Hollow fiber ultrafiltration membrane for hemodialysis having a symmetric channel structure and a method for preparing the same

Abstract

The application provides a hollow fiber ultrafiltration membrane for hemodialysis, which is a porous membrane prepared from a single material of a polysulfone-polyethylene glycol amphiphilic block copolymer through melt spinning and selective swelling, wherein the polyethylene glycol block ratio of the amphiphilic block copolymer is 30%; the porosity, average pore size and pore size distribution of the pores of the outer surface, inner part and inner surface of the hollow fiber ultrafiltration membrane are all in the same range, so that a symmetrical pore structure is formed in the thickness direction of the hollow fiber ultrafiltration membrane; the porosity of the pores of the outer surface, inner part and inner surface is all in the range of 20% to 80%, the average pore size is all in the range of 2nm to 20nm, and the pore size distribution is all in the range of 2nm to 50nm. The hollow fiber ultrafiltration membrane has excellent removal performance for toxic middle molecules and high retention performance for beneficial proteins, and also has ideal mechanical properties, and no organic component is dissolved during use. The application also provides a method for preparing the hollow fiber ultrafiltration membrane, and a hemodialysis assembly with the hollow fiber ultrafiltration membrane as membrane filaments.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of separation membranes, in particular to the field of hemodialysis membranes, and more particularly to a hollow fiber ultrafiltration membrane with symmetric pore structure for hemodialysis, a membrane module and a preparation method thereof. BACKGROUND

[0002] Hemodialysis is one of the renal replacement therapy methods for patients with acute and chronic renal failure. By draining the blood in the body to the outside of the body, the blood and dialysate are exchanged in the hollow fibers of the dialyzer composed of hollow fiber hemodialysis membranes through diffusion, ultrafiltration, adsorption and convection principles to achieve the purpose of removing metabolic waste in the body and maintaining electrolyte and acid-base balance. In addition to the need for high safety (i.e. no polymer and additive leaching during use) and good mechanical properties, an ideal hemodialysis membrane should also have precise separation performance for medium and large molecules and high removal performance for small molecule toxins.

[0003] Existing hemodialysis membranes can be divided into cellulose membranes and synthetic polymer membranes according to the membrane material. Traditional cellulose membranes contain a large number of hydroxyl groups, which can easily activate complement, resulting in poor biocompatibility compared with synthetic membranes, and can easily cause various complications in clinical use. Synthetic polymer membranes have relatively good biocompatibility and high permeability, and are the most widely used membrane material at present. Among them, polysulfone and polyether sulfone are the most commonly used in clinical applications.

[0004] At present, the hollow fiber hemodialysis membrane is mainly prepared by solution spinning method (NIPS). The solution of polysulfone or polyethersulfone is immersed in a non-solvent coagulation bath, the non-solvent in the coagulation bath diffuses into the casting solution, and the solvent diffuses from the casting solution to the coagulation bath, so that the polymer in the casting solution is rapidly precipitated from top to bottom, and the hollow fiber membrane is obtained. Solution spinning method can be used for large-scale preparation of the obtained membrane with high porosity, and is the most commonly used method in industry. However, a large amount of organic waste liquid and wastewater is generated in the production process of solution spinning method, which pollutes the environment; more importantly, the hollow fiber membrane prepared by the method has a typical asymmetric structure, which cannot meet the actual needs of hemodialysis. Because in this typical asymmetric structure, the inner and outer surfaces of the membrane are generally pore structures with pore diameters of several to several tens of nanometers, and the inside of the membrane is a finger-shaped large pore with a pore diameter of several tens of microns or even hundreds of microns. Although the nanoscale pores on the surface play a separation role, the finger-shaped large pores inside can ensure that the whole membrane has a high flux, but the large size of the internal pores, the large difference between the internal and surface pores, and the poor uniformity of the size of the internal and surface pores lead to the poor removal capacity of the hollow fiber membrane for middle and large molecular protein toxins. Moreover, the asymmetric structure generally has poor mechanical properties, and the thin effective separation layer is easy to be damaged. In addition, due to the high hydrophobicity of polysulfone materials, in order to meet the use requirements of hemodialysis, the polysulfone materials usually need to be surface modified. The modification methods include chemical grafting modification and blending modification, and the former method is complex and has low economic benefits; in the use of the latter method, the hydrophilic additive is gradually lost under the action of wall shear force or during the later sterilization process, which causes the performance of the membrane to decrease, and even the dissolution of the additive leads to complement activation and patient complications.

[0005] Therefore, it is urgent to develop a new type of hemodialysis membrane with precise separation capacity for middle and large molecules in blood, stable performance and simple preparation method, so as to better meet the needs of hemodialysis and be suitable for industrial production. SUMMARY

[0006] The purpose of the present application is to provide a hollow fiber ultrafiltration membrane more suitable for hemodialysis, which has a symmetric pore structure in the thickness direction, excellent removal performance for toxic middle molecules and high retention performance for beneficial proteins, a thicker effective separation layer, and ideal mechanical properties, without the need for surface modification and the dissolution of organic components during use.

[0007] Another purpose of the present application is to provide a method for preparing the hollow fiber ultrafiltration membrane for hemodialysis, so that the hollow fiber ultrafiltration membrane has a symmetric pore structure in the thickness direction, and the obtained pore structure has a small pore diameter and a narrow pore size distribution.

