CN113877006A - Modified polymer membrane material and preparation method thereof - Google Patents
Modified polymer membrane material and preparation method thereof Download PDFInfo
- Publication number
- CN113877006A CN113877006A CN202111123851.1A CN202111123851A CN113877006A CN 113877006 A CN113877006 A CN 113877006A CN 202111123851 A CN202111123851 A CN 202111123851A CN 113877006 A CN113877006 A CN 113877006A
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- China
- Prior art keywords
- membrane material
- polymer membrane
- phosphorylcholine
- heparin
- grafted
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- 239000000463 material Substances 0.000 title claims abstract description 77
- 229920005597 polymer membrane Polymers 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 229920000669 heparin Polymers 0.000 claims abstract description 75
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 70
- 229960002897 heparin Drugs 0.000 claims abstract description 70
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims abstract description 42
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- 239000012528 membrane Substances 0.000 claims description 28
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- 238000000034 method Methods 0.000 claims description 20
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- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 claims description 14
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- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 claims description 10
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- TYAVIWGEVOBWDZ-UHFFFAOYSA-K cerium(3+);phosphate Chemical compound [Ce+3].[O-]P([O-])([O-])=O TYAVIWGEVOBWDZ-UHFFFAOYSA-K 0.000 claims description 2
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- HKVFISRIUUGTIB-UHFFFAOYSA-O azanium;cerium;nitrate Chemical compound [NH4+].[Ce].[O-][N+]([O-])=O HKVFISRIUUGTIB-UHFFFAOYSA-O 0.000 claims 1
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- GUAQVFRUPZBRJQ-UHFFFAOYSA-N n-(3-aminopropyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCCN GUAQVFRUPZBRJQ-UHFFFAOYSA-N 0.000 description 7
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- NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical group OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 description 2
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Images
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- A61L33/0041—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate characterised by the choice of an antithrombatic agent other than heparin
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- C—CHEMISTRY; METALLURGY
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The invention relates to a modified polymer membrane material and a preparation method thereof, wherein the modified polymer membrane material is mainly characterized in that two coatings of phosphorylcholine zwitterions and heparin with anticoagulation effect are grafted on the surface of the polymer membrane material. The preparation method of the coating comprises the following steps: firstly, grafting phosphorylcholine and acrylamide copolymer on the surface of a polymer membrane material; secondly, putting the treated polymer membrane material into a cleaning solution for cleaning, soaking and drying; a third step of subjectingAnd reacting the residual amino grafted on the polymer membrane material after the second-step drying with a heparin solution activated by EDC and NHS to obtain the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine zwitterion and the heparin coating. The invention can prepare modified polymer membrane material with good mechanical property, good hydrophilicity and long-acting anticoagulation; the prepared heparin coating is uniform, the grafting amount of the heparin is high and can reach 6.3 mu g/cm2Has good market prospect.
Description
Technical Field
The invention relates to the field of biomedical polymer materials, in particular to a modified polymer membrane material and a preparation method thereof.
Background
High molecular materials are widely used for materials in contact with body fluids or blood due to their good mechanical properties, wear resistance and processability. Polyurethane is an important medical material, and has wide application in artificial heart and artificial blood vessel. The polyurethane biomaterial can be used for medical devices such as catheters for interventional operations, ureteral catheters, wound dressings, artificial hearts, artificial heart valves, venous transfusion ports and the like.
The medical polyurethane material may be classified into polyester polyurethane, polyether polyurethane, polycarbonate polyurethane, and the like according to chemical composition. The polyester polyurethane is a polyurethane material synthesized on the basis of polyester polyol, but ester bonds are also easily affected by water to generate degradation reaction, so that the application of the polyester polyurethane in the aspect of long-term implanted materials is limited; polyether polyurethane is a polyurethane material synthesized on the basis of polyether polyol, and the polyether chain of the polyether polyurethane material is easy to decompose, so that the application of the polyether polyurethane material in the aspect of implant materials is limited; in addition, due to the flexibility of the polyether chain, the polyether polyurethane material has high permeability to water and water vapor, and when the polyether polyurethane material is used as a medical equipment material, the polyether polyurethane material has great threat to metal parts of equipment; compared with other polyurethane materials, polycarbonate Polyurethane (PCU) has better biocompatibility, and simultaneously, the chemical structure of the PCU determines that the PCU is more stable in organisms, so that the PCU can meet the requirements of long-term implantation type application on the materials.
