Biodegradable magnesium alloy

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] This invention generally relates to biodegradable alloys. The invention also relates to the manufacturing process and techniques for these biodegradable alloys. Biodegradable alloys may be useful for orthopedic applications. [Background technology]

[0002] With the aging of the global population, the number of cases of age-related orthopedic diseases, such as osteoporosis and fractures, is increasing significantly. This is leading to a growing demand for effective and affordable orthopedic implants and instruments. Research and development to find the ideal orthopedic implant material is ongoing. Several material elements (e.g., orthopedic application / area, function, fit, and cost) and properties must be considered, including chemical and biological inertness, strength, rigidity, corrosion resistance, stability, biocompatibility, and tissue acceptability.

[0003] Currently, orthopedic implants and instruments are manufactured using polymers, ceramics, or metallic materials. Each has its own strengths and weaknesses. Metallic materials such as stainless steel, platinum, and titanium, as well as alloys such as titanium alloys and chromium-cobalt alloys, are commonly used due to their excellent strength and mechanical properties. However, these metal implants tend to have poor bone integration, which can lead to loosening and ultimately implant failure. Therefore, these metal implants may need to be removed after achieving their healing purpose due to the possibility of complications during recovery (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 potential for deformation, these are not suitable for heavy-duty orthopedic applications (such as bone healing).

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

[0006] Therefore, there is a need to provide materials suitable for orthopedic applications that overcome, or at least improve, one or more of the aforementioned drawbacks. Combining properties such as chemical inertness, strength, rigidity, stability, biocompatibility, tissue acceptability, and corrosion resistance would result in ideal materials for orthopedic implants and applications. [Overview of the project]

[0007] In one embodiment of the present disclosure, a biodegradable alloy of formula (I), Mg-Zn-X Equation (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 is based on the total weight of the alloy. Approximately 0.1% to 3.0% by weight of zinc; Approximately 0.1% by weight to approximately 0.7% by weight of Dy; Approximately 0.1% to 0.9% by weight of Sr; Approximately 0.1% to 1.5% by weight of Ca; Approximately 0.1% to 0.9% by weight of Mn; and A biodegradable alloy is provided, containing the remainder Mg and impurities.

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

[0009] Advantageously, the disclosed biodegradable alloys have zero cytotoxicity, which enables the effective use of the material in orthopedic, neurosurgical, craniofacial, and maxillofacial applications, reducing associated risks to patients.

[0010] A low weight fraction of alloying element (e.g., zinc) may be used in the biodegradable alloy. 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 satisfying all the necessary functions and properties.

[0011] In a further aspect of this disclosure, (a) A step of placing alloy components in a crucible, wherein the alloy components are arranged in a multilayer configuration within the crucible, (b) A step of melting the alloy components at approximately 700°C to approximately 850°C. (c) A step in which the molten material from step (b) is stirred at approximately 400 rpm to approximately 500 rpm. (d) A step in which the molten material from step (c) is atomized into millimeter-sized droplets using a jet of inert gas. (e) This minute Granulation The process involves cooling and depositing the resulting composite material to obtain an ingot. A method for manufacturing an alloy is provided, including the following.

[0012] Another embodiment of the present disclosure, a method for manufacturing an alloy of formula (I), Mg-Zn-X Equation (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 is based on the total weight of the alloy. Approximately 0.1% to 3.0% by weight of zinc; Approximately 0.1% by weight to approximately 0.7% by weight of Dy; Approximately 0.1% to 0.9% by weight of Sr; Approximately 0.1% to 1.5% by weight of Ca; Approximately 0.1% to 0.9% by weight of Mn; and The remainder contains Mg and impurities. This delicious, (a) A step of disposing alloy components in a crucible, wherein the alloy components are disposed in the crucible in a multi-layer arrangement, (b) A step of melting the alloy components at about 700 °C to about 850 °C, (c) A step of stirring the melt of step (b) at about 400 rpm to about 500 rpm, (d) A step of atomizing the melt of step (c) into millimeter-sized droplets using a jet of an inert gas, (e) The fine Granulation And cooling and depositing the molten alloy to obtain an ingot A method for manufacturing an alloy is provided.

