WO2013044603A1 - 一种介入医疗器械及其制备方法 - Google Patents

一种介入医疗器械及其制备方法 Download PDF

Info

Publication number
WO2013044603A1
WO2013044603A1 PCT/CN2012/070400 CN2012070400W WO2013044603A1 WO 2013044603 A1 WO2013044603 A1 WO 2013044603A1 CN 2012070400 W CN2012070400 W CN 2012070400W WO 2013044603 A1 WO2013044603 A1 WO 2013044603A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug
stent
medical device
stent body
proliferation
Prior art date
Application number
PCT/CN2012/070400
Other languages
English (en)
French (fr)
Inventor
张大东
蔡煦
乐承筠
李俊菲
胡燕
黄鹏
唐智荣
罗七一
Original Assignee
上海微创医疗器械（集团）有限公司
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 上海微创医疗器械（集团）有限公司 filed Critical 上海微创医疗器械（集团）有限公司
Priority to BR112014007580A priority Critical patent/BR112014007580A2/pt
Priority to EP12834752.3A priority patent/EP2762110A4/en
Priority to US14/348,857 priority patent/US20140248327A1/en
Priority to IN2578CHN2014 priority patent/IN2014CN02578A/en
Publication of WO2013044603A1 publication Critical patent/WO2013044603A1/zh
Priority to US14/677,741 priority patent/US9433709B2/en

Links

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
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • 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
    • A61L31/146—Porous materials, e.g. foams or sponges
    • 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
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices

Definitions

  • the present application relates to the field of medical device technology, and in particular to an interventional medical device containing a drug and a preparation method thereof.
  • Background technique
  • a drug-coated coating is applied to the stent implanted in the human body.
  • Most of the drug stents currently used are drugs that inhibit the intimal or mesenteric proliferation, such as: rapamycin, paclitaxel, and derivatives thereof.
  • the stent carrying the above drugs is implanted into the human body, the stent will be Drugs that inhibit the intimal or medial hyperplasia are continuously released to the vessel wall to reduce the incidence of in-stent restenosis.
  • intravascular restenosis is not only related to intimal or mesenteric hyperplasia after vascular injury, but also related to vascular remodeling, and vascular remodeling is the main factor in the formation of in-stent restenosis, which may account for restenosis. Seventy percent of the causes, and endocardial or medial hyperplasia accounted for only 30% of the possible causes of restenosis.
  • existing drug stents that inhibit intimal or medial hyperplasia do not minimize the incidence of in-stent restenosis.
  • existing drugs that inhibit the intimal or mesenteric proliferation such as rapamycin, paclitaxel, and their derivatives, inhibit the growth of endothelial cells, leading to delayed endothelialization, and may not be fully endothelialized. causess late thrombosis.
  • the embodiments of the present application provide an interventional medical device and a preparation method thereof, which can inhibit the proliferation of the outer membrane fibroblasts after being implanted into the human body, promote the compensatory expansion of the blood vessels, and can also inhibit the blood vessels. Intimal hyperplasia to reduce the incidence of in-stent restenosis.
  • An interventional medical device comprising: a stent body, the surface of the stent body is provided with a drug
  • the release structure, the drug in the drug release structure is a drug that inhibits proliferation of outer membrane fibroblasts and a drug that inhibits proliferation of endometrial and/or smooth muscle cells.
  • the drug releasing structure is a dense mixed layer of a high molecular polymer and a drug which inhibits proliferation of outer membrane fibroblasts and a drug which inhibits proliferation of endometrial and/or smooth muscle cells.
  • the high molecular polymer comprises: polylactic acid, polyethylene glycol, styrene butene copolymer, polycaprolactone, polybutyl methacrylate, polyethyl methacrylate, ethyl acetate ethyl acetate , polyurethane, polyvinylpyrrolidone, poly-tartrate, silk fibroin, gelatin, chitin and/or hyaluronic acid.
  • the drug release structure is a microporous coating structure formed on the surface of the stent body or formed on the surface of the stent body, and is contained in the microporous structure or the microporous coating structure. Into the drug.
  • the drug for inhibiting proliferation of outer membrane fibroblasts comprises at least one of tanshinone, asiaticoside, centella asiatica, ligustrazine, scutellarin, sulvastatin, and angiotensin.
  • the drug for inhibiting proliferation of endometrial and/or smooth muscle cells comprises: at least one of rapamycin and a derivative thereof, paclitaxel and a derivative thereof.
  • the stent body comprises: a coronary artery stent, an intracranial vascular stent, a peripheral vascular stent, an intraoperative stent, a heart valve stent, a biliary stent, an esophageal stent, an intestinal stent, a pancreatic duct stent, a urethral stent or a tracheal stent. .
  • a method of preparing an interventional medical device comprising:
  • the interventional medical device is obtained by drying the stent body.
  • the microporous structure is prepared on the surface of the stent body, specifically:
  • Micropores are formed on the surface of the stent body by anodization, micro-arc oxidation, and/or chemical etching.
  • the microporous structure is prepared on the surface of the stent body, specifically:
  • a coating having micropores is prepared on the surface of the stent body.
  • the drug in the formulated solution is loaded into the microporous structure, specifically: loading the drug in the solution by ultrasonic spraying, air spraying and/or dip coating In the micropore structure.
  • a method of preparing an interventional medical device comprising:
  • a mixed solution of a drug and a high molecular polymer for inhibiting proliferation of outer membrane fibroblasts a mixed solution of a drug and a high molecular polymer for inhibiting proliferation of endometrial and/or smooth muscle cells, or a membrane inhibiting proliferation of outer membrane fibroblasts a drug and a mixed solution of a drug and a high molecular polymer that inhibits proliferation of endometrial and/or smooth muscle cells;
  • a mixed solution of a drug and a high molecular polymer which inhibits proliferation of outer membrane fibroblasts, and a mixed solution of a drug and a high molecular polymer which inhibit proliferation of endometrial and/or smooth muscle cells are sequentially coated on the surface of the stent body, or may be inhibited a drug for proliferating outer membrane fibroblasts and a mixed solution of a drug and a high molecular polymer for inhibiting proliferation of endometrial and/or smooth muscle cells are coated on the surface of the stent body;
  • the interventional medical device is obtained by drying the stent body.
  • the coating comprises: ultrasonic spraying, air spraying, and/or dip coating.
  • the drug carried on the outer membrane fibroblast proliferation can be slowly released into the blood vessel wall cells in contact with the stent body, and further It can inhibit the proliferation of adventitial fibroblasts, inhibit the proliferation of fibroblasts and play a role in vascular remodeling, which is beneficial to the compensatory expansion of damaged vessels, thereby reducing the incidence of in-stent restenosis;
  • Membrane and/or smooth muscle cell proliferation drugs can also inhibit the intimal hyperplasia to a certain extent, and the two drugs work together to greatly reduce the incidence of in-stent restenosis.
  • the medical device provided by the embodiments of the present application not only has a lower inhibition rate on endothelial cells, but also promotes endothelial cells. Growth, speeding up the process of endothelialization.
  • FIG. 1 is a schematic structural view of a specific embodiment of an interventional medical device provided by the present application
  • 2 is a schematic structural view of another embodiment of the interventional medical device provided by the present application
  • FIG. 3 is a schematic structural view of another embodiment of the interventional medical device provided by the present application
  • FIG. 5 is another process flow of the preparation method of the interventional medical device provided by the present application
  • FIG. 6 is another process flow of the preparation method of the interventional medical device provided by the present application
  • 7 is another process flow of the method for preparing an interventional medical device provided by the present application.
  • An embodiment of the present application provides an interventional medical device, comprising: a stent body, wherein: a drug release structure is disposed on a surface of the stent body, and the drug in the drug release structure is a drug for inhibiting proliferation of outer membrane fibroblasts and inhibiting Membrane and/or smooth muscle cell proliferation drugs.
  • FIG. 1 is a schematic structural view of a specific embodiment of an interventional medical device provided by the present application.
  • 1 is a stent body
  • 2 is a drug # discharge coating
  • a drug release coating 2 is coated on the outer surface of the stent body 1, wherein:
  • the stent body 1 may be a coronary artery stent, an intracranial vascular stent, a peripheral vascular stent, an intraoperative stent, a heart valve stent, a biliary stent, an esophageal stent, an intestinal stent, a pancreatic duct stent, a urethral stent or a tracheal stent, and the stent body
  • the material of 1 may be stainless steel, cobalt-based alloy, nickel-based alloy, titanium alloy, degradable magnesium alloy or polymer material with good biocompatibility and mechanical properties.
  • the drug release coating 2 is a dense mixed layer formed of a high molecular polymer and a drug which inhibits proliferation of outer membrane fibroblasts and a drug which inhibits proliferation of endometrial and/or smooth muscle cells, that is, the drug release coating 2 as a carrier, which can make
