Preparation method of a degradable zinc-calcium compound composite material

Abstract

The present invention relates to a preparation method of a degradable zinc-calcium compound composite material. In this preparation method, pure zinc melt is pressed into the gaps between stacked zinc-calcium compound CaZn2 particles with a high calcium content. The calcium element on the surface layer of the CaZn2 particles diffuses into the zinc melt under the action of the high temperature of the zinc melt and reacts with zinc to form a zinc-calcium compound CaZn with a low calcium content 13 etc., to obtain a composite material composed entirely of zinc-calcium compounds. In the preparation process of the present invention, high pressure (50 MPa) is not required, and explosive-prone materials such as zinc powder are not used. The obtained composite material exhibits excellent ability to induce the deposition of Ca and P elements and excellent cell viability against L-929 cells.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of degradable biomedical metal implant materials, and particularly relates to a preparation method of a degradable zinc-calcium compound composite material. Background Art

[0002] In the field of degradable biomedical metal implant materials, the standard electrode potential of metallic zinc is -0.762V SHE , higher than that of magnesium (-2.372V) SHE and lower than that of iron (-0.44V). SHE This makes metallic zinc have weaker chemical activity than magnesium and stronger chemical activity than iron. Additionally, the density coefficient α of ZnO ZnO is 1.585, higher than 0.779 of MgO and lower than 1.778 of FeO. These factors make metallic zinc have a degradation rate slower than that of magnesium and faster than that of iron when used as a degradable metal implant material, and thus is more suitable to be used as a degradable material for temporary orthopedic implants. In addition, zinc is also an essential trace element for the human body. Many physiological functions of the human body, such as normal growth, wound healing, DNA and protein synthesis, immune function, cell and nucleic acid metabolism, etc., all require the participation of zinc. Zinc can also promote the adhesion and proliferation of osteoblasts, stimulate bone formation, growth and mineralization, and inhibit bone resorption. In view of this, zinc-based materials have greater advantages than magnesium-based and iron-based materials when used as degradable metal implant materials. Many zinc-based alloys, such as Zn-Mg, Zn-Ca, Zn-Sr, Zn-Mg-Ca, Zn-Mg-Sr, Zn-Ca-Sr, etc., have been developed and their related properties have been studied.

[0003] However, when zinc-based materials are used as orthopedic degradable metal implant materials, the degradation rate is still relatively slow, resulting in their long-term retention in the body after completing their mission. At the same time, the excessive zinc ions released during the degradation process of zinc-based materials will also cause serious cytotoxicity in vitro and delay bone integration in vivo, thereby leading to implant failure. Therefore, improving the degradation rate of zinc-based implant materials while reducing the dissolution amount of zinc ions during the degradation process of implant materials has become an urgent problem to be solved before the clinical application of degradable zinc-based implant materials.

[0004] To solve the above problems, introducing a material with a more negative electrode potential than zinc as a sacrificial anode in the zinc matrix is a feasible method. For this purpose, Literature 1 (Hongtao Yang, Xinhua Qu, Wenjiao Lin, et al. Enhanced osseointegration of Zn-Mg composites by tuning the release of Zn ions with sacrificial Mg-rich anode design. ACS Biomaterials Science & Engineering, 2019, 5: 453-467.) prepared Zn-xMg (x = 1, 2, 5 wt.%) composites using pure zinc powder and pure magnesium powder as raw materials by spark plasma sintering method. Zinc-magnesium compound particles that can be used as sacrificial anodes are distributed in the composite material. Although the degradation rate of this composite material is higher than that of pure zinc and it has better cell activity than pure zinc, both the pure zinc powder and pure magnesium powder used in the preparation process of this composite material are explosives, and a high pressure of 50 MPa (about 500 atm) is used in the preparation process. These factors all make the preparation process of this composite material very dangerous. In addition, since the electrode potential of metallic Ca is -2.87 V SHE , which is more negative than that of magnesium (-2.372 V) SHELower. Therefore, when zinc-calcium compounds are used as sacrificial anodes, they should have better performance than zinc-magnesium compounds. For this reason, in Document 2 (Li HF, Xie XH, Zheng YF, et al. Development of biodegradable Zn-1X binary alloys with nutrient alloying elements Mg, Ca and Sr. Scientific Reports, 2015, 5: 10719.), pure zinc ingots and pure calcium ingots were used as raw materials, and a rolled Zn-1Ca alloy containing zinc-calcium compounds was prepared by the method of casting heating and rolling. In Document 3 (Zou Yanlong, Chen Xia, Chen Bin. Effects of Ca concentration on degradation behavior of Zn-xCa alloys in Hank’s solution. Materials Letters, 2018, 218: 193-196.), pure zinc and pure calcium were used as raw materials, and Zn-xCa (x = 0.5, 1, 2, 3 wt.%) alloys containing zinc-calcium compounds were prepared by an electromagnetic induction furnace. However, when preparing Zn-Ca alloys by the melting and casting method, with the increase of Ca content, the viscosity of the alloy melt increases significantly, resulting in the inability to cast the alloy melt into a mold. Therefore, the Zn-Ca alloys prepared by the methods of Document 2 and Document 3 only contain zinc-calcium compounds CaZn with low calcium content 13 , and high-calcium-content zinc-calcium compounds CaZn2 cannot be obtained, which will significantly affect the performance of zinc-calcium compounds when used as sacrificial anodes. In addition, whether it is the Zn-xMg composite material prepared in Document 1 or the Zn-Ca alloys prepared in Documents 2 and 3, in these materials, in addition to the zinc-magnesium compounds and zinc-calcium compounds that act as sacrificial anodes, the protected cathode is zinc. Although the cathode zinc is protected by the anode, the cathode zinc will also undergo a degradation reaction in the corrosive solution, resulting in an increase in the dissolved zinc ions, which in turn affects the cell activity of the material. Summary of the Invention

