High-efficiency wet film plasma component separator and preparation method thereof

Abstract

The invention discloses a high-effect wet film plasma component separator and a preparation method thereof. The high-effect wet film plasma component separator comprises 10-35 parts of polyether sulfone, 3-20 parts of an amphiphilic polymer, 2-25 parts of a pore-forming agent, 40-84.5 parts of a solvent and 0.5-12 parts of a non-solvent. The invention provides a high-effect wet film plasma component separator and a preparation method thereof, the high-effect wet film plasma component separator is used for plasma component separation treatment, the fiber inner diameter is 100-300 [mu] m, the wall thickness is 20-50 [mu] m, the film aperture is 0.0084-0.0478 [mu] m, the albumin screening coefficient is 0.334-0.967, and the total protein screening coefficient is 0.268-0.772. The pore diameter of the hollow fiber membrane wall is uniformly distributed, so that blockage in the use process is avoided, and excellent performance stability is achieved.

Description

Technical Field

[0001] The invention relates to the technical field of plasma separation membranes, and in particular to a high-efficiency wet-membrane plasma component separator and a preparation method thereof. Background Art

[0002] The plasma component separator is mainly used to separate the plasma separated from the plasma separator into plasma components with larger molecular weight and smaller molecular weight. The larger molecular weight components containing pathogenic substances such as immunoglobulin G (IgG), immunoglobulin M (IgM), and low-density lipoprotein cholesterol (LDL-C) are discarded, while the small molecular weight components containing useful substances such as albumin are returned to the body.

[0003] Toxins accumulated in liver failure are mainly bound to albumin, so albumin is the main target for removal; for example, the autoantibody in macroglobulinemia is IgM, so IgM is the main target for removal; for example, the autoantibody in autoimmune diseases such as glomerular basement membrane nephritis, ANCA-associated vasculitis, Guillain-Barré syndrome, myasthenia gravis, and pemphigus is IgG, so IgG is the main target for removal. By separating and removing these pathogenic substances from plasma components, we can prevent the occurrence or development of certain diseases, reduce damage to tissues and organs, and even restore organ function.

[0004] The molecular weight of IgG is about 150 kDa, the molecular weight of IgM is about 970 kDa, and the molecular weight of LDL is about 2500 kDa. The molecular weights of pathogenic substances of different diseases are different. By controlling the pore size of the hollow fiber membrane side wall, the screening function of different target substances can be achieved. However, when preparing plasma component separation membranes for separating different target substances, it is necessary to switch different polymer spinning solutions to achieve different pore size requirements. The switching process is complicated and affects production efficiency.

[0005] After the finished product is produced, the plasma component separator that does not contain wet membrane liquid will generate a pyrogen inside due to factors such as storage and transportation. Polyvinyl pyrrolidone is easy to escape from it, causing the membrane pores to collapse, resulting in reduced membrane performance. Insufficient pre-flushing during use can also cause symptoms such as allergies, and even worse, cause adverse effects such as organ damage to the patient. As the blood purification process proceeds, the membrane's permeability flux and filtration performance will decay over time due to concentration polarization, membrane pore blockage, and biological contamination. Therefore, it is crucial to develop a new method for a blood purification membrane structure that is simple to prepare, can meet a wide range of medical needs, and can maintain excellent membrane separation performance during treatment. Summary of the invention

[0006] The purpose of the present invention is to provide a high-efficiency wet membrane plasma component separator and a preparation method thereof, so as to solve the problems in the prior art that the preparation process of plasma component separator membranes with different pore sizes is complicated, inefficient and the performance stability of the plasma component separator membranes is poor.

[0007] To achieve the above object, the present invention provides the following technical solutions: The invention provides a high-efficiency wet membrane plasma component separator, comprising the following components in parts by weight: polyethersulfone: 10-35 parts, amphiphilic polymer: 3-20 parts, pore former: 2-25 parts, solvent: 40-84.5 parts, and non-solvent: 0.5-12 parts.

[0008] Furthermore, the amphiphilic polymer includes a mixture of poly(lactic acid-glycolic acid)-polyethylene glycol and copolymer poly(lactic acid-glycolic acid) in a mass ratio of 50:50 to 75:25, a mixture of poly(lactic acid-glycolic acid)-poly(ethylene glycol) methyl ether copolymer and poly(lactic acid-glycolic acid) in a mass ratio of 50:50 to 75:25, and a stearic acid polyethylene glycol carboxylic acid and polyoxyethylene polyoxypropylene ether block copolymer.

