Blood purification membrane and its preparation method and application

Abstract

The present invention relates to a blood purification membrane and a preparation method and application thereof; the preparation method comprises the following steps: mixing a plant polyphenol compound, ferrocyanide, a first acidic substance and water to obtain an aqueous solution of a metal organic complex; mixing a polymer, a porogen and a first organic solvent, further adding a polyamine monomer to obtain a polymer solution; mixing the aqueous solution of the metal organic complex with the polymer solution to obtain a casting solution; and extruding the casting solution and an acidic inner gel bath through a spinneret, entering an acidic outer gel bath for phase inversion spinning, and obtaining a blood purification membrane, wherein the inner gel bath comprises a first zinc salt, and the outer gel bath comprises a second zinc salt and a second organic solvent. The blood purification membrane obtained by the preparation method realizes the integration of dialysis and perfusion, and can better purify blood.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a blood purification membrane and a preparation method and application thereof. Background Art

[0002] Blood purification refers to the process of removing pathogenic substances from the patient's blood through a blood purification device, thereby achieving the purpose of treating the disease. Methods include hemodialysis, hemofiltration, hemoperfusion, plasma exchange, immunoadsorption, etc. Since the problem of urgent kidney shortage is difficult to solve in the short term, blood purification has become one of the main means of treating uremia.

[0003] In traditional dialyzers, the average pore size of the membrane is between 1nm and 100nm, which can effectively remove small molecule toxins and some medium molecule toxins in the blood, but cannot remove large molecule toxins and protein-bound toxins. Therefore, patients still need blood perfusion during hemodialysis. When hemodialysis and hemoperfusion are used together, generally two hours of blood perfusion and hemodialysis are performed first, and then the perfusion device is removed for blood return. Two hours of hemodialysis alone is performed during which the priming fluid prefilling and blood return processes are required. The operation is very complicated and puts a heavy burden on the patient's cardiovascular and other organs, resulting in an increased incidence of complications, reduced quality of life of patients, and even reduced survival time of patients. Summary of the invention

[0004] Based on this, it is necessary to provide a blood purification membrane and its preparation method and application to address the above problems. The blood purification membrane obtained by the preparation method can remove small molecule toxins and medium molecule toxins in the blood through dialysis, and remove large molecule toxins and protein-bound toxins in the blood through adsorption, thereby realizing the integration of dialysis and perfusion and better purifying the blood.

[0005] The present invention provides a method for preparing a blood purification membrane, comprising the following steps:

[0006] Mixing the plant polyphenol compound, ferrocyanide, a first acidic substance and water to obtain an aqueous solution of a metal organic complex;

[0007] Mixing a polymer, a porogen and a first organic solvent, and further adding a polyamine monomer to obtain a polymer solution;

[0008] mixing the aqueous solution of the metal organic complex with the polymer solution to obtain a casting solution; and

[0009] The casting solution and the acidic inner gel bath are extruded through a spinneret and enter an acidic outer gel bath for phase inversion spinning to obtain a blood purification membrane, wherein the inner gel bath comprises a first zinc salt, and the outer gel bath comprises a second zinc salt and a second organic solvent.

[0010] In one embodiment, in the step of mixing the plant polyphenol compound, ferrocyanide, a first acidic substance and water, the mass ratio of the plant polyphenol compound, the ferrocyanide, the first acidic substance and the water is (1-5):(0.5-3):(1-5):(9-11).

[0011] In one embodiment, in the step of mixing the polymer, the porogen and the first organic solvent, the mass ratio of the polymer, the porogen and the first organic solvent is (7-30):(0.5-15):(55-92.5);

[0012] And / or, the mass fraction of the polyamine monomer in the polymer solution is 0.8%-10%.

[0013] In one embodiment, in the step of mixing the aqueous solution of the metal-organic complex with the polymer solution, the mass ratio of the aqueous solution of the metal-organic complex to the polymer solution is 0.02:1-0.20:1.

[0014] In one embodiment, the mass fraction of the first zinc salt in the inner gel bath is 0.40%-6%;

[0015] and / or, the mass fraction of the second zinc salt in the outer gel bath is 0.40%-6%, and the mass fraction of the second organic solvent in the outer gel bath is less than or equal to 50%;

[0016] And / or, the inner gel bath further includes a second acidic substance, the mass fraction of which is 0.1%-5%, and the outer gel bath further includes a third acidic substance, the mass fraction of which is 0.1%-5%.

