Degradable and absorbable magnesium biological internal fixation implant material and preparation method thereof

Abstract

The invention discloses a degradable magnesium-absorbing biological internal fixation implant material and a preparation method thereof, and belongs to the technical field of medical implant materials. The degradable magnesium-absorbing biological internal fixation implant material comprises the following materials: 0.2-3.0 wt.% of Mn; wt.% of Zn: 0.2 to 1.0 wt.%; wt.% of Ca: 0.2 to 0.5 wt.%; and the balance of magnesium and inevitable impurity elements. The Mg-Mn-Zn-Ca magnesium alloy biological material prepared by the scheme is a novel high-performance, low-cost, biodegradable and absorbable bio-friendly cast magnesium alloy biological material and wrought magnesium alloy biological material which do not contain rare earth elements and toxic and harmful elements, and the used raw materials are non-toxic and harmless medical-grade high-purity metals necessary for human bodies; the novel magnesium alloy biological implant material with better mechanical property, biological corrosion and degradation resistance, biocompatibility and bone regeneration capacity is prepared by adopting a fusion casting process and a plastic processing process technology; the mechanical property, the biological corrosion resistance and the biological property of the material are superior to those of a high-purity magnesium medical metal implant material authenticated by the State Market Supervision and Management Administration.

Description

Technical Field

[0001] The invention relates to the technical field of medical implant materials, and in particular to a biodegradable magnesium-absorbing internal fixation implant material and a preparation method thereof. Background Art

[0002] Every year, tens of millions of patients in my country suffer from soft and hard tissue injuries or functional disorders due to natural disasters, diseases, traffic accidents and accidental falls, and a large amount of bone tissue repair materials are required in their treatment process. Therefore, the development of a new type of degradable, high-performance metal implant internal fixation biomaterial with excellent biocompatibility and induction of cell proliferation and osteogenesis has become a hot topic and focus of research in the fields of materials science, biomedicine, clinical medicine, etc. At present, the metal materials used for bone tissue repair in clinical practice are mainly 316L stainless steel, titanium and titanium alloy implant materials. Among them, metal biomaterials such as 316L stainless steel, titanium and titanium alloy have very excellent in vitro mechanical properties, biocorrosion resistance and good biological properties. Despite this, the high elastic modulus of metal biomaterials such as 316L stainless steel, titanium and titanium alloy used in clinical practice can easily lead to secondary fractures after the new bone tissue heals, which is not conducive to the repair of damaged bone tissue and defective and missing tooth hard tissue. In addition, the excellent biocorrosion resistance of the above-mentioned metal biomaterials causes the damaged bone tissue to be removed through a secondary operation after healing, which poses an infection risk and also causes psychological and economic burdens to patients. Therefore, the development of a new type of degradable metal biomaterial has become a research hotspot and focus in the fields of materials science, biomedicine, clinical medicine, and oral medicine.

[0003] Magnesium and magnesium alloy biomaterials have gradually become a research hotspot in the field of metal implant internal fixation materials due to their mechanical properties close to those of the human body, good biodegradability, excellent biocompatibility, and biological properties such as inducing cell proliferation and osteogenesis. Currently, only high-purity magnesium and magnesium-calcium-zinc (Mg-Ca-Zn) bone repair materials have obtained clinical certification in relevant countries. Therefore, it is urgent to develop new high-performance, low-cost, biodegradable and absorbable magnesium alloy metal implant materials. Summary of the invention

[0004] The present invention aims to provide a novel high-performance, low-cost, low-elastic modulus biodegradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial.

[0005] In order to solve the above technical problems, the present invention provides the following technical solutions: a biodegradable and magnesium-absorbing biological internal fixation implant material, comprising the following materials according to components:

[0006] Mn: 0.2-3.0 wt.%;

[0007] Zn: 0.2-1.0wt.%;

[0008] Ca: 0.2-0.5wt.%;

[0009] The balance is magnesium and inevitable impurity elements.

