CN1618472A - Medicine eluent type blood vessel stent, and prepn. method therefor - Google Patents
Medicine eluent type blood vessel stent, and prepn. method therefor Download PDFInfo
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- CN1618472A CN1618472A CN 200410040450 CN200410040450A CN1618472A CN 1618472 A CN1618472 A CN 1618472A CN 200410040450 CN200410040450 CN 200410040450 CN 200410040450 A CN200410040450 A CN 200410040450A CN 1618472 A CN1618472 A CN 1618472A
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Abstract
A medicine eluting blood vessel scaffold is composed of blood vessel scaffold, TiO2 layer and medicine-polymer layer. It is prepared through roughening the surface of blood vessel scaffold, generating TiO2 layer on the rough surface, coating polymer layer, and combining medicine to the polymer layer. It can prevent said scaffold from renarrowing and thrombosis.
Description
Technical field
The present invention relates to the preparation method and the intravascular stent of intravascular stent, the particularly a kind of preparation method and medication eluting type blood vessel bracket that can discharge the medication eluting type blood vessel bracket of curative drug.This medication eluting type blood vessel bracket can effectively be prevented and treated restenosis and thrombosis behind the Stent.
Background technology
Dotter was placed on the close screw thread intravascular stent of homemade rustless steel in the peripheral vessels of dog under perspective in 1969, this support is kept vascular patency for 2 years half, he has proved rustless steel intravascular stent [the DotlerCT.Transluminally placed coil springs and arterial tube graffs.Long-tern patency in the carinepopliteal artery.Invest Radiol that can be integrated with blood vessel wall first, 1969,4:329-332].Sigwart in 1987 etc. have reported and laid intravascular stent in coronary artery, be mainly used in percutaneous coronary acute vascular obturation and PTCA postoperative restenosis [the Sigwart U that the dissatisfied or concurrent inner membrance avulsion of postoperative of (PTCA) art curative effect, interlayer cause that be shaped, et.al.Intravascular stents to prevent occlusion andrestenosis after tranaluminal angioplasty.N Engl J Med, 1987; 316:701].
At present, there is nearly 90% coronary artery interventional therapy all to comprise the implantable intravascular support.Lay intravascular stent in the coronary artery and have characteristics such as success rate height, curative effect is obvious, adaptability is strong, but because intravascular stent itself is as a kind of metallic foreign body, have the hyperamization bolt to form and foreign body reaction, the postoperative subacute stent thrombosis forms and restenosis is still two big major complications.For solving an above-mentioned difficult problem, people constantly design novel intravascular stent, and medication eluting type blood vessel bracket is exactly wherein a kind of.Medication eluting type blood vessel bracket (drug-eluting stent) directly is coated in certain medicine on the metallic blood vessel bracket, perhaps certain polymer is coated in the metallic blood vessel bracket surface, and on this basis in conjunction with one or more medicative medicine or antibody, medicine is transported to diseased region improves local drug concentration, reach therapeutic purposes.According to measuring and calculating, adopt this method can make local drug concentration reach 10 of whole body administration
6Doubly, thus more effectively prevent postoperative restenosis and thrombotic generation.
The drug main that drug-eluting stent is commonly used will be divided into following a few class at present:
1, the medicine that suppresses cell migration
The hypertrophy of tunica intima and vascular smooth muscle cell (SMC) migrated to the inner membrance growth after support was implanted substantial connection.Therefore, the migration that hinders SMC has also just reduced the hypertrophy of tunica intima, has reduced the generation of restenosis.As c-protease inhibitor (C-Proteinase inhibitors), prolyl 3-hydroxylase inhibitors (Prolyl Hydroxylase inhibitors), halofuginone etc.
2, the medicine that suppresses cell proliferation
Such medicine is the support eluting medicine of the present inhibition restenosis that generally adopts.Comprise rapamycin (Rapamycn), paclitaxel (Taxol), vincristine (Vincristine), mitomycin (Mitomycin), Paclitaxel etc.
