A hydrophilic anticoagulant-hydrophobic gas permeable asymmetric oxygenation membrane and method of making same

Abstract

The present application relates to the technical field of high molecular separation membrane, especially to a hydrophilic anticoagulant-hydrophobic gas permeable asymmetric oxygenation membrane and a preparation method thereof, comprising the following steps: adding an acid modifier into a PMP casting solution to obtain a modified PMP casting solution; extruding the modified PMP casting solution into a hollow fiber membrane through a spinneret, then sequentially entering a first coagulation bath and a second coagulation bath for solidification, and then winding the hollow fiber membrane to obtain the hollow fiber membrane; and then extracting and cross-linking the hollow fiber membrane to obtain the hydrophilic anticoagulant-hydrophobic gas permeable asymmetric oxygenation membrane; wherein the first coagulation bath is a polyethyleneimine or polyamide amine aqueous solution; and the second coagulation bath is a heparin aqueous solution.The preparation method of the hydrophilic anticoagulant-hydrophobic gas permeable asymmetric oxygenation membrane is simple, and the membrane structure can be accurately controlled, so that the membrane has high gas transmission, blood compatibility and anti-plasma leakage, and has good industrial production basis and broad application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer separation membranes, in particular to a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane and a preparation method thereof. Background Art

[0002] Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support system that uses a blood pump to extract venous blood with low oxygen content and high carbon dioxide content from the patient's body. The blood flows through an oxygenator, where oxygen and carbon dioxide are exchanged between the blood and the sweep gas, and then the blood is returned to the human body. It is often used to oxygenate blood and eliminate carbon dioxide, so it is also called an artificial lung.

[0003] The membrane lung is a core component of ECMO. It acts as a barrier between blood and air, enabling the exchange of carbon dioxide in the blood and oxygen in the air through a breathable oxygenation membrane without direct contact between the two. Furthermore, as a biomedical membrane in direct contact with human blood, the oxygenation membrane must exhibit excellent hemocompatibility and resist coagulation, hemolysis, or immune responses.

[0004] Poly (4-methyl-1-pentene) is a highly crystalline, transparent plastic with a stereoregular structure. It has excellent gas permeability and mechanical properties, and is resistant to high temperatures and corrosion. It has broad application prospects in the field of blood oxygenation membranes in hemodialysis for kidney disease and in extracorporeal membrane oxygenation systems for treating patients with severe cardiopulmonary and respiratory failure.

[0005] Because PMP has a high melting point of 240-260°C and suitable solvents are difficult to find at room temperature, PMP oxygenation membranes are primarily prepared through thermally induced phase separation. However, polymer membranes synthesized from single small molecules have poor blood compatibility and are no longer suitable for clinical medical applications. Therefore, surface modification of the membrane is required for practical applications.

[0006] However, since the PMP membrane surface only has methyl and methylene groups and no active groups, it poses a huge challenge to modification. In addition, traditional membrane surface modification basically uses inexpensive surface coating methods, but this method cannot completely suppress the human body's rejection reaction and requires the injection of large amounts of anticoagulants. How to simply and efficiently achieve surface blood compatibility modification has become a research hotspot.

[0007] In view of this, the present invention is proposed. Summary of the Invention

[0008] The present invention aims to provide a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane and a preparation method thereof. In this preparation method, a negatively charged PMP casting solution is extruded through a spinneret and sequentially enters a first coagulation bath and a second coagulation bath. Under the interaction between the charges, polyethyleneimine (or polyamidoamine) and heparin are sequentially fixed to the surface of the PMP membrane by layer-by-layer self-assembly. That is, the use of polyethyleneimine or polyamidoamine significantly increases the fixed amount of heparin, thereby significantly improving the anticoagulant performance of the PMP oxygenation membrane.

[0009] The present invention provides a method for preparing a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane, comprising the following steps:

[0010] A PMP casting liquid is prepared, and an acidic modifier is added to the PMP casting liquid to obtain a modified PMP casting liquid; the modified PMP casting liquid is extruded through a spinneret to form, and then sequentially enters a first coagulation bath and a second coagulation bath to be solidified and formed, and a hollow fiber membrane is obtained by winding and collecting the fibers; the hollow fiber membrane is sequentially extracted and cross-linked to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane; wherein the first coagulation bath is an aqueous solution of polyethyleneimine or polyamide amine; and the second coagulation bath is an aqueous solution of heparin.