[0005] The object of the present invention is to provide a preparation method of a composite material completely composed of zinc-calcium compounds for the above problems. In this preparation method, pure zinc melt is pressed into the gaps between the stacked CaZn2 particles with high calcium content. The calcium element on the surface layer of the CaZn2 particles diffuses into the zinc melt under the action of the high temperature of the zinc melt and reacts with zinc to generate zinc-calcium compounds CaZn with low calcium content 13Et cetera, a composite material composed entirely of zinc-calcium compounds is obtained. In the preparation process of the present invention, high pressure (50 MPa) is not required, and explosive precursors such as zinc powder are not used. The obtained composite material exhibits excellent ability to induce the deposition of Ca and P elements and excellent cell viability against L-929 cells.

[0006] The present invention is achieved through the following technical solutions:

[0007] A method for preparing a degradable zinc-calcium compound composite material, the method comprising the following steps:

[0008] The first step is to prepare zinc-calcium compound CaZn2 powder with a high calcium content:

[0009] (1) Lay a layer of pure zinc blocks at the bottom of a graphite-clay crucible, place calcium grains on top of the zinc blocks, and continue to lay the remaining zinc blocks on top of the calcium grains; after placing the crucible containing the calcium grains and zinc blocks into a vacuum high-frequency melting and casting furnace, evacuate the furnace body, and then start heating and melting under an argon atmosphere; after melting for 30 seconds to 1 minute within the heating and melting temperature range, stop heating and cool down to room temperature with the furnace, obtaining a zinc-calcium compound ingot;

[0010] (2) Smash and grind the obtained zinc-calcium compound ingot to obtain 100-200 mesh CaZn2 zinc-calcium compound powder;

[0011] Among them, the atomic ratio of calcium grains to zinc blocks is 1:2;

[0012] The purity of the calcium grains is ≥99.0%, and the purity of the zinc blocks is ≥99.995%.

[0013] The evacuation is 1.0×10 -3 Pa to 8.0×10 -3 Pa, and in the argon atmosphere, the argon pressure is 0.05-0.06 MPa.

[0014] The melting temperature is 750-860 °C.

[0015] The grinding is performed using a ball mill or ground fine through a ceramic mortar;

[0016] The second step is to prepare a degradable zinc-calcium compound composite material:

[0017] (1) Pour the zinc-calcium compound powder obtained in the previous step into a steel infiltration mold and compact it; then place the mold into a crucible resistance heating furnace and heat it to 390-410 °C and hold for 1-2 hours; while the mold is being heated and held, place a pure zinc ingot into a graphite-clay crucible and heat the crucible to 555-575 °C, and hold for 20 minutes to 1 hour after the zinc ingot melts;

[0018] Among them, the mass of zinc is 2 - 2.5 times the mass of the zinc-calcium compound powder;

[0019] (2) After the steel mold containing the zinc-calcium compound powder and the crucible containing the zinc melt are finished with heat preservation, pour the zinc melt into the steel infiltration mold; immediately cover the upper cover of the steel mold, and introduce compressed gas at 0.3 - 0.4 MPa into the mold for pressure infiltration for 1 - 5 minutes;

[0020] After the infiltration is completed, wait for the mold to cool and then take out the sample to obtain the zinc-calcium compound composite material.

