Modified polyether sulfone hollow fiber hemodialysis membrane and method for preparing the same

Abstract

The application discloses a modified polyether sulfone hollow fiber hemodialysis membrane and a preparation method thereof. The main part of the hemodialysis membrane is a polyether sulfone membrane, and a modifier comprises polyvinylpyrrolidone and citric acid. The modifier molecules are combined on the inner surface of the hollow fiber membrane to form the hemodialysis membrane. The polyether sulfone hollow fiber hemodialysis membrane has the advantages that the polyvinylpyrrolidone and citric acid added in the core liquid are used as the modifier, the hydrophilicity of the polyvinylpyrrolidone and the anticoagulant property of the citric acid are utilized, the hydrogen bonds are formed by the action of the proton-donating groups on the citric acid molecules, the carbonyl groups on the polyvinylpyrrolidone and the oxygen atoms on the polyether sulfone main chain in the spinning solution, the polyvinylpyrrolidone and the citric acid are combined on the inner surface of the hollow fiber membrane, the polyvinylpyrrolidone is further fixed by the entanglement of the polyvinylpyrrolidone and the polyether sulfone molecular chains, and the modified polyether sulfone hollow fiber hemodialysis membrane has the advantages of persistent and stable hydrophilicity and anticoagulant property.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, and particularly relates to a modified polyether sulfone hollow fiber hemodialysis membrane and a preparation method thereof. BACKGROUND

[0002] As a key component of blood purification consumables, the performance of the hollow fiber hemodialysis membrane directly affects the effectiveness and safety of dialysis. The dialysis membrane material mainly includes cellulose and high molecular synthetic materials. The high molecular synthetic membrane is usually prepared by a non-solvent induced phase separation (NIPS) method. The main process is as follows: preparing a homogeneous polymer solution (including a polymer, a solvent, and an additive), a core liquid, and a coagulation bath, then extruding the polymer solution through a spinning die (spinneret), and exchanging the polymer solution with the core liquid and the coagulation bath to change the thermodynamic state of the polymer solution, so that the polymer solution is phase separated from the homogeneous state to a three-dimensional macromolecular network gel structure, and finally solidified into a membrane.

[0003] Polyether sulfone is widely used in the preparation of hollow fiber hemodialysis membranes due to its good film-forming property, good mechanical property, chemical resistance, high temperature resistance, and other characteristics, and is a main high molecular synthetic membrane. However, due to the hydrophobicity of the polyether sulfone material itself, when in contact with blood, it can easily trigger the blood cascade to form thrombus on the surface of the dialysis membrane, and further cause the membrane hole to be blocked, the membrane flux to be greatly attenuated, the toxin removal rate to be reduced, and other problems. In addition, it can also cause the activation of the body's complement, so that the hemodialysis membrane is attacked by the human immune system. In clinical applications, heparin (unfractionated heparin or low molecular weight heparin) is usually injected to inhibit the formation of thrombus in the dialyzer. However, the metabolism of heparin is difficult, which is not suitable for some patients with bleeding symptoms, and long-term injection of heparin can also cause thrombocytopenia, hyperkalemia, osteoporosis, and other problems. Therefore, improving the hydrophilicity and anticoagulant property of the polyether sulfone membrane material is the development trend of hemodialysis.

[0004] At present, the hydrophilic and anticoagulant modification of polyether sulfone membranes is mainly through physical modification or chemical modification methods to introduce specific functional groups or substances, such as amino, carboxyl, sulfonic acid group, heparin, citric acid, and the like, to improve the hydrophilicity and anticoagulant property of the membrane. For example, Chinese patent CN 105311974A takes poly sulfone hemodialysis membrane as the modification target, first prepares a triblock copolymer containing poly sulfone or polyether sulfone and acrylic acid by atom transfer radical polymerization, then blends the copolymer with poly sulfone, spins, and prepares a poly sulfone hemodialysis membrane. The carboxyl group on the surface of the dialysis membrane is used to graft heparin onto the surface of the dialysis membrane to improve the hydrophilicity and anticoagulant property of the dialysis membrane.

