CN1748804A - Anti-blood coagulation surface modifying method of artificial implant - Google Patents
Anti-blood coagulation surface modifying method of artificial implant Download PDFInfo
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- CN1748804A CN1748804A CN 200510010231 CN200510010231A CN1748804A CN 1748804 A CN1748804 A CN 1748804A CN 200510010231 CN200510010231 CN 200510010231 CN 200510010231 A CN200510010231 A CN 200510010231A CN 1748804 A CN1748804 A CN 1748804A
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Abstract
The present invention belongs to the field of anticoagulant material technology. The anticoagulant surface modification process of artificial implant includes the following steps: cleaning artificial implant; preparing silicone rubber solution; coating the artificial implant with medical silicone rubber as support; coating perfluoro sulfonic acid on the surface of the silicone rubber coating; depositing polycation and polyanion alternately onto the surface of the perfluoro sulfonic acid coating via electrostatic attraction; and irradiating the artificial implant with ultraviolet light to produce photochemical reaction to convert the ionic bond between coating layers into covalent bond. The present invention has simple technological process, mild reaction condition, easy operation, high repeatability, environment friendship and thus excellent application foreground.
Description
Technical field:
The invention belongs to the anticoagulant material technical field, relate to and a kind ofly make the film modified artificial implant of soft support covalent bonding multilamellar heparin with silicone rubber coating and make its surface have the method for anticoagulation function.
Background technology:
In small-bore arteries reconstruction operations, very high to the blood compatibility requirement of tremulous pulse prosthese.In order to guarantee the long-term unobstructed property of postoperative, to use ASV usually as the tremulous pulse prosthese.But, when the patient can't provide ASV, just must adopt the artificial blood vessel to substitute.Although expanded PTFE successfully is applied to the manufacturing than the major diameter blood vessel, for the blood vessel of diameter less than 6mm, because blood clotting or tissue stop up, these materials are powerless.Though after through continuous improvement and modification, long-term patency rates improves, to compare with ASV and still can not obtain satisfied effect, the blood compatibility problem also solves far away, brings a series of problems to artery bypass surgery.Small-bore tremulous pulse prosthese not only should possess sufficient pliability and be beneficial to coincideing between itself and the arteries, also should possess good blood compatibility, can not cause the blood coagulation reaction, to keep secular unobstructed property.
Because have only artificial blood vessel's surface to contact with blood, thus present work mainly concentrate in current material finishing and the modification, to reach the requirement that blood vessel is implanted.By the method that improves its anticoagulation function on the surface that heparin molecule is fixed on the artificial blood vessel is the focus of research always.Early stage research worker uses 4 valency ammonium ions to come the bonding heparin, makes ion and polymeric matrix complexation by long alkyl chain then.Ionically bonded heparin slowly dissolves from the surface with antithrombase-III (AT-III) and bonds together the anticoagulant that formation is lived near surface.This method is applicable to the short-term blood catheter, but because dissolution, heparin exhausts very soon, and is therefore invalid to long-term blood catheter and artificial blood vessel.Second method is that heparin is directly connected in matrix surface by covalent bond.Though for the stability of immobilization heparin, by covalent bonds far beyond ionically bonded height, with regard to the anticoagulation function of immobilization heparin, generally but just in time opposite.Because hardwired heparin has not only reduced artificial blood vessel's elasticity but also can not well cooperate with antithrombase.Therefore, how to improve the anticoagulant property of covalent bonding heparin, do not influence the bulk properties of material simultaneously again, be the main contents of biomaterial heparinization research always.Studies show that if make heparin molecule and polymer surfaces keep certain distance will improve anticoagulation function.In addition, have higher anticoagulant property,, also should improve the concentration of material surface immobilization heparin except reducing immobilization to the bioactive influence of heparin in order to make fixing heparin.
