Volume-weight-controllable coral hydroxyapatite bone repair material and preparation method thereof
By using incomplete hydrothermal reaction and gradient acid treatment, combined with the use of penetrants and ethanol, the problem of excessively high density in coral hydroxyapatite materials was solved, resulting in a coral hydroxyapatite bone repair material with controllable density and a porous structure, thus improving bone integration efficiency.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- BEIJING YIHUAJIAN TECH & TRADE CO LTD
- Filing Date
- 2026-03-03
- Publication Date
- 2026-04-17
AI Technical Summary
Existing coral hydroxyapatite bone repair materials have excessively high density, resulting in insufficient porosity and small pore size, which restricts the migration and proliferation of osteoblasts and affects bone integration efficiency. Furthermore, existing improvement methods are difficult to achieve controllable density while preserving the natural porous structure.
The structure of coral (calcium carbonate) with a hydroxyapatite outer layer is formed through incomplete hydrothermal reaction. Gradient acid treatment is used, where weak acid reacts with calcium carbonate to remove unconverted calcium carbonate while retaining the hydroxyapatite framework. Combined with the use of penetrants and ethanol, a deep and uniform penetration reaction is achieved.
It effectively reduces the bulk density of coral hydroxyapatite while maintaining its natural porous structure, thereby improving the porosity and mechanical properties of the material and meeting multiple requirements for clinical applications.
Smart Images
Figure SMS_1
Abstract
Description
Technical Field
[0001] This application relates to the technical field of biomedical materials, and in particular to a coral hydroxyapatite bone repair material with controllable bulk density and its preparation method. Background Technology
[0002] Bone repair materials must meet multiple requirements in clinical applications, including biocompatibility, osteoconductivity, and mechanical properties. Current mainstream materials include autologous bone, allogeneic bone, and synthetic materials. However, autologous bone sources are limited, and allogeneic bone carries risks of immune rejection and infectious diseases. Synthetic materials, such as coral hydroxyapatite, have become a research hotspot due to their similar chemical composition and spatial structure to human bone. However, existing coral hydroxyapatite materials suffer from insufficient porosity and small pore size due to excessively high density, which restricts osteoblast migration and proliferation, affecting osseointegration efficiency. In recent years, researchers have attempted to improve material properties by adjusting the preparation process, but achieving controllable density while preserving the natural structure of coral remains a technical challenge.
[0003] Some studies have attempted to reduce density through physical pore creation or chemical etching, but this would damage the natural porous structure of coral hydroxyapatite materials, reduce osteoinductive properties, and make it difficult to achieve uniformity inside and outside the material, resulting in little improvement. Summary of the Invention
[0004] In order to reduce the bulk density of coral hydroxyapatite bone repair material while maintaining its natural porous structure, this application provides a coral hydroxyapatite bone repair material with controllable bulk density and a preparation method thereof.
[0005] In a first aspect, this application provides a method for preparing a coral hydroxyapatite bone repair material with controllable density, employing the following technical solution: A method for preparing a coral hydroxyapatite bone repair material with controllable bulk density, comprising the following preparation steps: S1. Crush the coral, wash it, and dry it to obtain coral particles; S2. The coral particles are subjected to an incomplete hydrothermal reaction to control the incomplete conversion of hydroxyapatite and obtain a coral-hydroxyapatite composite material. S3. The coral hydroxyapatite composite material is washed with purified water and then dried. S4. The cleaned coral hydroxyapatite composite material is subjected to gradient acid treatment. An acid treatment solution is prepared and immersed in the cleaned coral hydroxyapatite composite material. After the reaction, it is taken out, cleaned, and dried to obtain coral hydroxyapatite bone repair material. The acid in the acid treatment solution is a weak acid.
[0006] By employing the above-mentioned technical solution, this application achieves partial hydroxyapatite conversion of coral particles through incomplete hydrothermal reaction. By controlling the conversion rate of hydroxyapatite, a structure is formed where coral (calcium carbonate) is coated with a layer of hydroxyapatite. Then, through gradient acid treatment, an acid solution of a certain concentration passes through this hydroxyapatite coating and reacts with the unconverted calcium carbonate. After washing, the acid treatment byproducts are thoroughly removed. Weak acids do not react with hydroxyapatite; therefore, after gradient acid treatment, the structure of the hydroxyapatite coating is preserved, forming a hydroxyapatite framework. Ultimately, the resulting coral hydroxyapatite bone repair material achieves both controllable density and maintains the natural porous structure of coral, thus better meeting the needs of various clinical applications.
