WO2016145957A1 - Corrosion-resistant, high strength and ductility zn-fe zinc alloy degradable by human body and applications of the alloy - Google Patents

Corrosion-resistant, high strength and ductility zn-fe zinc alloy degradable by human body and applications of the alloy Download PDF

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WO2016145957A1
WO2016145957A1 PCT/CN2016/073438 CN2016073438W WO2016145957A1 WO 2016145957 A1 WO2016145957 A1 WO 2016145957A1 CN 2016073438 W CN2016073438 W CN 2016073438W WO 2016145957 A1 WO2016145957 A1 WO 2016145957A1
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zinc alloy
human body
degradable
stent
strength
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PCT/CN2016/073438
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French (fr)
Chinese (zh)
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周功耀
宫海波
屈功奇
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西安爱德万思医疗科技有限公司
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    • 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
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C18/00—Alloys based on zinc

Definitions

  • the present invention relates to a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy, which belongs to the technical field of medical implant materials.
  • Zinc ions are essential nutrients for the human body and participate in many metabolic activities of the human body.
  • the American Clinical Innovation Agency (ACI) recommends that the body must consume 2.5 to 6.4 mg of zinc per day, and adults who consume about 300 mg of zinc per day may have some toxic effects.
  • a zinc-based degradable bone nail releases about 0.3 to 0.3 mg of zinc per day. Even if all of these zinc ions are released into the blood vessels, they are far below the necessary intake. That is to say, the zinc ions released by the degradation of the zinc-based degradable orthopedic implant device do not cause systemic toxicity. Studies have also found that zinc ions are transported very quickly in human tissues, so zinc enrichment, cytotoxicity or necrosis does not occur near zinc-based degradable orthopedic implant devices.
  • Zinc ions have many functions in the human body and are very important to the human body. One of the most important functions is to promote bone tissue growth. The researchers found that zinc ions can activate the aminoacyl tRNA synthetase in osteoblasts and effectively inhibit the differentiation and growth of osteoclasts. Therefore, the presence of zinc ions not only promotes the increase of bone calcium content, but also facilitates bone. The increase in collagen content suggests that zinc ions have a direct osteogenesis. In addition, studies have found that zinc ions promote the binding of cartilage oligomeric matrix proteins to collagen and are catalytic elements for soft bone growth and regeneration.
  • Conventional vascular stents are generally made of non-degradable metal.
  • the disadvantage is that the metal is not degradable and cannot be removed, and retention in the blood vessel tends to cause late thrombosis.
  • a large number of clinical cases have confirmed that the thrombosis rate of patients with such stents is as high as 3% ⁇ 9 ⁇ 3 ⁇ 4 after 1 ⁇ 5 years, and the mortality after thrombosis is as high as 30%.
  • Bone nails and bone plates are commonly used medical implants for fixation of fractures and ligament injuries. Traditional bone nails and bone plates cannot be removed by non-degradable metals. Secondary surgery is required, which causes great trauma to patients. At the same time, the strength of traditional metal materials is too high, which tends to cause stress shielding, which makes it difficult for injured bone tissue to regenerate and heal.
  • Degradable medical materials in human body are becoming the focus of research and development.
  • degradable polymer materials, pure iron and iron-based alloys, pure magnesium and magnesium-based alloys are the most in-depth materials studied in recent years.
  • Degradable polymer The material strength is too low, and breakage accidents often occur during clinical use, and clinical applicability is greatly limited.
  • the strength and toughness of pure iron and iron-based alloys are much higher than those of polymer materials, but the degradation rate of iron is too slow, and the complete degradation of the day may last for several years. More seriously, the volume of rust-like substances generated during the degradation of iron has expanded several times and has a significant migration tendency.
  • the degradation products of pure magnesium and magnesium-based alloys are non-toxic and degradable, but their corrosion resistance is very poor, and they are quickly degraded in the human body, which cannot provide sufficient mechanical support.
  • the object of the present invention is to provide a Zn-Fe-based zinc with low cost, high strength, good plasticity, and controllable degradation rate, which can be degraded by the human body, in view of the deficiencies of the existing medical implant materials. Alloys and their applications.