Heparin itself has strong negative charge, hydrophilic and more active function groups.But the polymer such as politef that constitute the artificial blood vessel have very strong chemical inertness and hydrophobicity, can not with the heparin molecule direct reaction.Therefore, the key step of covalent bond method is that surface of polymer material is carried out Chemical Pretreatment, makes it have respond with heparin and then bonding heparin molecule.Though exist at present multiplely to the pretreated method of artificial blood vessel, all there are problems such as required instrument and equipment costliness,, operating procedure complexity influential to the material body structure, be difficult to be extensive use of.
Silicone rubber has excellent elasticity, flexibility, the hot and resistance to ag(e)ing of anti-height, but high-pressure steam sterilization; With tissue and blood compatibility, be the ideal material that applies the artificial blood vessel.Though silicone rubber has certain anticoagulation, it still is difficult to satisfy clinical requirement, must be on the surface of silicone rubber coating further the fixing heparin molecule to improve its anticoagulation function.But silicone rubber is the same with the material that constitutes the artificial blood vessel, has very strong chemical inertness and hydrophobicity, can not with the heparin molecule direct reaction.
Nafion (perfluorinated sulfonic acid) has very high stability and biologically inert, thereby has good biocompatibility.Because Nafion has the hydrophobic fluorine carbon key member structure similar to Teflon (Teflon), makes to have strong hydrophobic interaction between Nafion and the silicone rubber, help forming the Nafion coating on the surface of silicone rubber.Hydrophilic sulfonic group on the Nafion chain sling can be further fixing heparin molecule active group is provided.
The electrostatic attraction layer-layer self-assembling technique is subjected to paying attention to both at home and abroad extensively over past ten years, and its basic skills and principle are that the electrostatic attraction by polycation and polyanion acts on the multiple layer polymer molecular film that substrate surface alternately adsorbs polyanion and polycation.This technology is the composition of controlling diaphragm and structure on molecular level easily not only, and can be on nanoscale the thickness of controlling diaphragm.But the weak point of this method is the poor stability of ionically bonded molecular film in polar solvent.
Summary of the invention:
It is good inadequately to the objective of the invention is at hardwired heparin reduction artificial blood vessel's pliability and anticoagulation function, the monolayer heparin concentration of covalent bonding is too low, and there is the shortcoming of the poor stability of ionically bonded molecular film in polar solvent in the electrostatic attraction layer-layer self-assembling technique, a kind of anti-blood coagulation surface modifying method of artificial implant is provided, this method is made soft support assembling diazo resin and heparin multilayer film with silicone rubber coating, these characteristics of simplicity of stratiform static assembling had both been made full use of, combine diazonium groups and the sulfate group photochemical reaction in film again, make the ionic bond in the film be transformed into covalent bond, thereby the stability of heparin multilayer film is improved greatly.The present invention is achieved in that a, artificial implant is immersed in the organic solvent, ultrasonic cleaning 30～120 minutes, and then, drying is 0.5～2 hour under 30～90 ℃; B, with medical grade silicon rubber as the normal temperature cure binding agent, it is dissolved in the organic solvent, the preparation silicone rubber solution; C, on the inner surface of artificial implant coating medical silicone rubber as soft support; D, on the surface of silicone rubber coating, apply perfluorinated sulfonic acid; E, with positively charged polycation and electronegative polyanion by electrostatic attraction effect alternating deposit to the surface of perfluorinated sulfonic acid coating; F, utilize irradiation under ultraviolet ray artificial implant inwall, make the ionic bond between film inner layer be transformed into covalent bond, obtain anticoagulation surface ultrathin membrane by photochemical reaction.
Method of the present invention has the following advantages:
(1) do not need artificial implant is carried out Chemical Pretreatment, not only economy but also can avoid because the infringement that pretreatment causes the material body performance.
(2) not only increased the pliability of artificial implant at the surface coated silastic of artificial implant, and provide soft support for the artificial implant heparinization, make heparin molecule and artificial implant surface that certain distance be arranged, thereby improve its anticoagulation function, overcome the shortcoming that the surface that heparin is connected to firmly material in traditional heparinization method reduces anticoagulation function.
(3) the not only composition of controlling diaphragm and structure on molecular level easily, and can on nanoscale, control the thickness of the film of covalent bonding.Can be as required improve the concentration of surface immobilized heparin by the number of plies that increases heparin, overcome exist in traditional monolayer heparin curing heparin concentration low excessively, owing to dissolving or biodegradation consume too fast shortcoming.