[0007] Preferably, in S2, the conversion rate of hydroxyapatite in the coral particles is 30-70%.
[0008] By adopting the above technical solution, the conversion rate of hydroxyapatite is controlled within 30-70%, ensuring that the coral hydroxyapatite bone repair material has a certain strength and maintains a stable skeleton. Furthermore, after reacting with calcium carbonate in a weak acid, it exhibits a significant reduction in bulk density. This range effectively balances the bulk density, porosity, and mechanical properties of the final product.
[0009] As a preferred embodiment, the specific operation of S2 is as follows: Prepare 60-100 mL of phosphate solution with a concentration of 1.5-3 mol / L, adjust the pH to 9.5-11, add 15-20 g of coral particles, transfer to a polytetrafluoroethylene liner, seal in a high-pressure reactor, and carry out a hydrothermal reaction at 150-200℃ for 18-22 h to obtain coral hydroxyapatite composite material.
[0010] By adopting the above technical solution and limiting the process parameters of the incomplete hydrothermal reaction, the conversion rate of hydroxyapatite can be controlled between 30% and 70%.
[0011] As a preferred embodiment, the specific steps of S4 are as follows: Prepare an acid treatment solution with a weak acid concentration of 0.3-1.5 mol / L, immerse the coral hydroxyapatite composite material obtained in S3, shake and react for 10-12 hours, remove and clean; repeat the acid treatment and cleaning steps 2-4 times.
[0012] By adopting the above technical solution, gradient acid treatment is the key method of this application. The setting of weak acid concentration (0.3-1.5 mol / L) and single treatment time (10-12 h) avoids local over-reaction or structural damage caused by a single strong acid treatment. Its effect is to dissolve calcium carbonate uniformly from the surface to the interior, ensuring the consistency of the internal and external structure of the material.
[0013] Multiple treatment-washing cycles can thoroughly remove reaction byproducts and residual acid, greatly improving the biosafety of the product and reducing the risk of inflammation caused by chemical residues after implantation.
[0014] Preferably, the weak acid used to prepare the acid treatment solution is one or more of citric acid, acetic acid, and phosphoric acid.
[0015] By adopting the above technical solution, citric acid, acetic acid and phosphoric acid can all react with calcium carbonate without destroying the framework structure of hydroxyapatite, and the reaction products are easy to wash away.
[0016] Preferably, in step S4, the drying conditions are: vacuum drying, and the drying temperature is 100-250℃.
[0017] By employing the above-mentioned technical solution and using vacuum drying, moisture can be rapidly removed at a lower temperature (compared to high-temperature drying at atmospheric pressure), avoiding the damage (i.e., pore collapse) caused by the surface tension of water to the fragile porous support structure, thus maintaining high porosity. Appropriate drying temperatures (100-250℃) can completely remove moisture, preventing mold growth during storage and potentially making the hydroxyapatite crystal structure more stable.
[0018] Preferably, the acid treatment solution contains a penetrant with a mass fraction of 0.05-0.2%, wherein the penetrant is polysorbate.
[0019] By adopting the above technical solution and adding a penetrant, the wetting of the coral's micropores by the acid treatment solution can be improved, achieving a deep and uniform penetration reaction. This can improve the controllability of process parameters and increase product qualification rate and consistency.
[0020] Preferably, the solvent of the acid treatment solution is a mixture of water and ethanol, wherein the volume percentage of ethanol in the mixture is 1-3%.
[0021] By adopting the above technical solution, the addition of ethanol can further reduce the interfacial tension between the acid treatment solution and coral hydroxyapatite. Furthermore, ethanol has good compatibility with water and can be easily removed by washing and high temperature, thus reducing residue.
[0022] Preferably, in step S1, the particle size of the broken coral is 0.25-4.0 mm. 3 .
[0023] By adopting the above technical solution, the coral particles can be controlled to be between 0.25-4.0mm. 3 This ensures that reactants and products can be effectively transported within the particles, thus ensuring the uniformity of the reaction transformation.
[0024] Secondly, this application provides a coral hydroxyapatite bone repair material with controllable density, employing the following technical solution: A coral hydroxyapatite bone repair material with controllable density.
[0025] By adopting the above technical solution, the coral hydroxyapatite bone repair material prepared in this application can effectively reduce the bulk density of coral hydroxyapatite without damaging the natural porous structure of coral and without reducing its osteoinductive properties.