3, promote the medicine of healing and endothelialization
Can select for use BCP671, estrogen (Estrogen) and VEGF somatomedin to wait and promote blood vessel endotheliumization, prevent thrombosis and reduce restenosis rate.
4, the medicine of inflammation-inhibiting reaction
Glucocorticoid commonly used is as dexamethasone (Dexamethasone), radiosone (Methyl-prednisolone) etc.
Comprehensive said medicine can find that the medicine that medication eluting type blood vessel bracket discharges can go to prevent restenosis and thrombosis from a plurality of angles.However, thrombosis and restenosis still fail to be effectively controlled behind the Stent.For this reason, the present invention is different from above-mentioned approach, from antiplatelet and anticoagulant angle, selects suitable drug to make a kind of medication eluting type blood vessel bracket, thereby realizes reducing even eliminate thrombosis and restenosis behind the Stent.
The preparation method of existing medication eluting type blood vessel bracket all is that polymer, medicine, solvent are total to molten formation coating solution, again this solution is applied to the intravascular stent surface, form the polymeric layer that contains medicine on the intravascular stent surface behind the evaporating solvent, but it is still have defectives such as polymeric layer easily comes off, and unworkable at all for protein drug the method.
Medication eluting type blood vessel bracket research, report abroad is more, but only has minority mechanism to carry out this research at home, and relevant patent seldom.
Summary of the invention
The preparation method and the medication eluting type blood vessel bracket that the purpose of this invention is to provide a kind of medication eluting type blood vessel bracket.After this medication eluting type blood vessel bracket was implanted, function medicament discharged, and brings into play antiplatelet and anticoagulation efficiently at implant site, to overcome restenosis and subacute stent thrombosis formation and the caducous problem of polymeric layer that prior art exists.
The preparation method of newtype drug eluting type blood vessel bracket of the present invention, its concrete operations step is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is by following material and molar concentration rate preparation, metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=(0.5～5): (10～30): (0.5～5): (1～10), in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5～30 minutes intravascular stent, take out the back drying at room temperature, place heating furnace to be heated to 450～600 ℃ again, programming rate is 4～8 ℃/min, be incubated 0.5～5 hour, taking-up is also cooled off this intravascular stent, and making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.1～0.5 μ m;
(3) prepared polymer solution
Any one polymer in polylactic acid, polycaprolactone, poly-anhydride, the polyglycolic acid is dissolved in chloroform, oxolane, dimethylbenzene, the acetone in any one solvent, is mixed with concentration and is 1～20% polymer solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polymer solution, soak time is 1～30 minute, takes out and dry this intravascular stent, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polymeric layer of 10～100 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the hirudin or antiplatelet monoclonal antibody or any one pharmaceutical aqueous solution of protamine that concentration is 0.1～10.0mg/ml, soak time is 10～50 hours, and medicine accounts for 1～45% of coating gross weight.
Medication eluting type blood vessel bracket of the present invention is made up of the titanium dioxide layer and the lip-deep pharmaceutical polymer layer of titanium dioxide layer on intravascular stent and surface thereof, the roughness of titanium dioxide layer is 0.1～0.5 μ m, the gross thickness of pharmaceutical polymer layer is 15～110 μ m, and medicine accounts for 1～45% of coating gross weight.
The present invention has following technique effect compared with prior art:
The preparation method of medication eluting type blood vessel bracket of the present invention is carried out surface roughening to intravascular stent and is handled before coating the polymeric medicine layer, form the titanium dioxide layer of an even compact on the intravascular stent surface, not only increased the blood compatibility of intravascular stent but make polymer and the intravascular stent surface combination firm, difficult drop-off.
