Biodegradable magnesium alloys

Abstract

To provide a method for producing a biodegradable magnesium alloy useful for orthopedic applications.SOLUTION: A method for producing alloys comprises the steps of: (a) placing alloy components in a crucible, wherein the alloy components are placed in the crucible in a multilayer arrangement; (b) melting the alloy components at about 700°C to about 850°C; (c) stirring the melt of step (b) at about 400 rpm to about 500 rpm; (d) atomizing the melt of step (c) into millimeter size droplets using jets of inert gas; and (e) cooling and depositing the atomized alloy melt to obtain an ingot. The alloy is an alloy of Formula (I): Mg-Zn-X (I), wherein X represents -Ca-Mn or -Dy- Sr.SELECTED DRAWING: Figure 7

Description

Technical Field

[0001] The present invention generally relates to biodegradable alloys. The present invention also relates to the manufacturing processes and techniques of such biodegradable alloys. The biodegradable alloys may be useful for orthopedic applications.

Background Art

[0002] With the aging of the world's population, the number of cases of orthopedic diseases caused by aging, such as osteoporosis and fractures, has increased significantly. As a result, the demand for effective and inexpensive orthopedic implants and instruments has increased. Research and development continue to find an ideal orthopedic implant material. There are several material elements (e.g., orthopedic applications / areas, functions, compatibility, and costs) and characteristics to be considered, such as chemical and biological inertness, strength, rigidity, corrosiveness, stability, biocompatibility, and tissue acceptability.

[0003] Currently, orthopedic implants and instruments are manufactured using either polymers, ceramics, or metallic materials. Each has its own strengths and weaknesses. Metallic materials such as stainless steel, platinum, titanium, and alloys such as titanium alloys and chromium-cobalt alloys are commonly used due to their excellent strength and mechanical properties. However, these metallic implants tend to have an inappropriate combination with bone, and the implants may loosen and ultimately break. Therefore, these metallic implants may need to be removed after serving the healing purpose due to the possibility of recovery complications (such as allergies, infections, and sensitization).

[0004] Regarding polymers, polyethylene and polymethyl methacrylate are common examples used in orthopedic implants. However, due to their low strength and the possibility of deformation, they are not suitable for heavy-load orthopedic applications (such as bone healing).

[0005] Ceramics such as aluminum oxide, silicon oxide, zirconium oxide, and calcium phosphate have excellent mechanical properties and are also chemically and biocompatible. However, they are brittle.

[0006] Therefore, there is a need to provide a material suitable for orthopedic applications that overcomes or at least ameliorates one or more of the above-described drawbacks. Combining properties such as chemical inertness, strength, stiffness, stability, biocompatibility, tissue acceptability, and corrosion resistance would result in an ideal material for orthopedic implants and applications.

Summary of the Invention

[0007] In one aspect of the present disclosure, a biodegradable alloy of formula (I), Mg-Zn-X Formula (I) X represents -Ca-Mn or -Dy-Sr, Mg is magnesium, Zn is zinc, Dy is dysoprium, Sr is strontium, Ca is calcium, and Mn is manganese, This alloy, based on the total weight of the alloy, about 0.1 wt% to about 3.0 wt% of Zn; about 0.1 wt% to about 0.7 wt% of Dy; about 0.1 wt% to about 0.9 wt% of Sr; about 0.1 wt% to about 1.5 wt% of Ca; about 0.1 wt% to about 0.9 wt% of Mn; and a biodegradable alloy is provided that includes the balance of Mg and impurities.

[0008] In another aspect of the present disclosure, an implant comprising the alloy disclosed herein is provided.

[0009] Advantageously, the disclosed biodegradable alloy has zero-level cytotoxicity, thereby enabling the effective use of materials in orthopedic, neurosurgical, cranial, and maxillofacial applications and reducing the associated risks to the patient.

[0010] A biodegradable alloy may use alloying elements (e.g., zinc) with a low weight fraction. Advantageously, this reduces the cost of the alloy. Similarly, adding trace amounts of biocompatible elements such as calcium and manganese, or rare earth elements such as strontium and dysprosium can keep the cost of the biodegradable alloy low while meeting all functions and properties.

[0011] In a further aspect of the present disclosure, (a) placing alloy components in a crucible, the alloy components being placed in the crucible in a multi-layer arrangement; (b) melting the alloy components at about 700 °C to about 850 °C; (c) stirring the melt of step (b) at about 400 rpm to about 500 rpm; (d) atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas; (e) cooling and depositing the atomized alloy melt to obtain an ingot A method for manufacturing an alloy is provided, which includes the above steps.

[0012] In another aspect of the present disclosure, a method for manufacturing an alloy of formula (I), Mg-Zn-X formula (I) X represents -Ca-Mn or -Dy-Sr, Mg is magnesium, Zn is zinc, Dy is dysprosium, Sr is strontium, Ca is calcium, and Mn is manganese, This alloy is based on the total weight of the alloy, about 0.1 wt% to about 3.0 wt% of Zn; about 0.1 wt% to about 0.7 wt% of Dy; about 0.1 wt% to about 0.9 wt% of Sr; about 0.1 wt% to about 1.5 wt% of Ca; about 0.1 wt% to about 0.9 wt% of Mn; and the balance of Mg and impurities, This method is (a) Step of placing alloy components in a crucible, wherein the alloy components are placed in the crucible in a multi-layer arrangement, (b) Step of melting the alloy components at about 700 °C to about 850 °C, (c) Step of stirring the melt of step (b) at about 400 rpm to about 500 rpm, (d) Step of atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas, (e) Step of cooling and depositing the atomized alloy melt to obtain an ingot A method for manufacturing an alloy is provided, which includes the above steps.

