WO2014094655A1 - 一种可降解聚酯支架及其制备方法 - Google Patents

一种可降解聚酯支架及其制备方法 Download PDF

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Publication number
WO2014094655A1
WO2014094655A1 PCT/CN2013/090112 CN2013090112W WO2014094655A1 WO 2014094655 A1 WO2014094655 A1 WO 2014094655A1 CN 2013090112 W CN2013090112 W CN 2013090112W WO 2014094655 A1 WO2014094655 A1 WO 2014094655A1
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Prior art keywords
polyester
stent
metal
degradable
scaffold
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PCT/CN2013/090112
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English (en)
French (fr)
Inventor
陈树国
孟娟
陈宝爱
罗七一
Original Assignee
上海微创医疗器械（集团）有限公司
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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 US14/654,437 priority Critical patent/US9642731B2/en
Priority to EP13865747.3A priority patent/EP2937106A4/en
Publication of WO2014094655A1 publication Critical patent/WO2014094655A1/zh

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    • 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
    • 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
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/04—Ingredients treated with organic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/02—Elements
    • C08K3/08—Metals
    • C08K2003/0856—Iron
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K2201/00—Specific properties of additives
    • C08K2201/011—Nanostructured additives
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/02—Elements
    • C08K3/08—Metals
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/49—Method of mechanical manufacture
    • Y10T29/49826—Assembling or joining
    • Y10T29/49828—Progressively advancing of work assembly station or assembled portion of work