[0026] In summary, this application includes at least one of the following beneficial technical effects: 1. This application utilizes an incomplete hydrothermal reaction to partially convert coral particles into hydroxyapatite. By controlling the conversion rate of hydroxyapatite, a structure is formed where coral (calcium carbonate) is coated with a layer of hydroxyapatite. Then, through gradient acid treatment, an acid solution of a certain concentration passes through this hydroxyapatite coating and reacts with the unconverted calcium carbonate. After washing, the acid treatment byproducts are thoroughly removed. Weak acids do not react with hydroxyapatite, and the structure of the hydroxyapatite coating is preserved after gradient acid treatment, forming a hydroxyapatite framework. Ultimately, the resulting coral hydroxyapatite bone repair material has controllable density and maintains the natural porous structure of coral, thus better meeting the needs of various clinical applications.
[0027] 2. By adding penetrants and ethanol, the wetting of the coral's micropores by the acid treatment solution can be improved, achieving a deep and uniform penetration reaction. This can improve the controllability of process parameters and increase product qualification rate and consistency.
[0028] 3. The density qualification rate of the coral hydroxyapatite bone repair material prepared in this application can reach 90.6% or above, and its porosity can also reach 90.2% or above. Detailed Implementation
[0029] The following provides a more detailed description of this application in conjunction with specific details.
[0030] raw material The raw materials used in the embodiments of this application are all commercially available products. The natural coral blocks used, after complete hydroxyapatite conversion, have a bulk density of 0.9-1.0 g / cm³. 3 . Example
[0031] Example 1 A coral hydroxyapatite bone repair material with controllable density is prepared as follows: S1, Coral Pretreatment The natural coral blocks are cut and lightly crushed using a diamond saw, and then sieved to obtain particles with a diameter of 0.25-4.0mm. 3The selected coral particles were placed in purified water and ultrasonically cleaned for 15 minutes to remove surface deposits and dust. They were then removed and dried at 100°C for later use. S2, Incomplete hydrothermal reaction 80 mL of a 1.5 mol / L diammonium hydrogen phosphate solution was prepared as the reaction solution, and the pH was adjusted to 9.5. 20 g of pretreated coral particles were placed in a polytetrafluoroethylene liner, and the reaction solution was poured in. The liner was sealed in a high-pressure reactor, which was then placed in an oven and reacted at 150 °C for 24 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature (25-30 °C). At this point, the coral calcium carbonate was partially converted into hydroxyapatite, forming a coral-hydroxyapatite composite material. The conversion rate of hydroxyapatite was approximately 30% as determined by XRD. S3, coarse wash The coral hydroxyapatite composite material was washed repeatedly with purified water five times to remove residual reaction solution, and then dried at 100°C. S4, Gradient acid treatment Prepare a 1.5 mol / L citric acid solution as an acid treatment solution, immerse the finely washed coral hydroxyapatite composite material in it, and gently shake it at room temperature for 12 hours. Remove the material and wash it thoroughly with purified water until the washing solution is neutral (tested by pH test paper). Repeat the above acid treatment and cleaning process three times in total to gradually and gently dissolve the unreacted calcium carbonate while preserving the hydroxyapatite framework. S5, Fine Wash The coral hydroxyapatite composite material after gradient acid treatment was placed in purified water and washed by shaking for 30 minutes. After 5 cycles of washing, the acid treatment byproducts were completely removed. Then, it was vacuum dried at 150°C to obtain the coral hydroxyapatite bone repair material.
[0032] Example 2 A coral hydroxyapatite bone repair material with controllable density is prepared as follows: S1, Coral Pretreatment The natural coral blocks are cut and lightly crushed using a diamond saw, and then sieved to obtain particles with a diameter of 0.25-4.0mm. 3 The selected coral particles were placed in purified water and ultrasonically cleaned for 30 minutes to remove surface deposits and dust. They were then removed and dried at 100°C for later use. S2, Incomplete hydrothermal reaction 80 mL of a 3.0 mol / L diammonium hydrogen phosphate solution was prepared as the reaction solution, and the pH was adjusted to 11. 20 g of pretreated coral particles were placed in a polytetrafluoroethylene liner, and the reaction solution was poured in. The liner was sealed in a high-pressure reactor, which was then placed in an oven and reacted at 200 °C for 24 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature (25-30 °C). At this point, the coral calcium carbonate was partially converted into hydroxyapatite, forming a coral-hydroxyapatite composite material. The conversion rate of hydroxyapatite was approximately 70% as determined by XRD. S3, coarse wash The coral hydroxyapatite composite material was washed repeatedly with purified water five times to remove residual reaction solution, and then dried at 150°C. S4, Gradient acid treatment Prepare a 0.3 mol / L citric acid solution as an acid treatment solution, immerse the finely washed coral hydroxyapatite composite material in it, and gently shake it at room temperature for 12 hours. Remove the material and wash it thoroughly with purified water until the washing solution is neutral (tested by pH test paper). Repeat the above acid treatment and cleaning process twice in total to gradually and gently dissolve the unreacted calcium carbonate while preserving the hydroxyapatite framework. S5, Fine Wash The coral hydroxyapatite composite material after gradient acid treatment was placed in purified water and circulated for 60 minutes. After 5 cycles of rinsing, the acid treatment byproducts were completely removed. Then, it was vacuum dried at 250°C to obtain the coral hydroxyapatite bone repair material.