(4) the original position photochemical reaction makes the ionic bond of interlayer change covalent bond into, has avoided owing to heparin molecule stays hematoblastic absorption and the gathering that positively charged surface causes after the artificial implant surface discharges.
(5) film inner layer is that covalent bond is connected with interlayer, has overcome with shortcomings such as the ionic bonding film properties of conventional electrostatic self assembly preparation are stable inadequately.
(6) technology of the present invention is simple, and the reaction condition gentleness is easy to operate, favorable reproducibility, environmental friendliness is applicable to material surface, biomedical devices and the multi-porous tissue engineering supporting material of multiple complex shape and the anti-blood coagulation surface modifying of macroscopical goods thereof, has a good application prospect.
Description of drawings:
Fig. 1 is the multilayer film (DR/Hep) that is assembled on the quartz glass plate that has applied silicone rubber and Nafion in advance
nThe absorption spectrum of (n=1,2,3,4,5) is with the variation relation figure of the double-deck number of DR/Hep, and Fig. 2 is (DR/Hep) that is assembled on the quartz glass plate that has applied silicone rubber and Nafion in advance
5The absorption spectrum of multilayer film is with the variation relation figure of irradiation under ultraviolet ray time, Fig. 3 is heparinization artificial blood vessel's anticoagulant active variation relation figure, Fig. 4 goes up multilamellar heparin thin film behind the photochemical crosslinking to the influence of the thrombin inactivation variation relation figure with the double-deck number of DR/Hep for the artificial blood vessel, (DR/Hep) of Fig. 5 after for the last photochemical crosslinking of artificial blood vessel
5(DR/Hep)
10Multilamellar heparin thin film influences relationship change figure to the thrombin inactivation.
The specific embodiment:
The specific embodiment one: present embodiment is achieved in that a, artificial implant is immersed in the organic solvent, ultrasonic cleaning 30～120 minutes, and then, drying is 0.5～2 hour under 30～90 ℃; B, with medical grade silicon rubber as the normal temperature cure binding agent, it is dissolved in the organic solvent, the preparation silicone rubber solution; C, on the inner surface of artificial implant coating medical silicone rubber as soft support; D, on the surface of silicone rubber coating, apply perfluorinated sulfonic acid; E, with positively charged polycation and electronegative polyanion by electrostatic attraction effect alternating deposit to the surface of perfluorinated sulfonic acid coating; F, utilize irradiation under ultraviolet ray artificial implant inwall, make the ionic bond between film inner layer be transformed into covalent bond, obtain anticoagulation surface ultrathin membrane by photochemical reaction.
In the present embodiment, the organic solvent that the cleaning artificial implant is used is dehydrated alcohol, acetone or their mixture.
In the present embodiment, the organic solvent that is used for dissolves silicon rubber is alkane solvent (normal hexane or other alkane solvent).
In the present embodiment, artificial implant can be the artificial blood vessel of the various bores that comprise that the various materials of expanded PTFE are made, also can be blood conduit, polymeric film or the porous support of the various bores made of various materials, and the bio-medical instrument of the different shape made from materials such as glass, pottery, silicon, various metal or various polymer.
In the present embodiment, polyanion can be selected one or more the mixture in heparin, heparin sulfate, seaweeds sodium, kayexalate, sulphuric acid glucose, chondroitin sulfate, sodium polyacrylate, the polymethylacrylic acid for use.The also optional usefulness of above-mentioned anion has various albumen, somatomedin and branch's inducible factor of both sexes charge property, and these albumen, somatomedin and differentiation inducing factor can obtain different charged character by regulating pH value.
In the present embodiment, polycation is diphenylamines-4-diazo resin or substituted diphenylamine diazo resin, such as one or more the mixture in 3-methoxy diphenylamine-4-diazo resin, N-methyldiphenylamine-4-diazo resin, 2-nitrodiphenylamine-4-diazo resin, 2-sulfonic acid diphenylamines-4-diazo resin, the N-methyldiphenylamine-2-diazo resin etc.