Definitions

  • the invention belongs to the field of medical instruments, and particularly relates to a degradable polyester stent and a preparation method thereof. Background technique
  • biodegradable stents As an important device for the treatment of vascular stenosis, stents have been widely used in the field of cardiovascular diseases. At present, the clinical metal stent, because it will remain in the human body after completing the treatment task, there are MRI or CT images that weaken the coronary artery, interfere with the surgical revascularization, hinder the formation of collateral circulation, and inhibit the positive remodeling of blood vessels. . Biodegradable stents have attracted widespread attention as a possible alternative solution.
  • the biodegradable stent is made of a degradable polymer material or a metal material, and can be used to support blood vessels in a short period of time after implantation in a lesion site, thereby realizing revascularization.
  • the biodegradable scaffold degrades into an organic substance that can be absorbed and metabolized by the human body in the human environment, and eventually the scaffold disappears.
  • Common degradable polymer materials that can be used for stent preparation include polylactic acid, polyglycolic acid, polycaprolactone, etc.; degradable metal materials include magnesium alloys, iron-based alloys, and the like. Both magnesium and iron are indispensable trace elements in organisms, with good biocompatibility, unique degradation and absorption functions, excellent comprehensive mechanical properties and processing and forming properties. However, during the application process, the mechanical properties of the polymer scaffolds were generally lower than those of the metal scaffolds.
  • US2009240323 A1 discloses a method for performing a degradable polymer coating on the surface of a magnesium stent, which enables controlled degradation of the magnesium stent.
  • U.S. Patent No. 6,201,015,726 discloses a ceramic material as a reinforcing agent added to a degradable material to improve the mechanical properties of the degradable scaffold.
  • the degradation mechanism of ceramic materials in the blood is not clear, and the toughness of the material will be significantly reduced.
  • US2009248147A1 discloses the use of a homopolymer and an inorganic salt as a nucleating agent in a degradable copolymeric material to improve the mechanical properties of the degradable copolymer scaffold.
  • the crystallization rate of the copolymer itself is lower than that of the homopolymer, and the addition of the nucleating agent does not significantly increase the mechanical strength of the stent.
  • U.S. Patent Application No. US2009149940A1 discloses the application of a developing layer with developing particles on the surface of the stent to realize the overall development of the stent.
  • Chinese Patent Application No. CN102532835A discloses a polylactic acid/magnesium composite material prepared by solution blending, and then cast molding to prepare a stent.
  • the method utilizes magnesium as an inorganic reinforcing medium, improves the mechanical properties of the polylactic acid support, and neutralizes the acidic substances produced by the degradation of the polylactic acid.
  • the invention provides a degradable polyester stent and a preparation method thereof, the dispersible metal-based powder material is dispersed in a polyester matrix, thereby improving the crystallization property of the polyester material, and improving the mechanical properties of the stent as a reinforcing agent.
  • the metal ions generated by the release of degradable metals can prevent or inhibit the occurrence of vascular restenosis, and some degradable metals also have developing ability, thereby improving the developability of the polyester stent.
  • the present invention relates to a strippable polyester scaffold made of a polyester composite material in which a polyester composite material is composed of a biodegradable polyester material and a metal-based material, and a shape of a metal-based material. It is in powder form.
  • the biodegradable polyester material includes, but is not limited to, one or more of the following materials: polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), polyhexyl Lactone (PCL), polytrimethylene carbonate (PTMC), polyester amide, polybutylene succinate (PBS), polyhydroxybutyrate (PHBV), polyacetyl glutamate or poly-positive Polyester materials such as ester (POE);
  • the metal-based material includes, but is not limited to, one or more of the following materials: pure magnesium, pure iron, magnesium-based alloy, magnesium salt compound or iron-based alloy, etc.; wherein the iron-based material can improve the developing ability of the stent .
  • the proportion of the metal-based material in the polyester composite is 0.1 to 20% by weight, and the balance is a biodegradable polyester material.
  • the particle size of the metal-based material is between lOnm- ⁇ .
  • the invention also relates to a method for preparing a dissolvable polyester scaffold, which is characterized in that a metal-based material is dispersed in a polyester matrix to prepare a polyester composite material, which is prepared into a stent by extrusion molding, post-treatment and cutting, and includes the following Steps:
  • the metal-based powder material is added to the polyester matrix by solution blending, melt blending or mechanical blending to prepare a polyester composite material;
  • the compatibility of the matrix preferably, the surface modification of the metal powder, such as hydroxyl modification, organic functional group grafting, etc.;
