of the membrane surface (such as polyethylene glycol, heparin, chitosan, etc.), but the coating has problems of weak adhesion and poor stability.

[0004] Silk fibroin (SF) is a natural polymer with excellent biocompatibility, biodegradability, low immunogenicity, and good anticoagulant properties. While there are existing reports on the use of silk fibroin in medical materials, its application in PES hollow fiber hemodialysis membranes and addressing the issue of long-term stable functionalization remain challenging. Traditional methods involve simple blending or surface coating. The former may lead to significant loss or uneven distribution of silk fibroin during phase inversion, while the latter suffers from weak binding and susceptibility of the functional layer to blood erosion or damage during sterilization.

[0005] Therefore, developing a preparation method that enables silk fibroin to exist stably, uniformly, and for a long time within and on the surface of polyethersulfone (PES) membrane matrix without complex chemical modification, while simultaneously achieving synergistic multifunctional properties such as antifouling, anticoagulation, and high throughput, is a pressing technical challenge in the field of hemodialysis membranes. The core lies in how to guide the dynamic self-assembly of silk fibroin in situ during phase inversion and achieve structural locking, thereby overcoming the limitations of existing blending, coating, or grafting techniques.

[0006] Furthermore, with the development of precision medicine and personalized treatment, the "static" performance of traditional dialysis membranes can no longer meet the complex and ever-changing clinical needs. Especially when treating dialysis patients with complications (such as diabetes, acidosis, and high oxidative stress), dialysis membranes with fixed performance are unable to achieve optimal toxin removal and complication prevention. Therefore, developing "intelligent responsive" dialysis membranes that can dynamically adjust their performance according to the patient's physiological state or treatment needs has become a cutting-edge direction in the field of blood purification. However, how to stably and controllably integrate environmentally responsive functions into dialysis membranes without compromising their basic dialysis performance and biocompatibility remains a pressing technical challenge. Summary of the Invention

[0007] The technical problem to be solved by this invention is to overcome the shortcomings of existing PES hemodialysis membranes, such as insufficient hydrophilicity, easy contamination, and general blood compatibility, as well as the easy loss of protein, unstable functional layer, complex process or introduction of biological risks in existing silk fibroin (SF) modification methods. The invention provides a high-performance hollow fiber hemodialysis membrane with excellent long-lasting anti-fouling properties, excellent blood compatibility, and stable three-dimensional gradient structure, as well as its efficient and controllable preparation method.

[0008] The technical solution of the present invention is as follows:

[0009] A hollow fiber hemodialysis membrane based on in-situ self-assembly, having a three-dimensional gradient functional structure from the inner to the outer surface, comprising:

[0010] (1) Functional surface layer: rich in SF stable network formed by dynamic self-assembly, which provides a durable superhydrophilic and antifouling interface;

[0011] (2) Transitional regulation of intermediate layer: SF and PVP form a gradient distribution of composite microregions, which synergistically regulate the pore size distribution and mass transfer channels of the membrane.

[0012] (3) Mechanical support base layer: mainly composed of PES continuous phase, providing the overall mechanical strength of the membrane.

[0013] The preparation principle of this hollow fiber hemodialysis membrane is as follows: Silk fibroin (SF), under the synergistic effect of polyvinylpyrrolidone (PVP), undergoes multi-level dynamic phase separation via non-solvent-induced phase separation (NIPS) in an N,N-dimethylacetamide (DMAc) solvent system to first form a PVP-SF composite micelle precursor. Upon entry into the coagulation bath, stepwise dissociation and recombination occur. Ultimately, SF is "anchored" to the porous framework of the PES matrix through physical entanglement and micro-region interlocking mechanisms. Subsequent ethanol gradient dehydration not only replaces water but, more importantly, induces a conformational transition of the SF molecular chains from random coil to β-sheet, and further physical locking with the PES framework due to the dehydration shrinkage effect, thus forming an extremely stable composite structure in an aqueous environment.

[0014] Specifically, the following steps are included:

[0015] S1. Preparation of silk fibroin: Degummed silk is dissolved in lithium bromide solution, purified by dialysis to obtain a high-purity regenerated silk fibroin aqueous solution, which is then freeze-dried for later use.