[0008] The above purposes of the present application are achieved by the following solutions.

[0009] In a first aspect, the present application provides a hollow fiber ultrafiltration membrane for hemodialysis, which is a porous membrane prepared by melt spinning and selective swelling from a single material of a polysulfone-polyethylene glycol amphiphilic block copolymer, wherein the polyethylene glycol block ratio of the amphiphilic block copolymer is 30%; the pores of the outer surface, the inside and the inner surface of the hollow fiber ultrafiltration membrane all have similar structural characteristics, i.e., the porosity, the average pore size and the pore size distribution are all in the same range, thereby forming a symmetrical pore structure in the thickness direction thereof.

[0010] In a preferred scheme of the present application, the pores of the outer surface, the inside and the inner surface of the hollow fiber ultrafiltration membrane all have a porosity in the range of 10% to 80%, an average pore size in the range of 2 nm to 20 nm, and a pore size distribution in the range of 2 nm to 50 nm.

[0011] In a further preferred scheme of the present application, the pores of the outer surface, the inside and the inner surface of the hollow fiber ultrafiltration membrane all have a porosity in the range of 10% to 70%, an average pore size in the range of 2 nm to 20 nm, and a pore size distribution in the range of 2 nm to 25 nm.

[0012] In a still further preferred scheme of the present application, the pores of the outer surface, the inside and the inner surface of the hollow fiber ultrafiltration membrane all have a porosity in the range of 10% to 65%, an average pore size in the range of 3 nm to 12 nm, and a pore size distribution in the range of 2 nm to 15 nm.

[0013] In a more preferred scheme of the present application, the pores of the outer surface have a porosity in the range of 10% to 40%, an average pore size in the range of 2 nm to 10 nm, and a pore size distribution in the range of 2 nm to 15 nm; the pores of the inner surface have a porosity in the range of 10% to 40%, an average pore size in the range of 2 nm to 10 nm, and a pore size distribution in the range of 2 nm to 20 nm; and the pores in the inside of the membrane have a porosity in the range of 40% to 70%, an average pore size in the range of 5 nm to 20 nm, and a pore size distribution in the range of 2 nm to 25 nm.

[0014] In a most preferred scheme of the present application, the pores of the outer surface have a porosity in the range of 15% to 30%, an average pore size in the range of 3 nm to 6 nm, and a pore size distribution in the range of 2 nm to 8 nm; the pores of the inner surface have a porosity in the range of 10% to 25%, an average pore size in the range of 4 nm to 8 nm, and a pore size distribution in the range of 2 nm to 12 nm; and the pores in the inside of the membrane have a porosity in the range of 55% to 65%, an average pore size in the range of 8 nm to 12 nm, and a pore size distribution in the range of 2 nm to 15 nm.

[0015] In a second aspect, the present application provides a hemodialysis membrane assembly using the hollow fiber ultrafiltration membrane as the membrane filament.

[0016] In a third aspect, the present application further provides a method for preparing the hollow fiber ultrafiltration membrane for hemodialysis, comprising:

[0017] 1) preparing a hollow fiber by melt spinning from a polysulfone-polyethylene glycol block copolymer having a polyethylene glycol block ratio of 30%;

[0018] 2) immersing the hollow fiber obtained in 1) in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) for selective swelling treatment at 60-65°C for 0.5-3h, and then transferring to n-heptane for 5min, and drying to obtain the hollow fiber ultrafiltration membrane for hemodialysis having a symmetrical pore structure.

[0019] In a preferred method of the present application, the swelling treatment in 2) is carried out at 65°C for 1h.

[0020] In a preferred method of the present application, the swelling treatment in 2) is carried out using a microwave with a power of 160-800W for 15-60s.

[0021] In the early study of the present inventors' team on the preparation of hollow fiber porous membranes by selective swelling, the pore structure and performance were adjusted by adjusting the composition of the swelling agent for selective swelling, the swelling temperature and time, etc. However, the hollow fiber porous membranes obtained by the above adjustment scheme only achieved a certain degree of improvement in water flux, and it was still difficult to meet the requirements of removing small molecule impurities while effectively removing toxic medium molecules and retaining beneficial macromolecular proteins in hemodialysis. In particular, the removal rate of β2-microglobulin, myoglobin and other medium molecular toxins was too low, which made the treatment effect not ideal in hemodialysis. After in-depth research, the present inventors' team analyzed the relationship between the unique performance requirements of hemodialysis membranes and the pore structure characteristics of porous membranes, and based on this, a large number of hollow fiber membrane pore-forming screening experiments were carried out, including breaking the conventional idea of adjusting the selective swelling conditions, and instead, the ratio of hydrophilic blocks in amphiphilic block copolymers was screened. Finally, under specific selective swelling conditions, it was found that when the ratio of polyethylene glycol blocks in polysulfone-polyethylene glycol block copolymers was 30%, a hollow fiber ultrafiltration membrane with a symmetrical pore structure in the thickness direction could be prepared by using the methods of melt spinning and selective swelling, and the pores on the inner and outer surfaces and inside the membrane all had the characteristics of small pore size and narrow pore size distribution, i.e., the membrane surface and the inside of the membrane were both nanoscale bicontinuous pores between 2-50 nm, and the pore structures on the inner and outer surfaces of the membrane were almost identical, only the surface had slightly smaller pore size due to the enrichment of hydrophilic blocks on the surface. Compared with the existing hollow fiber porous membranes, the hollow fiber membrane described in the present application has a special symmetrical pore structure, which not only brings higher mechanical properties and flux to the hollow fiber membrane, but also has precise separation performance, and has a high removal rate of medium molecular toxins and small molecule impurities in blood, while almost no loss of beneficial proteins, and the performance of BSA rejection rate, lysozyme removal rate and myoglobin removal rate is significantly better than that of polyethylene glycol with other block ratios (see Figure 18 ). Moreover, due to the relative consistency of the inner and outer pore structures, the hollow fiber ultrafiltration membrane of the present application is almost not damaged during the use in hemodialysis, and the separation performance is not reduced.

