A biomedical Mg-Gd-Nd-Zr-In alloy and its preparation method

Abstract

The present invention relates to the technical field of biomedical materials, and specifically relates to a biomedical Mg-Gd-Nd-Zr-In alloy and a preparation method thereof. The Mg-Gd-Nd-Zr-In alloy comprises, by mass percentage: Gd: 5% - 10%, Nd: 1% - 5%, Zr: 0.5% - 1%, In: 0.2% - 1%, with a total of 100%. The present invention has developed a biomedical Mg-Gd-Nd-Zr-In alloy with both high mechanical strength and excellent corrosion resistance. By utilizing the differences in dissolution and deposition between elements, it promotes the formation of a dense protective film to improve the corrosion resistance of the alloy, and utilizes the strong precipitation effect of Gd and Nd to improve the mechanical strength of the alloy. This alloy has excellent mechanical properties, better degradation performance in simulated body fluid than high-purity Mg, no cytotoxicity, and excellent biocompatibility, meeting the dual requirements of mechanics and degradation for current degradable implants.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and particularly relates to a biomedical Mg-Gd-Nd-Zr-In alloy and a preparation method thereof. Background Art

[0002] With the aging of the population and the progress of medical technology, the demand for biomedical materials is increasing day by day. Among many biomedical materials, degradable metal materials have shown great potential and advantages because they can be gradually absorbed by the human body after completing their temporary functions, avoiding the need for secondary surgery to remove them.

[0003] Magnesium and its alloys often have good biocompatibility, and at the same time have the characteristics of low density, high specific strength, good damping and excellent processing performance. Coupled with mechanical properties very similar to those of human bones, these all make it a very promising biomedical material. However, the rapid corrosion rate of magnesium alloys and the resulting hydrogen release problem limit their clinical applications. Existing commercial magnesium alloys, such as AZ31, AZ91 containing Al element, were initially developed for structural materials and did not fully consider the safety issues as biomaterials. Therefore, developing high-performance magnesium alloys with high strength and high corrosion resistance based on considering the biological toxicity of alloy elements is the focus of current research.

[0004] The development of current high-strength magnesium alloys has gradually matured, but the corrosion resistance of these high-strength magnesium alloys is often very poor. At the same time, the mechanical strength of the currently reported high-corrosion-resistant magnesium alloys is often very low. Magnesium alloys are facing the dilemma of being difficult to have both mechanical strength and corrosion resistance. Summary of the Invention

[0005] Aiming at the deficiencies of the above-mentioned prior art, the purpose of the present invention is to provide a biomedical Mg-Gd-Nd-Zr-In alloy and a preparation method thereof. Based on the lack of high-performance biomedical magnesium alloy systems, the present invention provides a magnesium alloy with excellent corrosion resistance, mechanical properties and biocompatibility and a preparation method thereof.

[0006] To solve the above technical problems, the present invention adopts the following technical solutions:

[0007] A biomedical Mg-Gd-Nd-Zr-In alloy, by mass percentage, the Mg-Gd-Nd-Zr-In alloy includes:

[0008] Gd: 5% - 10%, Nd: 1% - 5%, Zr: 0.5% - 1%, In: 0.2% - 1%, the balance is Mg, totaling 100%.

[0009] The high-performance biomedical Mg-Gd-Nd-Zr-In alloy designed by the present invention first strengthens the alloy by the strong precipitation effect of Gd and Nd elements. At the same time, the dissolving and depositing of alloy elements are asynchronous, that is, Gd, Nd elements and Mg dissolve preferentially and rapidly, while In element enriches on the alloy surface and then dissolves completely at one time, obtaining a relatively high interfacial ion concentration. Then, due to the high ion concentration of In element at the interface, the deposition conditions of its corresponding degradation products are reached, so that nucleation and deposition occur most preferentially on the surface. Although a film layer that completely covers the alloy surface cannot be formed, it can provide a nucleation surface for the subsequent deposition of Gd and Nd elements, reduce the nucleation energy of the degradation products of the subsequently deposited Gd and Nd, and accelerate the nucleation rate of Gd and Nd elements; Subsequently, the deposition of Gd and Nd will further promote the deposition of Mg. This asynchronous dissolution and deposition will promote the formation of a dense degradation product film, thereby reducing the degradation rate of the alloy in simulated body fluid and effectively combining the mechanical strength and corrosion resistance of the alloy as a whole.

[0010] In addition, for the high-performance biomedical Mg-Gd-Nd-Zr-In alloy designed by the present invention, it should be noted that the content of micro / low alloying elements has a very complex and sensitive effect on corrosion resistance and mechanical properties, and the two restrict each other. If the content of micro alloying element In is too much, it will hinder the dissolution of low alloying elements Gd, Nd and Mg elements, resulting in too low ion concentration at the interface, too few degradation products formed and insufficient protection; if the content of In is too little, it cannot play the role of accelerating nucleation. If the content of low alloying elements Gd and Nd is too much, a large number of second phases will be formed to promote microgalvanic corrosion; if the content is too little, it cannot play the role of promoting the nucleation of Mg element and cannot form enough strengthening phases, which is not conducive to the mechanical properties and corrosion resistance of the alloy. The Zr element mainly plays the role of refining grains and improving mechanical properties.