[0005] The existing physical or chemical modification methods of polyether sulfone membranes have the problems that the modified groups or substances are gradually lost during use, or the compatibility of the modified groups or substances with the main body material of the membranes is poor, resulting in the decrease of the mechanical properties, chemical resistance, high temperature resistance and other properties of the modified hollow fiber hemodialysis membranes; for example, the hydrophilicity is improved by blending polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), but PVP and PEG are water-soluble polymers, which are easily precipitated during the preparation and use of the membranes, resulting in the decrease or loss of hydrophilicity; or the hydrophilicity and anticoagulant properties can be maintained for a long time by some complex modification methods, but the processes are complex, the cost is high, and it is difficult to scale up the production, for example, the hydrophilic and anticoagulant groups or substances are grafted on the polysulfone material by plasma, irradiation, photo initiation and other methods. SUMMARY

[0006] The purpose of the present application is to solve the problems of poor hydrophilicity and anticoagulant property of the existing polyether sulfone hollow fiber hemodialysis membrane, and the present application provides a modified polyether sulfone hollow fiber hemodialysis membrane with stable hydrophilicity and anticoagulant property. In the present application, a hydrophilic and anticoagulant modifier is added to the core liquid, and the hydrophilic and anticoagulant modifier is coated on the inner surface of the hollow fiber membrane during the exchange forming process of the hollow fiber membrane. The hydrophilic and anticoagulant modifier is firmly combined with the inner surface of the polyether sulfone membrane through chemical forces such as hydrogen bonds and entanglement of polymer chains, thereby providing stable hydrophilicity and anticoagulant property.

[0007] In order to achieve the purpose of the present application, the technical scheme adopted by the present application is as follows:

[0008] The first aspect of the present application provides a modified polyether sulfone hollow fiber hemodialysis membrane, the main part of the hemodialysis membrane is a polyether sulfone membrane, and the modifier comprises polyvinylpyrrolidone and citric acid. The modifier molecules are combined with the inner surface of the hollow fiber membrane.

[0009] The inner diameter of the hollow fiber hemodialysis membrane is 150-350 μm, and the wall thickness is 50-100 μm.

[0010] The second aspect of the present application provides a preparation method of the modified polyether sulfone hollow fiber hemodialysis membrane described above, which comprises the following steps:

[0011] S1, preparing a spinning solution: 14-22% of polyether sulfone, 3-15% of a pore former, 0-7% of a non-solvent and 56-83% of an organic solvent are mixed according to the weight percentage, heated and fully dissolved, and then static deaeration is performed to obtain the spinning solution;

[0012] S2, preparing a core liquid: the components of the core liquid are mixed and fully dissolved to obtain the core liquid; according to the weight percentage, the core liquid contains 1-10% of polyvinylpyrrolidone, 1-10% of citric acid, and the balance is water;

[0013] S3, hollow fiber membrane preparation: the spinning solution and the core solution are respectively delivered to the spinneret for extrusion, enter the water bath after air process for solidification and molding, and finally are washed by water, dried, and collected.

[0014] Preferably, the raw materials in step S1 are mixed and heated at a temperature of 60-90°C for 8-24h, and then left to stand for 12-24h for defoaming to obtain the spinning solution.

[0015] In step S2, the raw material components of the core solution are mixed and heated at 20-60°C to obtain the core solution.

[0016] Preferably, the specific operation of step S3 is as follows: the spinning solution and the core solution are respectively delivered to the spinneret for extrusion by a metering pump, the rotation speed of the metering pump is adjusted so that the flow rate of the spinning solution is 7-13ml / min and the flow rate of the core solution is 7.5-13.5ml / min, after an air process of 1-60cm, the spinning solution and the core solution enter a water bath with a temperature of 20-60°C for solidification and molding, then are driven by a roller with a linear speed of 10-40m / min, sequentially pass through a water washing tank with a temperature of 60-95°C for cleaning, an oven with a temperature of 80-140°C for drying, and finally are collected on a spinning reel.

[0017] Further preferably, the specific operation of step S3 is as follows: the spinning solution and the core solution are respectively delivered to the spinneret for extrusion by a metering pump, the rotation speed of the metering pump is adjusted so that the flow rate of the spinning solution is 9.4-9.8ml / min and the flow rate of the core solution is 9.8-10.2ml / min, after an air process of 40-50cm, the spinning solution and the core solution enter a water bath with a temperature of 50-60°C for solidification and molding, then are driven by a roller with a linear speed of 10-40m / min, sequentially pass through a water washing tank with a temperature of 70-90°C for cleaning, an oven with a temperature of 100-140°C for drying, and finally are collected on a spinning reel.

[0018] Preferably, in step S1,

[0019] The pore-forming agent is one or more of polyvinylpyrrolidone, polyethylene glycol, and polyvinyl alcohol in any proportion.

[0020] The non-solvent is one or more of water, ethanol, isopropyl alcohol, and glycerol in any proportion.

[0021] The organic solvent is dimethylacetamide.

[0022] Further preferably, in step S1, the pore-forming agent is polyvinylpyrrolidone, and the non-solvent is water.

[0023] Preferably, in step S1, the spinning solution contains 14%-20% of polyether sulfone, 5%-15% of the pore-forming agent, 1%-7% of the non-solvent, and 64%-75% of the organic solvent by weight percentage.