[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 using the disclosed method of the present invention, the disclosed biodegradable alloy can be efficiently manufactured without using any toxic flux materials and protective gases such as sulfur hexafluoride. Thus, advantageously, the manufacture of the disclosed biodegradable alloy is a safe, cost-effective, energy-efficient, and industrially scalable process. The disclosed biodegradable alloy and the disclosed method for forming the 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 and fixation applications used in biodegradable screws, plates, pins, and clips).

[0014]

[0015] Definition Unless otherwise defined herein, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. In general, the nomenclature used in connection with the chemistry described herein, and the chemical techniques described herein, are well known and commonly used in the art.

[0016] Unless the context requires otherwise or it is specifically stated otherwise, an integer, step, or component of the present invention described herein as a singular integer, step, or component clearly includes both the singular and plural forms of the integer, step, or component described herein.

[0017] As used herein, the term "biodegradable" means that it can be chemically broken down, degraded, and absorbed by the body, and therefore does not require manual removal. This is also known as biodegradability.

[0018] The word "substantially" does not exclude "completely"; for example, a composition that "substantially does not contain" Y does not have to contain Y completely. If necessary, the word "substantially" may be omitted from the definition of this invention.

[0019] Unless otherwise specified, the terms “comprising” and “comprise,” as well as their grammatical variations, are intended to represent an “open” or “inclusive” usage that includes the components they describe, but also allows for the inclusion of additional, undescribed components.

[0020] As used herein, the term “about” means, in the context of the concentration of components in a formulation, typically ±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 numerical range format. The use of numerical range format is solely for convenience and brevity and should not be interpreted as imposing any inalienable limitations on the numerical range disclosed. Therefore, numerical range descriptions should be considered to specifically disclose all possible subranges and individual numbers within that range. For example, a numerical range description such as 1–6 should be considered to specifically disclose subranges such as 1–3, 1–4, 1–5, 2–4, 2–6, 3–6, and individual numbers within that range, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the numerical range.

[0022] Specific embodiments may also be described broadly and generally herein. Each of the narrower types and subgroups of concepts contained within the comprehensive disclosure also forms part of this disclosure. This includes general descriptions of embodiments having conditional or negative limitations that remove any subject matter from this type, regardless of whether the deleted material is specifically described herein.

[0023] The accompanying drawings serve to illustrate the disclosed embodiments and to illustrate the principles of the disclosed embodiments. However, it should be understood that these drawings are intended for illustrative purposes only and are not intended to be limiting definitions of the invention. [Brief explanation of the drawing]

[0024] [Figure 1] The grain structure of the magnesium alloy of the present invention, as investigated under an optical microscope, is shown. (Photograph used as a substitute for drawing) [Figure 2] The results of optical microscope image analysis of a magnesium alloy are shown. (Image used as a substitute for diagram) [Figure 3] This indicates the degree of corrosion of magnesium alloys. [Figure 4A]The results of scanning electron microscopy (SEM) analysis of the magnesium alloys Mg-Zn-xSr, Mg-Zn-xDy-ySr, Mg-Zn-xDy-xSr, and Mg-Zn-xDy-zSr after corrosion, at the end of day 14, are shown. [Figure 4B] The results of scanning electron microscopy (SEM) analysis of magnesium alloys Mg-Zn-aCa, Mg-Zn-aCa-cMn, and Mg-Zn-aCa-dMn after corrosion, at the end of day 14, are shown. [Figure 5A] The compression properties of magnesium alloys Mg-Zn-xSr, Mg-Zn-xDy-ySr, Mg-Zn-xDy-xSr, and Mg-Zn-xDy-zSr are shown. [Figure 5B] The compression properties of magnesium alloys Mg-Zn-aCa, Mg-Zn-aCa-cMn, and Mg-Zn-aCa-dMn are shown. [Figure 6A] The cell viability of MC3T3-E1 preosteogenic cells is shown as a percentage of the viability of cells cultured in the negative control after incubation with magnesium alloys Mg-Zn-ySr, Mg-Zn-xDy-xSr, and Mg-Zn-xDy-zSr for 1, 3, and 5 days. [Figure 6B] The cell viability of MC3T3-E1 preosteogenic cells is shown as a percentage of the viability of cells cultured in the negative control after incubation for 1, 3, and 5 days in magnesium alloys Mg-Zn-aCa, Mg-Zn-aCa-cMn, and Mg-Zn-aCa-dMn. [Figure 7] This is a schematic cross-sectional diagram of a crucible showing the multilayer arrangement of alloy components. [Figure 8A] Compression fracture samples of magnesium alloys Mg-Zn-xSr, Mg-Zn-xDy-ySr, Mg-Zn-xDy-xSr, and Mg-Zn-xDy-zSr are shown. (Photo used as a substitute for drawing) [Figure 8B] Compression fracture samples of magnesium alloys Mg-Zn-aCa, Mg-Zn-aCa-cMn, and Mg-Zn-aCa-dMn are shown. (Photo used as a substitute for drawing) [Modes for carrying out the invention]