[0011] In a preferred embodiment of the present invention, by mass percentage, the Mg-Gd-Nd-Zr-In alloy comprises:

[0012] Gd: 9%, Nd: 2%, Zr: 0.5%, In: 0.5%, Fe < 0.015%, Cu < 0.015%, Ni < 0.005%, and the balance is Mg, totaling 100%.

[0013] The Mg-Gd-Nd-Zr-In alloy also includes impurity elements. By mass percentage: impurity Fe < 0.015%, Cu < 0.015%, Ni < 0.005%.

[0014] Another object of the present invention is to provide a preparation method of a biomedical Mg-Gd-Nd-Zr-In alloy, comprising the following steps:

[0015] Weigh the raw materials Mg, In, Mg-25Gd, Mg-25Nd and Mg-20Zr master alloys according to the mass percentages: Gd: 5% - 10%, Nd: 1% - 5%, Zr: 0.5% - 1%, In: 0.2% - 1%, Fe < 0.015%, Cu < 0.015%, Ni < 0.005%, and the balance is Mg, with a total of 100%, and carry out batching.

[0016] Under a protective atmosphere, heat and melt the weighed raw materials and stir them for homogenization treatment.

[0017] Cast the homogenized raw materials to obtain a Mg-Gd-Nd-Zr-In alloy ingot, and perform turning or milling on the Mg-Gd-Nd-Zr-In alloy ingot to remove the surface oxide layer and skin defects.

[0018] Heat and hold the Mg-Gd-Nd-Zr-In alloy ingot after turning or milling, and then perform hot extrusion treatment to obtain an extruded bar.

[0019] Perform aging treatment on the extruded bar to obtain a high-performance biomedical Mg-Gd-Nd-Zr-In alloy.

[0020] In a preferred embodiment of the present invention, the hot extrusion temperature is 400°C - 450°C, the extrusion ratio is 8 - 10:1, and the extrusion rate is 0.3 mm / s - 0.5 mm / s.

[0021] In a preferred embodiment of the present invention, the aging treatment temperature is 180°C - 250°C, and the aging treatment time is 80 hours - 100 hours.

[0022] In a preferred embodiment of the present invention, when performing hot extrusion treatment, the heating and holding temperature is 400°C - 450°C, and the holding time is 1 hour - 2 hours.

[0023] In a preferred embodiment of the present invention, when performing homogenization treatment, the heating temperature is 700°C - 740°C.

[0024] In a preferred embodiment of the present invention, the protective atmosphere is CO2 and SF6 with a volume ratio of 9:1.

[0025] In a preferred embodiment of the present invention, the purities of the raw materials Mg and In are both greater than 99.9%.

[0026] Compared with the prior art, the beneficial effects of the present invention are:

[0027] 1. The high-performance biomedical Mg-Gd-Nd-Zr-In alloy designed by the present invention first strengthens the alloy by the strong precipitation effect of Gd and Nd elements. At the same time, due to the asynchronous dissolution and deposition among alloy elements, that is, Gd, Nd elements and Mg dissolve preferentially and rapidly, while In element enriches on the alloy surface and then dissolves completely at one time, obtaining a higher interfacial ion concentration. Then, due to the high ion concentration of In element at the interface, the deposition condition of its corresponding degradation product is reached, so it nucleates and deposits most preferentially on the surface. Although a film layer that completely covers the alloy surface cannot be formed, it can provide a nucleation surface for the subsequent deposition of Gd and Nd elements, reduce the nucleation energy of the degradation products of the subsequently deposited Gd and Nd, and accelerate the nucleation rate of Gd and Nd elements; Subsequently, the deposition of Gd and Nd will further promote the deposition of Mg. This asynchronous dissolution and deposition will promote the formation of a dense degradation product film, thereby reducing the degradation rate of the alloy in simulated body fluid and effectively combining the mechanical strength and corrosion resistance of the alloy as a whole.

[0028] 2. For the high-performance biomedical Mg-Gd-Nd-Zr-In alloy designed by the present invention, it should be noted that the content of micro / low alloying elements has a very complex and sensitive effect on corrosion resistance and mechanical properties, and the two restrict each other. If the content of micro alloying element In is too much, it will hinder the dissolution of low alloying elements Gd, Nd and Mg elements, resulting in too low ion concentration at the interface, too few degradation products formed and insufficient protection; If the content of In is too little, it cannot play the role of accelerating nucleation. If the content of low alloying elements Gd and Nd is too much, a large number of second phases will be formed to promote microgalvanic corrosion; If the content is too little, it cannot play the role of promoting the nucleation of Mg element and cannot form enough strengthening phases, which is not conducive to the mechanical properties and corrosion resistance of the alloy. The Zr element mainly plays the role of refining grains and improving mechanical properties.

