Degradable alloy, preparation method, and medical device

Abstract

A degradable alloy, a preparation method, and a medical device. The degradable alloy comprises the following components in percentage by mass: 18-49 wt% of Re, 0-10 wt% of metal element X, 0-2 wt% of bioactive glass, and the balance of Mo, wherein the mass content of the bioactive glass is not 0, and the metal element X includes at least one of Li, Ti, Zn, Sr, Pt, Au, Nb, Ta, and a rare earth element. The degradable alloy can improve room-temperature brittleness and transverse plasticity, and has both good corrosion resistance and degradation performance.

Description

Degradable alloy, preparation method and medical device

[0001] Related applications

[0002] This application claims priority to the Chinese patent application filed with the China Patent Office on January 2, 2024, with application number 202410005441.4, entitled “Degradable alloy, preparation method and medical device”, the entire contents of which are incorporated by reference into this application. Technical Field

[0003] The present application relates to the field of alloy technology, and in particular to a biodegradable alloy, a preparation method and a medical device. Background Art

[0004] Molybdenum is a refractory, rare metal element located in Period 5, Group VIB of the periodic table. It is a transition element with atomic number 42 and an A2-type body-centered cubic structure. Compared to other refractory elements such as Ta, Nb, and Co, molybdenum not only possesses excellent thermal and electrical conductivity and corrosion resistance, but also has a low coefficient of thermal expansion, high hardness, and excellent high-temperature strength. Therefore, biodegradable alloys are widely used in high-tech fields such as electronics, aerospace, energy, and nuclear reactors. However, molybdenum's shortcomings, such as low-temperature brittleness, poor weldability, oxidation susceptibility, and recrystallization brittleness, have severely limited its wider application.

[0005] Currently, most research on biodegradable alloys focuses on transverse plasticity. While the transverse plasticity of biodegradable alloys has been greatly improved, they often exhibit poor transverse plasticity, with transverse elongation being almost zero, indicating strong anisotropy. This extremely poor transverse plasticity has become a limiting factor in their application in aviation components such as bearings, washers, wheel rims, nuts, quills, and pistons. Furthermore, the plasticity of most biodegradable alloys varies with temperature, causing the material to transition from ductile to brittle fracture within a very narrow temperature range. For example, the ductile-brittle transition temperature (DBTT) of pure molybdenum is near room temperature, making it impossible to plastically process molybdenum ingots at room temperature. Some biodegradable alloys also suffer from room-temperature brittleness. The room-temperature brittleness and low cross-sectional elongation of biodegradable alloys represent two major technical challenges that urgently need to be addressed. Currently, most industrialized biodegradable alloys are used under high temperature conditions, and little attention is paid to the room temperature mechanical properties and lateral plasticity of biodegradable alloys.

[0006] Biodegradable alloys can be used as a new type of biodegradable implant material due to their good biocompatibility, high strength, and excellent imaging performance in radiological diagnosis. However, the room temperature brittleness and transverse plasticity of biodegradable alloys limit their application in biomedical materials. For example, implantable medical devices are used at around human body temperature of 37°C, and the brittleness of biodegradable alloys at this temperature makes their application in medical devices extremely challenging. For example, for cardiovascular implantable alloy stents with transverse post-expansion plastic deformation properties, the poor transverse plasticity of biodegradable alloys limits their application. At the same time, as a biodegradable implant material, it must also have good corrosion resistance and degradation properties. Summary of the Invention

[0007] Based on this, it is necessary to provide a degradable alloy, a preparation method and a medical device that can improve room temperature brittleness and transverse plasticity and have good corrosion resistance and degradation performance.

[0008] In one aspect, the present application provides a biodegradable alloy comprising the following components, calculated by mass: 18wt%-49wt% Re, 0wt%-10wt% metal element X, 0wt%-2wt% bioactive glass, and the balance Mo; the mass content of the bioactive glass is not zero, and the metal element X comprises at least one of Li, Ti, Zn, Sr, Pt, Au, Nb, Ta, and rare earth elements.

[0009] The above-mentioned degradable alloy of the present application adds not less than 18wt% and not more than 49wt% of Re to the molybdenum matrix, and at the same time adds not more than 2wt% of bioactive glass BAG, so that the above-mentioned degradable alloy (Mo-Re-X alloy) has a lower DBTT, overcomes the problem of room temperature brittleness, and has good axial and lateral plasticity, good corrosion resistance and degradation performance.

[0010] In some embodiments, in the degradable alloy, the mass content of the metal element X is 0.2 wt %-10 wt %, and optionally 0.2 wt %-8 wt %.

[0011] In some embodiments, the rare earth element includes at least one of La, Ce, and Y.