The preparation method of medication eluting type blood vessel bracket of the present invention is coated in polymer solution on the titanium dioxide layer on intravascular stent surface earlier, dry back forms polymeric layer, this intravascular stent is soaked in the drug solution, medicine is attached in the polymer in the mode of passive absorption again.The method is different from the past to be total to molten formation coating solution with polymer, medicine, solvent, again this solution is applied to the intravascular stent surface, forms the medication eluting type blood vessel bracket preparation method of the polymeric layer that contains medicine behind the evaporating solvent on the intravascular stent surface.Because protein drug is dissolved in volatile organic solvent hardly, therefore this with polymer, medicine, solvent altogether the defective of the method maximum of molten formation coating solution be the preparation that can not be used for the protein drug eluting type blood vessel bracket.And the present invention is coated to polymer and medicine on the intravascular stent in two steps, has overcome the defective that polymer and medicine can not be dissolved in same volatile organic solvent altogether, thereby has opened up new world for the preparation method of protein drug eluting type blood vessel bracket.
The present invention adopts antiplatelet substance and the anticoagulant substances eluting medicine as intravascular stent, eluting medicine different from the past, as immunosuppressant rapamycin (Rapamycin) pair cell damaging action is arranged, influence the healing of endothelium, cause the formation of thrombosis.Platelet is particularly being played the part of important role in the artery thrombosis in thrombosis, and the main cause acute and that subacute stent thrombosis form of intravascular stent after implanting is blood coagulation system and the thrombogenicity of intravascular stent itself and the damage of implant site tunica intima that interventional procedure has activated blood, while thrombosis and restenosis substantial connection arranged.Therefore the present invention adopts antiplatelet substance and the anticoagulant substances eluting medicine as support, can reach efficient, the purpose of safety of local application, reduced the danger of hemorrhage complication again, also reach simultaneously the dual function of formation of anti-(Asia) acute thrombus and restenosis, improved patient's survival rate and quality of life greatly.
Description of drawings
Fig. 1: the structural profile sketch map of medication eluting type blood vessel bracket
Fig. 2: medication eluting type blood vessel bracket pictorial diagram
Fig. 3: the intravascular stent of roughening not under the inverted microscope
Fig. 4: the intravascular stent of roughening under the inverted microscope
Fig. 5: the sem photograph that does not contain the intravascular stent of antiplatelet monoclonal antibody
Fig. 6: the sem photograph of antiplatelet monoclonal antibody eluting type blood vessel bracket
1 is intravascular stent among Fig. 1; The 2nd, titanium dioxide layer; The 3rd, the pharmaceutical polymer layer
The specific embodiment
Embodiment 1
A kind of operating procedure of hirudin eluting type blood vessel bracket preparation method is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=0.5: 10: 0.5 by following material and molar concentration rate: 1, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 600 ℃, programming rate is 8 ℃/min, be incubated 5 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.5 μ m;
(3) prepared polymer solution
The 1g polylactic acid is dissolved in the 5ml chloroform, is mixed with concentration and is 20% polylactic acid solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polylactic acid solution, soak time is 30 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polylactic acid layers of 100 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the hirudin aqueous solution that concentration is 0.1mg/ml, soak time is 50 hours, and medicine accounts for 1% of coating gross weight.
Resulting hirudin eluting type blood vessel bracket, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.5 μ m, and the gross thickness of pharmaceutical polymer layer is 100 μ m, and medicine accounts for 1% of coating gross weight.This hirudin eluting type blood vessel bracket has the dual function of formation of anti-(Asia) acute thrombus and restenosis, can reach simultaneously that local application is efficient, purpose of safety, reduce the danger of hemorrhage complication again, improved patient's survival rate and quality of life greatly.
Embodiment 2
A kind of operating procedure of antiplatelet monoclonal antibody eluting type blood vessel bracket preparation method is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=3: 30: 3 by following material and molar concentration rate: 10, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 450 ℃, programming rate is 4 ℃/min, be incubated 0.5 hour, take out this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.1 μ m;
(3) prepared polymer solution
The poly-anhydride of 0.05g is dissolved in the 5ml oxolane, and being mixed with concentration is 1% poly-anhydride solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the poly-anhydride solution, soak time is 1 minute, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the poly-anhydride layer of 10 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the antiplatelet monoclonal anti liquid solution that concentration is 1mg/ml, soak time is 28 hours, and medicine accounts for 20% of coating gross weight.This intravascular stent with after citric acid anticoagulant fresh whole blood contacts 30 minutes, is observed under scanning electron microscope, and observed result is seen accompanying drawing 3,4.