[0024] In step S2, the core liquid comprises 2-10% polyvinylpyrrolidone, 1-10% citric acid, and the balance is water.

[0025] Further preferably, the spinning solution comprises 14-17% polyether sulfone, 8-15% porogen, 3-7% non-solvent, and 64-72% organic solvent.

[0026] The polyvinylpyrrolidone in the core liquid is 2-7% by weight, the citric acid is 4-10% by weight, and the balance is water.

[0027] The beneficial effects of the present application are:

[0028] 1. The modified polyether sulfone hollow fiber hemodialysis membrane provided by the present application is composed of polyether sulfone, the polyvinylpyrrolidone and citric acid added in the core liquid are modifiers, the hydrophilicity of polyvinylpyrrolidone and the anticoagulant property of citric acid are utilized, the hydrogen bonds are formed by the action of the proton-donating groups (such as -COOH and -OH) on the citric acid molecules with the carbonyl group on the polyvinylpyrrolidone and the oxygen atoms on the polyether sulfone main chain in the spinning solution, the polyvinylpyrrolidone and citric acid are combined on the inner surface of the hollow fiber membrane, and the polyvinylpyrrolidone is further fixed by winding with the polyether sulfone molecular chain, so that the modified polyether sulfone hollow fiber hemodialysis membrane has persistent, stable hydrophilicity and anticoagulant property.

[0029] 2. The present application mainly adds modified substances in the core liquid and fixes them on the inner surface of the hollow fiber membrane, and the main part of the hollow fiber membrane is still composed of polyether sulfone, so as to ensure that the modified hollow fiber hemodialysis membrane has good mechanical properties, chemical resistance, and high temperature resistance.

[0030] 3. The hydrophilic anticoagulant modifier used in the present application is composed of polyvinylpyrrolidone and citric acid, the modification process is simple, the preparation process of the present application is the same as the existing polyether sulfone hollow fiber hemodialysis membrane production process, the process route does not need to be changed, new machine equipment does not need to be added, and the production can be carried out on the original production line, so as to realize large-scale production and reduce the cost. DETAILED DESCRIPTION

[0031] The present application will be further described below in conjunction with examples, but the present application is not limited by the examples.

[0032] In the following examples, the experimental methods are conventional methods unless otherwise specified.

[0033] Example 1: Modified polyether sulfone hollow fiber hemodialysis membrane of the present application

[0034] I. Preparation of modified polyether sulfone hollow fiber hemodialysis membrane

[0035] The modified polyether sulfone hollow fiber hemodialysis membrane of the present application is prepared according to the following method:

[0036] Step one, preparation of spinning solution: prepare the spinning solution according to the weight percentage of each component in Table 1, heat at 80℃ for 10h, and then stand for 20h to remove bubbles, to obtain the spinning solution;

[0037] Step two, preparation of core solution: prepare the core solution according to the weight percentage of each component in Table 1, heat at 50℃ until dissolved to obtain the core solution;

[0038] Step three, preparation of hollow fiber membrane: deliver the spinning solution and the core solution through the metering pump to the spinneret for extrusion, adjust the speed of the metering pump to make the flow rate of the spinning solution 9.65ml / min and the flow rate of the core solution 10.05ml / min, pass through 40cm of air path, and then enter the water bath at 50℃ for solidification and shaping, then pass through the drum driven by the linear speed of 20m / min, sequentially pass through the water washing tank at 80℃ for cleaning, the oven at 120℃ for drying, and finally collect on the yarn wheel.

[0039] Table 1 Composition of spinning solution and core solution in each preparation example and comparative example

[0040]

[0041]

[0042] Note: The values in the table are the weight percentages of each component in the spinning solution or the core solution.

[0043] II. Performance test:

[0044] The modified polyether sulfone hollow fiber hemodialysis membrane prepared in Table 1 is tested for product performance according to YY / T 1920-2023 Dialyzer Blood Compatibility Test and GB / T 32360-2015 Ultrafiltration Membrane Test Method.

[0045] The results are shown in Table 2.

[0046] Table 2 Performance comparison of examples and comparative examples

[0047]

[0048] From Table 2, it can be seen that, compared with Comparative Examples 1-2, the contact angle of the modified polyethersulfone hollow fiber hemodialysis membrane of Examples 1-6 is reduced, the pure water flux recovery rate is improved, the hydrophilicity of the membrane is improved, the APTT time is prolonged, the anticoagulant property of the membrane is improved, and the pure water ultrafiltration rate shows that the hemodialysis membrane product meets the requirements of hemodialysis products. In summary, the comprehensive performance of the product of Example 1-3 is more optimal.