[0021] The compressed gas described is compressed air, compressed argon or compressed nitrogen.

[0022] The application of the degradable zinc-calcium compound composite material obtained by the method is used for orthopedic implant materials for temporary implantation in the body.

[0023] The application range of the orthopedic implant material is the repair and replacement of damaged bone tissues that require implant materials not to cause obvious cytotoxicity.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] Using the method of the present invention, a composite material completely composed of zinc-calcium compounds can be prepared, and in the preparation process of the composite material, high pressure (50 MPa) used in the preparation of Zn-xMg composite materials in Document 1 is not required, and explosive precursors such as zinc powder are not used. This composite material has a more negative electrode potential and a higher corrosion current density in Hank's solution than pure zinc. During the degradation process, the discontinuous phase CaZn2 in the composite material degrades preferentially as a sacrificial anode, thereby providing cathodic protection to zinc-calcium compounds with low calcium content such as CaZn 13 etc. In addition, after the zinc-calcium compound composite material prepared by the method of the present invention is soaked in Hank's solution for only 5 hours, the surface of the composite material is covered by a corrosion product layer containing Ca and P elements, and the composite material exhibits excellent ability to induce Ca and P element deposition. Moreover, the 100% extract of the zinc-calcium compound composite material prepared by the method of the present invention shows excellent cell viability (cytotoxicity grade is grade 1) to L-929 cells. Description of the Drawings

[0026] Figure 1 Scanning electron microscope photos of the 100 - 200 mesh zinc-calcium compound powder prepared in Example 1 of the present invention; among them, Figure 1 (a) is a low-magnification scanning electron microscope photo of the compound powder; Figure 1 (b) is a high-magnification scanning electron microscope photo of the compound powder;

[0027] Figure 2 X-ray diffraction pattern of the zinc-calcium compound composite material prepared in Example 1 of the present invention;

[0028] Figure 3 Light microscope photograph of the zinc-calcium compound composite material prepared in Example 1 of the present invention; wherein, Figure 3 (a) is the low-magnification light microscope photograph of the composite material; Figure 3 (b) is Figure 3 the high-magnification light microscope photograph of the white dotted rectangle area in (a);

[0029] Figure 4 Polarization curve of the zinc-calcium compound composite material prepared in Example 1 of the present invention measured in Hank's solution at 37 °C;

[0030] Figure 5 Scanning electron microscope photograph of the zinc-calcium compound composite material prepared in Example 1 of the present invention after being immersed in Hank's solution at 37 °C for 5 hours; wherein, Figure 5 (a) is the low-magnification scanning electron microscope photograph; Figure 5 (b) is Figure 5 the high-magnification scanning electron microscope photograph of the white dotted rectangle area in (a); Figure 5 (c) is Figure 5 the EDS spectrum of (b);

[0031] Figure 6 Scanning electron microscope photograph of the zinc-calcium compound composite material prepared in Example 1 of the present invention after being immersed in Hank's solution at 37 °C for 5 hours and removing the corrosion products with chromic acid; wherein, Figure 6 (a) is the low-magnification scanning electron microscope photograph; Figure 6 (b) is the high-magnification scanning electron microscope photograph of the white dotted rectangle area in 6(a); Figure 6 (c) is Figure 6 the high-magnification scanning electron microscope photograph of the white dotted rectangle area in (b);

[0032] Figure 7 Cell viability of L-929 cells after being cultured for 1 day with the extraction solution of the zinc-calcium compound composite material prepared in Example 1 of the present invention at different concentrations; wherein, 100%, 50%, 25%, 12.5% and 6.25% in the figure represent the concentrations of the extraction solution, and positive represents the positive control group. Detailed implementation manners

[0033] The present invention will be described in detail below with reference to the accompanying drawings and specific implementation manners. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

[0034] Example 1

[0035] (1) Preparation of zinc-calcium compound powder

[0036] Weigh 0.688 mol (i.e., 27.5737 g) of calcium grains with a particle size of 0.5 - 3 mm (purity ≥ 99.0%) and 1.376 mol (i.e., 90.0028 g) of zinc blocks with a particle size of 2 - 5 mm (purity ≥ 99.995%) respectively using an electronic balance. First, spread some of the zinc blocks on the bottom of a graphite-clay crucible, then place the calcium grains on top of the zinc blocks, and finally continue to place the remaining zinc blocks on top of the calcium grains. After placing the crucible containing the calcium grains and zinc blocks into a vacuum high-frequency melting and casting furnace, seal the furnace body and evacuate the furnace chamber to 6×10 - 3 Pa. Then, fill the furnace with argon to 0.05 MPa, and then evacuate the furnace chamber to 6×10 -3 Pa. Repeat the above steps of filling with argon and evacuating for the second furnace cleaning. After the furnace cleaning is completed, continue to fill the furnace with about 0.05 MPa of argon, and then start heating and melting. During the melting process, adjust the heating power to keep the temperature range of the materials in the crucible at 750 - 860 °C. After maintaining at this temperature range for about 1 minute, the melting is completed. After the furnace chamber temperature drops to room temperature, open the furnace lid and take out the crucible to obtain a zinc-calcium compound ingot.

