WO2010127584A1 - 一种凹槽携载式涂层可降解型药物洗脱支架 - Google Patents

一种凹槽携载式涂层可降解型药物洗脱支架 Download PDF

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Publication number
WO2010127584A1
WO2010127584A1 PCT/CN2010/071719 CN2010071719W WO2010127584A1 WO 2010127584 A1 WO2010127584 A1 WO 2010127584A1 CN 2010071719 W CN2010071719 W CN 2010071719W WO 2010127584 A1 WO2010127584 A1 WO 2010127584A1
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Prior art keywords
drug
stent
eluting stent
stent according
biodegradable polymer
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PCT/CN2010/071719
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English (en)
French (fr)
Inventor
吴常生
张劼
易博
唐智荣
罗七一
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微创医疗器械(上海)有限公司
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Publication of WO2010127584A1 publication Critical patent/WO2010127584A1/zh

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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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by 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
    • 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
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • 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
    • 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
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
    • A61F2230/0028—Shapes in the form of latin or greek characters
    • A61F2230/0054—V-shaped
    • 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

Definitions

  • Field of the Invention relates to the field of medical devices, and more particularly to a groove-carrying coating degradable blood vessel stent which can reduce restenosis in the stent and the incidence of late thrombosis in the blood vessel. Background technique
  • Cardiovascular disease is an important disease affecting human health. Since Cypher stent was approved by the US FDA in 2003, drug-eluting stent (DES) has been widely used. It is known as interventional heart disease after metal stent. Another milestone in the field of learning has opened up a new era of interventional cardiology. Large-scale randomized, double-blind clinical trials have shown that drug-eluting stents can significantly reduce the occurrence of in-stent restenosis (RS) and major adverse cardiac events (MACE).
  • RS in-stent restenosis
  • MACE major adverse cardiac events
  • the drug stents are coated with a drug on the inner and outer surfaces of the metal, so that the concentration of the drug in the blood vessel is large, the release speed is fast, and the release direction is not effectively controlled, so that a part of the drug cannot be absorbed by the blood vessel wall.
  • the drug coating applied to the place where the shape of the stent changes greatly is easy to fall off during the pushing and expanding process of the stent, and the peeling coating block flows with the blood, which easily forms a thrombus and causes harm.
  • existing drug-eluting stents typically use a non-degradable polymer (such as polybutyl methacrylate (PBMA)) as a carrier for the active drug, and a mixture of active drug and polymer is applied to all parts of the stent struts.
  • PBMA polybutyl methacrylate
  • the incidence of major adverse cardiac events (including late thrombotic events) and restenosis rates increased with the placement of non-degradable polymer-eluting stents over time, with the so-called "late catch-up phenomenon" [ Sousa JE, Costa MA, Abizaid A, et al. Four year angiographic and intravascular ultrasound follow-up of patients treated with sirolimus-eluting stents.
  • Biodegradable polymers are increasingly matured due to their good biocompatibility and absorbability, and eventually degrade into carbon dioxide and water.
  • polylactic acid began to be studied in the cardiovascular field as early as the early 1980s with the development of tissue engineering [Langer R, Vacanti J P. Tissue engineering. Science, 1993, 260:920 - 926.], so polylactic acid was used as a drug.
  • the carrier has become a direction for drug-eluting stent development.
  • polylactic acid has good biological properties and degradation properties, but because the material itself is brittle, hard and brittle, and the mechanical properties are poor, there is still some difficulty in replacing the stent body (such as the metal stent body) as a drug carrier and supporting blood vessels;
  • the drug eluting stent provided by the invention comprises a stent body and a drug coating, the outer surface of the stent body is provided with a drug loading groove, and the drug coating is coated in the drug loading tank, the drug coating Includes biodegradable polymers and active drugs.
  • the drug coating consists of a biodegradable polymer and an active drug.
  • the biodegradable polymer is from 0.5 to 99.5% by weight, and the active drug is from 0.5 to 99.5% by weight, based on the total weight of the drug coating.
  • the biodegradable polymer is selected from one or more of a homopolymer and a copolymer of an aliphatic hydroxycarboxylic acid.