  • the formed polyester composite material is processed into a tube shape by screw extrusion at a temperature higher than the melting point of the material, wherein the metal-based material acts as a reinforcing medium to improve the mechanical strength of the polyester material;
  • the pipe is cut into a bracket, or the pipe is processed and then cut into a bracket, wherein the pipe processing comprises a combination of one or more of the pipe processing methods such as annealing, inflation, and stretching, the purpose of which is to further improve the strength of the pipe. , ⁇ , crystallinity and other properties.
  • the temperature at which the pipe is treated is preferably selected between the glass transition temperature and the melting point of the polyester.
  • the present invention differs from the prior art in the composition of the polyester composite, the method of preparing the stent, and the performance of the stent.
  • the method of the invention can improve the crystallization ability of the degradable polyester, thereby improving the mechanical properties of the polyester and the stent; the stent forming process provided by the method of the invention is simple, operability is strong, and the yield production can be realized.
  • the stent of the invention has excellent biocompatibility, and some stents have better development effects, and can realize the main body of the stent and the overall development.
  • Figure 2 shows a schematic representation of the uniform distribution of metal-based particles in a polyester matrix, where 1 represents metal particles and 2 represents a polyester matrix.
  • the obtained pipe had a tensile strength of 70 MPa and an elastic modulus of 2.5 GPa, which was higher than the polylactic acid pipe of the same size.
  • the obtained pipe was blown into a pipe at 70 ° C, and the pipe outer diameter was 3.30 mm, and the inner diameter was 3.05 mm.
  • the resulting tubing was laser cut into a stent and pressed against the balloon of the delivery system.
  • the obtained stent has a radial crushing strength of 150 kPa and a crystallinity of 54%, which is higher than the polylactic acid stent of the same size.
  • the stent is packaged and sterilized, and the stent is sent to a narrow lesion position of the blood vessel through a delivery system during surgery, and the balloon is filled and pressurized, and the stent is expanded to expand the narrow blood vessel.
  • No significant inflammatory response was observed after implantation.
  • endothelialization was observed and the stent was completely degraded 2 years after implantation.
  • the clear outline of the entire stent can be seen through the X-ray machine. After 1 week of implantation, it was found that the developability of the stent under X-ray was significantly lowered, and the stent became blurred under X-ray.
  • 100 g of magnesium oxide powder (particle size ⁇ 100 nm) and 900 g of polyglycolic acid (weight average molecular weight 400,000) were blended and processed through a twin-screw extruder at 180-220 ° C to obtain a polyglycolic acid/magnesia composite pipe. , wherein the weight percentage of the magnesium alloy in the composite material is 10%.
  • the outer diameter of the pipe is 2.8mm and the inner diameter is 2.5mm.
  • the tube was annealed at 120 ° C for 1 hour, and the obtained tube had a tensile strength of 70 MPa and an elastic modulus of 3.5 GPa, which was higher than that of the same size polyglycolic acid tube.
  • the obtained tube was laser-cut into a stent and pressed on a balloon of a delivery system to obtain a stent having a radial crushing strength of 120 kPa and a crystallinity of 63%, which was higher than that of the same size polyglycolic acid stent.
  • the stent is packaged and sterilized, and the stent is sent to a narrow lesion position of the blood vessel through a delivery system during surgery, and the balloon is filled and pressurized, and the stent is expanded to expand the narrow blood vessel. No significant inflammatory response was observed after implantation. After 6 months of implantation, endothelialization was observed and the stent was completely degraded 1 year after implantation.
  • the present invention has the following advantages and effects:
  • the metal-based material is dispersed in the polyester matrix to improve the mechanical properties of the polyester material, thereby improving the mechanical strength of the polyester stent;
  • the metal-based material is uniformly dispersed in the polyester matrix, and acts as a nucleating agent in the blow molding process of the polyester pipe to improve the crystallization ability of the polyester material, prolong the degradation time of the polyester material, and improve the polyester material.
  • the magnesium ion produced by magnesium degradation can inhibit the inflammatory reaction generated during the degradation of the polyester, and further prevent vascular restenosis;
  • the released iron ions reduce the proliferation of vascular smooth muscle cells by affecting the expression of related genes, and further resist vascular restenosis;
  • the iron alloy material improves the developing ability of the polyester stent in the polyester stent, and gathers
  • the ester scaffold has developability under X;
  • the metal particles can disperse the stress in the stent and improve the fatigue life of the stent.
  • the enhanced polyester has a higher modulus and a lower compliance, which effectively reduces the creep deformation of the stent after implantation into the blood vessel.