  • the present invention provides a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy, the zinc alloy includes Zn and Fe elements; wherein the mass percentage of Zn element is: 90 ⁇ 99.998 ⁇ 3 ⁇ 4 The mass percentage of Fe element is: 0.002 ⁇ 10 ⁇ 3 ⁇ 4.
  • the zinc alloy further includes a trace element, wherein the trace element is at least one of Mg, Ca, Sr, Li, Si, Mn and a rare earth element, and the trace element and the Zn element
  • the present invention also provides a use of a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy for preparing a degradable medical device material.
  • the degradable medical device is an implanted stent, an orthopedic implant device, a dental implant device, a surgical suture or an anastomat.
  • the implanted stent comprises a vascular stent, a tracheal stent, a urethral stent, an esophageal stent, an intestinal stent or a biliary stent;
  • the orthopedic implant device comprises a fixing screw, a fixed rivet, a bone plate, a bone sleeve, an intramedullary nail or a bone tissue repairing stent;
  • the stapler includes an intestinal stapler, a vascular anastomat or a nerve stapler.
  • the alloy material has good strength and toughness.
  • Iron has the dual functions of solid solution strengthening and precipitation strengthening at room temperature and high temperature, can form a variety of stable intermetallic compounds with Zn, strengthens, and refines grains, improves plasticity, and improves alloys. Material strength and toughness.
  • FIG. 1 is a schematic view showing the microstructure of an alloy of the present invention degraded in an animal.
  • the corrosion potential of zinc is -0.76V
  • the corrosion potential of iron is -0.44V. Therefore, the addition of iron as an alloying element to zinc can produce two opposite effects.
  • the first effect is that iron is dissolved in the matrix zinc.
  • the corrosion potential of zinc is reduced, the corrosion resistance is enhanced, and the degradation rate is decreased.
  • the second effect is that the iron element and the zinc element form a granular compound, and the micro-battery is formed with the matrix zinc, the corrosion resistance is lowered, and the degradation rate is increased. .
  • By adjusting the iron content it is possible to control the degradation rate of the zinc alloy to suit the requirements of medical implant materials.
  • a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 90 ⁇ 3 ⁇ 4, Fe l0 ⁇ 3 ⁇ 4.
  • a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 99.998%, Fe 0.002%.
  • a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 99.975%, Fe O.01%, Mg0.015 ⁇ 3 ⁇ 4.
  • a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 98 ⁇ 3 ⁇ 4, Fe 1%, Mg 1%
  • a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 97.5 ⁇ 3 ⁇ 4, Fe 2%, Ce 0.5 ⁇ 3 ⁇ 4.
  • This embodiment studies the in vitro degradation mechanism and degradation performance of a zinc-based Zn-Fe alloy according to the ASTM-G31-72 standard test method, and simulates a human body fluid environment at 37 degrees Celsius to simulate a human body fluid environment. Among them, the degradation rate of the Zn-Fe-based zinc alloy is slow and controllable.
  • the tensile strength test was carried out by using the Zn-Fe-based zinc alloy prepared by the conventional method in the art in the elemental compositions of Examples 1 to 5, and the results are shown in Table 2.
  • the Zn-Fe-based zinc alloy prepared by the conventional method in the art was subjected to the elemental composition of Examples 1 to 5 to carry out an in vitro cytotoxicity test.
  • the in vivo implantation test was carried out using the Zn-Fe-based zinc alloy prepared in Example 3.
  • the Zn-Fe-based zinc alloy prepared in Example 3 was made into a filament implanted into the abdominal aorta of New Zealand white rabbit for 12 months, as shown in Fig. 1.
  • the bright area in the figure is the cross section of the alloy wire, which is close to the alloy wire.
  • the gray area is the degradation product, and the black area is the resin material for the fixed sample. It was found that the alloy filaments did not show any swelling and migration after degradation, and the degradation products remained in their original shape, and no particles or fragments were found.
  • the Zn-Fe-based zinc alloys prepared in Examples 4 and 5 were also subjected to in vivo implantation tests in the same manner, and the obtained microscopic images were similar to those of the Zn-Fe-based zinc alloy of Example 3.

Abstract

A corrosion-resistant, high strength and ductility Zn-Fe zinc alloy degradable by the human body and applications of the alloy. The zinc alloy comprises elements Zn and Fe, where the mass percentage of element Zn is: 90-99.998%, and the mass percentage of element Fe is: 0.002-10%.