[0009] Furthermore, the molecular weight of the poly(lactic acid-glycolic acid)-poly(ethylene glycol) is 10,000-30,000; the molecular weight of the poly(lactic acid-glycolic acid)-poly(ethylene glycol) methyl ether copolymer is 10,000-30,000; the molecular weight of the stearic acid polyethylene glycol carboxylic acid is 4,000-10,000; and the hydrophilic-lipophilic balance value of the polyoxyethylene polyoxypropylene ether block copolymer is 20-30.

[0010] Furthermore, the pore-forming agent is any one or any combination of polyvinyl pyrrolidone with a molecular weight of 20,000 to 700,000, polyvinyl alcohol with a molecular weight of 3,000 to 40,000, and polyethylene glycol with a molecular weight of 1,000 to 10,000.

[0011] Furthermore, the solvent is any one or any combination of dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, and N,N-dimethylformamide.

[0012] Furthermore, the non-solvent includes purified water, propylene glycol, and glycerol; and the molecular weight of the polyethersulfone is 30,000-150,000.

[0013] The present invention also provides a method for preparing a high-efficiency wet membrane plasma component separator, comprising the following steps: Step 1: Preparation of spinning solution 10-35 parts of polyethersulfone, 3-20 parts of amphiphilic polymer, 2-25 parts of pore-forming agent, 40-84.5 parts of solvent, 0.5-12 parts of non-solvent, stirring and dissolving at a temperature of 60-85°C for 8-48 hours, filtering and degassing to obtain a polymer spinning solution; Step 2: Preparation of core solution Take 15-75 parts of solvent and 25-85 parts of purified water and stir and mix at 15-80°C to prepare core liquid; Step 3: Dry-wet spinning The spinning solution and the core solution are respectively extruded through the outer annular slit and the inner hole of two concentric hollow fiber spinning nozzles to obtain primary fibers. After passing through an air bath, the primary fibers enter a coagulation bath to solidify into a film, and then are drawn and wound in a plasticizing bath to obtain hollow fibers, wherein the winding speed is 5-40 m / min. Step 4: Fiber post-processing Remove the residual solvent and pore-forming agent from the hollow fiber, and remove moisture through 2 to 10 stages of hot air drying at 20 to 100°C; Step 5. Preparation of wet membrane plasma component separator The inlet and outlet of the plasma chamber and the inlet and outlet of the filtrate chamber of the plasma component separator are connected to the water pipeline respectively, and the other end of the water pipeline is connected to the wet membrane liquid kettle; the wet membrane liquid flow rate is controlled at 100-400 mL / min, and the plasma component separator is flushed with the wet membrane liquid in three stages of low-high-low temperature. The process can remove the residual microparticles in the plasma component separator, disinfect and sterilize, and reduce the probability of allergies, micro-inflammation, etc.; finally, the wet membrane liquid temperature is controlled at 20-40℃, and the plasma chamber and filtrate chamber of the plasma component separator are filled with the wet membrane liquid.

[0014] Furthermore, the spinning conditions in step three are as follows: the spinneret and spinning solution temperatures are maintained at 50-70°C and 40-60°C respectively, the air humidity is maintained at 50-80%, the spinning solution pressure is 0.1-0.3 MPa, the spinning speed is 2-10 mL / min, and the core liquid flow rate is 10-50 mL / min.

[0015] Furthermore, in step 3, the air bath height is 1-50 cm, and the coagulation bath is purified water at a temperature of 20-70°C.

[0016] Furthermore, in step 4, the hollow fiber is treated in water at a temperature of 30-42° C. for 6-24 hours, during which the water needs to be changed continuously to remove the residual solvent and pore-forming agent.

[0017] Furthermore, in step 5, the temperature of the first wet film liquid is 30-50°C, and the flushing time is 1-3 minutes; the temperature of the second wet film liquid is 90-120°C, and the flushing time is 3-5 minutes; the temperature of the third wet film liquid is 40-55°C, and the flushing time is 2-3 minutes.