[0029] 3. The degradation performance of the high-performance biomedical magnesium alloy Mg-9Gd-2Nd-0.5Zr-0.5In designed by the present invention in simulated body fluid is better than that of high-purity magnesium, and a degradation product layer with a certain thickness and very dense can be formed, and the alloy shows excellent degradation performance.

[0030] 4. The high-performance biomedical magnesium alloy Mg-9Gd-2Nd-0.5Zr-0.5In designed by the present invention has excellent biocompatibility. The alloy has a beneficial effect on cell proliferation, with high cell activity and no cytotoxicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a comparison diagram of the stress-strain curves of the alloys prepared in Example 1 and Example 2 of the present invention.

[0032] Figure 2SEM photographs of the surfaces of the corrosion products of the test samples obtained in (a) Example 1 and (b) Comparative Example 1 of the present invention after long-term immersion.

[0033] Figure 3 SEM photographs of the surfaces of the test samples obtained in (a) Example 1 and (b) Comparative Example 1 of the present invention after removing the corrosion products after long-term immersion.

[0034] Figure 4 2D laser confocal images of the test samples obtained in (a) Example 1 and (b) Comparative Example 1 of the present invention after removing the surface corrosion products.

[0035] Figure 5 Electrochemical impedance spectroscopy diagrams of the test samples obtained in Example 1 of the present invention during regular monitoring in the long-term immersion cycle. (a) is for immersion for 0 - 30 days, (b) is for immersion for 36 - 60 days, (c) is for immersion for 66 - 90 days. Here, Z' represents the real part of the impedance and Z" represents the imaginary part of the impedance.

[0036] Figure 6 Statistical result diagram of the electrochemical impedance calculation of the test sample prepared in Example 1 of the present invention and the commercial high-purity magnesium test sample of the comparative example.

[0037] Figure 7 Fluorescence microscopic images of the precursor cells of mouse embryonic osteoblasts in the alloy prepared in Example 1 of the present invention, the commercial high-purity magnesium of the comparative example, and the implant of the blank group.

[0038] Figure 8 Absorbance statistical diagram (a) and statistical diagram of relative cell proliferation rate (b) measured after culturing and treating the precursor cells of mouse embryonic osteoblasts in the alloy prepared in Example 1 of the present invention, the commercial high-purity magnesium of Comparative Example 1, and the implant of the blank group. Detailed implementation manners

[0039] The following combines the embodiments of the present invention, and uses the preferred embodiments and the accompanying drawings to cooperate with a detailed description. The technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0040] It should be noted that all the professional terms used in the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the protection scope of the present invention. Unless otherwise specifically stated, all kinds of raw materials, reagents, instruments and equipment used in the following embodiments of the present invention can be obtained through market purchase or prepared by existing methods.

[0041] The present invention aims to solve a series of problems such as insufficient mechanical strength and corrosion resistance of biomedical magnesium alloys, and proposes a biomedical Mg-Gd-Nd-Zr-In alloy and a preparation method. The conventional three-electrode system is used for electrochemical testing, and the degradation rate of the alloy is analyzed by electrochemical impedance spectroscopy and polarization curves. The mechanical properties of the alloy are evaluated by tensile tests, and the biocompatibility of the alloy is evaluated by cytotoxicity experiments. The results show that the corrosion potential and corrosion current density are obtained by Tafel extrapolation of the polarization curve, and the corrosion rate is calculated. The corrosion rate of the alloy in simulated body fluid is significantly lower than that of high-purity Mg. The polarization resistance under long-term immersion is statistically analyzed, and the degradation performance of the alloy is significantly better than that of high-purity Mg. According to the results of the tensile test, the yield strength, tensile strength and elongation at break of the alloy after aging are 307.29±7.19 MPa, 321.78±3.65 MPa and 24.78±2.95%, respectively, and the mechanical strength and plasticity are excellent. Combined with the results of the cytotoxicity test, the alloy is non-cytotoxic and has no effect on cell morphology. In summary, the high-performance biomedical Mg-Gd-Nd-Zr-In alloy of the present invention meets the multiple requirements of current degradable implants for mechanical strength, degradation performance and biocompatibility, and is expected to be implemented in clinical medical research.

[0042] Example 1

[0043] A method for preparing a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy comprises the following steps:

[0044] (1) High-purity Mg and high-purity In with a purity greater than 99.9% and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are prepared according to the composition of Mg-9Gd-2Nd-0.5Zr-0.5In.