Description

一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金及其应用 技术领域  Human body degradable corrosion resistant high strength and toughness Zn-Fe system zinc alloy and application thereof
[0001] 本发明涉及一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 属于医用植入材料 技术领域。  [0001] The present invention relates to a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy, which belongs to the technical field of medical implant materials.
背景技术  Background technique
[0002] 锌离子是人体必需的营养元素， 参与人体很多的新陈代谢活动。 美国临床创新 机构 （ACI) 推荐人体每天必需摄入 2.5到 6.4毫克的锌， 成年人每天摄入大约 300 毫克锌才可能会有一定毒性反应。 一枚锌基可降解骨钉每天释放的锌大约为 0.2~ 0.3毫克， 即使这些锌离子全部释放到血管里， 也远远低于人体必需的摄入量。 也就是说， 锌基可降解骨科植入器械降解释放的锌离子不会引起全身毒性。 研 究还发现， 锌离子在人体组织中的运输非常迅速， 因此锌基可降解骨科植入器 械附近不会出现锌富集、 细胞毒性或坏死。  [0002] Zinc ions are essential nutrients for the human body and participate in many metabolic activities of the human body. The American Clinical Innovation Agency (ACI) recommends that the body must consume 2.5 to 6.4 mg of zinc per day, and adults who consume about 300 mg of zinc per day may have some toxic effects. A zinc-based degradable bone nail releases about 0.3 to 0.3 mg of zinc per day. Even if all of these zinc ions are released into the blood vessels, they are far below the necessary intake. That is to say, the zinc ions released by the degradation of the zinc-based degradable orthopedic implant device do not cause systemic toxicity. Studies have also found that zinc ions are transported very quickly in human tissues, so zinc enrichment, cytotoxicity or necrosis does not occur near zinc-based degradable orthopedic implant devices.
[0003] 锌离子在人体内的功能很多， 对人体非常重要， 其中很重要的一个功能就是促 进骨组织生长。 研究人员发现由于锌离子可以激活成骨细胞中的氨酰 tRNA合成 酶， 并可有效抑制破骨细胞的分化与生长， 因此锌离子的存在不仅促进了骨钙 盐含量的增加， 还有利于骨胶原蛋白含量的提高， 这说明锌离子有直接的促成 骨功能。 另外， 研究还发现锌离子促进软骨低聚基质蛋白与胶原的结合， 是软 骨成长与再生的催化元素。  [0003] Zinc ions have many functions in the human body and are very important to the human body. One of the most important functions is to promote bone tissue growth. The researchers found that zinc ions can activate the aminoacyl tRNA synthetase in osteoblasts and effectively inhibit the differentiation and growth of osteoclasts. Therefore, the presence of zinc ions not only promotes the increase of bone calcium content, but also facilitates bone. The increase in collagen content suggests that zinc ions have a direct osteogenesis. In addition, studies have found that zinc ions promote the binding of cartilage oligomeric matrix proteins to collagen and are catalytic elements for soft bone growth and regeneration.
[0004] 传统的血管支架一般采用不可降解的金属制成， 其缺点是金属不可降解、 无法 取出， 滞留在血管内容易引发晚期血栓。 大量的临床病例证实病人植入这类支 架 1〜5年后血栓形成率高达 3%〜9<¾， 血栓形成后死亡率高达 30%。 骨钉和骨板 是常用的固定骨折和韧带损伤的医疗植入器械， 传统骨钉和骨板由不可降解的 金属无法取出， 必须进行二次手术， 对患者带来极大的创伤。 同吋， 传统金属 材料强度过高， 容易带来应力屏蔽， 导致受伤的骨组织难以再生和愈合。  [0004] Conventional vascular stents are generally made of non-degradable metal. The disadvantage is that the metal is not degradable and cannot be removed, and retention in the blood vessel tends to cause late thrombosis. A large number of clinical cases have confirmed that the thrombosis rate of patients with such stents is as high as 3%~9<3⁄4 after 1~5 years, and the mortality after thrombosis is as high as 30%. Bone nails and bone plates are commonly used medical implants for fixation of fractures and ligament injuries. Traditional bone nails and bone plates cannot be removed by non-degradable metals. Secondary surgery is required, which causes great trauma to patients. At the same time, the strength of traditional metal materials is too high, which tends to cause stress shielding, which makes it difficult for injured bone tissue to regenerate and heal.
