CN1257753C - Method of preparing anticoagulant biological material using electrostatic self-assembling - Google Patents
Method of preparing anticoagulant biological material using electrostatic self-assembling Download PDFInfo
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Abstract
The present invention discloses a method for preparing anticoagulating biomaterials by adopting electrostatic self-assembly, which comprises the following procedures: 1. a charged current surface with a positive charge or a negative charge is obtained on a biomaterial surface by adopting the method of surface modification; 2. charged current materials prepared in 1 are immerged into polyelectrolyte water solution of charged opposite charges with the concentration of 0.01 mg/ml to 10 g/ml for 5 to 60 minutes of adsorption equilibrium, are washed by distilled water and are dried by air blow; the materials after being dried are immerged into polyelectrolyte water solution of charged opposite charges with the concentration of 0.01 mg/ml to 10 g/ml for 5 to 60 minutes of adsorption equilibrium, are washed by distilled water and are dried by air blow; the procedures are alternately repeated so as to obtain multilayer coating layer surfaces which are alternately assembled and comprise a positive charge polyelectrolyte and a negative charge polyelectrolyte, and each coating layer polyelectrolyte comprises one kind or more than kind of electrified anticoagulant. A coating layer polymer coats a layer in a water-soluble condition, and can realize the coating layer decoration for biological medical devices with complicated form structures so as to form a stable medical polymer coating layer. The anticoagulating property of materials is effectively improved.
Description
Technical field
The present invention relates to a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial.
Background technology
Blood environment is one of most important environment of human body, good blood compatibility material can be widely used in all kinds of medical intervention devices that contact with blood, blood purification and dialysis apparatus, various artificial internal organs such as extracorporeal circulation apparatus and artificial lung, artificial liver, artificial heart.Has huge clinical meaning.Can induce the multiple proteins absorption of (comprising thrombin) when but most synthetic materials contacts with blood non-specificly, induce the generation thromboplastin, activate platelet, finally cause blood coagulation by endogenous and exogenous cruor pathway.
People have the thrombogenic biomaterial of good resistance by the synthesizing new anticoagulant material with to the prepared by surface modification of current material.Because existing various biomaterials have good physical and mechanical properties and lower price usually, and be widely used in all kinds of biomedical devices, therefore by finishing to current material, on the basis of keeping material good physical mechanical performance, improving the anticoagulant property of material, is a kind of economy and effective and efficient manner.During present research is used, people adopt kinds of surface technology such as comprising surface chemistry grafting, surface light chemical graft and coating technology that material surface is modified, by regulating the various medicines of surface charge, hydrophilic and hydrophobic, load and the biomolecule of material, improve anticoagulation, the anti-infection property of material, obtained achievement preferably.Yet, because these finishing means ubiquities weakness such as solvent toxicity, complex technical process, adjustable ability, not only limited the designability of material surface greatly, and can't realize modification to medical apparatus with complex geometry profile, can not satisfy the needs of medical apparatus develop rapidly.
Summary of the invention
The purpose of this invention is to provide a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial.
Specifically may further comprise the steps:
1) adopt process for modifying surface to obtain charged surface at biomaterial surface with positive charge or negative charge;
2) will be by 1) charged material of preparation immerses in the polyelectrolyte aqueous solution of lotus opposite charges that concentration is 0.01mg/ml-10g/ml, and adsorption equilibrium 5-60 minute, use distilled water wash, nitrogen dries up; Dried material is immersed in the polyelectrolyte aqueous solution of lotus opposite charges that concentration is 0.01mg/ml-10g/ml, adsorption equilibrium 5-60 minute, use distilled water wash, nitrogen dries up; Alternately repeat above step and obtain to contain the alternatively stacked polyanion/polycation of positive and negative charge polyelectrolyte and replace coating surface, the coating polyelectrolyte comprises one or more charged anticoagulation medicine.
Advantage of the present invention:
1) this method technology is simple, can realize by simple dip coating apparatus, by simple alternately dip-coating technology, is implemented in nanometer at material surface, the layer structure design of submicron-scale
2) this method is based on the water technology, and solvent-free toxicity is a kind of eco-friendly preparation method
3) this method does not have special requirement to the three-dimensional-structure of material, can realize on multiple complex shape structural material surface.
