Plasma separation membrane, method for preparing the same, and use thereof

Abstract

This invention provides a plasma separation membrane, its preparation method, and its application. The preparation method of the plasma separation membrane includes the following steps: sulfonated polyethersulfone, sulfonated polyvinyl alcohol, polyvinylpyrrolidone, dimethylacetamide, and water are mixed uniformly to obtain a spinning solution; the spinning solution and core solution are co-extruded to form an initial membrane, wherein the core solution is an aqueous solution of dimethylacetamide, and the mass ratio of the spinning solution to the core solution is 0.5:1 to 0.7:1; the initial membrane is then washed, cured, and dried to obtain the plasma separation membrane. The surface of the plasma separation membrane of this invention simultaneously possesses amino and sulfonic acid groups. These two groups work synergistically, not only specifically adsorbing low-density lipoprotein (LDL) and improving the removal efficiency of LDL from the plasma separation membrane, but also reducing protein adhesion on the surface of the plasma separation membrane, thus preventing clogging and ensuring the membrane's performance.

Description

Technical Field

[0001] This invention relates to the field of blood purification materials technology, and more specifically, to a plasma separation membrane, its preparation method, and its application. Background Technology

[0002] Hyperlipidemia is a common condition caused by abnormal lipid metabolism, primarily characterized by excessively high levels of serum total cholesterol, triglycerides, and low-density lipoprotein (LDL), or excessively low levels of high-density lipoprotein (HDL). Hyperlipidemia can accelerate atherosclerosis; once arteries become blocked, it can lead to various diseases, such as cardiovascular disease, kidney disease, and liver disease. Traditional treatments involve controlling diet and using medication to lower LDL and cholesterol levels. However, oral lipid-lowering drugs can potentially damage the liver. Blood purification can effectively reduce LDL and cholesterol concentrations, thereby minimizing liver damage and achieving better results.

[0003] Existing blood purification treatments for hyperlipidemia primarily include plasma exchange and hemoperfusion. However, plasma exchange for hyperlipidemia presents challenges due to the effects of allergic plasma infusion, such as common allergic reactions, and also results in the loss of significant amounts of beneficial substances from the patient's own plasma. While double plasma exchange can reduce plasma loss, the molecular weight of lipid components like low-density lipoprotein (LDL) is close to 3 × 10⁻⁶. 6 LDL (low-density lipoprotein) molecules have a molecular size of approximately 18–25 nm, while the pore size of typical membrane-type plasma separators is in the range of 10–30 nm. Therefore, secondary membrane plasma separators, due to their pore size being close to that of LDL, cannot effectively filter it. Some LDL is reintroduced into the body with the plasma, resulting in low efficiency per treatment. Alternatively, adsorption columns containing special adsorbents can be used to specifically adsorb LDL from plasma. However, commercially available adsorbents are limited and expensive. Furthermore, in clinical use, adsorption columns place high demands on tubing and equipment, and require integration with plasma separators, making operation complex and clinical costs high. Summary of the Invention

[0004] The present invention aims to solve the problem that existing plasma separation membranes are not effective at removing low-density lipoprotein.

[0005] To address the above problems, the first aspect of the present invention provides a method for preparing a plasma separation membrane, comprising the following steps:

[0006] A spinning solution is prepared by uniformly mixing sulfonated polyethersulfone, sulfonated polyvinyl alcohol, polyvinylpyrrolidone, dimethylacetamide, and water.

[0007] The spinning solution and the core solution are co-extruded to form an initial film, wherein the core solution is an aqueous solution of dimethylacetamide, and the mass ratio of the spinning solution to the core solution is 0.5:1 to 0.7:1.

[0008] The initial membrane is then washed, aged, and dried to obtain a plasma separation membrane.

[0009] Furthermore, the sulfonated polyvinyl alcohol is prepared by the following method:

[0010] Polyvinyl alcohol is swollen to obtain swollen polyvinyl alcohol. The swollen polyvinyl alcohol is then mixed evenly with an amination agent and subjected to an amination reaction to obtain amination polyvinyl alcohol.

[0011] After the aminated polyvinyl alcohol is swollen, the swollen aminated polyvinyl alcohol is obtained. The swollen aminated polyvinyl alcohol is then subjected to a sulfonation reaction with a first sulfonating agent to obtain sulfonated polyvinyl alcohol.

[0012] Further, the step of uniformly mixing the swollen polyvinyl alcohol with an amination agent and then performing an amination reaction to obtain amination-modified polyvinyl alcohol includes:

[0013] The swollen polyvinyl alcohol and the amination agent are soaked at 0-4°C. After soaking, the temperature is raised to 20-30°C to carry out the amination reaction. After the reaction is completed, the temperature is lowered to 0-4°C to precipitate crystals. The crystals are then washed, rinsed, and vacuum dried to obtain amination polyvinyl alcohol.