[0005] 人体内可降解医用材料正在成为研究和幵发的重点， 其中可降解高分子材料、 纯铁及铁基合金、 纯镁及镁基合金是近年研究最为深入的材料。 可降解高分子 材料强度过低， 在临床使用过程中经常会发生断裂事故， 临床适用性收到极大 限制。 纯铁及铁基合金的强度和韧性远高于高分子材料， 但铁的降解速度太慢 ， 完全降解吋间可能长达数年。 更为严重的是， 铁降解过程中生成的铁锈状物 质体积膨胀了数倍， 并有明显的迁移趋势。 纯镁及镁基合金的降解产物无毒、 可降解， 但其耐蚀性非常差， 在人体内很快就会被降解， 无法提供足够的力学 支撑吋间。 [0005] Degradable medical materials in human body are becoming the focus of research and development. Among them, degradable polymer materials, pure iron and iron-based alloys, pure magnesium and magnesium-based alloys are the most in-depth materials studied in recent years. Degradable polymer The material strength is too low, and breakage accidents often occur during clinical use, and clinical applicability is greatly limited. The strength and toughness of pure iron and iron-based alloys are much higher than those of polymer materials, but the degradation rate of iron is too slow, and the complete degradation of the day may last for several years. More seriously, the volume of rust-like substances generated during the degradation of iron has expanded several times and has a significant migration tendency. The degradation products of pure magnesium and magnesium-based alloys are non-toxic and degradable, but their corrosion resistance is very poor, and they are quickly degraded in the human body, which cannot provide sufficient mechanical support.
[0006] 纯锌及其合金也是一种人体环境下可降解的材料， 但应用在医用材料方面仍然 存在力学强度低、 降解速率不可控的缺点， 目前都是通过向其添加其它物质来 达到改善力学性能和调控降解速率， 如申请号 201310756776.1公幵的锌中添加 Ce 、 Mg、 Cu、 Ca， 但该申请制备的锌合金材料塑性较低， 而目前还未发现将价格 低廉的铁作为锌的添加材料， 作为生物医用材料来使用。  [0006] Pure zinc and its alloys are also degradable materials in the human environment, but the application of medical materials still has the disadvantages of low mechanical strength and uncontrollable degradation rate. Currently, it is improved by adding other substances to it. Mechanical properties and regulation of degradation rate, such as Ce, Mg, Cu, Ca added to the zinc of application No. 201310756776.1, but the zinc alloy material prepared by the application has low plasticity, and it has not been found that low-cost iron is used as zinc. Add materials and use them as biomedical materials.
技术问题  technical problem
[0007] 本发明的目的是针对现有医用植入材料存在的不足， 提供一种添加材料成本低 ， 强度高、 塑性好， 降解速率可控， 同吋可被人体降解的 Zn-Fe系锌合金及其应 用。  [0007] The object of the present invention is to provide a Zn-Fe-based zinc with low cost, high strength, good plasticity, and controllable degradation rate, which can be degraded by the human body, in view of the deficiencies of the existing medical implant materials. Alloys and their applications.
问题的解决方案  Problem solution
技术解决方案  Technical solution
[0008] 本发明提供一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 所述的锌合金中包 括 Zn和 Fe元素； 其中 Zn元素的质量百分含量为： 90〜99.998<¾， Fe元素的质量百 分含量为： 0.002〜10<¾。  [0008] The present invention provides a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy, the zinc alloy includes Zn and Fe elements; wherein the mass percentage of Zn element is: 90~99.998<3⁄4 The mass percentage of Fe element is: 0.002~10<3⁄4.
[0009] 基于以上合金材料的组成， 为了优化力学性能和生物腐蚀性能， 我们对锌合金 材料优化为锌合金中 Zn元素的质量百分含量为： 92〜99.995%， Fe元素的质量百 分数为 0.005〜8<¾。 [0009] Based on the composition of the above alloy materials, in order to optimize the mechanical properties and biocorrosion properties, we optimize the zinc alloy material to the mass percentage of Zn element in the zinc alloy: 92~99.995%, and the mass percentage of Fe element is 0.005. ~8<3⁄4.