[0013] Advantageously, when the alloy components are arranged in this multi-layer or sandwich manner, the alloy element(s) in the second alloy component can have a different melting point compared to the alloy matrix material, so that the capture and wettability of the alloy matrix material (which may be the first alloy component) are maximally guaranteed. Using such layer-by-layer or multi-layer arrangements ensures that the alloy elements are maximally homogenized in the molten matrix metal / material. When the disclosed method of the present invention is used, the disclosed biodegradable alloy can be efficiently manufactured without using any toxic flux materials and protective gases such as sulfur hexafluoride. Therefore, advantageously, the production of the disclosed biodegradable alloy is a safe, cost-effective, energy-efficient, and industrially scalable process. The disclosed biodegradable alloy and the method for forming the disclosed alloy may be able to meet the high demand for materials required for orthopedic implants and instruments (e.g., temporary implants for neurosurgery, cranial, craniofacial, and orthopedic fractures, fixation applications used in biodegradable screws, plates, pins, and clips).

[0014] Definitions

[0015] Definitions Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings commonly understood by those skilled in the art. Generally, the nomenclature used in connection with the chemistry described herein, and the techniques of the chemistry described herein, are well known and commonly used in the art.

[0016] Unless the context requires otherwise or specifically states to the contrary, integers, steps, or components of the invention described herein as integers, steps, or components in the singular shall clearly include both the singular and plural forms of the recited integers, steps, or components.

[0017] As used herein, the term "biodegradable" refers to the ability to be chemically decomposed, degraded, and absorbed by the body, and thus does not require manual removal. This is also known as biodegradability.

[0018] The word "substantially" does not exclude "completely"; for example, a composition that is "substantially free of" Y may not be completely free of Y. If necessary, the word "substantially" may be omitted from the definitions of the invention.

[0019] Unless otherwise specified, the terms "comprising" and "comprise" and their grammatical variants are intended to represent an "open" or "inclusive" syntax that includes the recited components but also tolerates the inclusion of additional, unrecited components.

[0020] As used herein, the term "about" in the context of the concentration of a component of a formulation typically represents ±5% of the indicated value, more typically ±4% of the indicated value, more typically ±3% of the indicated value, more typically ±2% of the indicated value, even more typically ±1% of the indicated value, and even more typically ±0.5% of the indicated value.

[0021] Throughout this disclosure, certain embodiments may be disclosed in a numerical range format. The description in numerical range format is for convenience and brevity only and should not be construed as imposing an immutable limitation on the disclosed range of numerical values. Accordingly, a description of a numerical range should be considered to specifically disclose all the possible sub-ranges as well as the individual numerical values within that numerical range. For example, a description of a numerical range such as 1 to 6 should be considered to specifically disclose sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, as well as individual numerical values within that numerical range such as 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the numerical range.

[0022] Certain embodiments may also be described generally and broadly herein. Each of the narrower species and sub-conceptual groupings included within the general disclosure also forms part of this disclosure. This includes general descriptions of embodiments having conditional or negative limitations that exclude any object from this species, regardless of whether the excised material is specifically described herein.

[0023] The accompanying drawings illustrate the disclosed embodiments and serve to explain the principles of the disclosed embodiments. However, it should be understood that this drawing is intended for illustrative purposes only and not as a defining limitation of the present invention.

Brief Description of the Drawings

[0024]

Figure 1

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 5A

Figure 5B

Figure 6A

Figure 6B

Figure 7

Figure 8A

Figure 8B

Embodiments for Carrying Out the Invention

[0025] Detailed Description of the Drawings Referring to FIGS. 4A and 4B, FIGS. 4A and 4B show a scanning electron microscope (SEM) analysis of a magnesium alloy at the end of the 14th day after corrosion. The magnesium alloy shows crack formation due to water loss. The alloy surface is covered by acicular structures. The formation of the brucite compound is enhanced as the immersion time of the magnesium alloy in Hank's balanced salt solution (HBSS) increases. The range of compound formation is more uniformly distributed in the alloy sample. This behavior can promote the retention of the strength and ductility of the material after in vitro corrosion.

[0026] Referring to FIGS. 5A and 5B, FIGS. 5A and 5B show the compression characteristics of a magnesium alloy. FIGS. 5A and 5B show a stress-versus-strain graph or a compression test of the magnesium alloy, providing further insight into the mechanical integrity of this alloy. Based on FIGS. 5A and 5B, the amount of strength maintained by the material after implantation can be evaluated, and the functional life cycle requirements of the implant can be determined.

[0027] Referring to FIGS. 8A and 8B, FIGS. 8A and 8B show the fracture structure of the magnesium alloy after a compression test, which provides insight into the mechanism of fracture and the amount of energy absorbed by the implant before fracture.

[0028] Magnesium is non-toxic, biocompatible, bioabsorbable, low in density, and has mechanical properties similar to those of bone. However, monolithic magnesium shows low corrosion resistance in a physiological environment, has low retention of mechanical properties, and there is a possibility that the implant may break before complete bone repair. Improving magnesium using alloying techniques is extremely important for adjusting the properties of magnesium to match those of an ideal orthopedic implant material.

[0029] In the present invention, a unique magnesium-based biodegradable alloy with improved mechanical, degradation, and cytotoxic responses is developed by using suitable alloying elements such as zinc and biocompatible elements such as dysprosium, strontium, calcium, and manganese in an optimal amount in a magnesium matrix.