[0012] In some embodiments, in the degradable alloy, Re is 18 wt %-45 wt %, optionally 18 wt %-40 wt %, and more optionally 18 wt %-35 wt %.

[0013] In some embodiments, in the degradable alloy, the bioactive glass comprises 0.05 wt % to 2 wt %, and optionally 0.2 wt % to 2 wt %.

[0014] In some embodiments, the degradable alloy further comprises unavoidably introduced impurities with a total content of no more than 300 ppm, optionally no more than 200 ppm, and more optionally no more than 100 ppm.

[0015] In some embodiments, the sum of the weight percentages of Re and X, calculated by mass content, is not less than 20 wt %, optionally not less than 25 wt %, and more optionally not less than 28 wt %.

[0016] In some embodiments, the composition includes: 24 wt%-45 wt% of Re, 0.5 wt%-6 wt% of metal element X, 0.4 wt%-1.6 wt% of bioactive glass, and the balance of Mo.

[0017] In another aspect of the present application, a method for preparing any of the above-mentioned biodegradable alloys is provided, comprising the following steps:

[0018] Providing raw materials according to the composition of the degradable alloy;

[0019] The raw materials are mixed and smelted into shapes.

[0020] In another aspect of the present application, a medical device is provided, the body of which comprises any of the above-mentioned degradable alloys.

[0021] In some embodiments, the medical device includes at least one of a medical stent, a vascular filter, an atrial / ventricular septal occluder, and an embolic protector.

[0022] In some embodiments, the medical device further comprises a drug, and the drug is loaded on the body. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG1 is a SEM surface morphology of the degradable alloy sheet prepared in Example 11 after being extracted in PBS for one month. DETAILED DESCRIPTION

[0024] To facilitate understanding of the present application, a more comprehensive description of the present application will be provided below with reference to the accompanying drawings. The accompanying drawings illustrate preferred embodiments of the present application. However, the present application may be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and comprehensive understanding of the disclosure of the present application.

[0025] It should be noted that when an element is referred to as being “fixed to” another element, it may be directly on the other element or there may be an intermediate element. When an element is referred to as being “connected to” another element, it may be directly connected to the other element or there may be an intermediate element.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0027] One embodiment of the present application provides a biodegradable alloy. The biodegradable alloy comprises the following components, calculated by mass: 18-49 wt% Re (rhenium), 0-10 wt% metal element X, 0-2 wt% bioactive glass, and the balance Mo (molybdenum). The mass content of the bioactive glass is not zero, and the metal element X comprises at least one of lithium (Li), titanium (Ti), zinc (Zn), strontium (Sr), platinum (Pt), gold (Au), niobium (Nb), tantalum (Ta), and a rare earth element.

[0028] Studies have found that adding Re to the molybdenum matrix can lower the ductile-brittle transition temperature (DBTT) of the degradable alloy, and the degradable alloy gradually changes from the anisotropy of pure molybdenum to isotropy. However, the high Re content makes it difficult to achieve good corrosion resistance and there is a problem of low corrosion resistance breakdown potential.

[0029] The above-mentioned degradable alloy of the present application adds not less than 18wt% and not more than 49wt% of Re to the molybdenum matrix, and at the same time adds not more than 2wt% of bioactive glass BAG, so that the above-mentioned degradable alloy (Mo-Re-X alloy) has a lower DBTT, overcomes the problem of room temperature brittleness, and has good axial and lateral plasticity, good corrosion resistance and degradation performance.

[0030] Bioactive glass (BAG), also known as sodium calcium phosphosilicate, is a silicate glass composed of SiO2, Na2O, CaO, and P2O5. When biodegradable alloys containing bioactive glass are implanted in the human body as medical devices, their surface conditions dynamically change over time, forming a bioactive hydroxycarbonate apatite (HCA) layer, which provides a bonding interface for the subsequent rapid endothelialization of the medical device. Furthermore, bioactive glass is primarily composed of SiO2, CaO, P2O5, and SiO2, all essential elements for the human body. Its crystal structure is amorphous and bioactive. Bioactive glass contains both covalent and ionic bonds. The more ionic bonds, the higher the bioactivity. These ionic bonds can form chemical and high-strength bonds with metal atoms or ions, enhancing the alloy's strength and preventing interface fracture when the device is deformed by external forces. In addition, bioactive glass (BAG) can play a lubricating role in the powder forming process of the alloy and is beneficial to the dispersion and breakup of metal powder particle agglomerates, thereby improving the organizational density and uniform density distribution of powder metallurgy.

[0031] In addition, the glass network formed by the amorphous structure of bioactive glass has good deformation coordination, and the performance can be adjusted through composition design. For example, the composition or crystal type and content can be changed to adjust the bioactivity, degradability and mechanical properties of Mo-Re-X series biodegradable alloys.