  • the surface of the stent body 1 carries a drug.
  • the drug for inhibiting the proliferation of the outer membrane into the sputum cell comprises at least one of tanshinone, asiaticoside, hydroxysalicum, ligustrazine, scutellarin, sulvastatin, angiotensin, in the embodiment of the present application.
  • the drug which inhibits proliferation of endometrial and/or smooth muscle cells may be at least one of rapamycin and its derivatives, paclitaxel and derivatives thereof, preferably rapamycin.
  • the high molecular polymer in the drug release coating 2 may be a high molecular polymer having biocompatibility and controlled release properties, such as polylactic acid, polyethylene glycol, styrene butene copolymer, polycaprolactone.
  • polybutyl methacrylate polyethyl methacrylate, ethyl acetate ethyl acetate, polyurethane, polyvinylpyrrolidone, polycholine, silk fibroin, gelatin, chitin and/or hyaluronic acid.
  • Centella asiatica is a total sputum extracted from Centella asiatica, and it can inhibit the pathogenesis of TGF-
  • asiaticoside also promotes endothelial cell growth and accelerates the endothelialization process.
  • PCI classification number R541.4 article number: 1671-8259 (2005) 05-0477-03.
  • the interventional medical device provided by the embodiment of the present application can promote the growth of endothelial cells and accelerate the progress of endothelialization as compared with the prior art drug stents using rapamycin, paclitaxel and derivatives thereof.
  • FIG. 2 is a schematic structural view of another embodiment of the interventional medical device provided by the present application.
  • 1 is a stent body
  • 3 is a micropore formed on the surface of the stent.
  • the drug releasing structure is a micropore 3 which can be obtained by oxidizing or etching the surface of the stent body 1.
  • the drug can be loaded in the micropores 3, so that the surface of the stent body 1 can carry the drug.
  • FIG. 3 is a schematic structural view of still another embodiment of the interventional medical device provided by the present application.
  • the hole 3 is obtained by directly oxidizing or etching the surface of the stent body 1.
  • a layer can be prepared on the surface of the stent body 1.
  • FIG. 4 is a process flow of a method for preparing an interventional medical device provided by the present application.
  • the stent body is exemplified by a metal stent
  • the preparation method of the interventional medical device includes:
  • Step S101 Cleaning the stent body and drying.
  • Step S102 preparing micropores on the surface of the stent body.
  • Electroporation and/or chemical etching are used to form micropores on the surface of the stent body, wherein electro-chemical corrosion includes anodization, micro-arc oxidation, and the like. Through this step, micropores can be formed on the surface of the stent body, and a schematic structural view thereof is shown in FIG.
  • Step S103 A solution containing a drug that inhibits proliferation of outer membrane fibroblasts and a drug that inhibits proliferation of endometrial and/or smooth muscle cells is prepared.
  • the drug for inhibiting the proliferation of the outer membrane fibroblast is asiaticoside
  • the drug for inhibiting the proliferation of the inner membrane and/or the smooth muscle cell is rapamycin
  • the asiaticoside and the rapa are formulated.
  • 10 mg of rapamycin and 30 mg of asiaticoside can be dissolved in 10 ml of ethanol solution, dissolved and uniformly mixed.
  • Step S104 Loading the drug in the prepared solution into the pore of the stent body.
  • the stent body having the microporous surface obtained in the step S102 is immersed in the solution prepared in the step S103, so that the drug in the solution can be loaded in the micropores on the surface of the stent body.
  • Step S105 drying the stent body to obtain an interventional medical device.
  • FIG. 5 is another process flow of the method for preparing an interventional medical device provided by the present application.
  • the method for preparing the interventional medical device includes: Step S201: The holder body is cleaned and dried.
  • Step S202 preparing a coating having micropores on the surface of the stent body.
  • the specific operation procedure is as follows: the silk fibroin solution is covered on the surface of the stent body, denatured by heat or chemical reagent, and then infiltrated with pure water, then frozen and warmed to dry, and a coating having a microporous structure is formed on the surface of the stent body.
  • Floor the surface of the stent body.
  • Step S203 A solution containing a drug that inhibits proliferation of outer membrane fibroblasts and a drug that inhibits proliferation of endometrial and/or smooth muscle cells is prepared.
  • the drug for inhibiting the proliferation of the outer membrane fibroblast is asiaticoside
  • the drug for inhibiting the proliferation of the inner membrane and/or the smooth muscle cell is rapamycin
  • 10 mg may be used. Rapamycin and 50 mg of asiaticoside were dissolved in 10 ml of ethanol solution, dissolved and mixed well.
  • Step S204 The drug in the formulated solution is loaded into the micropores of the coating on the surface of the stent body.
  • the stent body having the microporous coating on the surface obtained in the step S202 is immersed in the prepared solution so that the drug in the solution can be loaded in the micropores of the surface of the stent body.
  • Step S205 drying the stent body to obtain an interventional medical device.
  • FIG. 6 is still another process flow of the method for preparing an interventional medical device provided by the present application.
  • the method for preparing the interventional medical device includes: Step S301: Cleaning the stent body and drying.
  • Step S302 A drug for inhibiting proliferation of outer membrane fibroblasts and a mixed solution of a drug and a high molecular polymer which inhibit proliferation of endometrial and/or smooth muscle cells are prepared.
  • the high molecular polymer is selected to be polylactic acid
  • the drug for inhibiting the proliferation of the outer membrane fibroblast is preferably asiaticoside
  • the drug for inhibiting the proliferation of the inner membrane and/or smooth muscle cells is preferably rapamycin.
  • a mixed solution of polylactic acid, asiaticoside and rapamycin is prepared, wherein: the ratio of asiaticoside to rapamycin is 2:1 ⁇ 5: 1, and the ratio of polylactic acid to asiaticoside is 1 : 1 to 5 : 1.
  • 1 Omg of rapamycin and 30 mg of asiaticoside and 100 mg of polylactic acid may be added to 1 Oml of tetrahydrofuran, fully dissolved, and uniformly mixed.
  • Step S303 The mixed solution is coated on the surface of the stent body.
  • the steps may be performed by ultrasonic spraying, air spraying or dip coating.
  • the mixed solution prepared in 302 was applied to the stent body.
  • Step S304 drying the stent body to obtain an interventional medical device.
  • a mixed solution of two drugs with a high molecular polymer is prepared.
  • the two drugs can be separately mixed with the high molecular polymer, and then the mixed solution of the two drugs is sequentially used. They are respectively coated on the surface of the stent body.
  • FIG. 7 is still another process flow of the method for preparing an interventional medical device provided by the present application.
  • the method for preparing the interventional medical device includes: Step S401: Cleaning the stent body and drying.
  • Step S402 separately preparing a mixed solution of a drug and a high molecular polymer for inhibiting proliferation of outer membrane fibroblasts, and a mixed solution of a drug and a high molecular polymer for inhibiting proliferation of endometrial and/or smooth muscle cells.
  • the high molecular polymer is selected as polylactic acid
  • the drug for inhibiting the proliferation of the outer membrane fibroblast is asiaticoside
  • the drug for inhibiting the proliferation of the intima and/or smooth muscle cells is rapamycin.
  • Step S403 The two mixed solutions obtained are sequentially coated on the surface of the stent body.
  • the asiaticoside/polylactic acid solution may be first applied to the surface of the stent body; then the sprayed stent body is placed open for 4 hours to make the surface dry; then rapamycin/poly A lactic acid solution is applied to the surface of the dried stent body.
  • Step S404 drying the stent body to obtain an interventional medical device.

