WO2018000219A1 - 一种生物医用可降解耐蚀高强韧镁合金及其制备方法 - Google Patents

一种生物医用可降解耐蚀高强韧镁合金及其制备方法 Download PDF

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Publication number
WO2018000219A1
WO2018000219A1 PCT/CN2016/087575 CN2016087575W WO2018000219A1 WO 2018000219 A1 WO2018000219 A1 WO 2018000219A1 CN 2016087575 W CN2016087575 W CN 2016087575W WO 2018000219 A1 WO2018000219 A1 WO 2018000219A1
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Prior art keywords
magnesium alloy
alloy
pure
resistance
biomedical
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PCT/CN2016/087575
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English (en)
French (fr)
Inventor
马国睿
马晓意
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北京美中双和医疗器械股份有限公司
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Application filed by 北京美中双和医疗器械股份有限公司 filed Critical 北京美中双和医疗器械股份有限公司
Priority to ES16906621T priority Critical patent/ES2912456T3/es
Priority to US16/312,261 priority patent/US11040126B2/en
Priority to PCT/CN2016/087575 priority patent/WO2018000219A1/zh
Priority to EP16906621.4A priority patent/EP3403676B1/en
Publication of WO2018000219A1 publication Critical patent/WO2018000219A1/zh

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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
    • 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
    • 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
    • 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

Definitions

  • the invention relates to a biomedical degradable corrosion resistant high strength and toughness magnesium alloy and a preparation method thereof, and belongs to the technical field of medical material preparation.
  • the vascular stents used in clinical practice are mainly made of inert metal materials such as stainless steel, nickel-titanium alloy and cobalt-chromium alloy.
  • inert metal materials such as stainless steel, nickel-titanium alloy and cobalt-chromium alloy.
  • Such stents can be implanted into the human body to provide long-lasting mechanical support for the blood vessels in the lesions, and avoid the elastic return of the blood vessels. Shrinkage reduces the rate of restenosis of blood vessels.
  • stents prepared with inert metal materials cause hypervascular intimal hyperplasia after implantation as a foreign body, which not only causes vascular restenosis and late thrombosis, but also requires long-term antiplatelet therapy.
  • degradable vascular stents There are two main types of degradable vascular stents that have obtained registration certificates or entered clinical trials: one is a degradable polymer stent, and the other is a degradable magnesium alloy stent.
  • Degradable polymer scaffolds have problems such as low mechanical properties, difficult processing, and inflammable and swollen products in vivo. A large number of clinical data indicate that patients have a 16% chance of developing late restenosis after implantation of a polymer stent.
  • degradable magnesium alloy scaffolds have the following advantages: (1) Complete degradation after implantation in human body. Generally, magnesium alloy stents can be completely absorbed by the human body within 4 months after implantation.
  • the complete degradation of the magnesium alloy stent not only improves the compliance and naturalness of the blood vessel to a certain extent, but also allows the stent to be placed again in the same lesion of the blood vessel without causing overlap of the stent, especially Suitable for cardiovascular disease treatment in infants and young children.
  • (2) Good biocompatibility Since magnesium is an essential element for the body to maintain normal physiological functions, and the size of the blood vessel stent is small (hollow tubular, diameter is about 2 mm, wall thickness is about 0.1 to 0.2 mm, length is about 15 mm), the metal released by the degradation process The number of ions is small.
  • magnesium alloy vascular stent not only does not cause harm to the human body, but can supplement the body with magnesium to ensure the normal physiological function of the human body.
  • the magnesium alloy stent can be completely absorbed by the human body, the follow-up after stent implantation can perform non-invasive examination.
  • (4) Have appropriate support strength.
  • the magnesium alloy does not have the problem of insufficient strength of the polymer material, and the blood vessel stent can have an appropriate supporting strength.
  • magnesium alloys As a bio-implant material, magnesium alloys must meet the necessary mechanical and morphological requirements during service, so the rate of corrosion degradation should not be too fast.
  • the normal pH of the human body environment is about 7.4, and there is a large amount of chloride ions in the body fluid, and the human body is a complex corrosive environment, which will cause the corrosion rate of the magnesium alloy in the human body to change.
  • medical corrosion resistant magnesium alloys such as the medical corrosion resistant magnesium alloy disclosed in CN101062427A and the medical high strength and toughness corrosion resistant magnesium alloy disclosed in CN101288776A have been developed.
  • magnesium alloys Another limitation of magnesium alloys is their low plasticity at room temperature and difficult deformation processing. This is because magnesium belongs to a metal with a hexagonal crystal structure, and there are few independent slip systems at room temperature, and only the base surface slips.
  • a high-strength and high-magnetity magnesium alloy disclosed in CN101643872A and a preparation method thereof, and a high-plasticity magnesium alloy disclosed in CN101985714A and preparation thereof are developed for the problem that the magnesium alloy has poor room temperature plasticity. method.
  • magnesium alloys in the above patent documents contain an Al element and a heavy rare earth element (Y, Gd, etc.).
  • Al may cause some degenerative neurological diseases such as dialysis encephalopathy syndrome and senile dementia, and is considered to be a neurotoxic element harmful to the human body.
  • heavy rare earth elements such as Y and Gd can improve the strength and corrosion resistance of magnesium alloys, the biological effects are still unclear. It is generally believed that the accumulation of heavy rare earth elements in the body is toxic.
  • CN101629260A discloses a medically absorbable Mg-Zn-Mn-Ca magnesium alloy, the composition and weight percentage of the magnesium alloy are: Zn 1.0-5.0%, Mn 0.2-2.0%, Ca 0.1-3.0%, and the balance is Mg.
  • the magnesium alloy has certain biocompatibility and mechanical properties, and can be made into implantable devices such as bone nails and bone plates.
  • the magnesium alloy can not be used for the preparation of vascular stents at present, mainly because: (1) due to the addition of Mn element and high content, the corrosion resistance of magnesium alloy is lowered, the degradation rate is too fast, and local degradation is likely to occur. Uniform problem; (2) The ductility of the alloy is not good, and the plastic processing is difficult, making secondary molding difficult to achieve.
  • CN103184379A discloses a biodegradable Mg-Gd-Zn-Ag-Zr magnesium alloy and a preparation method thereof, the composition and weight percentage of the magnesium alloy are: Gd 5-10%, Zn 0.5-3%, Ag 0.1 ⁇ 1%, Zr 0.1 to 1%, and the balance is Mg.