Resulting antiplatelet monoclonal antibody eluting type blood vessel bracket, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.1 μ m, the gross thickness of pharmaceutical polymer layer is 10 μ m, and medicine accounts for 20% of coating gross weight.This antiplatelet monoclonal antibody eluting type blood vessel bracket has the dual function of formation of anti-(Asia) acute thrombus and restenosis, can reach simultaneously that local application is efficient, purpose of safety, reduce the danger of hemorrhage complication again, improved patient's survival rate and quality of life greatly.
Embodiment 3
A kind of operating procedure of protamine eluting type blood vessel bracket preparation method is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=2: 20: 2 by following material and molar concentration rate: 5, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 20 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 550 ℃, programming rate is 6 ℃/min, be incubated 3 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.3 μ m;
(3) prepared polymer solution
The 0.5g polycaprolactone is dissolved in the 5ml acetone, and being mixed with concentration is 10% polycaprolactone solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polycaprolactone solution, soak time is 10 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polycaprolactone layer of 40 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the protamine aqueous solution that concentration is 10.0mg/ml, soak time is 10 hours, and medicine accounts for 45% of coating gross weight.
Resulting protamine eluting type blood vessel bracket, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.3 μ m, and the gross thickness of pharmaceutical polymer layer is 40 μ m, and medicine accounts for 45% of coating gross weight.This protamine eluting type blood vessel bracket has the dual function of formation of anti-(Asia) acute thrombus and restenosis, can reach simultaneously that local application is efficient, purpose of safety, reduce the danger of hemorrhage complication again, improved patient's survival rate and quality of life greatly.
Embodiment 4
A kind of operating procedure of antiplatelet monoclonal antibody eluting type blood vessel bracket preparation method is as follows
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=1: 20: 1 by following material and molar concentration rate: 3, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 10 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 500 ℃, programming rate is 5 ℃/min, be incubated 2 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.4 μ m;
(3) prepared polymer solution
The 0.25g polyglycolic acid is dissolved in the 5ml dimethylbenzene, and being mixed with concentration is 5% polyglycolic acid solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polyglycolic acid solution, soak time is 10 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polyglycolic acid layer of 20 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the antiplatelet monoclonal anti liquid solution that concentration is 2mg/ml, soak time is 30 hours, and medicine accounts for 30% of coating gross weight.
Resulting antiplatelet monoclonal antibody eluting type blood vessel bracket, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.4 μ m, the gross thickness of pharmaceutical polymer layer is 300 μ m, and medicine accounts for 30% of coating gross weight.This antiplatelet monoclonal antibody eluting type blood vessel bracket has the dual function of formation of anti-(Asia) acute thrombus and restenosis, can reach simultaneously that local application is efficient, purpose of safety, reduce the danger of hemorrhage complication again, improved patient's survival rate and quality of life greatly.
Claims (10)
1, a kind of preparation method of medication eluting type blood vessel bracket is characterized in that the operating procedure of this method is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is by following material and molar concentration rate preparation, metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=(0.5～5): (10～30): (0.5～5): (1～10), in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5～30 minutes intravascular stent, take out the back drying at room temperature, place heating furnace to be heated to 450～600 ℃ again, programming rate is 4～8 ℃/min, be incubated 0.5～5 hour, taking-up is also cooled off this intravascular stent, and making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.1～0.5 μ m;
(3) prepared polymer solution
Any one polymer in polylactic acid, polycaprolactone, poly-anhydride, the polyglycolic acid is dissolved in chloroform, oxolane, dimethylbenzene, the acetone in any one solvent, is mixed with concentration and is 1～20% polymer solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polymer solution, soak time is 1～30 minute, takes out and dry this intravascular stent, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polymeric layer of 10～100 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the hirudin or antiplatelet monoclonal antibody or any one pharmaceutical aqueous solution of protamine that concentration is 0.1～10.0mg/ml, soak time is 10～50 hours, and medicine accounts for 1～45% of coating gross weight.
