CN101195048A - Compound medicament washing bracket and method for preparing the same - Google Patents
Compound medicament washing bracket and method for preparing the same Download PDFInfo
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- CN101195048A CN101195048A CNA2006101193257A CN200610119325A CN101195048A CN 101195048 A CN101195048 A CN 101195048A CN A2006101193257 A CNA2006101193257 A CN A2006101193257A CN 200610119325 A CN200610119325 A CN 200610119325A CN 101195048 A CN101195048 A CN 101195048A
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Abstract
The invention discloses a compound drug elution cardiovascular stent and preparing process, and the drug elution stent of the invention adopts the drug combination of estrogen biological active drug and coagent. After the compound drug elution cardiovascular stent is implanted in a vivo lumen, the continuous release of drugs carried by the cardiovascular stent is used for inhibiting the smooth muscle cells from bleeding and extracellular stroma from synthesizing, simultaneously, the healing of injured vessel walls can be improved, the late thrombus is prevented, and the economic burden of intake of antithrombotic and platelet drugs is reduced after the operation is carried out to the patient.
Description
[technical field]
The present invention relates to a kind of combination drug coating bracket, belong to the medical apparatus and instruments scope.
[background technology]
There is the millions of people in the whole world because suffer from the narrow class disease of cardiovascular of atherosis class every year, accept percutaneous arteria coronaria plasty (PTCA) and support and implant the vascular interventional treatment of modes such as (stent) art, the greatest problem that is perplexing these interventional therapys is the restenosis problem of postoperative, according to statistics, the PTCA postoperative has 50%, and 20～30% patient behind the Stent is because vascular restenosis needs interventional therapy or surgical operation therapy once more.Select the medicine of blocking-up restenosis generating process, it be coated on rack surface, be implanted to the vascular lesion position after, medicine is local to be discharged, performance suppresses the intimal proliferation effect, is the main direction of present anti-restenosis research.The coating medicine that adopts comprises the medicine of immunosuppressant, anti-inflammatory drug, anti-smooth muscle proliferation and migration medicine and promotion endothelial cell proliferation and migration etc. at present.
Up to the present, bracket for eluting medicament by the U.S. FDA authentication has only the rapamycin FirebirdTM (CYPHER) of Cordis company and the paclitaxel FirebirdTM (TAXUS) of Boston science and technology, clinical use has very strong anti-restenosis effect, and patient's restenosis rate drops in 10% over the past half year.But because rapamycin and paclitaxel do not have selectivity for vascular endothelial cell and smooth muscle cell, in the strong inhibition vascular smooth muscle cell, propagation and migration that also can the strong inhibition endotheliocyte, endothelialization postpones after causing stenting, this is the main cause that causes bracket for eluting medicament postoperative advanced thrombus, height is disabled, high mortality because the present advanced thrombus that is caused by drug stent has, and is just causing increasing concern.
Accelerating bracket for eluting medicament and implant the early stage reparation of back damage endothelium, avoid the generation of endothelialization delay phenomenon at least, recover the endothelium normal physiological function, is the key that prevents that stent thrombosis from forming, and also is the important directions of present bracket for eluting medicament research.Promote the measure of support endothelialization to mainly contain two aspects, the one, promote migration, the propagation of local endotheliocyte, the 2nd, promote in the circulation endothelial progenitor cells to gather and break up partial.Reported the KAT-II clinical trial of topical application VEGF (VEGF) adenovirus and plasmid safety and feasibility in the human body coronary artery in 2003, but can not give up the misgivings of people to its safety, and the coronarography inspection is not observed it and can be reduced in-stent restenosis (Circulation after June, 2003,107:2677-2683), moreover the technology of preparing complexity, feasibility is relatively poor.The clinical trial HEALING-FIM registration studies that the interior application of human body in 2005 can be captured the anti-CD34 antibody coating support of endothelial progenitor cells shows, radiography was followed up a case by regular visits to and was shown that tube chamber was lost the luminal stenosis rate that shows with IVUS and compared with bare bracket and there is no significant advantage (J Am Coll Cardiol late period June, 2005,45:1574-1579), its main defective is anti-CD34 antibody behind the bracket coating activity is difficult to preserve.