[0022] Moreover, the commonly used solution spinning method (NIPS) at present often needs to modify the polysulfone material due to its high hydrophobicity, and the modification methods include chemical grafting modification and blending modification. The former method is complex and has low economic benefits; the latter method in use, the hydrophilic agent is gradually lost under the action of wall shear force or during the later sterilization treatment, leading to performance decline, and even the dissolution of additives leads to complement activation, causing complications in patients; and usually, the hollow fiber membrane obtained by the NIPS method has only nanoscale pores with small pore size on the outer surface, which can realize the separation of macromolecules in blood, and the internal micrometer-sized pore structure has no separation capacity for macromolecules in blood, so the actual separation layer is only a very thin layer on the inner and outer surfaces, and the thickness will not exceed 10 μm. Such a thin separation layer plus the internal micrometer-sized large pore structure means poor mechanical strength, and practice has proved that such a separation membrane is easy to be damaged in hemodialysis application, which brings high treatment cost to dialysis patients. Compared with the above, the hollow fiber ultrafiltration membrane of the application is prepared only by using a single material, without complex additional modification, which can significantly reduce the process cost. More worth mentioning is that under a specific block ratio, the polysulfone-polyethylene glycol amphiphilic block copolymer of the hollow fiber membrane of the application can be swelled to obtain a larger thickness, so that the entire thickness range of the hemodialysis membrane from the outer surface to the inner surface is uniformly distributed with nanoscale pores with a pore size in the range of 2-50 nm, and therefore the pore structure in the entire thickness range can play a precise and effective role in separating macromolecules, and the actual separation layer thickness of the hollow fiber membrane can reach 100-200 μm, which has surprisingly improved the mechanical properties and service life of the hollow fiber membrane prepared by the NIPS method, thereby greatly reducing the treatment cost of dialysis patients. It can be seen that whether in the preparation process or in the use performance, the application has made significant progress on the basis of NIPS.

[0023] Furthermore, for the hemodialysis industry, the preparation method of the hollow fiber ultrafiltration membrane of the application is simple, easy to operate and low in cost, and does not involve a complex membrane surface modification process, and has good scale-up preparation and practical application prospect. Some specific structure and polymer block ratio membranes prepared by the method can also be applied to the field of hemoperfusion. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 is the SEM image of the outer surface of the hemodialysis membrane obtained in Example 2.

[0025] Figure 2 is the SEM image of the inner surface of the hemodialysis membrane obtained in Example 2.

[0026] Figure 3 is the SEM image of the outer side cross section of the hemodialysis membrane obtained in Example 2.

[0027] Figure 4 is a SEM image of the blood dialysis membrane cross-section obtained in Example 2.

[0028] Figure 5 is a SEM image of the blood dialysis membrane inner side cross-section obtained in Example 2.

[0029] Figure 6 is a SEM image of the blood dialysis membrane cross-section obtained in Example 2.

[0030] Figure 7 is a graph of the toxin clearance performance of the blood dialysis assembly obtained in Example 2.

[0031] Figure 8 is a graph of the blood dialysis assembly performance compared to other kinds of performance obtained in Example 2.

[0032] Figure 9 is a graph of the blood dialysis assembly performance obtained in Example 1, Example 2, Example 3 and Example 4.

[0033] Figure 10 is a graph of the blood dialysis assembly performance obtained in Example 2, Example 5 and Example 6.

[0034] Figure 11 is a SEM image of the blood dialysis membrane outer surface obtained in Comparative Example 1.

[0035] Figure 12 is a SEM image of the blood dialysis membrane inner surface obtained in Comparative Example 1.

[0036] Figure 13 is a SEM image of the blood dialysis membrane cross-section obtained in Comparative Example 1.

[0037] Figure 14 is a SEM image of the blood dialysis membrane outer surface obtained in Comparative Example 2.

[0038] Figure 15 is a SEM image of the blood dialysis membrane inner surface obtained in Comparative Example 2.

[0039] Figure 16 is a SEM image of the blood dialysis membrane cross-section obtained in Comparative Example 2.

[0040] Figure 17 is a SEM image of the asymmetric blood dialysis membrane cross-section obtained in Comparative Example 3 by NIPS method.

