An anti-coagulation hemodialyzer and its preparation method and application

Abstract

The application relates to the technical field of blood purification, and particularly discloses an anticoagulant hemodialysis device and a preparation method and application thereof. The anticoagulant hemodialysis device mainly comprises a dialyzer shell, a dialysis membrane, an end cover, an O-shaped ring and a protective cap. The dialysis membrane is an anticoagulant hollow fiber membrane. The anticoagulant hollow fiber membrane is prepared by using a sulfonyl polymer, an amino-containing compound and an additive as main raw materials, and is prepared through wet spinning and solidification into a membrane, and then is treated by a hydrophilic compound containing a carbon-carbon double bond and a catalyst. The wet spinning process comprises co-extrusion of a dope and a core solution. The dope is prepared by using the sulfonyl polymer, the amino-containing compound and the additive as main raw materials, and the core solution is prepared by using a high-molecular polymer solution containing a double bond and an ester bond as a main raw material. The prepared anticoagulant hemodialysis device can be anticoagulated for a long time, can reduce protein adsorption during use, can increase the antifouling performance of the product, can reduce or avoid the coagulation of the product, and is easy to be industrialized.

Description

Technical Field

[0001] This invention relates to the field of blood purification technology, and in particular to an anticoagulant hemodialyzer, its preparation method, and its application. Background Technology

[0002] Currently, hollow fiber membranes are used in gas and liquid treatment, involving a wide range of industries, including chemical, pharmaceutical, medical device, and bioengineering technologies. Medical devices primarily utilize them in hemodialysis. There are three main treatment methods for kidney disease patients: peritoneal dialysis, hemodialysis, and kidney transplantation. In 2022, there were approximately 830,000 hemodialysis patients in my country, with a market size reaching 25.9 billion yuan. Due to cost and limited kidney donors, less than 5% of kidney disease patients can recover through kidney transplantation; the remaining patients rely on dialysis to sustain their lives. As the range of diseases treated by hemodialysis continues to expand, the demand for hemodialysis equipment is also increasing.

[0003] Polyethersulfone and polysulfone are important raw materials for dialysis membranes, which are the core technology of hemodialysis machines. The quality of the dialysis membrane directly determines the quality of the hemodialysis machine and the safety and efficiency of the dialysis process. Due to the inert and hydrophobic surface of conventional hollow fiber membranes, they easily adsorb proteins from the blood, causing membrane fouling and resulting in a decrease in water flux. In addition, different patients require different amounts of anticoagulant during hemodialysis, which can sometimes lead to blood clots in the hemodialysis machine.

[0004] Existing technologies often employ blending and grafting methods to modify dialysis membranes, aiming to improve their hydrophilicity, anticoagulation, and antifouling properties. However, modified hollow fiber membranes prepared by blending are prone to detachment during use, affecting their performance and lifespan. Grafting modification involves bonding organic compounds containing desired active functional groups to the membrane surface via covalent bonds, hydrogen bonds, etc. Covalent bond modification offers strong bonding and high stability, but its preparation process is complex and costly. Hydrogen bond modification, on the other hand, exhibits weak bonding, is prone to detachment, and is difficult to scale up for industrial production. Summary of the Invention

[0005] Based on this, the purpose of the present invention is to address the shortcomings of the prior art by providing an anticoagulant hemodialysis device, its preparation method, and its application.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides an anticoagulant hemodialysis device, comprising a dialyzer shell, a dialysis membrane, end caps, O-rings, and a protective cap. The dialysis membrane is characterized by being an anticoagulant hollow fiber membrane. The anticoagulant hollow fiber membrane is prepared using sulfone polymers, amino-containing compounds, and additives as main raw materials. It is first prepared by wet spinning and solidification into a film, followed by treatment with a hydrophilic compound containing carbon-carbon double bonds and a catalyst. The wet spinning process includes co-extrusion of the fiber solution and the core solution. The silk solution comprises the following components by mass: 16-24 parts of sulfone polymer, 2-7 parts of amino compound, 3-8 parts of auxiliaries, and 61-80 parts of solvent; The core fluid comprises the following components by mass: 50-90 parts of a polymer solution containing double bonds and ester bonds, 9-45 parts of a solvent, and 1-5 parts of an alkaline substance. The sulfone polymer includes polysulfone or polyethersulfone; the amino-containing compound includes one or more of methacrylamide gelatin, methacrylamide hyaluronic acid, methacrylamide heparin, and polyethyleneimine; the alkaline substance includes one or more of sodium bicarbonate, potassium bicarbonate, potassium hydroxide, and sodium hydroxide.