  • the biodegradable polymer is selected from one or more of a homopolymer and a copolymer of a C 2 -C 6 aliphatic hydroxycarboxylic acid.
  • the biodegradable polymer is selected from one or more of a homopolymer and a copolymer of a C 2 -C 6 aliphatic hydroxycarboxylic acid composed of C, H and 0.
  • the biodegradable polymer is:
  • the biodegradable polymer is selected from the group consisting of poly D, L-lactide, poly D-lactide, poly L-lactide, polyglycolide, polyglycolide-lactide and poly One or more of ⁇ -caprolactone, which can completely degrade within 2 years after completing the drug release function.
  • the biodegradable polymer has a weight average molecular weight of from 20,000 to 200,000.
  • the drug-loading groove is elongated, elliptical or circular, and the drug-loading grooves are continuous or discontinuous.
  • the material of the bracket is selected from one or more of metal, ceramic and carbon.
  • the material of the bracket is selected from one or more of a cobalt-based alloy, a stainless steel, a titanium alloy, an active ceramic, and carbon.
  • the active drug is rapamycin, paclitaxel, cilostazol, ticlopidine, triptolide or dexamethasone.
  • the stent body is composed of a plurality of main support unit rings and a connecting rod of a proximal end, a distal end and an intermediate portion, the main support unit loop being composed of a plurality of unit waves.
  • the cumulative length of the drug-loaded W-groove is 5% to 95% of the length of the stent rod.
  • the cumulative length of the drug-loading groove is 60%-75% of the length of the stent rod.
  • the depth of the drug-loading groove is 0.1%-60% of the thickness of the stent rod.
  • the width of the drug-loading groove is 1%-99% of the width of the stent pole.
  • the depth of the drug-loading groove is 10%-30% of the thickness of the stent rod.
  • the width of the drug-loading groove is 20%-70% of the width of the stent pole.
  • the present invention has the following advantages and effects:
  • the invention adopts the one-side coating method, enhances the controlled release ability of the medicine, reduces the side effects of the medicine, and improves the treatment efficiency of the medicine;
  • the invention adopts the groove type drug loading mode, which reduces the risk of the coating falling off during the conveying process, and improves the safety and effectiveness of the stent use process;
  • the biodegradable polymer coating used in the present invention is gradually degraded after completion of drug release, thereby avoiding the risk of late thrombosis of the drug stent due to the long-term presence of the polymer.
  • the drug eluting stent not only solves the problem of the combination of the coating and the stent, but also improves the effectiveness and safety of the drug stent during the operation and use, and solves the problem of narrow and late thrombosis in the stent.
  • the drug-eluting stent of the present invention can be used for coronary vessels, in which case it is preferred that the stent body is composed of a plurality of main support unit rings and connecting rods of the proximal end, the distal end and the intermediate portion, the main support unit ring being composed of a plurality of units Wave composition, the stent structure can enhance the supporting force on the lesion plaque; the drug-loading four grooves can be continuous or discontinuous, preferably the cumulative length is the length of the stent rod
  • 1 is a schematic plan view showing a planar structure of a drug eluting stent in an axial direction according to an embodiment of the present invention
  • 1, 8 - a main supporting unit ring
  • FIG. 2 is a schematic view showing a drug coating of a drug eluting stent according to an embodiment of the present invention. 11 a drug coating;
  • the bracket material is cobalt chrome alloy, and the structure is as shown in Fig. 1. It is composed of a plurality of main support unit rings 1, 8 and connecting rods 4 and 6 connecting the unit rings, and the main support unit ring is composed of a plurality of unit waves;
  • the reinforcing ring 9 of the circular arc segment and the straight section 10 of the pole section, and the transition section (such as 3, 5, 7), the outer surface of the unit pole is provided with a drug-loading drug-carrying tank 2;
  • the main supporting unit ring The width of the straight rod in the unit wave is 96 ⁇ , and the width of the reinforcing ring is 91 ⁇ ; the transition section smoothly connects the straight rod section and the reinforcing ring; the thickness of the bracket is 100 ⁇ .