[0016] S2. Preparation of spinning solution: PES, PVP, and SF solid obtained from S1 are added to N,N-dimethylacetamide solvent (DMAc) in a mass ratio of (14-18):(5-8):(1-4), wherein the total mass of PES, PVP, and silk fibroin accounts for 18-25% of the total mass of the solution. The mixture is mechanically stirred at 50-70℃ for 8-12 hours to form a homogeneous, transparent ternary blend solution. During the reaction, PVP and SF form a dynamic composite system through intermolecular forces.

[0017] S3. Hollow Fiber Spinning: A dry-wet spinning process is adopted. The spinning solution is extruded through an annular hollow fiber spinneret by a metering pump, while an inner coagulation bath is injected from the central channel of the spinneret. The extruded nascent fibers first pass through an air gap and then enter the outer coagulation bath for a complete and controlled phase transformation.

[0018] S4. Post-treatment and structural locking: After washing the fiber obtained in S3, it is subjected to gradient dehydration treatment in ethanol aqueous solution with progressively increasing concentrations.

[0019] Preferably, in step 2, the polyvinylpyrrolidone is PVP K85 or K90.

[0020] Preferably, in step 3, the temperature of the spinning solution is controlled at 40-60℃. Increased temperature reduces solution viscosity and enhances molecular chain mobility, which is beneficial for the recombination of microphase structures and the orientation of SF during subsequent phase separation.

[0021] Preferably, in step 3, the inner coagulation bath is an aqueous solution of DMAc with a concentration of 0-60 vol%, a temperature of 40-60°C, and a flow rate of 2 ml / min; the outer coagulation bath is an aqueous solution of DMAc with a concentration of 0-10 vol%, a temperature of 20-40°C, and a spinning speed of 15 m / min. A suitable solvent content can slow down the phase separation rate when the inner surface contacts the core liquid, avoiding the formation of excessively large pores and facilitating the formation of a dense and complete functional surface layer. The lower solvent content of the outer coagulation bath ensures the driving force for phase separation, while precisely controlled concentration can adjust the phase transformation rate, which is key to achieving a gradient transition between finger-like and sponge-like pores.

[0022] Preferably, in step 3, the air gap is 1-10 cm, and the relative humidity of the gap environment is controlled at 90-98%. A weak electric field, such as 50-100 V / cm, can be applied during this stage to guide the orientation of SF molecules. The high humidity environment can effectively suppress the rapid evaporation of solvent in the spinning stream, prevent premature skinning on the surface, ensure sufficient exchange between solvent and non-solvent, and promote the formation of gradient pore structure inside the membrane wall.

[0023] Step 3 involves synergistically regulating the above parameters to precisely control the phase separation kinetics, regulate the rate of solvent diffusion outward, and promote gradient phase separation and self-assembly of the PVP-SF composite system in the membrane wall, thereby forming a three-dimensional gradient pore structure from the inner dense surface layer, the transitional intermediate layer to the porous support layer, and achieving precise control over the gradient distribution of membrane pore size, porosity, and functional layer (SF distribution) from the inside to the outside.

[0024] Step 4 is crucial for achieving structural locking, as it induces an irreversible conformational change in SF and generates a contraction-locking effect.

[0025] Preferably, after the ethanol treatment in step 4, a mild gas-phase crosslinking agent (such as glutaraldehyde vapor) can be used for a brief treatment of 10-90 seconds to further improve the stability of the SF network without excessively affecting the membrane performance. Finally, the membrane is dried to obtain the finished product.

[0026] Preferably, before step 1, the environmentally responsive component can be grafted onto SF for modification, or the responsive nanoparticles can be directly mixed with other components in step 2 in a solvent.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] Innovative "In-situ Self-assembly - Physical Anchoring" Dual Mechanism: This invention proposes for the first time a dual mechanism that utilizes the dynamic interaction between PVP and SF to guide SF in in-situ multi-level self-assembly during the NIPS process, combined with ethanol post-treatment to achieve physical locking of the structure. This ensures that the SF functional phase exists stably within the membrane in a "rooted" rather than "attached" manner, solving the fundamental problem of low SF-base film bonding strength leading to easy loss in traditional simple blending or membrane surface coating methods.