Abstract

一种介入医疗器械及其制备方法，该介入医疗器械包括：支架本体(1)，所述支架本体(1)的表面设置有药物释放结构(3)，所述药物释放结构(3)中的药物为抑制外膜成纤维细胞增殖的药物及抑制内膜和/或平滑肌细胞增殖的药物。该介入医疗器械在使用时，当植入到人体后，其上携带的抑制外膜成纤维细胞增殖的药物可以促进血管的代偿性扩张，同时其上携带的抑制内膜和/或平滑肌细胞增殖的药物可以在一定程度上抑制血管内膜增生，两种药物共同作用，大大降低了支架内再狭窄的发生率。

Description

一种介入医疗器械及其制备方法
技术领域
本申请涉及医疗器械技术领域， 特别是涉及一种含有药物的介入医疗器 械及其制备方法。 背景技术
近年来， 为了避免介入治疗后支架内再狭窄的发生， 在植入人体的支架 上会涂覆有药物涂层。 目前应用的药物支架大多携带的药物为抑制血管内膜 或中膜增生的药物， 例如： 雷帕霉素、 紫杉醇及其衍生物等， 当携带有上述 药物的支架植入人体后， 支架就会持续向血管壁释放抑制血管内膜或中膜增 生的药物， 以降低支架内再狹窄的发生率。
研究表明， 血管内再狭窄的形成机制不仅与血管损伤后内膜或中膜增生 有关， 而且还与血管重构有关， 并且血管重构是支架内再狹窄形成的主要因 素， 约占再狹窄可能原因的七成， 而血管内膜或中膜增生仅占再狹窄可能原 因的三成。
因此现有的抑制内膜或中膜增生的药物支架无法最大程度地降低支架内 再狭窄的发生率。 另外， 现有的抑制血管内膜或中膜增生的药物如雷帕霉素、 紫杉醇及其衍生物会抑制内皮细胞的生长， 导致血管内皮化延迟的问题， 而 血管不能完全内皮化则可能会引起晚期血栓。
发明内容
有鉴于此， 本申请实施例提供一种介入医疗器械及其制备方法， 该介入 医疗器械植入人体后通过抑制外膜成纤维细胞的增殖， 促进血管的代偿性扩 张， 并且还可以抑制血管内膜增生， 以降低支架内再狹窄的发生率。
为了实现上述目的， 本申请实施例提供的技术方案如下：
一种介入医疗器械， 包括： 支架本体， 所述支架本体的表面设置有药物 释放结构， 所述药物释放结构中的药物为抑制外膜成纤维细胞增殖的药物及 抑制内膜和 /或平滑肌细胞增殖的药物。
优选地， 所述药物释放结构为高分子聚合物与抑制外膜成纤维细胞增殖 的药物及抑制内膜和 /或平滑肌细胞增殖的药物形成的致密混合层。
优选地， 所述高分子聚合物包括： 聚乳酸、 聚乙二醇、 苯乙烯丁烯共聚 物、 聚己内酯、 聚曱基丙烯酸丁酯、 聚曱基丙烯酸乙酯、 聚乙烯乙酸乙酯、 聚氨酯、 聚乙烯基吡咯烷酮、 聚磚酸胆碱、 蚕丝蛋白、 明胶、 曱壳素和 /或透 明质酸。
优选地， 所述药物释放结构为在所述支架本体表面制备^^孔结构或者在 所述支架本体表面形成的微孔涂层结构， 并在所述微孔结构或微孔涂层结构 中载入药物。
优选地， 所述抑制外膜成纤维细胞增殖的药物包括丹参酮、 积雪草苷、 羟基积雪草甙、 川芎嗪、 血竭素、 舒伐他汀、 血管紧张素中的至少一种。
优选地， 所述抑制内膜和 /或平滑肌细胞增殖的药物包括： 雷帕霉素及其 衍生物、 紫杉醇及其衍生物中的至少一种。
优选地， 所述支架本体包括： 冠状动脉血管支架、 颅内血管支架、 外周 血管支架、 术中支架、 心脏瓣膜支架、 胆道支架、 食道支架、 肠道支架、 胰 管支架、 尿道支架或气管支架。
一种介入医疗器械的制备方法， 包括：
在支架本体的表面制备微孔结构；
配制含有抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌细胞增 殖的药物的溶液；
将配制的所述溶液中的药物装载在所述微孔结构中；
将所述支架本体干燥后得到所述介入医疗器械。
优选地， 在支架本体的表面制备微孔结构， 具体为：
采用阳极氧化、微弧氧化和 /或化学腐蚀的方法在支架本体表面形成微孔。 优选地， 在支架本体的表面制备微孔结构， 具体为：
在所述支架本体的表面上制备具有微孔的涂层。
优选地， 将配制的所述溶液中的药物装载在所述微孔结构中， 具体为： 采用超声喷涂、 空气喷涂和 /或浸涂的方式将所述溶液中的药物装载在所 述微孔结构中。
一种介入医疗器械的制备方法， 包括：
分别配制抑制外膜成纤维细胞增殖的药物与高分子聚合物的混合溶液， 以及抑制内膜和 /或平滑肌细胞增殖的药物与高分子聚合物的混合溶液， 或者 配制抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌细胞增殖的药物 与高分子聚合物的混合溶液；
将抑制外膜成纤维细胞增殖的药物与高分子聚合物的混合溶液， 以及抑 制内膜和 /或平滑肌细胞增殖的药物与高分子聚合物的混合溶液依次涂覆在支 架本体表面， 或者将抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌 细胞增殖的药物与高分子聚合物的混合溶液涂覆在支架本体表面；
将所述支架本体干燥后得到所述介入医疗器械。
优选地， 所述涂覆包括： 超声喷涂、 空气喷涂和 /或浸涂。
由以上技术方案可见， 该介入医疗器械在使用时， 当植入到人体后， 其 上携带的抑制外膜成纤维细胞增殖的药物可以緩慢释放到与支架本体相接触 的血管壁细胞中， 进而可以抑制外膜成纤维细胞的增殖， 使成纤维细胞增殖 受阻而在血管重构中发挥作用， 有利于受损血管的代偿性扩张， 从而能够降 低支架内再狭窄的发生率； 同时抑制内膜和 /或平滑肌细胞增殖的药物还可以 在一定程度上抑制血管内膜增生， 两种药物共同作用， 大大降低了支架内再 狭窄的发生率。