  • the magnesium alloy can be used as an implant material with low degradation rate and uniform corrosion.
  • the magnesium alloy is disadvantageous in that the content of the heavy rare earth element Gd in the component is high ( ⁇ 5%), and the Gd element is considered to be a toxic element, which is disadvantageous for improving the biocompatibility of the alloy.
  • the magnesium alloy contains expensive Ag elements, and the storage and smelting conditions are harsh, thereby increasing the cost.
  • an object of the present invention is to provide a biomedical degradable corrosion resistant high strength tough magnesium alloy and a preparation method thereof.
  • the magnesium alloy has the advantages of non-toxicity, complete degradation, good corrosion resistance, high strength and toughness, and can be used for preparing a blood vessel stent.
  • the present invention firstly provides a biomedical degradable corrosion resistant high strength tough magnesium alloy, the composition of which comprises: Nd 1.0 to 4.5%, Zn 0.2 to 2.0, based on 100% of the total weight of the magnesium alloy. %, Ca 0 to 1.0%, Zr 0 to 1.0%, and Mg balance.
  • the composition of the biomedical degradable high-resistance tough magnesium alloy of the present invention is 100%, and the composition thereof comprises: Nd 1.5 to 3.5%, Zn 0.1 to 1.0%, and Ca 0.1. ⁇ 1.0%, Zr0.2 to 1.0%, and Mg balance.
  • the composition of the biomedical degradable high-resistance tough magnesium alloy of the present invention is 100%, and the composition thereof comprises: Nd 1.5 to 2.5%, Zn 0.4 to 0.8%, Ca 0.4 to 0.6%, Zr 0.4 to 0.8%, and Mg balance.
  • the preferred magnesium alloy composition level enables it to achieve better overall mechanical properties and biological corrosion properties.
  • the total amount of inclusion elements other than Mg, Nd, Zn, Ca, and Zr is 100% of the total weight of the magnesium alloy.
  • the amount is 0.05% or less.
  • the invention can make the magnesium alloy have better comprehensive mechanical properties and biological corrosion performance by strictly controlling the content of impurities such as Fe, Cu, Ni and the like.
  • the biomedical degradable high-resistance tough magnesium alloy is prepared by at least the following steps: preparing a magnesium alloy by vacuum semi-continuous casting according to the above-mentioned magnesium alloy composition and weight percentage.
  • the raw materials used include at least: pure Zn, Mg-Nd intermediate alloy and pure magnesium; more preferably, the raw materials used further include: pure Ca and/or Mg-Zr intermediate alloy; further preferably, The purity of pure Zn used is 99.99 wt.% or more, and the purity of pure Ca used is 99.99 wt.% or more.
  • the Mg-Nd master alloy used is Mg-30 wt.% Nd master alloy, and Mg used.
  • the -Zr master alloy is a Mg-30wt.% Zr master alloy, and the purity of the pure magnesium used is 99.99 wt.% or more. Further, the obtained magnesium alloy ingot may have a diameter of ⁇ 110 to 150 mm and a length of 2200 to 2600 mm.
  • the preparing step of the biomedical degradable high-resistance tough magnesium alloy further comprises: cutting the obtained magnesium alloy ingot into a certain length, and performing the solution treatment to perform extrusion.
  • the biomedical degradable corrosion resistant high strength tough magnesium alloy More preferably, the temperature of the solution treatment is 480 to 540 ° C, and the time is 8 to 12 hours, and the extrusion is performed at an extrusion ratio of 5 to 30 in an environment of 280 to 420 ° C.
  • the biomedical degradable high-resistance tough magnesium alloy obtained after extrusion is a round rod with a diameter of ⁇ 20-40 mm.
  • Nd can make the magnesium alloy have good aging precipitation strengthening and solid solution strengthening effect, because Nd forms a strengthening phase Mg 2 Nd in the magnesium alloy, and the strengthening phase can improve the strength and plasticity of the alloy.
  • the addition of Nd can greatly improve the electrode potential of the magnesium alloy matrix and reduce the potential difference between the galvanic corrosion of the matrix and the second phase, thereby significantly improving the corrosion resistance of the magnesium alloy.
  • Nd belongs to light rare earth elements and has good biosafety.
  • Zn is an element that has an important influence on cell growth and development, and is a micronutrient element essential to the human body. Zn can enhance the body's immune function and maintain the growth and development of the body. In vitro experiments have shown that Zn can maintain the barrier function of vascular endothelial cell membrane. From the viewpoint of mechanical properties of magnesium alloy, the solid solubility of Zn in magnesium alloy is 6.2%, which has a solid solution strengthening effect on magnesium alloy, and at the same time effectively promotes the occurrence of non-base slip of magnesium alloy at room temperature and improves magnesium. The plastic working ability of the alloy. It is another very effective alloying element other than Al. Further, when the Zn content is 2% or less, the local corrosion tendency of the magnesium alloy can be made small, thereby effectively improving the corrosion resistance of the magnesium alloy.
  • Ca can refine the grain of the magnesium alloy to achieve the effect of fine grain strengthening, and significantly improve the formability and strength of the magnesium alloy.
  • Ca can also inhibit the oxidation of molten metal and reduce the internal defects of the ingot.
  • Ca can reduce the microbattery effect of magnesium alloy and improve the corrosion resistance of magnesium alloy.
  • Ca is also one of the most abundant elements in the human body. About 99% of the body's Ca is present in the bone marrow and teeth, and the rest is mainly distributed in the body fluid to participate in some important enzyme reactions. Ca plays an important role in maintaining normal heart contraction, neuromuscular excitability, coagulation, and normal secretion of endocrine hormones, maintaining cell membrane integrity.
  • Zr has a strong solid solution strengthening effect, which can greatly improve the strength of magnesium alloy.
  • Zr is by far the most effective grain refiner with strong grain refinement.
  • Zr can significantly improve the tensile strength of magnesium alloy at room temperature, improve corrosion resistance and reduce stress corrosion sensitivity.
  • the addition of Zr to the Zn-containing magnesium alloy can reduce the embrittlement and hot brittleness of the magnesium alloy, and can reduce the content of impurities such as Fe, Al and Si in the alloy.
  • the present invention provides a method for preparing the above biomedical degradable high-resistance tough magnesium alloy, which comprises at least the following steps: preparing a magnesium by vacuum semi-continuous casting according to the above-mentioned magnesium alloy composition and weight percentage.
  • the purity of pure Zn used is 99.99 wt.% or more
  • the purity of pure Ca used is 99.99 wt.% or more
  • the Mg-Nd master alloy used is Mg-30wt.
