CN101429287B - Highly blood coagulation resistant cellulose membrane material and preparation method thereof - Google Patents
Highly blood coagulation resistant cellulose membrane material and preparation method thereof Download PDFInfo
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- CN101429287B CN101429287B CN2008102430719A CN200810243071A CN101429287B CN 101429287 B CN101429287 B CN 101429287B CN 2008102430719 A CN2008102430719 A CN 2008102430719A CN 200810243071 A CN200810243071 A CN 200810243071A CN 101429287 B CN101429287 B CN 101429287B
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- 229920002678 cellulose Polymers 0.000 title claims abstract description 48
- 239000001913 cellulose Substances 0.000 title claims abstract description 47
- 239000000463 material Substances 0.000 title claims abstract description 44
- 239000012528 membrane Substances 0.000 title claims abstract description 43
- 230000023555 blood coagulation Effects 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 11
- 238000000034 method Methods 0.000 claims abstract description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 239000000178 monomer Substances 0.000 claims description 28
- 239000003999 initiator Substances 0.000 claims description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- 238000005406 washing Methods 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
- 238000001291 vacuum drying Methods 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 11
- QLULGSLAHXLKSR-UHFFFAOYSA-N azane;phosphane Chemical group N.P QLULGSLAHXLKSR-UHFFFAOYSA-N 0.000 claims description 11
- 150000002500 ions Chemical class 0.000 claims description 11
- QATBRNFTOCXULG-UHFFFAOYSA-N n'-[2-(methylamino)ethyl]ethane-1,2-diamine Chemical compound CNCCNCCN QATBRNFTOCXULG-UHFFFAOYSA-N 0.000 claims description 11
- FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 claims description 10
- 150000004820 halides Chemical class 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 8
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 8
- HIVLDXAAFGCOFU-UHFFFAOYSA-N ammonium hydrosulfide Chemical compound [NH4+].[SH-] HIVLDXAAFGCOFU-UHFFFAOYSA-N 0.000 claims description 8
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 230000002459 sustained effect Effects 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229960001701 chloroform Drugs 0.000 claims description 6
- 238000013016 damping Methods 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 238000010559 graft polymerization reaction Methods 0.000 claims description 3
- 238000002203 pretreatment Methods 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 abstract description 9
- 108090000623 proteins and genes Proteins 0.000 abstract description 9
- 210000001772 blood platelet Anatomy 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229920000554 ionomer Polymers 0.000 abstract 3
- 230000007547 defect Effects 0.000 abstract 1
- 235000010980 cellulose Nutrition 0.000 description 31
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 12
- 229940124530 sulfonamide Drugs 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 7
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- AJXBTRZGLDTSST-UHFFFAOYSA-N amino 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)ON AJXBTRZGLDTSST-UHFFFAOYSA-N 0.000 description 4
- 229960002897 heparin Drugs 0.000 description 4
- 229920000669 heparin Polymers 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 3
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 241001044369 Amphion Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
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- -1 polyoxyethylene Polymers 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
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Images
Abstract
The invention relates to a highly ticoagulant cellulose membrane material, wherein an amphichroic ionomer layer is grafted on the surface of a cellulose membrane, and a 'brush'-shaped amphichroic ionomer layer is formed on the surface of the cellulose membrane. The cellulose membrane with good biocompatibility is prepared by grafting of amphichroic ionic molecules on the surface of the material. The neat 'brush'-shaped amphichroic ionomer layer is formed on the surface of cellulose, so that the defects on the surface of the material are overcome, and the action between the material and biomacromolecules is further reduced, thereby nonspecific protein absorption and blood platelet adhesion are reduced to the maximum degree. Therefore, the cellulose membrane material has high nonspecific protein absorption resistance and high ticoagulant performance. The invention discloses a method for manufacturing the highly ticoagulant cellulose membrane material.
Description
Technical field
The present invention relates to a kind of blood compatibility material and preparation method thereof, relate in particular to a kind of good blood compatibility cellulose membrane material and preparation method thereof that has.
Background technology
Cellulose membrane (Cellulose Membrane) is widely used in organizational project, sustained release, biologic medical fields such as blood purification purifying because of its favorable mechanical performance and potential biocompatibility.Yet its biocompatibility, especially blood compatibility also are not enough to reach the requirement of application.
