WO2021243684A1 - 一种可降解镁合金原位复合吻合钉及其制备方法 - Google Patents

一种可降解镁合金原位复合吻合钉及其制备方法 Download PDF

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WO2021243684A1
WO2021243684A1 PCT/CN2020/094574 CN2020094574W WO2021243684A1 WO 2021243684 A1 WO2021243684 A1 WO 2021243684A1 CN 2020094574 W CN2020094574 W CN 2020094574W WO 2021243684 A1 WO2021243684 A1 WO 2021243684A1
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magnesium alloy
staple
situ
degradable
situ composite
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PCT/CN2020/094574
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English (en)
French (fr)
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马政
谭丽丽
杨柯
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四川镁合医疗器械有限责任公司
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Priority to EP20938897.4A priority Critical patent/EP4163408A4/en
Priority to GB2218101.0A priority patent/GB2612205A/en
Priority to JP2022574633A priority patent/JP7557889B2/ja
Priority to PCT/CN2020/094574 priority patent/WO2021243684A1/zh
Priority to KR1020227046499A priority patent/KR20230022189A/ko
Publication of WO2021243684A1 publication Critical patent/WO2021243684A1/zh
Priority to US18/073,138 priority patent/US20230107960A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/064—Surgical staples, i.e. penetrating the tissue
    • A61B17/0644—Surgical staples, i.e. penetrating the tissue penetrating the tissue, deformable to closed position
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C1/00—Making non-ferrous alloys
    • C22C1/02—Making non-ferrous alloys by melting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/064—Surgical staples, i.e. penetrating the tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/11—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21C—MANUFACTURE OF METAL SHEETS, WIRE, RODS, TUBES OR PROFILES, OTHERWISE THAN BY ROLLING; AUXILIARY OPERATIONS USED IN CONNECTION WITH METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL
    • B21C1/00—Manufacture of metal sheets, metal wire, metal rods, metal tubes by drawing
    • B21C1/003—Drawing materials of special alloys so far as the composition of the alloy requires or permits special drawing methods or sequences
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21C—MANUFACTURE OF METAL SHEETS, WIRE, RODS, TUBES OR PROFILES, OTHERWISE THAN BY ROLLING; AUXILIARY OPERATIONS USED IN CONNECTION WITH METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL
    • B21C23/00—Extruding metal; Impact extrusion
    • B21C23/001—Extruding metal; Impact extrusion to improve the material properties, e.g. lateral extrusion
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21C—MANUFACTURE OF METAL SHEETS, WIRE, RODS, TUBES OR PROFILES, OTHERWISE THAN BY ROLLING; AUXILIARY OPERATIONS USED IN CONNECTION WITH METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL
    • B21C23/00—Extruding metal; Impact extrusion
    • B21C23/002—Extruding materials of special alloys so far as the composition of the alloy requires or permits special extruding methods of sequences
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21C—MANUFACTURE OF METAL SHEETS, WIRE, RODS, TUBES OR PROFILES, OTHERWISE THAN BY ROLLING; AUXILIARY OPERATIONS USED IN CONNECTION WITH METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL
    • B21C23/00—Extruding metal; Impact extrusion
    • B21C23/02—Making uncoated products
    • B21C23/04—Making uncoated products by direct extrusion
    • B21C23/08—Making wire, bars, tubes
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C23/00—Alloys based on magnesium
    • C22C23/04—Alloys based on magnesium with zinc or cadmium as the next major constituent
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C23/00—Alloys based on magnesium
    • C22C23/06—Alloys based on magnesium with a rare earth metal as the next major constituent
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22F—CHANGING THE PHYSICAL STRUCTURE OF NON-FERROUS METALS AND NON-FERROUS ALLOYS
    • C22F1/00—Changing the physical structure of non-ferrous metals or alloys by heat treatment or by hot or cold working
    • C22F1/06—Changing the physical structure of non-ferrous metals or alloys by heat treatment or by hot or cold working of magnesium or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C22/00—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C22/05—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions
    • C23C22/06—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions using aqueous acidic solutions with pH less than 6
    • C23C22/34—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions using aqueous acidic solutions with pH less than 6 containing fluorides or complex fluorides
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25F—PROCESSES FOR THE ELECTROLYTIC REMOVAL OF MATERIALS FROM OBJECTS; APPARATUS THEREFOR
    • C25F3/00—Electrolytic etching or polishing
    • C25F3/16—Polishing
    • C25F3/18—Polishing of light metals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00004—(bio)absorbable, (bio)resorbable or resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00526—Methods of manufacturing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00964—Material properties composite
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

Definitions

  • the invention relates to the technical field of biomedical materials, and in particular provides a degradable magnesium alloy in-situ composite anastomosis nail and a preparation method thereof.