[0017] In one embodiment, the plant polyphenol compound is selected from at least one of tannic acid, gallic acid, tea polyphenols, catechol or anthocyanidin;

[0018] And / or, the ferrocyanide is selected from at least one of sodium ferrocyanide, potassium ferrocyanide or ammonium ferrocyanide;

[0019] and / or, the polymer is selected from at least one of polysulfone, polyethersulfone, polymethyl methacrylate, polyamide, polyvinylidene fluoride, polystyrene or vinyl alcohol;

[0020] And / or, the porogen is selected from at least one of polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer 407, diethylene glycol, triethylene glycol or polyethylene oxide;

[0021] And / or, the polyamine monomer is at least one selected from o-phenylenediamine, m-phenylenediamine, p-phenylenediamine, diethylenetriamine, triethylenetetramine or polyethyleneimine;

[0022] And / or, the first zinc salt and the second zinc salt are independently selected from at least one of zinc chloride, zinc sulfate or zinc nitrate.

[0023] A blood purification membrane is prepared by the above-mentioned method for preparing a blood purification membrane, wherein the blood purification membrane comprises a polymer-based membrane and a bimetallic complex, wherein the pore size of the polymer-based membrane pores gradually increases from the center of the membrane to the membrane surface, and the bimetallic complex is distributed on the outer surface, inner surface and internal pore surface of the polymer-based membrane.

[0024] In one embodiment, the bimetallic complex forms a network cross-linked structure on the outer surface, inner surface and internal pore surface of the polymer-based membrane, and the mass fraction of the bimetallic complex in the blood purification membrane is 5%-20%.

[0025] In one embodiment, the initial contact angle of 2 microliters of water on the surface of the blood purification membrane is less than 60°, and the infiltration time of 2 microliters of water on the surface of the blood purification membrane is less than or equal to 20 seconds.

[0026] An application of the blood purification membrane as described above in a blood purification device.

[0027] In the preparation method of the blood purification membrane provided by the present invention, first, the plant polyphenol compound reacts with ferrocyanide to form a metal complex; secondly, the metal complex is dissolved in the casting solution under the synergistic solubilizing effect of the first acidic substance and water, and at the same time, the polyamine monomer in the polymer solution and the plant polyphenol compound undergo a weak cross-linking reaction, thereby in situ introducing the metal complex into the casting solution; thirdly, in the process of phase transformation, the first zinc salt in the inner gel bath and the second zinc salt in the outer gel bath can further complex with the metal complex to form a bimetallic complex, and then a blood purification membrane with a stable cross-linked network and a bimetallic complex is obtained through a hierarchical self-assembly reaction. Thus, the preparation method of the blood purification membrane provided by the present invention, while regulating the blood purification membrane to form a continuous network microporous structure, will in situ grow bimetallic complexes on the inner surface, outer surface and internal pore surface of the membrane, greatly improving the load and load stability of the bimetallic complex in the blood purification membrane.

[0028] In addition, the preparation method of the blood purification membrane provided by the present invention can multi-dimensionally regulate the dialysis removal performance of the blood purification membrane for small molecule toxins, medium molecule toxins and the specific adsorption removal performance of large molecule toxins through a rich combination of ferrocyanide and zinc salts, thereby broadening the designability of the structure and function of the blood purification membrane, as well as the designability and economic feasibility of the blood purification membrane structure.

[0029] In the blood purification membrane provided by the present invention, the bimetallic complex is stably, evenly and highly loaded on the inner surface, outer surface and internal pore surface of the membrane, and can remove small molecule toxins and medium molecule toxins in the blood through dialysis, and remove large molecule toxins and protein-bound toxins in the blood through adsorption, thereby realizing the integration of dialysis and perfusion, and better purifying the blood. In addition, the blood purification membrane provided by the present invention has good blood compatibility and hydrophilicity, effectively reducing the adhesion of proteins to platelets, and the plant polyphenol compounds and polyamine monomers increase the stability of the bimetallic complex in the blood purification membrane through cross-linking and anchoring, reduce dissolution, and improve biosafety. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a surface scanning electron micrograph of the polyethersulfone blood purification membrane prepared in Example 1;

[0031] Figure 2 This is a scanning electron microscopic image of a partially enlarged cross section of the polyethersulfone blood purification membrane prepared in Example 1;

[0032] Figure 3 This is a scanning electron microscopic image of a cross section of the polyethersulfone blood purification membrane prepared in Example 1;

[0033] Figure 4 This is a test diagram of the surface water drop contact angle of the polyethersulfone blood purification membrane prepared in Example 1;

[0034] Figure 5 This is a curve diagram showing the change of the surface water drop contact angle of the polyethersulfone blood purification membrane prepared in Example 1 over time;