  • the %Nd master alloy, the Mg-Zr master alloy used is a Mg-30wt.% Zr master alloy, and the purity of the pure magnesium used is 99.99 wt.% or more.
  • the vacuum semi-continuous casting comprises the following steps:
  • the SF 6 and CO 2 mixed gas is introduced into the surface of the melt for protection, and the molten metal is heated to 760 to 780 ° C for 30 to 40 minutes, and then the temperature of the melt is lowered to 700 to 720 ° C to be allowed to stand. 90 to 120 minutes;
  • the obtained magnesium alloy ingot may have a diameter of ⁇ 110 to 150 mm, a length of 2200 to 2600 mm, and more preferably ⁇ 120 22.4 mm.
  • the above preparation method further comprises the steps of: cutting the obtained magnesium alloy ingot into a certain length, and performing the solution treatment and then extruding to obtain the biomedical degradable corrosion resistance. Tough magnesium alloy.
  • the temperature of the solution treatment is 480 to 540 ° C (more preferably 520 ° C), the time is 8 to 12 hours (more preferably 10 hours), and the extrusion is at 280 to 420 ° C (further
  • the biomedical degradable high-resistance tough magnesium alloy obtained after extrusion is carried out at an extrusion ratio of 5 to 30 (more preferably 25) in an environment of 330 ° C., and has a diameter of ⁇ 20 to 40 mm (more preferably ⁇ 25 mm). Round bar.
  • the present invention Compared with the existing magnesium alloy for degradable vascular stent, the present invention has the following advantages:
  • the magnesium alloy of the invention has ideal corrosion resistance in vivo, and is uniform corrosion degradation, avoiding premature failure of the implant material due to local corrosion too fast, and achieving the ideal support effect of the biodegradable material.
  • the invention avoids the neurotoxicity caused by the Al element in the Al-containing magnesium alloy in the composition design, and does not contain heavy rare earth elements (Y, Gd, etc.), and the selected alloying and microalloying elements in the proposed composition It is non-cytotoxic in scope and has good biocompatibility.
  • the alloying element, especially the rare earth element, of the magnesium alloy of the invention has a lower content than the WE43 alloy, not only the alloy.
  • the blood compatibility performance is greatly improved, and the elements in the alloy are less segregated, have better corrosion resistance, the corrosion rate is significantly reduced, and the corrosion is more uniform.
  • the quasi-crystalline phase appearing in the magnesium alloy prepared by the method of the invention has excellent corrosion resistance and greatly improves the corrosion resistance of the alloy.
  • the appearance of the quasi-crystalline phase significantly improves the corrosion resistance of the magnesium alloy. Due to the special nature of the quasicrystal, the rigidity of the magnesium alloy can be improved to a certain extent, and the problem of insufficient rigidity of the magnesium alloy as a degradable vascular stent is solved.
  • the magnesium alloy of the invention has good comprehensive mechanical properties, excellent corrosion resistance and good biocompatibility after extrusion processing.
  • the magnesium alloy prepared by the invention has a tensile strength of 246 to 289 MPa, a yield strength of 207 to 232 MPa, and an elongation of 25 to 34%, which satisfies the mechanical properties of the intravascular stent material; Corrosion rate can reach 0.22 ⁇ 0.26mm/year, which meets the requirements of corrosion resistance of intravascular stent materials; and the magnesium alloy has no obvious cytotoxicity and good blood compatibility, which can meet the biocompatibility of intravascular stent materials. Claim.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 1.5%, Zn 0.4%, Ca 0.4%, Zr 0.4%, based on 100% of the total weight of the magnesium alloy. And the amount of Mg.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Ca-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is refined and uniform, and there is no solute segregation. .
  • the obtained Mg-Nd-Zn-Ca-Zr magnesium alloy ingot is cut into a certain length, and after being solution treated at 520 ° C for 10 hours, extruded into a round bar having a diameter of ⁇ 25 mm at 330 ° C to obtain the Biomedical degradable corrosion resistant Tough magnesium alloy.
  • the biomedical degradable high-resistance tough magnesium alloy has a tensile strength of 246 MPa, a yield strength of 207 MPa, and an elongation of 34%, and has good plasticity and mechanical properties.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.26 mm/year, and the corrosion mode is uniform corrosion.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the requirements of intravascular stent materials.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 2.0%, Zn 0.6%, Ca 0.5%, Zr 0.6%, based on the total weight of the magnesium alloy. And the amount of Mg.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Ca-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is refined and uniform, and there is no solute segregation. .
  • the obtained Mg-Nd-Zn-Ca-Zr magnesium alloy ingot is cut into a certain length, and after being solution treated at 520 ° C for 10 hours, extruded into a round bar having a diameter of ⁇ 25 mm at 330 ° C to obtain the Biomedical degradable corrosion resistant high strength tough magnesium alloy.
  • the biomedical degradable high-resistance tough magnesium alloy has a tensile strength of 277 MPa, a yield strength of 224 MPa, and an elongation of 28%, and has good plasticity and mechanical properties.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.24 mm/year, and the corrosion mode is uniform corrosion.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the requirements of intravascular stent materials.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 2.5%, Zn 0.8%, Ca 0.6%, Zr 0.8%, based on the total weight of the magnesium alloy. And the amount of Mg.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Ca-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is refined and uniform, and there is no solute segregation. .
  • the obtained Mg-Nd-Zn-Ca-Zr magnesium alloy ingot is cut into a certain length, and after being solution treated at 520 ° C for 10 hours, extruded into a round bar having a diameter of ⁇ 25 mm at 330 ° C to obtain the Biomedical degradable corrosion resistant high strength tough magnesium alloy.
  • the biomedical degradable corrosion resistant high-strength toughness magnesium alloy has a tensile strength of 289 MPa, a yield strength of 232 MPa, and an elongation of 25%, and has good plasticity and mechanical properties.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.22 mm/year, and the corrosion mode is uniform corrosion.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the requirements of intravascular stent materials.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 1.5%, Zn 0.4%, Zr 0.4%, and Mg balance, based on 100% of the total weight of the magnesium alloy. .
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is fine and uniform, and there is no solute segregation.
  • the biomedical degradable corrosion resistant high strength tough magnesium alloy has a tensile strength of 223 MPa, a yield strength of 188 MPa, and an elongation of 24%.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.32 mm/year.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the biocompatibility requirements of the intravascular stent materials.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 1.5%, Zn 0.4%, Ca 0.4%, and Mg balance, based on 100% of the total weight of the magnesium alloy. .