  • the existing titanium alloy nails are non-degradable and are foreign bodies in the human body. Long-term retention can easily lead to inflammation, delayed healing, sensitization, carcinogenesis and other adverse reactions in the body.
  • the implanted device is removed, and a second operation is required, which brings additional surgical risks, economic pressure and physical pain to the patient.
  • Magnesium alloys are degradable.
  • the use of magnesium's prone to corrosion in the human environment can achieve the medical and clinical purpose of gradual biodegradation of magnesium alloy implants in the body until the final disappearance.
  • it can avoid two Removal operation at one time can reduce the mental and economic burden of patients, but there are still problems such as too fast degradation rate, poor mechanical strength and plasticity.
  • Patent authorization announcement number CN106086562B prepares magnesium alloy staples containing Zn, Mn, Sn, Ag, HA powder through an alloying method, which improves the corrosion resistance and plasticity of the alloy to a certain extent; however, the preparation process is more complicated. Moreover, it is extremely difficult to directly form an anastomotic nail by extrusion, and there is no relevant academic literature report. Patent Authorization Announcement No. CN 201617885 U By preparing ceramic, metal, and oxide coatings on the surface of the staples, the corrosion resistance, strength and hardness of the staples are greatly improved, but the harder coating is deformed on the staples. The coating is easy to fall off during the anastomosis process, which affects the use effect of the staples. Patent Publication No.
  • CN 105326535 A adds a drug coating to the surface of the staple nail, which has biological functions such as anti-bacterial infection, hemostasis, and inhibiting vascular restenosis, but it does not fundamentally solve the problem of matching the mechanical properties of the degradable nail with the degradation rate.
  • the purpose of the present invention is to provide a degradable magnesium alloy in-situ composite anastomosis nail and a preparation method thereof, and solve the problems of the degradable magnesium alloy nail such as fast degradation rate, low mechanical strength and poor plasticity.
  • a degradable magnesium alloy in-situ composite anastomosing nail is a composite structural material. It is mainly divided into two parts. The inner part is composed of Mg-Zn-Nd magnesium alloy with high strength and good plasticity, and the outer part is made of magnesium alloy with high strength and good plasticity. It is composed of MgF 2 made of Mg-Zn-Nd magnesium alloy staples with in-situ composite MgF 2 on the outer layer.
  • the chemical composition and content of the Mg-Zn-Nd magnesium alloy staples are as follows: Zn 0.2% to 3.0%, Nd 0.2% to 2.3%, in terms of weight percentage, The balance is Mg.
  • the described degradable magnesium alloy in-situ composite staples in terms of weight percentage, the technical indicators of Mg-Zn-Nd magnesium alloy staples are as follows: the tensile strength range is 260-320MPa, the yield strength range is 170-240MPa, extension The rate ranges from 20 to 33%.
  • the thickness of the MgF 2 having a corrosion protection effect on the outer layer is 1.0 ⁇ m to 3.3 ⁇ m.
  • the preparation method of the degradable magnesium alloy in-situ composite anastomosis nail includes the following operation steps:
  • the magnesium alloy bar in step (2) is prepared by cold drawing into a wire with a diameter of 0.2-0.6 mm, and heat-treated and annealed at a temperature of 280-330° C., and a heat preservation time of 30 min-120 min;
  • step (5) Immerse the staples in step (5) in hydrofluoric acid for in- situ MgF 2 compounding.
