Modified hollow fiber membrane and application thereof

Abstract

The invention discloses a modified hollow fiber membrane which is composed of a separation layer, a supporting layer and a macroporous layer, the pore diameters of the separation layer, the supporting layer and the macroporous layer are sequentially increased, and a preparation method of the modified hollow fiber membrane comprises the following steps: weighing polyether sulfone / polysulfone, a pore-foaming agent, a solvent, an organic macromolecular additive and an inorganic salt additive according to the proportion to prepare a spinning solution; stirring and dissolving at 80-180 DEG C, centrifugally filtering, defoaming at 40-80 DEG C to obtain a spinning solution, carrying out coagulating bath on the spinning solution, molding, cleaning, stretching and drying to obtain the modified hollow fiber membrane. According to the preparation method, micromolecular inorganic salt pore-forming agents with different concentrations are added into a spinning solution and a coagulating bath, and interaction among inorganic salt, a polymer and a solvent is utilized, so that an inner skin layer structure and an outer skin layer structure of the hollow fiber membrane are adjusted, and a unique three-layer structure of a separation layer, a supporting layer and a macroporous layer is formed; the hydrophilic performance is stable, and the clearance on middle molecules is improved.

Description

Technical Field

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

[0002] Due to injuries and diseases such as diabetes and hypertension, the number of patients with renal failure is increasing at an alarming rate worldwide. Hemodialysis is the main treatment for patients with end-stage renal disease (ESKD), and hemodialysis membranes are the core components of hemodialysis treatment. At present, hemodialysis membranes made of second-generation polymers such as polysulfone (PSF) and polyethersulfone (PES) have excellent thermal stability, chemical stability, and mechanical stability. Polyethersulfone has high mechanical strength, stable chemical composition, good pressure resistance, heat resistance, aging resistance, corrosion resistance, etc. It can be steam sterilized multiple times, is easy to reuse, and has a long service life. It has occupied a dominant position in the membrane used for hemodialysis machines.

[0003] Hemodialysis membranes can remove excess water and medium and small molecular weight uremic toxins from the blood through diffusion, ultrafiltration and convection. The main problem with current hemodialysis treatment is that hemodialysis membranes have limited removal effects on medium molecular weight toxins, such as parathyroid hormone, β2-microglobulin, interleukin, etc. These medium molecular weight toxins are often closely related to complications such as inflammation, cardiovascular events, anemia and malnutrition in patients.

[0004] The traditional ultrafiltration membrane is composed of a central support layer and filter layers on both sides, and the filtration performance of the ultrafiltration membrane is determined by the filter layers. The filter layers on both sides of the ultrafiltration membrane prepared by the traditional method are the same. For example, CN106621866A discloses a polyethersulfone hollow fiber ultrafiltration membrane that can reduce concentration polarization, reduce the blockage of the inner pores of the membrane, increase the water flux of the membrane, and reduce the number of cleaning times during the use of the ultrafiltration membrane in the separation of raw water with too high a suspended matter concentration or a material with a large viscosity, and has high temperature resistance, good separation effect, and anti-pollution. The casting liquid formula is calculated by mass percentage: polyethersulfone 14-30%, solvent 35-80%, organic macromolecular additive 0.5-10%, organic small molecule additive 1-15%, inorganic salt additive: 0.5-5%, surfactant 1-10%, and the sum of each component is 100%. The appropriate use of inorganic salt additives in the casting liquid can adjust the size of the effective separation pore size, making the casting liquid relatively stable as a whole, and will not stratify when placed for a long time. The liquid remains stable at low temperatures, which prevents the liquid from gelling and makes it more soluble in the coagulation bath. The appropriate ratio of the components in the casting liquid together improves the lasting hydrophilicity of the polyethersulfone hollow fiber ultrafiltration membrane. The produced ultrafiltration membrane has a larger inner diameter and can be better applied to the separation of raw water with excessively high suspended matter concentration or materials with high viscosity. It can reduce concentration polarization, greatly reduce the blockage of the inner pores of the membrane fibers, prevent the attenuation of the water flux of the membrane fibers, and reduce the number of cleaning times during the use of the ultrafiltration membrane. It has the advantages of high temperature resistance, good separation effect, and good anti-pollution performance. The coagulation bath contains Tween, lithium chloride, water, dimethylformamide, and dimethylacetamide, which can form micelles and are relatively stable; Tween and lithium chloride are used together to effectively regulate the phase transformation mechanism of the feed liquid, effectively regulate the effective separation pore size of the polyethersulfone hollow fiber membrane, and can affect the hydrophilicity of the polyethersulfone hollow fiber membrane, so that the prepared polyethersulfone hollow fiber membrane maintains lasting hydrophilicity. The effective separation layer and support layer of the ultrafiltration membrane are formed at the same time and are a whole. The inner and outer surfaces of the membrane have effective separation layers, which can be used as internal pressure membranes or external pressure membranes. The two sides of the ultrafiltration membrane are the same, which is a traditional sandwich structure.