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  • Heart & Thoracic Surgery (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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Abstract

一种可降解聚酯支架，包括聚酯复合材料，其中聚酯复合材料由生物可降解聚酯材料和金属基材料制成。制备可降解聚酯支架的方法也被提及。该方法提高了可降解聚酯支架的力学性能，并实现了支架主体及整体的显影。

Description

一种可降解聚酯支架及其制备方法 技术领域
本发明属于医疗器械领域， 具体涉及一种可降解聚酯支架及其制 备方法。 背景技术
支架作为治疗血管狭窄的重要器械已经在心血管疾病领域得到了 、 越来越广泛的应用。 目前临床上的金属支架， 由于其在完成治疗任务 后将永久存留于人体， 存在削弱冠状动脉的 MRI或 CT影像、 干扰外 科血运重建、 阻碍侧枝循环的形成、 抑制血管正性重塑等缺陷。 生物 可降解支架作为可能的一种替代解决方案引起了人们的普遍关注。 生物可降解支架由可降解的聚合物材料或金属材料制成， 在植入 病变位置后可以在短期内起到支撑血管的作用， 实现血运重建。 在治 疗完成以后， 生物可降解支架在人体环境内会降解成为可被人体吸收、 代谢的有机物， 最终该支架会消失。 常见的可用于支架制备的可降解聚合物材料有聚乳酸、聚乙醇酸、 聚己内酯等； 可降解金属材料有镁合金、 铁基合金等。 镁和铁均是生 物体中不可缺少的微量元素， 具有良好的生物相容性、 独特的降解吸 收功能、 优异的综合力学性能及加工成形性能。 但是， 应用过程中发现， 聚合物支架的力学性能普遍低于金属支 架， 支架尺寸较大， 且具有较金属支架明显的血管内管腔丢失、 局部 炎症反应和内膜增生现象， 同时支架不具有显影性。 而镁合金支架的 降解速度太高， 导致镁支架在体内的力学强度衰减速率过快， 影响治 疗效果； 铁基合金支架虽然力学性能满足支架要求， 但铁支架的腐蚀 速度难以控制， 同时在模拟体液下和人体环境中的降解腐蚀机理不明， 从而限制了铁基支架作为心血管支架的应用。 为了解决镁支架过快降解的问题，美国专利申请 US2009240323 A1 公开了一种在镁支架表面进行可降解聚合物涂层的方法， 能够实现镁 支架的可控降解。 但是需要实现致密的聚合物涂层， 以避免体液从可 降解聚合物涂层渗透进入镁支架导致镁支架内部发生降解。 为了解决可降解聚合物支架力学性能较弱的问题， 美国专利申请 US20110015726 公开了一种将陶瓷材料作为增强剂， 加入可降解材料 中， 提高可降解支架的力学性能。 但陶瓷材料在血液中的降解机理不 甚清楚， 同时材料的韧性会有显著下降。 另一美国专利申请 US2009248147A1公开了一种将均聚物和无机盐作为成核剂，加入可降 解共聚材料中， 提高可降解共聚物支架的力学性能。 但共聚物本身的 结晶速率就低于均聚物， 加入成核剂对支架的力学强度提高并不显著。 为了解决显影问题， 美国专利申请 US2009149940A1 公开了一种 在支架表面覆盖一层带有显影微粒的显影层， 实现支架整体显影。 但 显影层的力学强度较低， 且显影效率较差， 且可能存在与支架主体层 的结合紧密等缺陷。 此外， 中国专利申请 CN102532835A公开了一种通过溶液共混制 备聚乳酸 /镁复合材料， 进而浇注成型制备支架。 该方法利用镁作为无 机增强介质， 提高聚乳酸支架力学性能， 并中和聚乳酸降解产生的酸 性物质。 但是， 由于镁的强度并不比聚乳酸高很多， 且两者界面相容 性不佳， 因而力学性能提高有限， 并且没有有效利用聚乳酸的结晶性 能， 导致支架的力学强度偏低。 由此可见， 现有技术对性能更佳的可降解支架仍有需求。 发明内容 本发明提供一种可降解聚酯支架及其制备方法， 将可降解金属基 粉末材料分散于聚酯基体中， 从而提高了聚酯材料的结晶性能， 并作 为增强剂提高了支架的力学性能。 可降解金属释放产生的金属离子能 预防或抑制血管再狭窄的发生， 同时有些可降解金属还具有显影能力， 从而改善了聚酯支架的显影性。 具体而言， 本发明涉及一种可條解聚酯支架， 由聚酯复合材料制 成， 其中聚酯复合材料由生物可降解聚酯材料和金属基材料复合而成, 以及金属基材料的形状为粉末状。 根据本发明， 生物可降解聚酯材料包括但不限于如下材料中的一 种或多种： 聚乳酸 （PLA) 、 聚乙醇酸 （PGA) 、 聚乳酸 -乙醇酸共聚 物 （PLGA) 、 聚己内酯 （PCL) 、 聚三亚甲基碳酸酯 （PTMC) 、 聚 酯酰胺、 聚丁二酸丁二醇酯 （PBS) 、 聚羟基丁酸戊酯 （PHBV) 、 聚 乙酰谷氨酸或聚正酯 （POE) 等聚酯材料；
根据本发明，金属基材料包括但不限于如下材料中的一种或多种： 纯镁， 纯铁， 镁基合金， 镁盐化合物或铁基合金等； 其中铁基材料可 以提高支架的显影能力。 根据本发明， 金属基材料在聚酯复合材料中的比例按重量百分比 计为 0.1~20%， 其余为生物可降解聚酯材料。 根据本发明， 金属基材料的粒径介于 lOnm-ΙΟμηι之间。 本发明还涉及可條解聚酯支架的制备方法， 其特征在于将金属基 材料分散于聚酯基体中， 制备成聚酯复合材料， 经过挤出成型、 后处 理和切割制备成支架， 包括下列步骤：
