CN105561406A - 一种含复合药物涂层的血管支架 - Google Patents
一种含复合药物涂层的血管支架 Download PDFInfo
- Publication number
- CN105561406A CN105561406A CN201610085845.4A CN201610085845A CN105561406A CN 105561406 A CN105561406 A CN 105561406A CN 201610085845 A CN201610085845 A CN 201610085845A CN 105561406 A CN105561406 A CN 105561406A
- Authority
- CN
- China
- Prior art keywords
- combination drug
- intravascular stent
- coating
- drug coating
- cyclodextrin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 85
- 238000000576 coating method Methods 0.000 title claims abstract description 63
- 239000011248 coating agent Substances 0.000 title claims abstract description 61
- 239000002131 composite material Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 29
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 24
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000008280 blood Substances 0.000 claims abstract description 14
- 210000004369 blood Anatomy 0.000 claims abstract description 14
- 239000002184 metal Substances 0.000 claims abstract description 14
- 229910052751 metal Inorganic materials 0.000 claims abstract description 14
- 239000000956 alloy Substances 0.000 claims abstract description 7
- 229910045601 alloy Inorganic materials 0.000 claims abstract description 6
- 230000036772 blood pressure Effects 0.000 claims abstract description 6
- 229940000425 combination drug Drugs 0.000 claims description 27
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 10
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 10
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 10
- 229960002855 simvastatin Drugs 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000011247 coating layer Substances 0.000 claims description 6
- 239000011159 matrix material Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
- 229960001130 urapidil Drugs 0.000 claims description 3
- 239000012503 blood component Substances 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 230000000717 retained effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- 208000037803 restenosis Diseases 0.000 abstract description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 5
- 239000008103 glucose Substances 0.000 abstract description 5
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 abstract description 3
- 229940080345 gamma-cyclodextrin Drugs 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 150000002632 lipids Chemical class 0.000 abstract 1
- 210000004204 blood vessel Anatomy 0.000 description 16
- 238000007306 functionalization reaction Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 3