The specific embodiment two: present embodiment is achieved in that
1) clean the artificial blood vessel: the expanded PTFE artificial blood vessel is immersed in the organic solvent, and ultrasonic 30～120 minutes, then, drying was 0.5～2 hour under 30～90 ℃.
2) dissolves silicon rubber: as the normal temperature cure binding agent, it is dissolved in the organic solvent medical grade silicon rubber, the preparation volumetric concentration is the silicone rubber solution of 0.1～100v/v%.
3) coating silicon rubber: the artificial blood vessel is connected with syringe, erects, with syringe silicone rubber solution is injected its intracavity from artificial blood vessel's end then, till tube chamber fills up.Then remove silicone rubber solution from artificial blood vessel's end, be placed under the air at room temperature dry 2～100 hours with syringe.
4) soak silicone rubber coating: sealing artificial blood vessel's end, in its tube chamber, fill up dehydrated alcohol, left standstill 0.5～10 hour.
5) preparation Nafion solution: will remove with Rotary Evaporators from the 5wt%Nafion solution that Aldrich company buys and desolvate, and add new organic solvent preparation 1～20wt%Nafion solution again, described new organic solvent is normal hexane or other alkane solvent.
6) apply Nafion: with syringe Nafion solution is injected its intracavity till tube chamber fills up from artificial blood vessel's end, remove Nafion solution and dry up with nitrogen.Repeat to inject, remove, nitrogen dries up three step processes 2～100 times.
7) electrostatic attraction layer-layer self assembly diphenylamine diazoresin and comprise the polyanion ultrathin membrane of heparin: being the positively charged diphenylamine diazoresin solution of 0.001～100mg/ml with syringe with concentration injects its intracavity from artificial blood vessel's end, till tube chamber fills up, adsorption time is 0.5～30 minute, after treating artificial blood vessel's inwall absorption last layer diphenylamine diazoresin, remove solution and clean, at this moment the surface lotus that becomes positively charged with deionized water wash; Use the same method and to fill with the artificial blood vessel for the electronegative polyanion solution of 0.001～100mg/ml, adsorption time is 0.5～30 minute, after treating artificial blood vessel's inwall absorption last layer polyanion, remove solution and clean with deionized water wash, at this moment negative charge is with on the surface.Repeat above-mentioned steps, diphenylamine diazoresin and polyanion alternate group are contained on artificial blood vessel's the inwall, (thickness is generally 1～1000nm) till reaching the needed number of plies.After reaction finished, it was clean with deionized water wash to take out solution, and vacuum drying is to constant weight under the room temperature.
8) utilize ultraviolet light that the ionic bond of self-assembled film interlayer is transformed into covalent bond: to be ultraviolet light or the radiation of visible light artificial blood vessel inwall of 365nm with wavelength, photochemical reaction takes place, and makes diphenylamine diazoresin and comprises that the ionic bond between the polyanion of heparin is transformed into covalent bond.
In the present embodiment step 1), ultrasonic time is preferably 30 minutes, and baking temperature is preferably 60 ℃, is preferably 0.5 hour drying time.
Present embodiment step 2) in, the concentration of dissolves silicon rubber is preferably 50v/v%.
In the present embodiment step 3), be preferably 24 hours in the exsiccant time of air neutralization chamber relaxing the bowels with purgatives of warm nature.
In the present embodiment step 4), be preferably 2 hours with time of soaked in absolute ethyl alcohol silicone rubber coating.
In the present embodiment step 6), preparation Nafion solution organic solvent is methanol, dehydrated alcohol or their mixture.The concentration of Nafion solution is preferably 5wt%, injects, removes three step process cycle-indexes such as Nafion solution, nitrogen dry up and be preferably 20 times.
In the present embodiment step 7), diphenylamine diazoresin and the preferred 0.1～10mg/ml of polyanion concentration of aqueous solution, adsorption time is preferably 1 minute.