[0014] Further, the step of swelling the aminated polyvinyl alcohol to obtain swollen aminated polyvinyl alcohol, and then subjecting the swollen aminated polyvinyl alcohol to a first sulfonating agent for sulfonation reaction to obtain sulfonated polyvinyl alcohol, includes:

[0015] After grinding the aminated polyvinyl alcohol into powder, the aminated polyvinyl alcohol is swollen with dimethylacetamide to obtain swollen aminated polyvinyl alcohol;

[0016] At 50–60°C, a first sulfonating agent is added dropwise to the swollen amination polyvinyl alcohol to carry out a sulfonation reaction. After the reaction is complete, the reaction product is washed with water until neutral and then dried to obtain sulfonated polyvinyl alcohol.

[0017] Furthermore, the amination agent is one or a combination of several of diethylenetriamine, trimethylamine, triethylenetetramine, and tetraethylenepentamine; the first sulfonating agent is chlorosulfonic acid.

[0018] Furthermore, the sulfonated polyethersulfone is prepared by the following method:

[0019] Polyethersulfone was dissolved in dimethyl sulfoxide, nitrogen gas was introduced, and then the polyethersulfone was activated with an activating agent to obtain activated polyethersulfone.

[0020] The activated polyethersulfone is subjected to a sulfonation reaction with a second sulfonating agent at 70–80°C to obtain sulfonated polyethersulfone.

[0021] Further, the activator is NaOH, and the amount of NaOH added is 10-15% of the mass of the polyethersulfone; the second sulfonating agent is propanesulfonate lactone or ethyl propanesulfonate, and the amount of the second sulfonating agent added is 5-7% of the mass of the polyethersulfone.

[0022] Further, the spinning solution comprises: 10-15% by mass of sulfonated polyethersulfone, 1-2% by mass of sulfonated polyvinyl alcohol, 2-6% by mass of polyvinylpyrrolidone, and 72-84% by mass of dimethylacetamide.

[0023] The second aspect of the present invention provides a plasma separation membrane, which is prepared by the preparation method described in any one of the first aspects, wherein the plasma separation membrane has an inner diameter of 67-77 μm, a wall thickness of 35-45 μm, and an average pore size of 0.029-0.075 μm.

[0024] A third aspect of the present invention provides a plasma component separator comprising a plasma separation membrane prepared by any of the preparation methods described in the first aspect, or a plasma separation membrane as described in the second aspect.

[0025] The method for preparing the plasma separation membrane of this invention uses sulfonated polyvinyl alcohol and sulfonated polyethersulfone as the main components of the spinning solution. Sulfonated polyvinyl alcohol possesses both amino and sulfonic acid groups, which work synergistically. On the one hand, this improves blood compatibility, facilitating the specific adsorption of more low-density lipoproteins (LDL) at the active sites on the polyvinyl alcohol surface, thus enhancing the LDL clearance effect of the plasma separation membrane. On the other hand, the addition of amino and sulfonic acid groups to the surface of the plasma separation membrane improves its hydrophilicity, reducing protein adhesion and preventing clogging that could affect its performance. Sulfonated polyethersulfone enhances its blendability with sulfonated polyvinyl alcohol, resulting in more uniform mixing of the spinning solution, and grafts onto the surface of the polyvinyl alcohol. The sulfonic acid group improves the hydrophilicity of polyvinyl alcohol, stabilizing hydrophilic substances on the surface of the plasma separation membrane and further enhancing its blood compatibility. Using dimethylacetamide aqueous solution as the core liquid, with the same solvent as the spinning solution, not only improves the compatibility of the core liquid and spinning solution and enhances the hydrophilicity of the initial membrane, but also facilitates the mutual diffusion between the spinning solution and the core liquid, forming a structurally stable plasma separation membrane. Furthermore, by controlling the mass ratio of the spinning solution to the core liquid, and by co-extruding the spinning solution and the core liquid sequentially through an air section and then through a coagulation bath, it is possible to control the process parameters such as the wall thickness, inner diameter, and pore size of the initial membrane. This helps reduce the resistance of the plasma separation membrane during dialysis and improves the efficiency of blood purification.

[0026] The plasma separation membrane described in this invention helps to reduce the resistance of the subsequently prepared plasma separation membrane during the dialysis process, thereby improving the efficiency of blood purification.

[0027] The plasma component separator of the present invention can specifically remove low-density lipoprotein from plasma. Attached Figure Description

[0028] Figure 1 A flowchart illustrating the preparation method of the plasma separation membrane provided in this embodiment of the invention;

[0029] Figure 2 This is a SEM image of the plasma separation membrane provided in Embodiment 1 of the present invention;

[0030] Figure 3 This is a SEM image of the plasma separation membrane provided in Embodiment 2 of the present invention;

[0031] Figure 4 This is a cross-sectional view of the plasma separation membrane provided in Embodiment 1 of the present invention. Detailed Implementation

[0032] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0033] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0034] Furthermore, the terms "comprising," "including," "containing," and "having" are non-restrictive and can refer to the addition of other steps and components that do not affect the results. Unless otherwise specified, all materials, equipment, and reagents are commercially available.

[0035] Furthermore, although the present invention describes each step in the preparation process in the form of S100, S110, S120, etc., this description is only for ease of understanding. The forms such as S100, S110, S120 do not indicate a limitation on the order of the steps.