[0010] A method for preparing a biodegradable and absorbable magnesium internal fixation implant material comprises the following steps:

[0011] S1, material preparation: raw materials are prepared according to the material components, and Mg is smelted at 670-750°C under the protection of high-purity argon or a mixed gas of carbon dioxide and sulfur hexafluoride or a covering agent. After all the Mg is melted and the temperature rises to 750°C and stabilizes, high-purity zinc and Mg-Mn master alloy and Mg-Ca master alloy preheated to 150°C are added successively, and a refining agent is used to fully stir for 3-6 minutes, and the melt is allowed to stand at 750°C for 20-30 minutes to remove the scum on the surface of the melt, and the molten metal liquid is poured into a mold preheated to 200-350°C at 750°C, and the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained after cooling;

[0012] S2, homogenization treatment: the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in step S1 is covered with high-purity graphite powder, homogenized at 300-550° C. for 12-24 hours, and cooled to obtain a homogenized Mg-Mn-Zn-Ca magnesium alloy biomaterial;

[0013] S3, preparation of deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material: remove the surface oxide scale of the Mg-Mn-Zn-Ca magnesium biological internal fixation implant material after homogenization treatment obtained in step S2, preheat it at 150°C to 450°C for 1 to 2 hours, and perform thermoplastic deformation (key parameters of plastic deformation: plastic deformation ratio: (10 to 30): 1; plastic deformation speed: 0.05 to 2.0 m / min; plastic deformation temperature: 150 to 500°C) on the above Mg-Mn-Zn-Ca magnesium alloy biomaterial in a sterile environment to obtain a new high-performance, low-cost, degradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial.

[0014] Furthermore, the material composition includes: Mn: 1.0 wt.%, Zn: 0.5 wt.%, Ca: 0.3 wt.%, and the balance is magnesium and inevitable impurity elements.

[0015] Furthermore, the Mg is selected from medical grade high purity Mg, the Zn is selected from medical grade high purity Zn, the Mg-Mn master alloy is selected from medical grade high purity Mg-Mn master alloy, and the Mg-Ca master alloy is selected from medical grade high purity Mg-Ca master alloy.

[0016] Further, the covering agent in step S1 comprises: MgCl2 24~30%, KCl 20~26%, CaF2: 13~15%, BaCl 2 :12~16%,NaCl+CaCl 2 <8%, insoluble matter <1.5%, MgO <1.5%, water content <2%.

[0017] Furthermore, the refining agent in step S1 is hexachloroethane or argon.

[0018] Furthermore, when cooling is performed in step S2, cooling is performed in air, water or an ice-water mixture.

[0019] Beneficial effects of the present invention:

[0020] 1. The Mg-Mn-Zn-Ca magnesium alloy biomaterial prepared in this scheme is a new type of high-performance, low-cost, biodegradable and absorbable bio-friendly cast magnesium alloy biomaterial and deformable magnesium alloy biomaterial that does not contain rare earth elements and toxic and harmful elements. The raw materials used are all non-toxic and harmless medical-grade high-purity metals that are essential to the human body. The melting and casting process and plastic processing technology are used to prepare a new type of magnesium alloy bio-implant material with good mechanical properties, biocorrosion and degradation resistance, biocompatibility and bone regeneration ability. Its mechanical properties, biocorrosion resistance and biological properties are better than those of the high-purity magnesium medical metal implant materials certified by the State Administration for Market Regulation.

[0021] 2. After being implanted into the human body, the Mg-Mn-Zn-Ca magnesium alloy biomaterial prepared by this scheme interacts with biological media such as blood, saliva, body fluids, cells, proteins, enzymes, etc. in the human body, and has relatively excellent resistance to biocorrosion and degradation and mechanical stability, and can stably construct a physical space for in situ regeneration of damaged bone tissue. At the same time, the slowly released metal ions such as Mg, Mn, Zn, Ca, etc. with good biocompatibility can stimulate the biological functions of cells such as macrophages, osteoprogenitor cells, and mesenchymal stem cells, promote the deposition of calcium ions and the biomineralization of the extracellular matrix, and achieve in situ regeneration and repair of damaged bone tissue.