[0007] As a further improvement of the present invention, the anticoagulant hollow fiber membrane is hydrophilic, and the contact angle of the anticoagulant hollow fiber membrane is 35-15°, the surface pore size is ≤2.5μm, and the water flux is 89-93mL (based on 50mmHg and 200ml / min).

[0008] The present invention also provides a method for preparing an anticoagulant hemodialysis device, comprising the following steps: S1 Preparation of Silk Solution Additives and solvents are added to the reaction vessel and stirred until dissolved. Then, sulfone polymers are added and stirred until completely dissolved. Next, amino compounds are added and stirred until completely dissolved. After cooling, vacuuming and degassing are performed while continuously stirring until all bubbles are expelled, thus obtaining the silk liquid. S2 Preparation of Core Fluid Polyols and purified water are added to a reaction vessel and dissolved. Then, acid anhydrides containing double bonds are added and reacted at 40-60℃ for 1-3 hours to obtain a polymer solution containing double bonds and ester bonds. Solvents and alkaline substances are then added and mixed evenly to obtain the core liquid. S3 prepares a hemodialysis machine. The filament liquid prepared in S1 and the core liquid prepared in S2 are extruded together to form hollow fiber filaments, which are then separated into membranes in a coagulation bath and further processed to produce a hemodialyzer. The hemodialyzer includes a blood chamber and a dialysate chamber. The blood chamber includes an inner layer of hollow fiber membrane, and the dialysate chamber includes an outer layer of hollow fiber membrane. S4 prepares an anticoagulant hemodialysis machine. S4-1: Add catalyst and purified water to reaction vessel, stir to dissolve, then add hydrophilic compound containing carbon-carbon double bonds, stir to dissolve, and obtain reaction solution. S4-2 The reaction solution is pumped into the blood chamber of the hemodialyzer prepared in S3 by a peristaltic pump. After being treated with the reaction solution for 1-4 hours, it is washed with water and dried by microwave to obtain an anticoagulant hollow fiber membrane, which is then used to obtain an anticoagulant hemodialyzer.

[0009] As a further improvement of the present invention, the cooling temperature in S1 is 45-55°C; the microwave drying temperature in S5 is 40-90°C.

[0010] As a further improvement of the present invention, the additives in S1 include one or more of polyethylene glycol and polyvinylpyrrolidone.

[0011] Preferably, the additive in S1 is polyvinylpyrrolidone.

[0012] As a further improvement of the present invention, the polyol substance in S2 includes one or more of polyvinyl alcohol and polyethylene glycol, and the amount of the polyol substance added accounts for 0.1-2% of the purified water.

[0013] Preferably, the polyol in S2 is polyvinyl alcohol.

[0014] As a further improvement of the present invention, the acid anhydride containing double bonds in S2 includes one or more of acrylic anhydride and methacrylic anhydride, and the amount of acid anhydride containing double bonds added accounts for 0.2-12% of the purified water.

[0015] Preferably, the acid anhydride containing a double bond in S2 is methacrylic anhydride.

[0016] As a further improvement of the present invention, the solvents in S1 and S2 include one or more of N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, dimethylacetamide, and purified water; Preferably, the solvent in S1 and S2 is dimethylacetamide.

[0017] As a further improvement of the present invention, the post-processing process in S3 includes drying, yarn taking, yarn cutting, sintering, glue filling, cutting, and capping; when the yarn liquid and core liquid are extruded together, the pressure of the yarn liquid is 500-850 kPa, and the pressure of the core liquid is 0.5-1.5 kPa.

[0018] As a further improvement of the present invention, the catalyst in S4-1 includes one or more of ammonium persulfate and potassium persulfate, and the amount of the catalyst added accounts for 0.1-2% of the purified water.

[0019] Preferably, the catalyst in S4-1 is potassium persulfate.

[0020] As a further improvement of the present invention, the hydrophilic functional group of the hydrophilic compound containing carbon-carbon double bonds in S4-1 includes one or more of sulfonic acid group, hydroxyl group, carboxyl group, lactam group, and phospholipid group; the hydrophilic compound containing carbon-carbon double bonds includes one or more of 2-acrylamido-2-methylpropanesulfonic acid, 2-methacryloyloxyethylphosphocholine, and N-vinylpyrrolidone; the amount of the hydrophilic compound containing carbon-carbon double bonds added accounts for 1-20% of the purified water.

[0021] This invention also provides an application of an anticoagulant hemodialyzer in the field of blood purification.

[0022] The beneficial effects of this invention are: 1. The hollow fiber membrane prepared by this invention maintains the original pore size while giving it a long-lasting anticoagulation effect. At the same time, it increases the hydrophilicity of the hollow fiber membrane. In actual use, it can reduce protein adsorption, increase the antifouling performance of the product, and reduce or avoid the occurrence of coagulation in the product.