[0036] Combination Figure 1 As shown, an embodiment of the present invention provides a method for preparing a plasma separation membrane, comprising the following steps:

[0037] Step S100: Mix sulfonated polyethersulfone, sulfonated polyvinyl alcohol, polyvinylpyrrolidone, dimethylacetamide and water evenly to prepare a spinning solution.

[0038] Specifically, the following mass percentages are prepared: 10-15% sulfonated polyethersulfone, 1-2% sulfonated polyvinyl alcohol, 2-6% polyvinylpyrrolidone, 72-84% dimethylacetamide, and the remainder is water; sulfonated polyvinyl alcohol is dissolved in dimethylacetamide, water and polyvinylpyrrolidone, and stirred for 2-3 hours to obtain a clear solution. Sulfonated polyethersulfone is then added to the clear solution, and stirring is continued to form a uniform light yellow solution. After vacuum degassing, the spinning solution is obtained.

[0039] Sulfonated polyethersulfone and sulfonated polyvinyl alcohol are the main components of the spinning solution, which is beneficial for the subsequent preparation of a plasma separation membrane that can specifically bind low-density lipoprotein in plasma. Polyvinylpyrrolidone is used as a hydrophilic modifier to improve the hydrophilicity of the spinning solution and the resulting plasma separation membrane. Dimethylacetamide and water are used as solvents to facilitate the miscibility of the components and improve the stability of the spinning solution. Limiting the proportions of each component in the spinning solution within a certain range helps to improve the surface properties of the plasma separation membrane, enhance its hydrophilicity, and improve its blood compatibility. Furthermore, it avoids excessive viscosity in the spinning solution, which would be detrimental to subsequent fiber drawing and film formation.

[0040] Sulfonated polyvinyl alcohol is prepared by the following method:

[0041] S101. Polyvinyl alcohol is swollen to obtain swollen polyvinyl alcohol. The swollen polyvinyl alcohol is mixed evenly with an amination agent and then subjected to an amination reaction to obtain amination polyvinyl alcohol.

[0042] Specifically, after polyvinyl alcohol is fully swollen in water, the swollen polyvinyl alcohol and amination agent are mixed and soaked at 0-4°C for 24 hours. After soaking, the mixture is stirred and mixed evenly, and the temperature is raised to 20-30°C for amination reaction. After the reaction is kept at a constant temperature for 8 hours, the temperature is lowered to 0-4°C to precipitate crystals. The crystals are then washed, rinsed, and vacuum dried to obtain amination polyvinyl alcohol.

[0043] In this embodiment, the polyvinyl alcohol is a polyvinyl alcohol with a medium to low degree of polymerization; specifically, the molecular weight of the polyvinyl alcohol is 2.5 × 10⁻⁶. 4 Up to 2.5×10 5 Da, low- to medium-polymerization-degree polyvinyl alcohol has a lower viscosity, which is beneficial for amination and sulfonation treatments. Furthermore, when it is blended with sulfonated polyethersulfone for spinning, the viscosity of the spinning solution can meet the requirements for spinning, which facilitates the subsequent preparation of the initial film.

[0044] As an alternative implementation, the amination agent is one or a combination of several of diethylenetriamine, trimethylamine, triethylenetetramine, and tetraethylenepentamine, and the mass ratio of the amination agent to polyvinyl alcohol is 1:10. Thus, by selecting the above-mentioned substances as amination agents and limiting the mass ratio of the amination agent to polyvinyl alcohol to the above range, it is beneficial to graft more amine groups onto the surface of polyvinyl alcohol.

[0045] As an optional implementation, the pure washing includes: washing the crystals with a large volume of purified water to remove unreacted amination agent until the filtrate is neutral and has no obvious odor. The rinsing includes: rinsing the crystals with 99% anhydrous ethanol or methanol, wherein the volume of anhydrous ethanol or methanol used for rinsing is at least four times the volume of polyvinyl alcohol.

[0046] In this embodiment, by swelling the polyvinyl alcohol and then immersing the swollen polyvinyl alcohol in an amination agent, it is beneficial to activate the active sites on the surface of the polyvinyl alcohol. This makes it easier for amino groups to be grafted onto the surface of the polyvinyl alcohol during the subsequent amination reaction. After the reaction is complete, cooling the temperature to 0-4°C helps to precipitate more reaction products, thereby increasing the yield of amination polyvinyl alcohol.

[0047] S102. After swelling the aminated polyvinyl alcohol, the swollen aminated polyvinyl alcohol is obtained. The swollen aminated polyvinyl alcohol is then subjected to a sulfonation reaction with the first sulfonating agent to obtain sulfonated polyvinyl alcohol.

[0048] Specifically, after grinding the amination polyvinyl alcohol into powder, dimethylacetamide and the amination polyvinyl alcohol are mixed. At 0°C, the amination polyvinyl alcohol is fully swollen with dimethylacetamide to obtain swollen amination polyvinyl alcohol. The temperature is raised to 50-60°C, and the first sulfonating agent is added dropwise to the swollen amination polyvinyl alcohol. After the addition is complete, the reaction is continued at a constant temperature for 4-6 hours to fully sulfonate the amination polyvinyl alcohol. After the reaction is complete, the reaction product is washed with water until neutral and dried to obtain sulfonated polyvinyl alcohol.