4) range of choice of this method coating molecule is wide, can be the synthesis type polyelectrolyte, also can be charged bioactive macromolecules such as protein, polysaccharide, DNA;
5) this method preparation method gentleness can be carried out under the aqueous environment of gentleness; The electrostatic interaction more weak with respect to covalent bonding can guarantee that anticoagulation molecule has the highly blood coagulation resistant biological activity.
The specific embodiment
This method is to adopt process for surface preparation on the charged surface that the material surface acquisition has positive charge or negative charge, obtains the coating of load anticoagulation medicine by the alternately assembling of polyanion and polycation.Specifically comprise following two steps:
The surperficial charged method of modifying of 1 biomaterial at first adopts the kinds of surface modification technology on the charged surface that polyurethane, polrvinyl chloride, polyester, silicone rubber and surface of stainless steel acquisition have positive charge or negative charge, and surface modifying method comprises:
1) directly adsorb polyelectrolyte at biomaterial surface, polyelectrolyte can be a polycation, comprises one or more mixture of polymine, lysine, polypropylene-base amine; Polyelectrolyte can be a polyanion also, comprises one or more mixture in polyacrylic acid, polymethylacrylic acid, the kayexalate.
2) Surface Treatment with Plasma and photo-grafting surface treatment.
3) surface modifying method is a surface chemical modification; adopt the 3-aminopropyl triethoxysilane alcoholic solution of 10-10000mM; after soaking 3-5 hour; rustless steel is transferred in the hydrochloric acid solution of 0.1M; hydrolysis is adsorbed onto 3-aminopropyl triethoxysilane 10-20 hour on the rustless steel; fall lip-deep hydrochloric acid with ethanol and washed with de-ionized water, dry up with nitrogen then, the nitrogen protection of 100-200 degree was solidified down 1-5 hour.
The alternately assembling of the polyanion of 2 charged biomaterial surfaces and polycation, wherein polycation comprises polymine, polylysine, polypropylene-base amine, chitosan and hyaluronic one or more mixture; Polyanion comprises one or more mixture of albumin, heparin, sulfonation glucosan, urokinase, kayexalate, sodium alginate.In the polyelectrolyte aqueous solution of the lotus opposite charges that preparation method is will be 0.01mg/ml-10g/ml by the 1 charged biomaterial immersion concentration for preparing, adsorption equilibrium 5-60 minute, use distilled water wash, air blow drying; Dried material is immersed in the polyelectrolyte aqueous solution of lotus opposite charges that concentration is 0.01mg/ml-10g/ml, adsorption equilibrium 5-60 minute, use distilled water wash, air blow drying; Alternately repeat above step and obtain to contain the alternatively stacked laminated coating of positive and negative charge polyelectrolyte surface, the coating polyelectrolyte comprises one or more charged anticoagulation medicine.Charged anticoagulation medicine comprises albumin, heparin, sulfonation glucosan, urokinase, kayexalate, can be assembled in the outermost layer of laminated coating; Also can be assembled in the internal layer of laminated coating.
Embodiment 1:
Medical 316L rustless steel at first is dipped into polyethyleneimine: amine aqueous solution 5-10 minute of 0.01-2mg/ml, washed with de-ionized water, nitrogen dries up the surface that obtains the polymine physical absorption, and this surface is electropositive under aqueous conditions.The above-mentioned material of lotus positive electricity is dipped into heparin sodium aqueous solution 5-10 minute of 0.01-10mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion anticoagulation heparin; The surface of the polyanion anticoagulation heparin of bear electricity is dipped into polyethyleneimine: amine aqueous solution 10-20 minute of 0.01-20mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeat above process acquisition polyanion anticoagulation heparin and polycation polymine 2-10 layer and replace coating surface.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes PEI and heparin sodium deposit to the 316L stainless steel surfaces layer by layer.The electrochemical impedance experiment has also proved deposition process layer by layer.Contact angle data and electrochemical impedance experiment show the existence that the multilayer film of acquisition can be stable in 30 days.The medical 316L of multiple calcification time showing heparin coating is stainless, and multiple the calcification time ratio is barren has prolonged 70～100 seconds.External whole blood experiment shows that no thrombosis forms on the medical stainless steel of heparin coating, and the platelet adhesion experiment shows that the medical 316L rustless steel platelet adhesion quantity of heparin coating is less than 1/10 of the medical 316L rustless steel of blank platelet adsorption number.