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Ca magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is fine and uniform, and there is no solute segregation.
  • the biomedical degradable corrosion resistant high-strength toughness magnesium alloy has a tensile strength of 228 MPa, a yield strength of 196 MPa, and an elongation of 21%.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.36 mm/year.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the biocompatibility requirements of the intravascular stent materials.
  • the present embodiment provides a biomedical degradable high-resistance tough magnesium alloy, which has a composition of: Nd 1.5%, Zn 2.0%, Ca 0.4%, Zr 0.4%, based on the total weight of the magnesium alloy. And the amount of Mg.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the melt in the crystallizer is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Nd-Zn-Ca-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is refined and uniform, and there is no solute segregation. .
  • the obtained Mg-Nd-Zn-Ca-Zr magnesium alloy ingot is cut into a certain length, and after being solution treated at 520 ° C for 10 hours, extruded into a round bar having a diameter of ⁇ 25 mm at 330 ° C to obtain the Biomedical degradable corrosion resistant high strength tough magnesium alloy.
  • the biomedical degradable corrosion resistant high strength tough magnesium alloy has a tensile strength of 256 MPa, a yield strength of 219 MPa, and an elongation of 18%.
  • the corrosion rate of the biomedical degradable high-resistance tough magnesium alloy in artificial plasma is 0.44 mm/year.
  • the biological test results show that the material has no obvious cytotoxicity and good blood compatibility, which can meet the biocompatibility requirements of the intravascular stent materials.
  • This comparative example provides a biomedical magnesium alloy having a composition of Y 1.5%, Zn 0.4%, Zr 0.4%, and Mg balance, based on 100% by weight of the total weight of the magnesium alloy.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Y-Zn-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is fine and uniform, and there is no solute segregation.
  • the obtained Mg-Y-Zn-Zr magnesium alloy ingot is cut to a certain length and solution treated at 520 ° C for 10 hours. Thereafter, it was extruded at 330 ° C into a round bar having a diameter of ⁇ 25 mm to obtain the biomedical magnesium alloy.
  • the biomedical magnesium alloy has a tensile strength of 216 MPa, a yield strength of 176 MPa, and an elongation of 19%.
  • the biomedical magnesium alloy has a corrosion rate of 0.37 mm/year in artificial plasma.
  • This comparative example provides a biomedical magnesium alloy having a composition of: Y 1.5%, Zn 0.4%, Ca 0.4%, and Mg balance, based on 100% by weight of the total weight of the magnesium alloy.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Y-Zn-Ca magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is fine and uniform, and there is no solute segregation.
  • the obtained Mg-Y-Zn-Ca magnesium alloy ingot is cut into a certain length, and after solution treatment at 520 ° C for 10 hours, it is extruded at 330 ° C into a round rod having a diameter of ⁇ 25 mm to obtain the living organism. Medical magnesium alloy.
  • the biomedical magnesium alloy has a tensile strength of 213 MPa, a yield strength of 172 MPa, and an elongation of 22%.
  • the biomedical corrosion rate in artificial plasma was 0.43 mm/year.
  • This comparative example provides a biomedical magnesium alloy having a composition of Y 1.5%, Zn 2.0%, Ca 0.4%, Zr 0.4%, and Mg balance, based on 100% by weight of the total weight of the magnesium alloy.
  • the magnesium alloy is prepared by the following steps:
  • the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) is applied to the surface of the molten metal for protection, and the molten liquid is heated to 760 to 780 ° C. Keep warm for 30min. After the high temperature heat preservation, the melting furnace is powered off, and the temperature of the molten metal is controlled at 700 to 720 ° C, and it is allowed to stand for 90 minutes.
  • a copper mold ingot is used on the semi-continuous casting machine, and the magnesium alloy melt is introduced into the shunt plate placed in the sleeve of the crystallizer, and the metal inner sleeve and the lead into the crystallizer are shunted by the splitter disc.
  • the protective gas ring is simultaneously opened to provide the alloy melt with the SF 6 and CO 2 mixed gas (the volume ratio of SF 6 :CO 2 in the mixed gas is 1:100) for protection.
  • the temperature of the molten metal in the vacuum melting furnace is controlled to be 700 to 720 ° C
  • the temperature of the molten metal in the mold is 680 to 690 ° C
  • the pulling speed is 40 mm / min.
  • High pressure water cooling is used at 400 mm near the crystallizer, and air cooling is used in the following parts.
  • the size of the semi-continuous ingot of Mg-Y-Zn-Ca-Zr magnesium alloy obtained by casting is ⁇ 120 ⁇ 2400mm, the appearance of the ingot is no crack, no shrinkage, the surface is smooth and smooth, the structure is refined and uniform, and there is no solute segregation. .
  • the biomedical magnesium alloy has a tensile strength of 236 MPa, a yield strength of 204 MPa, and an elongation of 17%.
  • the biomedical magnesium alloy has a corrosion rate of 0.48 mm/year in artificial plasma.
  • the magnesium alloy prepared by the most preferred embodiment of the present invention has a tensile strength of 246 to 289 MPa, a yield strength of 207 to 232 MPa, and an elongation of 25 to 34%, which satisfies the intravascular stent.
  • the mechanical properties of the material; its corrosion rate in artificial plasma can reach 0.22 ⁇ 0.26mm/year, which meets the requirements of corrosion resistance of intravascular stent materials; and the magnesium alloy has no obvious cytotoxicity and good blood compatibility. It can meet the biocompatibility requirements of endovascular stent materials.