[0023] 2. This invention utilizes the reaction between hydroxyl groups in polyols and acid anhydrides containing double bonds to generate a polymer solution containing double and ester bonds, which can increase the hydrophilicity of hollow fiber membranes. After adding solvents and alkaline substances, a core fluid is formed.

[0024] 3. The silk solution of the present invention contains an amino compound, which provides reactive amino groups for the synthesis of network-structured polymers.

[0025] 4. This invention utilizes the reaction between the amino groups in the amino-containing compounds in the silk solution and the unreacted acid anhydrides containing double bonds in the core solution to generate a polymer containing carbon-carbon double bonds and amide bonds. Under the action of heating and alkaline substances, the double bonds of the polymer containing double bonds and ester bonds in the core solution and the double bonds of the polymer containing carbon-carbon double bonds and amide bonds in the silk solution react to generate a polymer containing amide bonds and amino groups, providing a polymer with reactive groups for the grafting reaction of hollow fiber membranes.

[0026] 5. This invention utilizes the carbon-carbon double bonds of hydrophilic compounds containing carbon-carbon double bonds and the amino groups of high molecular polymers containing amide and amino groups in the inner wall of hollow fiber membranes. Under the action of heating and a catalyst, an addition reaction occurs to form stable chemical bonds that are firmly bonded and not easily detached. In actual use, this effectively reduces the risk of blood clotting in hemodialysis machines, thereby reducing economic losses or physical harm to patients.

[0027] 6. The reactants required for this invention are inexpensive and readily available, the reaction conditions are mild, the reaction time is short, and the bonds are strong.

[0028] 7. The present invention provides an anticoagulant hemodialysis device, its preparation method and application. The prepared anticoagulant hollow fiber membrane has a contact angle of 35-15°, a surface pore size of ≤2.5μm, and a water flux of 89-93mL (based on 50mmHg and 200ml / min), and has a significant anticoagulant effect.

[0029] 8. The present invention provides an anticoagulant hemodialysis device, its preparation method and application. The prepared anticoagulant hollow fiber membrane is hydrophilic, and the water flux test shows a water flux of 89-93 mL (based on 50 mmHg and 200 ml / min). The coagulation and recalcification experiment shows that it has a significant anticoagulant effect. The equipment used is simple, easy and safe to operate, and the experimental cycle is short. Moreover, our company has mature post-processing technology, which is easy to industrialize. Attached Figure Description

[0030] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0031] Appendix Figure 1 This is a schematic diagram of the overall structure of the hemodialyzer prepared according to the present invention.

[0032] Appendix Figure 2 The attachment of the hemodialysis device prepared by this invention Figure 1 A cross-sectional view along the AA direction.

[0033] Appendix Figure 3 The attachment of the hemodialysis device prepared by this invention Figure 1 A schematic diagram of the cross-section along the BB direction.

[0034] Appendix Figure 4 This is the reaction equation for the present invention.

[0035] Appendix Figure 5 This is a contact angle test diagram for Comparative Example 1.

[0036] Appendix Figure 6 This is a contact angle test diagram from Example 1.

[0037] Appendix Figure 7 This is a scanning electron microscope (SEM) image of Comparative Example 1.

[0038] Appendix Figure 8 This is a scanning electron microscope (SEM) image of Example 1.

[0039] Appendix Figure 9Infrared spectra of Comparative Example 1 and Example 1.

[0040] Appendix Figure 10 The graph shows the coagulation and recalcification test results for Comparative Example 1 and Example 1. Implementation

[0041] The technical solutions in the embodiments of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention. Example 1

[0042] S1 Preparation of Silk Solution Six parts of polyvinylpyrrolidone and 74 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 85°C. The dissolution time was 4 hours. Then, 16 parts of polyethersulfone were added, and the mixture was heated and stirred for another 6 hours. Next, 4 parts of polyethyleneimine were added, and the mixture was heated and stirred for another 3 hours. After complete dissolution, the temperature was cooled to 50°C. The polyethersulfone mixture was degassed using a vacuum system for 10 hours to obtain the silk solution. S2 Preparation of Core Fluid One part of polyvinyl alcohol and 90 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 9 parts of methacrylic anhydride were added, and the mixture was reacted at 50°C for 2 hours to obtain a polymer containing double bonds and ester bonds. Then, dimethylacetamide and sodium hydroxide were added, with the ratio of dimethylacetamide, sodium hydroxide, and the polymer solution containing double bonds and ester bonds being 38:2:60. The mixture was stirred until it was uniformly dissolved and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap for 2 seconds. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. S4 prepares an anticoagulant hemodialysis machine. Dissolve 1.5 parts of potassium persulfate in 93.5 parts of purified water. Add 5 parts of 2-acrylamide-2-methylpropanesulfonic acid to the potassium persulfate solution at 5°C until completely dissolved to obtain the reaction solution. Circulate the reaction solution in the blood chamber of a hemodialyzer at 50°C for 2 hours to obtain the modified hemodialyzer. Clean the blood chamber and dialysate chamber of the modified hemodialyzer with purified water at 80°C for 15 minutes, and then microwave dry at 80°C to obtain the anticoagulant hemodialyzer.