2, the operating procedure of the preparation method of the described a kind of medication eluting type blood vessel bracket of claim 1 is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=0.5: 12: 0.5 by following material and molar concentration rate: 1, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 600 ℃, programming rate is 8 ℃/min, be incubated 5 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.5 μ m;
(3) prepared polymer solution
Polylactic acid is dissolved in the chloroform, is mixed with concentration and is 20% polylactic acid solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polylactic acid solution, soak time is 30 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polylactic acid layers of 100 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the hirudin aqueous solution that concentration is 0.1mg/ml, soak time is 50 hours, and medicine accounts for 1% of coating gross weight.
3, the operating procedure of the preparation method of the described a kind of medication eluting type blood vessel bracket of claim 1 is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=3: 30: 3 by following material and molar concentration rate: 10, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 5 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 450 ℃, programming rate is 4 ℃/min, be incubated 0.5 hour, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.1 μ m;
(3) prepared polymer solution
To gather anhydride and be dissolved in the oxolane, being mixed with concentration is 1% poly-anhydride solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the poly-anhydride solution, soak time is 1 minute, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the poly-anhydride layer of 10 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the antiplatelet monoclonal anti liquid solution that concentration is 1mg/ml, soak time is 28 hours, and medicine accounts for 20% of coating gross weight.
4, the operating procedure of the preparation method of the described a kind of medication eluting type blood vessel bracket of claim 1 is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=2: 20: 2 by following material and molar concentration rate: 5, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 20 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 550 ℃, programming rate is 6 ℃/min, be incubated 3 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.3 μ m;
(3) prepared polymer solution
Polycaprolactone is dissolved in the acetone, and being mixed with concentration is 10% polycaprolactone solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polycaprolactone solution, soak time is 10 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polycaprolactone layer of 40 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the protamine aqueous solution that concentration is 10.0mg/ml, soak time is 10 hours, and medicine accounts for 45% of coating gross weight.
5, the operating procedure of the preparation method of the described a kind of medication eluting type blood vessel bracket of claim 1 is as follows:
(1) preparation metatitanic acid fourth lipoprotein solution
Metatitanic acid fourth lipoprotein solution is prepared metatitanic acid fourth fat: ethylene glycol monomethyl ether: ethyl acetoacetate: water=1: 20: 1 by following material and molar concentration rate: 3, in ethylene glycol monomethyl ether, add metatitanic acid fourth fat earlier, and add ethyl acetoacetate and water behind the mixing again;
(2) intravascular stent is placed metatitanic acid fourth lipoprotein solution handle
Place metatitanic acid fourth lipoprotein solution to soak 10 minutes intravascular stent, take out the back drying at room temperature, place Muffle furnace to heat-treat again in 500 ℃, programming rate is 5 ℃/min, be incubated 2 hours, take out also and at room temperature cool off this intravascular stent, making the intravascular stent surface form the layer of surface roughness is the titanium dioxide layer of 0.4 μ m;
(3) prepared polymer solution
Polyglycolic acid is dissolved in the dimethylbenzene, and being mixed with concentration is 5% polyglycolic acid solution;
(4) surface is had the intravascular stent of titanium dioxide layer be soaked in the polyglycolic acid solution, soak time is 10 minutes, takes out this intravascular stent, drying at room temperature, and making the titanium dioxide laminar surface formation thickness of intravascular stent is the polyglycolic acid layer of 20 μ m;
(5) intravascular stent after the above-mentioned processing is soaked in the antiplatelet monoclonal anti liquid solution that concentration is 2mg/ml, soak time is 30 hours, and medicine accounts for 30% of coating gross weight.