[0035] Figure 6 This is a surface scanning electron microscope image of the polyethersulfone blood purification membrane prepared in Comparative Example 1;

[0036] Figure 7 This is a scanning electron microscope image of a partially enlarged cross section of the polyethersulfone blood purification membrane prepared in Comparative Example 1;

[0037] Figure 8 This is a scanning electron micrograph of a cross section of the polyethersulfone blood purification membrane prepared in Comparative Example 1;

[0038] Fig. 9 This is a test diagram of the surface water drop contact angle of the polyethersulfone blood purification membrane prepared in Comparative Example 1;

[0039] Fig.10 This is a curve chart showing the change of the surface water drop contact angle of the polyethersulfone blood purification membrane prepared in Comparative Example 1 over time. DETAILED DESCRIPTION

[0040] The blood purification membrane provided by the present invention and its preparation method and application will be further described below.

[0041] The method for preparing the blood purification membrane provided by the present invention comprises the following steps:

[0042] S10, mixing the plant polyphenol compound, ferrocyanide, the first acidic substance and water to obtain an aqueous solution of the metal organic complex; mixing the polymer, the porogen and the first organic solvent, and further adding a polyamine monomer to obtain a polymer solution;

[0043] S20, mixing an aqueous solution of the metal organic complex with a polymer solution to obtain a casting solution; and

[0044] S30, extruding the casting solution and the acidic inner gel bath through a spinneret, and entering the acidic outer gel bath for phase inversion spinning to obtain a blood purification membrane.

[0045] It can be understood that the blood purification membrane prepared by the preparation method of the blood purification membrane provided by the present invention is formed as a hollow fiber membrane. In the preparation method of the blood purification membrane, first, in step S10, the plant polyphenol compound reacts with ferrocyanide to form a metal complex; secondly, the metal complex is dissolved in the casting liquid under the synergistic solubilizing effect of the first acidic substance and water, and at the same time, in step S20, the polyamine monomer in the polymer solution reacts with the plant polyphenol compound to undergo a weak cross-linking reaction, thereby introducing the metal complex in situ into the casting liquid; thirdly, in step S30, the first zinc salt in the inner gel bath and the second zinc salt in the outer gel bath can further complex with the metal complex to form a bimetallic complex, and then a blood purification membrane having a stable cross-linked network and a bimetallic complex is obtained through a hierarchical self-assembly reaction.

[0046] In step S10, the plant polyphenol compound and ferrocyanide undergo a complex reaction. In one embodiment, the plant polyphenol compound is selected from at least one of tannic acid, gallic acid, tea polyphenols, catechol or anthocyanidins; the ferrocyanide is selected from at least one of sodium ferrocyanide, potassium ferrocyanide or ammonium ferrocyanide; the first acidic substance is selected from at least one of concentrated hydrochloric acid, concentrated sulfuric acid or concentrated nitric acid; in order to better form a metal complex, the mass ratio of the plant polyphenol compound, ferrocyanide, the first acidic substance and water is (1-5):(0.5-3):(1-5):(9-11).

[0047] In one embodiment, in the step of mixing the plant polyphenol compound, ferrocyanide, the first acidic substance and water, the temperature is 20°C-50°C.

[0048] In the polymer solution, in order to avoid cross-linking of the polyamine monomer and the polymer chain segments and not affect each other's solubility, the polymer is first dissolved in an organic solvent and then the polyamine monomer is added. The polymer is preferably selected from at least one of polysulfone, polyethersulfone, polymethyl methacrylate, polyamide, polyvinylidene fluoride, polystyrene or vinyl alcohol; the porogen is preferably selected from at least one of polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer 407, diethylene glycol, triethylene glycol or polyethylene oxide; the first organic solvent is preferably selected from at least one of triethyl phosphate, tripropyl phosphate, dimethylformamide or dimethylacetamide; in order to better obtain a homogeneous solution, the mass ratio of the polymer, the porogen and the first organic solvent is (7-30):(0.5-15):(55-92.5).

[0049] In one embodiment, in the step of mixing the polymer, the porogen and the first organic solvent, the temperature is 60°C to 120°C.

[0050] In one embodiment, the polyamine monomer is selected from at least one of o-phenylenediamine, m-phenylenediamine, p-phenylenediamine, diethylenetriamine, triethylenetetramine or polyethyleneimine; and the mass fraction of the polyamine monomer in the polymer solution is 0.8%-10%.

[0051] In step S20, the mass ratio of the aqueous solution of the metal organic complex to the polymer solution is preferably 0.02:1-0.20:1.