[0025] Detailed description of the drawing Referring to Figures 4A and 4B, which show scanning electron microscopy (SEM) analysis of the magnesium alloy at the end of day 14 after corrosion. The magnesium alloy shows crack formation due to water loss. The alloy surface is covered with a needle-like structure. The formation of brucite compounds is enhanced as the immersion time of the magnesium alloy in Hank's equilibrium salt solution (HBSS) increases. The extent of compound formation was more uniformly distributed in the alloy sample. This behavior can promote the retention of material strength and ductility after in vitro corrosion.

[0026] Referring to Figures 5A and 5B, which show the compressive properties of the magnesium alloy, Figures 5A and 5B also show stress-versus-strain graphs or compression tests of the magnesium alloy, providing further insight into the mechanical integrity of this alloy. Based on Figures 5A and 5B, the amount of strength maintained by the material after implantation can be assessed, and the functional lifecycle requirements of the implant can be determined.

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

[0028] Magnesium is non-toxic, biocompatible, bioabsorbable, low-density, and possesses mechanical properties similar to those of bone. However, monolithic magnesium exhibits poor corrosion resistance in physiological environments, has low mechanical property retention, and may fail before complete bone restoration. Improving magnesium using alloying techniques is crucial to tailoring its properties to meet the requirements of an ideal orthopedic implant material.

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

[0030] The present invention relates to a biodegradable alloy of formula (I), Mg-Zn-X Equation (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 is based on the total weight of the alloy. Approximately 0.1% to 3.0% by weight of zinc; Approximately 0.1% by weight to approximately 0.7% by weight of Dy; Approximately 0.1% to 0.9% by weight of Sr; Approximately 0.1% to 1.5% by weight of Ca; Approximately 0.1% to 0.9% by weight of Mn; and The remainder consists of Mg and impurities, Regarding biodegradable alloys.

[0031] This biodegradable alloy is given by formula (IA) Mg-Zn-Ca-Mn That's fine.

[0032] This biodegradable alloy is given by formula (IB) Mg-Zn-Dy-Sr That's fine.

[0033] This alloy has a concentration of approximately 0.1% to 3.0%, 0.2% to 3.0%, 0.3% to 3.0%, 0.4% to 3.0%, 0.5% to 3.0%, 0.6% to 3.0%, 0.7% to 3.0%, 0.8% to 3.0%, 0.9% to 3.0%, and approximately 1.0% to3.0% 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% by weight Amount %~about 3.0 weight%, about 1.9 weight%~about 3.0 weight%, about 2.0 weight%~about 3.0 weight%, about 2.0 weight%~about 2.5 weight%, about 2.1 weight%~about 2.2 weight%, about 2.3 weight%~about 3.0 weight%, about 2.4 weight%~about 3.0 weight%, about 2.5 weight%~about 3.0 weight%, about 2 .6% by weight 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 Weight %, about 0.1 weight % to about 1.7 weight %, about 0.1 weight % to about 1.6 weight %, about 0.1 weight % to about 1.5 weight %, about 0.1 weight % to about 1.4 weight %, about 0.1 weight % to about 1.3 weight %, about 0.1 weight % to about 1.2 weight %, about 0.1 weight % to about 1.1 weight %, about 0.1 weight % 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% by weight It may contain zinc in amounts of % to approximately 0.2% by weight, or 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, approximately 0.9% by weight, approximately 1.0% by weight, approximately 1.1% by weight, approximately 1.2% by weight, approximately 1.3% by weight, approximately 1.4% by weight, approximately 1.5% by weight, approximately 1.6% by weight, approximately 1.7% by weight, approximately 1.8% by weight, approximately 1.9% by weight, approximately 2.0% by weight, approximately 2.1% by weight, approximately 2.2% by weight, approximately 2.3% by weight, approximately 2.4% by weight, approximately 2.5% by weight, approximately 2.6% by weight, approximately 2.7% by weight, approximately 2.8% by weight, approximately 2.It may contain 9% by weight, approximately 3.0% by weight, or any value or range of zinc between these two amounts.