  • the drug-carrying groove is cut by laser cutting technology, the groove width is 60 ⁇ , the depth is 30 ⁇ , and the cumulative groove length accounts for 60% of the total wave rod length of the main support unit ring, and is sprayed for use after processing.
  • Example 2 The poly D,L-lactide used in Example 1 degraded completely within 2 years after completion of the drug release function.
  • Example 2 The poly D,L-lactide used in Example 1 degraded completely within 2 years after completion of the drug release function.
  • the stent body is the same as in the first embodiment.
  • the laser-cutting technology is used to cut the drug-loading tank, the groove width is 60 ⁇ , the depth is 30 ⁇ , the cumulative groove length accounts for 60% of the length of the rod, and is sprayed for use after processing.
  • Example 2 Take O.lg poly L-lactide (PLLA, weight average molecular weight range 20,000-120,000) and O.lg polyglycolide (PGA, weight average molecular weight range 50,000-150,000), add to 10ml tetrahydrofuran at room temperature Prepare a uniform solution, add O.lg paclitaxel to mix evenly, spray the solution accurately into the drug-loading tank of the stent, place the stent in a vacuum oven and sterilize it with ethylene oxide.
  • the poly L-lactide used in Example 2 degraded completely within 2 years after completion of the drug release function.
  • Example 3
  • the stent body is the same as in the first embodiment.
  • the laser-cutting technology is used to cut the drug-loading tank, the groove width is 55 ⁇ , the depth is 25 ⁇ , and the cumulative groove length accounts for 65% of the length of the rod, which is sprayed for use after processing.
  • PLGA polyglycolide-lactide
  • Example 4 The polyglycolide-lactide used in Example 3 degraded completely within 2 years after completion of the drug release function.
  • the stent body is the same as in the first embodiment.
  • the laser-cutting technology is used to cut the drug-loading tank, the groove width is 55 ⁇ , the depth is 25 ⁇ , and the cumulative groove length accounts for 75% of the length of the rod, which is sprayed for use after processing.
  • PCL poly- ⁇ -caprolactone
  • Example 5 The poly ⁇ -caprolactone used in Example 4 will be in 2 years after the drug release function is completed. The internal degradation is complete.
  • Example 5 The poly ⁇ -caprolactone used in Example 4 will be in 2 years after the drug release function is completed. The internal degradation is complete.
  • the stent body is the same as in the first embodiment.
  • the laser-cutting technology is used to cut the drug-loading tank, the groove width is 50 ⁇ , the depth is 20 ⁇ , and the cumulative groove length accounts for 75% of the length of the rod, which is sprayed for use after processing.
  • Example 5 The poly D,L-lactide and polyglycolide-lactide used in Example 5 degraded completely within 2 years after completion of the drug release function.
  • the above description is only a preferred embodiment of the present invention, and it should be noted that those skilled in the art can also make several improvements and retouchings without departing from the principles of the present invention. It should be considered as the scope of protection of the present invention.