Estrogen is the endogenous hormone medicine that a class has the cardiovascular protection effect, can promote the partial endothelialization of injured blood vessel, suppresses propagation, migration and the blood vessel negativity of vascular smooth muscle cell and reinvents, and suppresses the partial inflammatory reaction of blood vessel.Zoopery shows that estrogen can improve the nitricoxide synthase at endothelial injury position (eNOS) level, strengthen the fixing and differentiation (Circulation.2003 of circulation endothelium progenitor cell in the blood, 107 (24): 3059-65), estradiol FirebirdTM clinical trial (EASTER) shows that it is safe and feasible (J Am Coll Cardiol.2004 that the estradiol support is used for human body, 43 (6): 1118-21), but its anti-restenosis effect is not also determined.
The estrogen biologically active drug that has that will have antithrombotic or antiproliferative anti-restenosis medicaments and promotion support endothelialization combines, prepare compound bracket for eluting medicament, make it when preventing thrombosis formation, keeping powerful anti-restenosis effect, and has an early stage support endothelialization, be expected to solve simultaneously restenosis and endothelialization and postpone two large problems, important clinic value is arranged.
The present invention uses the employing composite drug-eluting stent, to have bioactive medicine of estrogen and coagent and unite use, be applied to the intravascular stent surface, it is discharged by the certain hour order, it is synthetic to suppress smooth muscle cell proliferation and extracellular matrix, can promote simultaneously the healing of injured blood vessel wall, prevent the generation of advanced thrombus, reduce the financial burden that patient's postoperative is taken antithrombotic and platelet medicine.
[summary of the invention]
The present invention relates to be used to prevent and treat a kind of bracket for eluting medicament of the narrow property of cardiovascular disease, belong to the scope of medical apparatus and instruments.
Order of the present invention is on bracket for eluting medicament to adopt estradiol etc. to have the combination of the optional a kind of and coagent of the bioactive medicine of estrogen, is used for the narrow property of cardiovascular treatment of diseases.The generation of prevention of postoperative restenosis phenomenon also promotes the support process of endothelialization again.
The narrow property of cardiovascular disease, comprise heart and peripheral arterial because the narrow and acute obturation that atherosclerotic plaque forms and acute thrombus causes, as coronary stricture, cerebrovascular stenosis, carotid artery stenosis, iliac artery is narrow and shareholder's arteries and veins is narrow etc.
Have been found that now estradiol has the effects such as mobilization differentiation that promote the endothelial cell proliferation migration, promote endothelial progenitor cells (EPC) in the blood, can promote the process of endothelialization again of damaged part behind the cardiovascular interventional procedure.In addition, estradiol can also suppress the propagation of vascular smooth muscle cell, has certain anti-restenosis effect.Yet, use the estradiol FirebirdTM still to have higher restenosis separately and take place.
Estradiol etc. had the bioactive medicine of estrogen, optional a kind of and coagent such as anti-proliferative drugs united use preparation composite drug-eluting stent, can be used for the narrow property of cardiovascular treatment of diseases, the generation of prevention of postoperative restenosis phenomenon also promotes the support process of endothelialization again.
According to the present invention, estradiol etc. have the bioactive medicine of estrogen, and a kind of and one or more that can choose wantonly are selected from following coagent and share: immunosuppressant and anti-inflammatory drug, antithrombotic and anticoagulant, antiproliferative agents medicine, short endothelialization medicine again, anti-migration medicine and intercellular matrix regulator.
Of the present invention have a bioactive medicine of estrogen, the estrogen such as estradiol, estriol, estrone, estradiol benzoate, estradiol valerate, dipropionate estradiol, nilestriol, ethinylestradiol, female three methyl ethers of alkynes, ethinylestradiol methyl ether, diethylstilbestrol and structural derivative and the analog that comprise natural half-natural source, semi-synthetic and synthetic, comprise that also plant origin has the medicine of estrogen activity, as resveratrol, soybean isoflavone, Radix Puerariae flavone and structural derivative thereof and analog.
Immunosuppressant of the present invention is including, but not limited to rapamycin, tacrolimus, everolimus, ABT-578, mycophenolate and cyclosporin, interferon, mizoribine and leflunomide etc.
Anti-inflammatory agent of the present invention is including, but not limited to corticosteroid, such as prednisone, meticortelone, dexamethasone, prednisone and cortisone etc.; Comprise NSAID (non-steroidal anti-inflammatory drug), such as celecoxib, rofecoxib, aspirin etc.; Comprise ascosin, such as pimecrolimus etc.; Also comprise cytokine inhibitor.
