Hollow fiber membrane for continuous kidney replacement therapy and preparation method

Abstract

The invention discloses a hollow fiber membrane for continuous kidney replacement therapy and a preparation method thereof. The hollow fiber membrane comprises the following components in percentage by weight: 8-28% of a high polymer matrix, 5-20% of a hydrophilic additive, 0-3% of an antioxidant additive and the balance of a solvent. According to the invention, the high polymer containing hydrophilic modified group sulfonate radical and hydroxyl is blended and added into the high polymer matrix, the operation is simple, and no complex synthetic reaction process is needed, so that the proportion of the added hydrophilic additive can be obviously reduced, and the risk of more elution after film formation due to excessive addition of the hydrophilic modifier is reduced. In addition, anti-oxidation components can be added, so that the hemodialysis membrane is non-toxic, and the blood compatibility and the anti-oxidation performance of the hemodialysis membrane can be improved. The hemodialysis membrane can be used for continuous kidney replacement therapy, the service life of the membrane is greatly prolonged, and the blood coagulation risk is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of dialysis membrane, in particular to a hollow fiber membrane for continuous renal replacement therapy and a preparation method thereof. BACKGROUND

[0002] Continuous renal replacement therapy belongs to a kind of hemodialysis, which is a continuous extracorporeal blood purification treatment technology for 24 hours or close to 24 hours, and a continuous and slow treatment method for removing water and solutes. The difference is that the blood flow rate of conventional hemodialysis is 200-400 ml / min, the dialysate flow rate is usually 500-800 ml / min, and the treatment time is 4 hours. However, the blood flow rate and dialysate flow rate of continuous renal replacement therapy are usually lower, the blood flow rate is generally 50-200 ml / min, the dialysate flow rate is generally 10-50 ml / min, and the treatment time is more than 8 hours. If the filter used for dialysis does not cause blood clotting, the filter can be continuously treated for more than 24 hours without replacement. And patients may have various adverse reactions during dialysis due to allergic reactions to dialysis membranes, which has higher requirements for the stability and safety of dialysis membranes.

[0003] As the most critical part of the dialysis process, the current dialysis membrane mainly includes cellulose and its derivatives dialysis membrane and synthetic polymer dialysis membrane. High molecular weight dialysis membranes have been widely used in hemodialysis membranes due to their excellent mechanical properties, chemical corrosion resistance, thermal stability and good ductility, such as polysulfone, polyethersulfone, etc. However, most of the high molecular weight membranes have certain hydrophobicity, and the prepared membranes are easy to adsorb and accumulate proteins, etc., so they generally need to be modified before use. From the modification purpose, the modification can be divided into hydrophilic modification, antioxidant modification and blood compatibility modification, etc. From the modification method, it can be divided into blending modification, surface modification, etc. The introduction of hydrophilic substances (such as polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, etc.) on the surface of the membrane, blood compatibility, antioxidant substances (such as vitamin C, resveratrol and other polyphenolic compounds, scullcapflavone, etc.) can help to improve the blood compatibility of the dialysis membrane, alleviate the oxidative stress phenomenon in hemodialysis, improve the dialysis efficiency and improve the prognosis of patients.

[0004] Blood compatibility is an index for evaluating whether a reaction occurs and the degree of reaction when a foreign material contacts with blood, and the compatibility between the material and the components of blood. It mainly includes the adsorption of plasma proteins (such as albumin, etc.) in blood by the material, the deformation and rupture of red blood cells caused by the contact of the material with blood, the adhesion of white blood cells and platelets, etc. Hemodialysis patients are also prone to oxidative stress, mainly due to the loss of antioxidants during dialysis or complement activation, platelet adhesion and activation caused by poor biocompatibility of hemodialysis membranes.

[0005] At present, the dialysis membrane in China is mainly used for conventional dialysis, i.e. ordinary kidney replacement therapy, but the dialyzer for continuous kidney replacement therapy (treatment time close to or greater than 24h) mainly relies on imported dialysis membrane, and it is necessary to develop a dialysis membrane which can replace the imported dialysis membrane and is used for continuous kidney replacement therapy and has blood compatibility and oxidation resistance. SUMMARY

[0006] The purpose of the present application is to provide a hollow fiber membrane for continuous kidney replacement therapy and a preparation method, so as to solve the problems of few hollow fiber membrane products for continuous kidney replacement therapy in the prior art and unstable performance after long time use.

[0007] To achieve the above-mentioned purpose, the present application provides the following technical solutions: The present application provides a hollow fiber membrane for continuous kidney replacement therapy, comprising the following components by weight percentage: 8-28% of a polymer matrix, 5-20% of a hydrophilic additive, 0-3% of an antioxidant additive, and the balance of a solvent.