[0049] As an alternative implementation method, the first sulfonating agent is chlorosulfonic acid. Chlorosulfonic acid has high reactivity, a mild reaction temperature, and low requirements for reaction conditions, which is beneficial to improving the efficiency of the sulfonation reaction and the safety of the sulfonation reaction.

[0050] The amount of the first sulfonating agent is 3 to 7% of the mass of the aminated polyvinyl alcohol. By limiting the amount of the first sulfonating agent to the above range, the first sulfonating agent can sulfonate only some of the amino groups without sulfonating all of them. This allows the surface of the sulfonated polyvinyl alcohol to have both amino groups and sulfonic acid groups, which is beneficial to improving the removal effect of the plasma separation membrane on low-density lipoprotein.

[0051] As an optional implementation, the first sulfonating agent is added at a rate of 1 drop / min, and the stirring speed is 100 r / min to 150 r / min. This helps to control the sulfonation reaction rate and avoid excessive reaction of polyvinyl alcohol in a localized area, which would affect the amount of sulfonic acid groups on the surface of the sulfonated polyvinyl alcohol.

[0052] In this embodiment, the molecular structure of the obtained sulfonated polyvinyl alcohol is shown below:

[0053]

[0054] As can be seen from the above molecular structure, the sulfonated polyvinyl alcohol prepared in this embodiment contains both amino groups and sulfonic acid groups. In this embodiment, the amination reaction is first carried out to obtain amination polyvinyl alcohol, and then the amination polyvinyl alcohol is subjected to sulfonation reaction to obtain sulfonated polyvinyl alcohol. This allows for the grafting of more amino groups onto the surface of polyvinyl alcohol, improving the clearance effect on low-density lipoprotein. Sulfonation of some amino groups gives the surface of polyvinyl alcohol sulfonic acid groups, which can improve the hydrophilicity of polyvinyl alcohol and improve the blood compatibility of the plasma separation membrane. The sulfonated polyvinyl alcohol prepared in this embodiment has both amino groups and sulfonic acid groups. The two work synergistically to improve blood compatibility, making it easier for the active sites on the surface of polyvinyl alcohol to capture more low-density lipoprotein. On the other hand, it can reduce the adhesion of protein on the surface of the plasma separation membrane, avoiding blockage of the plasma separation membrane and affecting its performance.

[0055] Sulfonated polyethersulfone was prepared by the following method:

[0056] Polyethersulfone is dissolved in dimethyl sulfoxide, nitrogen gas is introduced, and then the polyethersulfone is activated with an activating agent to obtain activated polyethersulfone. At 70-80°C, the activated polyethersulfone is subjected to a sulfonation reaction with a second sulfonating agent to obtain sulfonated polyethersulfone.

[0057] Specifically, polyethersulfone is dissolved in dimethyl sulfoxide, nitrogen gas is introduced, and the temperature is raised to 100°C to completely dissolve the polyethersulfone. Then, an activator is added and activated for 2 hours to obtain activated polyethersulfone. The activated polyethersulfone is mixed evenly with a second sulfonating agent and reacted at 80°C for 12 hours. After the reaction is complete, it is cooled to room temperature, and the reaction solution is poured into anhydrous ethanol or methanol for precipitation. After filtration, the precipitate is obtained. The precipitate is washed with anhydrous ethanol or methanol and then vacuum dried to constant weight to obtain sulfonated polyethersulfone.

[0058] As an optional implementation, the activator is NaOH, and the amount of NaOH added is 10-15% of the mass of polyethersulfone. This is beneficial for activating the active sites on polyethersulfone, which facilitates the subsequent grafting of sulfonic acid groups.

[0059] As an optional implementation, the second sulfonating agent is propanesulfonate lactone or ethyl propanesulfonate, and the amount of the second sulfonating agent added is 5-7% of the mass of polyethersulfone. Thus, by sulfonating polyethersulfone with the second sulfonating agent and controlling the amount of the second sulfonating agent, the sulfonic acid groups grafted onto the surface of polyethersulfone are kept within a suitable range. This is beneficial for improving the blending properties of polyethersulfone and sulfonated polyvinyl alcohol, resulting in more uniform mixing of the spinning solution, improving the stability of the spinning solution, and consequently improving the quality of the plasma separation membrane subsequently prepared.

[0060] Step S110: The spinning solution and the core solution are co-extruded to form an initial film. The core solution is an aqueous solution of dimethylacetamide, and the mass ratio of the spinning solution to the core solution is 0.5:1 to 0.7:1.

[0061] Specifically, the spinning solution and the core liquid are extruded simultaneously from the spinneret by a centrifugal pump and a metering pump, respectively. According to the principle of double diffusion, the solvent in the spinning solution diffuses into the core liquid, and the core liquid diffuses into the spinning solution. The two diffuse into each other and then pass through an air section and a coagulation bath in sequence to form nascent filaments. The nascent filaments are then passed through a water washing tank and a rinsing tank in sequence to form an initial film.