  • the weight concentration of hydrofluoric acid is 20%-60%, the time is 3h-200h, and the treatment temperature is 20-35°C. ;
  • step (6) The in-situ composite magnesium alloy staples of step (6) are ultrasonically cleaned, dried, and vacuum packaged.
  • the bending part of the U-shaped staple is elliptical, the total length of the staple is 10-15mm, the height of the staple is 3-6mm, and the staple The diameter of the end face is 0.20 ⁇ 0.35mm.
  • the polishing time is 1-10min
  • the voltage is 10-20V
  • the weight concentration of phosphoric acid is 85%.
  • the design idea of the present invention is:
  • the invention prepares a magnesium-based composite material anastomosis nail.
  • the alloying elements Zn and Nd are used to improve the strength and plasticity of the alloy, and the degradation speed of magnesium alloy anastomo
  • the outermost layer of the nail is compounded with magnesium fluoride and magnesium oxide to improve the corrosion resistance of the staple nail.
  • the magnesium-based composite material anastomosis nail of the present invention has alloying elements of Zn and Nd.
  • Zn can form significant solid solution and age strengthening in Mg, improve alloy strength, effectively soften the sliding direction of the alloy cylinder, and improve the magnesium alloy
  • Zn is an essential trace element in the human body. It participates in the metabolism of proteins and enzymes, and has a close relationship with the operation of the nervous system and the maintenance of immune organs. It has high biological safety.
  • the solid solubility of Nd in magnesium is 3.6%, and the drawing performance and corrosion resistance of magnesium alloys can be improved through solution heat treatment, and the strength and plasticity of magnesium alloys can be improved at the same time through the refinement of crystal grains.
  • the appropriate amount of rare earth elements can promote the proliferation of osteoblasts, protect the nervous system, anticoagulant, prevent arteriosclerosis, treat diabetes, anti-cancer, anti-inflammatory and analgesic effects. Only when the rare earth elements are excessive, can they cause certain adverse effects on the human body.
  • the fluorine introduced in the in-situ compound is one of the important trace elements in the human body.
  • the fluorine element can stimulate the proliferation of osteoblasts and promote the deposition of minerals on the cancellous bone, promote the absorption of iron and the growth of bones and teeth, and improve Nervous system excitability and play a good anti-aging effect.
  • the safe and appropriate intake of fluorine announced by the Chinese Nutrition Society is 1.5 to 4.0 mg for adults.
  • the present invention first adopts an alloying strategy to prepare a Mg-Zn-Nd alloy, and after cooling The drawing and heat treatment process improves the mechanical strength and plasticity of the alloy, and finally prepares the staple nail, and then adopts the in-situ composite magnesium fluoride process, so that the designed staple nail has better corrosion resistance and biological safety.
  • the anastomotic nail can better meet the requirements of in vivo use.
  • the anastomotic nail of the present invention has good biological safety, mechanical properties and plasticity, excellent corrosion resistance, can meet the use requirements of the anastomosis nail, and can degrade and disappear after reaching the use effect in the matrix, avoiding secondary operations take out.
  • the magnesium-based composite material of the present invention can improve the mechanical properties of the staples, and obtain better corrosion resistance, which meets the use requirements of medical degradable staples.
  • Figure 1 shows the SEM morphology of magnesium-based composites.
  • 2 layers are in-situ composite MgF 2
  • 3 layers are magnesium alloy matrix
  • 1 layer is epoxy resin required for sample preparation.
  • the present invention prepares a degradable staple with good biological safety, mechanical properties and plasticity, and excellent corrosion resistance through alloying combined drawing and in-situ compounding processes.
  • the preparation method of anastomosis nails smelt pure magnesium, 1% Zn, 1% Nd into liquid metal by weight percentage, cast into ingots, remove surface defects and impurities, and perform homogenization heat treatment at 400°C for 4 hours ,
  • the magnesium alloy bar with a magnesium diameter of 10mm is processed by hot extrusion at 430°C (extrusion ratio is 70:1), and it is drawn to a wire with a diameter of 0.3mm by cold drawing, and heat-treated and annealed at 300°C for 60min.