[0041] Figure 18 is a graph of the blood dialysis assembly performance obtained in Example 2, Comparative Example 1, Comparative Example 2, Comparative Example 3. DETAILED DESCRIPTION

[0042] The present application provides a kind of hollow fiber ultrafiltration membrane for hemodialysis, it is by polysulfone-polyethylene glycol amphiphilic block copolymer as single material melt spinning and selective swelling preparation Porous membrane, in the amphiphilic block copolymer, polyethylene glycol block ratio is 30%;The hollow fiber ultrafiltration membrane outer surface, internal and inner surface channel all have similar structural characteristics, i.e. porosity, average pore size and pore size distribution are in the same range, thus forming symmetric channel structure in its thickness direction.

[0043] Further, the hollow fiber ultrafiltration membrane described in the present application is used as a membrane filament to prepare a hemodialysis assembly. The method comprises: folding and sterilizing the hollow fiber ultrafiltration membrane described in the present application, placing a certain number of membrane filaments in a dialyzer shell according to the required membrane area, sealing the two ends with polyurethane and epoxy resin glue, so that only the interior of the membrane filament can pass through liquid, and other positions are defect-free, and the hemodialysis assembly is obtained after placing at room temperature for one day. The sterilization and disinfection process in the above method is not particularly limited and can be various existing methods, including ethylene oxide, hydrogen peroxide or high-temperature sterilization, etc. The appropriate sterilization and disinfection method can be selected according to the specific use environment and conditions.

[0044] Experiments have proved that the hemodialysis assembly prepared based on the hollow fiber ultrafiltration membrane described in the present application exhibits 99.9% retention of macromolecular proteins, while maintaining a clearance rate of about 50%-70% for medium molecular toxins, and a clearance rate of up to 95% for small molecular toxins.

[0045] The present application will be further explained below in conjunction with examples. The following examples are only used to illustrate the present application, and the membrane area of the assembly is 0.1-1.5 m 2 , but not to limit the scope of the implementation of the present application. Example 1

[0046] PSF 35 -PEG 30 -PSF 35 The block copolymer is added to a twin-screw extruder and extruded through a spinneret, the obtained hollow fiber is immersed in a mixed solvent (20wt% acetone+80wt% n-propanol), treated in a 65°C water bath for 0.5 h, and then transferred to n-heptane for 5 min. Immediately after the treatment is completed, the hollow fiber is taken out and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The measurement of the membrane channel structure parameters shows that the outer surface channel of the hollow fiber membrane has a porosity of 35.1%, an average pore size of 5.5 nm, and a pore size distribution of 3 nm-8 nm; the inner surface channel has a porosity of 21.3%, an average pore size of 7.5 nm, and a pore size distribution of 5 nm-10 nm; and the internal channel has a porosity of 46.4%, an average pore size of 10.3 nm, and a pore size distribution of 2 nm-15 nm.

[0047] The hollow fiber membrane is used as a membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane is folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealing glue are used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 0.2 m 2 is obtained.

[0048] The hemodialysis assembly prepared in this example is used to perform a hemodialysis test, and the test method is as follows:

[0049] A mixture of urea (1.5 g / L) and lysozyme (0.2 g / L) and BSA (1 g / L) are used as simulated blood, and a PBS solution is used as simulated dialysate. During the dialysis process, the simulated blood and the simulated dialysate pass through the dialysis membrane assembly at a speed of 200 and 500 mL / min, respectively, in opposite directions. After 4 h of dialysis, 20 mL of test solution is taken from the simulated blood outlet for analysis.

[0050] The test results show that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in this example is 14.3 mL / (h·mmHg), the BSA retention is 98.7%, the lysozyme clearance rate is 39.0%, and the myoglobin clearance rate is 33.2%. Example 2

[0051] The hemodialysis membrane is prepared according to the method described in Example 1, and the swelling time is changed. The scheme is as follows:

[0052] The PSF 35 -PEG 30 -PSF 35 block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 1 h, and then transferred to n-heptane for 5 min. Immediately after the treatment is completed, the hollow fiber is taken out and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The hollow fiber membrane is observed under an electron microscope, and the results are shown in Figures 1-6 . Figure 1 、 Figure 2 、 Figure 3 、 Figure 4 、 Figure 5 and Figure 6respectively. As can be seen from the figures, in the case of a polyethylene glycol block ratio of 30%, the hollow fiber hemodialysis membrane prepared by melt spinning and selective swelling of the polysulfone-polyethylene glycol block copolymer has substantially uniform internal and external surface pore structure characteristics, the openings on the outer surface and the inside are relatively uniform, the pore size at all positions is relatively small, and the porosity is high. This makes it have good screening effect on large and medium molecular toxins. Measurement of the membrane pore structure parameters shows that the outer surface pore of the hollow fiber membrane has a porosity of 15.7%, an average pore size of 6.1 nm, and a pore size distribution of 2 nm-8 nm; the internal surface pore has a porosity of 22.4%, an average pore size of 7.8 nm, and a pore size distribution of 3 nm-12 nm; and the internal pore of the membrane has a porosity of 61.8%, an average pore size of 10.8 nm, and a pore size distribution of 3 nm-15 nm.

[0053] The hollow fiber membrane described above is used as a membrane filament to prepare a hemodialysis assembly. The specific method is as follows: the obtained hollow fiber membrane is folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealing glue are used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 0.2 m 2 is obtained.