[0052] In step S30, the inner gel bath comprises a first zinc salt. In one embodiment, the first zinc salt is selected from at least one of zinc chloride, zinc sulfate or zinc nitrate. The mass fraction of the first zinc salt in the inner gel bath is 0.40%-6%.

[0053] The inner gel bath also includes a second acidic substance. In one embodiment, the second acidic substance is selected from at least one of concentrated hydrochloric acid, concentrated sulfuric acid or concentrated nitric acid; the mass fraction of the second acidic substance in the inner gel bath is 0.1%-5%.

[0054] The outer gel bath includes a second zinc salt and a second organic solvent. In one embodiment, the second zinc salt is selected from at least one of zinc chloride, zinc sulfate or zinc nitrate. It is understandable that the first zinc salt and the second zinc salt may be of the same or different types.

[0055] In one embodiment, the mass fraction of the second zinc salt in the outer gel bath is 0.40%-6%; it can be understood that the mass fraction of the first zinc salt in the inner gel bath and the mass fraction of the second zinc salt in the outer gel bath may be the same or different, and preferably the mass fraction of the first zinc salt in the inner gel bath is greater than the mass fraction of the second zinc salt in the outer gel bath.

[0056] The preparation method of the blood purification membrane provided by the present invention can multi-dimensionally regulate the dialysis removal performance of the blood purification membrane for small molecule toxins, medium molecule toxins and the specific adsorption removal performance of large molecule toxins through a rich combination of ferrocyanide and zinc salt, thereby broadening the designability of the blood purification membrane structure and function, as well as the designability and economic feasibility of the blood purification membrane structure.

[0057] In one embodiment, the mass fraction of the second organic solvent in the outer gel bath is less than or equal to 50%.

[0058] The outer gel bath also includes a third acidic substance. In one embodiment, the third acidic substance is selected from at least one of concentrated hydrochloric acid, concentrated sulfuric acid or concentrated nitric acid; the mass fraction of the third acidic substance in the outer gel bath is 0.1%-5%.

[0059] In one embodiment, the obtained blood purification membrane is immersed in an external gel bath for 1 hour to 24 hours, then immersed in water for 3 hours to 24 hours, and finally taken out and dried at 15° C. to 40° C.

[0060] The preparation method of the blood purification membrane provided by the present invention, while regulating the blood purification membrane to form a continuous network microporous structure, in situ grows bimetallic complexes on the inner surface, outer surface and internal pore surface of the membrane, greatly improving the loading amount and loading stability of the bimetallic complex in the blood purification membrane.

[0061] The present invention also provides a blood purification membrane, which is prepared by the above blood purification membrane preparation method, and the blood purification membrane includes a polymer-based membrane and a bimetallic complex, wherein the pore size of the polymer-based membrane pores gradually increases from the center of the membrane to the membrane surface, and the bimetallic complex is distributed on the outer surface, inner surface and internal pore surface of the polymer-based membrane.

[0062] In the blood purification membrane provided by the present invention, the bimetallic complex is stably, evenly and highly loaded on the inner surface, outer surface and internal pore surface of the membrane, and can remove small molecule toxins and medium molecule toxins in the blood through dialysis, and remove large molecule toxins and protein-bound toxins in the blood through adsorption, thereby realizing the integration of dialysis and perfusion and better purifying the blood.

[0063] In one embodiment, the pore size of the blood purification membrane is 0.5 nm-100 nm.

[0064] In one embodiment, the bimetallic complex forms a network cross-linked structure on the surface of the polymer membrane and the surface of the internal pores, and the mass fraction of the bimetallic complex in the blood purification membrane is 5%-20%.

[0065] In one embodiment, the initial contact angle of 2 microliters of water on the surface of the blood purification membrane is less than 60°, and the infiltration time of 2 microliters of water on the surface of the blood purification membrane is less than or equal to 20 seconds.

[0066] The blood purification membrane provided by the present invention has good blood compatibility and hydrophilicity, effectively reduces the adhesion of proteins to platelets, and the plant polyphenol compounds and polyamine monomers increase the stability of the bimetallic complex in the blood purification membrane through cross-linking and anchoring, reduces dissolution, and improves biosafety.

[0067] The present invention also provides an application of the above-mentioned blood purification membrane in a blood purification device.

[0068] The present invention also provides an application of the blood purification membrane as described above in a water treatment device.

[0069] Hereinafter, the blood purification membrane and its preparation method and application will be further described through the following specific examples.