[0011] In the preparation process of the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane of the present invention, the PMP casting liquid is first modified with an acidic modifier to etch the PMP casting liquid. After acid etching, the PMP casting liquid will generate a negative charge. The negatively charged PMP casting liquid is extruded through a spinneret and sequentially enters a first coagulation bath of a polyethyleneimine or polyamideamine aqueous solution exhibiting a positive charge and a second coagulation bath of a heparin solution exhibiting a negative charge. In the first coagulation bath, a uniform polyethyleneimine layer or polyamideamine layer is formed on the surface of the PMP membrane filaments with a negative charge through charge adsorption. Since the positive charge density of polyethyleneimine or polyamideamine is relatively high, when the membrane filaments enter the negatively charged heparin coagulation bath again, a uniform heparin layer is formed on the surface of the polyethyleneimine layer or polyamideamine layer under the action of the charge. Therefore, under the interaction of charges, the present invention can sequentially fix polyethyleneimine and heparin on the surface of the PMP membrane by layer-by-layer self-assembly, that is, heparin is fixed by polyethyleneimine or polyamidoamine to increase the fixed amount of heparin, thereby improving the anti-coagulation performance of the PMP oxygenation membrane. Finally, the stability of the functional substance is further improved by cross-linking and curing, effectively solving the problem of no active groups on the surface of the PMP membrane and difficulty in modification.

[0012] The acidic modification of the present invention is mainly used to etch the PMP casting solution to produce a uniform layer of negative charge on the surface of the membrane filament. Therefore, there is no strict limitation on the specific type of the acidic modifier, and any one or more of sulfuric acid, hydrochloric acid, and nitric acid can be selected. There is no specific limitation on the concentration of the acid, and either dilute acid or concentrated acid can be used. Considering the etching effect, concentrated acid is preferred.

[0013] As a preferred embodiment of this technical solution, the following steps are included:

[0014] S1. PMP and a diluent are mixed, heated to 200-300°C in a protective gas atmosphere, stirred for 3-8 hours to form a homogeneous solution, and then an acidic modifier is added. After stirring and mixing evenly, vacuum degassing is performed to obtain a modified PMP casting solution;

[0015] S2, extruding the modified PMP casting solution through a spinneret, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form the solution while completing layer-by-layer self-assembly, and obtaining a hollow fiber membrane by winding and collecting the filaments;

[0016] S3, soaking the membrane obtained in step S2 in an extractant for 20-50 hours, and replacing the extractant every 10-15 hours;

[0017] S4, placing the film obtained after extraction in a third coagulation bath for cross-linking and solidification;

[0018] S5. The cross-linked and cured membrane is placed in a vacuum oven at 25-40° C. and dried for 10-15 hours to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane.

[0019] The present invention uses a thermally induced phase separation method to utilize the self-assembly method of positive and negative charges layer by layer to sequentially construct a polyethyleneimine layer (or polyamidoamine) and a heparin layer on the surface of the PMP membrane to prepare an asymmetric PMP oxygenation membrane with a gradient pore structure. The small pore side of the gradient pore membrane filament is a dense cortex, while the other side is a relatively loose porous structure. This effectively prevents plasma leakage while ensuring high carbon dioxide and oxygen transmission performance. The average pore size of the dense cortex is less than 1nm and the thickness is 100-500μm, while the average pore size of the loose porous layer is 2-10μm.

[0020] As a preferred embodiment of the present technical solution, in step S1, the mass fraction of PMP is preferably 15%-30%;

[0021] The diluent used is a conventional diluent, including any one of dibutyl phthalate, dioctyl phthalate and diphenyl ether.

[0022] As a preferred embodiment of this technical solution, in step S1, the modified PMP casting solution must consider both the degree of modification of the PMP casting solution and the effect of the acid modifier on the mechanical strength of the PMP oxygenated membrane filaments. Research has shown that when the mass fraction of the acid modifier is anywhere between 0.1% and 5%, these requirements can be met simultaneously.