[0032] Furthermore, after the biodegradable alloy is implanted as a medical device in the human body, the presence of the bioactive glass causes the device's surface condition to dynamically change over time, forming a bioactive, low-crystalline apatite layer on the surface, rendering the previously bioinert biodegradable alloy bioactive. The bioactive glass does not cause cellular damage, and its degradation products are non-toxic and non-polluting, enhancing the biosafety of the biodegradable alloy. Furthermore, the bioactive glass acts as a bridge, providing a chemically bonded interface between the implanted device and biological tissue, further facilitating endothelial cell coverage, enhancing the bond between the implanted alloy device and tissue, promoting the healing of damaged cells, reducing tissue rejection, and effectively lowering the risk of inflammation and thrombosis.

[0033] Metallic element X can form small, dispersed, high-melting-point carbides with the impurity carbon element within the molybdenum matrix, dispersing them within the matrix. This leads to dispersion strengthening, grain refinement, and the hindrance of dislocation motion, significantly improving the room-temperature mechanical properties of the molybdenum matrix. On the one hand, metallic element X has a strong bond with the molybdenum matrix and is primarily precipitated at molybdenum grain boundaries, reducing the driving force for the segregation of C, N, and O atoms toward these grain boundaries, thereby lowering the ductile-brittle transition temperature. On the other hand, metallic element X effectively strengthens the relatively weak interfaces of polycrystalline molybdenum, reducing the tendency for intergranular brittle fracture, improving anisotropy, and ultimately enhancing the plasticity of the degradable alloy.

[0034] Furthermore, the present application optionally adds the above-mentioned mass content of the metal element X to the molybdenum-rhenium matrix, which can not only reduce the content of the rare and expensive Re in the molybdenum-rhenium matrix, but also help to further reduce the DBTT of the degradable alloy, making it far below room temperature, avoiding room temperature brittleness, ensuring the use and storage safety of the stent product, and also play a role in strengthening the molybdenum matrix. The metal element X further cooperates with the bioactive glass BAG to jointly regulate the degradation rate of the alloy, so that it can achieve uniform degradation, and controls the degradation rate within a suitable range, so that its degradation rate is more compatible with clinical application requirements. In addition, due to the addition of the metal element X, the content of Re in the molybdenum-rhenium matrix can be reduced. This economical Mo-Re-X alloy has greater economic benefits.

[0035] The room temperature mechanical properties of the above-mentioned degradable alloy (Mo-Re-X alloy) in this application are significantly improved, especially the anisotropy of the cross-sectional mechanical properties is significantly improved, and it has a brittle-to-ductile transition temperature that is significantly lower than room temperature, making the implant material easy to process and form, and the tensile strength, elastic modulus and other properties meet the basic requirements of vascular stents. It can be used as a degradable molybdenum-based alloy implant material.

[0036] It should be noted that the above-mentioned degradable alloy may contain only the above-mentioned components, or other components may be added. It is understood that the content of the metal element X in the above-mentioned degradable alloy may be 0 or may not be 0.

[0037] In some embodiments, in the above-mentioned degradable alloy, the weight percentage of the bioactive glass BAG is no greater than 1.8 wt%, optionally no greater than 1.6 wt%, such as 0.4 wt% to 1.6 wt%, and more preferably no greater than 1.4 wt%. Furthermore, in the above-mentioned degradable alloy, the weight percentage of the bioactive glass BAG is no greater than 1.2 wt%, such as 0.8 wt% to 1.2 wt%, optionally no greater than 1 wt%, and more preferably no greater than 0.8 wt%. Furthermore, in the above-mentioned degradable alloy, the weight percentage of the bioactive glass BAG is no greater than 0.6 wt%, optionally no greater than 0.4%, and more preferably no greater than 0.3 wt%. Furthermore, in the above-mentioned degradable alloy, the weight percentage of the bioactive glass BAG is no greater than 0.2 wt%, and optionally no greater than 0.1 wt%.

[0038] As an example, in the above-mentioned degradable alloy, the weight percentage of the bioactive glass BAG may be 0.05 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.8 wt%, 1 wt%, 1.2 wt%, 1.4 wt%, 1.5 wt%, 1.6 wt%, 1.8 wt%, or 2 wt%. In some examples, the weight percentage of the bioactive glass BAG may be a range formed by any two of the above-mentioned points, and similarly, the following examples are similar. In some embodiments, the weight percentage of the bioactive glass BAG may be 0.05 wt%-2 wt%, 0.1 wt%-2 wt%, 0.2 wt%-2 wt%, or 0.1 wt%-1.8 wt%.