  • the magnesium alloy wire is prepared into a U-shaped staple, the bending part of the U-shaped staple is elliptical, the total length of the staple is 10-15mm, the height of the staple is 3-6mm, and the end surface diameter of the staple is 0.20-0.35mm.
  • the anastomotic nail is electrolytically polished to remove surface defects and impurities.
  • the polishing time is 5min, the voltage is 15V, and the weight concentration of phosphoric acid is 85%;
  • the staples are immersed in hydrofluoric acid for magnesium fluoride in-situ compounding.
  • the weight concentration of hydrofluoric acid is 35%.
  • the compound is compounded at room temperature for 6 hours.
  • the staples are cleaned ultrasonically and then blown dry. Vacuum Package.
  • the mechanical properties and cytotoxicity data of the staple nail in this example are shown in Table 1, and the corrosion performance data is shown in Table 2.
  • the preparation method of the staples in terms of weight percentage, pure magnesium, 1.73% Zn, 0.68% Nd are smelted into liquid metal, cast into ingots, surface defects and impurities are removed, and homogenization heat treatment is performed at 380°C for 6 hours ,
  • the magnesium alloy bar with a magnesium diameter of 10mm is processed by hot extrusion at 420°C (extrusion ratio is 60:1), and the wire is drawn to a wire with a diameter of 0.3mm by cold drawing, and heat-treated and annealed at 280°C for 120 minutes.
  • the magnesium alloy wire is prepared into a U-shaped staple, the bending part of the U-shaped staple is elliptical, the total length of the staple is 10-15mm, the height of the staple is 3-6mm, and the end surface diameter of the staple is 0.20-0.35mm. Electropolishing the staple nail to remove surface defects and impurities.
  • the polishing time is 3min, the voltage is 20V, and the weight concentration of phosphoric acid is 85%;
  • the staple nail is immersed in hydrofluoric acid for in-situ compounding of magnesium fluoride.
  • the weight concentration of hydrofluoric acid is 40%.
  • the compound is compounded at room temperature for 7 hours.
  • the staple nail is cleaned by ultrasonic and then blown dry. Package.
  • the mechanical properties and cytotoxicity data of the staple nail in this example are shown in Table 1, and the corrosion performance data is shown in Table 2.
  • the preparation method of the staples in terms of weight percentage, pure magnesium, 1.6% Zn, 0.7% Nd are smelted into liquid metal, cast into ingots, surface defects and impurities are removed, and homogenization heat treatment is performed at 420°C for 5 hours ,
  • the magnesium alloy rods with a magnesium diameter of 10mm are processed by hot extrusion at 410°C (extrusion ratio is 80:1), and they are drawn to a wire with a diameter of 0.3mm by cold drawing, and heat-treated and annealed at 320°C for 30 minutes.
  • the magnesium alloy wire is prepared into a U-shaped staple, the bending part of the U-shaped staple is elliptical, the total length of the staple is 10-15 mm, the height of the staple is 3-6 mm, and the end surface diameter of the staple is 0.20-0.35 mm.
  • the staples are immersed in hydrofluoric acid for magnesium fluoride in-situ compounding. The weight concentration of hydrofluoric acid is 45%.
  • the compound is compounded at room temperature for 8 hours.
  • the staples are cleaned ultrasonically and then blown dry. Vacuum Package.
  • the mechanical properties and cytotoxicity data of the staple nail in this example are shown in Table 1, and the corrosion performance data is shown in Table 2.
  • the staples of the present invention have higher tensile strength and excellent plasticity, and can meet their mechanical performance.
  • the cytotoxicity of the staples is 0 grade, indicating that they have higher cellularity. compatibility.
  • the magnesium alloy composite staples of the present invention have good plastic deformation ability and mechanical strength, slow degradation speed, excellent biological safety, and meet the requirements of implantation of staples in the body. After reaching the medical effect, it can be gradually degraded in the body, avoiding the second operation to take it out.