[0010] 更优选地， 所述的锌合金中还包括微量元素， 所述微量元素为 Mg、 Ca、 Sr、 L i、 Si、 Mn和稀土元素中至少一种， 所述微量元素与 Zn元素的质量比为 0〜0.056 ： 1 =  [0010] More preferably, the zinc alloy further includes a trace element, wherein the trace element is at least one of Mg, Ca, Sr, Li, Si, Mn and a rare earth element, and the trace element and the Zn element The mass ratio is 0~0.056: 1 =
[0011] 基于以上合金材料的组成， 为了优化力学性能和生物腐蚀性能， 我们对合金材 料进一步优化为， 所述锌合金中微量元素与 Zn元素的质量比为 0〜0.023： 1。 [0012] 上述发明所制备的人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 使用本领域常规 的方法制备成可降解医疗植入体。 [0011] Based on the composition of the above alloy material, in order to optimize the mechanical properties and the bio-corrosion properties, we further optimize the alloy material such that the mass ratio of the trace element to the Zn element in the zinc alloy is 0 to 0.023:1. [0012] The human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy prepared by the above invention is prepared into a degradable medical implant using a method conventional in the art.
[0013] 因此， 本发明还提供一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金在制备可降 解医疗器械材料中的应用。 Accordingly, the present invention also provides a use of a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy for preparing a degradable medical device material.
[0014] [0014]优选地， 所述可降解医疗器械为植入支架、 骨科植入器械、 齿科植入器 械、 手术缝合线或吻合器。 其中植入支架包括血管支架、 气管支架、 尿道支架 、 食道支架、 肠道支架或胆道支架； 骨科植入器械包括固定螺丝、 固定铆钉、 骨板、 骨套、 髓内针或骨组织修复支架； 吻合器包括肠道吻合器、 血管吻合器 或神经吻合器。 [0014] Preferably, the degradable medical device is an implanted stent, an orthopedic implant device, a dental implant device, a surgical suture or an anastomat. The implanted stent comprises a vascular stent, a tracheal stent, a urethral stent, an esophageal stent, an intestinal stent or a biliary stent; the orthopedic implant device comprises a fixing screw, a fixed rivet, a bone plate, a bone sleeve, an intramedullary nail or a bone tissue repairing stent; The stapler includes an intestinal stapler, a vascular anastomat or a nerve stapler.
发明的有益效果  Advantageous effects of the invention
有益效果  Beneficial effect
[0015] 1、 添加材料成本低廉， 制备的合金材料各成分降解产物可被人体代谢降解； [0016] 2、 耐蚀性远高于镁合金， 降解速率可控；  [0015] 1. The added material is low in cost, and the degradation products of the prepared alloy materials can be metabolically degraded by the human body; [0016] 2. The corrosion resistance is much higher than that of the magnesium alloy, and the degradation rate is controllable;
[0017] 3、 合金材料强度和韧性好。 铁元素在室温和高温下具有固溶强化和沉淀强化 的双重作用， 能与 Zn形成多种稳定的金属间化合物、 起到强化作用， 并有细化 晶粒、 提高塑性的效果， 提高了合金材料强度和韧性。  [0017] 3. The alloy material has good strength and toughness. Iron has the dual functions of solid solution strengthening and precipitation strengthening at room temperature and high temperature, can form a variety of stable intermetallic compounds with Zn, strengthens, and refines grains, improves plasticity, and improves alloys. Material strength and toughness.
对附图的简要说明  Brief description of the drawing
附图说明  DRAWINGS
[0018] 图 1为本发明合金在动物体内降解显微结构示意图。  [0018] FIG. 1 is a schematic view showing the microstructure of an alloy of the present invention degraded in an animal.
本发明的实施方式 Embodiments of the invention
[0019] 下面结合具体实施例对本发明做进一步说明。 [0019] The present invention will be further described below in conjunction with specific embodiments.