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Description

一种凹槽携载式涂层可降解型药物洗脱支架
本申请要求于 2009 年 5 月 7 日提交中国专利局、 申请号为 200910050767.4、 发明名称为"一种凹槽携载式涂层可降解型药物洗脱支 架"的中国专利申请的优先权， 其全部内容通过引用结合在本申请中。 技术领域
本发明涉及医疗器械领域，具体地说，涉及一种可降低支架内再狭窄 和血管晚期血栓发生率的 槽携载式涂层可降解型血管支架。 背景技术
心血管疾病是影响人体健康的重要疾病，自从 Cypher支架 2003年被 美国 FDA批准上市， 药物洗脱支架（drug-eluting stent, DES )被广泛应 用，是继金属棵支架之后被誉为介入心脏病学领域的又一个里程碑，开创 了介入心脏病学的新纪元。 大规模随机、双盲临床试验显示药物洗脱支架 能够显著降低支架内再狭窄 （restenosis , RS ) 和主要心脏不良事件 ( MACE ) 的发生。
目前大多数药物支架的金属内外表面都涂敷有药物，使得血管内药物 的浓度较大， 释放速度较快， 而且释放方向也得不到有效控制，造成一部 分药物不能被血管壁吸收。此外，涂敷在支架形状改变较大地方的药物涂 层， 在支架推送和扩张过程中容易脱落， 脱落的涂层块随血液流动， 容易 形成血栓， 造成危害。
而且，现有的药物洗脱支架通常使用不可降解聚合物（例如聚曱基丙 烯酸丁酯（PBMA ) )作为活性药物的载体， 在支架撑杆的所有部位都有 活性药物和聚合物的混合物涂层，随着时间的推移，置入聚合物不可降解 的药物洗脱支架后主要心脏不良事件（包括晚期血栓事件）发生率和再狭 窄率都有增加的趋势， 出现所谓"后期追赶现象" [ Sousa JE, Costa MA, Abizaid A, et al. Four year angiographic and intravascular ultrasound follow-up of patients treated with sirolimus-eluting stents. Circulation, 2005, 111 :2326-2329 l 目前，对于支架置入后发生再狭窄和晚期血栓（ late stent thrombosis, LST )的原因和机制仍知之甚少， 是聚合物的原因、 药物的原 因、药物剂量的原因，还是金属材料抑或支架制作工艺的原因尚不能下结 论。病理学研究认为其与药物所致的血管内皮愈合延迟、不可降解聚合物 永久残留导致的局部血管壁炎症反应和纤维素沉积有关。 因此，任何寻找 新的药物、 新的药物载体或改进支架工艺的研究都具有重大意义。
生物可降解聚合物因为其具良好的生物相容性和可吸收性，并最终会 降解为二氧化碳和水， 其制备与应用日益发展成熟。 例如聚乳酸早在 80 年代初随着组织工程的提出， 便开始在心血管领域研究 [Langer R, Vacanti J P. Tissue engineering. Science, 1993, 260:920 - 926.] ,因此以聚乳酸作为药 物的载体， 成为药物洗脱支架发展一个方向。
聚乳酸虽然具有良好的生物学性能和降解性能， 但由于材料本身较 脆、 坚硬易脆， 力学性能较差， 代替支架本体（例如金属支架本体）作为 药物载体和支撑血管仍存在一定的困难；采用传统的金属内外表面全涂敷 方法，又因其与金属表面较弱的粘附性能，涂层牢固度存在一定的安全的 风险。
如何将生物可降解聚合物与支架结合，并且降低药物支架因涂层长期 存在引起的安全性问题，以及药物支架在使用过程中的有效性和安全性问 题， 备受人们关注。 发明内容
本发明的目的在于提供一种药物洗脱支架，其能够降低支架内再狭窄 和血管晚期血栓发生率。
本发明提供的药物洗脱支架， 包括支架本体和药物涂层，所述支架本 体的外表面开有载药 槽，所述药物涂层涂敷在所述载药 槽内，所述药 物涂层包括生物可降解聚合物和活性药物。
优选地， 所述药物涂层由生物可降解聚合物和活性药物组成。
优选地， 所述生物可降解聚合物的重量百分比为 0.5-99.5%, 所述活 性药物的重量百分比为 0.5-99.5%, 这些百分比基于所述药物涂层的总重 量。 优选地，所述生物可降解聚合物选自脂肪族羟基羧酸的均聚物和共聚 物中的一种或多种。