[0043] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux. Example 2

[0044] S1 Preparation of Silk Solution Five parts of polyvinylpyrrolidone, one part of purified water, and 74 parts of dimethyl sulfoxide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm, the dissolution temperature was set to 80°C, and the dissolution time was 3 hours. Then, 16 parts of polyethersulfone were added and the mixture was heated and stirred for another 5 hours. Next, 4 parts of polyethyleneimine were added and the mixture was heated and stirred for another 2 hours. After complete dissolution, the temperature was cooled to 48°C, and the polyethersulfone mixture was degassed using a vacuum system for 9 hours to obtain the silk solution. S2 Preparation of Core Fluid One part of polyethylene glycol and 90 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 9 parts of methacrylic anhydride were added, and the mixture was reacted at 50°C for 1.5 hours to obtain a polymer containing double bonds and ester bonds. Dimethylacetamide and potassium hydroxide were added, with the ratio of dimethylacetamide, potassium hydroxide, and the polymer solution containing double bonds and ester bonds being 38:2:60. The mixture was stirred until it was uniformly dissolved and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1.5 s. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialysis machine. S4 prepares an anticoagulant hemodialysis machine. 1.5 parts of ammonium persulfate were dissolved in 93.5 parts of purified water. 5 parts of 2-methacryloyloxyethyl phosphocholine were added to the ammonium persulfate solution at 7°C and dissolved completely to obtain the reaction solution. The reaction solution was circulated in the blood chamber of a hemodialyzer at 50°C for 2 hours to obtain the modified hemodialyzer. The blood chamber and dialysate chamber of the modified hemodialyzer were circulated and washed with purified water at 75°C for 20 minutes, and then microwave-dried at 50°C to obtain the anticoagulant hemodialyzer.

[0045] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux. Example 3

[0046] S1 Preparation of Silk Solution Six parts of polyethylene glycol and 74 parts of N,N-dimethylformamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 85°C. The dissolution time was 4 hours. Then, 16 parts of polyethersulfone were added, and the mixture was heated and stirred for another 5 hours. Next, 4 parts of polyethyleneimine were added, and the mixture was heated and stirred for another 2 hours. After complete dissolution, the temperature was cooled to 52°C. The polyethersulfone mixture was degassed using a vacuum system for 10 hours to obtain the silk solution. S2 Preparation of Core Fluid One part of polyvinyl alcohol and 94 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 5 parts of acrylic anhydride were added, and the mixture was reacted at 50°C for 2 hours to obtain a polymer containing double bonds and ester bonds. N,N-dimethylformamide and sodium bicarbonate were added, with the ratio of N,N-dimethylformamide, sodium bicarbonate, and the polymer solution containing double bonds and ester bonds being 38:4:58. The mixture was stirred until homogeneous and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1 second. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. S4 prepares an anticoagulant hemodialysis machine. Dissolve 1.5 parts of potassium persulfate in 83.5 parts of purified water. Add 15 parts of N-vinylpyrrolidone to the potassium persulfate solution at 10°C until completely dissolved to obtain the reaction solution. Circulate the reaction solution in the blood chamber of a hemodialyzer at 50°C for 3 hours to obtain the modified hemodialyzer. Clean the blood chamber and dialysate chamber of the modified hemodialyzer with purified water at 70°C for 30 minutes, and then microwave dry at 75°C to obtain the anticoagulant hemodialyzer.

[0047] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux.

