WO2011160533A1 - Magnesium alloy used for degradable implant material of bone in vivo and preparation method thereof - Google Patents

Abstract

Disclosed is a magnesium alloy used for degradable implant material of bone in vivo. The components and their weight ratio of magnesium alloy are: Nd 1.5-4%, Zn 0.1-2%, Ag 0.01-1%, Zr 0-1.0%, impurities 0-0.2% and balance Mg. The magnesium alloy has excellent mechanical property, desired uniform corrosion resistance and good biocompatibility. The magnesium alloy can be applied to prepare biodegradable implant material of bone, such as bone plate, bone peg and tissue engineering support of bone.

Description

 In vivo degradable magnesium alloy for bone plant and manufacturing method thereof  Technical field

 The invention relates to an alloy and a preparation thereof in the technical field of biomedical materials, in particular to an in vivo degradable magnesium alloy for intra-plant plants and a preparation method thereof.

Background technique

Among the currently used intraosseous implant materials, stainless steel and titanium alloy have become widely used materials with good biocompatibility, corrosion resistance and mechanical properties. However, a common problem in metal implant materials such as stainless steel and titanium alloys is poor mechanical compatibility with biological bone. The tensile strength of stainless steel, titanium alloy, etc. is more than 5 times higher than that of natural bone, and the elastic modulus is more than 10 times higher. When such a material is implanted into the human body, it can have a large "stress occlusion" effect on the local bone tissue. As the stress stimulation of the matrix bone decreases, the bone remodeling presents a negative balance, resulting in increased bone resorption, reduced bone formation, and induced occlusion bone loss. In general, poor mechanical compatibility of implant materials with biological tissue can lead to three serious consequences in medicine: (1) the fragility of the original biological bone around the implant material; and (2) poor growth of new bone around the implant material. (3) Stress concentration occurs at the interface between the implant material and the biological bone, thereby causing inflammation. It can be seen that the elastic modulus of the implant material and the biological bone can not be too different, and the orthopedic plant material which is more ideal for the development of mechanics and biocompatibility is the fundamental way to solve the problems existing in the current implant materials. At the same time, the implants such as stainless steel, titanium alloy bone plate and bone nail need to be removed by reoperation after the bone tissue is healed, which increases the patient's pain and medical expenses.

Research and development of medical materials that are strong and tough and can be degraded in vivo become an important development direction of bone plants. Magnesium has a low corrosion potential, is prone to corrosion in the body environment containing chloride ions, and is completely degraded in the body in a slow corrosion manner. Therefore, magnesium alloy as an internal implant material can avoid the pain of removing the patient from the second operation. And the economic burden. In addition, magnesium is currently the metal material with the closest biomechanical properties to human bone. The elasticity of magnesium alloy is about 45 GPa is closer to the elastic modulus of human bone than the currently widely used biomaterial titanium alloy (100 GPa) (7~30) GPa) can effectively reduce the "stress shielding effect" and promote bone healing. At the same time, the magnesium alloy has a high yield strength and can withstand a large load, and is applied to the bearing portion of the bone tissue to support. Magnesium is one of the important nutrients in the human body. It is the fourth metal element in the human body and the second cation in the cell after K+. It catalyzes or activates 325 enzymes in the body and participates in all energy metabolism in the body. It plays an important role in muscle contraction, neuromotor function, physiological function and prevention of circulatory diseases and ischemic heart disease. Magnesium excretion mainly passes through the urinary system, and absorption of magnesium in the human body does not cause a significant increase in serum magnesium content. Therefore, the use of magnesium alloy as an intraosseous implant material has a good medical safety foundation.

However, existing commercial magnesium alloys have poor corrosion resistance and the corrosion forms typically exhibit severe localized corrosion (pitting) rather than the uniform corrosion degradation that must be exhibited by clinically demanding biodegradable biomaterials. In particular, localized corrosion is particularly severe in corrosive environments where chloride ions are present or when the pH of the medium is less than 11.5. As a bio-implant material, magnesium alloys must meet the necessary mechanical and morphological requirements during service, so the rate of corrosion degradation should not be too fast. At the same time, a uniform corrosion degradation mode must be present, because only the uniform corrosion degradation, the service life of magnesium alloy as an implant material in the body can be predicted. Otherwise, if it is a localized corrosion (pitting) that is usually exhibited by commercial magnesium alloys, sudden fractures can occur in the implants with internal fixation, with serious consequences. The normal pH of the human body environment is about 7.4, and there is a large amount of chloride ions in the body fluid, and the human body is a complex corrosive environment, which will cause the corrosion rate of the magnesium alloy in the human body to change. At present, research in the field of degradable medical implanted magnesium alloys mainly focuses on the development of alloys with good corrosion resistance and high mechanical properties, and these two points are difficult to satisfy at the same time. At present, the magnesium alloy orthopedic implant materials used in clinical experiments still have problems of low strength, excessive degradation rate, and severe local corrosion (pitting). In addition, most of the medical magnesium alloys currently studied contain Al element, which is not an essential trace element of the human body and is considered to be neurotoxic, which is a factor causing Alzheimer's disease. Therefore, it is necessary to avoid alloying elements such as Al which are obviously toxic. .

