Process method for large-scale preparation of calcium-deficient hydroxyapatite and product thereof
Through solid phase reaction method and weak alkali liquid phase transformation method, the problem of large-scale production of calcium-deficient hydroxyapatite was successfully solved, and an efficient and simplified preparation process was achieved, which was suitable for expanding production.
Patent Information
- Application Number
- CN202411872573.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-18
- Publication Date
- 2025-03-11
AI Technical Summary
The prior art is difficult to achieve large-scale production of calcium-deficient hydroxyapatite, and the preparation process is complex and difficult to control.
Calcium hydrogen phosphate and calcium carbonate were calcined at high temperature by solid phase reaction method, polyvinyl alcohol was added to avoid large-scale agglomeration of α-TCP after sintering, and crystalline α-TCP was prepared after quenching, and then phase was transformed in weak alkali liquid to form calcium-deficient hydroxyapatite.
It realizes efficient preparation of calcium-deficient hydroxyapatite, with high product conversion rate, simple and easy to control process, and is suitable for large-scale production.
Smart Images
Figure CN119591062A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a method in the technical field of biomedical materials, in particular to a process for preparing calcium-deficient hydroxyapatite on a large scale and a product thereof. Background Art
[0002] Hydroxyapatite (HA) is very similar to the inorganic composition of natural bone and is one of the main inorganic components of natural bone and teeth. However, the hydroxyapatite in natural bone is not in perfect stoichiometry, and it usually contains some defects, such as calcium defects or other ion substitutions, which affect its physical and chemical properties. Calcium-deficient hydroxyapatite (CDHA) is a variant of hydroxyapatite, a material with good bioactivity and osteoconductivity. It has less calcium content than hydroxyapatite with an ideal stoichiometric ratio. From the above perspective, CDHA may be closer to the inorganic composition of natural bone than hydroxyapatite with an ideal stoichiometric ratio in some aspects because it better simulates the actual situation of hydroxyapatite in natural bone, including its defective structure and ion substitution. In addition, CDHA has higher biodegradability, so it has more advantages in certain clinical application scenarios.
[0003] At present, the industrial preparation methods of hydroxyapatite mainly include hydrothermal synthesis, sol-gel method, solid phase reaction method, precipitation method, etc. Each method has its advantages and limitations. The selection of a suitable preparation method depends on the characteristics of the desired product, cost-effectiveness, and industrial production requirements. For example, the hydrothermal synthesis method can obtain high-purity hydroxyapatite, but the equipment cost is high; while the precipitation method is simple to operate and low in cost, but may require a subsequent heat treatment step to improve the crystallinity of the product. At the same time, it is limited by the solution concentration, the solid content in the solution is low, and the large-scale production water demand is large, involving subsequent water treatment issues. The industrial preparation method of CDHA is similar to the preparation method of hydroxyapatite (HA), but specific adjustments are made in the raw material ratio, reaction conditions or post-treatment steps to introduce calcium defects. Therefore, it is urgent to improve the production process to obtain a method for large-scale production of CDHA.
[0004] Based on the above background, the present invention provides a process for preparing calcium-deficient hydroxyapatite on a large scale, wherein raw materials of calcium hydrogen phosphate and calcium carbonate are calcined at high temperature by a solid phase reaction method, polyvinyl alcohol is added to prevent large-scale agglomeration of α-TCP after sintering, crystalline α-tricalcium phosphate (α-TCP) is prepared after rapid cooling, and then the α-TCP is phase-transformed in a weak alkaline solution to form calcium-deficient hydroxyapatite. The preparation process of the present invention is simple, easy to control, and suitable for expanded production. Summary of the invention
[0005] The present invention aims to provide a process for preparing calcium-deficient hydroxyapatite on a large scale, which not only has excellent performance but also simplifies the preparation process and is suitable for expanding production.
[0006] Another object of the present invention is to provide a calcium-deficient hydroxyapatite product prepared by a method.