[0062] In this embodiment, the core solution is a dimethylacetamide aqueous solution with a mass percentage of 60-65%. By selecting a dimethylacetamide aqueous solution as the core solution, it is beneficial to improve the compatibility between the core solution and the spinning solution, and also beneficial to improve the hydrophilicity of the initial membrane.

[0063] In this embodiment, by adjusting the mass ratio of the spinning solution and the core liquid, and by co-extruding the spinning solution and the core liquid sequentially through the air section and then through the coagulation bath, it is beneficial to control the process parameters such as the wall thickness, inner diameter, and membrane pore size of the initial membrane. This helps to reduce the resistance of the plasma separation membrane obtained later in the dialysis process and improve the efficiency of blood purification.

[0064] Step S120: After the initial membrane is washed, aged and dried, a plasma separation membrane is obtained.

[0065] Specifically, the initial membrane, after being washed and shaped with water, is washed for 12 hours, then matured in water at 50-60°C for 2 hours, and then dried in a microwave drying oven at 80°C to obtain a plasma separation membrane.

[0066] Washing with water can remove additives and solvents from the plasma separation membrane. Aging can leach out as many additives and solvents as possible. The residual amount of these chemicals has a great impact on blood compatibility. Drying removes water from the plasma separation membrane, which can eliminate internal stress and improve the dimensional stability of the plasma separation membrane.

[0067] The plasma separation membrane preparation method provided in this embodiment uses sulfonated polyvinyl alcohol and sulfonated polyethersulfone as the main components of the spinning solution. Sulfonated polyvinyl alcohol possesses both amino and sulfonic acid groups, which work synergistically. On one hand, it improves blood compatibility, facilitating the specific adsorption of more low-density lipoproteins (LDL) at the active sites on the polyvinyl alcohol surface, thus enhancing the LDL clearance effect of the plasma separation membrane. On the other hand, the addition of amino and sulfonic acid groups to the surface of the plasma separation membrane improves its hydrophilicity, reducing protein adhesion and preventing clogging that could affect its performance. Sulfonated polyethersulfone enhances its blendability with sulfonated polyvinyl alcohol, resulting in more uniform mixing of the spinning solution, and grafts onto the polyvinyl alcohol surface... The sulfonic acid group improves the hydrophilicity of polyvinyl alcohol, stabilizing hydrophilic substances on the surface of the plasma separation membrane and further enhancing its blood compatibility. Using dimethylacetamide aqueous solution as the core liquid, with the same solvent as the spinning solution, not only improves the compatibility of the core liquid and spinning solution and enhances the hydrophilicity of the initial membrane, but also facilitates the mutual diffusion between the spinning solution and the core liquid, forming a structurally stable plasma separation membrane. Furthermore, by controlling the mass ratio of the spinning solution to the core liquid, and by co-extruding the spinning solution and the core liquid sequentially through an air section and then through a coagulation bath, it is possible to control the process parameters such as the wall thickness, inner diameter, and pore size of the initial membrane. This helps reduce the resistance of the plasma separation membrane during dialysis and improves the efficiency of blood purification.

[0068] The second aspect of this embodiment provides a plasma separation membrane, which is prepared using the preparation method described in the first aspect. The plasma separation membrane has an inner diameter of 72±5 μm, a wall thickness of 40±5 μm, and an average pore size of 0.052±0.023 μm, meaning the inner diameter is 67–77 μm, the wall thickness is 35–45 μm, and the average pore size is 0.029–0.075 μm. Therefore, controlling the process parameters of the plasma separation membrane within the above range helps to reduce the resistance of the prepared plasma separation membrane during dialysis, thereby improving the efficiency of blood purification.

[0069] The third aspect of this embodiment provides a plasma component separator that includes the aforementioned plasma separation membrane, which is capable of specifically removing low-density lipoprotein from plasma.

[0070] To provide a more detailed description of the present invention, specific embodiments will be used to further illustrate the invention below. Unless otherwise specified, the experimental methods used in the embodiments of the present invention are conventional methods; unless otherwise specified, the materials and reagents used in the embodiments of the present invention are commercially available. The water used in the embodiments of the present invention is purified water or water used for hemodialysis.

[0071] Example 1

[0072] This embodiment provides a method for preparing a plasma separation membrane, including the following steps:

[0073] (1) Preparation of sulfonated polyvinyl alcohol:

[0074] Weigh out 50g of polyvinyl alcohol with a medium degree of polymerization (molecular weight 2.5 × 10⁻⁶). 5 According to the volume ratio of polyvinyl alcohol (PVA) to water of 1:3, purified water was added to PVA to allow it to swell completely. Then, 25g of diethylenetriamine was added to the swollen PVA. The PVA and diethylenetriamine were soaked in the solution at 4°C for 24 hours with slow stirring. After soaking, the temperature was raised to 25°C for amination reaction. After reacting at this temperature for 8 hours, the temperature was lowered to 4°C. At this point, PVA precipitated from the solution. The precipitated crystals were washed with 2L to 3L of purified water at 0–4°C. Unreacted diethylenetriamine was filtered out, and the crystals were then rinsed with 2L of 99% anhydrous ethanol. After rinsing, the anhydrous ethanol on the surface of the crystals was drained, and the crystals were vacuum dried at 60°C to constant weight to obtain amination-treated PVA solid.