6, a kind of medication eluting type blood vessel bracket, it is characterized in that by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.1～0.5 μ m, the gross thickness of pharmaceutical polymer layer is 15～110 μ m, and medicine accounts for 1～45% of coating gross weight.
7, the described a kind of medication eluting type blood vessel bracket of claim 6, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.5 μ m, the gross thickness of pharmaceutical polymer layer is 100 μ m, and medicine accounts for 1% of coating gross weight.
8, the described a kind of medication eluting type blood vessel bracket of claim 6, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.1 μ m, the gross thickness of pharmaceutical polymer layer is 10 μ m, and medicine accounts for 20% of coating gross weight.
9, the described a kind of medication eluting type blood vessel bracket of claim 6, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.3 μ m, the gross thickness of pharmaceutical polymer layer is 40 μ m, and medicine accounts for 45% of coating gross weight.
10, the described a kind of medication eluting type blood vessel bracket of claim 6, by intravascular stent and the surface titanium dioxide layer and the pharmaceutical polymer layer of titanium dioxide laminar surface form, the roughness of titanium dioxide layer is 0.4 μ m, the gross thickness of pharmaceutical polymer layer is 300 μ m, and medicine accounts for 30% of coating gross weight.
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| US8361536B2 (en) | 2007-05-23 | 2013-01-29 | Lepu Medical Technology (Beijing) Co., Ltd. | Method for fixing antibody on the surface of medical instrument |
| WO2016188342A1 (en) * | 2015-05-22 | 2016-12-01 | 先健科技(深圳)有限公司 | Implantable medical instrument preform, implantable medical instrument and preparation method thereof |
| CN107820416A (en) * | 2017-08-17 | 2018-03-20 | 鼎科医疗技术（苏州）有限公司 | Degradable metal support and its manufacture method |
| CN112791230A (en) * | 2021-01-28 | 2021-05-14 | 四川大学 | Gene elution coating material with oxidative stress damage repair function and preparation method thereof |
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| CN101172168B (en) * | 2007-10-10 | 2010-06-02 | 大连理工大学 | Metallic blood vessel bracket coating for osamine glycan load CD133 antibody and method for preparing the same |
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2004
- 2004-08-13 CN CN 200410040450 patent/CN1278743C/en not_active Expired - Fee Related
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| CN101437471B (en) * | 2006-04-12 | 2011-08-31 | 动脉再造技术股份有限公司 | Methods of smoothing and resurfacing polymeric stent surface to reduce biologically active sites |
| US8361536B2 (en) | 2007-05-23 | 2013-01-29 | Lepu Medical Technology (Beijing) Co., Ltd. | Method for fixing antibody on the surface of medical instrument |
| WO2016188342A1 (en) * | 2015-05-22 | 2016-12-01 | 先健科技(深圳)有限公司 | Implantable medical instrument preform, implantable medical instrument and preparation method thereof |
| US20180147322A1 (en) * | 2015-05-22 | 2018-05-31 | Lifetech Scientific (Shenzhen) Co., Ltd. | Implantable Medical Instrument Preform, Implantable Medical Instrument and Preparation Method Thereof |
| EP3299039A4 (en) * | 2015-05-22 | 2019-01-23 | Lifetech Scientific (Shenzhen) Co., Ltd. | Implantable medical instrument preform, implantable medical instrument and preparation method thereof |
| US10933162B2 (en) | 2015-05-22 | 2021-03-02 | Lifetech Scientific (Shenzhen) Co. Ltd. | Implantable medical instrument preform, implantable medical instrument and preparation method thereof |
| CN107820416A (en) * | 2017-08-17 | 2018-03-20 | 鼎科医疗技术（苏州）有限公司 | Degradable metal support and its manufacture method |
| CN112791230A (en) * | 2021-01-28 | 2021-05-14 | 四川大学 | Gene elution coating material with oxidative stress damage repair function and preparation method thereof |
| CN112791230B (en) * | 2021-01-28 | 2021-10-12 | 四川大学 | Gene elution coating material with oxidative stress damage repair function and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1278743C (en) | 2006-10-11 |
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