According to the search of the prior art, Chinese Patent No. CN101113502, published on Jan. No. 2008-1-30, describes a thermally conductive magnesium alloy and a preparation method thereof. The content of the magnesium alloy is: Zn content is 2.5 to 11 wt. %, Zr content is 0.15~1.5wt%, Ag content is 0.1~2.5wt%, Ce content is 0.3~3.5wt%, Nd content is 0~1.5wt%, La content is 0~2.5wt %, the content of Pr is 0 to 0.5 wt%, wherein Nd, La, and Pr are not equal to 0 at the same time, or Nd, La, and Pr are both 0 at the same time, and the rest is Mg. A pure Mg ingot, a pure Zn ingot, a Mg-Zr intermediate alloy, a pure Ag ingot or a Mg-Ag intermediate alloy, and a pure Ce ingot or a lanthanum-rich mixed rare earth ingot, or a Ce or a lanthanum mixed rare earth and magnesium intermediate alloy, Pure magnesium ingot is melted and alloyed; it is made into a casting, subjected to solution treatment and aging treatment; or made into a billet, homogenized heat treatment, and processed into a sheet, a pipe by rolling, extrusion, drawing or forging. Aging treatment of profiles, bars, wires or various forgings. The magnesium alloy of the invention has a thermal conductivity greater than 120 W. (m.K)-1 at 20 ° C, a tensile strength greater than 340 MPa, and a yield strength greater than 310 MPa. It can be used as a heat dissipation system structural material for power supplies and electronic devices in aerospace.

However, the prior art is mainly a heat conductive magnesium alloy material designed for a heat dissipation system structure such as an electronic device, and is not designed for a biological material, and the range of the main element Zn content (2.5 to 11 wt%) in the alloy far exceeds the alloy of the present invention. The content of Zn in the range (0.1 to 2 wt%), the content range of the alloying element Nd (0 to 1.5 wt%) is lower than the content of Nd in the present invention (1.5 to 4 wt%).

Summary of the invention

The invention aims at the problems caused by the current non-degradable in vivo metal implant materials in the body, and provides the shortcomings of the current commercial magnesium alloy as a degradable internal implant material in terms of mechanical properties, corrosion performance and biosafety. An in vivo degradable magnesium alloy for bone plant and a preparation method thereof, the material has excellent mechanical properties, ideal uniform corrosion resistance, good biocompatibility, and is suitable for use as a degradable bone plate, bone nail, Bone tissue engineering stents and other orthopedic implant materials.

The invention is achieved by the following technical solutions:

The invention relates to an in vivo degradable magnesium alloy for bone plant, the composition and the weight percentage thereof being: Nd 1.5~4%, Zn 0.1~2%, Ag 0.01~1%, Zr 0~1.0%, impurity 0~0.2%, and the rest is Mg.

The component weight percentage of the magnesium alloy for intra-bone plant is preferably Nd 2.5 to 3.5%, Zn 0.1 to 0.5%, Ag. 0.01~0.4%, Zr 0.3~0.6%, and the rest is Mg.

The impurities are Fe, Ni, Cu, Al or Si or a combination thereof.

The invention relates to a method for preparing the above-mentioned in vivo degradable magnesium alloy for bone plant, which is obtained by melting a raw material metal under a protective atmosphere and then casting the ingot, and extruding to obtain a magnesium alloy bar.

The protective atmosphere refers to a protective atmosphere composed of a mixed gas of CO2 and SF6.

The raw material metal is composed of a magnesium block having a purity of 99.99% by weight, a zinc block having a purity of 99.999% by weight, a silver block having a purity of 99.99% by weight, a magnesium-30% cerium alloy, and a magnesium-30% zirconium alloy.

The smelting refers to melting at 700-760 ° C in an electric resistance furnace.

The extrusion means that the extrusion ratio is 5-20 in an environment of 250-400 ° C.