[0054] The hemodialysis assembly prepared in this example is used for hemodialysis test, and the test method is the same as that in Example 1. The test results show that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in this example is 25.4 mL / (h·mmHg), the BSA retention is 99.9%, the lysozyme clearance rate is 69.2%, and the myoglobin clearance rate is 49.8%. As shown in Figure 7 , the hemodialysis membrane assembly prepared in this example also has an ideal clearance rate for other small and medium molecular toxins. In addition, the applicant compares and analyzes the test results of this example with the experimental data recorded in the previous studies, and the results are shown in Figure 8 . Figure 8 The "This work" marked with five-star shape in the middle represents the test results of this example. It can be seen that the hollow fiber membrane of this example surpasses other various types of hemodialysis membranes in terms of BSA retention rate and lysozyme clearance rate. Example 3

[0055] The hollow fiber membrane is prepared according to the method described in Example 1, and the swelling time is changed. The specific scheme is as follows:

[0056] PSF 35 -PEG 30 -PSF 35The block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 2 h, and then transferred to n-heptane for 5 min. The hollow fiber is immediately taken out after the treatment is completed and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The membrane pore structure parameters are measured to be: the outer surface pore of the hollow fiber membrane, the porosity is 23.7%, the average pore size is 7.1 nm, and the pore size distribution is 3 nm-10 nm; the pore of the inner surface, the porosity is 23.9%, the average pore size is 7.8 nm, and the pore size distribution is 2 nm-15 nm; the internal pore of the membrane, the porosity is 63.2%, the average pore size is 12.1 nm, and the pore size distribution is 5 nm-20 nm.

[0057] The above-mentioned hollow fiber membrane is used as a membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane is folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealing glue are used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 0.2 m 2 is obtained.

[0058] The hemodialysis assembly prepared in this example is used for hemodialysis test, and the test method is the same as that in Example 1. The test results show that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in this example is 26.1 mL / (h·mmHg), the BSA retention is 99.9%, the lysozyme clearance rate is 39.2%, and the myoglobin clearance rate is 40.4%. Example 4

[0059] The hollow fiber membrane is prepared according to the method described in Example 1, and the swelling time is changed. The specific scheme is as follows:

[0060] PSF 35 -PEG 30 -PSF 35 The block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 3 h, and then transferred to n-heptane for 5 min. The hollow fiber is immediately taken out after the treatment is completed and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The membrane pore structure parameters are measured to be: the outer surface pore of the hollow fiber membrane, the porosity is 28.6%, the average pore size is 7.5 nm, and the pore size distribution is 3 nm-13 nm; the pore of the inner surface, the porosity is 34.9%, the average pore size is 7.7 nm, and the pore size distribution is 5 nm-10 nm; the internal pore of the membrane, the porosity is 46.4%, the average pore size is 13.3 nm, and the pore size distribution is 5 nm-22 nm.

[0061] The hollow fiber membrane described above was used as the membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane was gathered and placed inside the dialyzer housing. Both ends were sealed with polyurethane and epoxy resin. After being left at room temperature for one day, a membrane area of ​​0.2 m² was obtained. 2 Hemodialysis components.

[0062] The hemodialysis module prepared in this embodiment was used for hemodialysis testing, and the testing method was the same as in Example 1. The test results showed that the ultrafiltration coefficient of the hemodialysis membrane module prepared in this embodiment was 27.1 mL / (h·mmHg), the BSA rejection rate was 99.9%, the lysozyme clearance rate was 38.0%, and the myoglobin clearance rate was 22.4%. The performance of the hemodialysis modules of Examples 1, 2, 3, and 4 was compared, and the results are shown in [Figure 1]. Figure 9 ,from Figure 9 It can be clearly seen that the 1-hour swelling time is the best for removing lysozyme and myoglobin, two types of medium-molecular-weight toxins, and its ultrafiltration coefficient is basically consistent with that of BSA. Example 5

[0063] Hollow fiber membranes were prepared according to the method described in Example 1, with the swelling temperature varied. The specific method is as follows:

[0064] PSF 35 -PEG 30 -PSF 35 Block copolymers were added to a twin-screw extruder and extruded through a spinneret. The resulting hollow fibers were immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 55°C water bath for 1 h, followed by treatment in n-heptane for 5 min. Immediately after treatment, the hollow fibers were removed and dried at 40°C to obtain a continuously open, symmetrical porous hollow fiber membrane. Measurements of the membrane pore structure parameters revealed the following: the outer surface pores of the hollow fiber membrane had a porosity of 10.1%, an average pore size of 6.2 nm, and a pore size distribution of 2 nm–9 nm; the inner surface pores had a porosity of 22.0%, an average pore size of 7.1 nm, and a pore size distribution of 5 nm–12 nm; and the inner surface pores had a porosity of 42.2%, an average pore size of 10.3 nm, and a pore size distribution of 3 nm–18 nm.

[0065] The hollow fiber membrane described above was used as the membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane was gathered and placed inside the dialyzer housing. Both ends were sealed with polyurethane and epoxy resin. After being left at room temperature for one day, a membrane area of ​​0.2 m² was obtained. 2 Hemodialysis components.