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Abstract

一种可降解镁合金原位复合吻合钉及其制备方法，涉及生物医用材料技术领域。该吻合钉为一种复合结构材料，主要分两部分，内部由强度高、塑性好的Mg-Zn-Nd镁合金组成，外部由起腐蚀保护作用的MgF 2组成，由Mg-Zn-Nd镁合金吻合钉的外层原位复合MgF 2而成。该镁合金复合材料吻合钉具有良好的塑性变形能力及力学强度，较慢的降解速度，优良的生物安全性，满足吻合钉在体内的植入要求，在生物体内达到医疗效果后可在体内逐步降解，避免二次手术取出。

Description

一种可降解镁合金原位复合吻合钉及其制备方法 技术领域
本发明涉及生物医用材料技术领域，特别提供一种可降解镁合金原位复合吻合钉及其制备方法。
背景技术
现有的钛合金钉是不可降解的，在人体内属于异物，长期驻留极易导致机体出现炎症、愈合迟缓、致敏、致癌等不良反应。当机体病患组织修复或愈合之后取出植入器件，需要二次手术，给患者带来额外的手术风险、经济压力和生理痛苦。
镁合金是可降解的，利用镁在人体环境中易发生腐蚀的特性，来实现镁合金植入物在体内逐渐生物降解直至最终消失的医学临床目的，与传统植入金属相比，可避免二次取出手术，减轻患者的精神和经济负担，但是仍存在降解速率太快，力学强度和塑性较差等问题。
专利授权公告号CN106086562B通过一种合金化方法，制备含Zn、Mn、Sn、Ag、HA粉的镁合金吻合钉，在一定程度上提高合金的耐腐蚀性能和塑性；但是该制备流程较为复杂，且直接通过挤压成型吻合钉难度极大，目前还未见过相关学术文献报道。专利授权公告号CN 201617885 U通过在吻合钉表面制备陶瓷、金属、氧化物涂层，在很大程度上提高吻合钉的耐腐蚀性能、强度和硬度，但是该较硬的涂层在吻合钉变形吻合的过程中容易涂层脱落，影响吻合钉的使用效果。专利公开号CN 105326535 A在吻合钉表面添加药物涂层，具备抗细菌感染，止血，抑制血管再狭窄等生物学功能，但是未从根本上解决可降解钉力学性能与降解速率相匹配的问题。
发明内容
本发明的目的是提供一种可降解镁合金原位复合吻合钉及其制备方法，解决可降解镁合金钉存在的降解速率快，力学强度低和塑性差等问题。
本发明的技术方案是：
一种可降解镁合金原位复合吻合钉，该吻合钉为一种复合结构材料，主要分两部分，内部由强度高、塑性好的Mg-Zn-Nd镁合金组成，外部由起腐蚀保护作用的MgF 2组成，由Mg-Zn-Nd镁合金吻合钉的外层原位复合MgF 2而成。
所述的可降解镁合金原位复合吻合钉，按重量百分比计，Mg-Zn-Nd镁合金吻合钉的化学成分和含量为：Zn0.2％～3.0％，Nd0.2％～2.3％，余量为Mg。
所述的可降解镁合金原位复合吻合钉，按重量百分比计，Mg-Zn-Nd镁合金吻合钉的技术指标如下：抗拉强度范围为260～320MPa，屈服强度范围为170～240MPa，延伸率范围为20～33％。
所述的可降解镁合金原位复合吻合钉，在外层起腐蚀保护作用的MgF 2厚度为1.0μm～3.3μm。
所述的可降解镁合金原位复合吻合钉的制备方法，包括如下操作步骤：
(1)将纯镁、Zn、Nd按比例熔炼镁合金，铸造成镁合金锭，均匀化热处理，温度为300～450℃，时间为3～7h；
(2)将步骤(1)中的镁合金锭，去除表面缺陷和杂质，挤压成直径为8～10mm的棒材，挤压比为60～80:1，挤压温度为390～470℃；