[0075] The amination of polyvinyl alcohol (PVA) solid was ground into a fine powder using a grinder and dried to constant weight in a forced-air oven at 40–50°C. The dried PVA was then placed in a three-necked flask containing DMAC (dimethylacetamide) and allowed to swell completely at 0°C for 24 hours. The mixture was stirred slowly, and the temperature was gradually increased to 60°C. Chlorosulfonic acid was then added dropwise to the flask at a rate of 3% wt of the PVA mass, with a dropping rate controlled at 1 drop / min and a stirring speed of 100–150 rpm. After the addition was complete, the reaction was continued at a constant temperature for 4 hours to ensure complete sulfonation of the PVA. After the reaction was complete, the reaction solvent was recovered by filtration. The filtered PVA solid was washed with purified water until neutral and then dried to constant weight at 40–60°C to obtain sulfonated PVA.

[0076] (2) Preparation of sulfonated polyethersulfone:

[0077] 500g of polyethersulfone was dissolved in 2L of DMSO (dimethyl sulfoxide), heated to 100℃ under nitrogen purging, and stirred until the polyethersulfone was completely dissolved. NaOH (10% wt of polyethersulfone) was slowly added to activate the polyethersulfone for 2 hours. Propanolactone (5% wt of polyethersulfone) was then slowly added to the activated polyethersulfone. The reaction was carried out at 80℃ for 12 hours. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was poured into a certain amount of anhydrous ethanol for precipitation. The precipitate was filtered and then washed with anhydrous ethanol. The washed precipitate was then vacuum dried at 40℃ to constant weight to obtain sulfonated polyethersulfone.

[0078] (3) Preparation of spinning solution:

[0079] Prepare the following mass percentages: 15% of sulfonated polyethersulfone from step (2), 2% of sulfonated polyvinyl alcohol from step (1), 6% of polyvinylpyrrolidone, and 72% of dimethylacetamide, and add water to make up to 100%; dissolve sulfonated polyvinyl alcohol in dimethylacetamide, water and polyvinylpyrrolidone, stir at 500 r / min for 2-3 h to obtain a clear solution, then add sulfonated polyethersulfone to the clear solution and continue stirring until a uniform light yellow solution is formed. After vacuum degassing, the spinning solution is obtained.

[0080] (4) Preparation of the initial membrane: Using a 60% dimethylacetamide aqueous solution as the core liquid, the spinning solution and core liquid in step (3) are extruded from the spinneret simultaneously through a centrifugal pump and a metering pump, respectively. After passing through an air bath of 20cm to 25cm and then through a coagulation bath, the initial filament is formed. The initial filament is then passed through a water washing tank and a rinsing tank in sequence to form the initial membrane.

[0081] (5) Preparation of plasma separation membrane: After washing and shaping the initial membrane with water, wash it with water for 12 hours, cut 20 to 30 bundles of the initial membrane with a length of 40 cm, mature it in water at 50-60℃ for 2 hours, and then dry it in a microwave drying oven at 80℃ to obtain the plasma separation membrane, which is recorded as sample one.

[0082] Example 2

[0083] This embodiment provides a method for preparing a plasma separation membrane, including the following steps:

[0084] (1) Preparation of sulfonated polyvinyl alcohol:

[0085] Weigh out 50g of low-polymerization polyvinyl alcohol (molecular weight 2.5×10⁻⁶). 4 According to the volume ratio of polyvinyl alcohol (PVA) to water of 1:3, purified water was added to PVA to allow it to swell completely. Then, 25g of trimethylamine was added to the swollen PVA. The swollen PVA and trimethylamine were soaked in the solution at 4°C for 24 hours with slow stirring. After soaking, the temperature was raised to 25°C for amination reaction. After reacting at this temperature for 8 hours, the temperature was lowered to 4°C. At this point, PVA precipitated from the solution. The precipitated crystals were washed with 2L to 3L of purified water at 0–6°C. Unreacted trimethylamine was filtered out, and the crystals were then rinsed with 2L of methanol. After rinsing, the methanol on the surface of the crystals was drained, and the crystals were vacuum dried at 60°C to constant weight to obtain amination-modified PVA solid.

[0086] The aminated polyvinyl alcohol (PVA) solid was ground into a fine powder using a grinder and dried to constant weight in a forced-air oven at 40–50°C. The dried PVA was then placed in a three-necked flask containing DMAC and allowed to swell completely at 0°C for 24 hours. The mixture was stirred slowly, and the temperature was gradually increased to 60°C. Chlorosulfonic acid was then added dropwise to the flask at a rate of 5% wt of the PVA mass, with a dropping rate controlled at 1 drop / min and a stirring speed of 100–150 rpm. After the addition was complete, the reaction was continued at a constant temperature for 6 hours to ensure complete sulfonation of the PVA. After the reaction was complete, the reaction solvent was recovered by filtration. The filtered PVA solid was washed with purified water until neutral and dried to constant weight at 40–60°C to obtain sulfonated PVA.