The present invention relates to the use of the above-described in vivo degradable magnesium alloy for intra-plant plants for the preparation of intraosseous implants such as bone plates, bone nails and bone tissue engineering scaffolds.

In view of the different requirements of material properties in orthopedic plants, the ingots prepared by the conventional casting process can be further refined by different extrusion (or rolling) thermal deformation processes and heat treatment processes, and the subsurfaces are subjected to compressive stress. Further, it is advantageous to further reduce the corrosion rate, and finally a biodegradable high-strength tough magnesium alloy having different performance combinations can be obtained.

The advantages and benefits of the present invention are:

(1) The magnesium alloy of the present invention can be naturally degraded in the body, and will disappear from the body within a certain period of time after reaching the medical effect, so that the patient can avoid the pain and trouble brought about by the second operation.

(2) The medical magnesium alloy of the present invention does not contain a toxic element in the composition design, and avoids adverse effects such as toxic elements such as neurotoxicity caused by Al element in the Mg-Al alloy, and has good biocompatibility.

(3) After the magnesium alloy of the present invention is deformed by extrusion or rolling, compressive stress is formed on the subsurface layer to further reduce the corrosion degradation rate, thereby facilitating the extension of the service life.

(4) The magnesium alloy of the invention has good comprehensive mechanical properties, uniform corrosion resistance and biocompatibility, and the comprehensive performance is superior to WE43. Can be widely used in bone plants, such as bone plates, bone nails, bone tissue engineering stents.

The typical as-cast microstructure of the Mg-Nd-Zn-Ag-Zr alloy is composed of an alpha-Mg matrix and a skeletal Mg12Nd second phase distributed along the grain boundary. See Figure 1. After hot extrusion deformation, the alloy structure is remarkably refined, and a large number of nano-sized Mg12Nd particles are precipitated in the crystal. The typical extrusion deformation microstructure is shown in Fig. 2. According to the requirements of material properties of different internal plants, different thermal processing and heat treatment processes can be used within a certain composition range to control the mechanical properties of the material. If different distribution ratios and different hot extrusion processes and heat treatment processes are used, the mechanical properties of the material can be varied within the following ranges: tensile yield strength: 188-373 MPa, tensile elongation 8-24%, see Table 1. At Hank’s Corrosion rate in simulated body fluid is 0.32~0.5 Mm/year, at the same time, the corrosion mode of the material of the invention in the simulated body fluid is uniform corrosion (see Fig. 3), which satisfies the requirements of the internal implant material for corrosion degradation performance. Moreover, the alloy material has no obvious cytotoxicity and good biocompatibility, and can meet the requirements of implant materials in vivo.

DRAWINGS

Figure 1 is a typical as-cast microstructure of Mg-Nd-Zn-Ag-Zr magnesium alloy, in which: (a) and its phase composition X-ray diffraction XRD pattern.

Fig. 2 is a typical microstructure of Mg-Nd-Zn-Ag-Zr magnesium alloy after extrusion deformation at an extrusion ratio of 5-20 at 350 ° C, in which: (a) is the microscopic direction of extrusion The structure, (b) is a TEM photograph of Mg12Nd particles precipitated inside the grains after extrusion and diffraction spots (c), (d) thereof.

Figure 3 is a SEM image of the corrosion surface morphology of the Mg-Nd-Zn-Ag-Zr magnesium alloy after immersion in Hank's simulated body fluid for 10 days, in which: (a) corrosion surface morphology; (b) Cross-sectional morphology of vertically corroded surfaces

detailed description

The embodiments of the present invention are described in detail below. The present embodiment is implemented on the premise of the technical solution of the present invention, and detailed implementation manners and specific operation procedures are given, but the scope of protection of the present invention is not limited to the following implementation. example.

Example 1:

Preparation of Mg-Nd-Zn-Ag magnesium alloy ingot by semi-continuous casting (phi-105×4500 Mm), wherein the alloying elements are 1.5% Nd, 2.0% Zn, 1.0% Ag, and the balance is magnesium. The purity of magnesium in the raw material is 99.99%, and the purity of Zn is 99.999%. The purity of silver is 99.99%. The addition of Nd was added in the form of a Mg-30% Nd master alloy. Intercept a certain length of ingot, after 540 °C, 10 h solution treatment and then extruded into 20 The round rod of mm has an extrusion temperature of 400 ° C and an extrusion ratio of 5-20. The mechanical properties obtained under this process are: tensile strength 288 MPa, yield strength 197 MPa, elongation at 14%, hardness Hv 70. The material has a corrosion rate of 0.5 in Hank’s simulated body fluid environment. Mm/year. The biological test results show that the material has no obvious cytotoxicity and good biocompatibility. It can be used to prepare intraosseous plants such as bone tissue engineering scaffolds.