Antiproliferative agents of the present invention is including, but not limited to taxanes, vinca alkaloids, Epothilones and derivant thereof, tyrosine kinase inhibitor and with receptors bind such as PDGF, EGF, VEGF or reduce the medicine of its expression.
Antithrombotic of the present invention and anticoagulant are including, but not limited to clopidogrel, low molecular heparin calcium, Lumbrukinase, low molecular sodium heparin, sodium ozagrel, alteplase enzyme, Enoxaparin Sodium, benzyl chloride pyridine, cilostazol, heparin sodium, hirudin, urokinase, heparin and glycoprotein iib/iiia inhibitor etc.
Short endothelialization medicine more of the present invention is including, but not limited to BCP671, VEGF, G-CSF, endothelial progenitor cells antibody and nitric oxide donors etc.
Anti-migration medicine of the present invention and intercellular matrix regulator are including, but not limited to batimastat, marimastat, probucol, C-protease inhibitor, halofuginone hydrobromide and prolyl hydroxylase inhibitor.
Support be mixed or be attached to active medicine combination of the present invention can by several different methods and any biocompatible materials; Medicine can be dissolved in polymer and obtain medicine and mixture of polymers in single solvent or the mixed solvent, be applied to rack surface, treat to obtain being embedded in after the solvent evaporates medication coat of medicine by methods such as spraying, dip-coating, brushings; Medicine can be participated in the degradable polymer, adopt the preparation of heating and melting or other method to contain the degradable FirebirdTM of drug regimen; Medicine can be inserted in the shrinkage pool of rack surface; Medicine can be mixed in the coatings such as biocompatibility porous ceramics coating, the poly-charcoal of fluorine; Medicine can chemical bond arrive polymer or rack surface, relates to the method for chemical derivatization; In addition, the preparation polymer coating is adsorbed onto medicine in the coating more earlier, obtains containing the coating of medicine.The medication coat gross thickness of this bracket for eluting medicament is 1～100um, and wherein the shared percentage by weight of active medicine is 1～40%.
Drug regimen of the present invention, can be simultaneously and polymeric material be dissolved in single solvent or the mixed solvent, be applied to rack surface by methods such as spraying, dip-coating, brushings again, treat to obtain the monolayer medication coat that embedding medicinal makes up after the solvent evaporates; Can be dissolved in single solvent or the mixed solvent with polymeric material respectively,, be applied to rack surface successively by methods such as spraying, dip-coating, brushings again, treat to obtain the multilayer medicine coating that embedding medicinal makes up after the solvent evaporates.Can be in the outside of medicine layer, repaste cloth one deck does not contain the polymer coating of medicine, is used for controlling the drug release behavior of medication coat.In addition,, can be coated with the one layer of polymeric coating earlier,, be used to strengthen the bond strength of medication coat and metal support surface as parylene C in the inboard of medication coat.
Polymer of the present invention is a biocompatible polymer, comprises biodegradable polymer and Biostatic polymer.Wherein biodegradable polymer comprises collagen, hyaluronic acid, gelatin, polyester, polyamino acid, polysaccharide, polyphosphazene, poly-(ether-ester), copolymer or its mixture.Wherein Biostatic polymer comprises: polyurethanes, polyolefin, polyester, polyamide, polycaprolactam, polyimides, polyvinyl methyl ether, polyvinyl alcohol or vinyl alcohol, olefin copolymer, polyacrylonitrile, polydimethylsiloxane, poly-(ethane-acetic acid ethyenyl ester), based on the polymer of acrylate or copolymer, polyvinylpyrrolidone, fluorinated polymer, cellulose esters, or its mixture.
Support under the present invention, comprise that balloon expandable stent, self-expanding stent and other are used for the support of cardiovascular interventional therapy, can be by metal racks such as Nitinol, cobalt alloy, titanium alloy, stainless steel alloies, also can be the polymer support of making by polymeric material, as the polylactic acid bracket that can degrade fully etc.
It is estradiol that the present invention preferably has the bioactive medicine of estrogen, and carries out once more preferably obtaining the compound FirebirdTM of preferred rapamycin estradiol on the basis in view of the above.Adopting degradable polylactic acid is the compound FirebirdTM of degradable coating rapamycin of polymer support preparation, can stablize release-more than individual month external.And in the porcine coronary restenosis model, has good anti-restenosis and short rapamycin support endothelialization dual function again.