[0066] The hemodialysis membrane assembly prepared in the example was used to perform hemodialysis test, and the test method was the same as that in Example 1. The test results showed that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in the example was 17.1 mL / (h·mmHg), the BSA rejection was 99.8%, the lysozyme clearance rate was 39.8%, and the myoglobin clearance rate was 24.9%. Example 6

[0067] The hollow fiber membrane was prepared according to the method described in Example 1, and the swelling temperature was changed. The specific scheme was as follows:

[0068] The PSF 35 -PEG 30 -PSF 35 The block copolymer was added to the twin-screw extruder and extruded through the spinneret. The obtained hollow fiber was immersed in a mixed solvent (20wt% acetone + 80wt% n-propanol) and treated in a 60°C water bath for 1h, and then transferred to n-heptane for 5min. The hollow fiber was immediately taken out after the treatment was completed, and dried at 40°C to obtain a continuous open porous symmetric porous hollow fiber membrane. The measurement of the membrane pore structure parameters showed that the outer surface channel of the hollow fiber membrane had a porosity of 11.9%, an average pore size of 7.5nm, and a pore size distribution of 2nm-11nm; the channel of the inner surface had a porosity of 30.9%, an average pore size of 8.1nm, and a pore size distribution of 5nm-12nm; and the internal channel of the membrane had a porosity of 47.4%, an average pore size of 11.0nm, and a pore size distribution of 2nm-20nm.

[0069] The hollow fiber membrane described above was used as a membrane filament to prepare a hemodialysis assembly. The specific method was as follows: the obtained hollow fiber membrane was folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealant were used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 0.2m 2 was obtained.

[0070] The hemodialysis assembly prepared in the example was used to perform hemodialysis test, and the test method was the same as that in Example 1. The test results showed that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in the example was 20.1 mL / (h·mmHg), the BSA rejection was 99.9%, the lysozyme clearance rate was 42.8%, and the myoglobin clearance rate was 35%. The performances of the hemodialysis assemblies of Example 2, Example 5, and Example 6 were compared, and the results were shown in Figure 10 , Figure 10 It can be found that when the swelling temperature was 65°C, the clearance effect of the two types of middle molecule toxins, lysozyme and myoglobin, was the best, and the ultrafiltration coefficient was also the best. Example 7

[0071] Hollow fiber membranes were prepared according to the method described in Example 1, with the swelling temperature varied. The specific method is as follows:

[0072] PSF 30 -PEG 25 -PSF 30 Block copolymers were added to a twin-screw extruder and extruded through a spinneret. The resulting hollow fibers were immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 55°C water bath for 1 h, followed by treatment in n-heptane for 5 min. Immediately after treatment, the hollow fibers were removed and dried at 40°C to obtain a continuously open, symmetrical porous hollow fiber membrane. Measurements of the membrane pore structure parameters revealed the following: the outer surface pores of the hollow fiber membrane had a porosity of 31.3%, an average pore size of 12.1 nm, and a pore size distribution of 5 nm–20 nm; the inner surface pores had a porosity of 35.3%, an average pore size of 12.6 nm, and a pore size distribution of 2 nm–18 nm; and the inner surface pores had a porosity of 60.3%, an average pore size of 15.8 nm, and a pore size distribution of 2 nm–22 nm.

[0073] The hollow fiber membrane described above was used as the membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane was gathered and placed inside the dialyzer housing. Both ends were sealed with polyurethane and epoxy resin. After being left at room temperature for one day, a membrane area of ​​0.2 m² was obtained. 2 Hemodialysis components.

[0074] The hemodialysis module prepared in this embodiment was used for hemodialysis testing. The testing method was the same as in Example 1. The test results showed that the ultrafiltration coefficient of the hemodialysis membrane module prepared in this embodiment was 40.3 mL / (h·mmHg), the BSA rejection rate was 95.3%, the lysozyme clearance rate was 45.5%, and the myoglobin clearance rate was 39.8%. Example 8

[0075] The hemodialysis membrane was prepared according to the method described in Example 1, with the swelling time varied as follows:

[0076] PSF 35 -PEG 30 -PSF 35The block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 1 h, and then transferred to n-heptane for 5 min. The hollow fiber is immediately taken out after the treatment is completed and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The membrane pore structure parameters are measured to be: the outer surface channel of the hollow fiber membrane, the porosity is 15.7%, the average pore size is 6.1 nm, and the pore size distribution is 2 nm-8 nm; the channel of the inner surface, the porosity is 22.4%, the average pore size is 7.8 nm, and the pore size distribution is 3 nm-12 nm; the internal channel of the membrane, the porosity is 61.8%, the average pore size is 10.8 nm, and the pore size distribution is 3 nm-15 nm.

[0077] The above-mentioned hollow fiber membrane is used as a membrane filament to prepare a hemodialysis assembly. Specifically, the obtained hollow fiber membrane is folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealing glue are used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 1.5 m 2 is obtained.