[0037] Grind off the dark substances on the surface of the obtained zinc-calcium compound ingot, and the surface of the compound ingot reveals a metallic luster. Use a small hammer to break the compound ingot, and then use a ball mill or a ceramic mortar to further grind the broken zinc-calcium compound particles. Finally, sieve the ground powder through 100-mesh and 200-mesh standard sieves respectively. Obtain 100 - 200-mesh zinc-calcium compound powder for standby. The scanning electron microscope photograph of this compound powder is as shown in the appendix Figure 1 as follows.

[0038] (2) Preparation of zinc-calcium compound composite material

[0039] Weigh 18.0030 g of 100 - 200-mesh zinc-calcium compound powder using an electronic balance and pour it into a steel infiltration mold with an inner diameter of 20 mm. Use a hammer to tap the mold to vibrate and compact the powder in the mold. Place the mold in a crucible resistance heating furnace and heat it to 405 °C and keep it warm for 1.5 h. While the mold is being heated and kept warm, place 45.0075 g of pure zinc ingot into a graphite-clay crucible, and place the crucible into another crucible resistance furnace and heat it to 560 °C. After the zinc ingot melts, keep it warm for 45 min.

[0040] After the heat preservation of the steel seepage mold filled with zinc-calcium compound powder and the crucible filled with zinc melt is completed, first take out the steel mold and place it at the designated position, then take out the graphite-clay crucible, and then quickly pour all the zinc melt onto the zinc-calcium compound powder in the steel mold. Immediately cover the upper cover of the steel mold, and introduce compressed air at 0.3 - 0.4 MPa into the mold for pressure infiltration. The pressure holding time is 3 min. During the infiltration process, the zinc melt seeps into the gaps between the compound particles under the action of pressure. Under the high temperature of the zinc melt, calcium elements in the surface layer of the compound particles diffuse into the zinc melt and react with zinc to form new compounds such as CaZn 13 etc. The part of the compound particles where calcium element diffusion does not occur inside remains the original phase.

[0041] After the infiltration is completed, take out the sample after the mold cools down to obtain the zinc-calcium compound composite material.

[0042] The X-ray diffraction pattern of this composite material is as shown in the appendix Figure 2 as follows. It can be seen that the phases existing in the composite material include CaZn 13 , CaZn2 and CaZn5, and the presence of Zn is not detected. Thus, it is determined that this composite material is completely composed of zinc-calcium compounds. The optical microscope photo of this composite material is as shown in the appendix Figure 3 as follows. Combining with the X-ray diffraction pattern in the appendix Figure 2 , it can be determined that the light-colored particles in the appendix Figure 3 are the original CaZn2 particles. The slightly darker shell layer on the surface of the CaZn2 particles is the area where calcium element diffusion occurs on the particle surface during the infiltration process. The dark phase around the shell layer is the matrix phase formed by the reaction of the zinc melt with calcium diffused from the surface layer of the CaZn2 particles into the zinc melt during the infiltration process, and its main component is CaZn 13 .

[0043] The polarization curve of this composite material measured in Hank's solution at 37°C using a CHI660E electrochemical workstation is as shown in the appendix Figure 4 as follows. It can be seen that the composite material has a lower corrosion potential and a larger corrosion current density than pure zinc.

[0044] The photos of this composite material taken using a Hitachi S-4800 scanning electron microscope after soaking in Hank's solution at 37°C for 5 hours are as shown in the appendix Figure 5 (a) and (b) as follows. The EDS energy spectrum results in the appendix Figure 5 (c) show that the corrosion product layer deposited on the surface of the composite material contains Ca and P elements.