[0087] (2) Preparation of sulfonated polyethersulfone:

[0088] 500g of polyethersulfone was dissolved in 2L of DMSO, heated to 100℃ under nitrogen purging, and stirred until the polyethersulfone was completely dissolved. NaOH (10% wt of polyethersulfone mass) was slowly added to activate the polyethersulfone for 2 hours. Propanolactone (7% wt of polyethersulfone mass) was then slowly added to the activated polyethersulfone. The reaction was carried out at 80℃ for 12 hours. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was poured into a certain amount of methanol for precipitation. The precipitate was filtered and then washed with methanol. The washed precipitate was then vacuum dried at 40℃ to constant weight to obtain sulfonated polyethersulfone.

[0089] (3) Preparation of spinning solution:

[0090] Prepare the following mass percentages: 10% of sulfonated polyethersulfone from step (2), 1% of sulfonated polyvinyl alcohol from step (1), 2% polyvinylpyrrolidone, and 84% dimethylacetamide, and add water to make up to 100%; dissolve sulfonated polyvinyl alcohol in dimethylacetamide, water and polyvinylpyrrolidone, stir at 500 r / min for 2-3 h to obtain a clear solution, then add sulfonated polyethersulfone to the clear solution and continue stirring until a uniform light yellow solution is formed. After vacuum degassing, the spinning solution is obtained.

[0091] (4) Preparation of the initial membrane: Using a 65% dimethylacetamide aqueous solution as the core liquid, the spinning solution and core liquid in step (3) are extruded from the spinneret simultaneously through a centrifugal pump and a metering pump, respectively. After passing through an air bath of 20cm to 25cm and then through a coagulation bath, the initial filament is formed. The initial filament is then passed through a water washing tank and a rinsing tank in sequence to form the initial membrane.

[0092] (5) Preparation of plasma separation membrane: After washing and shaping the initial membrane with water, wash it with water for 12 hours, cut 20 to 30 bundles of the initial membrane with a length of 40 cm, mature it in water at 50-60℃ for 2 hours, and then dry it in a microwave drying oven at 80℃ to obtain the plasma separation membrane, which is designated as sample two.

[0093] The process parameters of the plasma separation membranes prepared in Examples 1 and 2 were tested, and the test results are shown in Table 1.

[0094] Table 1

[0095] Process parameters Sample 1 Sample 2 Membrane inner diameter (μm) 72±3 75±2 Membrane wall thickness (μm) 40±5 41±3 Average membrane pore size (μm) 0.045±0.012 0.052±0.023

[0096] The plasma separation membranes prepared in Examples 1 and 2 were observed using SEM to obtain the external pore size and distribution parameters of the plasma separation membranes, as shown below. Figures 2 to 4 The SEM image shown, in which, Figure 2 and Figure 3 SEM images of the outer surface of the plasma separation membrane, all taken at an accelerating voltage of 3.2 HV. Figure 4 The cross-sectional view was used, and statistical analysis of the pore structure was performed using Matlab. It was found that the process parameters of the plasma separation membranes in Examples 1 and 2 were within the range of Table 1, and were determined by… Figure 2 and Figure 3 It can be seen that the surface of the plasma separation membrane has a lot of pores, which is beneficial for reducing the dialysis of plasma, adsorbing low-density lipoprotein in plasma, and improving the efficiency of blood purification.

[0097] Infrared spectroscopy analysis of the plasma separation membranes prepared in Examples 1 and 2 revealed that Sample 1 and Sample 2 showed a plasma separation efficiency of 3300 cm⁻¹. -1 1200cm -1 Characteristic absorption peaks were observed at all locations, indicating that the surface of the plasma separation membrane was grafted with amine and sulfonic acid groups.

[0098] The protein screening coefficients of the plasma separation membranes prepared in Examples 1 and 2 were tested according to YY0464-2019 "Disposable Hollow Fiber Plasma Separators and Plasma Component Separators" and ISO8637-3 "Extracorporeal systems for blood purification - Part 3: Plasma filters". The test results are shown in Table 2.

[0099] Table 2

[0100] substance Sample screening coefficient Sample 2 screening coefficient Total protein TP 0.15±0.02 0.16±0.03 Globulin G 0.20±0.03 0.21±0.02 Immunoglobulin IgG 0.01±0.002 0.01±0.001 Immunoglobulin IgM 0.01±0.002 0.01±0.001

[0101] As can be seen from Table 2, the protein screening coefficients of Sample 1 and Sample 2 are relatively low, indicating that Sample 1 and Sample 2 remove less of the beneficial components in the plasma, and can effectively avoid the loss of beneficial components in the plasma.

[0102] Commercially available plasma separators were used as reference standards. A plasma separator containing the plasma separation membrane of Example 1 was used as sample one, and a plasma separator containing the plasma separation membrane of Example 2 was used as sample two. The plasma separation process was simulated in vitro. The ability of the samples to clear low-density lipoprotein was detected by observing the change in the concentration of low-density lipoprotein in the plasma with externally added low-density lipoprotein. The test results are shown in Table 3.