[0034] The alloys are approximately 0.1% to 1.5% by weight, approximately 0.2% to 1.5% by weight, approximately 0.3% to 1.5% by weight, approximately 0.4% to 1.5% by weight, approximately 0.5% to 1.5% by weight, approximately 0.5% to 1.0% by weight, approximately 0.6% to 1.5% by weight, approximately 0.7% to 1.5% by weight, approximately 0.8% to 1.5% by weight, and approximately 0.9% to 1.5% by weight. 1.5% by weight, about 1.0% to about 1.5% by weight, about 1.1% to about 1.5% by weight, about 1.2% to about 1.5% by weight, about 1.3% to about 1.5% by weight, about 1.4% by weight ~1.5% by weight, approximately 0.1% by weight ~ approximately 1.4% by weight, approximately 0.1% by weight ~ approximately 1.3% by weight, approximately 0.1% by weight ~ approximately 1.2% by weight, approximately 0.1% by weight ~ approximately 1.1% by weight, approximately 0.1% by weight It may contain calcium in the following proportions: approximately 1.0% by weight, approximately 0.1% by weight to approximately 0.9% by weight, approximately 0.1% by weight to approximately 0.8% by weight, approximately 0.1% by weight to approximately 0.7% by weight, approximately 0.1% by weight to approximately 0.6% by weight, approximately 0.1% by weight to approximately 0.5% by weight, approximately 0.1% by weight to approximately 0.4% by weight, approximately 0.1% by weight to approximately 0.3% by weight, and approximately 0.1% by weight to approximately 0.2% by weight, or approximately 0. It may contain calcium in amounts of 1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, approximately 0.9% by weight, approximately 1.0% by weight, approximately 1.1% by weight, approximately 1.2% by weight, approximately 1.3% by weight, approximately 1.4% by weight, or approximately 1.5% by weight, or any value or range of calcium within these amounts.

[0035] The alloy is found in concentrations of approximately 0.1% to 0.9% by weight, 0.2% to 0.9% by weight, 0.2% to 0.8% by weight, 0.3% to 0.9% by weight, 0.4% to 0.9% by weight, 0.5% to 0.9% by weight, 0.6% to 0.9% by weight, 0.7% to 0.9% by weight, 0.8% to 0.9% by weight, 0.1% to 0.8% by weight, 0.1% to 0.7% by weight, and 0.1% to 0.6% by weight. It may contain manganese in amounts of %, approximately 0.1% to approximately 0.5% by weight, approximately 0.1% to approximately 0.4% by weight, approximately 0.1% to approximately 0.3% by weight, or approximately 0.1% to approximately 0.2% by weight, or it may contain manganese in amounts of approximately 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, or approximately 0.9% by weight, or any value or range of manganese among these.

[0036] The alloys are approximately 0.1% to 0.7% by weight, 0.2% to 0.7% by weight, 0.3% to 0.7% by weight, 0.4% to 0.7% by weight, 0.4% to 0.6% by weight, 0.5% to 0.7% by weight, 0.6% to 0.7% by weight, 0.1% to 0.6% by weight, 0.1% to 0.5% by weight, and 0.1% to 0% by weight. It may contain 0.4% by weight, approximately 0.1% to approximately 0.3% by weight, approximately 0.1% to approximately 0.2% by weight of dysprosium, or it may contain approximately 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight of dysprosium, or any value or range of dysprosium within these ranges.

[0037] The alloy is approximately 0.1% to 0.9% by weight, approximately 0.2% to 0.9% by weight, approximately 0.2% to 0.8% by weight, approximately 0.3% to 0.9% by weight, approximately 0.4% to 0.9% by weight, approximately 0.5% to 0.9% by weight, approximately 0.6% to 0.9% by weight, approximately 0.7% to 0.9% by weight, approximately 0.8% to 0.9% by weight, approximately 0.1% to 0.8% by weight, approximately 0.1% to 0.7% by weight, approximately 0.1% to 0.6% by weight, approximately 0 It may contain strontium in amounts of 0.1% to approximately 0.5% by weight, approximately 0.1% to approximately 0.4% by weight, approximately 0.1% to approximately 0.3% by weight, or approximately 0.1% to approximately 0.2% by weight, or it may contain strontium in amounts of approximately 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, or approximately 0.9% by weight, or any value or range of strontium within these ranges.