[0022] 3. The preparation and processing technology of the implant material in this scheme is simple to operate, the process parameters are easy to control, and it is suitable for industrial large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 A comparison chart of the mechanical stability and biodegradation resistance of a biodegradable and absorbable magnesium internal fixation implant material of the present invention and Mg;

[0024] Figure 2 A comparison diagram of the cell behavior of a biodegradable and magnesium-absorbing internal fixation implant material of the present invention and Mg;

[0025] Figure 3 A comparison diagram of a biodegradable and magnesium-absorbing internal fixation implant material of the present invention and a bone-related marker of Mg;

[0026] Figure 4 A biodegradable and absorbing magnesium internal fixation implant material of the present invention and a diagram showing the promotion of in situ regeneration of damaged bone tissue after Mg was implanted into SD rats;

[0027] Figure 5 The figure is a comparison chart of the compatibility of the biodegradable and magnesium-absorbing internal fixation implant material of the present invention with Mg to the tissues of the main organs of the heart, liver, spleen, lungs and kidneys. DETAILED DESCRIPTION

[0028] The following is further described in detail through specific implementation methods:

[0029] Example 1

[0030] A biodegradable and absorbable magnesium internal fixation implant material, comprising the following materials:

[0031] Mn: 0.2 wt. %; Zn: 0.2 wt. %; Ca: 0.2 wt. %; the balance being magnesium and inevitable impurity elements.

[0032] A method for preparing a biodegradable and absorbable magnesium internal fixation implant material comprises the following steps:

[0033] S1, material preparation: raw materials are prepared according to the material components, and medical-grade high-purity Mg is smelted at 670°C under the protection of high-purity argon or a mixed gas of carbon dioxide and sulfur hexafluoride or a covering agent. After all the Mg is melted and the temperature rises to 750°C and stabilizes, medical-grade high-purity Zn and medical-grade high-purity Mg-Mn master alloy and medical-grade high-purity Mg-Ca master alloy preheated to 150°C are added successively, and the refining agent hexachloroethane or argon is used to fully stir for 3 minutes, and the melt is allowed to stand at 750°C for 20 minutes to remove the scum on the surface of the melt, and the molten metal liquid is poured into a 304 stainless steel mold preheated to 200°C at 750°C, and the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained after cooling;

[0034] S2, homogenization treatment: the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in step S1 is covered with high-purity graphite powder, homogenized at 300° C. for 24 hours, and cooled in air, water or an ice-water mixture to obtain a homogenized Mg-Mn-Zn-Ca magnesium alloy biomaterial;

[0035] S3, preparation of deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material: remove the surface oxide scale of the Mg-Mn-Zn-Ca magnesium biological internal fixation implant material obtained after homogenization treatment in step S2, preheat it at 150°C for 1 hour, and extrude it under sterile environment at an extrusion ratio of 10:1, an extrusion speed of 0.05m / min, and an extrusion temperature of 150°C to obtain the deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material.

[0036] Example 2

[0037] A biodegradable and absorbable magnesium internal fixation implant material, comprising the following materials:

[0038] Mn: 1.0 wt. %; Zn: 0.5 wt. %; Ca: 0.3 wt. %; the balance being magnesium and inevitable impurity elements.

[0039] A method for preparing a biodegradable and absorbable magnesium internal fixation implant material comprises the following steps:

[0040] S1, material preparation: raw materials are prepared according to the material components, and medical-grade high-purity Mg is smelted at 710°C under the protection of high-purity argon or a mixed gas of carbon dioxide and sulfur hexafluoride or a covering agent. After all the Mg is melted and the temperature rises to 750°C and stabilizes, medical-grade high-purity Zn and medical-grade high-purity Mg-Mn master alloy and medical-grade high-purity Mg-Ca master alloy preheated to 150°C are added successively, and the refining agent hexachloroethane or argon is used to fully stir for 6 minutes, and the melt is allowed to stand at 750°C for 25 minutes to remove the scum on the surface of the melt, and the molten metal liquid is poured into a 304 stainless steel mold preheated to 280°C at a temperature of 750°C, and the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained after cooling;

[0041] S2, homogenization treatment: the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in step S1 is covered with high-purity graphite powder, homogenized at 480° C. for 18 hours, and cooled in air, water or an ice-water mixture to obtain a homogenized Mg-Mn-Zn-Ca magnesium alloy biomaterial;

[0042] S3, preparation of deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material: remove the surface oxide scale of the Mg-Mn-Zn-Ca magnesium biological internal fixation implant material obtained after homogenization treatment in step S2, preheat it at 350°C for 1.5 hours, and perform thermoplastic deformation processes such as extrusion, rolling, and forging on the above Mg-Mn-Zn-Ca magnesium alloy biomaterial at 150°C in a sterile environment; plastic deformation ratio: 10:1; plastic deformation speed: 0.05m / min, to obtain a new high-performance, low-cost, degradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial.