Although the polyurethane material has good biocompatibility, coagulation and hemolysis occur when it is in direct contact with blood, thereby causing thrombosis. To solve this problem, researchers have conducted studies on anticoagulation of materials by surface modification. Among them, heparin and Phosphorylcholine (PC) are the hot spots of research. Heparin can inhibit the activity of thromboplastin, so that prothrombin is inhibited from being changed into thrombin, the thrombin cannot play a role in promoting fibrinogen to be changed into fibrin, and the aggregation of platelets is organized, so that the heparin has an anticoagulant property. Phosphorylcholine is a hydrophilic end group of a basic unit forming a cell membrane, plays an important role in an outer cell membrane and directly influences organism cells to have an effect with the outside. The phosphorylcholine group contains a quaternary ammonium group and a phosphoryl group, has positive and negative charges, is a zwitterion structure, and has strong water binding capacity. By simulating the structure of an extracellular phospholipid double-layer membrane, the material rich in phosphorylcholine groups is modified into natural components in an organism, so that the material has excellent biocompatibility, the surface is not easy to adsorb platelets, and the anticoagulation performance of the material is improved.
Patent CN104629058A discloses a method for preparing heparinized polyurethane film, which uses polyurethane film with carboxyl as substrate, activates the carboxyl on the surface of polyurethane by 1-ethyl-3- (dimethylpropylamine) carbodiimide (WSC), and then grafts heparin to prepare heparinized polyurethane film. However, the amount of carboxyl groups on the surface of the polyurethane film is limited, and the active groups are fewer, so that the grafting efficiency of heparin is low.
Patent CN101967235A discloses a phosphorylcholine modified polyurethane biomaterial and a preparation method thereof, wherein a plasma surface modification method is adopted to introduce functional molecules or groups on the surface of the material, so as to reduce the contact angle and improve the anticoagulation performance. However, the surface grafting of the membrane treated by plasma is not firm and cannot meet the long-term requirement of surface modification.
Patent CN112316218A discloses a composite coating of zwitterionic polymer and heparin, and its preparation method and application, wherein a dopamine solution is used to form a mediating layer, and then amide bond grafted heparin is formed by immersing in the zwitterionic polymer solution. However, the content of amino or carboxyl on the surface of the membrane formed by the method is limited, so that the heparin grafting efficiency is low; at the same time, the dopamine adhesion method may affect the mechanical properties of the membrane.
Disclosure of Invention
One of the technical problems to be solved by the present invention is to provide a modified polymer membrane material with a surface compounded with grafted phosphorylcholine and a heparin anticoagulant coating, wherein phosphorylcholine is chemically grafted on the surface of the polymer membrane material, phosphorylcholine zwitterions and N- (3-aminopropyl) methacrylamide are introduced, a large number of heparin grafting sites (amino groups) are provided while the anticoagulant effect is achieved, then heparin is chemically grafted by using 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDC), and the anticoagulant effect of the modified polymer membrane material is more efficient and durable through the combination of two anticoagulant effects of the phosphorylcholine zwitterions and the bioactive heparin.
The second technical problem to be solved by the invention is to provide a preparation method of a modified polymer membrane material with a surface compounded with grafted phosphorylcholine and heparin anticoagulant coating, wherein the phosphorylcholine and heparin anticoagulant coating are only combined on the surface of the polymer membrane material.
The invention is solved by the following technical scheme:
in order to solve one of the technical problems, the surface of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulation coating is a coating of chemically grafted phosphorylcholine and heparin with two anticoagulation substances.
In one embodiment, the polymer film material comprises one or more of a Polyurethane (PU) film, a polyethylene terephthalate (PET) film, a Polytetrafluoroethylene (PTFE) film, a Polyetheretherketone (PEEK) film, a Polyimide (PI), a Polyamide (PA), an ultra polyurethane polyethylene (UMWPE) film, a polystyrene elastomer (SIBS) film in combination.