[0029] Three-dimensional gradient functional integrated structure: Through process control, the vertical functional gradient design of the membrane structure is achieved. The surface layer is mainly composed of SF network to achieve antifouling; the middle layer optimizes mass transfer with SF / PVP gradient distribution; and the base layer is PES to ensure strength. This biomimetic structure enables the membrane to possess both excellent surface properties and overall mechanical reliability.

[0030] Exceptional and long-lasting comprehensive performance: Durable hydrophilicity and antifouling properties, a stable SF network, ensuring the water contact angle on the dialysis membrane surface remains stable below 45°. Even after prolonged water flow impact or multiple contamination-washing cycles, the hydrophilicity and flux recovery rate (FRR>80%) show minimal decline. Systemic blood compatibility not only reduces platelet adhesion but also effectively reduces platelet activation (reduced PF4 release) and inhibits complement activation (C3a and C5a production significantly lower than the control), exhibiting comprehensive blood-friendly characteristics. Excellent clearance profile: The intermediate layer gradient distribution optimizes mass transfer while maintaining high flux (pure water flux>150L / (m³)). 2 While achieving efficient removal of small molecule toxins (urea clearance rate >85%) and moderate removal of medium molecule toxins (such as lysozyme clearance rate >35%), the albumin loss rate is extremely low.

[0031] The process is controllable, environmentally friendly, and easily industrialized: The main process of this invention is compatible with existing dry-wet spinning methods, requiring no complex chemical grafting or expensive bioactive molecules. High performance can be achieved through physicochemical process control. The introduced electric field assistance and gradient coagulation bath are all precisely controllable engineering parameters, making it highly suitable for large-scale stable production. Attached Figure Description

[0032] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained from these drawings without creative effort.

[0033] Figure 1 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the hollow fiber membrane in this invention, showing the integrated gradient function structure.

[0034] Figure 2 yes Figure 1 Enlarged cross-sectional view showing the integrated gradient function structure.

[0035] Figure 3 This is a flowchart of the method for preparing the hollow fiber membrane in this invention. Detailed Implementation

[0036] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of the embodiments of the invention. Therefore, the drawings and description are considered to be exemplary in nature and not restrictive.

[0037] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0038] Example 1:

[0039] S1: Preparation of regenerated silk fibroin: Dissolve 10g of degummed silk in 100ml of 9.3M LiBr solution and heat at 60℃ for 1 hour. After cooling, dialyze for 3 days and freeze-dry to obtain porous sponge-like silk fibroin.

[0040] S2: Preparation of spinning solution: Weigh PES:PVP K90:SF at a mass ratio of 16:6:2, with a total solids content of 20% (w / v). Add to DMAc and stir at 60°C for 10 hours to remove bubbles.

[0041] S3: Spinning: The dopant temperature is controlled at 50℃, and the spinneret is extruded through an annular spinneret (outer diameter 0.28mm, inner diameter 0.20mm). The inner coagulation bath (core solution) is an aqueous solution containing 30% DMAc (v / v), at a temperature of 50℃ and a flow rate of 2ml / min. The air gap is 5cm, and the ambient humidity is 95%. The flowing outer coagulation bath is an aqueous solution containing 5% DMAc (v / v) at a temperature of 50℃. The spinning speed is 15m / min.

[0042] S4: Post-treatment: The fibers are soaked in running water for 36 hours, then treated sequentially with 30%, 50%, 75%, and 95% ethanol aqueous solutions for 30 minutes each, and then air-dried at room temperature.

[0043] Performance Tests and Results:

[0044] Structural characterization: Figure 1 SEM showed that SF was uniformly distributed on the membrane surface and pore walls in the form of a continuous nanonetwork; XRD showed that the β-sheet structure content of SF increased from the initial 15% to 45% after ethanol treatment.

[0045] Hydrophilicity and stability: The initial water contact angle was 32±2°. After immersion in PBS at 37°C with dynamic shaking for 30 days, the contact angle was 34±3°, and the SF loss rate was <3%.