Embodiment 2
Medical 316L rustless steel at first is dipped into the 3-aminopropyl triethoxysilane alcoholic solution of 10-50mM; soak after 3 hours; rustless steel is transferred in the hydrochloric acid solution of 0.1M; hydrolysis is adsorbed onto the 3-aminopropyl triethoxysilane 20 hours on the rustless steel; fall lip-deep hydrochloric acid with ethanol and washed with de-ionized water; dry up with nitrogen then, 110 degree nitrogen protections were solidified 1 hour down.This surface is dipped into the aqueous hydrochloric acid solution of pH2.0, and deionization cleans then, and nitrogen dries up, and obtains the surface of stable positively charged.The above-mentioned material of lotus positive electricity is dipped into heparin sodium aqueous solution 20-30 minute of 20-40mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion anticoagulation heparin; The surface of the polyanion anticoagulation heparin of bear electricity is dipped into chitosan aqueous acetic acid 30-40 minute of 1-5mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeat above process acquisition polyanion anticoagulation heparin and polycation chitosan 2-10 layer and replace coating surface.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes heparin and chitosan deposit to the 316L stainless steel surfaces layer by layer.The electrochemical impedance experiment has also proved deposition process layer by layer.Contact angle data and electrochemical impedance experiment show the existence that the multilayer film of acquisition can be stable in 30 days.External whole blood experiment shows that no thrombosis forms on the medical stainless steel of heparin coating, and the platelet adhesion experiment shows that the medical 316L rustless steel platelet adhesion quantity of heparin coating is less than 1/10 of the medical 316L rustless steel of blank platelet adsorption number.
Embodiment 3:
Use dehydrated alcohol respectively, washed with de-ionized water medical PVC film, after nitrogen dries up, vacuum drying.Handle the PVC film with ammonia plasmas: the PVC film good drying is put in the plasma reactor, article on plasma precursor reactant device evacuation, the pressure of Cement Composite Treated by Plasma base material maintains 40-50Pa by logical ammonia, and discharge current is 25～100mA, processing time 5～15min.Make reactor return to normal pressure then, take out the PVC film of handling well.Amido functional group is contained on its surface.The PVC film that ammonia plasmas is handled is dipped into the aqueous hydrochloric acid solution 5～15min of pH0.5～2, and making the amide acidify is ammonium ion, takes out washed with de-ionized water, and nitrogen dries up and obtains positively charged surface.The above-mentioned material of lotus positive electricity is dipped into the albumin PBS buffer solution (pH7.4) 40-50 minute of 50-70mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the albuminous surface of lotus polyanion anticoagulation; The albuminous surface of polyanion anticoagulation of bear electricity is dipped into polyethyleneimine: ammonia spirit 50-60 minute of 70-100mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeat above process acquisition polyanion anticoagulation albumin and polycation polyethylene imido 20-40 layer and replace coating surface.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes PEI and albumin deposit to the PVC surface that ammonia plasmas is handled layer by layer.I
125The radio-labeled experiment has also proved deposition process layer by layer.Contact angle data and I
125The radio-labeled experiment shows the existence that the multilayer film of acquisition can be stable in 30 days.Tangible prolongation has taken place in the multiple calcification time of the medical PVC of multiple calcification time showing albumin coating.External whole blood experiment shows that no thrombosis forms on the medical PVC of albumin coating, and the platelet adhesion experiment shows that the medical PVC platelet adhesion quantity of albumin coating is lower than 1/8 of blank medical PVC platelet adhesion quantity.