- 239000000306 component Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 238000001069 Raman spectroscopy Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910018979 CoPt Inorganic materials 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 229910001260 Pt alloy Inorganic materials 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- GUBSQCSIIDQXLB-UHFFFAOYSA-N cobalt platinum Chemical compound [Co].[Pt].[Pt].[Pt] GUBSQCSIIDQXLB-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 125000002456 taxol group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
一种含复合药物涂层的血管支架，血管支架基体为常用的裸金属或合金制备成金属网，在血管支架金属网涂覆有复合药物涂层；所述复合药物涂层是一种基于环糊精组织的单种或者多种药物涂层；复合涂层中环糊精分子和药物的摩尔比，不低于2:1，不高于20：1。本发明是一种采用新型复合药物涂层功能化的血管支架。该新型复合涂层是一种基于环糊精组织的单种或者多种药物涂层，尤其是采用γ环糊精，该药物可以是具有抑制再狭窄、控制血脂、血糖、血压或控制血压组分的药物。
Description
一、技术领域
本发明涉及医用器械，一种将功能药物涂层负载在常见CoPt、不锈钢等合金网格组成的常见支架基材上形成的一种药物负载支架。
二、背景技术
血管支架一般是合金材质，比如医用不锈钢，Ta或者钴铂合金等，利用这类合金编织成网附着在一个球囊和导引装置上构成。在医疗实践中，依靠成像技术辅助，可将金属支架送至血管病变处，达到支撑狭窄闭塞段血管，减少血管弹性回缩及再塑形，保持管腔血流通畅的目的。(美国专利4969458，4733665，,4739762,4776337)。近来也在研究多种聚合物材料和可降解材料材质的支架。
近几十年来，血管支架临床疗效有目共睹，其医疗应用极大改善了患者的生命质量。但是临床中一个典型的问题就是血管再狭窄，普通金属裸支架在植入后会出现支架内血管再堵塞的现象，其发生概率最高达到40％以上，并且再狭窄后的血管修复将比较困难。所以，在支架制造中，将金属表面涂以含治疗功能的药物薄膜逐渐受到重视，并在医疗实践中被采用。多年前，美国专利5697967就公布了这样的一种药物负载支架。美国专利9204982公布了对这类支架进行药物注入的方法。将雷帕素负载在裸支架上应用在血管中，可以有效抑制再狭窄的发生。国外还有在研究紫杉醇等药物的药物涂层支架。
将药物负载在支架上是一个看似容易但实际上有技术要求的任务。一般操作人员很容易的想到：如果把一般需要的药物涂覆在支架上应该起到消毒抗菌或一定的治疗效果，但是实际上却远没有这么简单，其关键是释放速度。从数学上简单考虑药物溶解的模型就可以看出：可负载的药物涂层一般在数十微米厚度的水平，在固定的溶解度下，特别是血管中血液快速流动，等于药物永远面对一个自身的不饱和溶液，药物的释放会十分快速。典型的，药物会在两个小时的时间段释放80％以上，这原小于受损血管愈合所需的时间，所以这种简单处理的涂层最多可以起一点简单的消毒作用，对于血管的实际修复和再狭窄抑制帮助不大。所以，国际上研究者一直在采用各种药物载体或者其他物理、化学的技术组织药物涂层制成支架以期达到药物缓释的效果。比如采用环氧树脂将雷帕素组织制成涂层涂在支架上可以起到雷帕素在血液中缓释的作用。再比如，国外科学家将金属网加工成多孔的形式(比如生长一层多孔氧化铝，并将药物填充进去)制成支架支撑血管，可以起到缓释的作用，支架上药物在血液中释放的时间达到十天以上，也已经到了临床测试的阶段。具有限制再狭窄功效的载药血管支架目前在临床上已经广泛采用，抑制了修复中再狭窄的发生。
这种支架中药物的缓释往往依赖于药物分子与载体分子的特殊性质。环糊精是一种常用的有机分子，而且在食品药品中已经被使用。如图1，其分子结构中含有环状结构，可以束缚药物的分子形成相对稳定的状态，在水溶液中药物分子又可以被无损的受限制的释放。另外，目前流行的药物负载支架以单种功能药物为主。因其分子中含环的数量，有α、β、γ等多种环糊精，部分具有控制血糖和防止败血症的作用(欧洲专利EP1747785)。文献中已经有利用环糊精包裹多种药物分子协助药物缓释的结果(ChemPhramBull,52,900-915(2004))。这被认为是有临床前景的。目前现有技术发现：采用了防狭窄药物的血管支架仍然有一定的修复失败概率，这被认为与待修复区域局部的血脂、血糖环境有关。
三、发明内容
本发明目的是，提出采用环糊精负载药物分子形成复合涂层，并将该复合涂层应用在裸合金支架上形成复合药物涂层血管支架，而且可以负载多种药物形成协同作用。比如除已有的抑制再狭窄药物以外，还可以引入控制血脂、血糖的组分，结合环糊精分子本身的作用，达到控制局部血管微环境，从而改善血管愈合的效果。采用环糊精还有可能造成多种药物协同作用的疗效。尤其是防狭窄药物的血管支架的应用。
本发明技术方案是：一种含复合药物涂层的血管支架，即采用新型复合药物涂层功能化的血管支架，血管支架基体为常用的裸金属或合金(或其其他支架材料)，在血管支架金属网处涂覆有复合药物涂层。血管支架固定在导引装置上应用。
所述复合药物涂层是一种基于环糊精组织的单种或者多种药物涂层。复合药物涂层的组织采用γ型环糊精会有更好效果。
一种采用新型复合药物涂层功能化的血管支架，其复合涂层中环糊精分子和药物的摩尔比，不低于2:1，不高于20：1。