In recent years, in order to improve the biocompatibility of cellulose membrane, especially good blood compatibility has a large amount of reports about cellulose surface modification both at home and abroad.As the material that will have good blood compatibility such as heparin (Heparin), polyoxyethylene glycol (PEG) thus etc. have a good blood compatibility material fix or be grafted to material surface and make its blood compatibility obtain to improve greatly.But, along with research further deeply, its inherent defective appears gradually: the heparin in the coating can be slowly stripping and exhausting from coating, surperficial its activity of fixed heparin but is restricted; Polyoxyethylene glycol can or have degraded under the environment of transition metal ion and causes certain bio-toxicity or the like at aerobic.
Summary of the invention
The inventor is from the molecular engineering angle, proposed " main chain-side group synergy " hypothesis and " keeping normal conformation " hypothesis, and the material of (contain simultaneously in the molecular structure and have the yin, yang ionic group) will be the material with good blood compatibility to have proposed to have zwitter-ion (Zwitterion) structure.In recent years, this seminar with phosphorus ammonium, sulfanilamide (SN) and three kinds of zwitter-ions of carboxylic ammonium by common ozone activation and surface chemistry coupling method, the polymer surfaces commonly used in biologic medical fields such as urethane, silicon rubber, Mierocrystalline celluloses made up zwitterionic polymer layer or unimolecular layer, and has good anticoagulation function.But ozone activation and surface chemistry coupling method operating procedure complexity, be not suitable for suitability for industrialized production, for addressing this problem, the present invention controllably is directly grafted to surface of polymer substrates with zwitter-ion by living polymerization, thus the anticoagulation polymeric film material with neat " brush " shape amphoteric ion polymer surface of synthesizing new.
The object of the invention is to provide a kind of surface to have the blood coagulation resistant cellulose membrane material of neat " brush " shape amphoteric ion polymer.
Another object of the present invention is to provide the preparation method of above-mentioned materials.
For finishing the foregoing invention purpose, technical scheme provided by the invention is as follows:
A kind of highly blood coagulation resistant cellulose membrane material, it is at the cellulose membrane surface grafting one deck amphoteric ion polymer to be arranged, and forms " brush " shape amphoteric ion polymer layer on the cellulose membrane surface.
Above-mentioned highly blood coagulation resistant cellulose membrane material, described zwitterionic monomer can be phosphorus ammonium, carboxylic ammonium or sulphur ammonium zwitterionic monomer, and its structure is as follows respectively:
The phosphorus ammonium:
The sulphur ammonium:
The carboxylic ammonium:
R:
Or
Or
(methacrylate type) (methacrylic acid amino ester type) (styrene type)
Above-mentioned highly blood coagulation resistant cellulose membrane material, described have one deck amphoteric ion polymer at the cellulose membrane surface grafting, and the thickness of amphoteric ion polymer is 2～100nm.
A kind of method for preparing above-mentioned highly blood coagulation resistant cellulose membrane material, it is made up of the following step:
1. the pre-treatment of polymeric substrate: with crosslinked cellulose membrane (being cut into diameter is the 10mm sheet), through vacuum-drying under room temperature after the solvent wash;
2. the fixing initiator of substrate surface: in the reactor that contains pretreated rear film (5-20 sheet), add the tetrahydrofuran solution of 0.05～1.00mol/L amine, again with the ratio M of initiator according to amount of substance
Amine: M
Initiator=1.2:1～2:1 adds reactor.After the sustained reaction 1～24 hour, take out diaphragm, use washings 1 and washing with alcohol successively, then vacuum-drying.
3. zwitterionic monomer is at the material surface graft polymerization reaction: the film that initiator has been fixed on the surface is put into the methyl alcohol de-gassed solution of the zwitterionic monomer of 0.1～1mol/L, feeds nitrogen protection then, again with cuprous halide and the part ratio M according to amount of substance
Zwitter-ion: M
Cuprous halide: M
Part=2:1:1～10:1:1 joins in the reaction system.Stirring reaction is 1～24 hour under the room temperature, takes out diaphragm, use washings 2 and water washing successively after, vacuum-drying.