[0023] One thing that needs to be noted here is that, since an acid modifier needs to be added during the preparation of the casting liquid, considering the problem of corrosion of the reactor by the acid modifier, when the present invention is implemented, the reactor used is preferably a reactor with a corrosion-resistant coating on the inner wall of the reactor body, such as the corrosion-resistant chemical production reactor disclosed in application number CN201921831371.9.

[0024] As a preferred embodiment of this technical solution, in step S2, after the modified PMP casting solution is extruded through the spinneret, the drawing speed is controlled to be 0.1-1 m / s, and the gap of the air segment is 2-10 m. Considering that both the drawing speed and the length of the air segment affect the degree of phase separation and thus the distribution of the membrane pore structure, the drawing speed is preferably 0.1-0.5 m / s, and the gap of the air segment is preferably 2-5 m.

[0025] As a preferred embodiment of the present technical solution, in step S2, the mass fraction of polyethyleneimine or polyamidoamine in the first coagulation bath is 0.1-10%; and the mass fraction of heparin in the second coagulation bath is 0.1-20%.

[0026] By controlling the concentration of polyethyleneimine or polyamideamine in the first coagulation bath and the concentration of heparin in the second coagulation bath, the layer-by-layer self-assembly effect of polyethyleneimine (or polyamideamine) and heparin on the surface of the PMP membrane can be controlled so that heparin is evenly loaded on the surface of the PMP oxygenated membrane. In order to completely cover the surface of polyethyleneimine or polyamideamine with heparin, the concentration of heparin in the second coagulation bath is preferably twice or more than twice that of polyethyleneimine or polyamideamine in the first coagulation bath.

[0027] By varying the dwell time of the membrane filaments in the first and second coagulation baths, effective control of membrane pore size can be achieved. Therefore, based on the above technical solution, the temperature of the first coagulation bath is 25-30°C, and the dwell time of the membrane filaments in the first coagulation bath is 30 seconds to 10 minutes; the temperature of the second coagulation bath is 25-30°C, and the dwell time of the membrane filaments in the second coagulation bath is 30 seconds to 10 minutes.

[0028] As a preferred embodiment of the present technical solution, in step S3, the extractant is used to extract the diluent remaining on the membrane. The present invention does not strictly limit the specific type of the extractant, and any one of ethanol, methanol, acetone and n-hexane can be selected.

[0029] Finally, the extracted membrane fibers are placed in an aqueous solution of glutaraldehyde to crosslink the aldehyde groups of the glutaraldehyde with the amino groups, thereby improving the stability of the heparin functional substance. Specifically, in step S4, the third coagulation bath is an aqueous solution of glutaraldehyde with a mass fraction of 0.1-20%. The temperature of the third coagulation bath is 30-80°C, and the membrane fibers remain in the third coagulation bath for 30 seconds to 30 minutes.

[0030] Secondly, the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane prepared by the above preparation method has no coagulation phenomenon on the membrane surface after 5-10 hours of plasma flushing, which should also fall within the scope of protection of the present invention.

[0031] The method for preparing the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane of the present invention has at least the following technical effects:

[0032] 1. In the preparation process of the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane of the present invention, the PMP casting solution is first modified with an acidic modifier to etch the PMP casting solution. After acid etching, the PMP casting solution generates a negative charge. The negatively charged PMP casting solution is extruded through a spinneret and sequentially enters a first coagulation bath and a second coagulation bath, wherein the first coagulation bath is a positively charged aqueous solution of polyethyleneimine or polyamideamine, and the second coagulation bath is a negatively charged heparin solution. Therefore, under the interaction between the charges, polyethyleneimine (or polyamideamine) and heparin can be sequentially fixed to the surface of the PMP membrane by layer-by-layer self-assembly, that is, the polyethyleneimine or polyamideamine is used to achieve heparin fixation, thereby increasing the fixed amount of heparin and thereby improving the anticoagulant performance of the PMP oxygenation membrane;

[0033] 2. The extracted membrane fibers are placed in an aqueous solution of glutaraldehyde. The aldehyde group of glutaraldehyde undergoes a cross-linking reaction with the amino group, which can further improve the stability of the heparin functional substance and thereby increase the service life of the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane.