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Abstract

一种生物医用可降解耐蚀高强韧镁合金及其制备方法。以该镁合金的总重量为100％计，其成分组成包括：Nd 1.0～4.5％、Zn 0.2～2.0％、Ca 0～1.0％、Zr 0～1.0％以及Mg余量。该镁合金是采用真空半连续铸造方式并按照其成分及重量百分比制备镁合金铸锭，而后经过固溶处理和挤压，从而制备得到的。该生物医用可降解耐蚀高强韧镁合金兼具无毒、可完全降解、耐蚀性能好和高强韧等优点，可用于制备血管支架。

Description

一种生物医用可降解耐蚀高强韧镁合金及其制备方法 技术领域
本发明涉及一种生物医用可降解耐蚀高强韧镁合金及其制备方法，属于医用材料制备技术领域。
背景技术
目前临床上使用的血管支架主要是由不锈钢、镍钛合金和钴铬合金等惰性金属材料制成，此类支架植入人体内可对病变处血管提供持久的机械支撑，避免了血管的弹性回缩，降低了血管的再狭窄率。但是采用惰性金属材料制备的支架在植入后作为异物引起血管内膜过度增生，不仅造成血管再狭窄和晚期血栓的发生，而且还需要进行长期的抗血小板治疗。近年来药物洗脱支架的应用使血管的再狭窄率降到5％左右，但是当药物释放完毕后，支架本体仍然永久存在于体内，作为异物的支架与血管组织之间在力学性质上存在很大差异，会引起血管的慢性损伤，后期会造成血管中层萎缩、内膜增生，最终还会导致血管的再狭窄。而对于婴幼儿患者，由于植入固定尺寸的血管支架会阻碍血管的逐渐增大，更加不能适应其生长发育的需要。鉴于以上原因，开发生物可降解血管支架已经成为各国研究的热点项目。
现有取得注册证或进入临床试验的可降解血管支架主要有两类：一类是可降解聚合物支架，另一类是可降解镁合金支架。可降解聚合物支架存在力学性能偏低、加工困难、体内降解产物易引发炎症和肿胀等问题。大量临床数据表明，患者在植入聚合物支架后晚期再狭窄情况出现的几率达到16％。与可降解聚合物支架相比，可降解镁合金支架主要具有以下优势：(1)植入人体后能完全降解。一般镁合金支架在置入后4个月内能被人体完全吸收。镁合金支架可完全降解这一特性不仅可以在一定程度上改善血管的顺应性和自然性，而且亦可在血管的同一病变处进行再次支架的置入，并不会造成支架的重叠现象，尤其适用于婴幼儿的心血管疾病治疗。(2)良好的生物相容性。由于镁是人体维持正常的生理机能所必须的元素，而且血管支架尺寸微小(中空管状，直径约为2mm，壁厚约为0.1～0.2mm，长度为15mm左右)，其降解过程释放出的金属离子数量较少，因此，镁合金血管支架降解过程中释放出的少量镁离子不仅不会给人体带来危害，反而可以为人体补充镁，以保证人体正常生理机能对镁的需求。(3)因镁合金支架可以被人体完全吸收，因此支架植入后的随访能进行无创检查。(4)具有适当的支撑强度。镁合金作为血管支架材料不存在聚合物材料的强度不足问题，可以使血管支架具有适当的支撑强度。
然而镁合金的标准电极电位较低(-2.36V SCE)，导致其耐腐蚀性能较差，在氯离子(Cl-)存在的腐蚀环境中或者当介质的pH值≤11.5时，其腐蚀尤其严重。作为生物植入材料，镁合金必须在服役期间严格满足必要的力学与形态学要求，因此其腐蚀降解速率不宜过快。人体内环境的正常pH值在7.4左右，而且体液中存在大量的氯离子，加之人体内是一个复杂的腐蚀环境，这些都会造成镁合金在人体内的腐蚀速率变化。为此人们开发出医用耐蚀镁合金，例如CN101062427A中公开的医用耐蚀镁合金以及CN101288776A中公开的医用高强韧耐蚀镁合金。
另外一个限制镁合金广泛应用的是其室温下塑性较低，变形加工困难。这是因为镁属于密排六方晶体结构的金属，室温下独立滑移系少，只有基面滑移。针对镁合金室温塑性较差的问题，人们开发出高强韧性镁合金，例如CN101643872A中公开的一种高强度、高塑性镁合金及其制备方法以及CN101985714A中公开的一种高塑性镁合金及其制备方法。
上述专利文献中的镁合金大多含有Al元素和重稀土元素(Y，Gd等)。众所周知，Al元素可能引起透析性脑病综合征、老年性痴呆等一些退行性神经疾病，被认为是一种对人体有害的神经毒性元素。虽然Y、Gd等重稀土元素能提高镁合金的强度和耐蚀性，但是其生物学效应目前还不明确，一般认为重稀土元素在体内的累积表现为毒性作用。
CN101629260A中公开了一种医用可吸收Mg-Zn-Mn-Ca镁合金，该镁合金的成分及重量百分比为：Zn 1.0～5.0％，Mn 0.2～2.0％，Ca 0.1～3.0％，余量为Mg。该镁合金具有一定的生物相容性和力学性能，可制成体内植入器械如骨钉、骨板等。但是，该镁合金目前不能用于制备血管支架，原因主要是：(1)由于Mn元素的加入并且含量较高，使得镁合金的耐蚀性能降低，降解速率过快，且容易出现局部降解不均匀的问题；(2)合金的延展性不好，塑性加工难度较大，使得二次成型不易实现。
CN103184379A中公开了一种生物可降解Mg-Gd-Zn-Ag-Zr系镁合金及其制备方法，该镁合金的成分及重量百分比为：Gd 5～10％，Zn 0.5～3％，Ag 0.1～1％，Zr 0.1～1％，余量为Mg。该镁合金可以作为低降解率且均匀腐蚀的植入物材料。但是，该镁合金的不足之处在于组分中重稀土元素Gd的含量较高(≥5％)，而Gd元素被认为是毒性元素，不利于提高合金的生物相容性。另外，该镁合金中含有价格昂贵的Ag元素，并且保存和熔炼条件较为苛刻，从而增加了成本。
综上所述，亟待开发一种兼具无毒、可完全降解、耐蚀性能好和高强韧优点的新型生物医用镁合金，探索其在血管内支架方面应用的可能性。
发明内容
为解决上述技术问题，本发明的目的在于提供一种生物医用可降解耐蚀高强韧镁合金及其制备方法。该镁合金兼具无毒、可完全降解、耐蚀性能好和高强韧等优点，可用于制备血管支架。
为达到上述目的，本发明首先提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成包括：Nd 1.0～4.5％、Zn 0.2～2.0％、Ca 0～1.0％、Zr 0～1.0％以及Mg余量。
根据本发明一优选具体实施方式，以本发明的生物医用可降解耐蚀高强韧镁合金的总重量为100％计，其成分组成包括：Nd 1.5～3.5％、Zn 0.1～1.0％、Ca 0.1～1.0％、Zr0.2～1.0％以及Mg余量。
根据本发明一更优选的具体实施方式，以本发明的生物医用可降解耐蚀高强韧镁合金的总重量为100％计，其成分组成包括：Nd 1.5～2.5％、Zn 0.4～0.8％、Ca 0.4～0.6％、Zr 0.4～0.8％以及Mg余量。该优选的镁合金成分含量能够使其获得更佳的综合力学性能和生物学腐蚀性能。
在上述的生物医用可降解耐蚀高强韧镁合金中，优选地，以所述镁合金的总重量为100％计，其所含有的除Mg、Nd、Zn、Ca、Zr以外的夹杂元素总量为0.05％以下。本发明通过严格控制Fe、Cu、Ni等杂质的含量，能够使镁合金具有更佳的综合力学性能和生物学腐蚀性能。
根据本发明的具体实施方式，优选地，上述生物医用可降解耐蚀高强韧镁合金是通过至少以下步骤制备得到的：采用真空半连续铸造方式并按照上述的镁合金成分及重量百分比制备镁合金铸锭，其中，所采用的原料至少包括：纯Zn、Mg-Nd中间合金以及纯镁；更优选地，所采用的原料还包括：纯Ca和/或Mg-Zr中间合金；进一步优选地，所采用的纯Zn的纯度为99.99wt.％以上，所采用的纯Ca的纯度为99.99wt.％以上，所采用的Mg-Nd中间合金为Mg-30wt.％Nd中间合金，所采用的Mg-Zr中间合金为Mg-30wt.％Zr中间合金，所采用的纯镁的纯度为99.99wt.％以上。并且，得到的镁合金铸锭的尺寸可以为直径Φ110～150mm，长度2200～2600mm。