[0005] The molecular weight of middle-molecular toxins is large and difficult to remove through conventional hemodialysis methods. Once the pore size of the dialysis membrane is increased, a large amount of albumin will be lost, which is likely to increase the complications and mortality of patients. Therefore, it is of great clinical significance to modify the polyethersulfone membrane, adjust the structure of the dialysis membrane, improve the separation performance of the dialysis membrane for middle-molecular toxins, and reduce the loss of albumin. Summary of the invention

[0006] The object of the present invention is to overcome at least one disadvantage of the prior art and provide a modified hollow fiber membrane and application thereof.

[0007] The technical solution adopted by the present invention is: In a first aspect, the present invention provides a modified hollow fiber membrane, which is composed of a separation layer, a support layer and a macroporous layer, wherein the pore sizes of the separation layer, the support layer and the macroporous layer increase in sequence, and the preparation method thereof comprises the following steps: 1) Weighing polyethersulfone / polysulfone, porogen, solvent, organic macromolecular additive and inorganic salt additive according to the ratio to prepare spinning solution, stirring and dissolving at 80-180° C., centrifugally filtering, and degassing at 40-80° C. to obtain spinning solution; 2) The spinning solution is formed after passing through a coagulation bath, and the modified hollow fiber membrane is obtained after washing, stretching and drying; The mass ratio of the components of the spinning solution in step 1) is: 100 parts of solvent, 10-25 parts of polysulfone / polyethersulfone, 5-10 parts of organic macromolecular additive, 0.05-5 parts of inorganic salt additive, and 0.05-1 part of porogen.

[0008] In some examples, the inorganic salt additive is selected from at least one of lithium chloride, zinc chloride, calcium chloride, lithium nitrate, and calcium carbonate.

[0009] In some examples, the mass ratio of the inorganic salt additive to the organic macromolecular additive is: (0.05-1):1.

[0010] In some examples, 1 to 5 parts of an inorganic salt additive are further added to the coagulation bath in step 2), and the concentration of the inorganic salt additive in the coagulation bath is higher than the concentration of the inorganic salt additive in the spinning solution.

[0011] In some examples, the solvent in step 1) is at least one selected from dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide.

[0012] In some examples, the porogen in step 1) is at least one selected from polyethyleneimine, polyethylene glycol, polyvinyl alcohol, and polyamine.

[0013] In some examples, the organic macromolecular additive in step 1) is at least one selected from maleic anhydride copolymer, polyvinyl pyrrolidone, and polyimide.

[0014] In some examples, the temperature of the coagulation bath in step 2) is 20-50°C.

[0015] In some examples, the mass ratio of the inorganic salt additive to the organic macromolecular additive is: (0.1-0.5):1.

[0016] In a second aspect, the modified hollow fiber membrane provided in the first aspect of the present invention is used in preparing a membrane for a hemodialyzer.

[0017] The beneficial effects of the present invention are: (1) In the spinning solution, inorganic salt additives can form ion-dipole complexes with the carbonyl groups in the solvent. The interaction between the inorganic salt additives and the fiber membrane polymer formed by spinning can change the interaction force between the polymer chains and affect the interface between the solvent and the polymer, thereby changing the solvent properties, increasing the swelling of the polymer, and forming large molecular clusters, affecting the membrane formation process, thereby regulating the pore size distribution of the inner surface.

[0018] (2) Adding inorganic salts to the coagulation bath can increase the thermodynamic instability of the coagulation bath, making the phase separation process more likely to occur, thereby regulating the microstructure of the outer surface of the hollow fiber membrane.

[0019] (3) The introduction of inorganic salt additives can also increase the free polar groups on the membrane surface, making the membrane more hydrophilic and improving the membrane's anti-fouling properties.