Embodiment 4:
With washed with de-ionized water medical polyurethane film, after nitrogen dries up, vacuum drying.Handle dry good polyurethane film with oxygen gas plasma.The good polyurethane film of drying is put in the plasma reactor, article on plasma precursor reactant device evacuation, the pressure of Cement Composite Treated by Plasma base material maintains 40-50Pa by logical oxygen, and discharge current is 25～100mA, processing time 5～15min.Make reactor return to normal pressure then, take out the polyurethane film of handling well.Carboxyl functional group is contained on its surface.The polyurethane film that oxygen gas plasma is handled is dipped into the aqueous hydrochloric acid solution 5～15min of pH10～12, carboxyl is converted into is to take out washed with de-ionized water by the carboxylic ion, and nitrogen dries up and obtains electronegative surface.The above-mentioned material of bear electricity is dipped into the albuminous aqueous solution of 100-150mg/ml (so the albuminous isoelectric point, IP of pH3.9 is 5 to be lower than 5 o'clock albumin at pH and to show electropositive, regulate pH with the hydrochloric acid of 1M and sodium hydrate aqueous solution) 50-60 minute, deionized water (pH3.9) cleans, nitrogen dries up, and obtains the albuminous surface of lotus polycation anticoagulation; The albuminous surface of polycation anticoagulation of lotus positive electricity is dipped into the aqueous solution (pH3.9) 50-60 minute of the heparin of 150-1000mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polyanion, repeat above process acquisition polycation anticoagulation albumin and polyanion heparin 10-20 layer and replace coating surface.Glutaraldehyde cross-linking multilayer film 10～40min with 1%.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes albumin and heparin deposit to the polyurethane surface that oxygen gas plasma is handled layer by layer.The experiment of I125 radio-labeled has also proved deposition process layer by layer.Contact angle data and the experiment of I125 radio-labeled show the existence that the multilayer film of acquisition can be stable in 30 days.Blood coagulation does not take place in the medical polyurethane of multiple calcification time showing albumin and heparin coating in 30min.External whole blood experiment shows that no thrombosis forms on the medical polyurethane of albumin and heparin coating, and the platelet adhesion experiment shows that the medical polyurethane platelet adhesion quantity of albumin and heparin coating is lower than 1/8 of blank medical polyurethane platelet adhesion quantity.
Embodiment 5:
As embodiment 3 nitrogen plasma treatment medical grade silicon rubber.The silicone rubber of nitrogen plasma treatment is dipped into the aqueous hydrochloric acid solution 5～15min of pH0.5～2, and making the amide acidify is ammonium ion, takes out washed with de-ionized water, and nitrogen dries up and obtains positively charged surface.The above-mentioned material of lotus positive electricity is dipped into the acetate-sodium acetate buffer (pH5.2) 50-60 minute of the sodium alginate of 10-100mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion sodium alginate; The surface of the polyanion sodium alginate of bear electricity is dipped into the acetate-sodium acetate buffer (pH5.2) 50-60 minute of 5-10mg/ml chitosan, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeating above process acquisition chitosan is outer field sodium alginate and chitosan 60-80 layer coating surface, be dipped into then the polyanion anticoagulation heparin acetate-sodium acetate buffer (pH5.2) of 1000-1500mg/ml bear electricity 10-60 minute, obtaining outermost layer is the surface of anticoagulation polyanion heparin.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes sodium alginate and chitosan deposit to the silastic surface of nitrogen plasma treatment layer by layer.XPS experiment has also proved the outermost layer that deposits to of deposition process and heparin success layer by layer.Contact angle data and XPS experiment show the existence that the heparin coating of acquisition can be stable in 30 days.Tangible prolongation has taken place in the multiple calcification time of the medical grade silicon rubber of multiple calcification time showing heparin coating.External whole blood experiment shows that no thrombosis forms on the medical grade silicon rubber of heparin coating, and the platelet adhesion experiment shows that the medical grade silicon rubber platelet adhesion quantity of heparin coating is lower than 1/8 of blank medical grade silicon rubber platelet adhesion quantity.
Embodiment 6:
The medical grade silicon rubber of the lotus positive electricity that obtains as embodiment 5.The above-mentioned material of lotus positive electricity is dipped into the polyacrylic acid PBS buffer solution (pH7.2) 50-60 minute of 10-100mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the polyacrylic surface of lotus polyanion; The polyacrylic surface of the polyanion of bear electricity is dipped into the PBS buffer solution (pH7.2) 50-60 minute of the polypropylene-base amine of 1500-3000mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeating that above process obtains the polyanion polyacrylic acid and polycation polypropylene-base amine 2-10 layer replaces coating surface, is outermost layer the PBS buffer solution (pH7.2) 50-60 minute of the polyacrylic multilayer film urokinase that is dipped into 50-100mg/ml.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes sodium polyacrylate and polypropylene-base amine deposit to the silastic surface of nitrogen plasma treatment layer by layer.XPS experiment has also proved depositing on the multilayer film of deposition process and urokinase success layer by layer.Contact angle data and XPS experiment show the existence that anticoagulation urokinase multilayer film can be stable in 30 days that contains of acquisition.Tangible prolongation has taken place in the multiple calcification time of the medical grade silicon rubber of multiple calcification time showing urokinase coating.External whole blood experiment shows that no thrombosis forms on the medical grade silicon rubber of urokinase coating.