[0048] Example 4 S1 Preparation of Silk Solution Four parts of polyvinylpyrrolidone and 74 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 80°C. The dissolution time was 4 hours. Then, 20 parts of polyethersulfone were added, and the mixture was heated and stirred for another 8 hours. Next, 2 parts of methacrylamide gelatin were added, and the mixture was heated and stirred for another 3 hours. After complete dissolution, the temperature was cooled to 45°C. The polyethersulfone mixture was degassed using a vacuum system for 12 hours to obtain the silk solution. S2 Preparation of Core Fluid One part of polyvinyl alcohol and 92 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 7 parts of methacrylic anhydride were added, and the mixture was reacted at 50°C for 2 hours to obtain a polymer containing double bonds and ester bonds. Dimethylacetamide and potassium bicarbonate were added, with the ratio of dimethylacetamide, potassium bicarbonate, and the polymer solution containing double bonds and ester bonds being 38:4:58. The mixture was stirred until it was uniformly dissolved and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1.5 s. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialysis machine. S4 prepares an anticoagulant hemodialysis machine. Dissolve 1.5 parts of potassium persulfate in 94.5 parts of purified water. Add 4 parts of 2-acrylamide-2-methylpropanesulfonic acid to the potassium persulfate solution at 8°C until completely dissolved to obtain the reaction solution. Circulate the reaction solution in the blood chamber of a hemodialyzer at 50°C for 2 hours to obtain the modified hemodialyzer. Clean the blood chamber and dialysate chamber of the modified hemodialyzer with purified water at 85°C for 13 minutes, and then microwave dry at 70°C to obtain the anticoagulant hemodialyzer.

[0049] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux. Example 5

[0050] S1 Preparation of Silk Solution Five parts of polyethylene glycol and 72 parts of N-methylpyrrolidone were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 80°C. The dissolution time was 4 hours. Then, 18 parts of polyethersulfone were added, and the mixture was heated and stirred for another 6 hours. Next, 5 parts of methacryloyl hyaluronic acid were added, and the mixture was heated and stirred for another 2 hours. After complete dissolution, the temperature was cooled to 55°C. The polyethersulfone mixture was degassed using a vacuum system for 9 hours to obtain the silk solution. S2 Preparation of Core Fluid One part of polyvinyl alcohol and 95 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 4 parts of methacrylic anhydride were added, and the mixture was reacted at 50°C for 1.5 hours to obtain a polymer containing double bonds and ester bonds. N-methylpyrrolidone and potassium hydroxide were added. The ratio of N-methylpyrrolidone, sodium hydroxide, and the polymer solution containing double bonds and ester bonds was 38:2:60. The mixture was stirred and dissolved evenly. After degassing for 1 hour, the core liquid was obtained. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1 second. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. S4 prepares an anticoagulant hemodialysis machine. Dissolve 1.5 parts of potassium persulfate in 88.5 parts of purified water. Add 10 parts of 2-acrylamide-2-methylpropanesulfonic acid to the potassium persulfate solution at 12°C until completely dissolved to obtain the reaction solution. Circulate the reaction solution in the blood chamber of a hemodialyzer at 50°C for 3 hours to obtain the modified hemodialyzer. Clean the blood chamber and dialysate chamber of the modified hemodialyzer with purified water at 80°C for 20 minutes, and then microwave dry at 72°C to obtain the anticoagulant hemodialyzer.

[0051] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux. Example 6

[0052] S1 Preparation of Silk Solution Three parts of polyethylene glycol, two parts of purified water, and 71 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm, the dissolution temperature was set to 80°C, and the dissolution time was 3 hours. Then, 22 parts of polyethersulfone were added, and the mixture was heated and stirred for another 7 hours. Next, two parts of polyethyleneimine were added, and the mixture was heated and stirred for another 2 hours. After complete dissolution, the temperature was cooled to 50°C, and the polyethersulfone mixture was degassed using a vacuum system for 9 hours to obtain the silk solution. S2 Preparation of Core Fluid 0.5 parts of polyvinyl alcohol and 98.5 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 1 part of acrylic anhydride was added, and the mixture was reacted at 50°C for 1.5 hours to obtain a polymer containing double bonds and ester bonds. Dimethylacetamide and sodium hydroxide were added, with the ratio of dimethylacetamide, sodium hydroxide, and the polymer solution containing double bonds and ester bonds being 38:2:60. The mixture was stirred until it was uniformly dissolved and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 0.8 s. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialysis machine. S4 prepares an anticoagulant hemodialysis machine. One part of ammonium persulfate was dissolved in 89 parts of purified water. Ten parts of N-vinylpyrrolidone were added to the ammonium persulfate solution at 10°C until completely dissolved, yielding the reaction solution. The reaction solution was circulated in the blood chamber of a hemodialyzer at 50°C for 3 hours to obtain the modified hemodialyzer. The blood chamber and dialysate chamber of the modified hemodialyzer were then circulated and cleaned with purified water at 90°C for 10 minutes and dried by microwave at 76°C to obtain the anticoagulant hemodialyzer.