[0103] Table 3

[0104] Detection time (min) Sample 1 decrease rate (%) Sample 1 decrease rate (%) The rate of decrease in the reference standard (%) 0 0 0 0 30 15±2 17±3 5±2 60 20±4 21±2 7±1 120 28±5 29±3 7±2 180 32±3 33±4 8±2 240 35±3 36±2 10±1

[0105] As shown in Table 3, at 240 min, the plasma component separators containing the plasma separation membrane of Example 1 and Example 2 achieved a low-density lipoprotein (LDL) clearance rate of approximately 35%, which is significantly higher than the LDL clearance rate of the control plasma component separator. Furthermore, during the experiment, the transmembrane pressure of the plasma separation membranes of Example 1 and Example 2 remained stable, indicating that no membrane pore blockage occurred during plasma treatment. These results demonstrate that the plasma separation membranes and plasma component separators containing the plasma separation membranes provided in this example possess excellent LDL clearance capabilities and exhibit superior blood purification functions.

[0106] While the disclosure is as stated above, its scope of protection is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of this disclosure, and all such changes and modifications will fall within the protection scope of this invention.

Claims

1. A method for preparing a plasma separation membrane, characterized in that, Includes the following steps: A spinning solution is prepared by uniformly mixing sulfonated polyethersulfone, sulfonated polyvinyl alcohol, polyvinylpyrrolidone, dimethylacetamide, and water. The spinning solution and the core solution are co-extruded to form an initial film, wherein the core solution is an aqueous solution of dimethylacetamide, and the mass ratio of the spinning solution to the core solution is 0.5:1 to 0.7:

1. The initial membrane is then washed, aged, and dried to obtain a plasma separation membrane; The sulfonated polyvinyl alcohol was prepared by the following method: Polyvinyl alcohol is swollen to obtain swollen polyvinyl alcohol. The swollen polyvinyl alcohol is then mixed evenly with an amination agent and subjected to an amination reaction to obtain amination polyvinyl alcohol. After the aminated polyvinyl alcohol is swollen, the swollen aminated polyvinyl alcohol is obtained. The swollen aminated polyvinyl alcohol is then subjected to a sulfonation reaction with a first sulfonating agent to obtain sulfonated polyvinyl alcohol. The step of mixing the swollen polyvinyl alcohol with an amination agent and then performing an amination reaction to obtain amination-modified polyvinyl alcohol includes: The swollen polyvinyl alcohol and the amination agent are soaked at 0~4℃. After soaking, the temperature is raised to 20~30℃ to carry out the amination reaction. After the reaction is completed, the temperature is lowered to 0~4℃ to precipitate crystals. The crystals are then washed, rinsed, and vacuum dried to obtain amination polyvinyl alcohol. The amination agent is one or a combination of several of diethylenetriamine, trimethylamine, triethylenetetramine, and tetraethylenepentamine; the first sulfonating agent is chlorosulfonic acid.

2. The method for preparing the plasma separation membrane according to claim 1, characterized in that, The process involves swelling the aminated polyvinyl alcohol to obtain swollen aminated polyvinyl alcohol, and then subjecting the swollen aminated polyvinyl alcohol to a sulfonation reaction with a first sulfonating agent to obtain sulfonated polyvinyl alcohol, comprising: After grinding the aminated polyvinyl alcohol into powder, the aminated polyvinyl alcohol is swollen with dimethylacetamide to obtain swollen aminated polyvinyl alcohol; At 50-60°C, a first sulfonating agent is added dropwise to the swollen amination polyvinyl alcohol to carry out a sulfonation reaction. After the reaction is complete, the reaction product is washed with water until neutral and then dried to obtain sulfonated polyvinyl alcohol.

3. The method for preparing the plasma separation membrane according to claim 1, characterized in that, The sulfonated polyethersulfone was prepared by the following method: Polyethersulfone was dissolved in dimethyl sulfoxide, nitrogen gas was introduced, and then the polyethersulfone was activated with an activating agent to obtain activated polyethersulfone. The activated polyethersulfone is subjected to a sulfonation reaction with a second sulfonating agent at 70~80℃ to obtain sulfonated polyethersulfone.

4. The method for preparing the plasma separation membrane according to claim 3, characterized in that, The activator is NaOH, and the amount of NaOH added is 10-15% of the mass of the polyethersulfone; the second sulfonating agent is propanesulfonate lactone or ethyl propanesulfonate, and the amount of the second sulfonating agent added is 5-7% of the mass of the polyethersulfone.

5. The method for preparing the plasma separation membrane according to claim 1, characterized in that, The spinning solution comprises: 10-15% by mass of sulfonated polyethersulfone, 1-2% by mass of sulfonated polyvinyl alcohol, 2-6% by mass of polyvinylpyrrolidone, and 72-84% by mass of dimethylacetamide.

6. A plasma separation membrane, characterized in that, The plasma separation membrane is prepared by the preparation method according to any one of claims 1 to 5, and has an inner diameter of 67~77μm, a wall thickness of 35~45μm, and an average pore size of 0.029~0.075μm.

7. A plasma component separator, characterized in that, The plasma separation membrane comprises the plasma separation membrane prepared by the preparation method according to any one of claims 1 to 5, or the plasma separation membrane according to claim 6.

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