Embodiment 7:
Use absolute methanol, the medical polyester of washed with de-ionized water, nitrogen dries up.The polyester film that cleans is dipped into the PAH aqueous solution (pH11.5) soaking at room temperature 0.5-5 hour of 0.5～10mg/ml, obtains the surface of polypropylene-base amine aminolysis, after the washed with de-ionized water, be dipped into the deionized water 30 minutes of pH2.2, acquisition ammonia ionization surface, the reuse tri-distilled water cleans, drying for standby.The above-mentioned material of lotus positive electricity is dipped into the urokinase PBS buffer solution (pH7.2) 10-60 minute of 50-100mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion anticoagulation urokinase; The surface of the polyanion anticoagulation urokinase of bear electricity is dipped into the PBS buffer solution (pH7.2) 50-60 minute of the polylysine of 3-5mg/ml, washed with de-ionized water, nitrogen dries up, obtain the surface of lotus polycation, repeat above process acquisition polyanion urokinase and polycation polylysine 2-10 layer and replace coating surface, follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes sodium polyacrylate and polypropylene-base amine deposit to the silastic surface of nitrogen plasma treatment layer by layer.The XPS experiment has also proved deposition process layer by layer.Contact angle data and XPS experiment show the existence that anticoagulation urokinase multilayer film can be stable in 30 days that contains of acquisition.Tangible prolongation has taken place in the multiple calcification time of the medical polyester of multiple calcification time showing urokinase coating.External whole blood experiment shows that no thrombosis forms on the medical polyester film of urokinase coating.
Embodiment 8:
To be dissolved with light trigger, the graft copolymer solution of acrylic monomers is contained in reactor, and the medical PVC film is suspended from the solution top, and in water bath with thermostatic control medium ultraviolet rayed a period of time, light trigger, grafted monomers enter gas phase and film reaction under heat effect.Ultraviolet source is a fluorescent lamp, and general power is 40W, characteristic wavelength 340nm～360nm.Film after the grafting cleans for several times with acetone, places the acetone extraction fully to dry after 24 hours again.Obtain acrylic acid-grafted surface.Film is dipped into the aqueous hydrochloric acid solution 5～15min of pH10～12, carboxyl is converted into is to take out washed with de-ionized water by the carboxylic ion, and nitrogen dries up and obtains electronegative surface.The above-mentioned material of bear electricity is dipped into polypropylene amine aqueous solution 50-60 minute of 10-100mg/ml, washed with de-ionized water, nitrogen dries up, and obtains lotus polycation surface; The polycation surface of lotus positive electricity is dipped into kayexalate aqueous solution 50-60 minute of 3000-5000mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion, repeats above process acquisition polyanion anticoagulation kayexalate 2-10 layer and replaces coating surface.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes polypropylene amine and kayexalate deposit to the PVC surface that oxygen gas plasma is handled layer by layer.The XPS experiment has also proved deposition process layer by layer.Contact angle data and XPS experiment show the existence that the multilayer film of acquisition can be stable in 30 days.Blood coagulation does not take place in the medical PVC of multiple calcification time showing kayexalate coating in 30min.External whole blood experiment shows that no thrombosis forms on the medical PVC of kayexalate coating.The platelet adhesion experiment shows that the medical PVC platelet adhesion quantity of kayexalate coating is lower than 1/10 of blank medical PVC platelet adhesion quantity.
Embodiment 9:
Press embodiment 8 and obtain bear ammeter face.The above-mentioned material of bear electricity is dipped into polypropylene amine aqueous solution 50-60 minute of 5000-7000mg/ml, washed with de-ionized water, nitrogen dries up, and obtains lotus polycation surface; The polycation surface of lotus positive electricity is dipped into sulfonation glucan aqueous solution 50-60 minute of 7000-10000mg/ml, washed with de-ionized water, nitrogen dries up, and obtains the surface of lotus polyanion, repeats above process acquisition polyanion anticoagulation sulfonation glucosan 2-10 layer and replaces coating surface.Follow the tracks of discovery with contact angle, contact angle has illustrated that along with deposition number of plies generation zigzag changes polypropylene amine and sulfonation glucosan deposit to the PVC surface that oxygen gas plasma is handled layer by layer.The XPS experiment has also proved deposition process layer by layer.Contact angle data and XPS experiment show the existence that the multilayer film of acquisition can be stable in 30 days.Blood coagulation does not take place in the medical PVC of multiple calcification time showing sulfonation glucosan coating in 30min.External whole blood experiment shows that no thrombosis forms on the medical PVC of sulfonation glucosan coating.