复合药物涂层中可以含有多种功能组分的药物，比如降脂功能，限制狭窄、控血压、限制血液组分等，比如可以是辛伐他汀、阿司匹林、乌拉地儿、紫杉醇、雷帕素等，比如辛伐他汀/阿司匹林混合涂层。药物协同作用，可以取得单独采用一种药物更好的疗效。辛伐他汀、阿司匹林与雷帕素三种药物具有更好的疗效。药物的量指三种混和药物的量。
一种采用新型复合药物涂层功能化的血管支架，其涂层中的药物可以在血管环境中缓慢的释放，达到数星期的时间。
一种含复合药物涂层的血管支架的制备方法，其典型的复合药物涂层液体制造工艺是，将环糊精溶于乙醇和水的混合液中，之后将药物溶于其中并加热到40—80℃，并保持一段时间直至均匀。环糊精的质量数是药物质量的2～20倍之间。
一种采用新型复合药物涂层功能化的血管支架，其典型制造工艺是，将金属支架基体固定并保持在60±10℃，将复合药物涂层液体滴在支架基体上烘干，反复3-10次滴至涂层厚度达到10-100微米；或者将金属支架浸泡在复合药物涂层液体中，后烘干形成涂层，反复多次至需要的涂层厚度。
将支架基本固定在球囊和导引装置上形成完整的手术产品——复合涂层支架。
有益效果：本发明是一种采用新型复合药物涂层功能化的血管支架。该新型复合涂层是一种基于环糊精组织的单种或者多种药物涂层，尤其是采用γ环糊精，该药物可以是具有抑制再狭窄、控制血脂、血糖、血压或控制血压组分的药物，比如辛伐他汀、阿司匹林、乌拉地儿、紫杉醇、雷帕素等血液药物中的一种或者多种。本支架送入血管中可以观察到药物的缓慢释放，达到数星期的时间，并具有改善支架周围血管微环境的作用，实现更好的血管愈合并保持术后畅通。本发明得到涂层可以组织多种功能药物，并实现药物在血液中的长效缓释，已在动物实验中验证其辅助血管修复的效果。
四、附图说明
图1环糊精分子典型构形；
图2含复合涂层血管支架照片(长度尺度25mm)；
图3复合涂层支架的药物缓释效果，x轴为时间，y轴为已经释放的药物含量，1为100％；
图4猪后腿血管的修复效果对比，(a)：对照组，(b)：本发明效果图。
五、具体实施方式
举例说明本发明及有益效果。
将1mmolγ-环糊精溶入酒精/水混合液中，并加入0.05mmol阿司匹林，将溶液加热到60度并搅拌，静置15分钟。再加入0.05mmol辛伐他汀，将溶液加热到60度并搅拌，静置15分钟。
将裸支架金属丝网放置在80摄氏度的热盘上，将溶液反复滴在支架上，累积涂层厚度100微米。烘干24小时。
将该金属网固定在球囊和导引装置上形成支架系统组件。
一个典型的涂层液体的制造工艺是，将环糊精溶于酒精和水的混合液中，之后将药物溶于其中并加热到40—80摄氏度，并保持1个小时以上。环糊精的分子数是药物分子数的2～20倍之间。
一个典型的复合涂层支架的制造工艺是，将金属支架固定并保持在60℃，将涂层液体滴在支架上烘干，反复滴至涂层厚度达到10～100微米或者将金属支架浸泡在液体中，后烘干形成涂层。将支架固定在球囊和导引装置上形成复合涂层支架。
图2插图是我们制得的一个血管支架，利用拉曼光谱测量涂层的成分，从拉曼光谱、红外鉴定结果可以看出，被包裹的分子仍然能表现出阿司匹林和辛伐他汀的拉曼特征，这支持我们分子药物的药效可能被有效保持。
将支架浸泡在生理盐水中，利用紫外分光光度计测量了辛伐他汀的药物释放量。在图3中我们也展示了药物直接涂抹在支架上药物释放的效果。我们可以看出药物涂抹裸支架上分子仅两小时就释放了所有药量的80％(浅色最短的曲线)。我们处理好的支架如蓝色、黑色的曲线(深色)，经过1个星期以上才释放药量的80％。这指示我们的方法可以保证药物的缓释，星期级的保持接近了血管愈合的典型时间。阿司匹林的测量也展示了类似的结果。
将裸支架和本复合涂层支架植入实验用猪后腿血管上，饲养足月，检查支架处血管生长情况。发现，裸支架使用后会有一半概率出现血流堵塞的情况，堵塞后的血管造影照片如图4(a)所示。而采用了本方法涂覆药物的支架在目前无1例出现堵塞，会保证血流的通畅图4(b)，比单独采用采用一种药物的堵塞概率更低。
虽然本发明已以实施方式揭露如上，然其并非用以限定本发明，任何本领域普通技术人员，在不脱离本发明的精神和范围内，当可作各种的更动与润饰，因此本发明的保护范围当视后附的权利要求书所界定的范围为准。
Claims (8)
1.一种含复合药物涂层的血管支架，其特征是血管支架基体为常用的裸金属或合金制备成金属网，在血管支架金属网涂覆有复合药物涂层；所述复合药物涂层是一种基于环糊精组织的单种或者多种药物涂层；复合涂层中环糊精分子和药物的摩尔比，不低于2:1，不高于20：1。
2.根据权利要求1所述的含复合药物涂层的血管支架，其特征是复合药物涂层的组织采用γ型环糊精。
3.根据权利要求1所述的含复合药物涂层的血管支架，其特征是复合药物涂层中为溶血栓、降脂，限制狭窄、控血压、限制血液组分的药物的两种或多种。
4.根据权利要求3所述的含复合药物涂层的血管支架，其特征是复合药物涂层中辛伐他汀、阿司匹林、乌拉地儿、紫杉醇、雷帕素采用两种至三种混和药物。
5.根据权利要求4所述的含复合药物涂层的血管支架，其特征是复合药物为辛伐他汀+阿司匹林两种，或辛伐他汀、阿司匹林与雷帕素三种药物。
6.一种根据权利要求1-5之一所述的含复合药物涂层的血管支架的制备方法，其特征是将环糊精溶于乙醇和水的混合液中，之后将药物溶于其中并加热到40—80℃，并保持至液体均匀；环糊精的质量数是药物质量的2～20倍之间。
7.根据权利要求6所述的含复合药物涂层的血管支架的制备方法，其特征是将金属支架基体固定并保持在60±10℃，将复合药物涂层液体滴在支架基体上烘干，反复多次滴至涂层厚度达到10-100微米。
8.根据权利要求6所述的含复合药物涂层的血管支架的制备方法，其特征是将金属支架浸泡在复合药物涂层液体中，后烘干形成涂层，反复多次至需要的涂层厚度。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610085845.4A CN105561406A (zh) | 2016-02-15 | 2016-02-15 | 一种含复合药物涂层的血管支架 |
