A micro-arc oxidation electrolyte and its application, an implant material and its preparation method

Abstract

This invention relates to the field of medical materials, and discloses a micro-arc oxidation electrolyte, its application, and an implantable material and its preparation method. The electrolyte of this invention comprises phosphate, a strong base, and silver salt. The electrolyte of this invention is used to prepare a silver-doped micro-arc oxidation coating in one step via micro-arc oxidation. This coating exhibits good corrosion resistance, excellent antibacterial properties against Escherichia coli and Staphylococcus aureus, and significantly improved biocompatibility, making it suitable for use in medical implantable materials.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical materials, in particular to a micro-arc oxidation electrolyte and application thereof and an implant material and a preparation method thereof. BACKGROUND

[0002] Zinc is different from traditional "permanent" implant metal materials. It has good biocompatibility, and a standard corrosion potential between magnesium-based and iron-based metals, and theoretically has a more suitable degradation absorption rate. However, zinc-based degradable metals still have problems of too fast corrosion, too high zinc ions, and low biocompatibility in the body, which limit the clinical application of zinc-based degradable metals as degradable metal materials. In addition, bacterial infection is one of the main reasons for the failure of implantable degradable metals. Zinc-based degradable metals have certain antibacterial properties, but there is still a risk of surgical failure. How to impart zinc-based degradable metals with certain corrosion resistance, antibacterial ability and biocompatibility through surface treatment or coating technology is a problem to be solved for zinc-based degradable metal coatings. SUMMARY

[0003] Therefore, the purpose of the present application is to provide a micro-arc oxidation electrolyte which can significantly improve the biocompatibility of pure zinc medical implant materials prepared by micro-arc oxidation, and at the same time has certain corrosion resistance and antibacterial ability.

[0004] Another purpose of the present application is to provide the use of the above-mentioned electrolyte in the preparation of medical implant materials.

[0005] Another purpose of the present application is to provide a medical implant material obtained based on the above-mentioned electrolyte.

[0006] In order to solve the above technical problems or at least partially solve the above technical problems, the present application provides a method for solving the above technical problems or at least partially solving the above technical problems. As a first aspect of the present application, a micro-arc oxidation electrolyte is provided, which comprises a phosphate, a strong base and a silver salt.

[0007] Optionally, the concentration of the phosphate is 15-25 g / L; further optionally, the phosphate comprises one or more of sodium phosphate, disodium hydrogen phosphate and sodium dihydrogen phosphate.

[0008] Optionally, the concentration of the strong base is not more than 5 g / L; further optionally, the strong base comprises sodium hydroxide and / or potassium hydroxide.

[0009] Optionally, the concentration of the silver salt is 1-5 g / L; further optionally, the silver salt comprises one or more of silver carbonate, silver nitrate and silver fluoride.

[0010] As a second aspect of the present application, the electrolyte is provided for use in the preparation of a medical implant material.

[0011] As a third aspect of the present application, a medical implant material is provided, comprising a coating layer on the surface of a pure zinc material, the coating layer being formed by micro-arc oxidation in the electrolyte according to the present application.

[0012] As a fourth aspect of the present application, a method for preparing the medical implant material is provided, comprising:

[0013] Step 1, pre-treatment of the pure zinc material by polishing, degreasing and cleaning;

[0014] Step 2, micro-arc oxidation of the pre-treated pure zinc material as an anode in the electrolyte according to the present application.

[0015] Compared with the prior art, the present application has at least the following advantages:

[0016] (1) The coating layer prepared on the surface of the pure zinc material by the micro-arc oxidation electrolyte according to the present application has fewer cracks, moderate and uniform pore size, and moderate film thickness, which significantly reduces the corrosion rate of the pure zinc material and improves the corrosion resistance;

[0017] (2) The coating layer prepared on the surface of the pure zinc material by the micro-arc oxidation electrolyte according to the present application not only significantly improves the corrosion rate of the pure zinc material, but also improves the adhesion and proliferation of osteoblasts and promotes the biocompatibility of the medical pure zinc implant material;

[0018] (3) The coating layer prepared on the surface of the pure zinc material by the micro-arc oxidation electrolyte according to the present application is doped with a small amount of silver, which has a good antibacterial growth and anti-inflammatory effect on Escherichia coli and Staphylococcus aureus, can reduce the inflammatory reaction in the early stage of implantation of the implant material, and thus improves the success rate of implantation. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 SEM image of the micro-arc oxidation film layer on the surface of the medical pure zinc material in Example 1 of the present application.

[0020] Figure 2 EDS image of the micro-arc oxidation film layer on the surface of the medical pure zinc material in Example 1 of the present application.