[0030] The present invention relates to a biodegradable alloy of formula (I), Mg-Zn-X Formula (I) wherein X represents -Ca-Mn or -Dy-Sr, Mg is magnesium, Zn is zinc, Dy is dysprosium, Sr is strontium, Ca is calcium, and Mn is manganese, and this alloy contains, based on the total weight of the alloy, about 0.1 wt% to about 3.0 wt% of Zn; about 0.1 wt% to about 0.7 wt% of Dy; about 0.1 wt% to about 0.9 wt% of Sr; about 0.1 wt% to about 1.5 wt% of Ca; about 0.1 wt% to about 0.9 wt% of Mn; and the balance of Mg and impurities or consists of, a biodegradable alloy.

[0031] This biodegradable alloy may be of formula (IA) Mg-Zn-Ca-Mn and may be.

[0032] This biodegradable alloy may be of formula (IB) Mg-Zn-Dy-Sr and may be.

[0033] This alloy contains about 0.1 wt% to about 3.0 wt%, about 0.2 wt% to about 3.0 wt%, about 0.3 wt% to about 3.0 wt%, about 0.4 wt% to about 3.0 wt%, about 0.5 wt% to about 3.0 wt%, about 0.6 wt% to about 3.0 wt%, about 0.7 wt% to about 3.0 wt%, about 0.8 wt% to about 3.0 wt%, about 0.9 wt% to about 3.0 wt%, about 1.0 wt% to aboutIt may contain zinc in an amount of 3.0% by weight, about 1.1% to about 3.0% by weight, about 1.2% to about 3.0% by weight, about 1.3% to about 3.0% by weight, about 1.4% to about 3.0% by weight, about 1.5% to about 3.0% by weight, about 1.6% to about 3.0% by weight, about 1.7% to about 3.0% by weight, about 1.8% to about 3.0% by weight, about 1.9% to about 3.0% by weight, about 2.0% to about 3.0% by weight, about 2.0% to about 2.5% by weight, about 2.1% to about 2.2% by weight, about 2.3% to about 3.0% by weight, about 2.4% to about 3.0% by weight, about 2.5% to about 3.0% by weight, about 2.6% to about 3.0% by weight, about 2.7% to about 3.0% by weight, about 2.8% to about 3.0% by weight, about 2.9% to about 3.0% by weight, about 0.1% to about 2.9% by weight, about 0.1% to about 2.8% by weight, about 0.1% to about 2.7% by weight, about 0.1% to about 2.6% by weight, about 0.1% to about 2.5% by weight, about 0.1% to about 2.4% by weight, about 0.1% to about 2.3% by weight, about 0.1% to about 2.2% by weight, about 0.1% to about 2.1% by weight, about 0.1% to about 2.0% by weight, about 0.1% to about 1.9% by weight, about 0.1% to about 1.8% by weight, about 0.1% to about 1.7% by weight, about 0.1% to about 1.6% by weight, about 0.1% to about 1.5% by weight, about 0.1% to about 1.4% by weight, about 0.1% to about 1.3% by weight, about 0.1% to about 1.2% by weight, about 0.1% to about 1.1% by weight, about 0.1% to about 1.0% by weight, about 0.1% to about 0.9% by weight, about 0.1% to about 0.8% by weight, about 0.1% to about 0.7% by weight, about 0.1% to about 0.6% by weight, about 0.1% to about 0.5% by weight, about 0.1% to about 0.4% by weight, about 0.1% to about 0.3% by weight, about 0.1% to about 0.2% by weight, or 0.1% by weight, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, about 0.9% by weight, about 1.0% by weight, about 1.1% by weight, about 1.2% by weight, about 1.3% by weight, about 1.4% by weight, about 1.5% by weight, about 1.6% by weight, about 1.7% by weight, about 1.8% by weight, about 1.9% by weight, about 2.0% by weight, about 2.1% by weight, about 2.2% by weight, about 2.3% by weight, about 2.4% by weight, about 2.5% by weight, about 2.6% by weight, about 2.7% by weight, about 2.8% by weight, about 2.It may contain about 9 wt%, about 3.0 wt% of zinc, or any value or range between these of zinc.

[0034] The alloy may contain from about 0.1 wt% to about 1.5 wt%, from about 0.2 wt% to about 1.5 wt%, from about 0.3 wt% to about 1.5 wt%, from about 0.4 wt% to about 1.5 wt%, from about 0.5 wt% to about 1.5 wt%, from about 0.5 wt% to about 1.0 wt%, from about 0.6 wt% to about 1.5 wt%, from about 0.7 wt% to about 1.5 wt%, from about 0.8 wt% to about 1.5 wt%, from about 0.9 wt% to about 1.5 wt%, from about 1.0 wt% to about 1.5 wt%, from about 1.1 wt% to about 1.5 wt%, from about 1.2 wt% to about 1.5 wt%, from about 1.3 wt% to about 1.5 wt%, from about 1.4 wt% to about 1.5 wt%, from about 0.1 wt% to about 1.4 wt%, from about 0.1 wt% to about 1.3 wt%, from about 0.1 wt% to about 1.2 wt%, from about 0.1 wt% to about 1.1 wt%, from about 0.1 wt% to about 1.0 wt%, from about 0.1 wt% to about 0.9 wt%, from about 0.1 wt% to about 0.8 wt%, from about 0.1 wt% to about 0.7 wt%, from about 0.1 wt% to about 0.6 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 0.4 wt%, from about 0.1 wt% to about 0.3 wt%, from about 0.1 wt% to about 0.2 wt% of calcium, or about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt% of calcium, or any value or range among these of calcium.