[0038] Biodegradable alloys are Mg-Zn-Ca-Mn; Zn is 2.5% by weight, Ca is 1.0% by weight, Mn is 0.3% by weight, and Mg makes up the remainder. Mg-Zn-Ca-Mn; Zn is 2.5% by weight, Ca is 1.0% by weight, Mn is 0.5% by weight, and Mg makes up the remainder. Mg-Zn-Ca-Mn; Zn is 2.5 wt%, Ca is 1.0 wt%, Mn is 0.7 wt%, and Mg makes up the remainder. The mixture consists of 2.5% by weight of Zn, 0.5% by weight of Dy, 0.2% by weight of Sr, and the remainder being Mg, i.e., Mg-Zn-Dy-Sr; ·Mg-Zn-Dy-Sr, where Zn is 2.5% by weight, Dy is 0.5% by weight, Sr is 0.5% by weight, and Mg makes up the remainder; and The mixture consists of 2.5% by weight of Zn, 0.5% by weight of Dy, 0.8% by weight of Sr, and Mg making up the remainder: Mg-Zn-Dy-Sr You may choose from the group consisting of the following.

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

[0040] The alloy is advantageous in that it does not have to contain yttrium, which is known to be cytotoxic. To the inventors' surprise, yttrium can be removed from the alloy and replaced with strontium, calcium, and calcium. It has been found that similar functional benefits can be achieved with lower risks and lower costs by using trace amounts of sium, manganese, and dysprosium as additives.

[0041] This disclosure also relates to formula (I) Mg-Zn-X Equation (I) An implant containing a biodegradable alloy, 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 is based on the total weight of the alloy. Approximately 0.1% to 3.0% by weight of zinc; Approximately 0.1% by weight to approximately 0.7% by weight of Dy; Approximately 0.1% to 0.9% by weight of Sr; Approximately 0.1% to 1.5% by weight of Ca; Approximately 0.1% to 0.9% by weight of Mn; and This relates to an implant containing or consisting of the remainder of Mg and impurities.

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

[0043] This disclosure further describes a method for manufacturing an alloy, (a) A step of placing alloy components in a crucible, wherein the alloy components are arranged in a multilayer configuration within the crucible, (b) A step of melting the alloy components at approximately 700°C to approximately 850°C. (c) A step of stirring the molten material from step (b) at approximately 400 rpm to approximately 500 rpm, (d) A step of atomizing the molten material from step (c) into millimeter-sized droplets using an inert gas jet. (e) This minute Granulation The process involves cooling and depositing the resulting composite material to obtain an ingot. This relates to a method for manufacturing alloys, including those mentioned above.

[0044] This disclosure further states formula (I) Mg-Zn-X Equation (I) A method for manufacturing an alloy, 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. n and This alloy is based on the total weight of the alloy. Approximately 0.1% to 3.0% by weight of zinc; Approximately 0.1% by weight to approximately 0.7% by weight of Dy; Approximately 0.1% to 0.9% by weight of Sr; Approximately 0.1% to 1.5% by weight of Ca; Approximately 0.1% to 0.9% by weight of Mn; and The remainder consists of Mg and impurities, This is delicious, (a) A step of placing alloy components in a crucible, wherein the alloy components are arranged in a multilayer configuration within the crucible, (b) A step of melting the alloy components at approximately 700°C to approximately 850°C. (c) A step in which the molten material from step (b) is stirred at approximately 400 rpm to approximately 500 rpm. (d) A step in which the molten material from step (c) is atomized into millimeter-sized droplets using a jet of inert gas. (e) This minute Granulation The process involves cooling and depositing the resulting composite material to obtain an ingot. This relates to a method for manufacturing alloys, including those mentioned above.

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

[0046] Step (a) may include controlling the volume of this alloy component to approximately 70% to 75% of the crucible's volume. To the inventors' surprise, it was found that when the volume of the precursor material / alloy component is controlled to approximately 70% to 75% of the crucible's volume, the flow rate of the molten material is adjusted relative to the amount of material used as raw material. This engineering control is advantageous in that it ensures the reproducibility of the amount of material deposited in the mold. Furthermore, the homogenization of the molten metal flow rate also standardizes the amount of gas impacting the incoming molten metal, further controlling the heat removal from the molten metal flow. Controlling the impact volume of inert gas on the molten metal flow standardizes the gas-to-molten metal volume ratio, and therefore, advantageously, ensures the generation of similar microstructures and reproducibility of mechanical properties in the deposited material.