[0045] (2) Place the raw materials prepared in step (1) into a graphite crucible, heat them in a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, and keep them warm at 720°C. After ensuring that the raw materials are completely melted, mechanical stirring is performed for 10 minutes to ensure that the raw materials are evenly mixed. After that, the raw materials are allowed to stand for 10 minutes, slag is removed, and then allowed to stand for 15 minutes.

[0046] (3) The raw material in the crucible in step (2) is cast into a sand mold to obtain a cylindrical ingot.

[0047] (4) The ingot obtained in step (3) is turned or milled to remove the oxide layer and surface defects on the surface of the ingot, and then kept at 400°C for 2 hours, and then extruded at 400°C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy.

[0048] Example 2

[0049] A method for preparing a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy comprises the following steps:

[0050] (1) High-purity Mg and high-purity In with a purity greater than 99.9% and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are prepared according to the composition of Mg-9Gd-2Nd-0.5Zr-0.5In.

[0051] (2) Place the raw materials prepared in step (1) into a graphite crucible, heat them in a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, and keep them warm at 720°C. After ensuring that the raw materials are completely melted, mechanical stirring is performed for 10 minutes to ensure that the raw materials are evenly mixed. After that, the raw materials are allowed to stand for 10 minutes, slag is removed, and then allowed to stand for 15 minutes.

[0052] (3) The raw material in the crucible in step (2) is cast into a sand mold to obtain a cylindrical ingot.

[0053] (4) The ingot obtained in step (3) is turned or milled to remove the oxide layer and skin defects on the surface of the ingot, and then kept at 400° C. for 2 hours, and then extruded at 400° C. with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s.

[0054] (5) The magnesium alloy extruded rod in step (4) is kept at 200° C. for 96 hours for aging treatment to obtain a fine precipitate phase in the matrix structure, thereby obtaining a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy.

[0055] Example 3

[0056] A method for preparing a high-performance biomedical Mg-5Gd-1Nd-0.5Zr-0.2In alloy comprises the following steps:

[0057] (1) High-purity Mg and high-purity In with a purity greater than 99.9% and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are prepared according to the composition of Mg-5Gd-1Nd-0.5Zr-0.2In.

[0058] (2) Place the raw materials prepared in step (1) into a graphite crucible, heat them in a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, and keep them warm at 720°C. After ensuring that the raw materials are completely melted, mechanical stirring is performed for 10 minutes to ensure that the raw materials are evenly mixed. After that, the raw materials are allowed to stand for 10 minutes, slag is removed, and then allowed to stand for 15 minutes.

[0059] (3) Cast the raw materials in the crucible in step (2) into the sand mold to obtain a cylindrical ingot.

[0060] (4) Process the ingot obtained in step (3) by turning or milling to remove the oxide layer and skin defects on the surface of the ingot, then keep it warm at 400 °C for 2 hours, and then perform extrusion at 400 °C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a high-performance biomedical Mg-5Gd-1Nd-0.5Zr-0.2In alloy.

[0061] Example 4

[0062] A preparation method of a high-performance biomedical Mg-10Gd-5Nd-1Zr-1In alloy, comprising the following steps:

[0063] (1) Charge high-purity Mg with a purity greater than 99.9%, high-purity In, and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys according to the composition of Mg-10Gd-5Nd-1Zr-1In.

[0064] (2) Put the raw materials prepared in step (1) into a graphite crucible, heat it under a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, keep it warm at 720 °C, ensure that the raw materials are completely melted, then perform mechanical stirring for 10 minutes to ensure uniform mixing of the raw materials, then let it stand for 10 minutes, skim the slag, and then let it stand for 15 minutes.

[0065] (3) Cast the raw materials in the crucible in step (2) into the sand mold to obtain a cylindrical ingot.

[0066] (4) Process the ingot obtained in step (3) by turning or milling to remove the oxide layer and skin defects on the surface of the ingot, then keep it warm at 400 °C for 2 hours, and then perform extrusion at 400 °C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a high-performance biomedical Mg-10Gd-5Nd-1Zr-1In alloy.

[0067] Example 5

[0068] A preparation method of a high-performance biomedical Mg-7Gd-3Nd-0.8Zr-0.7In alloy, comprising the following steps:

[0069] (1) Charge high-purity Mg with a purity greater than 99.9%, high-purity In, and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys according to the composition of Mg-7Gd-3Nd-0.8Zr-0.7In.

[0070] (2) Put the raw materials prepared in step (1) into a graphite crucible, heat them under a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, keep them at 720 °C for heat preservation, ensure that the raw materials are completely melted, then carry out mechanical stirring for 10 minutes to ensure uniform mixing of the raw materials, then let it stand for 10 minutes and skim the slag, and then let it stand for 15 minutes.

[0071] (3) Pour the raw materials in the crucible in step (2) into a sand mold to obtain a cylindrical ingot.