The present invention will solve behind current use rapamycin FirebirdTM and the paclitaxel FirebirdTM endothelialization delay issue again, quicken the repair process (promptly endothelialization process) again of endothelial injury behind the stenting, reduce thrombosis and the acute myocardial infarction of initiation and the risk of death in the support in late period, in addition, can also shorten the time that patient takes dual Antiplatelet therapy medicine, reduce the burden of patient's economy, have good clinical and commercial promise.
Following examples are used to set forth the present invention, but do not limit the present invention.
[description of drawings]
Accompanying drawing 1, rapamycin and estradiol measure the HPLC collection of illustrative plates (A, rapamycin sample, B, estradiol sample, C, handkerchief mycin and estradiol biased sample, 1, rapamycin peak 2, rapamycin isomer peak 3, estradiol peak)
Accompanying drawing 2, the compound FirebirdTM release in vitro of embodiment 1 rapamycin estradiol curve chart
Accompanying drawing 3, paclitaxel and estradiol measure the HPLC collection of illustrative plates (A, paclitaxel sample, B, estradiol sample, C, paclitaxel and estradiol biased sample, 1, paclitaxel peak 2, estradiol peak)
Accompanying drawing 4, the compound FirebirdTM release in vitro of embodiment 2 thunder paclitaxel estradiol curve chart
Accompanying drawing 6, the compound FirebirdTM release in vitro of embodiment 3 dexamethasone estradiol curve chart
Accompanying drawing 7, the compound FirebirdTM sem photograph of embodiment 1 rapamycin estradiol
Accompanying drawing 8, the compound FirebirdTM of rapamycin estradiol are implanted 30 days support vessel segment transverse section of miniature pig arteria coronaria section light microscopic figure
Accompanying drawing 9, rapamycin FirebirdTM are implanted 30 days support vessel segment transverse section of miniature pig arteria coronaria section light microscopic figure
Accompanying drawing 10, the compound FirebirdTM of rapamycin estradiol are implanted the sem photograph of 14 days miniature pig coronary artery bracket vessel segment endotheliocytes
Accompanying drawing 11, rapamycin FirebirdTM are implanted the sem photograph of 14 days miniature pig coronary artery bracket vessel segment endotheliocytes
[specific embodiment]
Take by weighing rapamycin and polylactic acid is an amount of, both percentage by weights are 3: 7, and obtaining percentage by weight with the dichloromethane ultrasonic dissolution is 1% coating liquid.The coating liquid atomizing spraying of preparation is arrived through pretreated bare metal stent surface.Again that support is dry under 60 ℃ and 0.1Mpa vacuum, prepare the rapamycin layer.Take by weighing estradiol and polylactic acid is an amount of, both percentage by weights are 2: 8, and obtaining percentage by weight with the dichloromethane ultrasonic dissolution is 1% coating liquid.Adopt aforementioned coating process that estradiol layer coating liquid is coated onto the drug stent surface that coats rapamycin layer coating, obtain the compound FirebirdTM of rapamycin estradiol.
Take by weighing paclitaxel and the polymethyl methacrylate nano silicon dioxide composite material is an amount of, both percentage by weights are 3: 7, and obtaining percentage by weight with the oxolane ultrasonic dissolution is 1% coating liquid.The coating liquid atomizing spraying of preparation is arrived through pretreated bare metal stent surface.Again that support is dry under 60 ℃ and 0.1Mpa vacuum, prepare the paclitaxel coating.Take by weighing estradiol and the polymethyl methacrylate nano silicon dioxide composite material is an amount of, both percentage by weights are 3: 7, and obtaining percentage by weight with the oxolane ultrasonic dissolution is 1% coating liquid.Adopt aforementioned coating process that estradiol layer coating liquid is coated onto the drug stent surface that coats paclitaxel layer coating, obtain the compound FirebirdTM of paclitaxel estradiol.