[0021] Figure 3 Polarization curve of the micro-arc oxidation film layer on the surface of the medical pure zinc material in Example 1 of the present application; the left side is the polarization curve of the pure zinc material before preparation, and the right side is the polarization curve of the pure zinc material after micro-arc oxidation;

[0022] Figure 4 The cell proliferation rate of the coating layer prepared in Comparative Example 1 and Example 1 of the present application is shown. DETAILED DESCRIPTION

[0023] This invention discloses a micro-arc oxidation electrolyte and its application, as well as an implantable material and its preparation method. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The products, preparation methods, and applications of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the products, preparation methods, and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0024] In a first aspect of the invention, a micro-arc oxidation electrolyte is provided, comprising a phosphate, a strong base, and a silver salt.

[0025] In some embodiments of the present invention, the concentration of the phosphate is 15–25 g / L; in other embodiments, the concentration of the phosphate may be selected from 15 g / L, 20 g / L, or 25 g / L. In still other embodiments, the phosphate is one or more of sodium phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.

[0026] In some embodiments of the present invention, the concentration of the strong alkali is no greater than 5 g / L; in other embodiments of the present invention, the concentration of the strong alkali is 1 g / L, 2 g / L, 3 g / L, 4 g / L, or 5 g / L; in other embodiments of the present invention, the strong alkali includes sodium hydroxide and / or potassium hydroxide; in other embodiments of the present invention, comparative experiments have verified that the addition of the strong alkali helps to promote the adhesion and proliferation of osteoblasts and significantly improves biocompatibility.

[0027] In some embodiments of the present invention, the concentration of the silver salt is 1 to 5 g / L; in other embodiments of the present invention, the concentration of the silver salt is 1 g / L, 2 g / L, 3 g / L, 4 g / L or 5 g / L; in other embodiments of the present invention, the silver salt is one or more of silver carbonate, silver nitrate, and silver fluoride.

[0028] In some embodiments of the present invention, the electrolyte may be selected from any of the following compositions:

[0029] (1) Sodium phosphate, sodium hydroxide and silver carbonate;

[0030] (2) Sodium dihydrogen phosphate, sodium hydroxide and silver nitrate;

[0031] (3) Disodium hydrogen phosphate, potassium hydroxide and silver fluoride.

[0032] In a second aspect of the invention, the coating prepared by micro-arc oxidation using the electrolyte of the invention exhibits superior corrosion resistance and biocompatibility compared to coatings prepared with pure zinc materials and electrolytes without strong alkali. Furthermore, the coating formed by adding silver salts shows significant antibacterial effects against both Escherichia coli and Staphylococcus aureus. Thus, the invention proposes the application of the electrolyte in the preparation of medical implant materials.

[0033] In a third aspect of the present invention, a medical implant material is provided, wherein a coating formed by micro-arc oxidation of a pure zinc material by the electrolyte described in the present invention is provided on the surface of the pure zinc material, and the main elements of the coating are Zn, O, P, Ag, etc.; in some embodiments of the present invention, the thickness of the coating is 10 μm to 30 μm.

[0034] In some embodiments of the present invention, the pure zinc material contains Zn ≥ 99.99%; in other embodiments of the present invention, the pure zinc material is No. 0 pure zinc, and more specifically, the elemental composition (mass fraction) of the No. 0 pure zinc is: Al 0.001%, Mg 0.0003%, Fe 0.001%, Cu 0.003%, Pb 0.0005%, Cd 0.0001%, Sn 0.0002%, Zn ≥ 99.99%.

[0035] In a fourth aspect of the present invention, a method for preparing the medical implant material is provided, which can be summarized as several steps including grinding and polishing of pure zinc material, alkaline washing and degreasing, and micro-arc oxidation, specifically including:

[0036] Step 1: Pre-treatment of pure zinc material by grinding, degreasing and cleaning;

[0037] Step 2: The pretreated pure zinc material is used as the positive electrode. Micro-arc oxidation is carried out in the electrolyte of the present invention to form a coating on the surface of the pure zinc material, thereby obtaining a medical implant material.

[0038] In some embodiments of the present invention, the pure zinc material is polished in stages, using acetone, anhydrous ethanol, and water for ultrasonic cleaning, followed by degreasing and cleaning with an alkaline degreasing solution. The staged polishing is performed using silicon carbide sandpaper with progressively increasing grit, until the surface is smooth, free of obvious scratches, and has a consistent texture. The alkaline degreasing solution is sodium hydroxide, optionally a 10% sodium hydroxide solution.

[0039] In some embodiments of the present invention, the micro-arc oxidation is carried out in a constant voltage mode, with pure zinc material as the positive electrode and other suitable metals such as stainless steel as the negative electrode. The processing parameters are: voltage of 200V to 300V, pulse width of 1500 to 2500, time of 3 to 7 min, and electrolyte temperature of 10 to 30℃.