[0020] (4) By regulating the concentration of inorganic salt additives in the spinning solution and the coagulation bath, the hollow fiber membrane can have an inner-outer and support layer, a three-layer gradient pore structure, which can improve the clearance rate of medium-molecular toxins. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a cross-sectional view of the hollow fiber membrane prepared in Example 1.

[0022] Figure 2 This is a picture of the outer surface of the hollow fiber membrane prepared in Example 1.

[0023] Figure 3 This is the outer surface image of the hollow fiber membrane prepared in Comparative Example 2. DETAILED DESCRIPTION

[0024] The following disclosure provides many different embodiments or examples for implementing different solutions of the present invention.

[0025] Example 1: Preparation of inorganic salt modified polyethersulfone membrane① Spinning solution formula: Polyethersulfone 40 parts 20 parts of maleic anhydride copolymer 3 parts of inorganic salt additive (lithium chloride: zinc chloride: calcium chloride mass ratio = 1:1:1) 2 parts of water-soluble porogen (polyethyleneimine) Solvent DMF 200 parts Coagulation bath recipe: 2 parts of inorganic salt additive (lithium nitrate) 100 parts water (1) According to the above mass ratio, the required raw materials are weighed respectively, stirred and dissolved at 100°C to form a transparent solution, centrifuged and filtered, and allowed to stand at 80°C for 4 hours to degas to obtain a spinning solution.

[0026] (2) The spinning solution prepared in step 1 is extruded from a spinneret at an extrusion speed of 3-15 ml / min using a spinning device, passed through an air bath of 5-50 cm in the air, and then placed in a coagulation bath at 20-50° C. for solidification and forming, and then wound at a speed of 5-50 m / min to form the formed fiber filaments, and then immersed in water to remove the residual solvent and unreacted raw materials, and then dried to obtain a hollow fiber membrane.

[0027] Example 2: Preparation of inorganic salt modified polyethersulfone membrane② Spinning solution formula: Polyethersulfone 40 parts 20 parts of polyvinyl pyrrolidone 2 parts of inorganic salt additive (lithium chloride: zinc chloride mass ratio 1:1) 2 parts of water-soluble porogen (polyethyleneimine) Solvent DMAC 200 parts Coagulation bath recipe: 5 parts of inorganic salt additive (calcium chloride: lithium nitrate mass ratio = 1:1) 100 parts water (1) According to the above mass ratio, the required raw materials are weighed respectively, stirred and dissolved at 100°C to form a transparent solution, centrifuged and filtered, and allowed to stand at 80°C for 4 hours to degas to obtain a spinning solution.

[0028] (2) The spinning solution prepared in step 1 is extruded from a spinneret at an extrusion speed of 3-15 ml / min using a spinning device, passed through an air bath of 5-50 cm in the air, and then placed in a coagulation bath at 20-50°C for solidification and forming. The solution is then wound at a speed of 5-50 m / min, the formed fiber filaments are immersed in water, the residual solvent and unreacted raw materials are removed, and the hollow fiber membrane is obtained by drying.

[0029] Example 3: Preparation of inorganic salt modified polyethersulfone membrane ③ Spinning solution formula: Polyethersulfone 40 parts 20 parts of polyvinyl pyrrolidone 1 part of inorganic salt additive (lithium chloride: zinc chloride: calcium chloride: lithium nitrate = 1:1:1:1) 2 parts of water-soluble porogen (polyethyleneimine) Solvent DMAC 200 parts Coagulation bath recipe: 1 part of inorganic salt additive (lithium chloride: zinc chloride: calcium carbonate = 5:5:1) 100 parts water (1) According to the above mass ratio, the required raw materials are weighed respectively, stirred and dissolved at 100°C to form a transparent solution, centrifuged and filtered, and allowed to stand at 80°C for 4 hours to degas to obtain a spinning solution.

[0030] (2) The spinning solution prepared in step 1 is extruded from a spinneret at an extrusion speed of 3-15 ml / min using a spinning device, passed through an air bath of 5-50 cm in the air, and then placed in a coagulation bath at 20-50°C for solidification and forming. The solution is then wound at a speed of 5-50 m / min, the formed fiber filaments are immersed in water, the residual solvent and unreacted raw materials are removed, and the hollow fiber membrane is obtained by drying.