[0035] The alloy may contain manganese in an amount of from about 0.1 wt% to about 0.9 wt%, from about 0.2 wt% to about 0.9 wt%, from about 0.2 wt% to about 0.8 wt%, from about 0.3 wt% to about 0.9 wt%, from about 0.4 wt% to about 0.9 wt%, from about 0.5 wt% to about 0.9 wt%, from about 0.6 wt% to about 0.9 wt%, from about 0.7 wt% to about 0.9 wt%, from about 0.8 wt% to about 0.9 wt%, from about 0.1 wt% to about 0.8 wt%, from about 0.1 wt% to about 0.7 wt%, from about 0.1 wt% to about 0.6 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 0.4 wt%, from about 0.1 wt% to about 0.3 wt%, from about 0.1 wt% to about 0.2 wt%, or may contain manganese in an amount of about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, or may contain any value or range of manganese among these.

[0036] The alloy may contain dysprosium in an amount of from about 0.1 wt% to about 0.7 wt%, from about 0.2 wt% to about 0.7 wt%, from about 0.3 wt% to about 0.7 wt%, from about 0.4 wt% to about 0.7 wt%, from about 0.4 wt% to about 0.6 wt%, from about 0.5 wt% to about 0.7 wt%, from about 0.6 wt% to about 0.7 wt%, from about 0.1 wt% to about 0.6 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 0.4 wt%, from about 0.1 wt% to about 0.3 wt%, from about 0.1 wt% to about 0.2 wt%, or may contain dysprosium in an amount of about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, or may contain any value or range of dysprosium among these.

[0037] The alloy may contain strontium in an amount of about 0.1 wt% to about 0.9 wt%, about 0.2 wt% to about 0.9 wt%, about 0.2 wt% to about 0.8 wt%, about 0.3 wt% to about 0.9 wt%, about 0.4 wt% to about 0.9 wt%, about 0.5 wt% to about 0.9 wt%, about 0.6 wt% to about 0.9 wt%, about 0.7 wt% to about 0.9 wt%, about 0.8 wt% to about 0.9 wt%, about 0.1 wt% to about 0.8 wt%, about 0.1 wt% to about 0.7 wt%, about 0.1 wt% to about 0.6 wt%, about 0.1 wt% to about 0.5 wt%, about 0.1 wt% to about 0.4 wt%, about 0.1 wt% to about 0.3 wt%, about 0.1 wt% to about 0.2 wt%, or may contain about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt% of strontium, or may contain any value or range of strontium among these.

[0038] The biodegradable alloy is · Mg-Zn-Ca-Mn in which Zn is 2.5 wt%, Ca is 1.0 wt%, Mn is 0.3 wt%, and Mg constitutes the balance; · Mg-Zn-Ca-Mn in which Zn is 2.5 wt%, Ca is 1.0 wt%, Mn is 0.5 wt%, and Mg constitutes the balance; · Mg-Zn-Ca-Mn in which Zn is 2.5 wt%, Ca is 1.0 wt%, Mn is 0.7 wt%, and Mg constitutes the balance; · Mg-Zn-Dy-Sr in which Zn is 2.5 wt%, Dy is 0.5 wt%, Sr is 0.2 wt%, and Mg constitutes the balance; · Mg-Zn-Dy-Sr in which Zn is 2.5 wt%, Dy is 0.5 wt%, Sr is 0.5 wt%, and Mg constitutes the balance; and · Mg-Zn-Dy-Sr in which Zn is 2.5 wt%, Dy is 0.5 wt%, Sr is 0.8 wt%, and Mg constitutes the balance and may be selected from the group consisting of.

[0039] The alloy may contain trace impurities such as aluminum, iron, nickel, silicon, or copper. The total amount of each impurity or a plurality of impurities may account for about 20 ppm or less, or about 20 ppm, about 19 ppm, about 18 ppm, about 17 ppm, about 16 ppm, about 15 ppm, about 14 ppm, about 13 ppm, about 12 ppm, about 11 ppm, about 10 ppm, about 9 ppm, about 8 ppm, about 7 ppm, about 6 ppm, about 5 ppm, about 4 ppm, about 3 ppm, about 2 ppm, about 1 ppm, or about 0 ppm.

[0040] The alloy advantageously may not contain yttrium, which is known to be cytotoxic. The inventors have surprisingly found that yttrium may be removed from the alloy and replaced with trace additives of strontium, cal cium, manganese, and dysprosium to achieve similar functional advantages at low risk and low cost.

[0041] The present disclosure also relates to an implant comprising a biodegradable alloy of formula (I) Mg-Zn-X Formula (I) wherein X represents -Ca-Mn or -Dy-Sr, Mg is magnesium, Zn is zinc, Dy is dysoprium, Sr is strontium, Ca is calcium, and Mn is manganese, and the alloy, based on the total weight of the alloy, about 0.1 wt% to about 3.0 wt% of Zn; about 0.1 wt% to about 0.7 wt% of Dy; about 0.1 wt% to about 0.9 wt% of Sr; about 0.1 wt% to about 1.5 wt% of Ca; about 0.1 wt% to about 0.9 wt% of Mn; and the balance of Mg and impurities, or consisting of, relates to an implant.

[0042] This implant may be an orthopedic, cranial, maxillofacial, neurosurgical, or dental implant.