[0034] 3. The hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane prepared by this method mainly exhibits an asymmetric gradient pore structure. The small pore side of the gradient pore membrane is a dense cortex, while the other side is a relatively loose porous structure. This effectively prevents plasma leakage while ensuring high carbon dioxide and oxygen transmission performance.

[0035] 4. The preparation method of the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane of the present invention is simple, and the membrane structure can be precisely controlled so that it has high gas transmission, blood compatibility and anti-plasma leakage properties, and has a good industrial production foundation and broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0037] Figure 1 This is a microstructure diagram of the membrane surface of the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane obtained in Example 5 of the present invention after 5 hours of plasma flushing;

[0038] Figure 2 This is a microstructure diagram of the membrane surface of the PMP oxygenation membrane of the control example 1 of the present invention after 5 hours of plasma flushing;

[0039] Figure 3 This is the microscopic structure of the membrane surface of the PMP oxygenation membrane of the control example 2 of the present invention after 5 hours of plasma flushing. DETAILED DESCRIPTION

[0040] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present application belongs.

[0041] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular also includes the plural. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0042] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0043] Example 1

[0044] S11, PMP and dibutyl phthalate diluent are mixed to prepare a PMP casting solution with a mass fraction of 15%, and the mixture is heated to 200° C. in a protective gas atmosphere and stirred for 8 hours to form a homogeneous solution. 1% dilute sulfuric acid is then added, and the mixture is stirred and mixed uniformly, followed by vacuum degassing to obtain a modified PMP casting solution;

[0045] S12, extruding the modified PMP casting solution through a spinneret, controlling the drawing speed to 0.5 m / s and the gap of the air section to 5 m, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form while completing layer-by-layer self-assembly, and obtaining a hollow fiber membrane by winding and collecting the filaments;

[0046] The mass fraction of polyethyleneimine in the first coagulation bath was 0.1%, the temperature was 25°C, and the residence time of the membrane filaments in the first coagulation bath was 2 minutes. The mass fraction of heparin in the second coagulation bath was 0.5%, the temperature was 25°C, and the residence time of the membrane filaments in the second coagulation bath was 5 minutes.

[0047] S13, soaking the membrane obtained in step S12 in an ethanol extractant for 40 hours, and replacing the extractant every 10 hours;

[0048] S14, placing the membrane obtained after extraction in a 10% by mass glutaraldehyde aqueous solution for cross-linking and curing, and controlling the temperature of the glutaraldehyde aqueous solution to be 50° C. and the residence time to be 20 min;

[0049] S14. The cross-linked and cured membrane was placed in a vacuum oven at 30° C. and dried for 15 h to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membrane.

[0050] Example 2

[0051] S21, PMP and dioctyl phthalate diluent are mixed to prepare a PMP casting solution with a mass fraction of 20%, and the mixture is heated to 250° C. in a protective gas atmosphere and stirred for 5 hours to form a homogeneous solution. 2% dilute hydrochloric acid is then added, and the mixture is stirred and mixed uniformly, followed by vacuum degassing to obtain a modified PMP casting solution;

[0052] S22, extruding the modified PMP casting solution through a spinneret, controlling the drawing speed to 0.5 m / s and the gap of the air section to 5 m, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form while completing layer-by-layer self-assembly, and finally obtaining a hollow fiber membrane by winding and collecting the filaments;

[0053] The mass fraction of polyamidoamine in the first coagulation bath was 1%, the temperature was 25°C, and the residence time of the membrane fibers in the first coagulation bath was 2 minutes. The mass fraction of heparin in the second coagulation bath was 5%, the temperature was 25°C, and the residence time of the membrane fibers in the second coagulation bath was 2 minutes.

[0054] S23, soaking the membrane obtained in step S22 in an ethanol extractant for 40 hours, and replacing the extractant every 10 hours;

[0055] S24, placing the membrane obtained after extraction in a 10% by mass glutaraldehyde aqueous solution for cross-linking and curing, and controlling the temperature of the glutaraldehyde aqueous solution to be 50° C. and the residence time to be 20 min;

[0056] S24. The cross-linked and cured membrane is placed in a vacuum oven at 30° C. and dried for 15 hours to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membrane.