Take by weighing dexamethasone and poly-(ethane-acetic acid ethyenyl ester) in right amount, both percentage by weights are 4: 6, and obtaining percentage by weight with the oxolane ultrasonic dissolution is 1% coating liquid.The coating liquid atomizing spraying of preparation is arrived through pretreated bare metal stent surface.Again that support is dry under 60 ℃ and 0.1Mpa vacuum, prepare the paclitaxel coating.Take by weighing estradiol and poly-(ethane-acetic acid ethyenyl ester) material in right amount, both percentage by weights are 2: 8, and obtaining percentage by weight with the oxolane ultrasonic dissolution is 1% coating liquid.Adopt aforementioned coating process that estradiol layer coating liquid is coated onto the drug stent surface that coats dexamethasone layer coating, obtain the compound FirebirdTM of dexamethasone estradiol.
It is an amount of to take by weighing rapamycin, estriol and polylactic acid, and both percentage by weights are 1: 1: 3, and obtaining percentage by weight with the dichloromethane ultrasonic dissolution is 1% coating liquid.The coating liquid atomizing spraying of preparation is arrived through pretreated bare metal stent surface.Again that support is dry under 60 ℃ and 0.1Mpa vacuum, prepare rapamycin estriol layer.It is an amount of to take by weighing polylactic acid, and obtaining percentage by weight with the dichloromethane ultrasonic dissolution is 0.5% coating liquid.Adopt aforementioned coating process that polylactic acid coating liquid is coated onto the drug stent surface that coats rapamycin estradiol layer coating, obtain the compound FirebirdTM of rapamycin estradiol.
(methanol: 0.05MpH7.4PBS=20: 80) be medium, carry out the research of release in vitro degree in 37 ℃ of water bath chaders, frequency of oscillation is 100RPM with 10ml20% methanol will to prepare the compound FirebirdTM of rapamycin estradiol.Interval in accordance with regulations takes out whole media (staying 1ml is sample) and replenishes synthermal 20% methanol of equal-volume.Sample-20 is ℃ freezing, thaw before the mensuration and 15000rpm * 10min centrifugal, the supernatant sample introduction.Chromatographic condition: mobile phase: methanol: acetonitrile: water=27: 46: 27, λ=280nm, 55 ℃ of column temperatures, flow velocity=1ml/min.The HPLC chromatogram of rapamycin and estradiol such as accompanying drawing 1.The compound FirebirdTM release in vitro of the rapamycin estradiol curve of embodiment 1 preparation is seen accompanying drawing 2.
Embodiment 6
To prepare the compound FirebirdTM 10ml0.1%SLS of paclitaxel estradiol is medium, carries out the research of release in vitro degree in 37 ℃ of water bath chaders, and frequency of oscillation is 100RPM.Interval in accordance with regulations takes out whole media (staying 1ml is sample) and replenishes synthermal 20% methanol of equal-volume.Sample-20 is ℃ freezing, thaw before the mensuration and 15000rpm * 10min centrifugal, the supernatant sample introduction.Chromatographic condition: mobile phase: acetonitrile: water=50: 50, λ=230nm, 50 ℃ of column temperatures, flow velocity=1ml/min.The HPLC chromatogram of paclitaxel and estradiol such as accompanying drawing 3.The compound FirebirdTM release in vitro of the paclitaxel estradiol curve of embodiment 2 preparations is seen accompanying drawing 4.
Embodiment 7
(methanol: 0.05MpH7.4PBS=10: 90) be medium, carry out the research of release in vitro degree in 37 ℃ of water bath chaders, frequency of oscillation is 100RPM with 10ml10% methanol will to prepare the compound FirebirdTM of dexamethasone estradiol.Interval in accordance with regulations takes out whole media (staying 1ml is sample) and replenishes synthermal 20% methanol of equal-volume.Sample-20 is ℃ freezing, thaw before the mensuration and 15000rpm * 10min centrifugal, the supernatant sample introduction.Chromatographic condition: mobile phase: methanol: 0.02M sodium dihydrogen phosphate (pH4.0)=50: 50, λ
1=280nm; λ
255 ℃ of=230nm column temperatures, flow velocity=1ml/min.The HPLC chromatogram of dexamethasone and estradiol such as accompanying drawing 5.The compound FirebirdTM release in vitro of the dexamethasone estradiol curve of embodiment 3 preparations is seen accompanying drawing 6.
Embodiment 8
Adopt scanning electron microscope to carry out the observation of face coat form the compound FirebirdTM of the rapamycin estradiol of preparation.Can see that the rack surface coating of invention example 1 preparation is smooth smooth, the requirement of the clinical use mechanical performance of bracket for eluting medicament coating is satisfied in no obvious perk behind the balloon expandable, situation generation (seeing accompanying drawing 7) such as come off.