优选地，所述生物可降解聚合物选自 C2-C6脂肪族羟基羧酸的均聚物 和共聚物中的一种或多种。
优选地， 所述生物可降解聚合物选自由 C、 H和 0构成的 C2-C6脂肪 族羟基羧酸的均聚物和共聚物中的一种或多种。
优选地， 所述生物可降解聚合物是：
(1) D-乳酸、 L-乳酸、 乙醇酸或 ε-己内酯的均聚物中的一种或多种； 和 /或
(2) 由 D-乳酸、 L-乳酸、 乙醇酸和 ε-己内酯中任意两种以上作为单体 所形成的共聚物中的一种或多种。
优选地， 所述生物可降解聚合物选自聚 D,L-丙交酯、 聚 D-丙交酯、 聚 L-丙交酯、聚乙交酯、聚乙交酯 -丙交酯和聚 ε-己内酯中的一种或多种， 这些生物可降解聚合物在完成药物释放的功能后， 能够在 2 年内降解完 全。
优选地， 所述生物可降解聚合物的重均分子量为 20,000-200,000。 优选地， 所述载药凹槽为长条形、 椭圓形或圓形， 所述载药凹槽之间 是连续或不连续的。
优选地， 所述支架的材质选自金属、 陶瓷和碳素中的一种或多种。 优选地， 所述支架的材质选自钴基合金、 不锈钢、 钛合金、 活性陶瓷 和碳素中的一种或多种。
优选地， 所述活性药物为雷帕霉素、 紫杉醇、 西洛他唑（Cilostazol )、 噻氯匹定 （ Ticlopidine )、 雷公藤内酯 （ Triptolide ) 或地塞米松 ( Desamethasone )。
优选地，所述支架本体由近端、远端和中间部分的多个主支撑单元环 和连接杆组成， 所述主支撑单元环由多个单元波组成。
优选地， 所述载药 W槽的累计长度为支架波杆长度的 5%-95%。
优选地， 所述载药凹槽的累计长度为支架波杆长度的 60%-75%。 优选地， 所述载药凹槽的深度为支架波杆厚度的 0.1%-60%。 优选地， 所述载药凹槽的宽度为支架波杆宽度的 1%-99%。 优选地， 所述载药凹槽的深度为支架波杆厚度的 10%-30%。
优选地， 所述载药凹槽的宽度为支架波杆宽度的 20%-70%。
本发明与现有技术相比， 具有以下优点与效果：
(1) 本发明采用单面涂层方式， 增强了药物的控制释放能力， 降低了 药物的副作用， 提高了药物的治疗效率；
(2) 本发明采用凹槽式载药方式， 降低了支架在输送过程中涂层脱落 的风险， 提高了支架使用过程的安全性和有效性；
(3) 本发明采用的生物可降解聚合物涂层在完成药物释放后， 逐渐降 解完毕， 避免了由于聚合物的长期存在导致药物支架的晚期血栓的风险。
本发明提供的药物洗脱支架，既解决了涂层与支架的结合问题，提高 了药物支架在操作使用过程中的有效性和安全性，同时解决了支架内再狭 窄和晚期血栓问题。
本发明的药物洗脱支架可用于冠脉血管， 此时优选其支架本体由近 端、远端和中间部分的多个主支撑单元环和连接杆组成，所述主支撑单元 环由多个单元波组成，这种支架结构可以增强对病变斑块的支撑力；所述 载药四槽可以是连续或不连续的， 优选其累计长度为支架波杆长度的
60%-75%，此时支架本体的力学性能保持良好，并且药物能够在支架表面 均匀分布。 附图说明
图 1是本发明实施例的药物洗脱支架沿轴向展开的平面结构示意图； 1、 8—主支撑单元环；
2—载药槽；
3、 5、 7—过渡段；
4、 6—连接单元环的连接杆；
9一加强环；
10—直杆段；
图 2是本发明实施例的药物洗脱支架的药物涂层示意图； 11一药物涂层；
12—金属支架杆。 具体实施方式
本发明将在通过下面的实施例进一步说明，但这些实施例仅是示范性 的，其目的在于让本领域的技术人员理解本发明， 而不是限制本发明的保 护范围。除实施例外还可以有其他不同形式的变化，这里无需对所有的实 施方式予以穷举。本发明的保护范围由权利要求书确定，凡根据本发明精 神实质所作的等效变化或变动， 都涵盖在本发明的保护范围之内。 实施例 1
支架材质为钴铬合金， 结构如图 1所示， 由多个主支撑单元环 1、 8 和连接单元环的连接杆 4、 6组成， 主支撑单元环由多个单元波构成； 单 元波由圓弧段的加强环 9和波杆段的直杆段 10、 过渡段（如 3、 5、 7 )组 成， 单元波杆的外表面开有可装载药物的载药槽 2; 主支撑单元环单元波 中直杆段宽度为 96μηι, 加强环宽度 91μηι; 过渡段平滑衔接直杆段与加 强环； 支架厚度为 100μηι。
利用激光切割技术切割出载药槽， 槽宽为 60μηι, 深度为 30μηι, 累 计槽长占主支撑单元环的总波杆长度的 60%, 经过工艺处理喷涂待用。