[0007] The object of the present invention is achieved by the following scheme: a process for preparing calcium-deficient hydroxyapatite on a large scale, comprising the following steps: fully mixing calcium hydrogen phosphate and calcium carbonate powder in a molar ratio of 2:1 to obtain a mixed powder A, and then adding polyvinyl alcohol to obtain a mixed powder B; adopting a solid phase reaction method, calcining the mixed powder B at a high temperature for 2-4 hours, taking it out, and rapidly cooling it under a blast environment to obtain non-agglomerated α-TCP powder; ball milling the powder and passing it through a 500-mesh sieve; preparing a phosphate solution with a pH of 9-10, adding the powder to the solution during stirring, continuing to stir for 1-2 hours after the addition, and then standing it for sufficient phase transformation, and performing a filter press treatment on the product, drying it, and crushing it to obtain the calcium-deficient hydroxyapatite.
[0008] A process for large-scale preparation of calcium-deficient hydroxyapatite, characterized in that it comprises the following steps: (1) α-TCP is prepared by a solid phase reaction method: calcium hydrogen phosphate and calcium carbonate are mixed evenly at a molar ratio of 2:1 to obtain a mixed powder A; then 1%-20% by mass of polyvinyl alcohol is added to obtain a mixed powder B, which is calcined at high temperature and then rapidly cooled to room temperature to obtain α-TCP powder; (2) The product is ball milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a phosphate solution with a pH of 9-10, add the powder to the solution at a mass ratio of 1:9 to 1:2 during stirring, continue stirring for 1-2 hours after addition, and then let it stand for 4-24 hours to allow for a complete phase transition; the product is subjected to filter press treatment, dried at 60-100°C, and crushed to obtain calcium-deficient hydroxyapatite.
[0009] The powder mixing method in step (1) is dry stirring for 2-4 hours, supplemented by mechanical stirring.
[0010] The polyvinyl alcohol described in step (1) is low-polymerization degree polyvinyl alcohol powder.
[0011] The high temperature calcination in step (1) is to raise the temperature to 1000°C and keep it for 1 hour, and then calcine in a furnace at 1250-1400°C for 2-4 hours.
[0012] The phosphate solution described in step (3) comprises one of a disodium hydrogen phosphate solution and a dipotassium hydrogen phosphate solution.
[0013] The present invention provides a calcium-deficient hydroxyapatite, which is characterized in that it is prepared according to any of the above methods.
[0014] The present invention comprises the following steps: 1. Calcium hydrogen phosphate and calcium carbonate are mixed evenly at a molar ratio of 2:1 to obtain mixed powder A; then 1%-20% by mass of polyvinyl alcohol is added to obtain mixed powder B. The mixing method is dry stirring for 2-4 hours, supplemented by mechanical stirring.
[0015] 2. The mixed powder B is heated to 1000°C and kept at this temperature for 1 hour, then calcined in a furnace at 1250-1400°C for 2-4 hours, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder.
[0016] 3. The powder is ball-milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm.
[0017] 4. Prepare a phosphate solution with a pH of 9-10, including one of a disodium hydrogen phosphate solution and a dipotassium hydrogen phosphate solution.
[0018] 5. During the stirring process, add the powder to the solution at a mass ratio of 1:10 to 1:2. Continue stirring for 1-2 hours after adding, and then let it stand for 4-24 hours to allow for sufficient phase transformation.
[0019] 6. The product is subjected to filter pressing treatment, dried at 60-100°C, and crushed to obtain calcium-deficient hydroxyapatite.
[0020] The advantages of the present invention are: 1. The present invention provides a process for preparing calcium-deficient hydroxyapatite on a large scale, wherein raw materials of calcium hydrogen phosphate and calcium carbonate are calcined at high temperature by a solid phase reaction method, polyvinyl alcohol is added to avoid large-scale agglomeration of α-TCP after sintering, crystalline α-TCP is prepared after rapid cooling, and then it is phase-transformed in a weak alkaline solution to form calcium-deficient hydroxyapatite, and the product conversion rate is high.