[0033] Example 3 A coral hydroxyapatite bone repair material with controllable density is prepared as follows: S1, Coral Pretreatment The natural coral blocks are cut and lightly crushed using a diamond saw, and then sieved to obtain particles with a diameter of 0.25-4.0mm. 3 The selected coral particles were placed in purified water and ultrasonically cleaned for 10 minutes to remove surface deposits and dust. They were then removed and dried at 150°C for later use. S2, Incomplete hydrothermal reaction 80 mL of a 2.1 mol / L diammonium hydrogen phosphate solution was prepared as the reaction solution, and the pH was adjusted to 10. 20 g of pretreated coral particles were placed in a polytetrafluoroethylene liner, and the reaction solution was poured in. The liner was sealed in a high-pressure reactor, which was then placed in an oven and reacted at 180 °C for 20 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature (25-30 °C). At this point, the coral calcium carbonate was partially converted into hydroxyapatite, forming a coral-hydroxyapatite composite material. The conversion rate of hydroxyapatite was approximately 50% as determined by XRD. S3, coarse wash The coral hydroxyapatite composite material was washed repeatedly with purified water five times to remove residual reaction solution, and then dried at 100°C. S4, Gradient acid treatment Prepare a 0.8 mol / L citric acid solution as an acid treatment solution, immerse the finely washed coral hydroxyapatite composite material in it, and gently shake it at room temperature for 10 hours. Remove the material and wash it thoroughly with purified water until the washing solution is neutral (detected by pH test paper). Repeat the above acid treatment and cleaning process twice in total to gradually and gently dissolve the unreacted calcium carbonate while preserving the hydroxyapatite framework. S5, Fine Wash The coral hydroxyapatite composite material after gradient acid treatment was placed in purified water and washed by shaking for 30 minutes. After 5 cycles of washing, the acid treatment byproducts were completely removed. Then, it was vacuum dried at 150°C to obtain the coral hydroxyapatite bone repair material.
[0034] Example 4 A coral hydroxyapatite bone repair material with controllable density differs from Example 3 in that, in the S4 gradient acid treatment, the acid treatment solution is a 1.5 mol / L acetic acid solution, while the remaining steps are the same as in Example 3.
[0035] Example 5 A coral hydroxyapatite bone repair material with controllable density differs from Example 3 in that, in the S4 gradient acid treatment, the acid treatment solution is a 0.8 mol / L phosphoric acid solution, while the remaining steps are the same as in Example 3.
[0036] Example 6 A controllable density coral hydroxyapatite bone repair material differs from Example 3 in that its acid treatment solution also includes a penetrant with a mass fraction of 0.1% and is polysorbate 80 (Tween 80). The remaining steps are the same as in Example 3.
[0037] Example 7 A coral hydroxyapatite bone repair material with controllable density differs from Example 6 in that the solvent of its acid treatment solution is a mixture of water and ethanol, in which the volume percentage of ethanol is 2%, and the remaining steps are the same as in Example 6.
[0038] Example 8 A coral hydroxyapatite bone repair material with controllable bulk density differs from Example 3 in that the concentration of citric acid solution in its S4 gradient acid treatment is 0.1 mol / L, while the remaining steps are the same as in Example 3.
[0039] Comparative Example Comparative Example 1 A coral hydroxyapatite bone repair material with controllable bulk density, which is different from Example 3 in that gradient acid treatment is not carried out in its preparation steps, and the remaining steps are the same as those in Example 3.