[0070] Example 1

[0071] At 30°C, 5 g of potassium ferrocyanide, 20 g of tannic acid, and 10 mL of hydrochloric acid were fully dissolved in 50 mL of aqueous solution to obtain an organic metal complex aqueous solution.

[0072] At 80° C., 75 g of polyethersulfone, 15 g of polyvinylpyrrolidone, and 410 g of dimethylacetamide were mixed and stirred uniformly, and then 10 g of polyethyleneimine was added to obtain a polymer solution.

[0073] 50 g of an organic metal complex aqueous solution was added dropwise to the above polymer solution to obtain a casting solution.

[0074] At 60°C, 2L of water, 80g of zinc chloride, and 60mL of hydrochloric acid were mixed to obtain an inner gel bath agent; 480mL of water, 20g of zinc chloride, 15mL of hydrochloric acid, and 20mL of dimethylacetamide solvent were mixed to obtain an outer gel bath agent; the casting liquid and the inner gel bath agent were extruded through a spinneret, entered into the outer gel bath agent for phase inversion spinning, soaked for 5h and then soaked in deionized water for 12h, and dried at room temperature to obtain a polyethersulfone blood purification membrane.

[0075] The polyethersulfone blood purification membrane comprises a polyethersulfone-based membrane and a bimetallic complex, wherein, for example Figure 1 and Figure 2 As shown, part of the bimetallic complex is distributed on the outer and inner surfaces of the polymer-based membrane, and the other part is attached to the pore surface inside the polymer-based membrane. Figure 3 As shown in the figure, the pore size of the polyethersulfone-based membrane increases from the center of the membrane to the surface of the membrane.

[0076] The obtained polyethersulfone blood purification membrane was tested for performance, and the average pore size of the membrane pores was 40 nm. Figure 4 As shown in Figure 2, the initial contact angle of a 2 μl water droplet on the surface is 44.4°. Figure 5 As shown, the infiltration time is 15s and the ultrafiltration coefficient is 17.6mL·mmHg - 1 h -1 The clearance rates (CR) of small molecular weight toxins urea and creatinine were 190 mL min -1 、186mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate was 77 mg / g and 133 mg / g, respectively. -1 , 182mg·g -1 The activated partial thromboplastin time (APTT) of the polyethersulfone blood purification membrane is more than 240 seconds, and the thrombin time (TT) is 27 seconds, which has excellent anti-coagulation properties.

[0077] Example 2

[0078] Example 2 was carried out with reference to Example 1, except that the polymer was polysulfone.

[0079] The performance of the obtained polysulfone blood purification membrane was tested. The average pore size of the membrane pores was 42nm, the initial contact angle of a 2 microliter water droplet on the surface was 40°, the infiltration time was 12s, and the ultrafiltration coefficient was 18.0mL·mmHg -1 h -1 The clearance rates (CR) of small molecular weight toxins urea and creatinine were 185 mL min -1 、188mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate is 80 mg / g and 143 mg / g, respectively. -1 , 190mg·g -1 The activated partial thromboplastin time of the polysulfone blood purification membrane is more than 260 seconds, and the thrombin time is 28 seconds, which has excellent anti-coagulation properties.

[0080] Example 3

[0081] At 30°C, 10 g of ammonium ferrocyanide, 15 g of gallic acid, and 10 mL of sulfuric acid were fully dissolved in 50 mL of aqueous solution to obtain an aqueous solution of a metal organic complex.

[0082] At 80° C., 90 g of polyvinylidene fluoride, 15 g of polyvinyl pyrrolidone, and 395 g of triethyl phosphate were mixed and stirred evenly, and then 15 g of p-phenylenediamine was added to obtain a polymer solution.

[0083] 10 g of an organic metal complex aqueous solution was added dropwise to the above polymer solution to obtain a casting solution.

[0084] At 60°C, 2L of water, 60g of zinc chloride, and 20mL of hydrochloric acid were mixed to obtain an inner gel bath agent; 460mL of water, 15g of zinc chloride, 5mL of hydrochloric acid, and 40mL of triethyl phosphate solvent were mixed to obtain an outer gel bath agent; the casting liquid and the inner gel bath agent were extruded through a spinneret, entered into the outer gel bath agent for phase inversion spinning, soaked for 5h and then soaked in deionized water for 12h, and dried at room temperature to obtain a polyvinylidene fluoride blood purification membrane.