[0053] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux. Example 7

[0054] S1 Preparation of Silk Solution Four parts of polyethylene glycol, one part of water, and 73 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm, the dissolution temperature was set to 80°C, and the dissolution time was 4 hours. Then, 18 parts of polysulfone were added and the mixture was heated and stirred for another 6 hours. Next, 4 parts of polyethyleneimine were added and the mixture was heated and stirred for another 3 hours. After complete dissolution, the temperature was cooled to 52°C, and the polyethersulfone mixture was degassed using a vacuum system for 11 hours to obtain the silk solution. S2 Preparation of Core Fluid 1.5 parts of polyvinyl alcohol and 95 parts of purified water were added to a reaction vessel equipped with a stirrer. The dissolution speed was set to 20 rpm, and the mixture was dissolved for 1 hour. After dissolution, 3.5 parts of methacrylic anhydride were added, and the mixture was reacted at 50°C for 2 hours to obtain a polymer containing double bonds and ester bonds. Dimethylacetamide and sodium bicarbonate were added, with the ratio of dimethylacetamide, sodium bicarbonate, and the polymer solution containing double bonds and ester bonds being 38:4:58. The mixture was stirred until homogeneous and degassed for 1 hour to obtain the core liquid. S3 prepares a hemodialysis machine. Under pressures of 500 kPa and 0.8 kPa, filament liquid and core liquid at 50°C are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap for 2 seconds. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. S4 prepares an anticoagulant hemodialysis machine. Dissolve 1.5 parts of potassium persulfate in 93.5 parts of purified water. Add 5 parts of 2-methacryloyloxyethyl phosphocholine while the potassium persulfate solution is ice-cold at 15°C until completely dissolved to obtain the reaction solution. Circulate the reaction solution in the blood chamber of a hemodialyzer at 50°C for 2 hours to obtain the modified hemodialyzer. Clean the blood chamber and dialysate chamber of the modified hemodialyzer with purified water at 85°C for 15 minutes, and then microwave dry at 82°C to obtain the anticoagulant hemodialyzer.

[0055] S5 Test The anticoagulant hemodialyzer prepared by S4 was tested for contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification, and water flux.

[0056] Comparative Example 1 S1 Preparation of Silk Solution Six parts of polyethylene glycol and 78 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 85°C. The dissolution time was 4 hours. Then, 16 parts of polyethersulfone were added, and the mixture was heated and stirred for another 7 hours. After complete dissolution, the temperature was cooled to 50°C. The polyethersulfone mixture was degassed using a vacuum system for 9 hours to obtain the silk solution. S2 Preparation of Core Fluid Dimethylacetamide and purified water were mixed evenly at a ratio of 40:60 to obtain the core solution; S3 prepares a hemodialysis machine. Under pressures of 480 kPa and 0.7 kPa, a certain temperature of fiber solution and core solution are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap for 2 seconds. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. The blood chamber and dialysate chamber of the hemodialyzer are cleaned with purified water at 80°C for 15 minutes and then dried by microwave at 80°C to obtain hemodialyzer 1.

[0057] S4 Test The hemodialyzer 1 prepared by S3 was subjected to contact angle, scanning electron microscopy, infrared spectroscopy, coagulation and recalcification experiments, and water flux tests.

[0058] Comparative Example 2 S1 Preparation of Silk Solution Eight parts of polyvinylpyrrolidone and 76 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 85°C. The dissolution time was 6 hours. Then, 16 parts of polyethersulfone were added and the mixture was heated and stirred for another 6 hours. After complete dissolution, the temperature was cooled to 48°C. The polyethersulfone mixture was degassed using a vacuum system for 15 hours to obtain the silk solution. S2 Preparation of Core Fluid Dimethylacetamide and purified water were mixed evenly at a ratio of 42:58 to obtain the core solution; S3 prepares a hemodialysis machine. Under pressures of 480 kPa and 0.7 kPa, a certain temperature of fiber solution and core solution are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1.5 s. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. The blood chamber and dialysate chamber of the hemodialyzer are cleaned with purified water at 70°C for 30 min and then dried by microwave at 50°C to obtain hemodialyzer 2.

[0059] S4 Test The hemodialyzer 2 prepared by S3 was subjected to contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification experiment and water flux test.