另外， 与现有采用雷帕霉素、 紫^醇及其衍生物的药物支架相比， 本申 请实施例提供的谅介入医疗器械不仅对内皮细胞的抑制率较低， 而且还会促 进内皮细胞的生长， 加快内皮化的进程。
附图说明
为了更清楚地说明本申请实施例或现有技术中的技术方案， 下面将对实 施例或现有技术描述中所需要使用的附图作简单地介绍， 显而易见地， 下面 描述中的附图仅仅是本申请中记载的一些实施例， 对于本领域普通技术人员 来讲， 在不付出创造性劳动的前提下， 还可以根据这些附图获得其他的附图。
图 1为本申请提供的介入医疗器械的一个具体实施方式的结构示意图； 图 2为本申请提供的介入医疗器械的另一个具体实施方式的结构示意图； 图 3为本申请提供的介入医疗器械的又一个具体实施方式的结构示意图； 图 4为本申请提供的介入医疗器械的制备方法的一种工艺流程； 图 5为本申请提供的介入医疗器械的制备方法的另一种工艺流程； 图 6为本申请提供的介入医疗器械的制备方法的又一种工艺流程； 图 7为本申请提供的介入医疗器械的制备方法的又一种工艺流程。 具体实施方式
为了使本技术领域的人员更好地理解本申请中的技术方案， 下面将结合 本申请实施例中的附图， 对本申请实施例中的技术方案进行清楚、 完整地描 述， 显然， 所描述的实施例仅仅是本申请一部分实施例， 而不是全部的实施 例。 基于本申请中的实施例， 本领域普通技术人员在没有做出创造性劳动前 提下所获得的所有其他实施例， 都应当属于本申请保护的范围。 本申请实施例提供了一种介入医疗器械， 包括： 支架本体， 其中： 在支 架本体的表面设置有药物释放结构， 并且药物释放结构中的药物为抑制外膜 成纤维细胞增殖的药物以及抑制内膜和 /或平滑肌细胞增殖的药物。 一个实施例：
图 1为本申请提供的介入医疗器械的一个具体实施方式结构示意图。 如图 1所示， 1为支架本体， 2为药物 #放涂层， 药物释放涂层 2涂覆在 支架本体 1的外表面上， 其中：
支架本体 1 可以为冠状动脉血管支架、 颅内血管支架、 外周血管支架、 术中支架、 心脏瓣膜支架、 胆道支架、 食道支架、 肠道支架、 胰管支架、 尿 道支架或气管支架， 并且支架本体 1 的材料可以为具有良好生物相容性及力 学特性的不锈钢、 钴基合金、 镍基合金、 钛合金、 可降解镁合金或者聚合物 材料等。
药物释放涂层 2是由高分子聚合物与抑制外膜成纤维细胞增殖的药物以 及抑制内膜和 /或平滑肌细胞增殖的药物形成的致密混合层， 即药物释放涂层 2作为载体， 可以使得支架本体 1的表面携带有药物。 抑制外膜成紆维细胞增殖的药物包括丹参酮、 积雪草苷、 羟基积雪草甙、 川芎嗪、 血竭素、 舒伐他汀、 血管紧张素中的至少一种， 在本申请实施例中， 优选为积雪草苷； 而抑制内膜和 /或平滑肌细胞增殖的药物可以为雷帕霉素及 其衍生物、 紫杉醇及其衍生物中的至少一种， 优选为雷帕霉素。 另外， 药物 释放涂层 2 中的高分子聚合物可以为具有生物相容性及控释性能的高分子聚 合物， 例如聚乳酸、 聚乙二醇、 苯乙烯丁烯共聚物、 聚己内酯、 聚曱基丙烯 酸丁酯、 聚甲基丙烯酸乙酯、 聚乙烯乙酸乙酯、 聚氨酯、 聚乙烯基吡咯兢酮、 聚 酸胆碱、 蚕丝蛋白、 明胶、 甲壳素和 /或透明质酸等。
积雪草苷是伞形科植物积雪草中提取的总甙， 积雪草苷能够通过增加抑 制性 Smad转导信号的 Smad7的表达， 抑制 TGF- |3的病理作用， 使成纤维细 胞增殖受阻而在血管重构中发挥作用， 有利于受损血管的代偿性扩张， 从而 能够抑制再狹窄。
另外， 有研究发现， 积雪草苷还具有促进内皮细胞生长， 加快内皮化进 程的作用。 具体文献请参见《积雪草苷防治 PCI术后再狹窄的实验研究》（分 类号 R541.4 文章编号： 1671-8259 ( 2005 ) 05-0477-03 )。
由此可见， 与现有的单纯采用雷帕霉素、 紫杉醇及其衍生物的药物支架 相比， 本申请实施例提供的该介入医疗器械还会促进内皮细胞的生长， 加快 内皮化的进程。 另一个实施例：
图 2为本申请提供的介入医疗器械的另一个具体实施方式结构示意图。 如图 2所示， 1为支架本体， 3为支架表面形成的微孔。 在本申请实施例 中， 药物释放结构为微孔 3， 微孔 3可以通过氧化或腐蚀支架本体 1的表面得 到。 在微孔 3 内可以装载有药物， 这样就可以使得支架本体 1的表面携带药 物 又一个实施例：
图 3为本申请提供的介入医疗器械的又一个具体实施方式结构示意图。 在图 2所示的介入医疗器械中， ：孔 3是直接氧化或腐蚀支架本体 1的 表面得到的， 而在本申请实施例中， 还可以在支架本体 1 的表面制备一层具 有微孔的涂层， 如图 3所示， 1为支架本体， 4为微孔涂层。 这样就无需氧化 或腐蚀支架本体 1的表面， 而是直接在支架本体 1的表面制备微孔涂层 4, 即 可得到装载药物的微孔。 又一个实施例：
图 4为本申请提供的介入医疗器械的制备方法的一种工艺流程。
如图 4所示， 在本申请实施例中， 支架本体以金属支架为例， 该介入医 疗器械的制备方法包括：
步骤 S101 : 清洗支架本体并干燥。
在制备介入医疗器械时， 为了避免支架本体上残留的污渍影响介入医疗 器械的质量， 需要首先对支架本体进行清洗。
步骤 S102: 在支架本体的表面制备微孔。
采用电化学腐蚀和 /或化学腐蚀的方法在支架本体表面形成微孔， 其中电 化学腐蚀包括阳极氧化、 微弧氧化等。 通过该步骤可以在支架本体的表面形 成微孔， 其结构示意图如图 2所示。