[0049] The dialysis membranes of Comparative Examples 3-4 use other modifier combinations, and the hydrophilicity and anticoagulant property of the dialysis membranes are significantly poorer than the combination of polyvinylpyrrolidone + citric acid, and the comprehensive performance cannot be significantly improved. Through preliminary experiments, the present application has tried various modifiers and different combinations of modifiers, such as glycerol, polyethylene glycol, etc., and has tried adding modifiers to the core liquid in order to fix the modifiers on the inner surface of the hollow fibers of the dialysis membrane to significantly improve the hydrophilicity and anticoagulant property. Finally, the combination of polyvinylpyrrolidone + citric acid is determined, and all are added to the core liquid, and the prepared dialysis membrane product can achieve the preset target, while maintaining a simple production process and facilitating large-scale production.

Claims

1. A method for preparing a modified polyether sulfone hollow fiber hemodialysis membrane, characterized by, The preparation method comprises the following steps: S1, preparing a spinning solution: 14-22% polyether sulfone, 3-15% porogen, 0-7% non-solvent and 56-83% organic solvent are mixed according to the weight percentage, heated to fully dissolve, and then left to stand and degas to obtain the spinning solution; S2, preparing a core solution: the components of the core solution are mixed and fully dissolved to obtain the core solution; The core solution comprises 1-10% polyvinylpyrrolidone and 1-10% citric acid according to the weight percentage, and the balance is water; S3, hollow fiber membrane preparation: the spinning solution and the core solution are respectively delivered to the spinneret for extrusion, enter the water bath after air travel, and are solidified and formed, and finally are washed with water, dried, and collected.

2. The preparation method according to claim 1, wherein: in step S1, the raw materials are mixed and heated at a temperature of 60-90°C for 8-24h, and then left to stand and degas for 12-24h to obtain the spinning solution; in step S2, the components of the core solution are mixed and heated at 20-60°C to fully dissolve to obtain the core solution.

3. The preparation method according to claim 1, wherein: in step S3, the spinning solution and the core solution are respectively delivered to the spinneret for extrusion by the metering pump, the rotation speed of the metering pump is adjusted so that the flow rate of the spinning solution is 7-13 ml / min and the flow rate of the core solution is 7.5-13.5 ml / min, the obtained solution travels in the air for 1-60 cm, enters the water bath at a temperature of 20-60°C for solidification and formation, is then driven by the roller at a linear speed of 10-40 m / min, is sequentially cleaned in the water washing tank at 60-95°C and dried in the oven at 80-140°C, and is finally collected on the spinning wheel.

4. The preparation method according to claim 3, wherein: in step S3, the spinning solution and the core solution are respectively delivered to the spinneret for extrusion by the metering pump, the rotation speed of the metering pump is adjusted so that the flow rate of the spinning solution is 9.4-9.8 ml / min and the flow rate of the core solution is 9.8-10.2 ml / min, the obtained solution travels in the air for 40-50 cm, enters the water bath at a temperature of 50-60°C for solidification and formation, is then driven by the roller at a linear speed of 10-40 m / min, is sequentially cleaned in the water washing tank at 70-90°C and dried in the oven at 100-140°C, and is finally collected on the spinning wheel.

5. The method of claim 1, wherein: in step S1, the porogen is one or more of polyvinylpyrrolidone, polyethylene glycol and polyvinyl alcohol in any proportion; the non-solvent is one or more of water, ethanol, isopropanol and glycerol in any proportion; the organic solvent is dimethylacetamide.

6. The method of claim 5, wherein: in step S1, the porogen is polyvinylpyrrolidone, and the non-solvent is water.

7. The preparation method according to claim 5 or 6, wherein: in step S1, the spinning solution comprises 14-20% polyether sulfone, 5-15% porogen, 1-7% non-solvent and 64-75% organic solvent according to the weight percentage; in step S2, the core solution comprises 2-10% polyvinylpyrrolidone and 1-10% citric acid according to the weight percentage, and the balance is water.

8. The preparation method of claim 7, wherein: the spinning solution comprises 14-17% polyether sulfone, 8-15% porogen, 3-7% non-solvent and 64-72% organic solvent; the polyvinylpyrrolidone in the core solution has a weight percentage of 2-7%, the citric acid has a weight percentage of 4-10%, and the balance is water.

9. A modified polyether sulfone hollow fiber hemodialysis membrane characterized by: The main body of the hemodialysis membrane is a polyether sulfone membrane, the modifier thereof comprises polyvinylpyrrolidone and citric acid, the modifier molecules are combined on the inner surface of the hollow fiber membrane, and the hollow fiber hemodialysis membrane is prepared by the preparation method in any one of claims 1 to 8.

10. The modified polyether sulfone hollow fiber hemodialysis membrane of claim 9, wherein: the hollow fiber hemodialysis membrane has an inner diameter of 150-350 μm and a wall thickness of 50-100 μm.

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