[0043] The present disclosure further relates to a method for manufacturing an alloy, comprising: (a) placing alloy components in a crucible, wherein the alloy components are placed in the crucible in a multi-layer arrangement; (b) melting the alloy components at a temperature of about 700 °C to about 850 °C; (c) stirring the melt of step (b) at a speed of about 400 rpm to about 500 rpm; (d) atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas; (e) cooling and depositing the atomized alloy melt to obtain an ingot. The present disclosure further relates to a method for manufacturing an alloy of formula (I):

[0044] Mg-Zn-X (I) wherein X represents -Ca-Mn or -Dy-Sr; Mg is magnesium, Zn is zinc, Dy is dysprosium, Sr is strontium, Ca is calcium, and Mn is manganese; and the alloy comprises, based on the total weight of the alloy: about 0.1 wt% to about 3.0 wt% of Zn; about 0.1 wt% to about 0.7 wt% of Dy; about 0.1 wt% to about 0.9 wt% of Sr; about 0.1 wt% to about 1.5 wt% of Ca; about 0.1 wt% to about 0.9 wt% of Mn; and the balance of Mg and impurities; and the manufacturing method comprises: (a) placing alloy components in a crucible, wherein the alloy components are placed in the crucible in a multi-layer arrangement; (b) melting the alloy components at a temperature of about 700 °C to about 850 °C; (c) stirring the melt of step (b) at a speed of about 400 rpm to about 500 rpm; (d) atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas; (e) cooling and depositing the atomized alloy melt to obtain an ingot. , (d) Atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas; (e) Cooling and depositing the atomized alloy melt to obtain an ingot. The present invention relates to a method for manufacturing an alloy, comprising the above steps.

[0045] The crucible may be a graphite crucible or a metal crucible.

[0046] Step (a) may include controlling the volume of the alloy component to about 70% to about 75% of the volume of the crucible. The inventors were surprised to find that when the volume of the precursor material / alloy component is controlled within the range of about 70% to about 75% with respect to the volume of the crucible, the flow rate of the melt is adjusted with respect to the amount of material used as the raw material. Performing this engineering control advantageously ensures the reproducibility of the amount of material deposited in the mold. Furthermore, by equalizing the flow rate of the molten metal, the amount of gas colliding with the poured molten metal is also standardized, and heat extraction from the molten metal flow is further controlled. Controlling the collision volume of the inert gas with the molten metal flow standardizes the volume ratio of the gas to the molten metal, and thus advantageously ensures the generation of a similar microstructure and the reproducibility of the mechanical properties of the deposited material.

[0047] The volume of the alloy component may be about 70%, about 71%, about 72%, about 73%, about 74%, or about 75% of the volume of the crucible.

[0048] Moreover, in step (a), the multi-layer arrangement of step (a) may include an A-B-A arrangement, where A includes or consists of a first alloy component, and B includes or consists of a second alloy component. Each of the first and second alloy components may include or consist of a single alloy material or an alloy mixture mixed with two or more alloy materials.

[0049] Surprisingly, the inventors have found that when this alloy component is arranged in this multilayer or sandwich manner, the alloy element(s) in the second alloy component can have a different melting point compared to the alloy matrix material, thus ensuring maximum capture and wettability of the alloy matrix material (which may be the first alloy component). Using such layer-by-layer or multilayer arrangements ensures that the alloy elements are maximally homogenized in the molten matrix metal / material.

[0050] In another embodiment, the multilayer arrangement of step (a) may include an A-B-A-B-A arrangement, where A comprises or consists of a first alloy component and B comprises or consists of a second alloy component, and the first and second alloy components may each comprise or consist of a single alloy material or an alloy mixture of two or more alloy materials.

[0051] Figure 7 is a schematic cross-sectional view of a crucible showing a multilayer arrangement. (A) refers to the first alloy component layer and (B) refers to the second alloy component layer.

[0052] In one embodiment, A may consist of magnesium and B may consist of an alloy mixture of zinc and X.

[0053] In one embodiment, A may consist of magnesium and B may consist of an alloy mixture of zinc, calcium, and manganese.

[0054] In one embodiment, A may consist of magnesium and B may consist of an alloy mixture of zinc, dysprosium, and strontium.

[0055] Each layer of this multilayer arrangement may be of substantially equal volume. Advantageously, this aids in heating each layer uniformly within the furnace.

[0056] Surprisingly, the inventors have found that when the alloy components are arranged in this multilayer or sandwich manner, the alloying elements (including zinc, manganese, calcium, dysprosium, strontium, etc.) can have different melting points compared to magnesium, so that the capture and wettability of the magnesium matrix are maximally ensured. Magnesium may be arranged in a folded type in three equal-volume layers with an alloy layer mixture mixed between the magnesium layers sandwiched therebetween. After the melting of magnesium, such a layered / multilayer arrangement advantageously ensures the most likely homogenization of the alloying elements into the molten matrix metal.

[0057] The method of the present invention is a liquid-based treatment method. Magnesium may be a matrix material, and the constituent elements (zinc, manganese, calcium, dysprosium, and strontium) may be added to the crucible in a multilayer arrangement or a sandwich arrangement together with magnesium. Since the weight percentage of the constituent elements is low, using a multilayer arrangement or a sandwich arrangement advantageously ensures the proper pre-mixing of magnesium, which can be in a folded form, with these constituent elements. The structure of the constituent elements may be in the form of powder, ingot shot, or wire. Considering various possibilities, the multilayer arrangement or the sandwich arrangement provides the best uniformity during stirring and casting, as well as in the subsequent final casting.