根据本发明的具体实施方式，优选地，上述生物医用可降解耐蚀高强韧镁合金的制备步骤进一步包括：将得到的镁合金铸锭截取一定长度，经固溶处理后进行挤压，得到所述的生物医用可降解耐蚀高强韧镁合金。其中，更优选地，所述固溶处理的温度为480～540℃，时间为8～12小时，所述挤压是在280～420℃的环境下、以挤压比5～30进行的，并且挤压后得到的生物医用可降解耐蚀高强韧镁合金为直径Φ20～40mm的圆棒。
本发明提供的生物医用可降解耐蚀高强韧镁合金中各元素的作用分别如下：
Nd的加入可使镁合金具有良好的时效析出强化和固溶强化的效果，这是由于Nd在镁合金中形成强化相Mg2Nd，该强化相可提高合金的强度和塑性。同时Nd的加入可大幅度提高镁合金基体的电极电位，减小基体与第二相的电偶腐蚀的电位差，从而显著提高镁合金的耐蚀性能。此外Nd属于轻稀土元素，具有较好的生物安全性。
Zn是对细胞生长发育有重要影响的元素，是人体必须的微量营养元素。Zn能增强人体的免疫功能，维持机体的生长和发育。体外实验表明，Zn能维持血管内皮细胞膜的屏障功能。从镁合金的力学性能角度来看，Zn在镁合金中的固溶度为6.2％，对镁合金有固溶强化的作用，同时有效促进室温下镁合金非基面滑移的发生，提高镁合金的塑性加工能力。是除Al以外的另一种非常有效的合金化元素。此外，Zn含量在2％以下时能使镁合金的局部腐蚀倾向变小，从而有效提高镁合金的耐腐蚀性能。
Ca的加入可以细化镁合金晶粒，达到细晶强化的作用，显著提高镁合金的成型性和强度。Ca在镁合金的熔炼过程中还可以抑制熔融金属的氧化，减少铸锭内部缺陷。Ca能够降低镁合金的微电池效应，提高镁合金的耐腐蚀能力。同时，Ca也是人体内含量最多的元素之一，人体内的Ca有约99％存在于骨髓和牙齿中，其余主要分布于体液内，以参与某些重要的酶反应。Ca在维持心脏正常收缩、神经肌肉兴奋性、凝血以及内分泌激素正常分泌、保持细胞膜完整性等方面起到了重要的作用。
Zr有较强的固溶强化作用，可大幅度提高镁合金的强度。Zr还是目前为止最有效的晶粒细化剂，有很强的晶粒细化作用。除此之外，Zr可以明显改善室温下镁合金的抗拉强度，提高耐蚀性和降低应力腐蚀敏感性。在含Zn的镁合金加入Zr，可减少镁合金的脆化和热脆倾向，并可减少合金中Fe、Al、Si等杂质的含量。经国内外大量研究表明Zr在镁合金中少量添加无细胞毒性。
另一方面，本发明还提供了一种上述生物医用可降解耐蚀高强韧镁合金的制备方法，其至少包括以下步骤：采用真空半连续铸造方式并按照上述的镁合金成分及重量百分比制备镁合金铸锭，其中，所采用的原料至少包括：纯Zn、Mg-Nd中间合金以及纯镁；优选地，所采用的原料还包括：纯Ca和/或Mg-Zr中间合金。
在上述制备方法中，优选地，所采用的纯Zn的纯度为99.99wt.％以上，所采用的纯Ca的纯度为99.99wt.％以上，所采用的Mg-Nd中间合金为Mg-30wt.％Nd中间合金，所采用的Mg-Zr中间合金为Mg-30wt.％Zr中间合金，所采用的纯镁的纯度为99.99wt.％以上。
在上述制备方法中，优选地，所述真空半连续铸造包括以下步骤：
(1)在真空熔炼炉中熔化原料，熔化时控制熔液温度为740～760℃，待原料全部熔化后，再通入惰性气体(更优选为氩气)进行真空环境下的气体搅拌，搅拌时间为30-45min；
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体进行保护，同时将熔液升温至760～780℃保温30～40min，之后将熔液温度降至700～720℃静置90～120min；
(3)随后在半连续铸造机上进行铸造，半连续铸造过程中采用SF6与CO2混合气体进行保护，并控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为30～50mm/min，并且在近结晶器300～500mm处采用高压水冷，以下部位采用空冷，得到所述的镁合金铸锭。
在上述制备方法中，优选地，得到的镁合金铸锭的尺寸可以为直径Φ110～150mm，长度2200～2600mm，更优选为Φ120×2400mm。
根据本发明的具体实施方式，优选地，上述制备方法进一步包括以下步骤：将得到的镁合金铸锭截取一定长度，经固溶处理后进行挤压，得到所述的生物医用可降解耐蚀高强韧镁合金。其中，更优选地，所述固溶处理的温度为480～540℃(进一步优选520℃)、时间为8～12小时(进一步优选10小时)，所述挤压是在280～420℃(进一步优选330℃)的环境下、以挤压比5～30(进一步优选25)进行的，并且挤压后得到的生物医用可降解耐蚀高强韧镁合金为直径Φ20～40mm(进一步优选Φ25mm)的圆棒。
与现有的可降解血管支架用镁合金相比，本发明具有以下优点：
1.本发明的镁合金具有理想的体内耐腐蚀性能，并且是均匀腐蚀降解，避免因局部腐蚀过快导致植入材料过早失效，达到了生物可降解材料的理想支撑效果。
2.本发明在成分设计上避免了含Al镁合金中Al元素带来的神经毒性，并且不含重稀土元素(Y，Gd等)，选取的合金化和微合金化元素在所提出的成分范围内均是无细胞毒性的，具有良好的生物相容性。
3.在同种制备工艺状态下，与现有的可降解血管支架用镁合金相比，本发明的镁合金中合金化元素尤其是稀土元素与WE43合金相比含量较低，不仅使合金的血液相容性能有较大提高，同时合金中元素偏聚较少，具有更好的耐腐蚀性能，其腐蚀速率明显降低，且腐蚀较为均匀。
4.本发明方法制备的镁合金中出现的准晶相具有优异的腐蚀抗力，大幅度提高了合金的耐腐蚀性能。准晶相的出现在明显提高镁合金耐腐蚀性能的同时，由于准晶的特殊性质，在一定程度上能提高镁合金的刚性，解决了镁合金作为可降解血管支架刚性不足的问题。
5.本发明的镁合金经过挤压加工后具有良好的综合力学性能、优异的耐腐蚀性能和良好的生物相容性。本发明制备的镁合金的抗拉强度可达246～289MPa，屈服强度可达207～232MPa，延伸率可达25～34％，满足血管内支架材料对力学性能的要求；其在人工血浆中的腐蚀速率可达0.22～0.26mm/year，满足血管内支架材料对腐蚀性能的要求；并且该镁合金无明显的细胞毒性，血液相容性好，可满足血管内支架材料对生物相容性的要求。
具体实施方式
为了对本发明的技术特征、目的和有益效果有更加清楚的理解，现对本发明的技术方案进行以下详细说明，但不能理解为对本发明的可实施范围的限定。
实施例1
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 1.5％、Zn 0.4％、Ca 0.4％、Zr 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Nd中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Ca-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Ca-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强 韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为246MPa，屈服强度为207MPa，延伸率为34％，其具有良好的塑性和力学性能。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.26mm/year，腐蚀模式为均匀腐蚀。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料的要求。