Embodiment 9
(the support blood vessel diameter is than being 1.2-1.3: the compound FirebirdTM of rapamycin estradiol 1) forms the coronary artery injury model, and compares with the rapamycin FirebirdTM to implant overdistension at the miniature pig coronary artery.Postoperative the 14th day and the 30th day check coronary arteriography, histopathology is measured inner membrance area, inner membrance average thickness and the support endothelialization of support vessel segment. and the result shows: effect aspect and rapamycin FirebirdTM that the compound FirebirdTM of rapamycin estradiol suppresses neointimal hyperplasia relatively do not have significant difference (P＞0.05), but its support endothelialization degree in each time period significantly is better than rapamycin FirebirdTM (P＜0.05), sees Fig. 8～11.
Claims (11)
1. a bracket for eluting medicament is characterized in that the active component that this bracket for eluting medicament is loaded with is a kind of drug regimen, and this drug regimen is formed by having the bioactive medicine of estrogen and one or more coagents.
2. according to the described bracket for eluting medicament of claim 1, it is characterized in that the described bioactive medicine of estrogen that has, comprise the estrogen that is selected from natural half-natural source, semi-synthetic and synthetic, as estradiol, estriol, estrone, estradiol benzoate, estradiol valerate, dipropionate estradiol, nilestriol, ethinylestradiol, female three methyl ethers of alkynes, ethinylestradiol methyl ether, diethylstilbestrol and structural derivative and analog; Comprise that also plant origin has the medicine of estrogen activity, as resveratrol, soybean isoflavone, Radix Puerariae flavone and structural derivative thereof and analog.
3. according to the described bracket for eluting medicament of claim 1, it is characterized in that described coagent is selected from one or more of following various kinds of drug active component: immunosuppressant and anti-inflammatory drug, antithrombotic and anticoagulant, antiproliferative agents medicine, short endothelialization medicine again, anti-migration medicine and intercellular matrix regulator.
4. according to the arbitrary described bracket for eluting medicament of claim 1～3, it is characterized in that this bracket for eluting medicament is the medication coat metal rack, its metal material is selected from cobalt, tantalum, Nitinol, nitinol, medical stainless steel.
5. according to the arbitrary described bracket for eluting medicament of claim 1～3, it is characterized in that this bracket for eluting medicament is a Biodegradable scaffold, its composition material is selected from one or more in polyester, poly-anhydride, polyamino acid, poly phosphazene, poly-polysaccharide material or its mixture.
6. according to the described bracket for eluting medicament of claim 4～5, it is characterized in that the medication coat of this bracket for eluting medicament is made up of medicine and polymer support.
7. bracket for eluting medicament according to claim 4 is characterized in that the medication coat of this bracket for eluting medicament does not contain polymer support, directly is distributed in the shrinkage pool of metal rack rack surface or rack surface.
8. bracket for eluting medicament according to claim 6, the polymer support that it is characterized in that this bracket for eluting medicament is a Biostatic polymer, be selected from polyurethanes, polyolefin, polyester, polyamide, polycaprolactam, polyimides, polyvinyl methyl ether, polyvinyl alcohol or vinyl alcohol, olefin copolymer, polyacrylonitrile, polydimethylsiloxane, poly-(ethylene-vinyl acetate), polymer or copolymer based on acrylate, polyvinylpyrrolidone, fluorinated polymer, cellulose esters, the porous ceramics coating, fluorine gathers charcoal, or one or more of its mixture.
9. bracket for eluting medicament according to claim 6 is characterized in that the polymer support of this bracket for eluting medicament is a biological degradation polyalcohol, is selected from polyester, poly-anhydride, polyamino acid, poly phosphazene, poly-polysaccharide, or one or more of its mixture.