[0085] The performance of the obtained polyvinylidene fluoride blood purification membrane was tested. The average pore size of the membrane pores was 36nm, the initial contact angle of a 2 microliter water droplet on the surface was 45°, the infiltration time was 13s, and the ultrafiltration coefficient was 18.0mL·mmHg -1 h -1 The clearance rates (CR) of small molecular weight toxins urea and creatinine were 185 mL min -1 、188mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate is 83 mg / g and 140 mg / g, respectively. -1 , 174mg·g -1 The activated partial thromboplastin time of the polyvinylidene fluoride blood purification membrane is more than 230 seconds, and the thrombin time is 25 seconds, which has excellent anti-coagulation properties.

[0086] Example 4

[0087] At 30°C, 9 g of potassium ferrocyanide, 30 g of tea polyphenols, and 12 mL of nitric acid were fully dissolved in 90 mL of aqueous solution to obtain an aqueous solution of a metal organic complex.

[0088] At 80° C., 90 g of polymethyl methacrylate, 15 g of polyethylene glycol, and 395 g of dimethylformamide were mixed and stirred evenly, and then 50 g of m-phenylenediamine was added to obtain a polymer solution.

[0089] 100 g of an organic metal complex aqueous solution was added dropwise to the above polymer solution to obtain a casting solution.

[0090] At 60°C, 2L of water, 60g of zinc sulfate, and 20mL of sulfuric acid were mixed to obtain an inner gel bath agent, and 470mL of water, 30g of zinc chloride, 3mL of sulfuric acid, and 30mL of dimethylformamide solvent were mixed to obtain an outer gel bath agent; the casting liquid and the inner gel bath agent were extruded through a spinneret, entered into the outer gel bath agent for phase inversion spinning, soaked for 6h and then soaked in deionized water for 10h, and dried at room temperature to obtain a polyvinylidene fluoride blood purification membrane.

[0091] The performance of the obtained polyvinylidene fluoride blood purification membrane was tested. The average pore size of the membrane pores was 30nm, the initial contact angle of a 2 microliter water droplet on the surface was 42°, the infiltration time was 15s, and the ultrafiltration coefficient was 17.0mL·mmHg -1 h -1 The clearance rates (CR) of small molecular weight toxins urea and creatinine were 178 mL min -1 、175mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate is 90 mg / g and 146 mg / g, respectively. -1 , 180mg·g -1 The activated partial thromboplastin time of the polyvinylidene fluoride blood purification membrane is more than 270 seconds, and the thrombin time is 27 seconds, which has excellent anti-coagulation properties.

[0092] Comparative Example 1

[0093] 75 g of polyethersulfone, 15 g of polyvinylpyrrolidone, and 410 g of dimethylacetamide were mixed to obtain a casting solution.

[0094] Use 60°C water as the inner gel bath and the outer gel bath, extrude the casting liquid and the inner gel bath through a spinneret, enter the outer gel bath for phase inversion spinning, and then soak in water for 12 hours and dry at room temperature to obtain a polyethersulfone blood purification membrane.

[0095] like Figure 6 and Figure 7 As shown, polyethersulfone blood purification membranes do not include bimetallic complexes, such as Figure 8 As shown, the pore size of the polyethersulfone-based membrane gradually increases from the center of the membrane to the surface of the membrane.

[0096] The obtained polyethersulfone blood purification membrane was tested for performance, and the membrane pore size was 40nm. Fig. 9 As shown in Figure 2, the initial contact angle of a 2 μL water droplet on the surface is 84.2°. Fig.10 As shown, the water droplets are not wetted and the ultrafiltration coefficient is 15.9 mL·mmHg -1 h -1 The clearance rates of small molecular weight toxins urea and creatinine were 179 mL min -1、170mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate was 12 mg·g -1 , 35mg·g -1 , 23mg·g -1 ; The activated partial thromboplastin time of the polyethersulfone blood purification membrane is 45 seconds, and the thrombin time is 13 seconds.

[0097] Comparative Example 2

[0098] At 30°C, 5 g of potassium ferrocyanide, 20 g of tannic acid, and 10 mL of hydrochloric acid were fully dissolved in 50 mL of aqueous solution to obtain an aqueous solution of a metal organic complex.

[0099] At 80° C., 75 g of polyethersulfone, 15 g of polyvinylpyrrolidone, and 410 g of dimethylacetamide were mixed and stirred uniformly, and then 10 g of polyethyleneimine was added to obtain a polymer solution.

[0100] 50 g of the metal organic complex solution was added dropwise into the above polymer solution to obtain a casting solution.