[0072] (4) Process the ingot obtained in step (3) by turning or milling to remove the oxide layer and surface defects on the ingot surface, then keep it at 400 °C for 2 hours, and then carry out extrusion at 400 °C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a high-performance biomedical Mg-7Gd-3Nd-0.8Zr-0.7In alloy.

[0073] Example 6

[0074] A preparation method of a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy, comprising the following steps:

[0075] (1) Charge high-purity Mg with a purity greater than 99.9%, high-purity In, and Mg-25Gd, Mg-25Nd, Mg-20Zr master alloys according to the composition of Mg-9Gd-2Nd-0.5Zr-0.5In.

[0076] (2) Put the raw materials prepared in step (1) into a graphite crucible, heat them under a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, keep them at 700 °C for heat preservation, ensure that the raw materials are completely melted, then carry out mechanical stirring for 10 minutes to ensure uniform mixing of the raw materials, then let it stand for 10 minutes and skim the slag, and then let it stand for 15 minutes.

[0077] (3) Pour the raw materials in the crucible in step (2) into a sand mold to obtain a cylindrical ingot.

[0078] (4) Process the ingot obtained in step (3) by turning or milling to remove the oxide layer and surface defects on the ingot surface, then keep it at 420 °C for 1 hour, and then carry out extrusion at 420 °C with an extrusion ratio of 8 and an extrusion rate of 0.3 mm / s to obtain a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy.

[0079] Example 7

[0080] A preparation method of a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy, comprising the following steps:

[0081] (1) High-purity Mg and high-purity In with a purity greater than 99.9% and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are prepared according to the composition of Mg-9Gd-2Nd-0.5Zr-0.5In.

[0082] (2) The raw materials prepared in step (1) are placed in a graphite crucible, heated in a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, and kept warm at 740°C. After the raw materials are completely melted, mechanical stirring is performed for 10 minutes to ensure that the raw materials are evenly mixed. After that, the raw materials are allowed to stand for 10 minutes, slag is removed, and then allowed to stand for 15 minutes.

[0083] (3) The raw material in the crucible in step (2) is cast into a sand mold to obtain a cylindrical ingot.

[0084] (4) The ingot obtained in step (3) is turned or milled to remove the oxide layer and surface defects on the surface of the ingot, and then kept at 450° C. for 1.5 hours, and then extruded at 450° C. with an extrusion ratio of 10 and an extrusion rate of 0.5 mm / s to obtain a high-performance biomedical Mg-9Gd-2Nd-0.5Zr-0.5In alloy.

[0085] Comparative Example 1

[0086] Generally, due to the segregation of alloying elements and the presence of second phase particles in the structure, the corrosion rate of magnesium alloy is much higher than that of high-purity magnesium. Reducing the corrosion rate of magnesium alloy can usually only infinitely approach the corrosion rate of high-purity magnesium. Therefore, in the present invention, commercial high-purity magnesium with a purity of 99.99% is used as a comparative example.

[0087] Comparative Example 2

[0088] A method for preparing a biomedical Mg-4Gd-0.5Nd-0.5Zr-0.1In alloy comprises the following steps:

[0089] (1) High-purity Mg and high-purity In with a purity greater than 99.9% and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are prepared according to the composition of Mg-4Gd-0.5Nd-0.5Zr-0.1In.

[0090] (2) Place the raw materials prepared in step (1) into a graphite crucible, heat them in a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1, and keep them warm at 720°C. After ensuring that the raw materials are completely melted, mechanical stirring is performed for 10 minutes to ensure that the raw materials are evenly mixed. After that, the raw materials are allowed to stand for 10 minutes, slag is removed, and then allowed to stand for 15 minutes.

[0091] (3) The raw material in the crucible in step (2) is cast into a sand mold to obtain a cylindrical ingot.

[0092] (4) The ingot obtained in step (3) is processed by turning or milling to remove the oxide layer and surface defects on the ingot surface. Subsequently, it is held at 400 °C for 2 hours, and then extruded at 400 °C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a biomedical Mg-4Gd-0.5Nd-0.5Zr-0.1In alloy.

[0093] Comparative Example 3

[0094] A method for preparing a biomedical Mg-11Gd-6Nd-1.5Zr-1.5In alloy, comprising the following steps:

[0095] (1) High-purity Mg with a purity greater than 99.9%, high-purity In, and Mg-25Gd, Mg-25Nd, and Mg-20Zr master alloys are proportioned according to the composition of Mg-11Gd-6Nd-1.5Zr-1.5In.

[0096] (2) The raw materials proportioned in step (1) are placed in a graphite crucible and heated under a protective atmosphere of CO2 and SF6 with a volume ratio of 9:1. It is held at 720 °C to ensure complete melting of the raw materials, followed by 10 minutes of mechanical stirring to ensure uniform mixing of the raw materials. After that, it is left standing for 10 minutes, then slag is skimmed off, and then left standing for 15 minutes.