In one embodiment, the thickness of the modified polymer film material is 0.01-2 mm.
Furthermore, in order to solve the second technical problem, the preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating comprises the following steps:
(1) washing the polymer membrane material in isopropanol solution, washing with purified water, drying, and placing in a pretreatment solution containing N- (3-aminopropyl) methacrylamide hydrochloride (APMA) and dimethyl acryloxyethyl phosphorylcholine (MPC) to obtain a membrane material containing poly phosphorylcholine zwitterion (PMPC) and a plurality of heparin binding sites (amino groups of amino groups (PAPMA) of poly N- (3-aminopropyl) methacrylamide hydrochloride) under the initiation of a cerium-containing compound;
(2) putting the membrane material in the step (1) into a cleaning solution for cleaning, soaking and drying;
(3) and (3) placing the membrane material obtained in the step (2) into a heparin solution containing 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) for reaction, cleaning, and drying to obtain the modified polymer membrane material with the surface compositely grafted with the phosphorylcholine and the heparin anticoagulant coating.
In one embodiment, the polymer membrane material in step (1) is prepared by one or more of a weaving method, an electrospinning method, a solution coagulation method, a leaching method, and a spraying method.
In one embodiment, the concentration of the isopropanol solution in the step (1) is 2.5-25%; and the cleaning time of the isopropanol solution and the purified water is 10-30 min.
In one embodiment, the concentration of APMA in step (1) is 5-25% w/v; the concentration of the MPC is 5-25% w/v.
In one embodiment, the pretreatment solution in step (1) requires removing oxygen from the solution prior to adding the cerium-containing compound; the concentration of cerium ions in the cerium-containing compound is 0.01-0.1M.
In one embodiment, the cerium-containing compound comprises one or more combinations of cerium trioxide, cerium chloride, cerium fluoride, cerium carbonate, cerium phosphate, cerium nitrate, cerium ammonium nitrate.
In one embodiment, the reaction temperature in the step (1) is 40-60 ℃, the reaction time is 12-24 hours, no oxygen can participate in the reaction in the whole process, and the reaction is under the protection of argon.
In one embodiment, the washing solution in step (2) is one of purified water, phosphate buffered saline (PBS solution), Triton X-100 solution; the soaking time is 12-24 h; the drying mode is room temperature drying or vacuum drying.
In one embodiment, the solvent of the heparin solution in the step (3) is a 2-morpholinoethanesulfonic acid buffer (MES) solution with pH =5-6, and the MES content is 0.05-0.5M.
In one embodiment, the heparin solution in step (3) may be prepared from the heparin or heparin sodium; the concentration of the heparin solution is 0.5-5 mg/ml.
In one embodiment, the molar ratio of EDC to NHS in step (3) is 0.5 to 10; the concentration of the NHS is 0.02-0.04M.
In one embodiment, the step (3) is carried out at 37 ℃ for 12-24 hours in the absence of light.
In one embodiment, the washing in the step (3) is washing with purified water, a PBS solution, purified water and 30-95% ethanol; the drying is room temperature drying or vacuum drying.
In a preferred embodiment, the polymer film material is a polyurethane film.
In one embodiment, the pretreatment solution is prepared in the step (1), argon is introduced, and oxygen in the solution is removed; and (3) adding a cerium-containing compound when the temperature of the pretreatment liquid reaches a specified temperature, adding the membrane, and reacting.
In one embodiment, a method of making a polyurethane film includes the steps of: dissolving the polyurethane granules in one or more of dimethylacetamide (DMAc), Dimethylformamide (DMF), tetrahydrofuran and dioxane to prepare a polyurethane solution with the mass concentration of 10-15%, pouring the polyurethane solution into a polytetrafluoroethylene mold, and completely evaporating the solvent through vacuum drying to obtain a polyurethane film; and (3) cleaning the polyurethane film, and drying at room temperature or in vacuum for later use.
Compared with the prior art, the invention has the advantages that:
1. different from the prior art, in one embodiment of the invention, APMA and MPC are grafted to the surface of the polyurethane membrane by initiation of a cerium-containing compound, and anticoagulated phosphorylcholine is introduced to create a plurality of amino binding sites for heparin grafting, so that the grafting amount of heparin is increased, and the anticoagulation performance of the polyurethane membrane is improved.