取 0.2g聚 D,L-丙交酯（PDLLA,重均分子量范围为 30,000-140,000 ), 在室温下加入到 10ml乙酸正丙酯配制成均匀的溶液，再加入 O.lg雷帕霉 素混合均勾，将溶液准确的喷涂至支架的载药槽内，将支架置于真空烘箱 内烘干， 经环氧乙烷灭菌待用， 涂层结构状态见图 2所示， 其中药物涂层 11位于金属支架杆 12表面的载药槽内。
实施例 1所使用的聚 D,L-丙交酯在完成药物释放的功能后， 会在 2 年内降解完全。 实施例 2
支架本体和实施例 1相同。 利用激光切割技术切割出载药槽， 槽宽为 60μηι, 深度为 30μηι, 累 计槽长占波杆长度的 60%, 经过工艺处理喷涂待用。
取 O.lg聚 L-丙交酯 ( PLLA, 重均分子量范围为 20,000-120,000 )和 O.lg聚乙交酯 （PGA, 重均分子量范围为 50,000-150,000 ), 在室温下加 入到 10ml四氢呋喃配制成均匀的溶液， 再加入 O.lg紫杉醇混合均匀， 将 溶液准确的喷涂至支架的载药槽内，将支架置于真空烘箱内烘干，经环氧 乙烷灭菌待用。 实施例 2所使用的聚 L-丙交酯在完成药物释放的功能后， 会在 2年内降解完全。 实施例 3
支架本体和实施例 1相同。
利用激光切割技术切割出载药槽， 槽宽为 55μηι, 深度为 25μηι, 累 计槽长占波杆长度的 65%, 经过工艺处理喷涂待用。
取 0.2g聚乙交酯-丙交酯（ PLGA,重均分子量范围为 40,000-150,000 ), 在室温下加入到 10ml四氢呋喃配制成均匀的溶液，再加入 O.lg雷帕霉素 混合均匀，将溶液准确的喷涂至支架的载药槽内，将支架置于真空烘箱内 烘干， 经环氧乙烷灭菌待用。
实施例 3所使用的聚乙交酯-丙交酯在完成药物释放的功能后， 会在 2年内降解完全。 实施例 4
支架本体和实施例 1相同。
利用激光切割技术切割出载药槽， 槽宽为 55μηι, 深度为 25μηι, 累 计槽长占波杆长度的 75%, 经过工艺处理喷涂待用。
取 0.2g聚 ε-己内酯（PCL, 重均分子量范围为 30,000-140,000 ), 在 室温下加入到 10ml四氢呋喃配制成均匀的溶液，再加入 O.lg雷帕霉素混 合均匀，将溶液准确的喷涂至支架的载药槽内，将支架置于真空烘箱内烘 干， 经环氧乙烷灭菌待用。
实施例 4所使用的聚 ε-己内酯在完成药物释放的功能后， 会在 2年 内降解完全。 实施例 5
支架本体和实施例 1相同。
利用激光切割技术切割出载药槽， 槽宽为 50μηι, 深度为 20μηι, 累 计槽长占波杆长度的 75%, 经过工艺处理喷涂待用。
取 O.lg聚 D,L-丙交酯（PDLLA, 重均分子量范围为 30,000-140,000 ) 和 O.lg聚乙交酯-丙交酯 ( PLGA, 重均分子量范围为 40,000-150,000 ), 在室温下加入到 10ml乙酸丙酯配制成均匀的溶液，再加入 O.lg雷帕霉素 混合均匀，将溶液准确的喷涂至支架的载药槽内，将支架置于真空烘箱内 烘干， 经环氧乙烷灭菌待用。
实施例 5所使用的聚 D,L-丙交酯和聚乙交酯-丙交酯在完成药物释放 的功能后， 会在 2年内降解完全。 以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的 普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进 和润饰， 这些改进和润饰也应视为本发明的保护范围。

Claims

权 利 要 求
1. 一种药物洗脱支架， 包括支架本体和药物涂层， 其特征在于， 所述支 架本体的外表面开有载药 槽，所述药物涂层涂敷在所述载药 槽内，所 述药物涂层包括生物可降解聚合物和活性药物。
2. 如权利要求 1所述的药物洗脱支架， 其特征在于， 所述药物涂层由生 物可降解聚合物和活性药物组成。
3. 如权利要求 1或 2所述的药物洗脱支架， 其特征在于， 所述生物可降 解聚合物的重量百分比为 0.5-99.5% , 所述活性药物的重量百分比为 0.5-99.5%, 这些百分比基于所述药物涂层的总重量。
4. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物选自脂肪族羟基羧酸的均聚物和共聚物中的一种或多种。
5. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物选自 C2-C6脂肪族羟基羧酸的均聚物和共聚物中的一种 或多种。
6. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物选自由 C、 H和 0构成的 C2-C6脂肪族羟基羧酸的均聚物 和共聚物中的一种或多种。
7. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物是：
(1) D-乳酸、 L-乳酸、 乙醇酸或 ε-己内酯的均聚物中的一种或多种； 和 / 或
(2) 由 D-乳酸、 L-乳酸、 乙醇酸和 ε-己内酯中任意两种以上作为单体所形 成的共聚物中的一种或多种。
8. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物选自聚 D,L-丙交酯、 聚 D-丙交酯、 聚 L-丙交酯、 聚乙交 酯、 聚乙交酯 -丙交酯和聚 ε-己内酯中的一种或多种。
9. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述生 物可降解聚合物的重均分子量为 20,000-200,000。
10. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述载 药 槽为长条形、 橢圓形或圓形， 所述载药 槽之间是连续或不连续的。
11. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述支 架的材质选自金属、 陶瓷和碳素中的一种或多种。
12. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述支 架的材质选自钴基合金、 不锈钢、钛合金、 活性陶瓷和碳素中的一种或多 种。
13. 如前述权利要求任何一项所述的药物洗脱支架， 其特征在于， 所述活 性药物为雷帕霉素、 紫杉醇、 西洛他唑、 噻氯匹定、 雷公藤内酯或地塞米 松。
14. 如前述权利要求任何一项所述的药物洗脱支架， 所述支架本体由近 端、远端和中间部分的多个主支撑单元环和连接杆组成，所述主支撑单元 环由多个单元波组成。
15. 如述权利要求 14所述的药物洗脱支架， 其特征在于， 所述载药凹槽 的累计长度为支架波杆长度的 5%-95%。
16. 如权利要求 14或 15所述的药物洗脱支架， 其特征在于， 所述载药凹 槽的累计长度为支架波杆长度的 60%-75%。
17. 如权利要求 14-16任何一项所述的药物洗脱支架， 其特征在于， 所述 载药 槽的深度为支架波杆厚度的 0.1%-60% , 宽度为支架波杆宽度的 1%-99%。
18. 如权利要求 14-17任何一项所述的药物洗脱支架， 其特征在于， 所述 载药 槽的深度为支架波杆厚度的 10%-30% , 宽度为支架波杆宽度的 20%-70%。
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CN101406713A (zh) * 2007-10-12 2009-04-15 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

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US11241322B2 (en) 2014-10-28 2022-02-08 Jimro Co., Ltd. Drug-eluting stent
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EP3967279A4 (en) * 2019-05-10 2023-06-07 Shanghai MicroPort Medical (Group) Co., Ltd. DRUG-LOADED DEGRADABLE STENT AND METHOD OF ITS MANUFACTURE
JP7334338B2 (ja) 2019-05-10 2023-08-28 上海微▲創▼医▲療▼器械（集▲團▼）有限公司 分解性薬剤保持ステントおよびその製造方法

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