[0101] At 60°C, 2L of water, 60g of zinc chloride, and 20mL of hydrochloric acid were mixed to obtain an inner gel bath agent, and 480mL of water, 20g of zinc chloride, 15mL of hydrochloric acid, and 20mL of dimethylacetamide solvent were mixed to obtain an outer gel bath agent. The casting liquid and the inner gel bath agent were extruded through a spinneret, entered into the outer gel bath agent for phase inversion spinning, soaked for 5h and then soaked in deionized water for 12h, and dried at room temperature to obtain a polyvinylidene fluoride blood purification membrane.

[0102] Use 60°C water as the inner gel bath and the outer gel bath, extrude the casting liquid and the inner gel bath through a spinneret, enter the outer gel bath for phase inversion spinning, and then soak in water for 12 hours and dry at room temperature to obtain a polyethersulfone blood purification membrane.

[0103] The performance of the obtained polyethersulfone blood purification membrane was tested. The membrane pore size was 40nm, the initial contact angle of 2 microliters of water droplet on the surface was 60.5°, the infiltration time was 20s, and the ultrafiltration coefficient was 16.0mL·mmHg -1 h -1 The clearance rates of small molecular weight toxins urea and creatinine were 180 mL min -1 、176mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate was 15 mg·g -1 , 35mg·g -1 , 26mg·g -1The activated partial thromboplastin time of the polyethersulfone blood purification membrane is 48 seconds, and the thrombin time is 13 seconds.

[0104] Comparative Example 3

[0105] At 30°C, 5 g of potassium ferrocyanide, 20 g of tannic acid, and 10 mL of hydrochloric acid were fully dissolved in 50 mL of aqueous solution to obtain an aqueous solution of a metal organic complex.

[0106] At 80° C., 75 g of polyethersulfone, 15 g of polyvinylpyrrolidone, and 410 g of dimethylacetamide were mixed and stirred uniformly, and then 10 g of polyethyleneimine was added to obtain a polymer solution.

[0107] 50 g of the metal organic complex solution was added dropwise into the above polymer solution to obtain a casting solution.

[0108] At 60°C, 2L of water and 20mL of hydrochloric acid were mixed to obtain an inner gel bath agent, and 480mL of water, 15mL of hydrochloric acid and 20mL of dimethylacetamide solvent were mixed to obtain an outer gel bath agent. The casting liquid and the inner gel bath agent were extruded through a spinneret, entered into the outer gel bath agent for phase inversion spinning, soaked for 5 hours and then soaked in deionized water for 12 hours. After drying at room temperature, a polyethersulfone blood purification membrane was obtained.

[0109] The performance of the obtained polyethersulfone blood purification membrane was tested. The membrane pore size was 39nm, the initial contact angle of 2 microliters of water droplet on the surface was 58.5°, the infiltration time was 20s, and the ultrafiltration coefficient was 17.0mL·mmHg -1 h -1 The clearance rates of small molecular weight toxins urea and creatinine were 178 mL min -1 、165mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate was 21 mg·g -1 , 40mg·g -1 , 27mg·g -1 ; The activated partial thromboplastin time of the polyethersulfone blood purification membrane is 200 seconds, and the thrombin time is 21 seconds.

[0110] Comparative Example 4

[0111] At 30°C, 20 g of tannic acid and 10 mL of hydrochloric acid were fully dissolved in 50 mL of aqueous solution to obtain a tannic acid aqueous solution.

[0112] At 80° C., 75 g of polyethersulfone, 15 g of polyvinylpyrrolidone, and 410 g of dimethylacetamide were mixed and stirred uniformly, and then 10 g of polyethyleneimine was added to obtain a polymer solution.

[0113] 50 g of tannic acid aqueous solution was added dropwise to the above polymer solution to obtain a casting solution.

[0114] At 60°C, 2L of water, 80g of zinc chloride, 60mL of hydrochloric acid, and 80g of potassium ferrocyanide are mixed to obtain an inner gel bath agent; 480mL of water, 20g of zinc chloride, 15mL of hydrochloric acid, 20g of potassium ferrocyanide and 20mL of dimethylacetamide solvent are mixed to obtain an outer gel bath agent; the casting liquid and the inner gel bath agent are extruded through a spinneret, enter the outer gel bath agent for phase inversion spinning, soak for 5h and then soak in deionized water for 12h, and after drying at room temperature, a polyethersulfone blood purification membrane is obtained.

[0115] The performance of the obtained polyethersulfone blood purification membrane was tested. The average pore size of the membrane pores was 41nm, the initial contact angle of a 2 microliter water droplet on the surface was 65°, no wetting, and the ultrafiltration coefficient was 17.2mL·mmHg -1 h -1 The clearance rates (CR) of small molecular weight toxins urea and creatinine were 185 mL min -1 、179mL·min -1 The adsorption capacity of macromolecular toxins such as hippuric acid, p-cresol sulfate, and indoxyl sulfate is 13 mg / g and 32 mg / g, respectively. -1 , 20mg·g -1 ; The activated partial thromboplastin time of the polyethersulfone blood purification membrane is 46 seconds, and the thrombin time is 12 seconds.