[0078] The hemodialysis assembly prepared in this embodiment is used for hemodialysis test, and the test method is the same as that in Example 1. The test results show that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared in this embodiment is 28.9 mL / (h·mmHg), the BSA retention is 99.9%, the lysozyme clearance rate is 69.8%, and the myoglobin clearance rate is 50.1%. Compared with Example 2, the membrane area of the hemodialysis assembly in this embodiment is expanded from 0.2 m 2 to 1.5 m 2 . The experimental results prove that the dialysis performance of the hemodialysis assembly does not decrease with the expansion of the membrane area, and even has a certain improvement. Comparative Example 1

[0079] The hollow fiber membrane is prepared according to the method described in Example 1, and the block copolymer ratio is changed. The specific scheme is as follows:

[0080] PSF 40 -PEG 20 -PSF 40 The block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 1 h, and then transferred to n-heptane for 5 min. The hollow fiber is immediately taken out after the treatment is completed and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The membrane pore structure parameters are measured to be: the outer surface channel of the hollow fiber membrane, the porosity is 15.7%, the average pore size is 6.1 nm, and the pore size distribution is 2 nm-8 nm; the channel of the inner surface, the porosity is 22.4%, the average pore size is 7.8 nm, and the pore size distribution is 3 nm-12 nm; the internal channel of the membrane, the porosity is 61.8%, the average pore size is 10.8 nm, and the pore size distribution is 3 nm-15 nm. Figures 11-13 Figure 11 、 Figure 12 ,​Figure 13 The outer surface, inner surface, cross-sectional SEM images of the hemodialysis membrane prepared under the condition of the pair of examples are shown in the figures, respectively. It can also be clearly seen from the figures in Comparative Example 2 that the pore size distribution range of the membrane prepared under the block ratio condition is large. The measurement of the membrane pore structure parameters shows that the outer surface pore of the hollow fiber membrane has a porosity of 25.4%, an average pore size of 7.1 nm, and a pore size distribution of 6 nm-25 nm; the inner surface pore has a porosity of 30.0%, an average pore size of 8.8 nm, and a pore size distribution of 3 nm-19 nm; and the internal pore of the membrane has a porosity of 59.2%, an average pore size of 20.8 nm, and a pore size distribution of 5 nm-30 nm.

[0081] The above hollow fiber membrane is used as a membrane filament to prepare a hemodialysis assembly. The specific method is as follows: the obtained hollow fiber membrane is folded and placed in a dialyzer shell, and polyurethane and epoxy resin sealing glue are used at both ends. After being placed at room temperature for one day, a hemodialysis assembly with a membrane area of 0.2 m 2 is obtained.

[0082] The hemodialysis assembly prepared by the present comparative example is used for hemodialysis test, and the test method is the same as that in Example 1. The test results show that the ultrafiltration coefficient of the hemodialysis membrane assembly prepared by the present example is 36.0 mL / (h·mmHg), the BSA retention is 95.6%, the lysozyme clearance rate is 34.2%, and the myoglobin clearance rate is 22.2%.

[0083] In the hemodialysis test of the present comparative example, the pore size distribution of the membrane is wide. Since BSA is a protein with a long axis of 14.1 nm, and lysozyme is an elliptical protein with a long axis of 4.5 nm and a short axis of 3.0 nm, it is easy to be intercepted by the membrane prepared by the present comparative example during dialysis, thus resulting in a large ultrafiltration coefficient and a low toxin clearance rate in the test results. Comparative Example 2

[0084] The hollow fiber membrane is prepared according to the method described in Example 1, and the block ratio of the polymer is changed. The specific scheme is as follows:

[0085] The PSF 30 -PEG 40 -PSF 30 block copolymer is added to a twin-screw extruder and extruded through a spinneret. The obtained hollow fiber is immersed in a mixed solvent (20 wt% acetone + 80 wt% n-propanol) and treated in a 65°C water bath for 1 h, and then transferred to n-heptane for 5 min. Immediately after the treatment is completed, the hollow fiber is taken out and dried at 40°C to obtain a continuous open-pore symmetric porous hollow fiber membrane. The hollow fiber porous membrane is observed under an electron microscope, and the results are shown in Figures 14-16 . Figure 14 ,Figure 15 , Figure 16 respectively are the outer surface, inner surface, cross-sectional SEM images of the hemodialysis membrane prepared under the condition of the comparative example, it can be clearly found that in the images of comparative example 2, the pores formed by the membrane prepared under the block ratio condition are basically larger, and the dense regions are more. The membrane pore structure parameters are measured to obtain: the outer surface of the hollow fiber membrane, the outer surface basically cannot see obvious pores; the inner surface of the pores, the porosity is 7.8%, the average pore size is 5.5 nm, and the pore size distribution is 1 nm~21 nm; the internal pores of the membrane, the porosity is 34.2%, the average pore size is 22.4 nm, and the pore size distribution is 5 nm~30 nm.

[0086] The above hollow fiber membrane is used as a membrane filament to prepare a hemodialysis assembly, and the specific method is: the obtained hollow fiber membrane is folded and placed in a dialyzer shell, polyurethane and epoxy resin sealing glue are used at both ends, and the hemodialysis assembly with a membrane area of 0.2m 2 is obtained after placing at room temperature for one day.

[0087] The hemodialysis assembly prepared by the present comparative example is used for hemodialysis test, and the test method is the same as that of example 1. The test results show that the ultrafiltration coefficient of the membrane assembly prepared by the present comparative example is 19.4mL / (h·mmHg), the BSA retention is 99.9%, the lysozyme clearance rate is only 4.2%, and the myoglobin clearance rate is only 2.0%.