[0043] The prepared magnesium alloy biomaterial has a yield strength of 200 MPa, a tensile strength of 260 MPa, an elongation of 25%, and a biocorrosion rate of 0.02 mm / y in SBF solution.

[0044] The prepared magnesium alloy biomaterial can significantly promote the proliferation, migration, adhesion, etc. of cells such as macrophages, osteoprogenitor cells, and mesenchymal stem cells, and is beneficial to the relative expression of osteogenesis-related gene mRNA such as ALP, OCN, RUNX2, and OPG, promotes calcium ion deposition, realizes the biomineralization of the extracellular matrix, is beneficial to the regeneration of new bone tissue, and realizes the in situ regeneration and repair of damaged bone tissue. Compared with pure magnesium bioimplant materials, it has more excellent bone formation performance.

[0045] Example 3

[0046] A biodegradable and absorbable magnesium internal fixation implant material, comprising the following materials:

[0047] Mn: 3.0 wt. %; Zn: 1.0 wt. %; Ca: 0.5 wt. %; the balance being magnesium and inevitable impurity elements.

[0048] A method for preparing a biodegradable and absorbable magnesium internal fixation implant material comprises the following steps:

[0049] S1, material preparation: raw materials are prepared according to the material components, and medical-grade high-purity Mg is smelted at 750°C under the protection of high-purity argon or a mixed gas of carbon dioxide and sulfur hexafluoride or a covering agent. After all the Mg is melted and the temperature is kept stable at 750°C, medical-grade high-purity Zn and medical-grade high-purity Mg-Mn master alloy and medical-grade high-purity Mg-Ca master alloy preheated to 150°C are added successively, and the refining agent hexachloroethane or argon is used to fully stir for 6 minutes, and the melt is allowed to stand at 750°C for 30 minutes to remove the scum on the surface of the melt, and the molten metal liquid is poured into a 304 stainless steel mold preheated to 350°C at a temperature of 750°C, and the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained after cooling;

[0050] S2, homogenization treatment: the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in step S1 is covered with high-purity graphite powder, homogenized at 550° C. for 12 hours, and cooled in air, water or an ice-water mixture to obtain a homogenized Mg-Mn-Zn-Ca magnesium alloy biomaterial;

[0051] S3, preparation of deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material: remove the surface oxide scale of the Mg-Mn-Zn-Ca magnesium biological internal fixation implant material obtained after homogenization treatment in step S2, preheat it at 500°C for 2 hours, and perform thermoplastic deformation processes such as extrusion, rolling, forging, etc. on the above Mg-Mn-Zn-Ca magnesium alloy biomaterial at 300°C in a sterile environment. The plastic deformation ratio is 20:1; the plastic deformation speed is 1.0 m / min, and a new high-performance, low-cost, degradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained.

[0052] The prepared magnesium alloy biomaterial has a yield strength of 260 MPa, a tensile strength of 300 MPa, an elongation of 18%, and a biocorrosion rate of 0.015 mm / y in SBF solution;

[0053] The prepared magnesium alloy biomaterial can significantly promote the proliferation, migration, adhesion, etc. of cells such as macrophages, osteoprogenitor cells, and mesenchymal stem cells, and is beneficial to the relative expression of osteogenesis-related gene mRNA such as ALP, OCN, RUNX2, and OPG, promotes calcium ion deposition, realizes the biomineralization of the extracellular matrix, is beneficial to the regeneration of new bone tissue, and realizes the in situ regeneration and repair of damaged bone tissue. Compared with pure magnesium bioimplant materials, it has more excellent bone formation performance.