[0039] In some embodiments, in the above-mentioned degradable alloy, the weight percentage of X is 0.2wt%-10wt%. Further, the weight percentage of X is no greater than 8wt%, and can be 0.2wt%-8wt%. Further, the weight percentage of X is no greater than 6wt%, and can be 0.2wt%-6wt%, or 0.5wt%-6wt%. Further, the weight percentage of X is no greater than 4wt%, and can be 0.2wt%-4wt%. Further, the weight percentage of X is no greater than 2wt%, and can be 0.2wt%-2wt%. Further, the weight percentage of X is no greater than 1wt%, and can be 0.2wt%-1wt%. Further, the weight percentage of X is no greater than 0.8wt%, and can be 0.2wt%-0.8wt%.

[0040] As an example, in the above-mentioned degradable alloy, the weight percentage of X may be 0.2 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.8 wt%, 1 wt%, 1.2 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, or 10 wt%. In some examples, the weight percentage of X may be a range formed by any two of the above-mentioned values, for example, 0.2 wt% to 10 wt%.

[0041] The metal element X includes at least one of platinum (Pt), gold (Au), niobium (Nb), and tantalum (Ta), which can further improve the developability of the degradable alloy. It is understood that the degradable alloy described herein does not contain these metal elements X and still has good developability.

[0042] In some embodiments, the rare earth element includes but is not limited to at least one of La (lanthanum), Ce (cerium) and Y (yttrium), and may also be other rare earth elements.

[0043] In some embodiments, in the degradable alloy, Re is 18 wt % to 45 wt %, optionally 18 wt % to 40 wt % or 24 wt % to 45 wt %.

[0044] Furthermore, the weight percentage of Re is 18 wt%-35 wt%, optionally 18 wt%-30 wt% or 30 wt%-35 wt%.

[0045] Furthermore, the weight percentage of Re is 18 wt%-27 wt%, optionally 18 wt%-24 wt%, and more optionally 18 wt%-21 wt%.

[0046] As an example, in the above-mentioned degradable alloy, the weight percentage of Re may be 18 wt%, 20 wt%, 21 wt%, 24 wt%, 25 wt%, 27 wt%, 30 wt%, 33 wt%, 35 wt%, 40 wt%, 42 wt%, 45 wt%, 46 wt%, or 49 wt%. In some examples, the weight percentage of Re may be a range formed by any two of the above-mentioned points, and similarly, the following descriptions are similar.

[0047] In some embodiments, in the above-mentioned degradable alloy, the sum of the weight percentages of Re and X is not less than 20 wt%, optionally not less than 25 wt%, and more optionally not less than 28 wt%. As an example, the sum of the weight percentages of Re and X can be 20 wt%, 22 wt%, 25 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 38 wt%, 40 wt%, 42 wt%, 45 wt%, 46 wt%, 49 wt%, 50 wt%, 55 wt%, 59 wt%, or a range consisting of any two of the above values. Furthermore, in the above-mentioned degradable alloy, the sum of the weight percentages of Re and X does not exceed 50 wt%, and can further be 20 wt%-50 wt%, or 28 wt%-50 wt%. Further, it may be 33 wt%-46 wt%, or 34 wt%-46 wt%, or 40 wt%-46 wt%.

[0048] In some embodiments, the biodegradable alloy described herein may further include impurities inevitably introduced during the preparation process, such as other metals, semi-metals, metal salts and / or non-metals.

[0049] Unavoidable impurities may include at least one of tungsten (W), iron (Fe), chromium (Cr), aluminum (Al), phosphorus (P), copper (Cu), zirconium (Zr), potassium (K), calcium (Ca), nickel (Ni), silicon (Si), manganese (Mn), oxygen (O), nitrogen (N), carbon (C), and hydrogen (H). The upper limit for tungsten and iron is 100 ppm, and the upper limit for chromium, aluminum, and phosphorus is 80 ppm. The upper limit for copper and zirconium is 30 ppm. The upper limit for potassium, calcium, nickel, and silicon is 50 ppm. The upper limit for manganese, oxygen, nitrogen, carbon, and hydrogen is 20 ppm.

[0050] The total content of all impurity elements does not exceed 300 ppm, optionally does not exceed 200 ppm, and more optionally does not exceed 100 ppm.

[0051] In some embodiments, the biodegradable alloy comprises the following components by mass: 18 wt%-49 wt% Re, 0 wt%-10 wt% metal element X, 0.2 wt%-2 wt% bioactive glass, and the balance Mo.

[0052] Furthermore, the above-mentioned degradable alloy comprises the following components by mass: 24wt%-45wt% of Re, 0.5wt%-6wt% of metal element X, 0.4wt%-1.6wt% of bioactive glass and the balance of Mo.

[0053] Furthermore, the above-mentioned degradable alloy comprises the following components by mass: 30wt%-45wt% of Re, 0.5wt%-4wt% of metal element X, 0.4wt%-1.2wt% of bioactive glass and the balance of Mo.