[0020] 由于生物环境和功能需求的差异， 不同的可降解植入器械对降解速度的要求是 不一样的。 锌的的腐蚀电位是 -0.76V, 铁的腐蚀电位是 -0.44V, 因此铁作为合金 元素加入锌中可同吋产生两种相反的效果， 第一种效果是铁元素固溶到基体锌 中， 锌的腐蚀电位降低、 耐蚀性增强、 降解速度降低； 第二种效果是铁元素与 锌元素生成颗粒状化合物， 与基体锌形成微电池、 耐蚀性下降、 降解速度升高 。 通过调节铁的含量， 可以达到控制锌合金的降解速度使其适于医用植入材料 的要求。 [0020] Due to differences in biological environment and functional requirements, different degradable implant devices have different requirements for degradation rate. The corrosion potential of zinc is -0.76V, and the corrosion potential of iron is -0.44V. Therefore, the addition of iron as an alloying element to zinc can produce two opposite effects. The first effect is that iron is dissolved in the matrix zinc. The corrosion potential of zinc is reduced, the corrosion resistance is enhanced, and the degradation rate is decreased. The second effect is that the iron element and the zinc element form a granular compound, and the micro-battery is formed with the matrix zinc, the corrosion resistance is lowered, and the degradation rate is increased. . By adjusting the iron content, it is possible to control the degradation rate of the zinc alloy to suit the requirements of medical implant materials.
[0021] 实施例 1 Embodiment 1
[0022] 本发明的一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其元素组成及质量百 分比为： Zn 90<¾， Fe l0<¾。  [0022] A human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 90<3⁄4, Fe l0<3⁄4.
[0023] 实施例 2 [0023] Example 2
[0024] 本发明的一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其元素组成及质量百 分比为： Zn 99.998% , Fe 0.002%。  [0024] A human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 99.998%, Fe 0.002%.
[0025] 实施例 3 Embodiment 3
[0026] 本发明的一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其元素组成及质量百 分比为： Zn 99.975%， Fe O.01% , Mg0.015<¾。  [0026] A human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 99.975%, Fe O.01%, Mg0.015<3⁄4.
[0027] 实施例 4 Embodiment 4
[0028] 本发明的一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其元素组成及质量百 分比为： Zn 98<¾， Fe 1% , Mg 1%  [0028] A human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 98<3⁄4, Fe 1%, Mg 1%
[0029] 实施例 5 [0029] Example 5
[0030] 本发明的一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其元素组成及质量百 分比为： Zn 97.5<¾， Fe 2% , Ce 0.5<¾。  [0030] A human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy of the present invention has an elemental composition and mass percentage: Zn 97.5<3⁄4, Fe 2%, Ce 0.5<3⁄4.
[0031] 实施例 6 Example 6
[0032] 以实施例 1〜5中元素组成使用本领域常规方法制得的 Zn-Fe系锌合金， 进行模 拟人体体液浸泡试验， 测试 Zn-Fe系锌合金降解速率实验测试结果如表一： [0033] 表一  [0032] The Zn-Fe-based zinc alloy prepared by the conventional method in the prior art using the elemental composition in Examples 1 to 5 was subjected to a simulated human body liquid immersion test, and the experimental results of testing the degradation rate of the Zn-Fe-based zinc alloy are shown in Table 1: [0033] Table 1
[] []
序号 隨醇（聽年 Serial number with alcohol
1 实施例 :1 0.47 1 Example: 1 0.47
',■ 实施例 : I 0.08 ', ■ Example : I 0.08
3 实施例 . 3 0.13 3 Examples . 3 0.13
4 实施例 4 0.26 实施例 5 0.22 纖 3.53 4 Example 4 0.26 Example 5 0.22 fiber 3.53
:  :
WE 3镁令 3.8  WE 3 magnesium order 3.8
[0034] 本实施例依据 ASTM-G31-72标准测试方法对锌基 Zn-Fe系合金的体外降解机理 与降解性能进行了研究， 37摄氏度的模拟人体体液模拟人体体液环境， 发现在 这种环境中， Zn-Fe系锌合金的降解速度缓慢且可控。 [0034] This embodiment studies the in vitro degradation mechanism and degradation performance of a zinc-based Zn-Fe alloy according to the ASTM-G31-72 standard test method, and simulates a human body fluid environment at 37 degrees Celsius to simulate a human body fluid environment. Among them, the degradation rate of the Zn-Fe-based zinc alloy is slow and controllable.
[0035] 实施例 7 [0035] Example 7
[0036] 以实施例 1〜5中元素组成使用本领域常规方法制得的 Zn-Fe系锌合金进行拉伸 强度试验， 结果如表二所示。  The tensile strength test was carried out by using the Zn-Fe-based zinc alloy prepared by the conventional method in the art in the elemental compositions of Examples 1 to 5, and the results are shown in Table 2.