[0097] (3) The raw materials in the crucible in step (2) are cast into a sand mold to obtain a cylindrical ingot.

[0098] (4) The ingot obtained in step (3) is processed by turning or milling to remove the oxide layer and surface defects on the ingot surface. Subsequently, it is held at 400 °C for 2 hours, and then extruded at 400 °C with an extrusion ratio of 9 and an extrusion rate of 0.4 mm / s to obtain a biomedical Mg-11Gd-6Nd-1.5Zr-1.5In alloy.

[0099] Examples 3 to 7 are high-performance biomedical Mg-Gd-Nd-Zr-In alloys prepared by changing the amounts of alloying elements and process conditions. Comparative Examples 2 and 3 are Mg-Gd-Nd-Zr-In alloys prepared by changing the percentages of different alloying elements. Since the contents of micro / low alloying elements in the alloys designed in the present invention have a very complex and sensitive effect on the corrosion resistance and mechanical properties, and the two restrict each other. If the content of the micro-alloying element In is too high, it will hinder the dissolution of the low alloying elements Gd, Nd and Mg elements, resulting in too low ion concentration at the interface, too few degradation products formed and insufficient protection; if the content of In is too low, it cannot play the role of accelerating nucleation. If the contents of the low alloying elements Gd and Nd are too high, a large amount of second phases will be formed to promote micro-galvanic corrosion; if the contents are too low, they cannot play the role of promoting the nucleation of Mg elements, nor can sufficient strengthening phases be formed, which is not conducive to the mechanical properties and corrosion resistance of the alloys. Therefore, the alloys obtained in Comparative Examples 2 and 3 cannot effectively improve the mechanical properties and corrosion resistance at the same time.

[0100] The Mg-9Gd-2Nd-0.5Zr-0.5In alloy bars after aging treatment were cut by wire cutting to make 20 mm×20 mm×5 mm and sheet dog-bone-shaped tensile specimens respectively. The gauge length of the tensile specimens was 15 mm, the width was 3.6 mm, and the thickness was 2.5 mm for subsequent electrochemical tests and room temperature tensile tests. Before the tests, all specimens were polished with SiC sandpaper.

[0101] The room temperature tensile properties were tested according to GB / T 228.1-2010 "Metallic materials-Tensile testing-Part 1: Method of test at room temperature" using an INSTRON 55822 electronic universal testing machine.

[0102] After connecting the samples with copper wires, they were embedded in epoxy resin. The connection between the samples and the wires should be sealed in the epoxy resin. After the epoxy resin solidified, the surfaces of the samples without connected wires were ground with 140-mesh, 600-mesh, 1200-mesh and 2000-mesh sandpapers respectively to expose the material surfaces, which were used as the test surfaces. The areas of the test surfaces were measured and recorded. Then the samples were used as the anodes, platinum wires as the counter electrodes, and saturated calomel reference electrodes were inserted near the test surfaces of the samples as reference electrodes. The impedance spectra and polarization curves of the samples after soaking in simulated body fluid for different times were tested using an electrochemical workstation.

[0103] Before the electrochemical impedance test, the samples were stabilized for 30 minutes to 60 minutes, the test frequency was 100 kHz to 10 mHz, and the amplitude was set to 10 mV.

[0104] The chromic acid solution used to clean the degradation products on the sample surface was composed of 200 g / L CrO3 and 10 g / L AgNO3.

[0105] After the test, the samples were taken out, and the degradation products were cleaned with chromic acid, and the degradation morphology was characterized by scanning electron microscopy. At the same time, the depth of local corrosion pits on the surface of the samples was measured by laser confocal microscopy.

[0106] An extract of Mg-Gd-Nd-Zr-In alloy was prepared and the cytotoxicity of the alloy was tested. The specific operations are as follows:

[0107] (1) The Mg-Gd-Nd-Zr-In alloy was cut into cylinders with a diameter of 10 mm and a height of 2 mm, polished successively with 800#, 1000#, 1500# and 2000# sandpapers, ultrasonically cleaned with absolute ethanol for 5 minutes, and dried for standby.

[0108] (2) The precursor cells of mouse embryonic osteoblasts were added to a modified minimum essential medium (α-MEM) containing 10% (v / v) fetal bovine serum (FBS), placed in a cell incubator with 5% (v / v) CO2 at 37 °C, and passaged by digestion with 0.25% (v / v) trypsin.

[0109] (3) The specimens were placed in 24-well plates and soaked in α-MEM medium containing 10% (v / v) FBS according to the soaking ratio of 1.25 cm 2 / mL according to the ISO10993 international standard, placed in a cell incubator with 5% (v / v) CO2 at 37 °C to prepare the extract. After that, the volume fraction of the extract was diluted 6 times and an in vitro cytotoxicity test was carried out.