[0054] As attached Figure 1 ~Attached Figure 5 As shown in FIG. 1 , compared with the degradable pure magnesium bone nails certified by the State Administration for Market Regulation and the European Union (CE), the high-performance, low-cost, degradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in the embodiment of the present invention has more excellent mechanical stability and bio-corrosion and degradation resistance (see Appendix 1). Figure 1 At the same time, in vitro cell biology studies have confirmed that the magnesium alloy biomaterial has good biocompatibility, can significantly promote the proliferation, migration, adhesion and calcium deposition of cells such as bone marrow mesenchymal stem cells, stimulate the relative expression of ALP, OCN, RUNX2, OPG and other osteogenic related gene mRNA, achieve biomineralization of the extracellular matrix, and then promote the in situ regeneration of new bone tissue (see Appendix Figure 2 and attached Figure 3 Animal in vivo experiments showed that the magnesium alloy biomaterial implanted in SD rats can significantly promote the in situ regeneration of damaged bone tissue (see Appendix Figure 4), and had no obvious toxicity to the heart, liver, spleen, lungs, kidneys and other major organs, indicating that the implant material has good tissue compatibility (see Appendix Figure 5 ), is an ideal medical metal implant material.

Claims

1. A biodegradable and absorbable magnesium biological internal fixation implant material and a preparation method thereof, characterized in that: The components include the following materials: Mn: 0.2-3.0 wt.%; Zn: 0.2-1.0wt.%; Ca: 0.2-0.5wt.%; The balance is magnesium and inevitable impurity elements.

2. The method for preparing a biodegradable and absorbable magnesium biological internal fixation implant material according to claim 1, characterized in that: The following steps are involved: S1, material preparation: raw materials are prepared according to the material components, and Mg is smelted at 670-750°C under the protection of high-purity argon or a mixed gas of carbon dioxide and sulfur hexafluoride or a covering agent. After all the Mg is melted and the temperature rises to 750°C and stabilizes, high-purity zinc and Mg-Mn master alloy and Mg-Ca master alloy preheated to 150°C are added successively, and a refining agent is used to fully stir for 3-6 minutes, and the melt is allowed to stand at 750°C for 20-30 minutes to remove the scum on the surface of the melt, and the molten metal liquid is poured into a mold preheated to 200-350°C at 750°C, and the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial is obtained after cooling; S2, homogenization treatment: the cast Mg-Mn-Zn-Ca magnesium alloy biomaterial obtained in step S1 is covered with high-purity graphite powder, homogenized at 300-550° C. for 12-24 hours, and cooled to obtain a homogenized Mg-Mn-Zn-Ca magnesium alloy biomaterial; S3, preparation of deformed Mg-Mn-Zn-Ca magnesium biological internal fixation implant material: remove the surface oxide scale of the Mg-Mn-Zn-Ca magnesium biological internal fixation implant material after homogenization treatment obtained in step S2, preheat it at 150°C to 450°C for 1 to 2 hours, and perform thermoplastic deformation (key parameters of plastic deformation: plastic deformation ratio: (10 to 30): 1; plastic deformation speed: 0.05 to 2.0 m / min; plastic deformation temperature: 150 to 500°C) on the above Mg-Mn-Zn-Ca magnesium alloy biomaterial in a sterile environment to obtain a new high-performance, low-cost, degradable and absorbable Mg-Mn-Zn-Ca magnesium alloy biomaterial.

3. The biodegradable and absorbable magnesium biological internal fixation implant material according to claim 2, characterized in that: The material components include: Mn: 1.0wt.%, Zn: 0.5wt.%, Ca: 0.3wt.%, and the balance is magnesium and inevitable impurity elements.

4. The method for preparing a biodegradable and absorbable magnesium biological internal fixation implant material according to claim 3, characterized in that: The Mg is selected from medical grade high purity Mg, the Zn is selected from medical grade high purity Zn, the Mg-Mn master alloy is selected from medical grade high purity Mg-Mn master alloy, and the Mg-Ca master alloy is selected from medical grade high purity Mg-Ca master alloy.

5. The method for preparing a biodegradable and absorbable magnesium biological internal fixation implant material according to claim 4, characterized in that: The covering agent in step S1 includes the following components: MgCl2 24-30%, KCl 20-26%, CaF2: 13-15%, BaCl2: 12-16%, NaCl+CaCl2<8%, insoluble matter<1.5%, MgO<1.5%, and water content<2%.

6. The method for preparing a biodegradable and absorbable magnesium biological internal fixation implant material according to claim 5, characterized in that: The refining agent in step S1 is hexachloroethane or argon.

7. The method for preparing a biodegradable and absorbable magnesium biological internal fixation implant material according to claim 6, characterized in that: When cooling is performed in step S2, cooling is performed in air, water or an ice-water mixture.

Images