[0058] Step (b) may be carried out at a temperature of about 700 °C to about 850 °C, about 725 °C to about 850 °C, about 750 °C to about 850 °C, about 775 °C to about 850 °C, about 800 °C to about 850 °C, about 825 °C to about 850 °C, about 700 °C to about 825 °C, about 700 °C to about 800 °C, about 700 °C to about 775 °C, about 700 °C to about 750 °C, about 700 °C to about 725 °C, or about 700 °C, about 725 °C, about 750 °C, about 775 °C, about 800 °C, about 825 °C, about 850 °C, or any value or range of temperatures therebetween.

[0059] The stirring in step (c) may be carried out at about 400 rpm to about 500 rpm, about 425 rpm to about 450 rpm, about 450 rpm to about 500 rpm, about 475 rpm to about 500 rpm, about 400 rpm to about 475 rpm, about 400 rpm to about 450 rpm, about 400 rpm to about 425 rpm, or about 400 rpm, about 425 rpm, about 450 rpm, about 475 rpm, about 500 rpm, or any value or range therebetween.

[0060] With the selected stirring speed, advantageously, the second-phase particles in the melt can be uniformly dispersed. With the optimized stirring speed, agglomeration in the melt is avoided and the constituent elements are thoroughly mixed in the melt state or semi-solid state. In the disclosed method, the alloy components are introduced in a sandwich form or a multi-layer form. Thus, with the use of optimized stirring, advantageously, the wettability between the first alloy component and the second alloy component is improved.

[0061] The jet of inert gas in step (d) may be a jet of nitrogen or argon. The number of jets used may be 2, 3, 4, 5, or 6 jets. The diameter of each jet nozzle may be about 1 mm to about 2 mm, and the gas flow rate may be about 20 L / min to about 30 L / min. The number of gas jets and the gas flow rate may be adjusted to break up the melt into millimeter-sized droplets. The flow rate and the number of jets affect the decomposition of the molten metal while it is being push-cast into the melt. Optimizing these parameters aids in the high wettability of the molten metal during the deposition process as well as chemical and thermal homogenization.

[0062] The diameter of each jet nozzle may be about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2.0 mm. The gas flow rate may be about 20 L / min, about 2120 L / min, about 22 L / min, about 23 L / min, about 24 L / min, about 25 L / min, about 26 L / min, about 27 L / min, about 28 L / min, about 29 L / min, or about 30 L / min.

[0063] In step (d), the droplets may be millimeter-sized. The volume of each droplet is about 1 mm 3 , about 2 mm 3 , about 3 mm 3 , about 4 mm 3 , about 5 mm 3 , about 6 mm 3 , about 7 mm 3 , about 8 mm 3 , or about 9 mm 3 and may be.

[0064] This method may further include a step (f) of subjecting this ingot to hot extrusion at about 250 °C to about 400 °C. The temperature is about 250 °C to about 400 °C, about 275 °C to about 400 °C, about 300 °C to about 400 °C, about 325 °C to about 400 °C, about 350 °C to about 400 °C, about 375 °C to about 400 °C, about 250 °C to about 375 °C, about 250 °C to about 350 °C, about 250 °C to about 325 °C, about 250 °C to about 300 °C, about 250 °C to about 275 °C, or about 250 °C, about 275 °C, about 300 °C, about 325 °C, about 350 °C, about 375 °C, about 400 °C, or any value or range between these may be.

[0065] The hot extrusion step may be carried out for about 1 hour to about 2 hours, or about 60 minutes, 65 minutes, 70 minutes, 75 minutes, 80 minutes, 85 minutes, 90 minutes, 95 minutes, 100 minutes, 105 minutes, 110 minutes, 115 minutes, or about 120 minutes.

[0066] The extrusion ratio may be in the range of 25:1 to 12:1, or 24:1, 23:1, 23:1, 22:1, 21:1, 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, or 12:1.

Examples

[0067] Non-limiting examples and comparative examples of the present invention will be described in more detail by referring to specific examples, but this specific example should not be construed as limiting the scope of the present invention in any way.

[0068] Example 1: Synthesis of Magnesium Alloy The raw materials were arranged in a multi-layer sandwich pattern in a graphite crucible with a diameter of 140 mm and a length of 200 m, and melted in a controlled argon gas environment within a temperature range of 700 - 850 °C (depending on the composition). To uniformly disperse the second-phase particles in the melt, the stirring conditions were optimized within the range of 400 - 500 rpm. The molten metal was pushed up and cast into a steel mold and decomposed by 2 - 4 annular jets of argon gas with a gas jet diameter of 1 - 2 mm and a gas flow rate of 20 - 30 L / m (liters per minute). The number and flow rate of the gas jets were optimized to decompose the melt into millimeter-sized droplets. A cast ingot with a diameter of 40 mm was obtained by depositing and solidifying these millimeter-sized (mm 3 size-controlled volume) droplets. This cast ingot was processed to specific dimensions, homogenized at 300 - 400 °C for 1 - 2 hours, and hot extruded at 250 - 400 °C with an extrusion ratio in the range of 25:1 - 12:1 to obtain rods with a diameter range of 7 - 10 mm depending on the composition. Cylindrical rods were used for various characterizations. The weight percentages of Mg, Zn, Dy, Sr, Ca, and Mn in the magnesium alloy are shown in Table 1.

[0069]

Table 1

[0070] Example 2: Evaluation of Microstructural Characteristics of Magnesium Alloy Microstructural characteristic evaluations were performed to calculate the average grain size and to characterize the distribution of the second phase in the magnesium alloy matrix.