[0037] 表二 [0037] Table 2
[] []
[0038] 本实施例根据 GB/T228.1-2010测试标准， 对 Zn-Fe系锌合金实施例 1〜5进行拉 伸力学性能测试， 结果如表二所示。 发现 Zn-Fe系锌合金屈服强度最高可达 380M Pa, 断裂延伸率高达 28%， 这是由于铁与锌生成弥散分布的细小化合物颗粒， 达 到细化晶粒的效果， 而加入的微量元素进一步改善材料力学性能。 [0038] In this example, according to the GB/T228.1-2010 test standard, the tensile mechanical properties of the Zn-Fe-based zinc alloy examples 1 to 5 were tested, and the results are shown in Table 2. It is found that the yield strength of Zn-Fe-based zinc alloy is up to 380M Pa and the elongation at break is as high as 28%. This is due to the formation of finely dispersed fine particles of iron and zinc to achieve the effect of refining the grains, and the added trace elements are further Improve the mechanical properties of materials.
[0039] 实施例 8 Example 8
[0040] 以实施例 1〜5中元素组成使用本领域常规方法制得的 Zn-Fe系锌合金， 进行体 外细胞毒性测试。  The Zn-Fe-based zinc alloy prepared by the conventional method in the art was subjected to the elemental composition of Examples 1 to 5 to carry out an in vitro cytotoxicity test.
[0041] 本实施例根据 GB/T 16886.5-2003对锌合金进行了体外细胞毒性测试， 将成纤维 细胞 L-929培养在锌合金降解产物的提取液里， 测量 24小吋和 72小吋的细胞活性 ， 并与培养在常规培养液的细胞活性作对比， 发现培养在锌合金降解产物提取 液里的细胞活性均高于 90%， 且细胞形貌非常健康， 因此可以认为锌合金降解产 物对细胞活性没有影响， 细胞对锌合金降解产物没有毒性反应。 [0041] In this example, an in vitro cytotoxicity test was performed on a zinc alloy according to GB/T 16886.5-2003, and fibroblast L-929 was cultured in an extract of a zinc alloy degradation product, and cells of 24 hours and 72 cells were measured. Activity, and compared with the cell viability of the culture in the conventional culture, it was found that the culture was extracted in the zinc alloy degradation product. The cell activity in the liquid is higher than 90%, and the cell morphology is very healthy. Therefore, it can be considered that the zinc alloy degradation product has no effect on the cell activity, and the cell has no toxicity reaction to the zinc alloy degradation product.
[0042] 实施例 9 Example 9
[0043] 以实施例 3中制得的 Zn-Fe系锌合金， 进行体内植入测试。 将实施例 3制备的 Zn- Fe系锌合金制成细丝植入新西兰白兔腹主动脉中 12个月， 如图 1所示， 图中亮区 为合金丝横截面， 紧贴合金丝的灰色区域即为降解产物， 黑色区域为固定样品 用的树脂材料。 研究发现合金丝在降解后没有发现任何膨胀和迁移的情况， 其 降解产物仍维持原来的形状， 没有发现掉落颗粒、 碎片的现象。 同吋对实施例 4 和 5制备的 Zn-Fe系锌合金同样进行体内植入测试， 得到的显微图像与以实施例 3 的 Zn-Fe系锌合金相似。  [0043] The in vivo implantation test was carried out using the Zn-Fe-based zinc alloy prepared in Example 3. The Zn-Fe-based zinc alloy prepared in Example 3 was made into a filament implanted into the abdominal aorta of New Zealand white rabbit for 12 months, as shown in Fig. 1. The bright area in the figure is the cross section of the alloy wire, which is close to the alloy wire. The gray area is the degradation product, and the black area is the resin material for the fixed sample. It was found that the alloy filaments did not show any swelling and migration after degradation, and the degradation products remained in their original shape, and no particles or fragments were found. The Zn-Fe-based zinc alloys prepared in Examples 4 and 5 were also subjected to in vivo implantation tests in the same manner, and the obtained microscopic images were similar to those of the Zn-Fe-based zinc alloy of Example 3.