[0031] Comparative Example 1: Unmodified polyethersulfone membrane There is no inorganic salt additive in the spinning solution formula and the coagulation bath, and the other preparation processes are the same as those in Example 1.

[0032] Comparative Example 2: Modified polyethersulfone membrane with only inorganic salt additive added to the spinning solution Spinning solution formula: Polyethersulfone 40 parts 20 parts of polyvinyl pyrrolidone 3 parts of inorganic salt additive 2 parts of water-soluble porogen (polyethyleneimine) Solvent DMF 200 parts Coagulation bath recipe: Inorganic salt additives 0 parts 100 parts water The spinning solution formula is as above, and the rest is the same as Example 1.

[0033] Comparative Example 3: Modified polyethersulfone membrane with coagulation bath of water + inorganic salt additive + organic solvent Spinning solution formula: Polyethersulfone 40 parts 20 parts of polyvinyl pyrrolidone 3 parts of inorganic salt additive 2 parts of water-soluble porogen (polyethyleneimine) Solvent DMF 200 parts Coagulation bath recipe: Inorganic salt additive 1 part 10 parts water 40 parts of dimethylformamide 40 parts of dimethylacetamide Tween 10 parts The spinning solution and coagulation bath formulas are as above, and the rest are the same as in Example 1.

[0034] Experimental analysis Figure 1 This is a cross-sectional view of the hollow fiber membrane prepared in Example 1. Figure 2 This is a picture of the outer surface of the hollow fiber membrane prepared in Example 1. Figure 3 This is a diagram of the outer surface of the hollow fiber membrane prepared in Comparative Example 2. Figure 1-3 As shown, the hollow fiber membrane formed in Example 1 has a three-layer structure of separation layer-support layer-macroporous layer. The inner surface separation layer has the smallest pore size, a narrow pore size distribution, and a dense structure. The support layer is a sponge-like structure with gradually expanding pore size. Compared with Comparative Example 2, the outer surface macroporous layer of Example 1 has the largest pore size, and some large cavities may be formed.

[0035] Inorganic salt additives are added to the spinning solution, and the interaction between organic additives and inorganic additives is used to regulate the structure of the inner surface separation layer: a dense separation layer is formed, and its pore size distribution is narrow and relatively small, which is beneficial to the removal of medium-molecular toxins without losing too much large molecular weight beneficial proteins (for example, the molecular weight of the toxic medium-molecular β2 microglobulin is 11,800, and that of the beneficial albumin is 66,000. The smaller pore size and narrow pore size distribution are beneficial to the separation of only the toxic β2 microglobulin and the isolation of the precipitation of the beneficial protein-albumin).

[0036] Adding inorganic salt additives to the coagulation bath without adding an organic phase can increase the concentration of the PES non-solvent phase and promote the phase separation process on the outer surface, thereby forming large or ultra-large pores on the outer surface, making it easier for the extramembrane solution to carry the precipitated toxic middle molecules away from the filter membrane, thereby improving the removal efficiency of the PES membrane.

[0037] Performance Test: The specific performance tests of each embodiment and comparative example are shown in Table 1. The test methods of different performances are as follows: 1) Water contact angle test: The fiber membranes obtained in the example and the comparative example were respectively taken, dried at 105° C. for 4 hours to remove moisture, ground, and prepared into sheet samples with a diameter of 13 mm and a thickness of 1 mm using an oil pressure tablet press, and then the contact angle test was performed.

[0038] 2) Pure water flux test: Refer to the pure water permeability part of GB / T 32360-2015.

[0039] 3) Activated partial thromboplastin time (APTT) test: refer to YY / T0659-2017.

[0040] 4) Platelet count: hematological analyzer method.

[0041] 5) Beta 2 Microglobulin clearance rate: refer to supplementary test method YY0053-2016.

[0042] 6) Albumin retention rate: refer to GB / T 32360-2015 test method.

[0043] Table 1. Performance comparison of different embodiments and comparative examples

[0044] From the data in Table 1, we can see that: 1) The water contact angles of Examples 1, 2, and 3 are all lower than those of Comparative Example 1, and the pure water flux increases, indicating that the hollow fiber membrane modified by adding inorganic salts to both the spinning solution and the coagulation bath has a better improvement in hydrophilicity. At the same time, the APTT (partial thromboplastin time) of Examples 1, 2, and 3 is significantly prolonged, the platelet count is reduced, and the anticoagulant effect is significantly improved.