实施例2
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 2.0％、Zn 0.6％、Ca 0.5％、Zr 0.6％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Nd中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Ca-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Ca-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为277MPa，屈服强度为224MPa，延伸率为28％，其具有良好的塑性和力学性能。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.24mm/year，腐蚀模式为均匀腐蚀。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料的要求。
实施例3
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 2.5％、Zn 0.8％、Ca 0.6％、Zr 0.8％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Nd中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Ca-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Ca-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为289MPa，屈服强度为232MPa，延伸率为25％，其具有良好的塑性和力学性能。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.22mm/year，腐蚀模式为均匀腐蚀。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料的要求。
实施例4
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 1.5％、Zn 0.4％、Zr 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以 上的纯Zn、Mg-30wt.％Nd中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为223MPa，屈服强度为188MPa，延伸率为24％。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.32mm/year。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料对生物相容性的要求。
实施例5
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 1.5％、Zn 0.4％、Ca 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Nd中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔 炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Ca镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Ca镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为228MPa，屈服强度为196MPa，延伸率为21％。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.36mm/year。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料对生物相容性的要求。
实施例6
本实施例提供了一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成为：Nd 1.5％、Zn 2.0％、Ca 0.4％、Zr 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Nd中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结 晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Nd-Zn-Ca-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Nd-Zn-Ca-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用可降解耐蚀高强韧镁合金。
该生物医用可降解耐蚀高强韧镁合金的抗拉强度为256MPa，屈服强度为219MPa，延伸率为18％。该生物医用可降解耐蚀高强韧镁合金在人工血浆中的腐蚀速率为0.44mm/year。生物学试验结果表明该材料无明显的细胞毒性、具有良好的血液相容性，可满足血管内支架材料对生物相容性的要求。
对比例1
本对比例提供了一种生物医用镁合金，以该镁合金的总重量为100％计，其成分组成为：Y 1.5％、Zn 0.4％、Zr 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、Mg-30wt.％Y中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Y-Zn-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Y-Zn-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理 后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用镁合金。
该生物医用镁合金的抗拉强度为216MPa，屈服强度为176MPa，延伸率为19％。该生物医用镁合金在人工血浆中的腐蚀速率为0.37mm/year。
对比例2
本对比例提供了一种生物医用镁合金，以该镁合金的总重量为100％计，其成分组成为：Y 1.5％、Zn 0.4％、Ca 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Y中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Y-Zn-Ca镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Y-Zn-Ca镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用镁合金。
该生物医用镁合金的抗拉强度为213MPa，屈服强度为172MPa，延伸率为22％。该生物医用在人工血浆中的腐蚀速率为0.43mm/year。
对比例3
本对比例提供了一种生物医用镁合金，以该镁合金的总重量为100％计，其成分组成为：Y 1.5％、Zn 2.0％、Ca 0.4％、Zr 0.4％以及Mg余量。
该镁合金是通过以下步骤制备得到的：