2. Different from the prior art, in one embodiment of the invention, the phosphorylcholine zwitterion and heparin are grafted to the surface of the polyurethane membrane, so that the platelet adhesion can be effectively reduced, and the anticoagulation performance is improved.
3. Different from the prior art, the phosphorylcholine zwitterion and heparin are fixed on the surface of the polyurethane membrane by a chemical grafting method in one embodiment of the invention, so that the firmness of the heparin can be ensured, and the prepared material can meet the requirement of in vivo anticoagulation and realize long-acting anticoagulation.
4. Compared with the prior art, the preparation method of the modified polyurethane film in one embodiment of the invention is simple, the preparation conditions are mild and environment-friendly, and the modified polyurethane film has good market application prospect; in addition, other materials in contact with blood and body fluids, besides polyurethane films, can be improved using this technique.
Embodiments of the present application are capable of achieving other advantageous technical effects not listed individually, which other technical effects may be described in part below and are anticipated and understood by those of ordinary skill in the art upon reading the present application.
Drawings
Fig. 1 is a reaction flow diagram of a method for preparing a modified polymer membrane material according to various embodiments of the present invention.
FIG. 2 is a graph showing the water contact angle of an unmodified polyurethane film in example 1 of the present invention.
Fig. 3 is a water contact angle of the modified polyurethane film with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating in example 1 of the invention.
FIG. 4 is a scanning electron microscope image of the platelet adhesion of the unmodified polyurethane film in example 1 of the present invention.
Fig. 5 is a scanning electron microscope image of platelet adhesion of the modified polyurethane film with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating in example 1 of the invention.
Fig. 6 is a scanning electron microscope image of platelet adhesion after the modified polyurethane film with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating is washed by the PBS solution for 30 days in the embodiment 1 of the invention.
Detailed Description
While the following description and the annexed drawings set forth in detail certain illustrative embodiments of the invention, other embodiments of the invention as taught by the appended claims can be practiced by those skilled in the relevant art without one or more of the details set forth herein. It is the intention, therefore, of applicants to restrict or in any way limit the scope of the appended claims to the detailed description. Although the following text sets forth a detailed description of various steps in order with reference to the figures, the steps and sequence of steps described, as well as the nomenclature thereof, should not be construed to imply that all of the embodiments taught herein are required to practice.
Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
The present application will be described in more detail below with reference to various embodiments and examples of several aspects of the application.
Example 1:
in this embodiment, the polymer film material is a polyurethane film.
Dissolving polyurethane granules in dimethylacetamide to prepare a 12% polyurethane solution, pouring the polyurethane solution into a polytetrafluoroethylene mold, uniformly spreading the polyurethane solution, putting the polytetrafluoroethylene mold into a vacuum drying oven, carrying out vacuum drying at 50 ℃ for 24 hours, taking out the mold, cooling the temperature to room temperature, adding purified water, taking out the film, cleaning, and carrying out room temperature or vacuum drying for later use to obtain a flat polyurethane film, wherein the polyurethane film is divided into a control group and a test group, and each group comprises 3 sheets; wherein the content of the first and second substances,
control group: cleaning the flat polyurethane film in a PBS solution, cutting the flat polyurethane film into 10 x 10mm sheets, and testing the contact angle and the platelet adhesion;
test groups: step one, preparing 100ml of pretreatment solution containing 10% w/v APMA and 10% w/v MPC, pouring the solution into a three-neck flask, introducing argon at the speed of 1L/min for 10min, and removing oxygen in the solution; secondly, adding 0.02M ammonium ceric nitrate when the temperature of the solution reaches 50 ℃, uniformly stirring, adding a film, and reacting for 18 hours under the protection of argon; thirdly, rinsing the pretreated membrane with purified water, preparing a PBS (phosphate buffer solution) with the pH =7.4 +/-0.2, immersing the membrane in the PBS, soaking for 24 hours at room temperature, then rinsing the membrane with purified water, and drying in the air; fourthly, preparing MES solution with pH =5.5 +/-0.5, wherein the molar concentration of MES is 0.05M, adding 1.25mg/ml heparin sodium into the MES solution, adding 0.03M EDC and NHS, stirring uniformly, immersing the membrane, and reacting for 24 hours at 37 ℃ in a dark place; fifthly, taking out the reacted film, sequentially washing the film with purified water, PBS solution, purified water and 70% ethanol, and drying the film in the air, wherein the preparation reaction flow of the modified polyurethane film is shown in figure 1; the test group modified polyurethane film was cut into 10mm by 10mm sheets for contact angle, heparin graft density, and platelet adhesion tests.