[0045] The photos of this composite material taken using a Hitachi S-4800 scanning electron microscope after soaking in Hank's solution at 37°C for 5 hours and removing the corrosion products using chromic acid are as followsFigure 6 As shown, it can be seen that the CaZn2 particles in the composite material, as sacrificial anodes, have undergone severe corrosion ( Figure 6 (c)). When this composite material is used as an orthopedic implant material, it can be expected that the CaZn2 particles of zinc-calcium compounds with a high calcium content in the composite material will also preferentially degrade as sacrificial anodes. At the same time, it will play a cathodic protection role for matrix phases such as zinc-calcium compounds CaZn 13 and so on, thereby improving the cell activity of the composite material. Eventually, this composite material can be used for the repair and replacement of damaged bone tissues where implant materials do not cause obvious cytotoxicity.

[0046] Attached Figure 7 is the cell activity measured by the MTT method after L-929 cells are cultured in the leaching solution of the composite material with different concentrations for 1 day. It can be seen that even after being cultured in the 100% leaching solution of the composite material for 1 day, the cell activity of L-929 is still higher than 80%, and the composite material shows excellent cell activity.

[0047] Example 2

[0048] Other steps are the same as those in Example 1, except that in the pressure infiltration process of the step (2) for preparing the zinc-calcium compound composite material, the compressed air of 0.3 - 0.4 MPa is replaced by compressed argon of 0.3 - 0.4 MPa;

[0049] The material properties obtained are similar;

[0050] Example 3

[0051] Other steps are the same as those in Example 1, except that in the step (2) for preparing the zinc-calcium compound composite material, the heating temperature of the mold filled with CaZn2 particles in the crucible resistance heating furnace is replaced from 405 °C to 390 °C, and the heating temperature of the graphite-clay crucible filled with pure zinc ingots in another crucible resistance furnace is replaced from 560 °C to 575 °C;

[0052] The material properties obtained are similar;

[0053] Matters not covered in this invention are well-known technologies.

Claims

1. A method for preparing a degradable zinc-calcium compound composite material, characterized in that the method comprises the following steps: The first step is to prepare zinc-calcium compound CaZn2 powder with a high calcium content: (1) Lay a layer of pure zinc blocks at the bottom of a graphite-clay crucible, place calcium grains on top of the zinc blocks, and continue to lay the remaining zinc blocks on top of the calcium grains; after placing the crucible containing the calcium grains and zinc blocks into a vacuum high-frequency melting and casting furnace, evacuate the air, and start heating and melting under an argon atmosphere; after melting for 30 seconds to 1 minute within the heating and melting temperature range, cool down to room temperature with the furnace to obtain a zinc-calcium compound ingot; (2) Smash the obtained zinc-calcium compound ingot and grind it to obtain 100-200 mesh CaZn2 zinc-calcium compound powder; Among them, The atomic ratio of calcium grains to zinc blocks is 1:2; The second step is to prepare a degradable zinc-calcium compound composite material: (1) Pour the zinc-calcium compound powder obtained in the previous step into a steel infiltration mold and compact it; then place the mold into a crucible resistance heating furnace and heat it to 390-410 °C and keep it warm for 1 to 2 hours; while the mold is being heated and kept warm, place a pure zinc ingot into a graphite-clay crucible, heat the crucible to 555-575 °C, and keep it warm for 20 minutes to 1 hour after the zinc ingot melts; Among them, the mass of zinc is 2-2.5 times the mass of the zinc-calcium compound powder; (2) After the steel mold containing the zinc-calcium compound powder and the crucible containing the zinc melt finish keeping warm, pour the zinc melt into the steel infiltration mold; immediately cover the upper cover of the steel mold, and introduce compressed gas at 0.3-0.4 MPa into the mold for pressure infiltration for 1 to 5 minutes; After the infiltration ends, take out the sample after the mold cools down to obtain a zinc-calcium compound composite material.

2. The method for preparing a degradable zinc-calcium compound composite material according to claim 1, characterized in that the purity of the calcium grains is ≥99.0%, and the purity of the zinc blocks is ≥99.995%.

3. The preparation method of the degradable zinc-calcium compound composite material according to claim 1, characterized in that The vacuum pumping is 1.0×10 -3 Pa~8.0×10 -3 Pa, in argon atmosphere, the argon pressure is 0.05-0.06MPa.

4. The method for preparing a degradable zinc-calcium compound composite material according to claim 1, characterized in that the melting temperature is 750-860 °C.

5. The preparation method of the degradable zinc-calcium compound composite material according to claim 1, characterized in that The grinding is carried out by a ball mill or by grinding finely with a ceramic mortar.

6. The method for preparing a degradable zinc-calcium compound composite material according to claim 1, characterized in that the compressed gas is compressed air, compressed argon or compressed nitrogen.

7. The application of the degradable zinc-calcium compound composite material obtained by the method according to claim 1, characterized in that it is used as an orthopedic implant material for temporary implantation in the body.

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