[0057] Example 3

[0058] S31, PMP and dibutyl phthalate diluent are mixed to prepare a PMP casting solution with a mass fraction of 25%, and the mixture is heated to 300° C. in a protective gas atmosphere and stirred for 5 hours to form a homogeneous solution. 2% dilute hydrochloric acid is then added, and the mixture is stirred and mixed until uniformly mixed, and vacuum degassing is performed to obtain a modified PMP casting solution;

[0059] S32, extruding the modified PMP casting solution through a spinneret, controlling the drawing speed to 0.5 m / s and the gap of the air section to 5 m, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form while completing layer-by-layer self-assembly, and finally obtaining a hollow fiber membrane by winding and collecting the filaments;

[0060] The mass fraction of polyethyleneimine in the first coagulation bath was 5%, the temperature was 25°C, and the residence time of the membrane filaments in the first coagulation bath was 1 minute. The mass fraction of heparin in the second coagulation bath was 10%, the temperature was 25°C, and the residence time of the membrane filaments in the second coagulation bath was 2 minutes.

[0061] S33, soaking the membrane obtained in step S32 in an ethanol extractant for 40 hours, and replacing the extractant every 10 hours;

[0062] S34, placing the membrane obtained after extraction in a 10% by mass glutaraldehyde aqueous solution for cross-linking and curing, and controlling the temperature of the glutaraldehyde aqueous solution to be 50° C. and the residence time to be 20 minutes;

[0063] S34. The cross-linked and cured membrane was placed in a vacuum oven at 30° C. and dried for 15 hours to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membrane.

[0064] Example 4

[0065] S41, mixing PMP and dibutyl phthalate diluent to prepare a PMP casting solution with a mass fraction of 30%, heating to 300° C. in a protective gas atmosphere, stirring for 8 hours to form a homogeneous solution, adding 5% dilute hydrochloric acid, stirring and mixing until uniform, and vacuum degassing to obtain a modified PMP casting solution;

[0066] S42, extruding the modified PMP casting solution through a spinneret, controlling the drawing speed to 0.5 m / s and the gap of the air section to 5 m, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form while completing layer-by-layer self-assembly, and finally obtaining a hollow fiber membrane by winding and collecting the filaments;

[0067] The mass fraction of polyethyleneimine in the first coagulation bath was 10%, the temperature was 25°C, and the residence time of the membrane fibers in the first coagulation bath was 30 seconds. The mass fraction of heparin in the second coagulation bath was 20%, the temperature was 25°C, and the residence time of the membrane fibers in the second coagulation bath was 1 minute.

[0068] S43, soaking the membrane obtained in step S42 in an ethanol extractant for 40 hours, and replacing the extractant every 10 hours;

[0069] S44, placing the membrane obtained after extraction in a 10% by mass glutaraldehyde aqueous solution for cross-linking and curing, and controlling the temperature of the glutaraldehyde aqueous solution to be 50° C. and the residence time to be 20 min;

[0070] S44. The cross-linked and cured membrane was placed in a vacuum oven at 30° C. and dried for 15 h to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membrane.

[0071] Example 5

[0072] S51, PMP and dibutyl phthalate diluent are mixed to prepare a PMP casting solution with a mass fraction of 25%, and the mixture is heated to 250° C. in a protective gas atmosphere and stirred for 5 hours to form a homogeneous solution. 3% dilute hydrochloric acid is then added, and the mixture is stirred and mixed uniformly, followed by vacuum degassing to obtain a modified PMP casting solution;

[0073] S52, extruding the modified PMP casting solution through a spinneret, controlling the drawing speed to be 0.5 m / s, and the gap of the air section to be 5 m, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form while completing layer-by-layer self-assembly, and finally obtaining a hollow fiber membrane by winding and collecting the filaments;

[0074] The mass fraction of polyamidoamine in the first coagulation bath was 5%, the temperature was 25°C, and the residence time of the membrane fibers in the first coagulation bath was 1 minute. The mass fraction of heparin in the second coagulation bath was 10%, the temperature was 25°C, and the residence time of the membrane fibers in the second coagulation bath was 2 minutes.