Present embodiment is coated silicone rubber as soft support on the surface of bio-medical instruments such as artificial blood vessel, coat Nafion again and provide active group for the layer upon layer electrostatic assembling on the surface of silicone rubber coating.Then with positively charged diphenylamine diazoresin and electronegative heparin molecule by electrostatic attraction effect alternating deposit to the surface of Nafion coating.Then, the artificial blood vessel is placed under the ultraviolet light, the diazo of DR is positively charged, and the sulfate of heparin is electronegative, by the electrostatic attraction effect, induce between the sulfate group of diazonium groups and heparin photochemical reaction takes place, the two forms ion complex, generates sulfuric ester, makes the ionic bond in the film be transformed into covalent bond, just made the multilayer film of covalent bonding, the stability of heparin in film is improved greatly.Heparin molecule still keeps its original biological activity after self assembly layer by layer and photochemical reaction, have tangible blood coagulation resisting function.The surface of the heparin thin film that present embodiment is prepared has active group, also can continue the thin film of other material of assembling on its surface, as polyelectrolyte, biologically functional molecule, conducting polymer etc.The photochemical reaction equation of heparin (Hep) and diphenylamine diazoresin (DR) is:
The specific embodiment three: present embodiment is achieved in that
A, the expanded PTFE artificial blood vessel is immersed in the dehydrated alcohol, ultrasonic 30 minutes, then 60 ℃ dry 1 hour down.
B, with medical grade silicon rubber as the normal temperature cure binding agent, it is dissolved in the organic solvent, preparation 50v/v% silicone rubber solution;
C, the artificial blood vessel is connected with syringe, upright, with syringe the 50v/v% silicone rubber solution is injected its intracavity from artificial blood vessel's end then, till tube chamber fills up.Remove silicone rubber solution, drying is 24 hours under air at room temperature.With clamp artificial blood vessel's end, in its tube chamber, fill up dehydrated alcohol, left standstill 2 hours.
D, remove ethanol, with syringe 5wt%Nafion solution is injected its intracavity from artificial blood vessel's end, till tube chamber fills up.Remove Nafion solution, after drying up with nitrogen.Repeat to inject, remove, nitrogen dries up three step processes 20 times.
E, to be the positively charged diphenylamine diazoresin solution of 1mg/ml with syringe with concentration inject its intracavity from artificial blood vessel's end, till tube chamber fills up, adsorption time is 15 minutes, after treating artificial blood vessel's inwall absorption last layer diphenylamine diazoresin, remove solution and clean, at this moment the surface lotus that becomes positively charged with deionized water wash.Use the same method concentration is filled with the artificial blood vessel for the 1mg/ml heparin solution, adsorption time is 1 minute, treat artificial blood vessel's inwall absorption last layer heparin after, remove solution and clean with deionized water wash, at this moment negative charge is with on the surface.Repeat above-mentioned steps, diphenylamine diazoresin and heparin alternate group are contained on artificial blood vessel's the inwall, reaction is removed solution and clean with deionized water wash after finishing, and at room temperature vacuum drying is to constant weight.Except that the adsorption time of ground floor diphenylamine diazoresin is 15 minutes, the adsorption time of remaining diphenylamine diazoresin layer and all heparin layer is 1 minute.In order to prove that DR and Hep can form uniform multilayered polymer film by electrostatic interaction, replace the artificial blood vessel to do substrate with quartz glass plate and repeat above-mentioned steps.
As can be seen from Figure 1, maximum absorption wavelength is that the absworption peak of 377nm belongs to DR and goes up diazo π-π
*Move more.Along with the increase of the double-deck number of DR/Hep, the absorbance at the maximum wavelength place is linear to be increased, and has convincingly demonstrated DR and Hep and can form uniform coating by the electrostatic attraction effect.The generation that this has not only illustrated the layer upon layer electrostatic self assembling process has illustrated that also DR and Hep have formed uniform polymeric coating layer.
F, make light source irradiation DR/Hep multilayer film with elongated long wavelength ultraviolet lamp [365nm, diameter 0.95cm, long 5.4cm], the distance of sample and light source is 3cm (relative intensity 2mW/cm
2).