[0088] In the hemodialysis test of the present comparative example, the dialysis assembly has a certain ultrafiltration coefficient due to the large pore size distribution, but the low porosity basically prevents the toxin molecules from passing through the membrane pores, so that the toxin clearance rate is low. Comparative example 3

[0089] An asymmetric hemodialysis membrane is prepared by NIPS method, and the specific scheme is as follows:

[0090] PSF 40 -PEG 20 -PSF 40 is dissolved in N-methyl-2-pyrrolidone (NMP) at 60°C to obtain a PSF b -PEG casting solution with a mass fraction of 17-25 wt%. Then the PSF b -PEG casting solution is placed in a blast drying oven for 12 h and cooled to room temperature. About 5 mL of PSF b -PEG casting solution is poured onto a clean glass plate, and a doctor blade with a height of 300μm is used to uniformly coat the PSF b -PEG liquid film. After being placed in air for 10 s, the PSF b- The PEG film spontaneously detached from the glass plate, and was removed and rinsed with deionized water to remove residual solvent, and the film was stored in deionized water. b - The PEG film spontaneously detached from the glass plate, and was removed and rinsed with deionized water to remove residual solvent, and the film was stored in deionized water.

[0091] Figure 17 The asymmetric hemodialysis membrane prepared by the NIPS method was observed by SEM, and it can be seen from the figure that the upper layer is small round holes, and the lower layer is large finger-shaped holes, which leads to a large ultrafiltration coefficient, but due to the too wide pore size distribution, there are still many large molecular proteins lost from the large holes under the condition of low lysozyme removal rate.

[0092] The pore structure parameters of the hemodialysis hollow fiber membrane prepared in this example are: the separation layer thickness of the hollow fiber membrane is 300-1400 nm, the porosity is 15.0%, the average pore size is 6.1 nm, and the pore size distribution is 3 nm-9.4 nm; the internal finger-shaped hole porosity is 62.1%, the average pore size is 7 μm, and the pore size distribution is 5 μm-20 μm. The ultrafiltration coefficient is 100.2 mL / (h·mmHg), the BSA retention is 93.2%, and the lysozyme removal rate is 36.3%.

Claims

1. A hollow fiber ultrafiltration membrane for hemodialysis, which is a porous membrane prepared by melt spinning and selective swelling using a single material of a polysulfone-polyethylene glycol amphiphilic block copolymer, characterized by: The amphiphilic block copolymer has a polyethylene glycol block ratio of 30%; the porosity, average pore size and pore size distribution of the pores on the outer surface, inside and inner surface of the hollow fiber ultrafiltration membrane are in the same range, thereby forming a symmetrical pore structure in the thickness direction thereof; the porosity of the pores on the outer surface, inside and inner surface is in the range of 10% to 70%, the average pore size is in the range of 2 nm to 20 nm, and the pore size distribution is in the range of 2 nm to 25 nm.

2. The hollow fiber ultrafiltration membrane according to claim 1, wherein: The porosity of the pores on the outer surface, inside and inner surface of the hollow fiber ultrafiltration membrane is in the range of 10% to 65%, the average pore size is in the range of 3 nm to 12 nm, and the pore size distribution is in the range of 2 nm to 15 nm.

3. The hollow fiber ultrafiltration membrane according to claim 1, wherein: The porosity of the pores on the outer surface is in the range of 10% to 40%, the average pore size is in the range of 2 nm to 10 nm, and the pore size distribution is in the range of 2 nm to 15 nm; the porosity of the pores on the inner surface is in the range of 10% to 40%, the average pore size is in the range of 2 nm to 10 nm, and the pore size distribution is in the range of 2 nm to 20 nm; the porosity of the pores inside the membrane is in the range of 40% to 70%, the average pore size is in the range of 5 nm to 20 nm, and the pore size distribution is in the range of 2 nm to 25 nm.

4. The hollow fiber ultrafiltration membrane according to claim 1, wherein: The porosity of the pores on the outer surface is in the range of 15% to 30%, the average pore size is in the range of 3 nm to 6 nm, and the pore size distribution is in the range of 2 nm to 8 nm; the porosity of the pores on the inner surface is in the range of 10% to 25%, the average pore size is in the range of 4 nm to 8 nm, and the pore size distribution is in the range of 2 nm to 12 nm; the porosity of the pores inside the membrane is in the range of 55% to 65%, the average pore size is in the range of 8 nm to 12 nm, and the pore size distribution is in the range of 2 nm to 15 nm.

5. A hemodialysis membrane assembly using the hollow fiber ultrafiltration membrane for hemodialysis according to claim 1 as a membrane filament.

6. A method for producing the hollow fiber ultrafiltration membrane for hemodialysis according to claim 1, characterized by, Comprising: 1) preparing a hollow fiber by melt spinning from an amphiphilic block copolymer of polysulfone-polyethylene glycol, wherein the polyethylene glycol block ratio is 30%; 2) immersing the hollow fiber obtained in 1) in a mixed solvent containing 20 wt% acetone and 80 wt% n-propanol, and selectively swelling at 60-65°C for 0.5-3 h, and then transferring to n-heptane for 5 min, and drying to obtain the hollow fiber ultrafiltration membrane for hemodialysis having a symmetrical pore structure.

7. The method of claim 6, wherein: 2) the swelling treatment is at 65°C for 1 h.

8. The method of claim 6, wherein: 2) the swelling treatment is treated by microwave with a power of 160-800 W for 15-60 s. 2) the swelling treatment is treated by microwave with a power of 160-800 W for 15-60 s.

Images