[0110] (4) 100 μL of MC3T3-E1 cell suspension with a concentration of 3×10 4 / mL was inoculated into 96-well plates, with 5 wells inoculated in each group, and cultured in a cell incubator with 5% (v / v) CO2 at 37 °C for 24 hours. After the cells adhered and grew, the original medium was discarded. 100 μL of the extract of Mg-Gd-Nd-Zr-In alloy was added to each well. The control group was α-MEM medium containing 10% (v / v) FBS. The culture was continued. The 96-well plates were taken out after 24, 48 and 72 hours respectively. The supernatant was carefully aspirated, rinsed 3 times with phosphate buffer (PBS), and then 100 μL of α-MEM medium containing 10% (v / v) CCK 8 reagent was added to each well and cultured for another 2 hours. The cell OD values of each well were measured with an automatic microplate reader at a wavelength of 450 nm to calculate the cell survival rate.

[0111] During the sample soaking process, the water bath temperature was set at 37 °C to simulate the human body temperature. Simulated body fluids such as SBF, Hank's solution, and MEM can be selected.

[0112] In the long-term immersion experiment of the samples, the simulated body fluid was replaced every 24 hours to eliminate the influence of the change in the pH value of the simulated body fluid on the test results.

[0113] Result analysis

[0114] Figure 1 The stress-strain curve diagrams of the alloys prepared in Example 1 and Example 2 of the present invention are as follows Figure 1 shown. The yield strength, tensile strength, and elongation at break of the alloy prepared in Example 1 are 307.29 ± 7.19 MPa, 321.78 ± 3.65 MPa, and 24.78 ± 2.95% respectively. The yield strength, tensile strength, and elongation at break of the alloy prepared in Example 2 are 272.66 ± 5.12 MPa, 300.67 ± 2.18 MPa, and 26.38 ± 2.28% respectively. Both Example 1 and Example 2 have excellent mechanical properties.

[0115] Figure 2 The surface SEM images of the corrosion products of the test samples obtained from Example 1 of the present invention and Comparative Example 1 after long-term immersion are as follows; among them, (a) is Example 1, and (b) is Comparative Example 1, as Figure 2 shown. After long-term immersion, due to the asynchronous dissolution and deposition between alloy elements, the surface of the sample in Example 1 has been completely covered by corrosion products, and the corrosion products are closely packed. While the corrosion product particles on the surface of the sample in Comparative Example 1 are fine, and cracks appear due to dehydration of the surface layer. The formation of the dense degradation product layer significantly reduces the degradation rate of Example 1.

[0116] Figure 3 The surface SEM images of the test samples obtained from Example 1 of the present invention and Comparative Example 1 after removing the corrosion products after long-term immersion are as follows; among them, (a) is Example 1, and (b) is Comparative Example 1, as Figure 3 shown. After long-term immersion, there is no serious local corrosion on the surface of Example 1, while Comparative Example 1 shows relatively serious local corrosion, indicating that Example 1 can undergo uniform degradation.

[0117] Figure 4 The 2D laser confocal images of the test samples obtained from Example 1 of the present invention and the comparative example after removing the surface corrosion products are as follows; among them, (a) is Example 1, and (b) is Comparative Example 1, as Figure 4 shown. On the cross-section with the largest online roughness, Example 1 is significantly lower than Comparative Example 1, which also reflects that the local corrosion of Comparative Example 1 is more serious.

[0118] Figure 5The electrochemical impedance spectroscopy diagram obtained by periodically monitoring the test sample obtained in Example 1 of the present invention during the long-term immersion cycle; wherein, (a) is for Example 1 immersed for 0 - 30 days, (b) is for Example 1 immersed for 36 - 60 days, (c) is for Example 1 immersed for 66 - 90 days, as Figure 5 shown, the impedance on the electrochemical spectroscopy diagram is always in the order of 10 4 during the immersion period, and this result indicates that the dense degradation product layer formed on the surface of the alloy provides continuous protection for the alloy matrix.

[0119] Figure 6 The corrosion rate change with time obtained by fitting the electrochemical impedance of Example 1 of the present invention and the commercial high-purity magnesium of the comparative example. After soaking for 15 days, the degradation rates of Example 1 and the commercial high-purity magnesium of the comparative example are close. After 15 days, the difference rate of the degradation rates of the two gradually becomes larger, and the degradation rate of Example 1 is significantly lower than that of the commercial high-purity magnesium of the comparative example.

[0120] Figure 7 The cell fluorescence microscopic images of the precursor cells of mouse embryonic osteoblasts co-cultured in the leaching solutions of Example 1 of the present invention and the commercial high-purity magnesium of the comparative example for 1 - 3 days. As the number of culture days extends, the number of cells in the three groups of experiments all increases and the morphology is similar, which indicates that Example 1 has no influence on the cell morphology.