Above-mentioned preparation method, the described solvent of step 1 is tetrahydrofuran (THF), acetone or methylene dichloride.
Above-mentioned preparation method, the described initiator of step 2 is 2-bromo isobutyl-acylbromide or dichloroacetyl chloride; Described amine is Trimethylamine 99 or triethylamine; Washings 1 is trichloromethane or methylene dichloride.
Above-mentioned preparation method, the described cuprous halide of step 3 is CuBr or CuCl; Part is five methyl diethylentriamine or bipyridine; Washings 2 is PBS damping fluid or ethanol; Zwitterionic monomer is phosphorus ammonium, sulphur ammonium or carboxylic ammonium zwitter-ion, and its structure is as follows respectively:
The phosphorus ammonium:
The sulphur ammonium:
The carboxylic ammonium:
R:
Or
Or
(methacrylate type) (methacrylic acid amino ester type) (styrene type)
Beneficial effect of the present invention:
The present invention will have the zwitterionic monomer that can keep the normal conformation of biomacromolecule and be grafted to material surface, prepare the cellulosefilm with excellent biological compatibility.
The present invention forms neat " brush " shape amphoteric ion polymer layer at cellulose surface, reduced the defective of material surface, further reduced itself and biomacromolecule between effect, thereby reduced the absorption of platelet adhesion reaction and nonspecific proteins to greatest extent.Thereby make cellulose membrane material have highly blood coagulation resistant performance and anti-protein adsorption characteristic.
The prepared material of the present invention has suitable length between zwitter-ion and material surface molecular chain is as interval body, overcome because of material the constraint of bioactive molecule its active influence; The zwitterionic monomer that is adopted is because structural advantage (compare with PEG, in the molecular formula not the easy chemical bond of oxidation and decomposition such as ether-containing key), has satisfactory stability when having good biocompatibility in physiological environment again.
The zwitterionic monomer that the present invention will have good blood compatibility is directly grafted to polymer film surface, thereby has enlarged zwitter-ion with the good blood compatibility wide applications more beyond inorganic, metal field.
Technology of the present invention is simple, and the reaction conditions gentleness is easy to operate, has broad application prospects in the biologic medical field.
Description of drawings
Fig. 1 is the atomic force microscope contrast photo of cellulose membrane surface topography before and after the grafting.
Fig. 2 is the absorption (CM be modification preceding cellulose membrane, CMG-4 be graft reaction 4 hour later cellulose membrane) of cellulose membrane grafting front and back to the human serum gross protein.
Fig. 3 is that the scanning electronic microscope to platelet adhesion reaction contrasts photo before and after the cellulose membrane grafting.
From relatively can finding out of Fig. 1 and Fig. 2, amphion is grafted to cellulose surface after, material surface almost no longer is stained with blood platelet. As can be seen from Figure 3, amphion makes cellulose membrane to greatly reduction of nonspecific proteins absorption.
Embodiment
Below by embodiment the present invention is specifically described, be necessary to be pointed out that at this, following examples only are used for further specifying of the present invention, can not be interpreted as limiting the scope of the invention.
Embodiment 1
Containing 10 tetrahydrofuran solutions that in the reactor of the pretreated rear film of tetrahydrofuran (THF), add 25ml 0.05mol/L triethylamine, again with the ratio M of initiator 2-bromo isobutyl-acylbromide according to amount of substance
Trimethylamine 99: M
2-bromo isobutyl-acylbromide=1.2:1 adds reactor.After the sustained reaction 1 hour, take out diaphragm, wash successively with trichloromethane and ethanol, then vacuum-drying.The film of again surface having been fixed initiator is put into the methyl alcohol de-gassed solution of the phosphorus ammonium zwitterionic monomer of 0.1mol/L (R is a methacrylate type), feeds nitrogen protection then, again with CuCl and the bipyridine ratio M according to amount of substance
Zwitter-ion: M
CuCl: M
Bipyridine=2:1:1 joins in the reaction system.Stirring reaction is 16 hours under the room temperature, takes out diaphragm, after washing successively with PBS damping fluid and water, and vacuum-drying.