[0018] Based on the above technical solution, the embodiments of the present invention can at least produce the following technical effects: The present invention provides a high-efficiency wet membrane plasma component separator and a preparation method thereof, which is used for plasma component separation treatment, wherein the fiber inner diameter is 100-300 μm, the wall thickness is 20-50 μm, the membrane pore size is 0.0084-0.0478 μm, the albumin screening coefficient is 0.334-0.967, and the total protein screening coefficient is 0.268-0.772. The pore size of the hollow fiber membrane wall is evenly distributed, which avoids blockage during use and has excellent performance stability. Specifically:

[0019] (1) The present invention introduces an amphiphilic block copolymer, which has excellent biocompatibility and a unique microphase separation structure, and forms a uniform microdomain size, which is conducive to forming a uniform pore size with a narrow pore size distribution, and improving porosity and hydrophilicity. The hydrophobic segment of the amphiphilic block polymer has good compatibility with polyethersulfone and plays an anchoring role in the matrix. The hydrophilic segment at the other end is not easily eluted like other hydrophilic additives, and can form a highly hydrated layer on the surface, preventing membrane contamination and maintaining the stability of membrane performance for a long time.

[0020] (2) By adjusting the core liquid composition, plasma component separation membranes with different pore sizes are prepared to achieve the screening function of different target substances, which has a wide range of applications. The process is simple and easy to operate, and the pore size distribution of the plasma component separator membrane wall is uniform, with excellent separation performance.

[0021] (3) When preparing the wet membrane plasma component separator, the wet membrane liquid is introduced to fill the plasma chamber and the filtrate chamber after a three-stage flushing method of low-high-low temperature, thereby removing the residual microparticles in the preparation process, disinfecting and sterilizing, and reducing the probability of allergies, micro-inflammation, etc.; the plasma component separator is kept moistened to facilitate pre-flushing and defoaming; the pore-forming agent is effectively inhibited from dissolving from the membrane body, ensuring the long-term stability and safety of the plasma component separator performance; the protein adhesion is reduced, so that the probability of membrane clogging is greatly reduced; the wet membrane liquid has low production cost and is easy to obtain. DETAILED DESCRIPTION

[0022] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of the present invention.

[0023] The chemical reagents involved in the present invention are all commercially available, and all technical and scientific terms used have the same meanings as commonly understood by those skilled in the art in the art to which the present invention relates.

[0024] Example 1 15 parts of polyethersulfone, 7 parts of poly(lactic acid-glycolic acid)-poly(ethylene glycol) methyl ether copolymer, 3 parts of polyoxyethylene polyoxypropylene ether block copolymer, 3 parts of polyvinyl pyrrolidone, 66 parts of N,N-dimethylacetamide, and 6 parts of glycerol were stirred and dissolved at a temperature of 60-85°C for 24 hours, and the polymer spinning solution was obtained by filtering and degassing. The viscosity of the polymer spinning solution at 50°C is 4280mPa·s.

[0025] Take 20 parts of N,N-dimethylacetamide and 80 parts of purified water and stir and mix them at 50~70℃ to obtain the core liquid. The spinning liquid and the core liquid are extruded through the outer annular seam and inner hole of two concentric hollow fiber spinning nozzles respectively. The temperature of the spinneret and the spinning liquid are maintained at 50℃, the air humidity is maintained at 60~75%, the spinning liquid pressure is 0.25 MPa, the spinning speed is 8 mL / min, and the core liquid flow rate is 25 mL / min. After passing through an air bath with a height of 15 cm, the nascent fiber enters a coagulation bath with a temperature of 50~65℃ to undergo phase inversion and solidification into a film, and then is stretched and wound in a plasticizing bath at a winding speed of 25 m / min. The imitation hollow fiber is treated in water at a temperature of 40℃ for 8 hours, during which the water needs to be changed continuously to remove residual solvents and pore-forming agents. After 2~10 sections of hot air drying at 20~100℃, the moisture is removed. The fiber is collected to make a finished plasma component separator.

[0026] The inlet and outlet of the plasma chamber and the inlet and outlet of the filtrate chamber of the plasma component separator were connected to the water pipeline respectively, and the other end of the water pipeline was connected to the wet membrane liquid kettle. The wet membrane liquid flow rate was controlled at 200 mL / min, and the plasma component separator was flushed in three stages of low-high-low temperature. Among them, the temperature of the first stage wet membrane liquid was 30~50℃, and the flushing time was 1~3 minutes; the temperature of the second stage wet membrane liquid was 90~120℃, and the flushing time was 3~5 minutes; the temperature of the third stage wet membrane liquid was 40~55℃, and the flushing time was 2~3 minutes. Finally, the temperature of the wet membrane liquid was controlled at 20~40℃, and the plasma chamber and filtrate chamber of the plasma component separator were filled with wet membrane liquid. A high-efficiency wet membrane plasma component separator was obtained, with a fiber inner diameter of 186 μm, a wall thickness of 42 μm, and a membrane pore size of 0.0089 μm.