[0008] Further, the polymer matrix is obtained by blending modified polysulfone or polyethersulfone and unmodified polysulfone or polyethersulfone, the modified polysulfone or polyethersulfone is 3-10%, and the unmodified polysulfone or polyethersulfone is 5-18%.

[0009] Further, the modified polysulfone or polyethersulfone is modified by sulfonation or hydroxylation, and a sulfonic acid group or a hydroxyl group is introduced on the polysulfone or polyethersulfone molecule.

[0010] Polysulfone is a thermoplastic resin containing sulfone groups (-SO 2- ) and arylene groups in the molecular backbone.

[0011] Sulfonation and hydroxylation modification of materials is a method for increasing the hydrophilicity of materials, and sulfonation / hydroxylation reaction refers to the reaction in which hydrogen atoms in an organic polymer are replaced by sulfonic acid groups (-SO3H) or hydroxyl groups (-OH). The introduction of sulfonic acid groups (-SO3H) or hydroxyl groups (-OH) can increase the heat resistance, emulsifying property, wetting property and hydrophilicity of organic matter. While improving the hydrophilicity and heat resistance of the membrane material, the separation and permeation properties of the functional membrane and the protein adhesion performance can also be effectively improved.

[0012] In the present application, sulfonated or hydroxylated polysulfone or polyethersulfone is used as one of the hydrophilic modification materials, and is blended with the polysulfone or polyethersulfone bulk material to form the polymer matrix of the hollow fiber membrane. The blending can maintain the original structure and performance of the modified material, and the operation is simple.

[0013] Further, the hydrophilic additive is one or two of polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone.

[0014] Further, the antioxidant additive is one of silymarin, resveratrol, and vitamin C.

[0015] Further, the solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone.

[0016] The application also provides a preparation method of a hollow fiber membrane for continuous renal replacement therapy, comprising the following steps: Step one, preparation of casting solution The modified polysulfone or polyethersulfone and the unmodified polysulfone or polyethersulfone are blended in a certain proportion, and then a hydrophilic additive and / or an antioxidant additive are added, and the above-mentioned substances are added to a solvent for blending, heating and dissolving, and then defoaming to prepare a casting solution; Step two, preparation of core solution The solvent and water are taken to prepare a core solution with a concentration of 10-60%; Step three, dry-wet spinning The casting solution and the core solution are pressed into the spinneret at a pressure of 0.1-0.3 MPa, the casting solution and the core solution are extruded through the nozzles in the spinneret to form nascent fibers, the nascent fibers are passed through an air bath and into a coagulation bath to form, and then they are pulled to a washing area for multi-stage washing to remove excess solvent, and then the hollow fiber membrane filaments are pulled to a drying section for drying to obtain a hollow fiber membrane for continuous renal replacement therapy.

[0017] Further, the casting solution can also be used to prepare a flat sheet membrane, specifically: a film applicator is used, the thickness of the doctor blade is adjusted to be 20-500 μm, the temperature is set to be 40-60 ℃, the speed is set to be 5-40 mm / S, the coagulation bath is solvent and water, the ratio of the solvent and water is 0-50%, and the temperature is 25-60 ℃; the flat sheet membrane scraped by the film applicator is placed into the coagulation bath to form a flat sheet membrane.

[0018] Based on the above technical solution, the application embodiment can at least produce the following technical effects: Most of the existing hemodialysis membranes are composed of a single high polymer component such as polysulfone or polyethersulfone. The hydrophobicity and protein adsorption defects of the high polymer itself require the addition of a modified component to improve its hydrophilicity. Most of the hemodialysis membranes are modified by adding a certain amount of hydrophilic modifier. The hollow fiber membrane for continuous renal replacement therapy and the preparation method provided by the present application add a high polymer containing a hydrophilic modification group such as sulfonate and hydroxyl to the high polymer matrix, which is simple to operate and has no complex synthetic reaction process. Therefore, the proportion of the added hydrophilic additive can be significantly reduced, and the risk of excessive addition of the hydrophilic modifier and elution after film formation is reduced. In addition, the present application can also add an antioxidant component which is non-toxic and can improve the blood compatibility and antioxidant performance of the hemodialysis membrane. The hemodialysis membrane in the present application can be used for continuous renal replacement therapy, greatly prolonging the service life of the membrane and reducing the risk of blood clotting. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings described below are only some embodiments of the present application, and for those skilled in the art, other drawings can be obtained from the structures shown in the drawings without creative labor.

[0020] Figure 1 is a schematic diagram of the membrane assembly of the embodiment of the present application. DETAILED DESCRIPTION

[0021] The technical solutions in the embodiments of the present application will be described clearly and completely in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0022] Embodiment 1 7% sulfonated polysulfone, 10% polyethersulfone, 10% polyethylene glycol, 1% resveratrol, 72% N,N-dimethylformamide were blended and heated to dissolve for more than 24 hours. After dissolution, the solution was degassed for more than 24 hours to form a uniform solution. A film coating machine was used, the thickness of the doctor blade was adjusted to 200 microns, the temperature was set to 45 DEG C, the speed was set to 15 mm / s, and the coagulation bath was 40% N,N-dimethylformamide aqueous solution with a temperature of 40 DEG C. The flat plate film scraped by the film coating machine was placed in the coagulation bath to form a film.