[0021] 2. The method provided by the present invention has a large processing capacity, simple raw materials, simplified process, easy control, short production cycle, and is suitable for expanding production. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 XRD spectrum of calcium-deficient hydroxyapatite prepared in Example 1 of the present invention; Figure 2 This is a SEM image of the calcium-deficient hydroxyapatite prepared in Example 1 of the present invention. DETAILED DESCRIPTION
[0023] The following examples are implemented based on the technical solutions of the invention, and provide detailed implementation methods and specific operation processes, but the protection scope of the present invention is not limited to the following examples.
[0024] Example 1 A large-scale preparation of calcium-deficient hydroxyapatite is prepared according to the following steps: (1) α-TCP was prepared by a solid phase reaction method: 500 g of calcium hydrogen phosphate dihydrate and 145 g of calcium carbonate were mixed under mechanical stirring to obtain a mixed powder A; then 6.5 g of polyvinyl alcohol (1% by mass) was added to obtain a mixed powder B, the mixed powder B was heated to 1000°C and kept at this temperature for 1 h, then calcined in a furnace at 1400°C for 2 h, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder; (2) α-TCP powder was ball-milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a phosphate solution with a pH of 9, add the powder to the solution at a mass ratio of 1:4 during stirring, continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation; the product is subjected to filter press treatment, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
[0025] The XRD spectrum of the prepared calcium-deficient hydroxyapatite is shown in Figure 1 , SEM images are shown in Figure 2 .
[0026] Example 2 A large-scale preparation of calcium-deficient hydroxyapatite is prepared according to the following steps: (1) α-TCP was prepared by a solid phase reaction method: 500 g of calcium hydrogen phosphate dihydrate and 145 g of calcium carbonate were mixed under mechanical stirring to obtain a mixed powder A; 71.6 g of polyvinyl alcohol was added at a mass fraction of 10% to obtain a mixed powder B; the mixed powder B was heated to 1000°C and kept at this temperature for 1 h, then calcined in a furnace at 1400°C for 2 h, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder; (2) The powder is ball-milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a sodium dihydrogen phosphate solution with a pH of 9, add the powder to the solution at a mass ratio of 1:2 during stirring, continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation; the product is subjected to filter press treatment, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
[0027] Example 3 A large-scale preparation of calcium-deficient hydroxyapatite is prepared according to the following steps: (1) Preparation of α-TCP by solid phase reaction method: 500 g of calcium hydrogen phosphate dihydrate and 145 g of calcium carbonate were mixed under mechanical stirring to obtain mixed powder A; 71.6 g of polyvinyl alcohol was added at a mass fraction of 10% to obtain mixed powder B. The mixed powder B was heated to 1000°C and kept at this temperature for 1 h, then calcined in a furnace at 1400°C for 2 h, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder; (2) The powder is ball-milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a potassium dihydrogen phosphate solution with a pH of 9, add the powder to the solution at a mass ratio of 1:4 during stirring, continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation; the product is subjected to filter press treatment, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
Claims
1. A process for large-scale preparation of calcium-deficient hydroxyapatite, characterized in that: The following steps are involved: (1) α-TCP was prepared by solid-phase reaction method: calcium hydrogen phosphate and calcium carbonate were mixed uniformly at a molar ratio of 2:1 to obtain mixed powder A; then 1%-20% by mass of polyvinyl alcohol was added to obtain mixed powder B, which was calcined at high temperature and then rapidly cooled to room temperature to prepare α-TCP powder; (2) The product is crushed by ball milling and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a phosphate solution with a pH of 9-10, add the powder to the solution at a mass ratio of 1:9 to 1:2 during stirring, continue stirring for 1-2 hours after addition, and then let it stand for 4-24 hours to allow for complete phase transformation; the product is subjected to filter press treatment, dried at 60-100°C, and crushed to obtain calcium-deficient hydroxyapatite.