[0060] Comparative Example 3 S1 Preparation of Silk Solution Five parts of polyvinylpyrrolidone, one part of water, and 76 parts of dimethylacetamide were added to a reaction vessel equipped with a mechanical stirrer. The dissolution speed was set to 30 rpm and the dissolution temperature was set to 80°C. The dissolution time was 4 hours. Then, 18 parts of polyethersulfone were added, and the mixture was heated and stirred for another 7 hours. After complete dissolution, the temperature was cooled to 52°C. The polyethersulfone mixture was degassed using a vacuum system for 9 hours to obtain the silk solution. S2 Preparation of Core Fluid Dimethylacetamide and purified water were mixed evenly at a ratio of 35:65 to obtain the core solution; S3 prepares a hemodialysis machine. Under pressures of 480 kPa and 0.7 kPa, a certain temperature of fiber solution and core solution are extruded together through a spinneret to form hollow fiber filaments. After leaving the spinneret, the hollow fiber filaments are immersed in a coagulation bath after passing through an air gap of 1 second. Phase separation occurs in the coagulation bath to form a membrane, which is the initial hollow fiber membrane. The initial hollow fiber membrane is collected and processed through drying, fiber winding, fiber cutting, sintering, glue filling, cutting, and capping to prepare a hemodialyzer. The blood chamber and dialysate chamber of the hemodialyzer are cleaned with purified water at 90°C for 10 minutes and then dried by microwave at 75°C to obtain hemodialyzer 3.

[0061] S4 Test The hemodialyzer 3 prepared by S3 was subjected to contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification experiment and water flux test.

[0062] Table 1. Water flux test results

[0063] Examples 1 to 7 and Comparative Examples 1 to 3 were subjected to "contact angle, scanning electron microscopy, infrared spectroscopy, coagulation recalcification experiment and water flux test". The results of the water flux test are shown in Table 1. The contact angle, scanning electron microscopy, infrared spectroscopy and coagulation recalcification experiment are illustrated with the accompanying drawings based on the best example 1.

[0064] Taking 50 mmHg and 200 ml / min as an example, the water flux can reflect the ultrafiltration capacity of the hemodialysis machine. The anticoagulant hemodialysis machine provided by the present invention has significantly enhanced ultrafiltration capacity, with a water flux of 89-93 ml, as shown in Table 1.

[0065] In Comparative Examples 1-3, the contact angle range of the hollow fiber membrane was 45-50°, see Figure 5 The contact angle range of the anticoagulant hollow fiber membranes in Examples 1-7 was 15-35°. The contact angle of Examples 1-7 decreased from 45.519° in Comparative Example 1 to 15.067°, indicating that the anticoagulant hollow fiber membrane has good hydrophilicity. Figure 6 .

[0066] In Comparative Examples 1-3, the surface pore size of the hollow fiber membrane was ≤2.1 μm, see... Figure 7 In Examples 1-7, the anticoagulant hollow fiber membranes had a surface pore size ≤2.5 μm, which remained essentially unchanged with a slight increase. Consequently, the water flux of the hemodialysis machine also increased slightly. Figure 8 .

[0067] Infrared spectra showed that the hollow fiber membranes in Comparative Examples 1-3 had a wavelength of 1728 cm⁻¹. -1 The vibrational peak at 1038 cm⁻¹ is absent due to the absence of -C=O bonds. -1There is no vibrational peak for -CN- bonds, while the anticoagulant hollow fiber membranes of Examples 1-7 show a peak at 1728 cm⁻¹. -1 and 1038cm -1 The presence of vibrational peaks for -C=O and -CN- bonds at these locations indicates that the hydrophilic compound containing a carbon-carbon double bond has successfully reacted. (See...) Figure 9 .

[0068] The hollow fiber membranes in Comparative Examples 1-3 showed no significant anticoagulant effect, while the anticoagulant hollow fiber membranes in Examples 1-7 exhibited anticoagulant effects, which were superior to those in Comparative Examples 1-3. Figure 10 The reaction equation for this invention is shown below. Figure 4 .

[0069] It is understood that the above specific description of the present invention is only for illustrating the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that modifications or equivalent substitutions can still be made to the present invention to achieve the same technical effect; as long as the use needs are met, they are all within the protection scope of the present invention.

[0070] Finally, it should be noted that in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0071] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0072] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0073] The above are the implementation methods of the embodiments of this application. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the embodiments of this application, and these improvements and modifications are also considered to be within the protection scope of this application.

Claims

1. An anticoagulant hemodialysis device, mainly comprising a dialyzer shell, a dialysis membrane, end caps, O-rings, and a protective cap, characterized in that, The dialysis membrane is an anticoagulant hollow fiber membrane. The anticoagulant hollow fiber membrane is prepared by using sulfone polymers, amino compounds, and additives as the main raw materials. It is first prepared by wet spinning and solidification into a membrane, and then treated with a hydrophilic compound containing carbon-carbon double bonds and a catalyst. The wet spinning process includes the co-extrusion of the fiber solution and the core solution. The silk solution comprises the following components by mass: 16-24 parts of sulfone polymer, 2-7 parts of amino compound, 3-8 parts of auxiliaries, and 61-80 parts of solvent; The core fluid comprises the following components by mass: 50-90 parts of a polymer solution containing double bonds and ester bonds, 9-45 parts of a solvent, and 1-5 parts of an alkaline substance. The polymer solution containing double bonds and ester bonds is obtained by adding polyols and purified water to a reaction vessel, dissolving them, and then adding an acid anhydride containing double bonds. The amount of polyols added is 0.1-2% of the purified water, and the amount of acid anhydride containing double bonds added is 0.2-12% of the purified water. The sulfone polymers include polysulfone or polyethersulfone; the amino-containing compounds include one or more of methacrylamide gelatin, methacrylamide hyaluronic acid, methacrylamide heparin, and polyethyleneimine; the hydrophilic compounds containing carbon-carbon double bonds include one or more of 2-acrylamido-2-methylpropanesulfonic acid, 2-methacryloyloxyethyl phosphocholine, and N-vinylpyrrolidone.