[0040] In other embodiments of the present invention, a method for preparing the medical implant material is specifically provided, including:

[0041] 1. Pretreatment of pure zinc material plates

[0042] Pure zinc materials are cut, ground, and subjected to ultrasonic cleaning with solvents.

[0043] 2. Ultrasonic degreasing

[0044] The bright and clean pure zinc material is immersed in an alkaline degreasing solution, then ultrasonically cleaned and dried.

[0045] 3. Prepare micro-arc oxidation electrolyte

[0046] Add phosphate, strong alkali and silver salt to water, stir well and let stand to obtain micro-arc oxidation electrolyte;

[0047] 4. Micro-arc oxidation

[0048] The pretreated pure zinc material was placed in a micro-arc oxidation electrolyte, with the pure zinc material connected to the positive terminal of the power supply as the positive electrode, and the stainless steel electrolytic cell connected to the negative terminal of the power supply as the negative electrode. The cooling device was turned on to control the temperature between 10 and 30°C. Micro-arc oxidation was performed using a constant voltage mode, with a voltage of 200V to 300V, a pulse width of 1500 to 2500, and a time of 3 to 7 minutes, to obtain a pure zinc material (medical implant material) with a micro-arc oxidation coating on its surface.

[0049] 5. Post-board processing

[0050] All samples were rinsed with deionized water and dried at ambient temperature.

[0051] Unless otherwise specified, the experimental environment and parameter conditions of each group in the test remain the same, except for the differences that are clearly pointed out.

[0052] The following provides a further description of the electrolyte for micro-arc oxidation, its application, and the implant material and its preparation method provided by the present invention.

[0053] Example 1: Preparation of coated medical implant materials

[0054] 1. Pretreatment of pure zinc substrate

[0055] First, the medical-grade pure zinc material is processed into a 20mm×20mm×2mm rectangle using wire cutting equipment, then polished with 400-2000# sandpaper, and then treated with solvent ultrasonic cleaning.

[0056] 2. Ultrasonic degreasing

[0057] The bright and clean pure zinc material is immersed in an alkaline degreasing solution, then ultrasonically cleaned and dried.

[0058] 3. Prepare micro-arc oxidation electrolyte

[0059] Mix 20 g / L sodium phosphate, 2 g / L sodium hydroxide, and 2 g / L silver carbonate (the remainder is water), stir well, and let stand to obtain a micro-arc oxidation electrolyte.

[0060] 4. Micro-arc oxidation

[0061] Using a pulsed micro-arc oxidation device, the positive terminal of the power supply is connected to the pure zinc material through aluminum wires and fixing clamps, and the negative terminal of the power supply is connected to stainless steel. Then, the whole unit is placed in an electrolyte tank and a constant voltage mode is set with a voltage of 200V, a pulse width of 2000, a time of 5min, and an electrolyte temperature of 30℃ to conduct micro-arc oxidation experiments, resulting in pure zinc material with a micro-arc oxidation coating on the surface.

[0062] 5. Post-board processing

[0063] All samples were rinsed with deionized water and dried at ambient temperature.

[0064] Figure 1 The image shown is a SEM image of the micro-arc oxidation film layer on the surface of the medical pure zinc material prepared in Example 1 of the present invention, which shows that a coating with a three-dimensional structure and high porosity composed of randomly distributed micro-nano pores and in-situ grown particles was successfully prepared on the surface of the pure zinc material.

[0065] Figure 2 The image shown is an EDS image of the micro-arc oxidation film layer on the surface of the medical pure zinc material prepared in Example 1 of the present invention. It shows that the main elements of the coating are Zn, O, P, Ag, and C and Na (which vary depending on the phosphate and silver salt).

[0066] Electrochemical tests were performed in this embodiment, and the polarization curve of the surface coating of the medical pure zinc material of the present invention is as follows: Figure 3 As shown, the corrosion potential shifts significantly in the positive direction compared to the unprepared pure zinc material, resulting in a substantial improvement in corrosion resistance.

[0067] Example 2: Preparation of coated medical implant materials

[0068] The difference from Example 1 is that the electrolyte consists of 15 g / L sodium dihydrogen phosphate, 5 g / L sodium hydroxide, 4 g / L silver nitrate, and the remainder is water.

[0069] Example 3: Preparation of orthopedic implant materials with porous coatings

[0070] The difference from Example 1 is that the electrolyte consists of 25 g / L disodium hydrogen phosphate, 2 g / L potassium hydroxide, 3 g / L silver fluoride, and the remainder is water.