(3)将步骤(2)中镁合金棒材通过冷拉拔制备成直径0.2～0.6mm的丝材，进行热处理退火，温度为280～330℃，保温30min～120min；
(4)将步骤(3)中镁合金丝材制备成U形吻合钉；
(5)将步骤(4)中镁合金吻合钉电解抛光，去除表面缺陷，超声清洗后吹干；
(6)将步骤(5)中的吻合钉浸入氢氟酸中进行MgF 2原位复合，氢氟酸的重量浓度为20％～60％，时间为3h～200h，处理温度为20～35℃；
(7)将步骤(6)的原位复合镁合金吻合钉超声清洗后吹干，真空封装。
所述的可降解镁合金原位复合吻合钉的制备方法，步骤(4)中，U形吻合钉的弯折部位为椭圆形，吻合钉总长10～15mm，吻合钉高3～6mm，吻合钉端面直径0.20～0.35mm。
所述的可降解镁合金原位复合吻合钉的制备方法，步骤(5)中，采用电解精抛光，抛光液采用体积比为乙二醇乙醚:无水乙醇:磷酸＝1:2:2的混合液，抛光时间1～10min，电压为10～20V，磷酸的重量浓度为85％。
本发明的设计思想是：
针对目前使用的钛合金吻合钉不可降解，长期驻留在人体内容易引发的感染和等问题。本发明制备一种镁基复合材料吻合钉，采用合金化元素Zn和Nd提高合金的强度和塑性，针对镁合金吻合钉的降解速度太快等问题，采用化学原位复合技术，在镁基吻合钉最外层复合氟化镁和氧化镁材料，提高吻合钉的耐蚀性能。
本发明所述的镁基复合材料吻合钉，合金化元素为Zn和Nd，Zn在Mg中能形成显著固溶和时效强化，提高合金强度，可有效软化合金柱面滑移方向，提高镁合金的塑性变形能力和加工性能。Zn是人体内必需的微量元素，参与蛋白质和酶类的代谢，并与神经系统的运行、免疫器官的维持有着密切的关系，具有较高的生物安全性。Nd在镁中的固溶度为3.6％，可以通过固溶热处理强化提高镁合金的拉拔性能和耐蚀性，通过晶粒的细化同时提高镁合金的强度和塑性。临床研究表明适量的稀土元素可促进成骨细胞增殖、保护神经系统、抗凝血、预防动脉硬化、治疗糖尿病、抗癌及消炎镇痛等作用。只有当稀土元素过量时，才可能对人体造成一定的不良影响。另外，原位复合中引入的氟是人体内重要的微量元素之一，氟元素能够刺激成骨细胞增殖及促进松质骨上矿物质沉积，促进铁的吸收和骨骼及牙齿的生长，具有改善神经系统兴奋性和发挥良好的抗衰老作用。中国营养学会公布的对氟的安全和适量摄入量为成年人1.5～4.0mg。
本发明的优点及有益效果是：
1、针对目前可降解镁合金钉存在的降解速率快，涂层结合力弱，力学强度低和塑性差等问题，本发明首先采用合金化策略，制备一种Mg-Zn-Nd合金，经过冷拉拔和热处理工艺，提高合金的力学强度和塑性，最终制备成吻合钉，接着采用原位复合氟化镁工艺，使得设计的吻合钉具有更好的耐腐蚀性能和生物安全性，通过上述发明的吻合钉，能够更好地满足体内使用要求。
2、本发明的吻合钉兼具良好的生物安全性、力学性能和塑性，优良的耐腐蚀性能，能够满足吻合钉的使用要求，且能够在基体内达到使用效果后降解消失，避免二次手术取出。
3、本发明的镁基复合材料，可改善吻合钉力学性能，并且获得较好的耐蚀性能，满足医用可降解吻合钉的使用要求。
附图说明
图1为镁基复合材料的SEM形貌。图中，2层是原位复合MgF 2，3层是镁合金基体，1层是制备样品所需的环氧树脂。
具体实施方式
在具体实施过程中，本发明通过合金化结合拉拔和原位复合工艺，制备一种良好的生物安全性、力学性能和塑性，优良的耐腐蚀性能的可降解吻合钉。