步骤 S103: 配制含有抑制外膜成纤维细胞增殖的药物以及抑制内膜和 / 或平滑肌细胞增殖的药物的溶液。
在本申请实施例中， 优选地， 抑制外膜成纤维细胞增殖的药物为积雪草 苷， 抑制内膜和 /或平滑肌细胞增殖的药物为雷帕霉素， 配制积雪草苷和雷帕 霉素药物的混合溶液。 其中积雪草苷： 雷帕霉素 =2 : 1~5 : 1。 在具体配制时， 可以将 lOmg雷帕霉素和 30mg积雪草苷溶解于 10ml的乙醇溶液中， 溶解并 混合均匀。
步骤 S104: 将配制的溶液中的药物装载在支架本体的 史孔中。
将步骤 S102中得到的表面为微孔的支架本体浸没于步骤 S103配制得到 的溶液中， 使得溶液中的药物可以装载在支架本体表面的微孔中。
步骤 S105: 将支架本体进行干燥， 即可得到介入医疗器械。 又一个实施例：
图 5为本申请提供的介入医疗器械的制备方法的另一种工艺流程。
如图 5所示， 在本申请实施例中， 该介入医疗器械的制备方法包括： 步骤 S201 : 清洗支架本体并干燥。
步骤 S202: 在支架本体的表面上制备具有微孔的涂层。
具体操作流程为： 将蚕丝蛋白溶液均勾地覆盖在支架本体的表面， 进行 热或化学试剂变性， 再用纯水浸润， 然后进行冷冻和升温干燥， 在支架本体 表面形成具有微孔结构的涂层。
步骤 S203: 配制含有抑制外膜成纤维细胞增殖的药物以及抑制内膜和 / 或平滑肌细胞增殖的药物的溶液。
在本申请实施例中， 优选地， 抑制外膜成纤维细胞增殖的药物为积雪草 苷， 抑制内膜和 /或平滑肌细胞增殖的药物为雷帕霉素， 在具体配制时， 可以 将 lOmg雷帕霉素和 50mg积雪草苷溶解于 10ml的乙醇溶液中， 溶解并混合 均匀。
步骤 S204:将配制的溶液中的药物装载在支架本体表面的涂层的微孔中。 将步骤 S202中得到的表面具有微孔涂层的支架本体浸没于配制得到的溶 液中， 使得溶液中的药物可以装载在支架本体表面涂层的微孔中。
步骤 S205: 将支架本体进行干燥， 即可得到介入医疗器械。 又一个实施例：
图 6为本申请提供的介入医疗器械的制备方法的又一种工艺流程。
如图 6所示， 在本申请实施例中， 该介入医疗器械的制备方法包括： 步骒 S301 : 清洗支架本体并干燥。
步骤 S302: 配制抑制外膜成纤维细胞增殖的药物以及抑制内膜和 /或平滑 肌细胞增殖的药物与高分子聚合物的混合溶液。
在本申请实施例中， 高分子聚合物选择为聚乳酸， 抑制外膜成纤维细胞 增殖的药物优选为积雪草苷， 抑制内膜和 /或平滑肌细胞增殖的药物优选为雷 帕霉素。 配制聚乳酸、 积雪草苷和雷帕霉素药物的混合溶液， 其中： 积雪草 苷与雷帕霉素的比例为 2: 1~5 : 1， 聚乳酸与积雪草苷的比例为 1 : 1〜5 : 1。 在配 制时， 可以在 1 Oml 四氢呋喃中加入 1 Omg雷帕霉素和 30mg积雪草苷药物和 lOOmg聚乳酸， 充分溶解后并混合均匀。
步骤 S303: 将混合溶液涂覆在支架本体的表面。
在本申请实施例中， 可以采用超声喷涂、 空气喷涂或浸涂的方式将步骤 302中配制得到的混合溶液涂覆到支架本体上。
步骤 S304: 将支架本体进行干燥， 即可得到介入医疗器械。 又一个实;^例：
在图 6 中配制的是两种药物的与高分子聚合物的混合溶液， 在实际应用 中， 还可以将两种药物分别与高分子聚合物进行混合， 然后再依次将两种药 物的混合溶液分别涂覆在支架本体表面。
图 7为本申请提供的介入医疗器械的制备方法的又一种工艺流程。
如图 7所示， 在本申请实施例中， 该介入医疗器械的制备方法包括： 步骤 S401 : 清洗支架本体并干燥。
步骤 S402: 分别配制抑制外膜成纤维细胞增殖的药物与高分子聚合物的 混合溶液， 以及抑制内膜和 /或平滑肌细胞增殖的药物与高分子聚合物的混合 溶液。
在本申请实施例中， 优选地， 高分子聚合物选择为聚乳酸， 抑制外膜成 纤维细胞增殖的药物为积雪草苷， 抑制内膜和 /或平滑肌细胞增殖的药物为雷 帕霉素。 分别配制聚乳酸和积雪草苷以及聚乳酸和雷帕霉素的溶液， 其中： 聚乳酸与积雪草苷的比例为 1:1 4:1； 聚乳酸与雷帕霉素的比例为 1 : 1〜4: 1。 在 具体配制时， 在〗 0ml 四氢呋喃中加入 30mg积雪草苷药物和 60mg聚乳酸， 溶解并混匀， 得到一种药物溶液； 另外在 10ml 四氢呋喃中加入 10mg雷帕霉 素药物和 20mg聚乳酸， 溶解并混勾， 得到第二种药物溶液。
步骤 S403: 分别将得到的两种混合溶液依次涂覆在支架本体的表面。 在具体涂覆时， 可以先将积雪草苷 /聚乳酸溶液涂敷于支架本体表面； 然 后将喷涂后的支架本体敞口放置 4小时， 使其表面干燥； 再将雷帕霉素 /聚乳 酸溶液涂敷于干燥后的支架本体表面。
上迷喷涂时， 先喷涂积雪草苷 /聚乳酸溶液， 然后再喷涂雷帕霉素 /聚乳酸 溶液。 这只是本申请的一个实施例， 不应构成对本申请的限制， 本领域普通 技术人员应该知道， 在其他实施例中， 两种药物溶液的喷涂顺序可以自由选 择。
另外， 在本申请实施例中， 可以采用超声喷涂、 空气喷涂或浸涂等方式。 步骤 S404: 将支架本体进行干燥， 即可后得到介入医疗器械。 以上所述仅是本申请的优选实施方式， 使本领域技术人员能够理解或实 现本申请。 对这些实施例的多种修改对本领域的技术人员来说将是显而易见 的， 本文中所定义的一般原理可以在不脱离本申请的精神或范围的情况下， 在其它实施例中实现。 因此， 本申请将不会被限制于本文所示的这些实施例， 而是要符合与本文所 ^^开的原理和新颖特点相一致的最宽的范围。