[0046] Contamination resistance: In the BSA solution (1g / L) contamination test, the flux recovery rate (FRR) was 95% in the first round and remained at 92% after 5 contamination-wash cycles.

[0047] Blood compatibility systematic review:

[0048] Platelet adhesion (SEM counting): 75% less than pure PES membrane;

[0049] Release of PF4, a platelet activation marker: reduced by 60%;

[0050] In vitro recalcification time: extended to 48s (30s for pure PES membrane).

[0051] Dialysis performance: Under standard dialysis conditions (25℃, 0.1MPa), the pure water flux is 185L / (m²). 2 •h), urea clearance rate 88%, creatinine clearance rate 85%, lysozyme (14.4kDa) clearance rate 42%, albumin (66kDa) retention rate >98%.

[0052] Mechanical properties: tensile strength ≥4.5MPa, which meets the standards for medical membrane materials.

[0053] Example 2

[0054] The spinning solution formulation was adjusted to PES:PVP K85:SF = 17:5:3, with a total solids content of 22%. The inner coagulation bath was a 20% DMAc aqueous solution at 55°C; the outer coagulation bath was a 5% DMAc (v / v) aqueous solution at 55°C to delay phase separation. Other steps were the same as in Example 1. Results showed that the uniformity of SF distribution on the membrane surface was significantly improved, the finger-like pore structure inside the membrane was more developed, and the initial water contact angle was 30±2°. The lysozyme removal rate increased to 46%, the creatinine removal rate to 89%, and the pure water flux reached 195 L / (m²). 2 • h), albumin (66kDa) retention rate >98%, and mechanical strength maintained well. After 30 days of dynamic shaking soaking in PBS at 37℃, the water contact angle was 32±3°, and the SF loss rate was <3%. In the BSA solution (1g / L) contamination test, the flux recovery rate (FRR) was 95% in the first round, and remained at 92% after 5 contamination-wash cycles.

[0055] Example 3

[0056] Based on the process in Example 1, a transverse DC electric field (intensity 80 V / cm) was applied to the air gap section, while other steps remained the same as in Example 1. The results showed that the water contact angle was further reduced to 28 ± 2°, and the BSA adsorption amount was reduced by approximately 20% compared to the membrane without the electric field.

[0057] Example 4

[0058] Based on the process in Example 1, the inner coagulation bath was pure water (0% DMAc, temperature 25°C), and the outer coagulation bath was also pure water (0% DMAc, temperature 25°C). Other steps were the same as in Example 1. Results showed that the resulting membrane surface was smoother, but the internal gradient pore structure was not fully developed. The initial water contact angle was 28±2°. The lysozyme removal rate decreased to 38%, the creatinine removal rate was 84%, and the pure water flux reached 200 L / (m²). 2 •h), albumin (66kDa) retention rate >98%.

[0059] Example 5

[0060] Based on the process in Example 1, the inner coagulation bath was a 60% DMAc aqueous solution at 25°C, and the outer coagulation bath was a 10% DMAc aqueous solution at 25°C. Other steps were the same as in Example 1. Results showed that due to delayed phase separation, the density of the resulting membrane skin and support layer increased, and the binding force between silk fibroin and the base membrane cross-section was strong. The initial water contact angle was 43±2°, the lysozyme removal rate decreased to 36%, the creatinine removal rate decreased to 80%, and the initial pure water flux decreased to 150 L / (m²). 2 •h), albumin (66kDa) retention rate >95%.

[0061] Example 6 (pH-responsive dialysis membrane)

[0062] Before step S1, SF was modified: poly(dimethylaminoethyl methacrylate) (PDMAEMA) was grafted onto SF using the EDC / NHS chemical method. Specifically, 1g of regenerated SF was dissolved in 50ml of PBS buffer (pH 6.0); 0.1g of EDC and 0.05g of NHS were added, and the mixture was stirred at room temperature for 30 minutes to activate it; 0.5g of PDMAEMA (Mn=5000) was added, and the reaction was continued to be stirred for 12 hours; the mixture was dialyzed for 3 days and then freeze-dried to obtain SF-g-PDMAEMA solid.