[0071] Analysis of the Average Grain Size of Magnesium Alloy In accordance with the standard test method (ASTM E112-13) for determining the average grain size, samples were tested under a digital optical microscope equipped with LES 4.0 software to investigate the grain size distribution. A JEOL JSM-5800LV scanning electron microscope (SEM, Kyoto, Japan) was used to investigate the distribution of the second phase.

[0072] The samples were immersed for 14 days in Hank's Balanced Salt Solution (HBSS) procured from Lonza Chemicals Pte Ltd., Singapore. Falcon tubes were filled with the required amount of HBSS and kept in a water bath maintained at 37 °C to simulate the human body temperature. The weight loss and pH were measured after 1, 2, 3, 4, 7, and 14 days. The corrosion products from the sample surface after immersion were removed using a solution containing 20 g of CrO3 and 1.9 g of AgNO3 dissolved in 100 mL of deionized water. The corroded samples were analyzed using SEM and Energy Dispersive X-ray Spectroscopy (EDS) to gain further insight into the corrosion mechanism observed in the samples. The corrosion rate was calculated using Equation (1).

[0073]

Number

[0074] Where K, W i (g), W f (g), ρ (g / cc), A (cm 2 ), T (h) are the time conversion factor, the initial weight of the sample, the final weight of the sample, the density of the sample, and the immersion time, respectively.

[0075] Analysis of the microhardness of magnesium alloys The microhardness of the extruded samples was measured with an indentation load of 245 mN for a holding time of 15 s according to the standard test method for microhardness of materials (ASTM E384 - 08). For the measurement, a Shimadzu HMV automatic digital microhardness tester (Kyoto, Japan) equipped with a Vickers indenter (a pyramid-shaped diamond indenter with a square base and an included angle of 136°) was used.

[0076] Tables 2 and 3 show the results of the grain size and microhardness of the magnesium alloys.

[0077]

Table 2

[0078]

Table 3

[0079] As shown in Table 2, in the presence of Dy, as the addition amount of Sr increases, the average crystal grain size decreases and is the smallest in Mg-Zn-xDy-zSr. The microhardness is the largest in Mg-Zn-xDy-zSr.

[0080] Figure 1 shows the crystal grain size structure of the magnesium alloy investigated under an optical microscope. As shown in Figure 1, improvements in strength, corrosion resistance, and biocompatibility response are shown from the substantially equiaxed crystal grain structure of the magnesium alloy, where the majority is Mg-Zn-xDy-zSr. Therefore, the inventors found that the high microhardness of the magnesium alloy may be due to (a) Zn strengthening the solid solution in the Mg melt, (b) the resistance provided against local plastic deformation by the second-phase particles in the matrix, and (c) the refinement of the crystal grain size, as shown in Figure 1.

[0081] Furthermore, Figure 2 shows the results of the optical micrograph analysis of the magnesium alloy. A mostly uniform distribution of the second phase was observed, further confirming the importance of the selection of processing parameters during the processing steps. It is clear from Figure 2 that Mg 17 Sr2 is formed.

[0082] Example 3: Determination of the corrosion degree of the magnesium alloy For magnesium-based alloys and composites to be targeted as bioabsorbable implants, high corrosion resistance is extremely important to maintain load-bearing strength while minimizing the inflammatory response. The corrosion degree of the magnesium alloy was investigated using Hank's balanced salt solution (HBSS). The HBSS was replaced regularly to maintain the pH equal to that of the body fluid. The measured values of the corrosion degree are summarized in Table 3. Figure 3 shows a graph of the corrosion degree of the magnesium alloy against the immersion time (days).

[0083]

Table 4

[0084] Table 4 and Figure 3 both show the corrosion degree of the magnesium alloy. The corrosion degree of this alloy was high at the end of the first day for all samples, fluctuated slightly and was small until the end of the fourth day, and then remained less than 0.2 mm / y until the end of the 14-day cycle, and it was observed that the corrosion degree was almost uniform or decreased. This is considered to be because Mg was anodically dissolved to Mg 2+ from the 0th day to the 1st day, which increased the corrosion degree. The ionic interaction between Mg 2+ and OH - forms a protective layer of magnesium hydroxide. As a result, the hydroxide layer forms a diffusion barrier between the matrix and the solution, reducing the corrosion degree. Cl - ions with a small radius diffuse through the layer, interact with the surface, cause local depressions, interact with the second phase, and cause micro-galvanic corrosion.

[0085] Example 4: Cell viability test of magnesium alloy The biocompatibility test can evaluate the biocompatibility of implant materials. The cell viability test is the most important and commonly used cell compatibility test.

[0086] For cell culture, osteoblast-like mouse MC3T3-E1 cells were used. As the medium, α-minimum essential medium (MEM) (Gibco) supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin was used. The cells were incubated at 37 °C and 5% CO2 in a humidified atmosphere. For the direct assay, 5 mm × 2 mm disks were used. The cells were seeded directly onto this disk. The direct assay (registered trademark) was performed in a 96-well plate. For the cell proliferation assay, an MTS solution (Promega's CellTiter 96 Aqueous Assay System) was used. MC3T3-E1 (8000 cells) were seeded directly onto the disks in a 96-well plate and incubated for 1, 3, and 5 days. After the incubation period, the samples containing the cells were washed with phosphate-buffered saline (PBS), and 100 μl of αMEM medium was added to the wells. 20 μl of the MTS reagent was added to the wells in a dark environment and incubated at 37 °C and 5% CO2 for 2 hours. After incubation, the absorbance of the well plate was read at a wavelength of 490 nm in a 96-well plate reader. The absorbance (OD) obtained with the well plate reader was plotted, and the percentage of viable cells was calculated using Equation (2).