将金属基粉末材料通过溶液共混、 熔融共混或机械共混等方式加 入至聚酯基体中， 制备成聚酯复合材料；
为使金属基粉末材料能均匀分散在聚酯基体中， 提高粉末和聚酯 基体的相容性， 优选可对金属粉末进行表面改性， 如羟基改性， 有机 官能团接枝等；
形成的聚酯复合材料在高于该材料熔点以上的温度通过螺杆挤出 加工成管材形状， 其中金属基材料作为增强介质， 提高聚酯材料的力 学强度；
管材切割成支架， 或者管材经过处理后再切割成支架， 其中所述 管材处理包括退火、 吹胀、 拉伸等管材处理方式中的一种或多种的组 合， 其目的是进一步提高管材的强度、 轫性、 结晶度等性能。 为提高管材的结晶度， 管材处理的温度优先选择在聚酯的玻璃化 转变温度 -熔点之间。 本发明与现有技术的区别在于聚酯复合材料的组成、 支架的制备 方法以及支架的性能。 本发明方法可以提高可降解聚酯的结晶能力， 进而提高聚酯及支架的力学性能； 本发明方法提供的支架成型工艺简 单， 可操作性强， 可实现产量化生产。 本发明支架具有优异的生物相 容性， 有些支架具有较好的显影效果， 可以实现支架主体及整体显影。 附图说明
为了更清楚地描述本发明的技术方案， 下面将结合附图作简要介 绍。 显而易见， 这些附图仅是本申请记载的一些具体实施方式。 本发 明包括但不限于这些附图。 图 1示出了本发明最终得到的支架的结构图； 以及
图 2示出了金属基颗粒均匀分布在聚酯基体中示意图， 其中 1代 表金属颗粒， 2代表聚酯基体。 具体实施方式
为了进一步理解本发明， 下面将结合实施例对本发明的优选方案 进行描述。 这些描述只是举例说明本发明可降解聚酯支架的特征和优 点， 而非限制本发明的保护范围。 实施例 1
将一定量的纳米铁粉 (4-8g， 粒径小于 ΙΟμιη)加入至 500~1000ml 的二氯甲垸溶液中， 溶液搅拌并超声使得纳米铁粉均匀分散在溶液中， 继续加入重均分子量 30万的聚左旋乳酸粒子 96~192g， 完全溶解并搅 拌均匀， 经过冷冻干燥后粉碎成粒子， 得到聚乳酸 /铁复合材料， 其中 纳米铁粉占复合材料的重量百分比为 4%。 将聚乳酸 /铁复合材料进行单螺杆挤出加工成管材， 管材的外径
1.8mm, 内径 0.5mm。 得到的管材拉伸强度 70MPa, 弹性模量 2.5GPa， 高于同样尺寸的聚乳酸管材。 将得到的管材在 70°C 吹塑成管材， 管材外径 3.30mm， 内径 3.05mm。 将得到的管材通过激光切割成支架并压握在输送系统的球囊上。 得到的支架径向抗挤压强度 150kPa， 结晶度 54%， 高于同样尺寸的聚 乳酸支架。 将支架包装后灭菌， 手术时通过输送系统将支架送到血管的狭窄 病变位置， 对球囊进行充盈加压， 扩张支架， 从而撑开狭窄的血管。 植入后没有观察到明显炎症反应， 植入 6个月后， 观察到血管内皮化， 植入 2年后支架完全降解。 在整个手术过程中， 通过 X光机可看到整个支架的清晰轮廓。 植 入 1周天后， 发现支架在 X光下的显影性明显降低， 支架在 X光下变 得模糊。 植入 1个月后， 支架在 X光下不显影， 说明支架内的显影材 料已经代谢完毕。 在此一个月中， 未发现明显的炎症反应。 支架植入 6 个月后， 观察到血管内皮化， 部分支架波杆被血管内皮包裹， 此时支 架内层已经降解完毕， 没有对内皮细胞产生不良影响。 实施例 2
将 100g氧化镁粉末 （粒径≤100nm) 和 900g聚乙醇酸 （重均分子 量 40万）在 180-220°C通过双螺杆挤出机共混并加工， 得到聚乙醇酸 / 氧化镁复合材料管材， 其中镁合金在复合材料中的重量百分比为 10%。 管材外径 2.8mm， 内径 2.5mm。 将管材在 120°C下退火 1小时， 得到 的管材拉伸强度 70MPa， 弹性模量 3.5GPa， 高于同样尺寸的聚乙醇酸 管材。 将得到的管材通过激光切割成支架并压握在输送系统的球囊上， 得到的支架径向抗挤压强度 120kPa， 结晶度 63%， 高于同样尺寸的聚 乙醇酸支架。 将支架包装后灭菌， 手术时通过输送系统将支架送到血管的狭窄 病变位置， 对球囊进行充盈加压， 扩张支架， 从而撑开狭窄的血管。 植入后没有观察到明显炎症反应， 植入 6个月后， 观察到血管内皮化， 植入 1年后支架完全降解。 本发明与现有技术相比， 具有以下优点和效果：
( 1 )金属基材料分散于聚酯基体中，提高了聚酯材料的力学性能， 进而提高了聚酯支架的力学强度；
(2 )金属基材料均匀分散于聚酯基体中， 在聚酯管材吹塑过程中 作为成核剂， 提高了聚酯材料的结晶能力， 延长了聚酯材料的降解时 间和提高聚酯材料的力学性能；
( 3 )在聚酯支架的降解过程中， 镁降解产生的镁离子能抑制聚酯 降解过程中产生的炎症反应， 进一步预防血管再狭窄；
(4 )在聚酯支架的降解过程中， 释放的铁离子通过影响相关基因 表达减小血管平滑肌细胞的增殖， 进一步对抗血管再狭窄；
( 5 )铁合金材料在聚酯支架中， 提高了聚酯支架的显影能力， 聚 酯支架在 X下具有显影性；
( 6 )金属颗粒可以分散支架中的应力， 提高支架的疲劳寿命。 增 强后的聚酯具有较高的模量和较低的柔量， 有效降低了支架植入血管 后的蠕变形变。 以上实施例的说明只是用于帮助理解本发明的核心思想。 应当指 出， 对于本领域的普通技术人员而言， 在不脱离本发明原理的前提下， 还可以对本发明方法进行若干改进和修饰， 但这些改进和修饰也落入 本发明权利要求请求保护的范围内。