Claims (8)
1. method that adopts the static self assembly to prepare anticoagulant biomaterial is characterized in that its step is as follows:
1) adopt surface modifying method to obtain charged surface at biomaterial surface with positive charge or negative charge;
2) will be by 1) charged material of preparation immerses in the polyelectrolyte aqueous solution of lotus opposite charges that concentration is 0.01mg/ml-10g/ml, and adsorption equilibrium 5-60 minute, use distilled water wash, nitrogen dries up; Dried material is immersed in the polyelectrolyte aqueous solution of lotus opposite charges that concentration is 0.01mg/ml-10g/ml, adsorption equilibrium 5-60 minute, use distilled water wash, nitrogen dries up; Alternately repeat above step and obtain to contain the alternatively stacked laminated coating of positive and negative charge polyelectrolyte surface, the coating polyelectrolyte comprises one or more charged anticoagulation medicine.
2. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1 is characterized in that said biomaterial is polyurethane, polrvinyl chloride, polyester, silicone rubber or stainless steel material.
3. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1, it is characterized in that said surface modifying method is directly to adsorb polyelectrolyte at biomaterial surface, polyelectrolyte is a polycation, comprise polymine, one or more mixture of polylysine and polypropylene-base amine; Polyelectrolyte is a polyanion, comprises one or more mixture in polyacrylic acid, polymethylacrylic acid and the kayexalate.
4. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1 is characterized in that said surface modifying method is Surface Treatment with Plasma method or photo-grafting surface treatment method.
5. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1; it is characterized in that said surface modifying method is a surface chemical modification; adopt the 3-aminopropyl triethoxysilane alcoholic solution of 10-10000mM; after soaking 3-5 hour; medical 316L rustless steel is transferred in the hydrochloric acid solution of 0.1M; hydrolysis is adsorbed onto 3-aminopropyl triethoxysilane 10-20 hour on the medical 316L rustless steel; fall lip-deep hydrochloric acid with ethanol and washed with de-ionized water; dry up with nitrogen then, the nitrogen protection of 100-200 degree was solidified down 1-5 hour.
6. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1, it is characterized in that said polyelectrolyte is a polycation, comprise one or more mixture of polymine, polylysine, polypropylene-base amine and chitosan.
7. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1, it is characterized in that said polyelectrolyte is a polyanion, comprise one or more mixture of albumin, heparin, sulfonation glucosan, urokinase, kayexalate and sodium alginate.
8. a kind of method that adopts the static self assembly to prepare anticoagulant biomaterial according to claim 1 is characterized in that said charged anticoagulation medicine, comprises albumin, heparin, sulfonation glucosan, urokinase or kayexalate.
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| CN113499479B (en) * | 2021-07-19 | 2023-03-17 | 科凯(南通)生命科学有限公司 | Preparation method of modified biological material and obtained modified biological material |
| CN113786518A (en) * | 2021-09-15 | 2021-12-14 | 海思盖德(苏州)生物医学科技有限公司 | Preparation method of composite coating for surface modification of medical material |
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| CN114748699A (en) * | 2022-04-08 | 2022-07-15 | 华南理工大学 | Bifunctional support material capable of resisting bacteria and resisting coagulation and gradient regulation and control integrated forming preparation method thereof |
| WO2024045119A1 (en) * | 2022-09-01 | 2024-03-07 | 北京化工大学 | Universal method for optimizing counter anion to improve hemostatic performance of biological material |
| CN115337444B (en) * | 2022-09-01 | 2023-10-20 | 北京化工大学 | Preparation method of electronegative micromolecule-regulated procoagulant surface |
-
2003
- 2003-04-28 CN CN 03116748 patent/CN1257753C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009049550A1 (en) * | 2007-10-10 | 2009-04-23 | Dalian University Of Technology | Blood vessel scaffold coating of amidoglucosan polysaccharide loaded with cd133 antibody and its preparation method |
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| CN1448189A (en) | 2003-10-15 |
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