In this example, the test group-modified polyurethane film was washed with 1X PBS solution at 37 ℃ for 30 days at 500 rpm, and then washed with deionized water to perform the platelet adhesion test.
And (4) analyzing results: as shown in fig. 2 and 4, after the polyurethane films were treated differently, the water contact angle α of the polyurethane film of the control group was 96 °, and platelet adhesion was extremely high; as shown in FIGS. 3 and 5, the water contact angle beta of the polyurethane film modified by the test group is 40 degrees, the platelet adhesion is almost zero, and the heparin graft density is 6.3 mug/cm2The difference is obvious; as shown in fig. 6, the test group-modified polyurethane film was washed with PBS solution for 30 days, and the platelet adhesion remained very low.
And (4) conclusion: by utilizing the method of the embodiment 1 of the invention, heparin can be effectively grafted to the surface of the polyurethane film, and the contact angle is effectively reduced, so that the anticoagulation performance of the polyurethane film is greatly improved.
Example 2:
the difference from example 1 is that:
dissolving polyurethane granules in dioxane to prepare a 15 mass percent polyurethane solution, pouring the polyurethane solution into a polytetrafluoroethylene mold, uniformly spreading the solution, putting the polytetrafluoroethylene mold into a vacuum drying oven, carrying out vacuum drying at 50 ℃ for 24 hours, taking out the mold, cooling the temperature to room temperature, adding purified water, taking out the film, cleaning, and carrying out room temperature or vacuum drying for later use to obtain a flat polyurethane film, wherein the polyurethane film is divided into a control group and a test group, and each group comprises 3 sheets; wherein the content of the first and second substances,
control group: cleaning the flat polyurethane film in a PBS solution, cutting the flat polyurethane film into 10 x 10mm sheets, and testing the contact angle and the platelet adhesion;
test groups: firstly, preparing 100ml of pretreatment solution containing 15% w/v APMA and 15% w/v MPC, pouring the solution into a three-neck flask, introducing argon at the speed of 1.5L/min for 20min, and removing oxygen in the solution; secondly, adding 0.03M cerium nitrate when the temperature of the solution reaches 50 ℃, uniformly stirring, adding a film, and reacting for 18 hours under the protection of argon; thirdly, rinsing the pretreated membrane with purified water, preparing a PBS (phosphate buffer solution) with the pH =7.4 +/-0.2, immersing the membrane in the PBS, soaking for 12 hours at room temperature, then rinsing the membrane with purified water, and drying in the air; fourthly, preparing MES solution with pH =5.5 +/-0.5, wherein the molar concentration of MES is 0.1M, adding 2mg/ml heparin sodium into the MES solution, adding 0.06M EDC and 0.03M NHS, stirring uniformly, immersing the membrane, and reacting for 18h at 37 ℃ in a dark place; fifthly, taking out the reacted film, sequentially washing the film with purified water, PBS solution, purified water and 75% ethanol, and drying the film in the air, wherein the preparation reaction flow of the modified polyurethane film is shown in figure 1; the modified polyurethane film of the test group was cut into 10mm by 10mm sheets for contact angle, heparin graft density, and platelet adhesion tests.
And (4) analyzing results: after the unmodified polyurethane film is subjected to different treatments, the water contact angle of the polyurethane film of the control group is 102 degrees, and the platelet adhesion is extremely high; the water contact angle of the polyurethane film modified by the test group is 50 degrees, the platelet adhesion is almost zero, and the heparin grafting density is 4.3 mu g/cm2With significant variability.