Claims

权 利 要 求 书
1.一种可降解聚酯支架， 其特征在于， 由聚酯复合材料制成， 所 述聚酯复合材料由生物可降解聚酯材料和金属基材料复合而成， 所述 金属基材料为粉末状。
2. 权利要求 1的可降解聚酯支架， 其中生物可降解聚酯材料选自 聚乳酸（PLA) 、 聚乙醇酸（PGA) 、 聚乳酸-乙醇酸共聚物（PLGA) 、 聚己内酯 （PCL) 、 聚三亚甲基碳酸酯 （PTMC) 、 聚酯酰胺、 聚丁二 酸丁二醇酯 （PBS) 、 聚羟基丁酸戊酯 （PHBV) 、 聚乙酰谷氨酸或聚 正酯 （POE) 中的一种或多种。
3. 权利要求 1的可降解聚酯支架， 其中金属基材料选自纯镁， 纯 铁， 镁基合金， 镁盐化合物或铁基合金中的一种或多种。
4. 权利要求 3的可降解聚酯支架， 其中金属基材料在聚酯复合材 料中的比例按重量百分比计为 0.1~20%， 其余为生物可降解聚酯材料。
5. 权利要求 1的可降解聚酯支架， 其中所述金属基材料的粒径介 于 ΙΟηηι-ΙΟμηι之间。
6. 权利要求 1-5任一项的可降解聚酯支架的制备方法， 包括下列 步骤：
将金属基粉末材料通过溶液共混、 熔融共混或机械共混方式加入 至聚酯基体中， 制备成聚酯复合材料；
上述聚酯复合材料在高于其熔点以上的温度通过螺杆挤出加工成 管材；
管材切割成支架， 或者管材经处理后再切割成支架， 其中管材处 理包括退火、 吹胀、 拉伸方式中的一种或多种的组合。
7. 权利要求 6的制备方法，其中对金属基粉末材料进行表面改性， 如羟基改性和 /或有机官能团接枝。
8. 权利要求 6或 7的制备方法， 其中管材处理的温度在聚酯的玻 璃化转变温度 -熔点之间。
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