10. as the arbitrary described bracket for eluting medicament of claim 1～9, its feature can adopt following any preparation method that medicine and biocompatible materials are mixed or be attached to support: 1) medicine and polymer are dissolved in and obtain medicine and mixture of polymers in single solvent or the mixed solvent, be applied to rack surface by methods such as spraying, dip-coating, brushings, treat to obtain being embedded in after the solvent evaporates medication coat of medicine; 2) medicine is participated in the degradable polymer, adopt the preparation of heating and melting or other method to contain the degradable FirebirdTM of drug regimen; 3) medicine is inserted in the shrinkage pool of rack surface; 4) medicine is mixed in the coatings such as biocompatibility porous ceramics coating, the poly-charcoal of fluorine; 5) pharmaceutical chemistry is attached to polymer or rack surface, relates to the method for chemical derivatization; 6) prepare polymer coating earlier, again medicine is adsorbed onto in the coating, obtain containing the coating of medicine.
11., it is characterized in that this bracket for eluting medicament is used to prevent intravascular stent implantation and the generation of percutaneous arteria coronaria molding postoperative restenosis and promotes the postoperative intravascular stent process of endothelialization again as the arbitrary described bracket for eluting medicament of claim 1～10.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101193257A CN101195048A (en) | 2006-12-08 | 2006-12-08 | Compound medicament washing bracket and method for preparing the same |
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| CNA2006101193257A CN101195048A (en) | 2006-12-08 | 2006-12-08 | Compound medicament washing bracket and method for preparing the same |
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| CN101195048A true CN101195048A (en) | 2008-06-11 |
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| CN102462862A (en) * | 2010-11-17 | 2012-05-23 | 重庆润泽医疗器械有限公司 | Preparation method for porous tantalum serving as medical metal implant material |
| CN102475904A (en) * | 2010-11-29 | 2012-05-30 | 重庆润泽医疗器械有限公司 | Preparation method of medical porous metal implant material |
| CN102475903A (en) * | 2010-11-29 | 2012-05-30 | 重庆润泽医疗器械有限公司 | Preparation method for medical metal implant material porous niobium |
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| CN105771005A (en) * | 2016-03-24 | 2016-07-20 | 乐普（北京）医疗器械股份有限公司 | Anti-rheumatic blood vessel stenosis drug-eluting stent and preparation method and application thereof |
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| CN102258805B (en) * | 2010-05-28 | 2016-08-10 | 温州智创科技有限公司 | medical metal implant material porous niobium and preparation method thereof |
| CN102258805A (en) * | 2010-05-28 | 2011-11-30 | 重庆润泽医疗器械有限公司 | Medical metal implanted material porous niobium and preparation method thereof |
| CN102462862B (en) * | 2010-11-17 | 2013-10-09 | 重庆润泽医药有限公司 | Preparation method for porous tantalum serving as medical metal implant material |
| CN102462862A (en) * | 2010-11-17 | 2012-05-23 | 重庆润泽医疗器械有限公司 | Preparation method for porous tantalum serving as medical metal implant material |
| CN102475903A (en) * | 2010-11-29 | 2012-05-30 | 重庆润泽医疗器械有限公司 | Preparation method for medical metal implant material porous niobium |
| CN102475904B (en) * | 2010-11-29 | 2013-09-18 | 重庆润泽医药有限公司 | Preparation method of medical porous metal implant material |
| CN102475903B (en) * | 2010-11-29 | 2013-09-18 | 重庆润泽医药有限公司 | Preparation method for medical metal implant material porous niobium |
| CN102475904A (en) * | 2010-11-29 | 2012-05-30 | 重庆润泽医疗器械有限公司 | Preparation method of medical porous metal implant material |
| CN104027849A (en) * | 2014-06-30 | 2014-09-10 | 四川大学 | Soy isoflavone supported biological composite material porous scaffold and preparation |
| CN104027849B (en) * | 2014-06-30 | 2016-02-10 | 四川大学 | Carry Biocomposite material porous support and the preparation of soybean isoflavone |
| CN105771005A (en) * | 2016-03-24 | 2016-07-20 | 乐普（北京）医疗器械股份有限公司 | Anti-rheumatic blood vessel stenosis drug-eluting stent and preparation method and application thereof |
| CN113289072A (en) * | 2021-05-24 | 2021-08-24 | 哈尔滨医科大学 | Liquid medicine for stent, medicine eluting stent and preparation method thereof |
| CN116712620A (en) * | 2023-04-27 | 2023-09-08 | 雅伦生物科技(北京)有限公司 | Drug coating, drug eluting stent containing same and preparation method thereof |
| CN116712620B (en) * | 2023-04-27 | 2023-12-12 | 雅伦生物科技(北京)有限公司 | Drug coating, drug eluting stent containing same and preparation method thereof |
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