[0045] 2) The clearance rates of the middle molecules (β2 microglobulin) in Examples 1, 2, and 3 are higher than those in Comparative Example 1, indicating that the addition of inorganic salts in the spinning solution and the coagulation bath adjusts the pore structure formed by the fiber membrane to increase the pore size and relatively narrow the pore size distribution, which is beneficial to the separation of the middle molecules (β2 microglobulin); while the clearance rates are still higher than those in Comparative Examples 2 and 3, indicating that the formula of the coagulation bath has a greater influence on the outer surface of the pore structure, and the formed macropores and cavity structures are beneficial to the separated middle molecules (β2 microglobulin) to flush out of the fiber membrane, thereby improving the clearance rate.

[0046] 3) The retention rate of molecules (albumin) in Examples 1, 2, and 3 is higher than that in Comparative Example 3, which indicates that the different formulations of the coagulation bath will also synergistically affect the inner surface pore size of the membrane. The inner surface pore size formed in Comparative Example 3 is larger, and the albumin retention rate is lower, while the inner surface pore size of Examples 1, 2, and 3 is smaller, and the clearance rate for β2 microglobulin is higher, while the albumin retention rate is higher.

[0047] 4) The hydrophilicity and the removal effect of middle-molecular toxins of Examples 1, 2, and 3 are not much different, indicating that the three-layer gradient pore structure formed by adding inorganic salts to both the spinning solution and the coagulation bath can improve the hydrophilicity and middle-molecular toxin removal rate of polyethersulfone.

[0048] The above is a further detailed description of the present invention, which should not be regarded as a limitation on the specific implementation of the present invention. For ordinary technicians in the technical field to which the present invention belongs, simple deduction or replacement without departing from the concept of the present invention is within the protection scope of the present invention.

Claims

1. A modified hollow fiber membrane, characterized in that: The invention is composed of three layers: a separation layer, a support layer and a macroporous layer. The pore sizes of the separation layer, the support layer and the macroporous layer increase in sequence. The preparation method thereof comprises the following steps: 1) Weighing polyethersulfone / polysulfone, porogen, solvent, organic macromolecular additive and inorganic salt additive according to the ratio to prepare spinning solution, stirring and dissolving at 80-180° C., centrifugally filtering, and degassing at 40-80° C. to obtain spinning solution; 2) The spinning solution is formed after passing through a coagulation bath, and the modified hollow fiber membrane is obtained after washing, stretching and drying; The mass ratio of the components of the spinning solution in step 1) is: 100 parts of solvent, 10-25 parts of polysulfone / polyethersulfone, 5-10 parts of organic macromolecular additive, 0.05-5 parts of inorganic salt additive, and 0.05-1 part of porogen.

2. The modified hollow fiber membrane according to claim 1, characterized in that The inorganic salt additive is selected from at least one of lithium chloride, zinc chloride, calcium chloride, lithium nitrate and calcium carbonate.

3. The modified hollow fiber membrane according to claim 1, characterized in that: The mass ratio of the inorganic salt additive to the organic macromolecular additive is: (0.05-1):

1.

4. The modified hollow fiber membrane according to claim 1 or 2, characterized in that: In the coagulation bath of step 2), 1 to 5 parts of an inorganic salt additive are also added, and the concentration of the inorganic salt additive in the coagulation bath is higher than the concentration of the inorganic salt additive in the spinning solution.

5. The modified hollow fiber membrane according to claim 1, characterized in that: In the step 1), the solvent is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide.

6. The modified hollow fiber membrane according to claim 1, characterized in that: In the step 1), the porogen is selected from at least one of polyethyleneimine, polyethylene glycol, polyvinyl alcohol and polyamine.

7. The modified hollow fiber membrane according to claim 1 or 3, characterized in that: In the step 1), the organic macromolecular additive is selected from at least one of maleic anhydride copolymer, polyvinyl pyrrolidone and polyimide.

8. The modified hollow fiber membrane according to claim 1, characterized in that: The temperature of the coagulation bath in step 2) is 20-50°C.

9. The modified hollow fiber membrane according to claim 3, characterized in that: The mass ratio of the inorganic salt additive to the organic macromolecular additive is: (0.1-0.5):

1.

10. Use of the modified hollow fiber membrane according to any one of claims 1 to 9 in preparing a membrane for a hemodialyzer.

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