[0087]

Number

[0088]

Table 5

[0089] Figures 6A and 6B show the cell viability of MC3T3-E1 pre-osteoblast cells, expressed as a ratio to the viability of cells cultured in a negative control after incubation of the magnesium alloy for 1, 3, and 5 days. Referring to both Table 5 and Figures 6A and 6B, the cell viability of all the alloys increased by the end of day 3, showing a significant improvement. Furthermore, no signs of cytotoxicity to MC3T3-E1 cells were shown over time, although the cell viability values of the materials decreased. According to the ISO10993-5:2009 standard of the MTT assay, if the cell viability exceeds 70% of the negative control, there is no possibility of cytotoxicity in the alloy. The improvement in the cytotoxicity results is due to (a) a fine grain structure, (b) high surface energy, (c) corrosion inhibition, and (d) the formation of an apatite layer with bioactivity.

[0090] Comparative Example Comparative Example 1: Test of Compressive Properties To investigate the compressive properties of the magnesium alloy, a quasi-static compression test was carried out as described in the standard test method for compression testing of metallic materials at room temperature (ASTM E9-89a). At room temperature, cylindrical samples with an inner diameter (Φ) of 8 mm × 8 mm were tested using an 810 material test system (MTS) at a strain rate of 8.3×10 -5 per second. To ensure consistent and reproducible results, at least 5 samples were tested. Table 6 shows the compression test results of magnesium alloys including commercially available magnesium alloys.

[0091]

Table 6

[0092] As shown in Table 6, the compressive yield strength (CYS) at room temperature is Dy, Sr, Ca, and M It was found to increase as the weight percentage of n increased. The results of the compression test were compared with those of other commercially available magnesium alloys and also with natural bone samples. The compression test results of the magnesium alloy were much better than those of commercially available magnesium alloys such as Mg-6Zn / 10β-TCP, AZ91D, AM50, WE43 + apatite, and ZK60.

Industrial Applicability

[0093] The disclosed magnesium alloy contains suitable alloying elements such as zinc and biocompatible elements such as dysprosium, strontium, calcium, and manganese. This alloy does not contain rare elements such as neurotoxic aluminum or cytotoxic yttrium. Advantageously, the magnesium-based alloy has properties such as chemical inertness, high strength, rigidity, stability, biocompatibility, tissue tolerance, and corrosion resistance, and this alloy is an optimal and safe material for orthopedic applications and implants.

[0094] Without departing from the spirit and scope of the present invention, various other changes and adaptations of the present invention will be apparent to those skilled in the art who have read the foregoing disclosure, and it will be obvious that all such changes and adaptations are intended to fall within the scope of the appended claims.

Claims

1. (a) A step of placing alloy components in a crucible, wherein the alloy components are placed in the crucible in a multi-layer arrangement; (b) A step of melting the alloy components at 700°C to 850°C; (c) A step of stirring the melt of step (b) at 400 rpm to 500 rpm; (d) A step of atomizing the melt of step (c) into millimeter-sized droplets using a jet of inert gas; (e) A step of cooling and depositing the atomized alloy melt to obtain an ingot A method for manufacturing an alloy, comprising: The method for manufacturing an alloy, wherein step (a) includes controlling the volume of the alloy components to 70% to 75% of the volume of the crucible.

2. The alloy is an alloy of formula (I), Mg - Zn - X Formula (I) X represents -Ca - Mn or -Dy - Sr, Mg is magnesium, Zn is zinc, Dy is dysprosium, Sr is strontium, Ca is calcium, and Mn is manganese, The alloy is based on the total weight of the alloy, 0.1 wt% to 3.0 wt% of Zn; 0.1 wt% to 0.7 wt% of Dy; 0.1 wt% to 0.9 wt% of Sr; 0.1 wt% to 1.5 wt% of Ca; 0.1 wt% to 0.9 wt% of Mn; and The balance of Mg and impurities, the method according to claim 1.

3. The multi-layer arrangement of step (a) includes an A - B - A arrangement, where A consists of a first alloy component and B consists of a second alloy component. Each of the first and second alloy components may consist of a single alloy material or an alloy mixture of two or more alloy materials. The method according to claim 1 or 2.

4. The multi-layer arrangement of step (a) includes an A - B - A - B - A arrangement, where A consists of a first alloy component and B consists of a second alloy component. Each of the first and second alloy components may consist of a single alloy material or an alloy mixture of two or more alloy materials. The method according to any one of claims 1 to 3.

5. A consists of magnesium and B consists of an alloy mixture of zinc and X. The method according to claim 3 or 4.

6. Each layer of the multi-layer arrangement has a substantially equal volume. The method according to any one of claims 1 to 5.

7. Step (d) includes using 2 to 4 jets of inert gas. The method according to any one of claims 1 to 6. Claim 8 The method according to any one of claims 1 to 7, wherein the inert gas in step (d) is argon. Claim 9 The method according to any one of claims 1 to 8, wherein the diameter of each jet in step (d) is 1 mm to 2 mm. . Claim 10 The method according to any one of claims 1 to 9, wherein the gas flow rate in step (d) is 20 to 30 liters per minute. Claim 11 The method according to any one of claims 1 to 10, further comprising a step (f) of subjecting the ingot to hot extrusion at 250°C to 400°C. Claim 12 The method according to claim 11, wherein the range of the extrusion ratio is 25:1 to 12:1.

Images