Claims

权 利 要 求 书
1、 一种介入医疗器械， 其特征在于， 包括： 支架本体， 所述支架本体的 表面设置有药物释放结构， 所述药物释放结构中的药物为抑制外膜成纤维细 胞增殖的药物及抑制内膜和 /或平滑肌细胞增殖的药物。
2、 根据权利要求 1所述的介入医疗器械， 其特征在于， 所述药物释放结 构为高分子聚合物与抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌 细胞增殖的药物形成的致密混合层。
3、 根据权利要求 2所述的介入医疗器械， 其特征在于， 所述高分子聚合 物包括： 聚乳酸、 聚乙二醇、 苯乙烯丁烯共聚物、 聚己内酯、 聚甲基丙烯酸 丁酯、 聚甲基丙烯酸乙酯、 聚乙烯乙酸乙酯、 聚氨酯、 聚乙烯基吡咯烷酮、 聚碑酸胆碱、 蚕丝蛋白、 明胶、 甲壳素和 /或透明质酸。
4、 根据权利要求 1所述的介入医疗器械， 其特征在于， 所述药物释放结 构为在所述支架本体表面制备微孔结构或者在所述支架本体表面形成的微孔 涂层结构 , 并在所述微孔结构或微孔涂屋结构中载入药物。
5、 根据权利要求 1所述的介入医疗器械， 其特征在于， 所述抑制外膜成 紆维细胞增殖的药物包括丹参酮、 积雪草苷、 羟基积雪草甙、 川芎嗪、 血竭 素、 舒伐他汀、 血管紧张素中的至少一种。
6、 根据权利要求 1所述的介入医疗器械， 其特征在于， 所述抑制内膜和
/或平滑肌细胞增殖的药物包括： 雷帕霉素及其衍生物、 紫^醇及其衍生物中 的至少一种。
7、 根据权利要求 1所述的介入医疗器械， 其特征在于， 所述支架本体包 括： 冠状动脉血管支架、 颅内血管支架、 外周血管支架、 术中支架、 心脏瓣 膜支架、 胆道支架、 食道支架、 肠道支架、 胰管支架、 尿道支架或气管支架。
8、 一种介入医疗器械的制备方法， 其特征在于， 包括：
在支架本体的表面制备微孔结构；
配制含有抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌细胞增 殖的药物的溶液；
将配制的所述溶液中的药物装载在所述^:孔结构中； 将所述支架本体干燥后得到所述介入医疗器械。
9、 根据权利要求 8所述的方法， 其特征在于， 在支架本体的表面制备微 孔结构， 具体为：
采用阳极氧化、微弧氧化和 /或化学腐蚀的方法在支架本体表面形成微孔。
10、 根据权利要求 8所述的方法， 其特征在于， 在支架本体的表面制备 微孔结构， 具体为：
在所述支架本体的表面上制备具有微孔的涂层。
11、 根据权利要求 8所述的方法， 其特征在于， 将配制的所述溶液中的 药物装载在所述微孔结构中， 具体为：
采用超声喷涂、 空气喷涂和 /或浸涂的方式将所述溶液中的药物装载在所 述微孔结构中。
12、 一种介入医疗器械的制备方法， 其特征在于， 包括：
分别配制抑制外膜成纤维细胞增殖的药物与高分子聚合物的混合溶液， 以及抑制内膜和 /或平滑肌细胞增殖的药物与高分子聚合物的混合溶液， 或者 配制抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌细胞增殖的药物 与高分子聚合物的混合溶液；
将抑制外膜成纤维细胞增殖的药物与高分子聚合物的混合溶液， 以及抑 制内膜和 /或平滑肌细胞增殖的药物与高分子聚合物的混合溶液依次涂覆在支 架本体表面， 或者将抑制外膜成纤维细胞增殖的药物及抑制内膜和 /或平滑肌 细胞增殖的药物与高分子聚合物的混合溶液涂覆在支架本体表面；
将所述支架本体干燥后得到所述介入医疗器械。
13、 根据权利要求 12所述的方法， 其特征在于， 所述涂覆包括： 超声喷 涂、 空气喷涂和 /或浸涂。
PCT/CN2012/070400 2011-09-29 2012-01-16 一种介入医疗器械及其制备方法 WO2013044603A1 (zh)

Priority Applications (5)

Application Number Priority Date Filing Date Title
BR112014007580A BR112014007580A2 (pt) 2011-09-29 2012-01-16 dispositivo médico de intervenção e método de fabricação do mesmo
EP12834752.3A EP2762110A4 (en) 2011-09-29 2012-01-16 MEDICAL INTERVENTION DEVICE AND METHOD FOR MANUFACTURING THE SAME
US14/348,857 US20140248327A1 (en) 2011-09-29 2012-01-16 Interventional medical device and manufacturing method thereof
IN2578CHN2014 IN2014CN02578A (zh) 2011-09-29 2012-01-16
US14/677,741 US9433709B2 (en) 2011-09-29 2015-04-02 Interventional medical device and manufacturing method thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201110295324.9 2011-09-29
CN2011102953249A CN102499798A (zh) 2011-09-29 2011-09-29 一种介入医疗器械及其制备方法

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/348,857 A-371-Of-International US20140248327A1 (en) 2011-09-29 2012-01-16 Interventional medical device and manufacturing method thereof
US14/677,741 Continuation US9433709B2 (en) 2011-09-29 2015-04-02 Interventional medical device and manufacturing method thereof

Publications (1)

Publication Number Publication Date
WO2013044603A1 true WO2013044603A1 (zh) 2013-04-04

Family

ID=46211977

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2012/070400 WO2013044603A1 (zh) 2011-09-29 2012-01-16 一种介入医疗器械及其制备方法

Country Status (7)

Country Link
US (2) US20140248327A1 (zh)
EP (1) EP2762110A4 (zh)
JP (1) JP2014530058A (zh)
CN (1) CN102499798A (zh)
BR (1) BR112014007580A2 (zh)
IN (1) IN2014CN02578A (zh)
WO (1) WO2013044603A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170066450A (ko) * 2014-10-06 2017-06-14 가트 테크놀로지스 비.브이. 조직-접착 다공성 지혈 제품

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102397119A (zh) * 2011-09-29 2012-04-04 微创医疗器械(上海)有限公司 一种介入医疗器械及其制备方法
DE112014007192T5 (de) * 2014-12-25 2017-08-24 Olympus Corporation Osteosynthetisches Implantat und Herstellungsverfahren hierfür
CN105816921A (zh) * 2016-04-20 2016-08-03 山东百多安医用材料改性工程技术中心 一种仿生血管支架及其制备方法
CN106512188A (zh) * 2016-12-13 2017-03-22 天津飞捷科技有限公司 机电一体化靶向药物释放介入类医疗器械及其制备方法
CN109602523B (zh) * 2019-01-03 2024-02-09 科塞尔医疗科技（苏州）有限公司 一种可回收的药物支架
CN110283296B (zh) * 2019-06-20 2020-07-31 中国科学院长春应用化学研究所 双功能聚氨酯及其制备方法与应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1935274A (zh) * 2006-10-20 2007-03-28 东南大学 冠状动脉药物涂层支架
EP2014308A2 (en) * 2007-07-10 2009-01-14 Cordis Corporation A coating employing an anti-thrombotic conjugate
CN101879102A (zh) * 2009-05-07 2010-11-10 微创医疗器械(上海)有限公司 一种凹槽携载式涂层可降解型药物洗脱支架