And (4) conclusion: by utilizing the method of the embodiment 2 of the invention, heparin can be effectively grafted to the surface of the polyurethane film, and the contact angle is effectively reduced, so that the anticoagulation performance of the polyurethane film is greatly improved.
Example 3:
the difference from example 1 is that:
in this example, the unmodified polyurethane film was prepared by dissolving polyurethane pellets in tetrahydrofuran/dioxane = 1: 1, pouring the polyurethane solution into a polytetrafluoroethylene mold, uniformly spreading the polyurethane solution, putting the mold into a vacuum drying oven, carrying out vacuum drying at 50 ℃ for 24 hours, taking out the mold, cooling the mold to room temperature, adding purified water, taking out the film, washing the film, and carrying out room-temperature or vacuum drying for later use to obtain a flat polyurethane film, wherein the polyurethane film is divided into a control group and a test group, and each group comprises 3 sheets; wherein the content of the first and second substances,
control group: cleaning the flat polyurethane film in a PBS solution, cutting the flat polyurethane film into 10 x 10mm sheets, and testing the contact angle and the platelet adhesion;
test groups: step one, preparing 100ml of pretreatment solution containing 20% w/v APMA and 20% w/v MPC, pouring the solution into a three-neck flask, introducing argon at the speed of 1.5L/min for 20min, and removing oxygen in the solution; secondly, adding 0.1M cerium nitrate when the temperature of the solution reaches 50 ℃, uniformly stirring, adding a film, and reacting for 24 hours under the protection of argon; thirdly, rinsing the pretreated membrane with purified water, preparing a PBS (phosphate buffer solution) with the pH =7.4 +/-0.2, immersing the membrane in the PBS, soaking for 24 hours at room temperature, then rinsing the membrane with purified water, and drying in the air; fourthly, preparing MES solution with pH =5.5 +/-0.5, wherein the molar concentration of MES is 0.5M, adding 2mg/ml heparin sodium into the MES solution, adding 0.3M EDC and 0.03M NHS, stirring uniformly, immersing the membrane, and reacting for 24 hours at 37 ℃ in a dark place; fifthly, taking out the reacted film, sequentially washing the film with purified water, PBS solution, purified water and 75% ethanol, and drying the film in the air, wherein the preparation reaction flow of the modified polyurethane film is shown in figure 1; the membranes of the test groups were cut into 10mm by 10mm sheets for contact angle, heparin graft density, platelet adhesion tests.
And (4) analyzing results: after the unmodified polyurethane film is subjected to different treatments, the water contact angle of the polyurethane film of the control group is 98 degrees, and the platelet adhesion is extremely high; the water contact angle of the test group modified polyurethane film is 45 degrees, and the platelet adhesion is almostZero, heparin graft density of 5.8. mu.g/cm2With significant variability.
And (4) conclusion: by utilizing the method of the embodiment 3 of the invention, heparin can be effectively grafted to the surface of the polyurethane film, and the contact angle is effectively reduced, so that the anticoagulation performance of the polyurethane film is greatly improved.
In summary, the foregoing is only a preferred embodiment of the present invention, and those skilled in the art will appreciate that the invention is not limited to the specific embodiments and applications of the invention.
Claims (16)
1. The modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating is characterized in that: the surface of the modified polymer membrane material is the coating which is chemically grafted with two substances with anticoagulation effect, namely phosphorylcholine and heparin.
2. The modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 1, is characterized in that: the polymer film material comprises one or more of a polyurethane film, a polyethylene terephthalate film, a polytetrafluoroethylene film, a polyether-ether-ketone film, polyimide, polyamide, a polyethylene film with super polyurethane content and a polystyrene elastomer film.
3. The modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 1, is characterized in that: the thickness of the modified polymer film material is 0.01-2 mm.
4. A preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating, which is based on the claims 1 to 3, is characterized by comprising the following steps:
(1) putting the polymer membrane material into an isopropanol solution for cleaning, then washing with purified water, drying, putting into a pretreatment solution containing N- (3-aminopropyl) methacrylamide hydrochloride and dimethylacryloyloxyethyl phosphorylcholine, and obtaining the membrane material containing polyphosphocholine zwitterions and a plurality of heparin binding sites (amino groups of poly N- (3-aminopropyl) methacrylamide hydrochloride) under the initiation of a cerium-containing compound;
(2) putting the membrane material in the step (1) into a cleaning solution for cleaning, soaking and drying;
(3) and (3) placing the membrane material dried in the step (2) into a heparin solution containing 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide and N-hydroxysuccinimide for reaction, cleaning and drying to obtain the modified polymer membrane material with the surface compositely grafted with the phosphorylcholine and the heparin anticoagulant coating.
5. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the polymer membrane material in the step (1) can be prepared by one or more methods of a weaving method, an electrostatic spinning method, a solution solidification method, a leaching method and a spraying method.
6. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: in the step (1), the concentration of the isopropanol solution is 2.5-25%; and the cleaning time of the isopropanol solution and the purified water is 10-30 min.
7. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the concentration of the N- (3-aminopropyl) methacrylamide hydrochloride in the step (1) is 5-25% w/v; the concentration of the dimethyl acryloyl oxyethyl phosphorylcholine is 5-25% w/v.
8. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the pretreatment solution in the step (1) needs to remove oxygen in the solution first and then add the cerium-containing compound; the concentration of cerium ions in the cerium-containing compound is 0.01-0.1M.
9. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the cerium-containing compound comprises one or more of cerium oxide, cerium chloride, cerium fluoride, cerium carbonate, cerium phosphate, cerium nitrate and ammonium cerium nitrate.
10. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the reaction temperature in the step (1) is 40-60 ℃, the reaction time is 12-24 h, and no oxygen can participate in the reaction in the whole process.
11. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the cleaning solution in the step (2) is one of purified water, phosphate buffer solution and Triton X-100 solution; the soaking time is 12-24 h; the drying mode is room temperature drying or vacuum drying.
12. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the solvent of the heparin solution in the step (3) is a 2-morpholinoethanesulfonic acid buffer solution with the pH =5-6, and the content of the 2-morpholinoethanesulfonic acid buffer solution is 0.05-0.5M.
13. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the heparin solution in the step (3) can be prepared from heparin or heparin sodium; the concentration of the heparin solution is 0.5-5 mg/ml.
14. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: the molar ratio of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide to the N-hydroxysuccinimide in the step (3) is 0.5-10; the concentration of the N-hydroxysuccinimide is 0.02-0.04M.
15. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: and (4) reacting the reaction in the step (3) at 37 ℃ in a dark place for 12-24 hours.
16. The preparation method of the modified polymer membrane material with the surface compounded with the grafted phosphorylcholine and the heparin anticoagulant coating according to claim 4, which is characterized in that: cleaning in the step (3) by using purified water, phosphate buffer solution, purified water and 30-95% ethanol; the drying is room temperature drying or vacuum drying.
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| CN202111123851.1A CN113877006A (en) | 2021-09-24 | 2021-09-24 | Modified polymer membrane material and preparation method thereof |
| PCT/CN2022/120718 WO2023046044A1 (en) | 2021-09-24 | 2022-09-23 | Modified polymer membrane material having surface composite grafted phosphorylcholine and heparin anticoagulant coating and preparation method therefor |
| CN202280058209.6A CN117940174A (en) | 2021-09-24 | 2022-09-23 | Modified polymer membrane material with surface compositely grafted with phosphorylcholine and heparin anticoagulation coating and preparation method thereof |
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| CN115337473A (en) * | 2022-08-11 | 2022-11-15 | 北京航空航天大学 | Blood compatible coating for gas exchange membrane of extracorporeal membrane oxygenation system and preparation method and application thereof |
| CN115558148A (en) * | 2022-09-28 | 2023-01-03 | 浙江大学 | Anti-adhesion medical polyurethane film and preparation method and application thereof |
| WO2023046044A1 (en) * | 2021-09-24 | 2023-03-30 | 宁波健世科技股份有限公司 | Modified polymer membrane material having surface composite grafted phosphorylcholine and heparin anticoagulant coating and preparation method therefor |
| WO2024078355A1 (en) * | 2022-10-09 | 2024-04-18 | 北京博辉瑞进生物科技有限公司 | Biological mesh, preparation method therefor and use thereof |
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| CN117940174A (en) | 2024-04-26 |
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