(1)在真空熔炼炉中依次熔化纯度为99.99wt.％以上的纯镁、纯度为99.99wt.％以 上的纯Zn、纯度为99.99wt.％以上的纯Ca、Mg-30wt.％Y中间合金、Mg-30wt.％Zr中间合金，熔化时控制合金熔液温度为740～760℃。待原料全部熔化后，再通入氩气进行真空环境下的气体搅拌，搅拌时间为40min。
(2)完成搅拌后向熔液表面通入SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护，同时将熔液升温至760～780℃保温30min。高温保温后将熔炼炉断电，控制熔液温度在700～720℃，静置90min。
(3)随后在半连续铸造机上采用铜质结晶器铸锭，将镁合金熔液引入置于结晶器内套心部的分流盘中，由分流盘分流后进入结晶器的金属内套与引锭组成的空间中，同时开启保护气环为合金熔液提供SF6与CO2混合气体(该混合气体中SF6:CO2的体积比为1:100)进行保护。半连续铸造过程中控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为40mm/min。在近结晶器400mm处采用高压水冷，以下部位采用空冷。
(4)铸造得到的Mg-Y-Zn-Ca-Zr镁合金半连续铸锭尺寸为Φ120×2400mm，铸锭外观无裂纹、无缩松、表面平整光洁、组织细化且均匀、无溶质偏析。
(5)将得到的Mg-Y-Zn-Ca-Zr镁合金铸锭截取一定长度，经520℃×10小时固溶处理后，在330℃挤压成直径为Φ25mm的圆棒，得到所述的生物医用镁合金。
该生物医用镁合金的抗拉强度为236MPa，屈服强度为204MPa，延伸率为17％。该生物医用镁合金在人工血浆中的腐蚀速率为0.48mm/year。
表1.镁合金成分组成及其相关性能
Figure PCTCN2016087575-appb-000001
Figure PCTCN2016087575-appb-000002
由表1可以看出，采用本发明的最优选实施方式制备的镁合金的抗拉强度可达246～289MPa，屈服强度可达207～232MPa，延伸率可达25～34％，满足血管内支架材料对力学性能的要求；其在人工血浆中的腐蚀速率可达0.22～0.26mm/year，满足血管内支架材料对腐蚀性能的要求；并且该镁合金无明显的细胞毒性，血液相容性好，可满足血管内支架材料对生物相容性的要求。

Claims (19)

  1. 一种生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成包括：Nd 1.0～4.5％、Zn 0.2～2.0％、Ca 0～1.0％、Zr 0～1.0％以及Mg余量。
  2. 根据权利要求1所述的生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成包括：Nd 1.5～3.5％、Zn 0.1～1.0％、Ca 0.1～1.0％、Zr 0.2～1.0％以及Mg余量。
  3. 根据权利要求1所述的生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其成分组成包括：Nd 1.5～2.5％、Zn 0.4～0.8％、Ca 0.4～0.6％、Zr 0.4～0.8％以及Mg余量。
  4. 根据权利要求1-3任一项所述的生物医用可降解耐蚀高强韧镁合金，以该镁合金的总重量为100％计，其所含有的除Mg、Nd、Zn、Ca、Zr以外的夹杂元素总量为0.05％以下。
  5. 根据权利要求1所述的生物医用可降解耐蚀高强韧镁合金，其是通过至少以下步骤制备得到的：采用真空半连续铸造方式并按照所述的生物医用可降解耐蚀高强韧镁合金的成分及重量百分比制备镁合金铸锭，其中，所采用的原料至少包括：纯Zn、Mg-Nd中间合金以及纯镁。
  6. 根据权利要求5所述的生物医用可降解耐蚀高强韧镁合金，其中，所采用的原料还包括：纯Ca和/或Mg-Zr中间合金。
  7. 根据权利要求5所述的生物医用可降解耐蚀高强韧镁合金，其中，所采用的纯Zn的纯度为99.99wt.％以上，所采用的Mg-Nd中间合金为Mg-30wt.％Nd中间合金，所采用的纯镁的纯度为99.99wt.％以上。
  8. 根据权利要求6所述的生物医用可降解耐蚀高强韧镁合金，其中，所采用的纯Ca的纯度为99.99wt.％以上，所采用的Mg-Zr中间合金为Mg-30wt.％Zr中间合金。
  9. 根据权利要求5所述的生物医用可降解耐蚀高强韧镁合金，其中，得到的镁合金铸锭的尺寸为直径Φ110～150mm，长度2200～2600mm。
  10. 根据权利要求5所述的生物医用可降解耐蚀高强韧镁合金，其中，所述生物医用可降解耐蚀高强韧镁合金的制备步骤进一步包括：将得到的镁合金铸锭截取一定长度，经固溶处理后进行挤压，得到所述的生物医用可降解耐蚀高强韧镁合金。
  11. 根据权利要求10所述的生物医用可降解耐蚀高强韧镁合金，其中，所述固溶处理的温度为480～540℃、时间为8～12小时，所述挤压是在280～420℃的环境下、以挤压比5～30进行的，并且挤压后得到的生物医用可降解耐蚀高强韧镁合金为直径Φ20～40mm 的圆棒。
  12. 一种权利要求1-11任一项所述的生物医用可降解耐蚀高强韧镁合金的制备方法，其至少包括以下步骤：采用真空半连续铸造方式并按照所述的生物医用可降解耐蚀高强韧镁合金的成分及重量百分比制备镁合金铸锭，其中，所采用的原料至少包括：纯Zn、Mg-Nd中间合金以及纯镁。
  13. 根据权利要求12所述的制备方法，其中，所采用的原料还包括：纯Ca和/或Mg-Zr中间合金。
  14. 根据权利要求12所述的制备方法，其中，所采用的纯Zn的纯度为99.99wt.％以上，所采用的Mg-Nd中间合金为Mg-30wt.％Nd中间合金，所采用的纯镁的纯度为99.99wt.％以上。
  15. 根据权利要求13所述的制备方法，其中，所采用的纯Ca的纯度为99.99wt.％以上，所采用的Mg-Zr中间合金为Mg-30wt.％Zr中间合金。
  16. 根据权利要求12所述的制备方法，其中，所述真空半连续铸造包括以下步骤：
    (1)在真空熔炼炉中熔化原料，熔化时控制熔液温度为740～760℃，待原料全部熔化后，再通入惰性气体进行真空环境下的气体搅拌，搅拌时间为30-45min；
    (2)完成搅拌后向熔液表面通入SF6与CO2混合气体进行保护，同时将熔液升温至760～780℃保温30～40min，之后将熔液温度降至700～720℃静置90～120min；
    (3)随后在半连续铸造机上进行铸造，半连续铸造过程中采用SF6与CO2混合气体进行保护，并控制真空熔炼炉内熔液温度为700～720℃，结晶器内熔液温度为680～690℃，拉锭速度为30～50mm/min，并且在近结晶器300～500mm处采用高压水冷，以下部位采用空冷，得到所述的镁合金铸锭。
  17. 根据权利要求12所述的制备方法，其中，得到的镁合金铸锭的尺寸为直径Φ110～150mm，长度2200～2600mm。
  18. 根据权利要求12所述的制备方法，其进一步包括以下步骤：将得到的镁合金铸锭截取一定长度，经固溶处理后进行挤压，得到所述的生物医用可降解耐蚀高强韧镁合金。
  19. 根据权利要求18所述的制备方法，其中，所述固溶处理的温度为480～540℃、时间为8～12小时，所述挤压是在280～420℃的环境下、以挤压比5～30进行的，并且挤压后得到的生物医用可降解耐蚀高强韧镁合金为直径Φ20～40mm的圆棒。
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