[0054] Furthermore, the biodegradable alloy comprises the following components by mass: 40 wt%-45 wt% of Re, 0.5 wt%-0.8 wt% of metal element X, 0.4 wt%-0.6 wt% of bioactive glass and the balance of Mo.

[0055] Another embodiment of the present application provides a method for preparing the above-mentioned degradable alloy, comprising the following steps S10-S20.

[0056] S10: providing raw materials according to the composition of the degradable alloy;

[0057] S20: Mix the raw materials and smelt them into shapes.

[0058] In some embodiments, the smelting forming method includes but is not limited to at least one of powder metallurgy and ingot melting.

[0059] Furthermore, the powder metallurgy preparation process includes providing a powder raw material of a biodegradable alloy, mixing the powder raw materials, pressing and molding the powder raw materials into a compact, and then sintering at high temperature; optionally, it also includes subsequent processing. Furthermore, the powder raw material can be a high-purity powder raw material obtained through ion exchange or chemical extraction technology.

[0060] In some examples, the powder raw materials are all pure elements or powder particles with a purity of ≥99.95%, with rhenium powder having a purity of ≥99.98%, a higher requirement for controlling impurity content. Furthermore, the powder raw materials required to prepare the biodegradable alloy are mixed mechanically or chemically in a mixing machine such as a ball mill or V-type mixer to achieve uniformity.

[0061] Furthermore, press forming includes, but is not limited to, at least one of the following near-full-density processes: hot isostatic pressing (HIP), warm compacting, warm flow compaction (WFC), powder forging (P / F), metal injection molding (MIM), rolling, hot pressing and extrusion, and high-speed powder compaction (HVC). After the loose powder raw material is subjected to a certain pressing pressure, the powder particles as a whole move and rearrange, forming cold welds between the surfaces of adjacent particles, forming a compact with a certain size, shape, density, and strength.

[0062] Furthermore, the pressing pressure is 200 MPa-700 MPa, and the time is 10 min-120 min.

[0063] Furthermore, high-temperature sintering is performed under vacuum conditions or in a reducing atmosphere. Furthermore, high-temperature sintering includes solid-solid doping, solid-liquid doping, and liquid-liquid doping processes. The liquid-liquid doping process can achieve the most uniform mixing between ions, ultimately achieving significant improvements in the material's structural uniformity and mechanical properties. Through solid-phase or liquid-phase sintering, atoms migrate due to thermal activation, resulting in metallurgical bonding of powder particles and the formation of grain boundaries. Alloying elements form new compounds at the matrix grain boundaries through dissolution reactions, alloying reactions, and solid-state diffusion.

[0064] Specifically, the uniformly mixed raw material powders are reduced and then pressed into a green compact under a stress of 200-700 MPa. The green compact is then sintered at high temperature in a non-oxidizing atmosphere (e.g., argon or hydrogen, preferably with a mixed argon and hydrogen gas ratio of Ar:H2 = 9:1 by volume) to produce a high-density biodegradable alloy. The high-temperature sintering can be performed in one or more steps, with a sintering temperature range of 1400-2500°C and a sintering time of 3-120 hours. Furthermore, the cooling rate after sintering is less than 10°C / min.

[0065] After sintering, biodegradable alloys typically require subsequent processing, such as rolling, extrusion, and drawing, to produce products of desired size and shape. The deformed biodegradable alloys can also undergo stress relief annealing and recrystallization annealing to further improve their structure and properties. For example, they can be processed into wires, sheets, tubes, or sheets.

[0066] Furthermore, subsequent processing includes at least one of thermal deformation and machining. Furthermore, thermal deformation includes subjecting the sintered blank to heat treatments such as rolling, hot extrusion, hot piercing, forging, solutionizing, and annealing to obtain a biodegradable alloy profile of the desired shape. This further reduces the porosity in the profile and improves the mechanical properties of the biodegradable alloy, resulting in a biodegradable alloy profile with high strength and toughness.

[0067] Furthermore, the process includes machining the heat-deformed profile, for example, by drilling a tube blank, drawing the tube, performing stress relief annealing, and laser cutting to obtain an implantable vascular stent, which is a degradable alloy stent.

[0068] In some embodiments, the biodegradable alloy stent may be sequentially subjected to pickling, heat treatment, and electrochemical polishing. The purpose of pickling is to remove surface cutting debris, heat-affected layers, and contaminants. The purpose of heat treatment is to remove processing stress, improve material anisotropy, and enhance plasticity. The purpose of electrochemical polishing is to remove the oxide layer, obtain a bright, smooth surface, and reduce surface roughness, thereby reducing the risk of thrombosis and tissue reactions after implantation of the medical device and achieving dimensions that meet the stent design requirements.