Embodiment 2
Containing 10 tetrahydrofuran solutions that in the reactor of the pretreated rear film of acetone, add 20mL 0.5mol/L Trimethylamine 99, again with the ratio M of 2-bromo isobutyl-acylbromide according to amount of substance
Trimethylamine 99: M
2-bromo isobutyl-acylbromide=1.8:1 adds reactor.After the sustained reaction 8 hours, take out diaphragm, wash successively with methylene dichloride and ethanol, then vacuum-drying.The film of again surface having been fixed initiator is put into the methyl alcohol de-gassed solution of the sulfanilamide (SN) zwitterionic monomer of 1mol/L (R is a methacrylic acid amino ester type), feeds nitrogen protection then, again with CuBr and the five methyl diethylentriamine ratio M according to amount of substance
Zwitter-ion: M
CuBr: M
Five methyl diethylentriamine=4:1:1 joins in the reaction system.Stirring reaction is 1 hour under the room temperature, takes out diaphragm, and after washing successively with the second alcohol and water, vacuum-drying promptly gets highly blood coagulation resistant cellulose membrane material.
Embodiment 3
Containing 20 tetrahydrofuran solutions that in the reactor of the pretreated rear film of tetrahydrofuran (THF), add 50mL 1mol/L triethylamine, again with the ratio M of dichloroacetyl chloride according to amount of substance
Trimethylamine 99: M
Dichloroacetyl chloride=1.2:1 adds reactor.After the sustained reaction 1 hour, take out diaphragm, wash successively with trichloromethane and ethanol, then vacuum-drying.The film of again surface having been fixed initiator is put into the methyl alcohol de-gassed solution of the sulfanilamide (SN) zwitterionic monomer of 0.1mol/L (R is a styrene type), feeds nitrogen protection then, again with CuBr and the five methyl diethylentriamine ratio M according to amount of substance
Zwitter-ion: M
CuBr: M
Five methyl diethylentriamine=10:1:1 joins in the reaction system.Stirring reaction is 24 hours under the room temperature, takes out diaphragm, and after washing successively with PBS damping fluid and water, vacuum-drying promptly gets highly blood coagulation resistant cellulose membrane material.
Embodiment 4
Containing 20 tetrahydrofuran solutions that in the reactor of the pretreated rear film of tetrahydrofuran (THF), add 40mL 1mol/L triethylamine, again with the ratio M of dichloroacetyl chloride according to amount of substance
Triethylamine: M
Dichloroacetyl chloride=2:1 adds reactor.After the sustained reaction 4 hours, take out diaphragm, wash successively with trichloromethane and ethanol, then vacuum-drying.The film of again surface having been fixed initiator is put into the methyl alcohol degassing solvent of the sulfanilamide (SN) zwitterionic monomer of 0.7mol/L (R is a styrene type), feeds nitrogen protection then, again with CuBr and the five methyl diethylentriamine ratio M according to amount of substance
Zwitter-ion: M
CuBr: M
Five methyl diethylentriamine=5:1:1 joins in the reaction system.Stirring reaction is 8 hours under the room temperature, takes out diaphragm, and after washing successively with the second alcohol and water, vacuum-drying promptly gets highly blood coagulation resistant cellulose membrane material.
Embodiment 5
Containing 5 tetrahydrofuran solutions that in the reactor of the pretreated rear film of tetrahydrofuran (THF), add 25mL 1mol/L Trimethylamine 99, again with the ratio M of dichloroacetyl chloride according to amount of substance
Trimethylamine 99: M
Dichloroacetyl chloride=1.5:1 adds reactor.After the sustained reaction 12 hours, take out diaphragm, wash successively with methylene dichloride and ethanol, then vacuum-drying.The film of again surface having been fixed initiator is put into the methyl alcohol degassing solvent of the sulfanilamide (SN) zwitterionic monomer of 0.7mol/L (R is a methacrylate type), feeds nitrogen protection then, again with CuCl and the five methyl diethylentriamine ratio M according to amount of substance
Both sexes from Son: M
CuCl: M
Five methyl diethylentriamine=5:1:1 joins in the reaction system.Stirring reaction is 6 hours under the room temperature, takes out diaphragm, and after washing successively with PBS damping fluid and water, vacuum-drying promptly gets highly blood coagulation resistant cellulose membrane material.