[0116] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0117] The above embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for those of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing a blood purification membrane, characterized in that: The following steps are involved: Mixing the plant polyphenol compound, ferrocyanide, a first acidic substance and water to obtain an aqueous solution of a metal organic complex; Mixing a polymer, a porogen and a first organic solvent, and further adding a polyamine monomer to obtain a polymer solution; mixing the aqueous solution of the metal organic complex with the polymer solution to obtain a casting solution; and The casting solution and the acidic inner gel bath are extruded through a spinneret and enter an acidic outer gel bath for phase inversion spinning to obtain a blood purification membrane, wherein the inner gel bath comprises a first zinc salt, and the outer gel bath comprises a second zinc salt and a second organic solvent.

2. The method for preparing a blood purification membrane according to claim 1, characterized in that: In the step of mixing the plant polyphenol compound, ferrocyanide, a first acidic substance and water, the mass ratio of the plant polyphenol compound, the ferrocyanide, the first acidic substance and the water is (1-5):(0.5-3):(1-5):(9-11).

3. The method for preparing a blood purification membrane according to claim 1, characterized in that: In the step of mixing the polymer, the porogen and the first organic solvent, the mass ratio of the polymer, the porogen and the first organic solvent is (7-30):(0.5-15):(55-92.5); And / or, the mass fraction of the polyamine monomer in the polymer solution is 0.8%-10%.

4. The method for preparing a blood purification membrane according to any one of claims 1 to 3, characterized in that: In the step of mixing the aqueous solution of the metal organic complex with the polymer solution, the mass ratio of the aqueous solution of the metal organic complex to the polymer solution is 0.02:1-0.20:

1.

5. The method for preparing a blood purification membrane according to any one of claims 1 to 3, characterized in that: The mass fraction of the first zinc salt in the inner gel bath agent is 0.40%-6%; and / or, the mass fraction of the second zinc salt in the outer gel bath is 0.40%-6%, and the mass fraction of the second organic solvent in the outer gel bath is less than or equal to 50%; And / or, the inner gel bath further includes a second acidic substance, the mass fraction of which is 0.1%-5%, and the outer gel bath further includes a third acidic substance, the mass fraction of which is 0.1%-5%.

6. The method for preparing a blood purification membrane according to any one of claims 1 to 3, characterized in that: The plant polyphenol compound is selected from at least one of tannic acid, gallic acid, tea polyphenols, catechol or anthocyanidin; And / or, the ferrocyanide is selected from at least one of sodium ferrocyanide, potassium ferrocyanide or ammonium ferrocyanide; and / or, the polymer is selected from at least one of polysulfone, polyethersulfone, polymethyl methacrylate, polyamide, polyvinylidene fluoride, polystyrene or vinyl alcohol; And / or, the porogen is selected from at least one of polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer 407, diethylene glycol, triethylene glycol or polyethylene oxide; And / or, the polyamine monomer is at least one selected from o-phenylenediamine, m-phenylenediamine, p-phenylenediamine, diethylenetriamine, triethylenetetramine or polyethyleneimine; And / or, the first zinc salt and the second zinc salt are independently selected from at least one of zinc chloride, zinc sulfate or zinc nitrate.

7. A blood purification membrane, characterized in that: The blood purification membrane is prepared by the preparation method of any one of claims 1 to 6, wherein the blood purification membrane comprises a polymer-based membrane and a bimetallic complex, wherein the pore size of the polymer-based membrane pores gradually increases from the center of the membrane to the surface of the membrane, and the bimetallic complex is distributed on the outer surface, inner surface and internal pore surface of the polymer-based membrane.

8. The blood purification membrane according to claim 7, characterized in that: The bimetallic complex forms a network cross-linked structure on the outer surface, the inner surface and the inner pore surface of the polymer-based membrane. The mass fraction of the bimetallic complex in the blood purification membrane is 5%-20%.

9. The blood purification membrane according to claim 7, characterized in that: The initial contact angle of 2 microliters of water on the surface of the blood purification membrane is less than 60°, and the infiltration time of 2 microliters of water on the surface of the blood purification membrane is less than or equal to 20 seconds.

10. Use of the blood purification membrane according to any one of claims 7 to 9 in a blood purification device.

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