[0069] Another embodiment of the present application further provides a medical device, the body of which comprises any of the above-mentioned degradable alloys.

[0070] The body of the medical device utilizes the aforementioned degradable alloy, which exhibits high density, uniform tissue distribution, good degradability, a moderate degradation rate, and good degradation uniformity. Furthermore, its DBTT is controlled to be well below room temperature, resulting in excellent room-temperature processing performance, ensuring the device possesses excellent mechanical properties under in vivo temperature conditions. Furthermore, it exhibits good transverse plasticity, resulting in a medical device with high strength, high corrosion resistance, and uniform performance. This ensures the device's biosafety and satisfies the transverse elongation requirements required for post-expansion during use. Furthermore, the medical device exhibits excellent developability and a suitable elastic modulus, resulting in low stent rebound resilience.

[0071] In some embodiments, the medical device includes, but is not limited to, at least one of a medical stent, a vascular filter, an atrial / ventricular septal occluder, and an embolic protector. The medical stent may be an implantable stent, such as one implanted in a human body cavity, or a non-implantable stent.

[0072] Implantable stents include vascular stents and non-vascular stents. Vascular stents include, but are not limited to, at least one of coronary stents, peripheral stents, covered stents, intracranial stents, venous stents, left atrial appendage occluders, vascular filters, atrial / ventricular septal occluders, and embolic protectors. Non-vascular stents include, but are not limited to, at least one of esophageal stents, biliary stents, and nasal stents.

[0073] The surface of a medical device, such as a medical stent, may be smooth or rough, may have grooves or not, may have holes or not, or may include but not be limited to any other grooves or micropores that can carry drugs.

[0074] In some embodiments, the medical device further comprises a drug, and the drug is loaded on the body.

[0075] In some embodiments, a biodegradable alloy is formed into a tubular member, which is then cut into a corrugated rod. Grooves or micropores can be drilled into the rod for drug delivery; the drug is located in these grooves or micropores to form a drug-active layer. It is understood that in other examples, the drug can also be located on the surface of the medical device to form a drug-active layer.

[0076] Furthermore, the drug in the drug active layer may vary depending on the application of the stent. For example, the drug in the drug active layer includes but is not limited to at least one of drugs for treating cardiovascular and cerebrovascular diseases, drugs for treating tumors, drugs for treating intestinal diseases, drugs for treating urinary tract diseases, and the like.

[0077] Furthermore, the drug includes but is not limited to at least one of paclitaxel, docetaxel, copper aspirinate, tacrolimus, hydroxycamptothecin, vinblastine, doxorubicin, rapamycin and rapamycin derivatives.

[0078] In order to make the purpose, technical solutions and advantages of this application more concise and clear, this application is illustrated with the following specific examples, but this application is by no means limited to these examples. The embodiments described below are only preferred embodiments of this application and can be used to describe this application. They should not be understood as limiting the scope of this application. It should be pointed out that any modifications, equivalent replacements and improvements made within the spirit and principles of this application should be included in the scope of protection of this application.

[0079] In order to better illustrate the present application, the present application is further described below in conjunction with the embodiments. The following are specific embodiments.

[0080] 1. The preparation methods of the alloys of Examples 1 to 10 and the comparative examples are as follows.

[0081] (1) Powder mixing: Provide raw materials according to the composition and proportion of Examples 1 to 10 and the comparative alloys in Table 1, and mix the raw materials uniformly in a V-type mixer.

[0082] (2) Compression molding: The powder obtained in step (1) was subjected to hot isostatic pressing (HIP) for 60 min in a pressing mold under a pressure of 500 MPa (argon and hydrogen mixed protective atmosphere, gas composition is Ar:H2 volume ratio = 9:1) to form a compact.

[0083] (3) Sintering: The compact obtained in step (2) was solid-phase sintered at a temperature of 2000° C. under vacuum conditions for 10 h.

[0084] (4) Subsequent deformation processing: The sintered powder billet is subjected to rolling, extrusion, forging hot forming processing, solid solution and annealing heat treatment to obtain biodegradable alloy rods, namely alloys 1 to 10.

[0085] Table 1

[0086] 2. Performance testing.

[0087] The degradable alloy rods obtained in step (4) of the above Examples 1-10 and Comparative Examples 1-6 were tested for physical properties, mechanical properties, corrosion resistance and degradation performance. The test results are shown in Table 2.

[0088] Physical properties include density and DBTT, among which density affects developability.

[0089] Mechanical properties include elastic modulus, tensile strength, and elongation. The elastic modulus influences the stent's resilience. Tensile strength and elongation, including comparative tests of transverse and axial tensile strength and elongation, demonstrate isotropic mechanical properties.