[0063] Spinning solution: PES:PVP K90:SF-g-PDMAEMA = 16:6:2 (total solids content 20%), other details are the same as in Example 1.

[0064] Performance testing: Under pH 7.4 and 6.8 conditions, the water contact angle decreased from 35° to 28°; BSA adsorption decreased by 40%; and urea clearance in the serum of acidosis model mice increased by 18%.

[0065] Example 7 (Temperature-Oxidation Dual-Response Dialysis Membrane)

[0066] Before step S2, responsive nanoparticles were prepared: self-assembled nanoparticles of PNIPAM-b-PEG block copolymer containing disulfide bonds were synthesized and loaded with curcumin. The specific operation was as follows: reversible addition-fragmentation chain transfer (RAFT) polymerization was employed. First, using 2-(dodecyltrithiocarbonate)-2-methylpropionic acid as a chain transfer agent, a poly(N-isopropylacrylamide) (PNIPAM) macromolecular chain transfer agent (Mn≈8000) was synthesized. Subsequently, using this macromolecular chain transfer agent, polyethylene glycol methacrylate (PEGMA, Mn=500), and bis(2-methacryloyloxyethyl) disulfide as comonomers, the reaction was initiated by azobisisobutyronitrile (AIBN) and carried out at 70°C in N,N-dimethylformamide (DMF) for 24 hours to obtain the PNIPAM-bP (DMA-co-SS) block copolymer containing disulfide bonds. 10 mg of the copolymer and 2 mg of curcumin were dissolved together in 5 mL of tetrahydrofuran (THF). The mixture was then added dropwise to 20 mL of ultrapure water under vigorous stirring. The THF was subsequently removed by rotary evaporation under reduced pressure at 40 °C to obtain a responsive nanoparticle colloidal solution loaded with curcumin. Dynamic light scattering (DLS) showed that the hydrated particle size was approximately 80 nm.

[0067] Spinning solution: PES:PVP K85:SF:responsive nanoparticles = 17:5:2:1, dissolved in DMAc, stirred at 60°C for 12 hours to form a homogeneous spinning solution. Other procedures are the same as in Example 1.

[0068] Performance testing: When the temperature increased from 25℃ to 37℃, the membrane pore size decreased by 15%; in the presence of 10μM GSH, the drug release rate reached 75% after 24 hours; and it showed better anti-inflammatory effects in the oxidative stress model.

[0069] Example 8 (Glucose-responsive anti-glycation membrane)

[0070] Before step S1, SF was modified: SF was modified with 3-aminophenylboronic acid to obtain SF-PBA. The specific procedure was as follows: 1 g of regenerated silk fibroin (SF) was dissolved in 50 mL of borate buffer at pH 8.5 and stirred in an ice bath. 0.15 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 0.09 g of N-hydroxysuccinimide (NHS) were added, and the mixture was activated for 30 minutes. 0.3 g of 3-aminophenylboronic acid (APBA) was added, and the mixture was reacted at 4°C in the dark for 24 hours. The reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 3500, and dialyzed against deionized water for 4 days to completely remove unreacted reagents. The solution was then freeze-dried to obtain solid SF-PBA. The grafting rate of phenylboronic acid was calculated to be approximately 8 mol% by 1H NMR spectroscopy.

[0071] Spinning solution: PES:PVP K90:SF-PBA = 16:6:3, dissolved in DMAc, stirred at 60°C for 10 hours to form a homogeneous spinning solution. Other procedures are the same as in Example 1.

[0072] Performance testing: When the glucose concentration increased from 5mM to 20mM, the water contact angle decreased by 12°; the adsorption of AGEs decreased by 50%; and the removal of toxins from the serum of diabetic patients was more efficient.

[0073] Comparative Example 1

[0074] No silk fibroin was added; the spinning solution was PES:PVP K90 = 18:7, with a total solids content of 20%. Other steps were the same as in Example 1.

[0075] Comparative Example 2

[0076] A surface coating method was used: first, a PES hollow fiber membrane without SF was prepared (same as Comparative Example 1), then it was immersed in a 1% silk fibroin aqueous solution for 2 hours, and then dried after being treated with ethanol. After 24 hours of simulated blood circulation, the surface SF loss rate exceeded 40%, and the flux recovery rate decreased from the initial 88% to 65%.