下面，结合附图对本发明的实施例作详细说明，本实施例在以本发明技术方案为 前提下进行实施，给出详细的实施方式和具体的操作过程，但本发明的保护范围不限于下述的实施例。
实施例1
本实施例中，吻合钉的制备方法：按重量百分比计，将纯镁和1％Zn、1％Nd熔炼成液态金属，浇铸成锭，去除表面缺陷和杂质，在400℃做均匀化热处理4h，通过430℃热挤压加工出镁直径10mm的镁合金棒材(挤压比为70:1)，通过冷拉拔拉到直径为0.3mm的丝材，300℃保温60min进行热处理退火。将镁合金丝制备成U形吻合钉，U形吻合钉的弯折部位为椭圆形，吻合钉总长10～15mm，吻合钉高3～6mm，吻合钉端面直径0.20～0.35mm。将吻合钉电解抛光去除表面缺陷和杂质，抛光液采用体积比为乙二醇乙醚:无水乙醇:磷酸＝1:2:2的混合液，抛光时间5min，电压为15V，磷酸的重量浓度为85％；超声清洗并吹干后，将吻合钉浸入氢氟酸中进行氟化镁原位复合，氢氟酸的重量浓度为35％，室温下复合6h，超声清洗吻合钉后吹干，真空封装。
本实施例吻合钉的力学性能和细胞毒性数据见表1，腐蚀性能数据见表2。
实施例2
本实施例中，吻合钉的制备方法：按重量百分比计，将纯镁和1.73％Zn、0.68％Nd熔炼成液态金属，浇铸成锭，去除表面缺陷和杂质，在380℃做均匀化热处理6h，通过420℃热挤压加工出镁直径10mm的镁合金棒材(挤压比为60:1)，通过冷拉拔拉到直径为0.3mm的丝材，280℃保温120min进行热处理退火。将镁合金丝制备成U形吻合钉，U形吻合钉的弯折部位为椭圆形，吻合钉总长10～15mm，吻合钉高3～6mm，吻合钉端面直径0.20～0.35mm。将吻合钉电解抛光去除表面缺陷和杂质，抛光液采用体积比为乙二醇乙醚:无水乙醇:磷酸＝1:2:2的混合液，抛光时间3min，电压为20V，磷酸的重量浓度为85％；超声清洗并吹干后，将吻合钉浸入氢氟酸中进行氟化镁原位复合，氢氟酸的重量浓度为40％，室温下复合7h，超声清洗吻合钉后吹干，真空封装。
本实施例吻合钉的力学性能和细胞毒性数据见表1，腐蚀性能数据见表2。
实施例3
本实施例中，吻合钉的制备方法：按重量百分比计，将纯镁和1.6％Zn、0.7％Nd熔炼成液态金属，浇铸成锭，去除表面缺陷和杂质，在420℃做均匀化热处理5h，通过410℃热挤压加工出镁直径10mm的镁合金棒材(挤压比为80:1)，通过冷拉拔拉到直径为0.3mm的丝材，320℃保温30min进行热处理退火。将镁合金丝制备成U形吻合钉，U形吻合钉的弯折部位为椭圆形，吻合钉总长10～15mm，吻合钉高3～6mm， 吻合钉端面直径0.20～0.35mm。将吻合钉电解抛光去除表面缺陷和杂质，抛光液采用体积比为乙二醇乙醚:无水乙醇:磷酸＝1:2:2的混合液，抛光时间6min，电压为10V，磷酸的重量浓度为85％；超声清洗并吹干后，将吻合钉浸入氢氟酸中进行氟化镁原位复合，氢氟酸的重量浓度为45％，室温下复合8h，超声清洗吻合钉后吹干，真空封装。
本实施例吻合钉的力学性能和细胞毒性数据见表1，腐蚀性能数据见表2。
表1吻合钉的力学性能和细胞毒性
  抗拉强度(MPa) 屈服强度(MPa) 延伸率(％) 细胞毒性
实施例1 310.2 236.2 25 0级
实施例2 296.4 221.6 27 0级
实施例3 314.2 239.7 29 0级
表2吻合钉的腐蚀性能数据
  E 0(V) I c(A/cm 2) R p(Ω/cm 2)
实施例1 -1.56 5.23×10 -7 3.65×10 5