[0090] The test methods for the above parameters are as follows:

[0091] Elastic modulus, tensile strength, and elongation were measured according to ISO 6892. Degradation performance was characterized by degradation rate, tested and calculated according to ASTM G102-89(2015)e1. Degradation performance was characterized by degradation rate, tested and calculated according to ASTM G102-89(2015)e1. The test samples were the degradable alloy bars prepared in the above examples and comparative examples.

[0092] Corrosion resistance was evaluated using the corrosion breakdown potential (Eb) vs. SCE (V) parameter. The test samples were biodegradable alloy rods prepared in the aforementioned embodiments and comparative examples, further processed into tube blanks, which were then drawn into capillary tubing, which was then processed into vascular stents. Considering that vascular stents are Class III medical implants, they must exhibit excellent corrosion resistance, requiring a breakdown potential ≥ 0.6V to meet the product requirements for Class III medical implant stents. In accordance with Standard Test Method for Corrosion Susceptibility of Small Implantable Devices by Cyclic Potentiodynamic Polarization (ASTM F 2129-06), the following method was used to test the corrosion resistance of vascular stent samples after post-expansion: Following the standard medical device implantation process, the vascular stent was first pressed onto a balloon and placed in a 37°C PBS (phosphate buffered saline) solution to simulate human passage three times. The stent was then expanded to its nominal size using an inflator. Pressure was then increased until the stent reached its maximum size, after which it was expanded. On this basis, the embodiment of the present application further expands the vascular stent to its maximum expansion size and then continues to expand the vascular stent with a post-expansion balloon until the support rods of the vascular stent are straightened. The actual post-expansion limit size of the vascular stent is approximately 25% larger than the specified limit size. A corrosion resistance test is performed under this extreme condition, and the corrosion resistance breakdown potential in Table 2 is obtained, which can verify the effectiveness of the present application.

[0093] Table 2

[0094] Comparative Examples 1 to 3 are pure Mo-Re alloys without any other components.

[0095] Comparative Example 1 is a Mo-Re alloy with a Re content of 55wt%. When the Re content is too high, hard and brittle phases are easily precipitated, so the plasticity of the alloy decreases sharply, and the axial and lateral plasticity is basically 0. In addition, its corrosion resistance is reduced, and the corrosion resistance breakdown potential is only 0.2V.

[0096] Comparative Example 2 is a Mo-Re alloy with a Re content of 12 wt%. The Re content is too low. Although the alloy has an axial elongation of up to 40%, its lateral elongation is only 0.5%, with obvious anisotropy, and the tensile strength of the alloy is low.

[0097] Comparative Example 3 is a Mo-Re alloy with a Re content of 3 wt %. Its performance is close to that of pure molybdenum, but it does not solve the anisotropy and room temperature brittleness problems of the degradable alloy.

[0098] Comparative Example 4 is a Mo-Re alloy with a Re content of 40 wt%, and 13% La is added to the alloy. Compared with Example 3 with the same rhenium content, the excessively high content of the X alloying element forms a large amount of precipitates at the alloy grain boundaries, resulting in reduced corrosion resistance. The corrosion resistance breakdown potential is only 0.3 V, which does not meet the use requirements of stent products (>0.6 V). At the same time, the tensile strength and elongation of the alloy are also significantly reduced.

[0099] Control Example 5 is a Mo-Cu alloy with a Cu content of 25wt%, and Control Example 6 is a Mo-Mn alloy with a Mn content of 10wt%. Both alloys still have obvious anisotropy, and the DBTT is higher than room temperature, with obvious room temperature brittleness. The corrosion resistance does not meet the product use requirements. Therefore, the degradation rate test was not continued.

[0100] The Mo-Re-X alloys prepared in each embodiment, to which no more than 10 wt% of the metal element X and no more than 2 wt% of the bioactive glass are added, can achieve a good elastic modulus while also achieving good isotropic mechanical properties and low DBTT, as well as good corrosion resistance and degradation performance.

[0101] It is worth noting that, as shown by a comparison of Examples 5 and 6, the addition of metal element X can reduce the Re content and further lower the alloy's elastic modulus, preventing stent rebound, while maintaining equivalent or even superior mechanical properties and developability. More importantly, compared to an equivalent amount of Re, metal element X significantly lowers the DBTT of the degradable alloy, bringing it well below room temperature, preventing room-temperature brittleness and ensuring the safe use and storage of the stent product. Furthermore, the addition of bioactive glass (BAG) modulates the degradation rate of the Mo-Re alloy, bringing it closer to the ideal degradation rate of 20 μm / y.

[0102] As shown in Tables 1 and 2, the degradation rate of the Mo-Re-X alloys in the examples of this application gradually increases slightly with increasing bioactive glass BAG content, reaching the ideal degradation rate of 20 μm / y. In Example 10, the bioactive glass BAG content was 2.0 wt%, and its degradation rate was 20.5 μm / y, slightly exceeding the ideal degradation rate of 20 μm / y. This indicates that the maximum bioactive glass BAG content is 2.0 wt%.