[0027] Example 2 Take 42 parts of N,N-dimethylacetamide and 58 parts of purified water and stir and mix at 50-70°C to obtain a core liquid. The same operation steps as in Example 1 were subsequently performed, wherein the spinning solution pressure was changed to 0.20 MPa, the spinning speed was 6 mL / min, the core liquid flow rate was 28 mL / min, and the winding speed was 24 m / min. A high-efficiency wet membrane plasma component separator was obtained, with a fiber inner diameter of 192 μm, a wall thickness of 40 μm, and a membrane pore size of 0.0258 μm.

[0028] Example 3 Take 55 parts of N,N-dimethylacetamide and 45 parts of purified water and stir and mix at 50-70°C to obtain a core liquid. The same operation steps as in Example 1 were subsequently performed, wherein the spinning solution pressure was changed to 0.26 MPa, the spinning speed was 10 mL / min, the core liquid flow rate was 22 mL / min, and the winding speed was 26 m / min. A high-efficiency wet membrane plasma component separator was obtained, with a fiber inner diameter of 188 μm, a wall thickness of 46 μm, and a membrane pore size of 0.0310 μm.

[0029] Example 4 Take 72 parts of N,N-dimethylacetamide and 28 parts of purified water and stir and mix at 50-70°C to obtain a core liquid. The same operation steps as in Example 1 were subsequently performed, wherein the spinning solution pressure was 0.28 MPa, the spinning speed was 12 mL / min, the core liquid flow rate was 26 mL / min, and the winding speed was 27 m / min. A high-efficiency wet membrane plasma component separator was obtained, with a fiber inner diameter of 186 μm, a wall thickness of 42 μm, and a membrane pore size of 0.0435 μm.

[0030] The high-performance wet membrane plasma component separator obtained in Examples 1-4 was tested for plasma protein screening coefficients, and the results are shown in Tables 1 and 2.

[0031] Table 1 Screening coefficients of plasma proteins in Examples 1-4 Plasma proteins Example 1 Screening Coefficient Example 2 Screening Coefficient Example 3 Screening Coefficient Example 4 Screening Coefficient albumin 0.443 0.529 0.736 0.841 Total Protein 0.312 0.442 0.616 0.687 IgG 0.153 0.378 0.576 0.725 IgM 0.002 0.005 0.104 0.150 Total cholesterol 0.114 0.178 0.352 0.443 LDL 0.001 0.002 0.085 0.103 The high-efficiency wet membrane plasma component separator of Example 1-4 removes less beneficial components in plasma, avoiding the loss of a large amount of beneficial components, and can effectively remove large molecular pathogenic substances. According to the different screening performances of different plasma proteins, appropriate specifications are selected, which can effectively remove target substances and lose very little non-pathogenic substances such as albumin that are useful to the patient himself.

[0032] Table 2 Screening coefficients of plasma albumin in Examples 1-4 albumin Example 1 Screening Coefficient Example 2 Screening Coefficient Example 3 Screening Coefficient Example 4 Screening Coefficient Cycle for 5 minutes 0.538 0.574 0.747 0.849 15 minutes of circulation 0.552 0.580 0.845 0.939 Cycle 30 minutes 0.461 0.531 0.762 0.848 60 minutes cycle 0.445 0.529 0.739 0.880 90 minutes cycle 0.443 0.529 0.736 0.841 After 90 minutes of circulation, the plasma albumin screening coefficients of the high-performance wet membrane plasma component separators of Examples 1-4 only decreased by 17.66%, 7.8%, 1.47% and 0.94%, respectively, indicating that the products can still maintain stable performance after long-term therapeutic use.

[0033] The above is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A high-efficiency wet membrane plasma component separator, characterized in that: The invention comprises the following components in parts by weight: 10 to 35 parts of polyether sulfone, 3 to 20 parts of amphiphilic polymer, 2 to 25 parts of pore former, 40 to 84.5 parts of solvent and 0.5 to 12 parts of non-solvent.