Example 2:

Preparation of Mg-Nd-Zn-Ag-Zr magnesium alloy ingot by semi-continuous casting method (phi-105×4500 Mm), wherein the alloying elements are 2.0% Nd, 0.5% Zn, 0.5% Ag, 0.3% Zr, and the balance is magnesium. The purity of magnesium in the raw material is 99.99%, and the purity of Zn is 99.999%. The purity of silver is 99.99%. The addition of Nd and Zr was added in the form of a Mg-30% Nd and Mg-30% Zr binary intermediate alloy, respectively. Intercept a certain length of ingot, after 540 °C, 10 h After solution treatment, it is extruded into a round rod of phi-20 mm, the extrusion temperature is 350 °C, and the extrusion ratio is 5-20. The mechanical properties obtained under this process are: tensile strength 239 MPa, yield strength 188 MPa, elongation is 24%, hardness is Hv 68. The material has a corrosion rate of 0.45 in Hank’s simulated body fluid environment. Mm/year. The biological test results show that the material has no obvious cytotoxicity and good biocompatibility. Can be used as a plant material in bone.

Example 3:

Preparation of Mg-Nd-Zn-Ag-Zr magnesium alloy ingot by semi-continuous casting method (phi-105×4500 Mm), wherein the alloying elements are 2.5% Nd, 0.2% Zn, 0.3% Ag, 0.5% Zr, and the balance is magnesium. The purity of magnesium in the raw material is 99.99%, and the purity of Zn is 99.999%. The purity of silver is 99.99%. The addition of Nd and Zr was added in the form of a Mg-30% Nd and Mg-30% Zr binary intermediate alloy, respectively. Intercept a certain length of ingot, after 540 °C, 10 h After solution treatment, it is extruded into a round rod of phi-20 mm, the extrusion temperature is 350 °C, and the extrusion ratio is 5-20. Then aging treatment, aging process is 200 °C, insulation 10 h. The mechanical properties of the magnesium alloy obtained under this process are: tensile strength 292 MPa, yield strength 257 MPa, elongation 16%, hardness Hv 69. The material has a corrosion rate of 0.40 in Hank’s simulated body fluid environment. Mm / year, the corrosion mode is uniform corrosion. The biological test results show that the material has no obvious cytotoxicity and good biocompatibility. Can be used as an orthopedic plant material.

Example 4:

Preparation of Mg-Nd-Zn-Ag-Zr magnesium alloy ingot by semi-continuous casting method (phi-105×4500 Mm), wherein the alloying elements are 3.0% Nd, 0.2% Zn, 0.01% Ag, 0.5% Zr, and the balance is magnesium. The purity of magnesium in the raw material was 99.99%, the purity of Zn was 99.999%, and the purity of silver was 99.99%. The addition of Nd and Zr was added in the form of a Mg-30% Nd and Mg-30% Zr binary intermediate alloy, respectively. Intercept a certain length of ingot, through 540 °C, 4 h solution treatment and extrusion into a phi-20 mm round bar, the extrusion temperature is 300 °C, the extrusion ratio is 5-20. The mechanical properties of the magnesium alloy obtainable under this process are tensile strength 332. MPa, yield strength is 326 MPa, elongation is 11%, and hardness is Hv 70. Corrosion rate in Hank’s simulated body fluid environment is 0.32 Mm/year, the corrosion mode is uniform corrosion. At Hank’s A cross-sectional view of the corroded surface and its vertical corrosion surface after the corrosion product was removed after 10 days of immersion in the simulated body fluid is shown in FIG. The biological test results show that the material has no obvious cytotoxicity and good biocompatibility. It can meet the performance requirements of plant materials in orthopedics.

Example 5:

Preparation of Mg-Nd-Zn-Ag-Zr magnesium alloy ingot by semi-continuous casting method (phi-105×4500 Mm), wherein the alloying elements are 3.5% Nd, 0.2% Zn, 0.4% Ag, 0.6% Zr, and the balance is magnesium. The purity of magnesium in the raw material was 99.99%, the purity of Zn was 99.999%, and the purity of silver was 99.99%. The addition of Nd and Zr was added in the form of a Mg-30% Nd and Mg-30% Zr binary intermediate alloy, respectively. Intercept a certain length of ingot, through 540 °C, 10 h solution treatment, extruded into a phi-20 mm round bar, extrusion temperature is 250 °C, extrusion ratio is 5-20, and then aging treatment, aging process is 200 °C, insulation 10 h. The mechanical properties of the magnesium alloy obtained under this process have a tensile strength of 389 MPa, a yield strength of 373 MPa, an elongation of 9%, and a hardness of Hv. 72. Corrosion rate in Hank’s simulated body fluid environment is 0.40 Mm/year, the corrosion mode is uniform corrosion, biological test results show that the material has no obvious cytotoxicity and good biocompatibility. Can make bone plant material.