[0044] 以上内容是结合具体的实施方式对本发明所做的进一步详细说明， 不能认定本 发明的具体实施只局限于这些说明。 对于本发明所属技术领域的普通技术人员 来说， 在不脱离本发明构思的前提下， 还可以做出若干简单推演或替换， 都应 当视为属于本发明的保护范围。  The above is a further detailed description of the present invention in connection with the specific embodiments, and the specific embodiments of the present invention are not limited to the description. It will be apparent to those skilled in the art that the present invention may be practiced without departing from the spirit and scope of the invention.

Claims

权利要求书 Claim
[权利要求 1] 一种人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其特征在于： 所述的 锌合金中包括 Zn和 Fe元素； 其中 Zn元素的质量百分含量为： 90〜99.9 98% , Fe元素的质量百分含量为： 0.002〜10<¾。  [Claim 1] A human body degradable corrosion-resistant high-strength and toughness Zn-Fe-based zinc alloy, characterized in that: the zinc alloy includes Zn and Fe elements; wherein the mass percentage of Zn element is: 90~ 99.9 98%, the mass percentage of Fe element is: 0.002~10<3⁄4.
[权利要求 2] 如权利要求 1所述的人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其特征 在于： 所述锌合金中 Zn元素的质量百分含量为： 92〜99.995%， Fe元 素的质量百分数为 0.005〜8%。  [Claim 2] The human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy according to claim 1, wherein: the mass percentage of Zn element in the zinc alloy is: 92 to 99.995%, The mass percentage of Fe element is 0.005 to 8%.
[权利要求 3] 如权利要求 1或 2所述的人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其 特征在于： 所述的锌合金中还包括微量元素， 所述微量元素为 Mg、 C a、 Sr、 Li、 Si、 Mn和稀土元素中至少一种， 所述微量元素与 Zn元素 的质量比为 0〜0.056： 1。  [Claim 3] The human body degradable high-strength and toughness Zn-Fe-based zinc alloy according to claim 1 or 2, wherein: the zinc alloy further includes a trace element, and the trace element is Mg. At least one of C a, Sr, Li, Si, Mn and a rare earth element, the mass ratio of the trace element to the Zn element is 0 to 0.056:1.
[权利要求 4] 如权利要求 3所述的人体可降解的耐蚀高强韧 Zn-Fe系锌合金， 其特征 在于： 所述锌合金中微量元素与 Zn元素的质量比为 0〜0.023： 1。  [Claim 4] The human body degradable high-strength and toughness Zn-Fe-based zinc alloy according to claim 3, wherein the mass ratio of the trace element to the Zn element in the zinc alloy is 0 to 0.023: .
[权利要求 5] —种如权利要求 1〜4中任一项所述的人体可降解的耐蚀高强韧 Zn-Fe 系锌合金在制备可降解医疗器械材料中的应用。  [Claim 5] The use of a human body degradable corrosion-resistant high-strength Zn-Fe-based zinc alloy according to any one of claims 1 to 4 for the preparation of a degradable medical device material.
[权利要求 6] 如权利要求 5所述的人体可降解的耐蚀高强韧 Zn-Fe系锌合金在制备可 降解医疗器械材料中的应用， 其特征在于： 所述可降解医疗器械为植 入支架、 骨科植入器械、 齿科植入器械、 手术缝合线或吻合器； 其中 植入支架包括血管支架、 气管支架、 尿道支架、 食道支架、 肠道支架 或胆道支架； 骨科植入器械包括固定螺丝、 固定铆钉、 骨板、 骨套、 髓内针或骨组织修复支架； 吻合器包括肠道吻合器、 血管吻合器或神 经吻合器。  [Claim 6] The use of a human body degradable corrosion-resistant high-toughness Zn-Fe-based zinc alloy according to claim 5 for preparing a degradable medical device material, characterized in that: the degradable medical device is implanted Stent, orthopedic implant device, dental implant device, surgical suture or stapler; wherein the implant stent includes a vascular stent, a tracheal stent, a urethral stent, an esophageal stent, an intestinal stent or a biliary stent; the orthopedic implant device includes a fixation Screws, fixed rivets, bone plates, bone sleeves, intramedullary needles or bone tissue repair stents; staplers include intestinal staplers, vascular anastomoses or nerve staplers.
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