[0023] A control group flat plate film was prepared by the same method. The composition of the control group flat plate film was 17% polyethersulfone, 10% polyethylene glycol and 73% N,N-dimethylformamide.

[0024] One of the main methods to evaluate the hydrophilic or hydrophobic property of the membrane surface is water contact angle test. The dried membrane is fixed on a glass slide, and the contact angle test is performed on a contact angle tester at room temperature. The water contact angle of the membrane is calculated at 10s, and its value is recorded. Each membrane is measured at least three times, and the average value is taken.

[0025] The blood compatibility and oxidative stress of the membrane are evaluated in relation to platelet adhesion. The change in the number of platelets before and after the membrane of a certain size contacts blood is tested with rabbit blood to calculate the platelet adhesion rate. The higher the adhesion rate, the worse the compatibility of the membrane. The contact angle and platelet adhesion are tested respectively. The results are shown in Table 1.

[0026] Table 1 Test item Example 1 film Control film Water contact angle 42° 95° Platelet adhesion rate 14.78% 58.39% Example 2 6% of hydroxyl polyether sulfone, 8% of polyether sulfone, 6% of polyethylene glycol, 2% of polyvinyl alcohol, 1% of silymarin, 77% of N,N-dimethylacetamide are blended and heated to dissolve for more than 24h. After the dissolution is completed, the casting solution is degassed for more than 24h to form a casting solution. The core solution is prepared as a 40% N,N-dimethylacetamide solution.

[0027] The casting and core solutions are pressed into the spinneret plate at a certain pressure. The spinning solution and the core solution are extruded through the nozzles in the spinneret to form nascent fibers. The nascent fibers fall into the coagulation bath through an air gap to form a hollow fiber membrane. The membrane is drawn to the water washing area for multi-stage water washing to remove excess solvent. The hollow fiber membrane is then drawn to the drying section for drying. Finally, the dried fibers are wound into a fiber bundle through the fiber winding frame.

[0028] The spinning solution of the control group hollow fiber membrane is composed of 16% polyether sulfone, 6% polyethylene glycol, and 78% N,N-dimethylacetamide. The core solution is a 35% N,N-dimethylacetamide solution. The hollow fiber membrane is spun by the same method.

[0029] The spun fiber bundle is assembled into a membrane assembly for testing. The change rate of platelets before and after circulation of the two groups of membranes is tested with bovine blood, as shown in Table 2.

[0030] The blood circulation flow rate is 200ml / min, and the circulation time is 8h. Blood samples are taken at 0h, 4h, and 8h for testing. The circulation device is shown in Figure 1 .

[0031] Example 3 The difference between Example 1 is that 7% sulfonated polysulfone, 10% polyether sulfone, 10% polyethylene glycol, 73% N,N-dimethylformamide are blended and heated to dissolve for more than 24 hours. After the dissolution is completed, the solution is degassed for more than 24 hours to form a uniform solution. A coating machine is used, the doctor blade thickness is adjusted to 200 pm, the temperature is set to 45°C, the speed is set to 15 mm / s, and the coagulation bath is 40% N,N-dimethylformamide aqueous solution with a temperature of 40°C. The flat film scraped by the coating machine is placed into the coagulation bath to form a film.

[0032] A control flat film is prepared in the same way. The composition of the control flat film is 17% polyether sulfone, 10% polyethylene glycol, and 73% N,N-dimethylformamide.

[0033] One of the main methods for evaluating the hydrophilicity or hydrophobicity of the film surface is water contact angle testing. The dried film is fixed on a glass slide, and the contact angle test is performed on a contact angle tester at room temperature. The water contact angle of the film is calculated at 10 s, and the value is recorded. Each film is measured at least three times, and the average value is taken.

[0034] The blood compatibility and oxidative stress of the film are related to platelet adhesion. The change in the number of platelets before and after the film contacts blood is tested to calculate the platelet adhesion rate. The higher the adhesion rate, the worse the compatibility of the film. The contact angle and platelet adhesion are tested respectively. The results are shown in Table 3.

[0035] Table 3 Test item Example 3 film Control film Water contact angle 40° 95° Platelet adhesion rate 20.58% 58.39% Example 4 The difference between Example 2 is that 3% hydroxyl polyether sulfone, 18% polyether sulfone, 3% polyethylene glycol, 2% polyvinyl alcohol, 1% silymarin, and 73% N,N-dimethylacetamide are blended and heated to dissolve for more than 24 hours.