实施例2 -1.53 6.59×10 -8 5.3×10 5
实施例3 -1.49 3.59×10 -8 6.8×10 5
由表1和表2可以看出，本发明的吻合钉具有较高的抗拉强度和优异的塑性，能够满足其力学使用性能，吻合钉的细胞毒性为0级，表明其具有较高的细胞相容性。
如图1所示，从镁基复合材料的SEM形貌可以看出，复合材料的基体和原位复合MgF 2之间无明显的分层，与传统意义的涂层不同，保证材料的结构和性能稳定性，原位复合的MgF 2层提高合金的耐腐蚀性能。
实施例结果表明，本发明的镁合金复合材料吻合钉，具有良好的塑性变形能力及力学强度，较慢的降解速度，优良的生物安全性，满足吻合钉在体内的植入要求，在生物体内达到医疗效果后可在体内逐步降解，避免二次手术取出。

Claims (7)

  1. 一种可降解镁合金原位复合吻合钉，其特征在于，该吻合钉为一种复合结构材料，主要分两部分，内部由强度高、塑性好的Mg-Zn-Nd镁合金组成，外部由起腐蚀保护作用的MgF 2组成，由Mg-Zn-Nd镁合金吻合钉的外层原位复合MgF 2而成。
  2. 按照权利要求1所述的可降解镁合金原位复合吻合钉，其特征在于，按重量百分比计，Mg-Zn-Nd镁合金吻合钉的化学成分和含量为：Zn0.2％～3.0％，Nd0.2％～2.3％，余量为Mg。
  3. 按照权利要求2所述的可降解镁合金原位复合吻合钉，其特征在于，按重量百分比计，Mg-Zn-Nd镁合金吻合钉的技术指标如下：抗拉强度范围为260～320MPa，屈服强度范围为170～240MPa，延伸率范围为20～33％。
  4. 按照权利要求1所述的可降解镁合金原位复合吻合钉，其特征在于，在外层起腐蚀保护作用的MgF 2厚度为1.0μm～3.3μm。
  5. 一种权利要求1至4之一所述的可降解镁合金原位复合吻合钉的制备方法，其特征在于，包括如下操作步骤：
    (1)将纯镁、Zn、Nd按比例熔炼镁合金，铸造成镁合金锭，均匀化热处理，温度为300～450℃，时间为3～7h；
    (2)将步骤(1)中的镁合金锭，去除表面缺陷和杂质，挤压成直径为8～10mm的棒材，挤压比为60～80:1，挤压温度为390～470℃；
    (3)将步骤(2)中镁合金棒材通过冷拉拔制备成直径0.2～0.6mm的丝材，进行热处理退火，温度为280～330℃，保温30min～120min；
    (4)将步骤(3)中镁合金丝材制备成U形吻合钉；
    (5)将步骤(4)中镁合金吻合钉电解抛光，去除表面缺陷，超声清洗后吹干；
    (6)将步骤(5)中的吻合钉浸入氢氟酸中进行MgF 2原位复合，氢氟酸的重量浓度为20％～60％，时间为3h～200h，处理温度为20～35℃；
    (7)将步骤(6)的原位复合镁合金吻合钉超声清洗后吹干，真空封装。
  6. 按照权利要求5所述的可降解镁合金原位复合吻合钉的制备方法，其特征在于，步骤(4)中，U形吻合钉的弯折部位为椭圆形，吻合钉总长10～15mm，吻合钉高3～6mm，吻合钉端面直径0.20～0.35mm。
  7. 按照权利要求5所述的可降解镁合金原位复合吻合钉的制备方法，其特征在于，步骤(5)中，采用电解精抛光，抛光液采用体积比为乙二醇乙醚:无水乙醇:磷酸＝1:2:2的混合液，抛光时间1～10min，电压为10～20V，磷酸的重量浓度为85％。
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