Embodiment 6
With embodiment 1 described method, different is that initiator is a dichloroacetyl chloride, and the initiator fixation response time is 16 hours, and cuprous halide and part are respectively CuCl and bipyridine.
Embodiment 7
With embodiment 2 described methods, different is the 0.6mol/L triethylamine, and initiator is a dichloroacetyl chloride, the sulfanilamide (SN) zwitterionic monomer of 0.6mol/L (R is a methacrylate type), and the graft reaction time is 4 hours.
Embodiment 8
With embodiment 3 described methods, the zwitterionic monomer that different are to use is 0.4mol/L carboxylic ammonium zwitterionic monomer (R is a styrene type), and cuprous halide is CuCl, and the graft reaction time is 12h.
Embodiment 9
With embodiment 4 described methods, different is is 12h the initiator set time, and employed zwitterionic monomer is 0.8mol/L phosphorus ammonium zwitterionic monomer (R is a methacrylate type), and part is a bipyridine, and the graft reaction time is 12h.
Embodiment 10
With embodiment 5 described methods, different amine be triethylamine, initiator is a 2-bromo isobutyl-acylbromide, the initiator set time is 8h, employed zwitterionic monomer is 0.9mol/L carboxylic ammonium zwitterionic monomer (R is a methacrylic acid amino ester type).
Embodiment 11
Characterize the above material to following (the reference Biomaterials of protein adsorption experimental technique cardinal principle, 2008,29,1367-1376.):, in human body platelet-poor plasma (PPP), soaked 90 minutes down then in 37 ℃ earlier with cellulose membrane soaked overnight in PBS solution.Take out the film that blood plasma soaked, with the physical adsorption of PBS flush away and adsorb not firm protein to be placed on 1% middle the washing 1 hour of sodium dodecyl sulfate solution (SDS).Adopt the BCA method to come the quantitative assay material that nonspecific proteins is adsorbed again.
It is as follows substantially to the experimental technique of platelet adhesion reaction to characterize the above material: earlier with cellulose membrane soaked overnight in PBS solution, be rich in the thrombocyte blood plasma (PRP) at human body then and soaked 120 minutes down in 37 ℃.Take out the film that blood plasma soaked, with the physical adsorption of PBS flush away and adsorb not firm protein with immersion in the PBS solution that is placed on 2.5% glutaraldehyde 20 minutes.Again with ethanol-PBS solution of 0%, 25%, 50%, 75% and 100% final vacuum drying of dewatering step by step.After adopt scanning electronic microscope to observe material surface behind the metal spraying to hematoblastic adhesion.
Claims (7)
1. highly blood coagulation resistant cellulose membrane material, its feature: it is at the cellulose membrane surface grafting one deck amphoteric ion polymer to be arranged, and forms " brush " shape amphoteric ion polymer layer on the cellulose membrane surface, it prepares with following steps:
The pre-treatment of step 1. polymeric substrate: with crosslinked cellulose membrane through vacuum-drying under room temperature after the solvent wash;
Step 2. substrate surface is initiator fixedly: add the tetrahydrofuran solution of 0.05～1.00mol/L amine in containing the reactor of pretreated rear film, again with the ratio M of initiator according to amount of substance
Amine: M
InitiatorAdd reactor at=1.2: 1～2: 1, and sustained reaction was taken out diaphragm after 1～24 hour, and with washings 1 and washing with alcohol, vacuum-drying then, described washings 1 is trichloromethane or methylene dichloride;
Step 3. zwitterionic monomer is at the material surface graft polymerization reaction: the film that initiator has been fixed on the surface is put into the methyl alcohol de-gassed solution of the zwitterionic monomer of 0.1～1mol/L; feed nitrogen protection then, again with cuprous halide and part ratio M according to amount of substance
Zwitter-ion: M
Cuprous halide: M
Part=2: joined in the reaction system in 1: 1～10: 1: 1, stirring reaction is 1～24 hour under the room temperature, takes out diaphragm, after washings 2 and water washing, vacuum-drying, described part are five methyl diethylentriamine or bipyridine, and described washings 2 is PBS damping fluid or ethanol.