| PCT/CN2016/107020 WO2017140152A1 (zh) | 2016-02-15 | 2016-11-24 | 一种含复合药物涂层的血管支架 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610085845.4A CN105561406A (zh) | 2016-02-15 | 2016-02-15 | 一种含复合药物涂层的血管支架 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105561406A true CN105561406A (zh) | 2016-05-11 |
Family
ID=55872395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610085845.4A Pending CN105561406A (zh) | 2016-02-15 | 2016-02-15 | 一种含复合药物涂层的血管支架 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN105561406A (zh) |
| WO (1) | WO2017140152A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017140152A1 (zh) * | 2016-02-15 | 2017-08-24 | 丹阳纳瑞康纳米科技有限公司 | 一种含复合药物涂层的血管支架 |
| CN114521996A (zh) * | 2022-01-19 | 2022-05-24 | 株洲茂物医疗科技有限公司 | 一种复合药物支架及其制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1533813A (zh) * | 2003-03-28 | 2004-10-06 | 微创医疗器械〔上海〕有限公司 | 预防/治疗皮腔内冠状动脉成形术后再狭窄的药物涂层支架 |
| CN1568166A (zh) * | 2001-10-15 | 2005-01-19 | 荷姆泰克股份有限公司 | 预防再狭窄的涂层支架 |
| US20070224116A1 (en) * | 2006-03-27 | 2007-09-27 | Chandru Chandrasekaran | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
| CN101636187A (zh) * | 2007-01-30 | 2010-01-27 | 汉莫堤克股份有限公司 | 生物可降解性血管支持器 |
| CN105031748A (zh) * | 2015-08-03 | 2015-11-11 | 丹阳纳瑞康纳米科技有限公司 | 一种可控缓释的阿司匹林金属复合材料制备 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001240024A1 (en) * | 2000-03-31 | 2001-10-15 | Supergen, Inc. | Camptothecin complexes |
| FR2877846B1 (fr) * | 2004-11-15 | 2008-12-05 | Univ Lille Sciences Tech | Biomateriaux porteurs de cyclodextrines aux proprietes d'absorption ameliorees et de liberation progressive et retardee de molecules therapeutiques |
| US20070298069A1 (en) * | 2006-06-26 | 2007-12-27 | Boston Scientific Scimed, Inc. | Medical devices for release of low solubility therapeutic agents |
| FR2908047B1 (fr) * | 2006-11-06 | 2009-10-30 | Perouse Soc Par Actions Simpli | Procede de preparation d'une prothese tubulaire implantable a partir d'un corps tubulaire de base en materiau poreux, et prothese associee |
| ES2310122B1 (es) * | 2007-04-20 | 2009-10-30 | Instituto Cientifico Y Tecnologico De Navarra, S.A | Nanoparticulas que comprenden una ciclodextrina y una molecula biologicamente activa y sus aplicaciones. |
| US10045937B2 (en) * | 2009-06-03 | 2018-08-14 | Case Western Reserve University | Therapeutic agent delivery system and method |
| CN105561406A (zh) * | 2016-02-15 | 2016-05-11 | 丹阳纳瑞康纳米科技有限公司 | 一种含复合药物涂层的血管支架 |
-
2016
- 2016-02-15 CN CN201610085845.4A patent/CN105561406A/zh active Pending
- 2016-11-24 WO PCT/CN2016/107020 patent/WO2017140152A1/zh not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1568166A (zh) * | 2001-10-15 | 2005-01-19 | 荷姆泰克股份有限公司 | 预防再狭窄的涂层支架 |