[0077] Performance Tests and Results:

[0078] The hollow fiber membranes obtained in Examples 1, 2, 4, 5 and Comparative Examples 1 and 2 were subjected to performance tests:

[0079] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0080] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. It should be noted that any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A hollow fiber hemodialysis membrane based on in-situ self-assembly, characterized in that, include: The surface has a three-dimensional gradient functional structure from the inside to the outside, consisting of a functional surface layer, a transition and regulation intermediate layer, and a mechanical support base layer. The functional surface layer is rich in a silk fibroin SF stable network formed by dynamic self-assembly, the intermediate layer is a composite micro-region formed by gradient distribution of SF and PVP, and the base layer is a continuous PES phase.

2. The method for preparing a hollow fiber hemodialysis membrane based on in-situ self-assembly as described in claim 1, characterized in that, Includes the following steps: S1. Preparation of silk fibroin: Degummed silk is dissolved in lithium bromide solution, purified by dialysis to obtain a regenerated silk fibroin aqueous solution, which is then freeze-dried for later use. S2. Preparation of spinning solution: PES, PVP and SF solid obtained from S1 are added to N,N-dimethylacetamide solvent in a mass ratio of 14-18:5-8:1-4, wherein the total mass of PES, PVP and SF accounts for 18-25% of the total mass of the solution. The mixture is mechanically stirred at 50-70℃ for 8-12 hours to form a homogeneous and transparent ternary blend solution. S3, Hollow fiber spinning: The spinning solution is extruded through an annular hollow fiber spinneret, and an inner coagulation bath is injected from the central channel of the spinneret. The extruded fibers first pass through an air gap and then enter the outer coagulation bath. S4. Post-treatment and structural locking: After washing the fiber obtained in S3, it is subjected to gradient dehydration treatment in ethanol aqueous solution with progressively increasing concentrations.

3. The method for preparing the hollow fiber hemodialysis membrane according to claim 2, characterized in that, The polyvinylpyrrolidone mentioned in step 2 is PVP K85 or K90.

4. The method for preparing the hollow fiber hemodialysis membrane according to claim 2, characterized in that, In step 3, the temperature of the spinning solution is controlled at 40-60℃, the inner coagulation bath is an aqueous solution of N,N-dimethylacetamide (DMAc) at 0-60 vol%, the temperature is 40-60℃, and the flow rate is 2 ml / min; the outer coagulation bath is an aqueous solution of DMAc at 0-10 vol%, the temperature is 20-40℃, and the spinning speed is 15 m / min.

5. The method for preparing the hollow fiber hemodialysis membrane according to claim 2, characterized in that, In step 3, the air gap is 1-10cm, the relative humidity of the gap environment is controlled at 90-98%, and a weak electric field of 50-100V / cm is applied.

6. The method for preparing the hollow fiber hemodialysis membrane according to claim 2, characterized in that, The concentrations of the ethanol solution in step 4 are 30%, 50%, 75%, and 95% respectively, and each treatment lasts for 30 minutes.

7. The method for preparing the hollow fiber hemodialysis membrane according to claim 2, characterized in that, After the ethanol treatment in step 4, the mixture is treated with vapor crosslinking agent for 10-90 seconds.

8. The method for preparing the hollow fiber hemodialysis membrane according to claims 2-7, characterized in that, Before step 1, an environmentally responsive component is grafted onto SF for modification. The environmentally responsive component is a pH-responsive component, a temperature-oxidation dual-responsive component, or a glucose-responsive component.

9. The method for preparing the hollow fiber hemodialysis membrane according to claims 2-7, characterized in that, In step 2, the responsive nanoparticles are directly mixed with the other components from step 2 in a solvent. The nanoparticles are self-assembled PNIPAM-b-PEG block copolymer nanoparticles containing disulfide bonds and loaded with curcumin.

10. The method for preparing the hollow fiber hemodialysis membrane according to claim 8, characterized in that, The pH-responsive component is poly(dimethylaminoethyl methacrylate), and the glucose-responsive component is 3-aminophenylboronic acid.

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