2. The process for large-scale preparation of calcium-deficient hydroxyapatite according to claim 1, characterized in that: The powder mixing method in step (1) is dry stirring for 2-4 hours, supplemented by mechanical stirring.
3. The process for large-scale preparation of calcium-deficient hydroxyapatite according to claim 1, characterized in that: The polyvinyl alcohol described in step (1) is low-polymerization degree polyvinyl alcohol powder.
4. The process for large-scale preparation of calcium-deficient hydroxyapatite according to claim 1, characterized in that: The high temperature calcination in step (1) is to raise the temperature to 1000°C and keep it for 1 hour, and then calcinate in a furnace at 1250-1400°C for 2-4 hours.
5. The process for large-scale preparation of calcium-deficient hydroxyapatite according to claim 1, characterized in that: The phosphate solution described in step (3) comprises one of a disodium hydrogen phosphate solution and a dipotassium hydrogen phosphate solution.
6. A process for large-scale preparation of calcium-deficient hydroxyapatite according to any one of claims 1 to 5, characterized in that: Prepare as follows: (1) α-TCP was prepared by solid-phase reaction method: 500 g of calcium hydrogen phosphate dihydrate and 145 g of calcium carbonate were mixed under mechanical stirring to obtain mixed powder A; then 6.5 g of polyvinyl alcohol (1% by mass) was added to obtain mixed powder B, and the mixed powder B was heated to 1000 °C and kept at this temperature for 1 h, then calcined in a furnace at 1400 °C for 2 h, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder; (2) α-TCP powder was ball-milled and passed through a 500-mesh sieve, with a particle size range of 1-30 μm; (3) Prepare a phosphate solution with a pH of 9. Add the powder to the solution at a mass ratio of 1:4 during stirring. Continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation. The product is filter-pressed, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
7. A process for large-scale preparation of calcium-deficient hydroxyapatite according to any one of claims 1 to 5, characterized in that: Preparation was carried out according to the following steps: (1) α-TCP was prepared by solid phase reaction method: 500 g of calcium hydrogen phosphate dihydrate and 145 g of calcium carbonate were mixed under mechanical stirring to obtain mixed powder A; 71.6 g of polyvinyl alcohol was added at a mass fraction of 10% to obtain mixed powder B; the mixed powder B was heated to 1000 °C and kept at this temperature for 1 h, then calcined in a furnace at 1400 °C for 2 h, taken out, and rapidly cooled under a blast environment to obtain α-TCP powder; (2) The powder is ball-milled and passed through a 500-mesh sieve to obtain a particle size range of 1-30 μm; (3) Prepare a sodium dihydrogen phosphate solution with a pH of 9. Add the powder to the solution at a mass ratio of 1:2 during stirring. Continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation. The product is filter-pressed, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
8. A process for large-scale preparation of calcium-deficient hydroxyapatite according to any one of claims 1 to 5, characterized in that: α-TCP was prepared using the following steps: 500g of calcium hydrogen phosphate dihydrate and 145g of calcium carbonate were mixed under mechanical stirring to obtain mixed powder A; 71.6g of polyvinyl alcohol (10% by mass) was added to obtain mixed powder B. Mixed powder B was heated to 1000°C and held for 1 hour, then calcined in a furnace at 1400°C for 2 hours, removed, and rapidly cooled under a forced air environment to obtain α-TCP powder. (1) The powder is ball-milled and passed through a 500-mesh sieve to obtain a particle size range of 1-30 μm; (2) Prepare a potassium dihydrogen phosphate solution with a pH of 9. Add the powder to the solution at a mass ratio of 1:4 during stirring. Continue stirring for 2 hours after addition, and then let it stand for 24 hours to allow for complete phase transformation. The product is filter-pressed, dried at 80°C, and crushed to obtain calcium-deficient hydroxyapatite.
9. A calcium-deficient hydroxyapatite, characterized in that Prepared according to any one of claims 1 to 5.