[0047] The volume of the alloy components may be approximately 70%, 71%, 72%, 73%, 74%, or 75% of the crucible's volume.

[0048] Furthermore, in step (a), the multilayer arrangement of step (a) may include an ABA arrangement, where A includes or consists of a first alloying component, and B includes or consists of a second alloying component, and each of the first and second alloying components may include or consist of a single alloying material or an alloy mixture of two or more alloying materials.

[0049] To their surprise, the inventors discovered that when this alloying component is arranged in this multilayer or sandwich configuration, the alloying elements (including multiple elements) in the second alloying component can have different melting points compared to the alloying matrix material, thus maximizing the capture and wettability of the alloying matrix material (which may be the first alloying component). Using such layer-by-layer or multilayer arrangements ensures that the alloying elements are homogenized to the maximum extent within the molten matrix metal / material.

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

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

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

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

[0054] In one embodiment, A may consist of magnesium, and B may consist of a mixed alloy of zinc, dysoprium, and strontium.

[0055] Each layer in this multi-layered arrangement may have substantially equal volume. Advantageously, this helps to ensure uniform heating of each layer within the furnace.

[0056] To the inventors' surprise, it was found that arranging the alloy components in this multilayer or sandwich configuration ensures maximum capture and wettability of the magnesium matrix because the alloying elements (including multiple elements) (such as zinc, manganese, calcium, dysoprium, and strontium) can have different melting points compared to magnesium. The magnesium may be arranged in a folded configuration, with three equal-volume layers in which the mixed alloy layer mixture is sandwiched between the magnesium layers. After the melting of the magnesium, such a layered / multilayer arrangement advantageously ensures the most possible homogenization of the alloying elements into the molten matrix metal.

[0057] The method of the present invention is a liquid-based processing method. Magnesium may be the matrix material, and constituent elements (zinc, manganese, calcium, dysoprium, and strontium) may be added to the crucible with magnesium in a multilayer or sandwich configuration. Since the weight percentage of the constituent elements is low, using a multilayer or sandwich configuration is advantageous because it ensures that the magnesium and these constituent elements are adequately pre-mixed, allowing for the formation of folded magnesium. The structure of the constituent elements may be powder, ingot shot, or wire. Considering the various possibilities, the multilayer or sandwich configuration provides the best uniformity during stirring and casting, and in the subsequent final casting.

[0058] Step (b) may be performed at temperatures of approximately 700°C to 850°C, approximately 725°C to 850°C, approximately 750°C to 850°C, approximately 775°C to 850°C, approximately 800°C to 850°C, approximately 825°C to 850°C, approximately 700°C to 825°C, approximately 700°C to 800°C, approximately 700°C to 775°C, approximately 700°C to 750°C, approximately 700°C to 725°C, or approximately 700°C, approximately 725°C, approximately 750°C, approximately 775°C, approximately 800°C, approximately 825°C, approximately 850°C, or any value or range in between these.

[0059] The stirring in step (c) may be performed at approximately 400 rpm to 500 rpm, approximately 425 rpm to 450 rpm, approximately 450 rpm to 500 rpm, approximately 475 rpm to 500 rpm, approximately 400 rpm to 475 rpm, approximately 400 rpm to 450 rpm, approximately 400 rpm to 425 rpm, or approximately 400 rpm, approximately 425 rpm, approximately 450 rpm, approximately 475 rpm, approximately 500 rpm, or any value or range in between.

[0060] The selected stirring speed can, advantageously, uniformly disperse the second phase particles in the molten material. The optimized stirring speed avoids aggregation in the molten material, and the constituent elements are thoroughly mixed in a molten or semi-solid state. In the disclosed method, a sandwich or multilayer configuration is introduced to the alloy components. Therefore, using optimized stirring advantageously improves the wettability between the first and second alloy components.

[0061] The inert gas jet in step (d) may be a nitrogen or argon jet. The number of jets used may be 2, 3, 4, 5, or 6. 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 decompose the molten material into millimeter-sized droplets. The flow rate and the number of jets affect the decomposition of the molten metal while it is being pushed up and cast into the molten material. Optimizing these parameters helps to improve the wettability of the molten metal and to promote chemical and thermal homogenization during the deposition process.