[0040] Performance Detection Test Detection Method / Test Method According to the preparation methods of Examples 1-8 and Comparative Example 1, 400 g of coral hydroxyapatite bone repair materials were prepared in batches, 20 g for each batch, and then they were detected. The detection results are shown in Table 1.
[0041] Bulk density qualification rate: When measuring the bulk density, the actually measured bulk density within the range of ±0.05 g / cm 3 is qualified, and the bulk density qualification rate is the percentage of qualified products to the total mass.
[0042] Pore penetration rate: Randomly select 5 samples for detection and calculate their average value. [[ID=二十二]]
[0043] Table 1 Detection Results of Examples 1-8 and Comparative Example 1
[0044] From the detection data in Table 2, it can be seen that the bulk density qualification rate of the coral hydroxyapatite bone repair materials prepared in this application can reach 90.6% or more, and at the same time, its pore penetration rate can also reach 90.2% or more; it shows that while reducing the bulk density of coral hydroxyapatite in this application, the natural porous structure of coral can be maintained.
[0045] Combined with Examples 1-3 and Comparative Example 1, this application can control the conversion rate of coral hydroxyapatite in the incomplete hydrothermal reaction, and then react and remove the unhydroxyapatited calcium carbonate by adjusting the gradient acid treatment, so as to achieve the controllable reduction of the bulk density of coral hydroxyapatite.
[0046] Combined with Example 3 and Examples 6-7, by adding a penetrant, the wetting of the acid treatment solution to the micro-pores of coral can be improved, the deep and uniform penetration reaction can be realized, the controllability of process parameters can be improved, and the product qualification rate and consistency can be improved. And the safety of polysorbate is relatively high and it is easy to wash off. The addition of ethanol can further reduce the interfacial tension between the acid treatment solution and coral hydroxyapatite, and the compatibility of ethanol and water is good, and it is easy to be removed by washing and high temperature, reducing the residue.
[0047] Combined with Example 3 and Example 8, the weak acid concentration of the acid treatment solution prepared with weak acid needs to reach a certain concentration to effectively and uniformly remove coral apatite.
[0048] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.
Claims
1. A method for preparing a controllable bulk density of coral hydroxyapatite bone repair material, characterized by: It includes the following preparation steps: S1. Crush the coral, wash it, and dry it to obtain coral particles; S2. The coral particles are subjected to an incomplete hydrothermal reaction to control the incomplete conversion of hydroxyapatite and obtain a coral-hydroxyapatite composite material. S3. The coral hydroxyapatite composite material is washed with purified water and then dried. S4. The cleaned coral hydroxyapatite composite material is subjected to gradient acid treatment. An acid treatment solution is prepared and immersed in the cleaned coral hydroxyapatite composite material. After the reaction, it is taken out, cleaned, and dried to obtain coral hydroxyapatite bone repair material. The acid in the acid treatment solution is a weak acid.
2. The method of claim 1, wherein the method of preparing a controllable density coral hydroxyapatite bone repair material is characterized by: In S2, the conversion rate of hydroxyapatite in the coral particles is 30-70%.
3. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: The specific operation of S2 is as follows: Prepare 60-100 mL of phosphate solution with a concentration of 1.5-3 mol / L, adjust the pH to 9.5-11, add 15-20 g of coral particles, transfer to a polytetrafluoroethylene liner, seal in a high-pressure reactor, and carry out a hydrothermal reaction at 150-200℃ for 18-22 h to obtain coral hydroxyapatite composite material.
4. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: The specific steps of S4 are as follows: Prepare an acid treatment solution with a weak acid concentration of 0.3-1.5 mol / L, immerse the coral hydroxyapatite composite material obtained in S3, shake and react for 10-12 hours, remove and clean; repeat the acid treatment and cleaning steps 2-4 times.
5. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: The weak acid used to prepare the acid treatment solution is one or more of citric acid, acetic acid, and phosphoric acid.
6. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: In step S4, the drying conditions are: vacuum drying, and the drying temperature is 100-250℃.
7. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: The acid treatment solution contains a penetrant with a mass fraction of 0.05-0.2%, and the penetrant is polysorbate.
8. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 7, characterized in that: The solvent of the acid treatment solution is a mixture of water and ethanol, wherein the volume percentage of ethanol in the mixture is 1-3%.
9. The method for preparing a controllable density coral hydroxyapatite bone repair material according to claim 1, characterized in that: In the S1, the broken size of the coral is 0.25-4.0mm 3 .
10. A coral hydroxyapatite bone repair material with controllable density as described in any one of claims 1-9.