As can be seen from Figure 2, light application time is respectively: 0s, 30s, 50s, 90s, 150s, and along with irradiation time increases, the absorbance at the 377nm place significantly reduces, and absworption peak disappears; Simultaneously, a new peak occurred at the 290nm place, absorbance increases with irradiation time.This has convincingly demonstrated and between the sulfate group of the diazonium groups of DR and Hep photochemical reaction has taken place and generate sulfuric ester, thereby makes the ionic bond in the film be transformed into covalent bond.
It is the 18mm sequin that the artificial blood vessel of heparinization is cut into diameter, puts into 37 ℃ Hepes buffer solution (20mM Hepes+190mM NaCl+0.5mg/ml BSA+0.02%NaN
3) the middle cultivation, (antithrombin AT-III), cultivated 5 minutes, then added thrombin (thrombin) and began reaction to add human antithrombase then.The final concentration of thrombin and antithrombase is respectively 10nM and 20nM.Take out 16 μ L reactant liquors at set intervals, add 368 μ L and contain the Tris buffer solution (50mM Tris+175mM NaCl+0.5mg/ml BSA) of 20mM EDTA with stopped reaction.Add 16 μ L color development substrate S-2238 (ultimate density is 0.2mM), detect thrombin with the UV/vis spectrophotometer at the 405nm place.
As can be seen from Figure 3, and do not contain comparing of heparin with reference to sample, contain heparin [(PLL/Hep)
4(DR/Hep)
4] plural layers have accelerated thrombin inactivation (PLL is a poly-L-Lysine) greatly.Before the photo-crosslinking, ionically bonded (DR/Hep)
4(PLL/Hep)
4Similar, because the dissolution heparin is discharged in the solution at short notice very soon, concentration of thrombin is sharply descended.In 37 ℃ PBS buffer solution, cultivate after the week, because the solution loss of heparin, (DR/Hep)
4(PLL/Hep)
4To the influence of thrombin inactivation with very approaching with reference to sample.Otherwise,, cultivate (DR/Hep) after a week because photo-crosslinking makes the interlayer ion key change covalent bond into
4Influence to the thrombin inactivation does not have obvious variation, illustrates that the stability of the heparin thin film of covalent bonding improves greatly.The plural layers that contain heparin [(PLL/Hep)
4(DR/Hep)
4] have good anticoagulant active, with the plural layers (DR/Hep) of covalent bonds
4Has better stability.
As can be seen from Figure 4, within four bilayers, heparin to the influence of thrombin inactivation along with the double-deck number of DR/Hep increases and increases.Behind four bilayers, further increase the double-deck number of DR/Hep, the influence of thrombin inactivation there is not tangible difference.This shows to have only outermost heparin just the thrombin inactivation to be had a direct impact.Within four bilayers why the influence of thrombin inactivation being increased along with the increase of double-deck number is because the concentration of outermost layer heparin does not reach capacity as yet.
As can be seen from Figure 5, in 37 ℃ buffer solution, cultivate after 10 days, the heparinization surface still keeps good active, but between 5 bilayers and 10 bilayers, there is not tangible difference, further the heparin multilayer film of proof covalent bonding has advantages of higher stability, and the heparin surface concentration reaches capacity when double-deck number reaches 4.
Fig. 4 and Fig. 5 show to have only outermost heparin just the thrombin inactivation to be had a direct impact.
Claims (10)
1, the anti-blood coagulation surface modifying method of artificial implant is characterized in that it is achieved in that
A, artificial implant is immersed in the organic solvent, ultrasonic cleaning 30～120 minutes, then, 30～90 ℃ dry 0.5～2 hour down;
B, with medical grade silicon rubber as the normal temperature cure binding agent, it is dissolved in the organic solvent, the preparation silicone rubber solution;
C, on the inner surface of artificial implant coating medical silicone rubber as soft support;
D, on the surface of silicone rubber coating, apply perfluorinated sulfonic acid;
E, with positively charged polycation and electronegative polyanion by electrostatic attraction effect alternating deposit to the surface of perfluorinated sulfonic acid coating;
F, utilize irradiation under ultraviolet ray artificial implant inwall, make the ionic bond between film inner layer be transformed into covalent bond, obtain anticoagulation surface ultrathin membrane by photochemical reaction.
2, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 is characterized in that the used organic solvent of described cleaning artificial implant is dehydrated alcohol, acetone or their mixture.
3, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 and 2, it is characterized in that described artificial implant is artificial blood vessel, blood conduit, polymeric film or porous support, or the bio-medical instrument of the different shape made from glass, pottery, silicon, various metal or various polymeric material.
4, the anti-blood coagulation surface modifying method of artificial implant according to claim 1, the organic solvent that it is characterized in that described dissolves silicon rubber is an alkane solvent.
5, the anti-blood coagulation surface modifying method of artificial implant according to claim 4 is characterized in that described alkane solvent is a normal hexane.
6, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 is characterized in that described silicone rubber solution volumetric concentration is 0.1～100v/v%.
7, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 is characterized in that described polyanion is one or more the mixture in heparin, heparin sulfate, seaweeds sodium, kayexalate, sulphuric acid glucose, chondroitin sulfate, sodium polyacrylate, the polymethylacrylic acid.
8, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 is characterized in that described polycation is diphenylamines-4-diazo resin or substituted diphenylamine diazo resin.
9, the anti-blood coagulation surface modifying method of artificial implant according to claim 8 is characterized in that described substituted diphenylamine diazo resin is one or more the mixture in 3-methoxy diphenylamine-4-diazo resin, N-methyldiphenylamine-4-diazo resin, 2-nitrodiphenylamine-4-diazo resin, 2-sulfonic acid diphenylamines-4-diazo resin, the N-methyldiphenylamine-2-diazo resin.
10, the anti-blood coagulation surface modifying method of artificial implant according to claim 1 is characterized in that the thickness of described anticoagulation surface ultrathin membrane is 1～1000nm.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100431625C (en) * | 2006-06-27 | 2008-11-12 | 哈尔滨工业大学 | Electrochemical cross-linking process for surface modification of biological material |
| CN106659737A (en) * | 2014-04-29 | 2017-05-10 | 艾里尔大学研究与开发有限公司 | Anticoagulant and decoagulant methods, compositions and devices |
| CN107854721A (en) * | 2017-11-07 | 2018-03-30 | 青岛大学 | A kind of anti-bacterial hydrogel and preparation method thereof |
| CN111330090A (en) * | 2020-03-02 | 2020-06-26 | 中国科学院宁波材料技术与工程研究所 | Surface anticoagulation modification method of hemodialyzer and application thereof |
| CN111867647A (en) * | 2018-03-09 | 2020-10-30 | 卡梅达股份公司 | Improvements in methods for immobilizing biological materials |
-
2005
- 2005-07-29 CN CN 200510010231 patent/CN1748804A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100431625C (en) * | 2006-06-27 | 2008-11-12 | 哈尔滨工业大学 | Electrochemical cross-linking process for surface modification of biological material |
| CN106659737A (en) * | 2014-04-29 | 2017-05-10 | 艾里尔大学研究与开发有限公司 | Anticoagulant and decoagulant methods, compositions and devices |
| CN107854721A (en) * | 2017-11-07 | 2018-03-30 | 青岛大学 | A kind of anti-bacterial hydrogel and preparation method thereof |
| CN107854721B (en) * | 2017-11-07 | 2021-04-20 | 青岛大学 | Antibacterial hydrogel and preparation method thereof |
| CN111867647A (en) * | 2018-03-09 | 2020-10-30 | 卡梅达股份公司 | Improvements in methods for immobilizing biological materials |
| CN111330090A (en) * | 2020-03-02 | 2020-06-26 | 中国科学院宁波材料技术与工程研究所 | Surface anticoagulation modification method of hemodialyzer and application thereof |
| CN111330090B (en) * | 2020-03-02 | 2022-04-05 | 中国科学院宁波材料技术与工程研究所 | Surface anticoagulation modification method of hemodialyzer and application thereof |
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