2. The high-efficiency wet membrane plasma component separator according to claim 1, characterized in that: The amphiphilic polymer includes a mixture of poly(lactic acid-glycolic acid)-polyethylene glycol and copolymer poly(lactic acid-glycolic acid) in a mass ratio of 50:50 to 75:25, a mixture of poly(lactic acid-glycolic acid)-poly(ethylene glycol) methyl ether copolymer and poly(lactic acid-glycolic acid) in a mass ratio of 50:50 to 75:25, and a stearic acid polyethylene glycol carboxylic acid and polyoxyethylene polyoxypropylene ether block copolymer.

3. The high-efficiency wet membrane plasma component separator according to claim 2, characterized in that: The molecular weight of the poly(lactic acid-glycolic acid)-poly(ethylene glycol) is 10,000-30,000; the molecular weight of the poly(lactic acid-glycolic acid)-poly(ethylene glycol) methyl ether copolymer is 10,000-30,000; the molecular weight of the stearic acid polyethylene glycol carboxylic acid is 4,000-10,000; and the hydrophilic-lipophilic balance value of the polyoxyethylene polyoxypropylene ether block copolymer is 20-30.

4. The high-efficiency wet membrane plasma component separator according to claim 1, characterized in that: The pore-forming agent is any one or any combination of polyvinyl pyrrolidone with a molecular weight of 20,000 to 700,000, polyvinyl alcohol with a molecular weight of 3,000 to 40,000, and polyethylene glycol with a molecular weight of 1,000 to 10,000.

5. The high-efficiency wet membrane plasma component separator according to claim 1, characterized in that: The solvent is any one or any combination of dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, and N,N-dimethylformamide.

6. The high-efficiency wet membrane plasma component separator according to claim 1, characterized in that: The non-solvent includes purified water, propylene glycol and glycerol; the molecular weight of the polyethersulfone is 30,000-150,000.

7. The method for preparing a high-efficiency wet membrane plasma component separator according to any one of claims 1 to 6, characterized in that: The following steps are involved: Step 1: Preparation of spinning solution 10-35 parts of polyethersulfone, 3-20 parts of amphiphilic polymer, 2-25 parts of pore-forming agent, 40-84.5 parts of solvent, 0.5-12 parts of non-solvent, stirring and dissolving at a temperature of 60-85°C for 8-48 hours, filtering and degassing to obtain a polymer spinning solution; Step 2: Preparation of core solution Take 15-75 parts of solvent and 25-85 parts of purified water and stir and mix at 15-80°C to prepare core liquid; Step 3: Dry-wet spinning The spinning solution and the core solution are respectively extruded through the outer annular slit and the inner hole of two concentric hollow fiber spinning nozzles to obtain primary fibers. After passing through an air bath, the primary fibers enter a coagulation bath to solidify into a film, and then are drawn and wound in a plasticizing bath to obtain hollow fibers, wherein the winding speed is 5-40 m / min. Step 4: Fiber post-processing Remove the residual solvent and pore-forming agent from the hollow fiber, and remove moisture through 2 to 10 stages of hot air drying at 20 to 100°C; Step 5. Preparation of wet membrane plasma component separator The inlet and outlet of the plasma chamber and the inlet and outlet of the filtrate chamber of the plasma component separator are connected to the water pipeline respectively, and the other end of the water pipeline is connected to the wet membrane liquid kettle; the wet membrane liquid flow rate is controlled at 100-400 mL / min, and the plasma component separator is flushed with the wet membrane liquid in three stages of low-high-low temperature; finally, the wet membrane liquid temperature is controlled at 20-40°C, and the plasma chamber and filtrate chamber of the plasma component separator are filled with the wet membrane liquid.

8. The method for preparing a high-efficiency wet membrane plasma component separator according to claim 7, characterized in that: The spinning conditions in step 3 are as follows: the spinneret and spinning solution temperatures are maintained at 50-70°C and 40-60°C respectively, the air humidity is maintained at 50-80%, the spinning solution pressure is 0.1-0.3 MPa, the spinning speed is 2-10 mL / min, and the core liquid flow rate is 10-50 mL / min.

9. The method for preparing a high-efficiency wet membrane plasma component separator according to claim 7, characterized in that: In step 3, the air bath height is 1-50 cm, and the coagulation bath is purified water at a temperature of 20-70°C.

10. The method for preparing a high-efficiency wet membrane plasma component separator according to claim 7, characterized in that: In step 5, the temperature of the first wet film liquid is 30-50°C, and the flushing time is 1-3 minutes; the temperature of the second wet film liquid is 90-120°C, and the flushing time is 3-5 minutes; the temperature of the third wet film liquid is 40-55°C, and the flushing time is 2-3 minutes.