[0103] 3. Uniform degradation performance of the alloy of this application

[0104] Example 11: Using the same preparation steps (1) to (4) as Example 5 of the present application, a degradable alloy rod with a diameter of 10 mm was prepared. The rod was cut into small cubes of 1*1*1 mm and polished for degradation immersion experiment. Specifically, the small cubes were placed on a shaker at a speed of 100 rpm. After immersion in PBS at 37°C for 1 month, the sample was taken out for surface morphology testing, and the scanning electron microscope image was obtained as shown in Figure 1. It is a degradation sheet at the nanometer thickness level, and the appearance is about equiaxed about 10 μm. This shows that the degradable alloy of the present application can achieve uniform degradation, and the equiaxed degradation sheet is obtained by uniformly peeling off layer by layer and stably degrading.

[0105] Further analysis of the extract after one month of leaching revealed degradation products containing Mo, O, Ca, Ma, Na, and P. These O, Ca, Ma, Na, and P are unavoidable impurities, demonstrating that the biodegradable alloys of the present invention are soluble in human body-simulating fluid. Furthermore, no significant accumulation of large degradation products or precipitates occurred during the degradation process, ensuring the biosafety of the biodegradable alloys for medical applications.

[0106] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0107] The above-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present patent application shall be determined by the appended claims.

Claims

1. A degradable alloy, by mass content, comprises the following components: 18 wt% - 49 wt% of Re, 0 wt% - 10 wt% of metal element X, 0 wt% - 2 wt% of bioactive glass, and the balance of Mo; the mass content of the bioactive glass is not 0, and the metal element X includes at least one of Li, Ti, Zn, Sr, Pt, Au, Nb, Ta and rare earth elements.

2. The degradable alloy according to claim 1, wherein, In the degradable alloy, the mass content of the metal element X is 0.2 wt% - 10 wt%.

3. The degradable alloy according to any one of claims 1 to 2, wherein, In the degradable alloy, the mass content of the metal element X is 0.2 wt% - 8 wt%.

4. The degradable alloy according to any one of claims 1 to 3, wherein, The rare earth elements include at least one of La, Ce and Y.

5. The degradable alloy according to any one of claims 1 to 4, wherein, In the degradable alloy, Re is 18 wt% - 45 wt%.

6. The degradable alloy according to any one of claims 1 to 5, wherein, In the degradable alloy, Re is 18 wt% - 40 wt%.

7. The degradable alloy according to any one of claims 1 to 6, wherein, In the degradable alloy, Re is 18 wt% - 35 wt%.

8. The degradable alloy according to any one of claims 1 to 7, wherein, In the degradable alloy, the bioactive glass is 0.05 wt% - 2 wt%.

9. The degradable alloy according to any one of claims 1 to 8, wherein, In the degradable alloy, the bioactive glass is 0.2 wt% - 2 wt%.

10. The degradable alloy according to any one of claims 1 to 9, wherein, The total content of unavoidably introduced impurities in the degradable alloy does not exceed 300 ppm.

11. The degradable alloy according to claim 10, wherein, The total content of unavoidably introduced impurities is not more than 200 ppm.

12. The degradable alloy according to claim 11, wherein, The total content of unavoidably introduced impurities is not more than 100 ppm.

13. The degradable alloy according to any one of claims 1 to 12, wherein, By mass content, the sum of the weight percentages of Re and X is not less than 20 wt%.

14. The degradable alloy according to any one of claims 1 to 13, wherein, By mass content, the sum of the weight percentages of Re and X is not less than 25 wt%.

15. The degradable alloy according to any one of claims 1 to 14, wherein, By mass content, the sum of the weight percentages of Re and X is not less than 28 wt%.

16. The degradable alloy according to any one of claims 1 to 15, wherein, Comprises the following components: 24 wt% - 45 wt% of Re, 0.5 wt% - 6 wt% of metal element X, 0.4 wt% - 1.6 wt% of bioactive glass, and the balance of Mo.

17. A method for preparing a degradable alloy according to any one of claims 1 to 16, wherein, Comprises the following steps: Provide raw materials according to the components of the degradable alloy; Mix the raw materials and carry out smelting and forming.

18. A medical device, wherein, Its body contains the degradable alloy as described in any one of claims 1 to 17.

19. The medical device according to claim 18, wherein, The medical device includes at least one of a medical stent, a vascular filter, an atrial / ventricular septal occluder and an embolism protector.

20. The medical device according to any one of claims 18 to 19, wherein, The medical device further contains a drug, and the drug is loaded on the body.

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