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

[0065] The hot extrusion step may be carried out for about 1 hour to about 2 hours, or about 60 minutes, about 65 minutes, about 70 minutes, about 75 minutes, about 80 minutes, about 85 minutes, about 90 minutes, about 95 minutes, about 100 minutes, about 105 minutes, about 110 minutes, about 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 structure in a graphite crucible 140 mm in diameter and 200 m in length, and melted in a controlled argon gas environment at a temperature range of 700-850°C (depending on the composition). To uniformly disperse the second phase particles in the molten material, 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 molten material into millimeter-sized droplets. 40 mm diameter cast ingots were then processed using these millimeter-sized (mm 3 Droplets of a controlled volume were deposited and obtained after solidification. These cast ingots were processed to specific dimensions, soaked 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 the microstructure properties of magnesium alloys Microstructure characterization was 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 alloys The grain size distribution was investigated by testing samples under a digital optical microscope equipped with LES 4.0 software, following the standard test method for determining average grain size (ASTM E112-13). A JEOL JSM-5800LV scanning electron microscope (SEM, Kyoto, Japan) was used to investigate the distribution of the second phase.

[0072] Samples were immersed for 14 days in Hank's equilibrium 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 human body temperature. Weight loss and pH were measured after 1, 2, 3, 4, 7, and 14 days. 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. Corroded samples were analyzed using SEM and energy-dispersive X-ray spectroscopy (EDS) to further gain insight into the corrosion mechanism observed in the samples. The degree of corrosion was calculated using formula (1).

[0073]

number

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

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

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

[0077] [Table 2]

[0078] [Table 3]

[0079] As shown in Table 2, the average grain size decreases as the amount of Sr added increases in the presence of Dy, and is lowest for Mg-Zn-xDy-zSr. Microhardness is highest for Mg-Zn-xDy-zSr.

[0080] Figure 1 shows the grain size structure of the magnesium alloy as investigated under an optical microscope. As shown in Figure 1, the nearly equiaxed grain structure of the magnesium alloy, which is predominantly Mg-Zn-xDy-zSr, indicates improved strength, corrosion resistance, and biocompatibility response. 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 molten product, (b) resistance to local plastic deformation provided by the second phase particles in the matrix, and (c) grain refinement, as shown in Figure 1.

[0081] Furthermore, Figure 2 shows the results of optical microscopy analysis of the magnesium alloy. A nearly uniform distribution of the second phase was observed, further confirming the importance of selecting processing parameters during the processing steps. The second phase is nearly uniform, Mg 17 Figure 2 clearly shows that Sr2 has been formed.

[0082] Example 3: Determination of the degree of corrosion of magnesium alloy For magnesium-based alloys and composite materials to be used as bioabsorbable implants, high corrosion resistance is crucial to maintain load-bearing strength while minimizing inflammatory responses. The corrosion degree of magnesium alloys was investigated using Hank's equilibrium salt solution (HBSS). The HBSS was periodically replaced to maintain a pH equal to that of body fluids. Table 3 summarizes the measured corrosion degrees. Figure 3 shows a graph of the corrosion degree of magnesium alloys against immersion time (days).

[0083] [Table 4]

[0084] Table 4 and Figure 3 both show the degree of corrosion of the magnesium alloy. The degree of corrosion of this alloy was observed to be high at the end of day 1 for all samples, fluctuating slightly until the end of day 4, and then remaining almost uniform or decreasing until the end of the 14-day cycle, remaining below 0.2 mm / y. This suggests that from day 0 to day 1, Mg... 2+ This is thought to be because it underwent anodic dissolution, which increased the degree of corrosion. 2+ and OH - Ionic interactions with the matrix form a protective layer of magnesium hydroxide. This reduces the degree of corrosion because the hydroxide layer forms a diffusion barrier between the matrix and the solution. - Ions diffuse through the layer, interact with the surface, create localized depressions, interact with the second phase, and cause microscopic galvanic corrosion.