[0075] S53, soaking the membrane obtained in step S52 in an ethanol extractant for 40 hours, and replacing the extractant every 10 hours;

[0076] S54, placing the membrane obtained after extraction in a 10% by mass glutaraldehyde aqueous solution for cross-linking and curing, and controlling the temperature of the glutaraldehyde aqueous solution to be 50° C. and the residence time to be 20 min;

[0077] S54. The cross-linked and cured membrane is placed in a vacuum oven at 30° C. and dried for 15 hours to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membrane.

[0078] Comparative Example 1

[0079] No acidic modifier was used to modify the PMP casting solution;

[0080] Other steps and parameters are basically the same as those in Example 5.

[0081] Comparative Example 2

[0082] First, a PMP hollow fiber membrane is prepared, and then the surface of the PMP hollow fiber membrane is washed with 5% dilute hydrochloric acid; then, the PMP hollow fiber membrane is immersed in a polyamide amine aqueous solution, a heparin aqueous solution, and a glutaraldehyde aqueous solution in sequence to obtain a PMP oxygenation membrane;

[0083] The mass fraction of polyamidoamine is 5%, the temperature is 25°C, and the residence time is 1 min; the mass fraction of heparin is 10%, the temperature is 25°C, and the residence time is 2 min;

[0084] Other steps and parameters are basically the same as those in Example 5.

[0085] In order to study the performance of the oxygenation membrane, the protein adsorption performance and coagulation index of the PMP oxygenation membranes prepared in Examples 1-5 and Comparative Examples 1-2 were tested. The specific test methods are as follows:

[0086] Protein adsorption capacity test: Prepare a 0.5 g / L BSA solution in PBS buffer. Cut 2 cm long membrane threads with a scalpel and soak the modified membrane threads in 5 mL of the prepared BSA solution. Oscillate the solution in a thermostat at 25°C for 24 hours to achieve protein adsorption equilibrium on the membrane thread surface. Prepare three replicate samples for each membrane thread for surface adsorption. Label 10 mL centrifuge tubes and add 100 μL of the BSA solution before and after adsorption to each tube. Dilute the solution with 400 μL of PBS buffer and stain with 5 mL of 1× G520 staining solution. Measure the absorbance of the solution in each tube using a UV-Vis spectrophotometer. Calculate the concentration of the BSA solution before and after adsorption using a BSA standard curve to estimate the amount of BSA adsorbed on the PMP membrane surface (Q).

[0087] Coagulation index testing: Cut the membrane material into small pieces and place them in a well plate, covering the bottom of the wells. Dilute whole blood with physiological saline, and add 250 μL of the diluted whole blood to the surface of the material in the well plate. Then quickly add CaCl2 (0.02 mol / L) solution. After every 10, 20, 30, 40, and 50 minutes, quickly add 100 μL of distilled water to terminate the coagulation reaction. Then, incubate in a constant temperature shaking water bath at 37°C for 10 minutes. Take 200 μL of the supernatant from each group and add it to the well plate. Use a microplate reader to measure the OD value and calculate the coagulation index.

[0088] At the same time, SEM scanning electron microscopy was used to further characterize its anticoagulant effect. Figure 1 This is a microstructure diagram of the membrane surface after the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane obtained in Example 5 was flushed with plasma for 5 hours; Figure 2 This is the microstructure of the membrane surface of the PMP oxygenation membrane in control example 1 after 5 hours of plasma flushing; Figure 3 This is the microstructure of the membrane surface of the control example 2 PMP oxygenation membrane after 5 hours of plasma flushing.

[0089] Table 1 PMP oxygenation membrane performance

[0090] <![CDATA[Protein adsorption amount (μg / cm 2 )]]> Coagulation index (%) Example 1 50 110 Example 2 42 124 Example 3 39 132 Example 4 30 140 Example 5 20 138 Comparative Example 1 300 80 Comparative Example 2 203 98

[0091] As shown in Table 1, the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenated membranes prepared in Examples 1-5 of the present invention exhibit low protein adsorption (less than 50%), a coagulation index greater than 110%, and no coagulation on the membrane surface after 5-10 hours of plasma flushing. The poor anticoagulant effect of Control Example 1 may be due to the lack of active groups on the PMP membrane surface, making it difficult to modify the PMP membrane surface directly via thermally induced phase separation. Control Example 2, in which the membrane is modified after formation and a heparin layer is constructed on the membrane surface via a layer-by-layer self-assembly method, improves its anticoagulant effect to a certain extent, but the improvement is limited to the membrane surface and is limited in effectiveness.