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6273913B1 (en) * 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
US6908624B2 (en) * 1999-12-23 2005-06-21 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
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
EP1308179A1 (en) * 2001-10-30 2003-05-07 Boehringer Ingelheim Pharma GmbH & Co.KG Improved endoprosthetic device
US20050019404A1 (en) * 2003-06-30 2005-01-27 Hsing-Wen Sung Drug-eluting biodegradable stent
JP4588986B2 (ja) * 2002-08-20 2010-12-01 テルモ株式会社 体内埋込医療器具
AU2004216541A1 (en) 2003-02-28 2004-09-10 Howard Florey Institute Of Experimental Physiology And Medicine Therapeutic compositions
US7488343B2 (en) * 2003-09-16 2009-02-10 Boston Scientific Scimed, Inc. Medical devices
US20070219613A1 (en) 2003-10-06 2007-09-20 Xtent, Inc. Apparatus and methods for interlocking stent segments
US8003122B2 (en) 2004-03-31 2011-08-23 Cordis Corporation Device for local and/or regional delivery employing liquid formulations of therapeutic agents
US20050266040A1 (en) * 2004-05-28 2005-12-01 Brent Gerberding Medical devices composed of porous metallic materials for delivering biologically active materials
EA016906B1 (ru) * 2004-08-13 2012-08-30 Рутгерс, Дзе Стейт Юниверсити Рентгеноконтрастные полимерные стенты
US20060199876A1 (en) * 2005-03-04 2006-09-07 The University Of British Columbia Bioceramic composite coatings and process for making same
US20070224235A1 (en) * 2006-03-24 2007-09-27 Barron Tenney Medical devices having nanoporous coatings for controlled therapeutic agent delivery
US8187620B2 (en) * 2006-03-27 2012-05-29 Boston Scientific Scimed, Inc. Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents
US20070292470A1 (en) * 2006-06-15 2007-12-20 Medtronic Vascular, Inc. Implantable Medical Devices and Methods for Making the Same
NZ574597A (en) * 2006-07-03 2011-11-25 Hemoteq Ag Stent coated with a biodegradable polymer and rapamycin
CN101199873B (zh) * 2006-12-14 2013-06-19 乐普（北京）医疗器械股份有限公司 药物洗脱器械用纳米级孔洞药物释放结构及其制备方法
US8187255B2 (en) * 2007-02-02 2012-05-29 Boston Scientific Scimed, Inc. Medical devices having nanoporous coatings for controlled therapeutic agent delivery
CA2680229A1 (en) * 2007-03-09 2008-09-18 Jay S. Yadav Bioabsorbable coatings for medical devices
CN101318032B (zh) 2007-06-06 2012-11-21 李京倖 小口径组织工程学人工血管及其制备方法
CN101406713B (zh) 2007-10-12 2012-09-19 微创医疗器械(上海)有限公司 一种人工血管支架及其制备方法
CN101945621B (zh) * 2007-12-18 2014-06-18 因特尔赛克特耳鼻喉公司 自扩展装置及用于其的方法
KR100947094B1 (ko) * 2008-01-02 2010-03-10 주식회사 디오 의료용 스텐트 및 그 제조방법
JP5530361B2 (ja) 2008-09-17 2014-06-25 テルモ株式会社 ステント
US20100280600A1 (en) * 2009-04-30 2010-11-04 Vipul Bhupendra Dave Dual drug stent
CN102397119A (zh) 2011-09-29 2012-04-04 微创医疗器械(上海)有限公司 一种介入医疗器械及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1935274A (zh) * 2006-10-20 2007-03-28 东南大学 冠状动脉药物涂层支架
EP2014308A2 (en) * 2007-07-10 2009-01-14 Cordis Corporation A coating employing an anti-thrombotic conjugate
CN101879102A (zh) * 2009-05-07 2010-11-10 微创医疗器械(上海)有限公司 一种凹槽携载式涂层可降解型药物洗脱支架

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2762110A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170066450A (ko) * 2014-10-06 2017-06-14 가트 테크놀로지스 비.브이. 조직-접착 다공성 지혈 제품
JP2017531488A (ja) * 2014-10-06 2017-10-26 ガット テクノロジーズ ビー．ブイ．Ｇａｔｔ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｂ．Ｖ． 組織接着性多孔質止血製品
KR102514142B1 (ko) 2014-10-06 2023-03-27 가트 테크놀로지스 비.브이. 조직-접착 다공성 지혈 제품

Also Published As

Publication number Publication date
US20150209485A1 (en) 2015-07-30
BR112014007580A2 (pt) 2017-04-11
EP2762110A4 (en) 2015-05-06
IN2014CN02578A (zh) 2015-08-07
US20140248327A1 (en) 2014-09-04
JP2014530058A (ja) 2014-11-17
EP2762110A1 (en) 2014-08-06
CN102499798A (zh) 2012-06-20
US9433709B2 (en) 2016-09-06

Similar Documents

Publication Publication Date Title
WO2013044605A1 (zh) 一种介入医疗器械及其制备方法
WO2013044603A1 (zh) 一种介入医疗器械及其制备方法
JP5368991B2 (ja) 薬剤徐放性ステント
Nazneen et al. Surface chemical and physical modification in stent technology for the treatment of coronary artery disease
WO2008071047A1 (fr) Structure de libération de medicament nanoporeuse pour instruments d'élution de médicaments et son procédé de préparation
CN101327343B (zh) 一种复合药物血管支架及其制备方法
WO2010081393A1 (zh) 一种储存和释放多种药物的微孔结构药物洗脱器械及其制备方法
CN101869723A (zh) 抑制心血管再狭窄的复合药物支架及制备方法
CN107913119A (zh) 一种介入医疗器械及其制备方法
CN101081316A (zh) 一种新型药物洗脱支架
CN101195048A (zh) 一种复合药物洗脱支架及其制备方法
WO2008061431A1 (fr) Stent à plusieurs couches de médicaments
Li et al. In vitro release study of sirolimus from a PDLLA matrix on a bioresorbable drug-eluting stent
US8591571B2 (en) Drug-eluting stent
KR101595267B1 (ko) 재협착과 염증 조절을 위한 순차적 약물 방출 스텐트의 제조방법
JP5422999B2 (ja) コーティング層を有するインプラント
Wang et al. Effects of controlled-released sirolimus from polymer matrices on human coronary artery smooth muscle cells
JP2016163619A (ja) 防食効果を利用したマグネシウムの分解速度制御
WO2019029334A1 (zh) 冠脉药物洗脱支架的复合抗再狭窄药物及其控释系统
JP2002085549A (ja) 血管内治療用材料および血管内治療用器具
JP2015226574A (ja) 薬剤放出層を有するステント
JP2015154921A (ja) 薬剤徐放性ステント
JP2016005533A (ja) ステント
EP4103245A1 (en) Administration of calcium channel trpc6 inhibitors using balloons, stents or other medical devices
JP2008119199A (ja) カルシニューリン産生亢進を抑制する薬剤コーティングステント

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12834752

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2014532219

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 14348857

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2012834752

Country of ref document: EP

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112014007580

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112014007580

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20140328