[0036] The casting film and core liquid are pressed into the spinneret plate at a certain pressure. The spinning solution and core liquid are extruded through the nozzles in the spinneret plate to form nascent fibers. The nascent fibers fall into the coagulation bath to form a hollow fiber membrane. The membrane is drawn to the washing area for multi-stage washing to remove excess solvent. The hollow fiber membrane is then drawn to the drying section for drying. Finally, the dried fibers are wound into a fiber bundle through the fiber collection frame.

[0037] The control hollow fiber membrane spinning solution is composed of 3% hydroxyl polyether sulfone, 18% polyether sulfone, 3% polyethylene glycol, 2% polyvinyl alcohol, and 74% N,N-dimethylacetamide solution. The hollow fiber membrane is spun in the same way.

[0038] The spun fiber bundle is assembled into a membrane assembly for testing. The change rate of platelet circulation before and after the membrane is tested using bovine blood. The results are shown in Table 4.

[0039] Example 5 The difference from Example 2 is that: 10% hydroxy polyether sulfone, 5% polyether sulfone, 10% polyethylene glycol, 8% polyvinyl alcohol, 1% vitamin C, and 66% N-methyl pyrrolidone are blended and heated to dissolve for more than 24 hours, the casting membrane and core liquid are pressed into the spinneret at a certain pressure, the spinning liquid and core liquid are extruded through the nozzle in the spinneret to form nascent fibers, the nascent fibers pass through an air gap and fall into the coagulation bath to be formed, they are pulled to the washing area for multiple water washings to remove excess solvent, and then the hollow fiber membrane filaments are pulled to the drying section for drying, and finally the dried filaments are wound into a bundle through a wire collection rack.

[0040] The above description is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this field, several variations and improvements can be made without departing from the creative concept of the present invention, which all fall within the scope of protection of the present invention.

Claims

1. A hollow fiber membrane for continuous renal replacement therapy, characterized in that: The invention comprises the following components in weight percentage: 8-28% of a polymer matrix, 5-20% of a hydrophilic additive, 0-3% of an antioxidant additive, and the balance being a solvent.

2. The hollow fiber membrane for continuous renal replacement therapy according to claim 1, characterized in that The polymer matrix is ​​obtained by blending modified polysulfone or polyethersulfone and unmodified polysulfone or polyethersulfone, wherein the modified polysulfone or polyethersulfone accounts for 3-10% and the unmodified polysulfone or polyethersulfone accounts for 5-18%.

3. The hollow fiber membrane for continuous renal replacement therapy according to claim 2, characterized in that The modified polysulfone or polyethersulfone is modified by sulfonation or hydroxylation, and sulfonic acid groups or hydroxyl groups are introduced into the polysulfone or polyethersulfone molecules.

4. The hollow fiber membrane for continuous renal replacement therapy according to claim 1, characterized in that The hydrophilic additive is one or two of polyethylene glycol, polyvinyl alcohol and polyvinyl pyrrolidone.

5. The hollow fiber membrane for continuous renal replacement therapy according to claim 1, characterized in that The antioxidant additive is one of silybin, resveratrol and vitamin C.

6. The hollow fiber membrane for continuous renal replacement therapy according to claim 1, characterized in that The solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone.

7. The method for preparing a hollow fiber membrane for continuous renal replacement therapy according to any one of claims 1 to 6, characterized in that: The following steps are involved: Step 1: Preparation of casting solution The modified polysulfone or polyethersulfone and the unmodified polysulfone or polyethersulfone are blended in proportion, and then a hydrophilic additive and / or an antioxidant additive are added. The above substances are added into a solvent, blended, heated and dissolved, and degassed after dissolution to prepare a casting solution; Step 2: Preparation of core solution Prepare a core solution with a concentration of 10-60% by taking solvent and water; Step 3: Dry-wet spinning The casting liquid and core liquid are pressed into the spinneret at a pressure of 0.1-0.3MPa. The casting liquid and core liquid are extruded through the nozzle in the spinneret to form nascent fibers. The nascent fibers pass through an air bath and enter a coagulation bath to be formed. They are then pulled to a water washing area for multiple water washings to remove excess solvent. The hollow fiber membrane filaments are then pulled to a drying section for drying to obtain hollow fiber membranes for continuous renal replacement therapy.

8. The method for preparing a hollow fiber membrane for continuous renal replacement therapy according to claim 7, characterized in that: The casting solution in step 1 can also be used to prepare a flat film, specifically: using a film coater, a film blade with a thickness adjustment range of 20-500 μm, a temperature set to 40-60°C, a speed set to 5-40 mm / s, a coagulation bath of solvent and water, a solvent-water ratio of 0-50%, and a temperature of 25-60°C; placing the flat film scraped by the film coater into the coagulation bath to form a film to obtain a flat film.

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