[0071] Comparative Example 1: Preparation of coating with electrolyte without sodium hydroxide

[0072] Following the preparation process of Example 1, sodium hydroxide is not added in step 3.

[0073] Comparative Example 2: Preparation of coatings using electrolyte without sodium hydroxide

[0074] Following the preparation process of Example 1, silver carbonate is not added in step 3.

[0075] Experimental Example: Biocompatibility and Antibacterial Capacity Test

[0076] 1. Biocompatibility

[0077] Biocompatibility tests were conducted on the pure zinc material, the implant material of Example 1, and the implant material of Comparative Example 1. Specifically:

[0078] According to ISO 10993-5:2009, mouse osteoblast-like cells (MC3T3-E1) were used to assess cell compatibility. Samples should be sterilized before use. Samples were cultured in α-MEM cell culture medium for 24 hours under standard cell culture conditions, and extracts were collected at a rate of 1.25 mL per square centimeter. The collected extracts are expressed as 100% extract. Cells were seeded in 96-well cell culture plates at a density of 5 × 10⁶ cells per 100 μL of medium. 3 Cells were collected. The cells were then cultured for 1 day. At the end of the time point, the material extract was replaced with cell culture medium from a 10% Cell Count Kit-8 (CCK8, Dojindo, Japan) and cultured at 37°C for 1 hour. The spectrophotometry of each group was measured at 450 nm using a microplate reader (Bio-RAD680).

[0079] The results are as follows Figure 4 As shown, after 1 day of cell culture, the proliferation rate in the leaching culture medium of Comparative Example 1 was not only lower than that in the leaching culture medium of Example 1, but also significantly lower than that in the leaching culture medium of pure zinc material. This indicates that strong alkali has a huge impact on the biocompatibility of the coating, and not adding strong alkali will reduce cell compatibility.

[0080] 2. Antibacterial ability

[0081] Using Escherichia coli and Staphylococcus aureus as test strains, the immersion method was employed for testing:

[0082] (1) The concentration of Escherichia coli and Staphylococcus aureus in the bacterial culture was controlled at 1*10^7 cfu / mL;

[0083] (2) After disinfection and sterilization, the first group of Example 1 and the second group of Comparative Example 2 were placed in a six-well cell culture plate, and 3 mL of the prepared bacterial solution was added (enough to cover the sample). The plates were then shaken and cultured at 37°C for 2, 4 and 6 hours respectively. 0.1 mL of the solution was diluted and plated, and the plates were cultured at 37°C for 18-24 hours.

[0084] (3) Calculate the antibacterial rate using the following formula:

[0085] R(%) = [(BA) / B] x 100%;

[0086] R represents the antibacterial rate, where A (CFU / mL) is the average number of bacteria in the experimental group and B (CFU / mL) is the average number of bacteria in the control group. The results are shown in Table 1.

[0087] Table 1

[0088]

[0089] As shown in Table 1, the pure zinc material with silver-doped micro-arc oxidation coating has obvious antibacterial effects against Escherichia coli and Staphylococcus aureus. The antibacterial coating prepared with silver salt-containing micro-arc oxidation electrolyte has better antibacterial effect, while the coating without silver doping has poor antibacterial properties.

[0090] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A micro-arc oxidation electrolyte, characterized in that, The electrolyte is composed of phosphate, strong alkali, silver salt and water, wherein the concentration of the phosphate is 15-25 g / L, including one or more than two of sodium phosphate, disodium hydrogen phosphate and sodium dihydrogen phosphate; the concentration of the strong alkali is 1-5 g / L, including sodium hydroxide and / or potassium hydroxide; the concentration of the silver salt is 1-5 g / L, including one or more than two of silver carbonate, silver nitrate and silver fluoride. The micro-arc oxidation is carried out in a constant voltage mode, and the treatment parameters are as follows: voltage 200-300 V, pulse width 1500-2500, time 3-7 min, electrolyte temperature 10-30 DEG C.

2. Use of the electrolyte in claim 1 in the preparation of medical implant materials.

3. A medical implant material, characterized in that, The surface of the pure zinc material comprises a coating layer formed by micro-arc oxidation in the electrolyte in claim 1.

4. The method of producing a medical implant material as claimed in claim 3, characterized in that The method comprises: Step 1, pre-treatment of the pure zinc material by polishing, oil removal and cleaning; Step 2, the zinc alloy material after the pre-treatment is used as a positive electrode, and micro-arc oxidation is carried out in the electrolyte in claim 1; the micro-arc oxidation is carried out in a constant voltage mode, and the treatment parameters are as follows: voltage 200-300 V, pulse width 1500-2500, time 3-7 min, electrolyte temperature 10-30 DEG C.

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