2. The anticoagulant hemodialysis device according to claim 1, characterized in that, The anticoagulant hollow fiber membrane is hydrophilic, with a contact angle of 35-15°, a surface pore size ≤2.5μm, and a water flux of 89-93mL. The water flux is measured at 50mmHg and 200ml / min.

3. A method for preparing an anticoagulant hemodialysis device according to any one of claims 1 to 2, characterized in that, Includes the following steps: S1 Preparation of Silk Solution Add the additives and solvents into the reaction vessel, stir to dissolve, then add the sulfone polymer and stir until completely dissolved, then add the amino compound and stir until completely dissolved. After cooling to 45-55℃, perform vacuuming and bubble removal while continuously stirring until all bubbles are removed to obtain the silk liquid. S2 Preparation of Core Fluid Polyols and purified water are added to a reaction vessel and dissolved. Then, acid anhydrides containing double bonds are added and reacted at 40-60℃ for 1-3 hours to obtain a polymer solution containing double bonds and ester bonds. Solvents and alkaline substances are then added and mixed evenly to obtain the core liquid. S3 prepares a hemodialysis machine. The silk liquid prepared by S1 and the core liquid prepared by S2 are extruded together to form hollow fiber filaments, which are then separated into membranes in a coagulation bath and then processed into a hemodialyzer through a post-processing process. The hemodialyzer includes a blood chamber and a dialysate chamber, with the inner cavity of the hollow fiber membrane forming the blood chamber; S4 prepares an anticoagulant hemodialysis machine. S4-1: Add catalyst and purified water to reaction vessel, stir to dissolve, then add hydrophilic compound containing carbon-carbon double bonds, stir to dissolve thoroughly, and obtain reaction solution; S4-2 The reaction solution is pumped into the blood chamber of the hemodialyzer prepared in S3 by a peristaltic pump. After being treated with the reaction solution for 1-4 hours, it is washed with water and dried by microwave at 40-90℃ to obtain an anticoagulant hollow fiber membrane, which is then used to obtain an anticoagulant hemodialyzer.

4. The method for preparing an anticoagulant hemodialysis device according to claim 3, characterized in that, The additives in S1 include one or more of polyethylene glycol and polyvinylpyrrolidone.

5. The method for preparing an anticoagulant hemodialysis device according to claim 3, characterized in that, The polyols in S2 include one or more of polyvinyl alcohol and polyethylene glycol; the alkaline substances include one or more of sodium bicarbonate, potassium bicarbonate, potassium hydroxide, and sodium hydroxide.

6. The method for preparing an anticoagulant hemodialysis device according to claim 3, characterized in that, The acid anhydride containing a double bond in S2 includes one or more of acrylic anhydride and methacrylic anhydride.

7. The method for preparing an anticoagulant hemodialysis device according to claim 3, characterized in that, The solvents in S1 and S2 include one or more of N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, dimethylacetamide, and purified water; the catalyst in S4-1 includes one or more of ammonium persulfate and potassium persulfate, and the amount of catalyst added accounts for 0.1-2% of the purified water.

8. The method for preparing an anticoagulant hemodialysis device according to claim 3, characterized in that, The post-processing in S3 includes drying, yarn taking, yarn cutting, sintering, glue filling, cutting, and capping; when the yarn liquid and core liquid are extruded together, the pressure of the yarn liquid is 500-850 kPa, and the pressure of the core liquid is 0.5-1.5 kPa.

9. The method for preparing an anticoagulant hemodialysis device according to any one of claims 4-8, characterized in that, The hydrophilic functional groups of the hydrophilic compound containing carbon-carbon double bonds in S4-1 include one or more of sulfonic acid groups, hydroxyl groups, carboxyl groups, lactam groups, and phospholipid groups; the amount of the hydrophilic compound containing carbon-carbon double bonds added accounts for 1-20% of the purified water.

10. The application of any one of the anticoagulant hemodialyzers according to claims 1-2 in the field of blood purification.

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