| CN1533813A (zh) * | 2003-03-28 | 2004-10-06 | 微创医疗器械〔上海〕有限公司 | 预防/治疗皮腔内冠状动脉成形术后再狭窄的药物涂层支架 |
| US20070224116A1 (en) * | 2006-03-27 | 2007-09-27 | Chandru Chandrasekaran | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
| CN101636187A (zh) * | 2007-01-30 | 2010-01-27 | 汉莫堤克股份有限公司 | 生物可降解性血管支持器 |
| CN105031748A (zh) * | 2015-08-03 | 2015-11-11 | 丹阳纳瑞康纳米科技有限公司 | 一种可控缓释的阿司匹林金属复合材料制备 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017140152A1 (zh) * | 2016-02-15 | 2017-08-24 | 丹阳纳瑞康纳米科技有限公司 | 一种含复合药物涂层的血管支架 |
| CN114521996A (zh) * | 2022-01-19 | 2022-05-24 | 株洲茂物医疗科技有限公司 | 一种复合药物支架及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017140152A1 (zh) | 2017-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4868565B2 (ja) | 血管用ステント | |
| EP1518570B1 (en) | Preparation process for a laminated drug-polymer coated stent with dipped and cured layers | |
| US10688190B2 (en) | Medication system | |
| CN102958544B (zh) | 用于积分或切割气囊导管的改进涂层制剂 | |
| US10596211B2 (en) | Medication dispensing system | |
| CA2927238C (en) | Methods and systems for inhibiting foreign-body responses in diabetic patients | |
| KR20080073328A (ko) | 약제 방출 제어 조성물 및 약제 방출성 의료 기구 | |
| JP2006500996A (ja) | 溶出性生体適合性移植可能医療器具を介してマイトマイシンを送達するための装置および方法 | |
| US10675314B2 (en) | Medication dispensing system | |
| KR20030029934A (ko) | 스텐트 | |
| BR112012026686B1 (pt) | fórmulas melhoradas para dispositivos médicos revestidos com droga | |
| CN104740692A (zh) | 一种骨内固定植入物及其制备方法 | |
| Münchow et al. | Development of an antibacterial and anti-metalloproteinase dental adhesive for long-lasting resin composite restorations | |
| US20250195212A1 (en) | Method for generating in-situ vascular stent and photocurable drug-loaded balloon catheter for implementing the method | |
| CN105561406A (zh) | 一种含复合药物涂层的血管支架 | |
| CN101711710B (zh) | 药物洗脱支架及其制备方法 | |
| CN107198792A (zh) | 生物可降解的支撑装置 | |
| CN101049518A (zh) | 血管支架的表面改性涂层及其制备方法 | |
| EP4400126B1 (en) | Drug-loaded balloon and preparation method therefor | |
| US20090112307A1 (en) | Stent having a base body of a bioinert metallic implant material | |
| CN101703428A (zh) | 一种具有防再狭窄涂层的血管支架及其制备方法 | |
| FR3053892A1 (fr) | Pansement permettant la liberation controlee et prolongee de la metformine | |
| CA2947421A1 (en) | Endodontic treatment with long term drug delivery system | |
| JP2016510608A (ja) | 大環状トリエンラクトン薬物および最少量の抗酸化安定剤を含む埋込型医療機器ならびに製造方法 | |
| CN113730644B (zh) | 一种具有凝胶涂层的缝合线及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160511 |
|
| RJ01 | Rejection of invention patent application after publication |