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

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

[0087]

number

[0088] [Table 5]

[0089] Figures 6A and 6B show the cell viability of MC3T3-E1 preosteoblastic cells, expressed as a percentage of the viability of cells cultured in the negative control, after incubation of magnesium alloys for 1, 3, and 5 days. Referring to both Table 5 and Figures 6A and 6B, the cell viability of all alloys increased at the end of day 3 and showed a significant improvement. Furthermore, although no signs of cytotoxicity to MC3T3-E1 cells were shown over time, the cell viability values ​​of the materials decreased. According to the ISO 10993-5:2009 standard for MTT assays, if the cell viability exceeds 70% of the negative control, the alloy is not cytotoxic. The improvement in cytotoxicity results is attributed to (a) the fine grain structure, (b) high surface energy, (c) corrosion inhibition, and (d) the formation of a bioactive apatite layer.

[0090] Comparative Example Comparative Example 1: Compression Characteristics Test To investigate the compressive properties of magnesium alloys, quasi-static compression tests were performed as described in the standard test method for compression testing of metallic materials at room temperature (ASTM E9-89a). At room temperature, a cylindrical sample with an inner diameter (Φ) of 8 mm × 8 mm was subjected to 8.3 × 10⁻⁶ compression per second. -5 The samples were tested using the 810 Material Testing System (MTS) at the specified strain rate. A minimum of five samples were tested to ensure consistent and reproducible results. Table 6 shows the compression test results for 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 as follows: Dy, Sr, Ca, and M It was found that the compression test results increased as the weight percentage of n increased. The results of the compression test were compared with other commercially available magnesium alloys and natural bone samples. The compression test results of the magnesium alloys 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, as well as biocompatible elements such as dysprosium, strontium, calcium, and manganese. This alloy does not contain rare elements such as neurotoxic aluminum or cytotoxic yttrium. Advantageously, magnesium-based alloys possess properties such as chemical inertness, high strength, rigidity, stability, biocompatibility, tissue acceptability, and corrosion resistance, making this alloy an ideal and safe material for orthopedic applications and implants.

[0094] It will be apparent to those skilled in the art, having read the foregoing disclosure, that various other modifications and adaptations of the present invention can be made without departing from the spirit and scope of the invention, and it will be clear that all such modifications 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 arranged in a multilayer configuration in the crucible; (b) A step of melting the alloy components at 700°C to 850°C; (c) A step in which the molten material from step (b) is stirred at 400 rpm to 500 rpm; (d) A step of atomizing the molten material from step (c) into droplets using a jet of inert gas; (e) The step of cooling and depositing the atomized composite financial material to obtain an ingot. A method for manufacturing an alloy, including, Step (a) includes controlling the volume of the alloy component to 70% to 75% of the volume of the crucible, The aforementioned 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. Based on the total weight of the alloy, 0.1% to 3.0% by weight of Zn; 0.1% to 1.5% by weight of Ca; 0.1% to 0.9% by weight of Mn; and The remainder consists of Mg and impurities, or based on the total weight of the alloy, 0.1% to 3.0% by weight of Zn; Dy in an amount of 0.1% to 0.7% by weight; 0.1% to 0.9% by weight of Sr; and A method for manufacturing an alloy consisting of the remainder Mg and impurities.

2. The method according to claim 1, wherein the multilayer arrangement of step (a) includes an A-B-A arrangement, where A is a first alloy component and B is a second alloy component, and the first and second alloy components may each consist of a single alloy material or an alloy mixture of two or more alloy materials, where A is magnesium and B is an alloy mixture of zinc and X.

3. The method according to claim 1 or 2, wherein the multilayer arrangement of step (a) includes an A-B-A-B-A arrangement, where A is a first alloy component and B is a second alloy component, and the first and second alloy components may each consist of a single alloy material or an alloy mixture of two or more alloy materials, where A is magnesium and B is an alloy mixture of zinc and X.

4. The method according to any one of claims 1 to 3, wherein each layer in the multilayer arrangement has an equal volume.

5. The method according to any one of claims 1 to 4, wherein the number of inert gas jets used in step (d) is 2 to 4.

6. The method according to any one of claims 1 to 5, wherein the inert gas in step (d) is argon.

7. The method according to any one of claims 1 to 6, wherein the diameter of each jet in step (d) is 1 mm to 2 mm.

8. The method according to any one of claims 1 to 7, wherein the gas flow rate in step (d) is 20 to 30 liters per minute.

9. The method according to any one of claims 1 to 8, further comprising the step (f) of subjecting the ingot to hot extrusion at 250°C to 400°C.

10. The method according to claim 9, wherein the extrusion ratio in the hot extrusion is in the range of 25:1 to 12:1.

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