[0092] and Figure 1-3 It is further shown that the hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane obtained in Example 5 of the present invention has a superior anticoagulant effect compared to control examples 1-2.

[0093] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane, characterized in that: The following steps are involved: preparing a PMP casting solution, and adding an acidic modifier to the PMP casting solution to obtain a modified PMP casting solution; The modified PMP casting solution is extruded through a spinneret and then sequentially enters a first coagulation bath and a second coagulation bath for solidification, and a hollow fiber membrane is obtained by winding the filaments; the hollow fiber membrane is sequentially extracted and cross-linked to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane; Wherein, the acidic modifier includes any one or more of sulfuric acid, hydrochloric acid, and nitric acid; The first coagulation bath is an aqueous solution of polyethyleneimine or polyamidoamine; The second coagulation bath is an aqueous solution of heparin.

2. The preparation method according to claim 1, characterized in that The following steps are involved: S1. PMP and a diluent are mixed, heated to 200-300°C in a protective gas atmosphere, stirred for 3-8 hours to form a homogeneous solution, and then an acidic modifier is added. After stirring and mixing evenly, vacuum degassing is performed to obtain a modified PMP casting solution; S2, extruding the modified PMP casting solution through a spinneret, and then sequentially entering the first coagulation bath and the second coagulation bath to solidify and form the solution while completing layer-by-layer self-assembly, and obtaining a hollow fiber membrane by winding and collecting the filaments; S3, soaking the membrane obtained in step S2 in an extractant for 20-50 hours, and replacing the extractant every 10-15 hours; S4, placing the film obtained after extraction in a third coagulation bath for cross-linking and solidification; S5. The cross-linked and cured membrane is placed in a vacuum oven at 25-40° C. and dried for 10-15 hours to obtain a hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane.

3. The preparation method according to claim 2, characterized in that In step S1, the mass fraction of PMP is 15%-30%; The diluent includes any one of dibutyl phthalate, dioctyl phthalate and diphenyl ether.

4. The preparation method according to claim 2, characterized in that In step S1, the mass fraction of the acidic modifier in the modified PMP casting solution is 0.1%-5%.

5. The preparation method according to claim 2, characterized in that In step S2, after the modified PMP casting solution is extruded through a spinneret, the drawing speed is controlled to be 0.1-1 m / s, and the gap of the air section is 2-10 m.

6. The preparation method according to claim 2, characterized in that In step S2, the mass fraction of polyethyleneimine or polyamidoamine in the first coagulation bath is 0.1-10%; In the second coagulation bath, the mass fraction of heparin is 0.1-20%.

7. The preparation method according to claim 2, characterized in that In step S2, the temperature of the first coagulation bath is 25-30°C, and the residence time of the membrane filaments in the first coagulation bath is 30s-10min; The temperature of the second coagulation bath is 25-30° C., and the residence time of the membrane filaments in the second coagulation bath is 30 s-10 min.

8. The preparation method according to claim 2, characterized in that In step S3, the extractant includes any one of ethanol, methanol, acetone and n-hexane.

9. The preparation method according to claim 2, characterized in that In step S4, the third coagulation bath is an aqueous solution of glutaraldehyde, and the mass fraction of glutaraldehyde is 0.1-20%; The temperature of the third coagulation bath is 30-80° C., and the residence time of the membrane filaments in the third coagulation bath is 30 s-30 min.

10. A hydrophilic anticoagulant-hydrophobic breathable asymmetric oxygenation membrane, characterized in that: The oxygenated membrane is prepared by the preparation method according to any one of claims 1 to 9, and there is no coagulation phenomenon on the membrane surface after the oxygenated membrane is flushed with plasma for 5 to 10 hours.

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