[0121] Figure 8 The absorbance statistics and relative cell proliferation rate statistical chart measured after culturing the precursor cells of mouse embryonic osteoblasts in the leaching solutions of Example 1 of the present invention and the commercial high-purity magnesium of the comparative example for different days. Among them, (a) is the absorbance statistical chart, and (b) is the relative cell proliferation rate statistical chart. As Figure 8 shown, the cell activity and relative cell proliferation rate of Example 1 are higher than those of the commercial high-purity magnesium of the comparative example on the third day, and the cytotoxicity is at level 0, which indicates that Example 1 has excellent biocompatibility.

[0122] In summary, the high-performance biomedical Mg-Gd-Nd-Zr-In alloy prepared by the present invention has high mechanical strength, excellent degradation performance, no cytotoxicity, and excellent biocompatibility, meeting the multiple requirements of current degradable implants for mechanical strength, degradation performance, and biocompatibility, and is expected to be implemented in clinical medical research.

[0123] It should be noted that when the present invention involves a numerical range, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the adopted step method is the same as that of the embodiment, in order to prevent repetition, the present invention describes the preferred embodiments. Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications to these embodiments once they know the basic creative concept. Therefore, the appended claims are intended to be construed as including the preferred embodiments and all changes and modifications falling within the scope of the present invention.

[0124] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the present invention and its equivalent technologies, the present invention also intends to include these modifications and variations.

Claims

1. A biomedical Mg-Gd-Nd-Zr-In alloy, characterized in that: In terms of mass percentage, the Mg-Gd-Nd-Zr-In alloy comprises: Gd: 5%~10%, Nd: 1%~5%, Zr: 0.5%~1%, In: 0.2%~1%, the balance is Mg, totaling 100%; The preparation method of the biomedical Mg-Gd-Nd-Zr-In alloy comprises the following steps: Weigh raw materials Mg, In, Mg-25Gd, Mg-25Nd and Mg-20Zr master alloy, and mix them according to the mass percentage of Gd: 5%~10%, Nd: 1%~5%, Zr: 0.5%~1%, In: 0.2%~1%, and the balance is Mg, which is 100% in total; The symmetrically taken raw materials are heated, melted and stirred under a protective atmosphere to perform a homogenization treatment; Casting the homogenized raw material to obtain a Mg-Gd-Nd-Zr-In alloy ingot, turning or milling the Mg-Gd-Nd-Zr-In alloy ingot to remove the oxide layer and skin defects on the surface; The Mg-Gd-Nd-Zr-In alloy ingot after turning or milling is heated and kept warm, and then subjected to hot extrusion treatment to obtain the biomedical Mg-Gd-Nd-Zr-In alloy.

2. The biomedical Mg-Gd-Nd-Zr-In alloy according to claim 1, characterized in that: In terms of mass percentage, the Mg-Gd-Nd-Zr-In alloy comprises: Gd: 9%, Nd: 2%, Zr: 0.5%, In: 0.5%, and the balance is Mg, totaling 100%.

3. A method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 1, characterized in that: The following steps are involved: Weigh raw materials Mg, In, Mg-25Gd, Mg-25Nd and Mg-20Zr master alloy, and mix them according to the mass percentage of Gd: 5%~10%, Nd: 1%~5%, Zr: 0.5%~1%, In: 0.2%~1%, and the balance is Mg, which is 100% in total; The symmetrically taken raw materials are heated, melted and stirred under a protective atmosphere to perform a homogenization treatment; Casting the homogenized raw material to obtain a Mg-Gd-Nd-Zr-In alloy ingot, turning or milling the Mg-Gd-Nd-Zr-In alloy ingot to remove the oxide layer and skin defects on the surface; The Mg-Gd-Nd-Zr-In alloy ingot after turning or milling is heated and kept warm, and then subjected to hot extrusion treatment to obtain the biomedical Mg-Gd-Nd-Zr-In alloy.

4. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 3, characterized in that: The hot extrusion temperature is 400℃~450℃, the extrusion ratio is 8~10:1, and the extrusion rate is 0.3 mm / s~0.5 mm / s.

5. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 4, characterized in that: When hot extrusion treatment is performed, the heating and insulation temperature is 400°C to 450°C, and the insulation time is 1 hour to 2 hours.

6. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 3, characterized in that: When the homogenization treatment is performed, the heating temperature is 700°C~740°C.

7. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 3, characterized in that: The alloy after hot extrusion treatment is subjected to aging treatment to obtain a biomedical Mg-Gd-Nd-Zr-In alloy.

8. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 7, characterized in that: The aging treatment temperature is 180°C~250°C, and the aging treatment time is 80 hours~100 hours.

9. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 3, characterized in that: The protective atmosphere is CO2 and SF6 in a volume ratio of 9:

1.

10. The method for preparing the biomedical Mg-Gd-Nd-Zr-In alloy according to claim 3, characterized in that: The purity of raw materials Mg and In is greater than 99.9%.

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