2. highly blood coagulation resistant cellulose membrane material according to claim 1 is characterized in that: described zwitterionic monomer is phosphorus ammonium, sulphur ammonium or carboxylic ammonium zwitterionic monomer, and its structure is as follows respectively:
The phosphorus ammonium:
The sulphur ammonium:
The carboxylic ammonium:
R：
3. highly blood coagulation resistant cellulose membrane material according to claim 1 is characterized in that: described have one deck amphoteric ion polymer at the cellulose membrane surface grafting, and the thickness of amphoteric ion polymer is 5～100nm.
4. method for preparing the described highly blood coagulation resistant cellulose membrane material of claim 1, it is made up of the following step:
The pre-treatment of step 1. polymeric substrate: with crosslinked cellulose membrane through vacuum-drying under room temperature after the solvent wash;
Step 2. substrate surface is initiator fixedly: add the tetrahydrofuran solution of 0.05～1.00mol/L amine in containing the reactor of pretreated rear film, again with the ratio M of initiator according to amount of substance
Amine: M
InitiatorAdd reactor at=1.2: 1～2: 1, and sustained reaction was taken out diaphragm after 1～24 hour, and with washings 1 and washing with alcohol, vacuum-drying then, described washings 1 is trichloromethane or methylene dichloride;
Step 3. zwitterionic monomer is at the material surface graft polymerization reaction: the film that initiator has been fixed on the surface is put into the methyl alcohol de-gassed solution of the zwitterionic monomer of 0.1～1mol/L; feed nitrogen protection then, again with cuprous halide and part ratio M according to amount of substance
Zwitter-ion: M
Cuprous halide: M
Part=2: joined in the reaction system in 1: 1～10: 1: 1, stirring reaction is 1～24 hour under the room temperature, takes out diaphragm, after washings 2 and water washing, vacuum-drying, described part are five methyl diethylentriamine or bipyridine, and described washings 2 is PBS damping fluid or ethanol.
5. preparation method according to claim 4 is characterized in that: the described solvent of step 1 is tetrahydrofuran (THF), acetone or methylene dichloride.
6. preparation method according to claim 4 is characterized in that: the described initiator of step 2 is 2-bromo isobutyl-acylbromide or dichloroacetyl chloride; Described amine is Trimethylamine 99 or triethylamine.
7. preparation method according to claim 4 is characterized in that: the described cuprous halide of step 3 is CuBr or CuCl; Zwitterionic monomer is phosphorus ammonium, carboxylic ammonium or sulphur ammonium zwitterionic monomer, and its structure is as follows respectively:
The phosphorus ammonium:
The sulphur ammonium:
The carboxylic ammonium:
R：
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| CN102181145A (en) * | 2011-02-24 | 2011-09-14 | 南京师范大学 | PluronicF127-micro-porous polyurethane (PU) film as well as preparation method and application thereof |
| CN102174190A (en) * | 2011-02-24 | 2011-09-07 | 南京师范大学 | Method for preparing polyethylene glycol complex with ammonium phosphate zwitterionic structure at terminal |
| CN102432904B (en) * | 2011-08-24 | 2013-06-19 | 南京师范大学 | Surface-controlled and polymerization-modification biological material and preparation method thereof |
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| CN104045846B (en) * | 2014-05-30 | 2016-08-17 | 天津工业大学 | Double ion modified cellulose film and preparation method thereof |
| CN104031154B (en) * | 2014-06-20 | 2016-08-24 | 天津大学 | Containing zwitterionic 3-dimethyl propylene ammonium propane sulfonic acid starch and preparation method thereof |
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| JP6916644B2 (en) * | 2017-03-24 | 2021-08-11 | ナガセケムテックス株式会社 | A sulfobetaine group-containing reactive compound, a polymer thereof, and a method for producing the polymer. |
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| CN111701077B (en) * | 2020-06-24 | 2021-05-11 | 四川大学 | Valve with antithrombotic and anticalcification functions and preparation method and application thereof |
| CN113430828B (en) * | 2021-06-23 | 2023-04-07 | 清华大学 | Fiber product and preparation method thereof |
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