Example 6

Preparation of Mg-Nd-Zn-Ag-Zr magnesium alloy ingot by semi-continuous casting method (phi-105×4500 Mm), wherein the alloying elements are 4% Nd, 0.1% Zn, 0.4% Ag, 1.0% Zr, and the balance is magnesium. The purity of magnesium in the raw material was 99.99%, the purity of Zn was 99.999%, and the purity of silver was 99.99%. The addition of Nd and Zr was added in the form of a Mg-30% Nd and Mg-30% Zr binary intermediate alloy, respectively. Intercept a certain length of ingot, through 540 °C, 10 h solution treatment, extruded into a phi-20 mm round bar, the extrusion temperature is 300 °C, the extrusion ratio is 5-20. Then aging treatment, aging process is 225 ° C, insulation 8 h. The mechanical properties of the magnesium alloy obtained under this process are tensile strength of 378 MPa, yield strength of 356 MPa, elongation of 8%, and hardness of Hv. 73. Corrosion rate in Hank’s simulated body fluid environment is 0.48 Mm / year, the corrosion method is uniform corrosion. The biological test results show that the material has no obvious cytotoxicity and good biocompatibility. Can be used to prepare intraosseous implant materials.

Table 1 Chemical composition and mechanical properties of the alloy

 Example  Composition (wt%)  Extrusion temperature ( °C )  Extrusion ratio Tensile strength (MPa)  Yield strength ( MPa )  Elongation rate (%) Hardness ( Hv )  1  Mg-1.5Nd-2Zn-1Ag  400  9  288  197  14  70  2  Mg-2.0Nd-0.5Zn-0.5Ag-0.3Zr  350  9  239  188  twenty four  68  3  Mg-2.5Nd-0.2Zn-0.3Ag-0.5Zr  350  9  292  257  16  69  4  Mg-3.0Nd-0.2Zn-0.01Ag-0.5Zr  300  9  332  326  11  70  5  Mg-3.5Nd-0.2Zn-0.4Ag-0.6Zr  250  9  389  373  9  72  6  Mg-4Nd-0.1Zn-0.4Ag-1.0Zr  300  9  378  356  8  73

Claims (10)

An in vivo degradable magnesium alloy for bone plant, characterized in that its composition and weight percentage are: Nd 1.5~4%, Zn 0.1~2%, Ag 0.01~1%, Zr 0~1.0%, impurity 0~0.2%, and the rest is Mg. The in vivo degradable magnesium alloy for bone plant according to claim 1, wherein the composition and weight percentage are Nd 2.5 to 3.5%, Zn 0.1~0.5%, Ag 0.01~0.4%, Zr 0.3~0.6%, and the rest is Mg. The in vivo degradable magnesium alloy for bone plant according to claim 1, wherein the impurity is Fe, Ni, Cu, Al or Si or a combination thereof. A method for preparing an in vivo degradable magnesium alloy for bone plant according to any of the preceding claims, characterized in that the ingot is obtained by smelting the raw material metal under a protective atmosphere, and the magnesium alloy rod is obtained by extrusion. material. The preparation method according to claim 4, wherein the protective atmosphere means a protective atmosphere composed of a mixed gas of CO ₂ and SF ₆ . The preparation method according to claim 4, wherein the raw material metal is composed of a magnesium block having a purity of 99.99% by weight, a zinc block having a purity of 99.999% by weight, a silver block having a purity of 99.99% by weight, and a magnesium-30. Composition of % niobium alloy and magnesium-30% zirconium alloy. The production method according to claim 4, wherein the smelting is performed by melting at 700 to 760 ° C in an electric resistance furnace. The preparation method according to claim 4, wherein said pressing means pressing at an extrusion ratio of 5 to 20 in an environment of 250 to 400 °C. Use of an in vivo degradable magnesium alloy for intraosseous plants according to any of the preceding claims, characterized in that it is used for the preparation of an intraosseous implant. The use of claim 9 wherein said intraosseous implant comprises: a bone plate, a bone nail, and a bone tissue engineering scaffold.

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