Preparation method of spherical beta-tricalcium phosphate
The preparation of β-tricalcium phosphate by spherical CaCO3 template combined with chemical precipitation and hydrothermal method was solved, and the problem of difficulty in purity and size control in the prior art was achieved, and the high purity, uniform size and controllable morphology of β-tricalcium phosphate was achieved The preparation of powder has enhanced its application potential in the field of biomedical use.
Patent Information
- Application Number
- CN202411115932.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-14
- Publication Date
- 2024-12-10
AI Technical Summary
The existing preparation methods for β-tricalcium phosphate have problems such as low purity, difficult particle size control, and complex preparation process. It is difficult to produce high-purity, uniform size, and controllable morphology on a large scale.
Using spherical CaCO3 as a template, through the preparation method of combining chemical precipitation and hydrothermal method, NaHCO3 solution was used to drop into a soluble calcium salt solution containing amide bimini quaternary ammonium salt to form a spherical CaCO3 template, and then water was carried out in dilute phosphoric acid solution. Thermal reaction is finally calcined to obtain spherical β-tricalcium phosphate.
The prepared spherical β-tricalcium phosphate has high purity, small particle size, good crystallinity and dispersion, and uniform morphology. It is suitable for bone transplantation and drug carriers, which improves its application prospects in the field of biomedical .
Smart Images
Figure CN119100344A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a preparation method of spherical beta-tricalcium phosphate, belonging to the technical field of biomedical materials. Background Art
[0002] β-tricalcium phosphate, β-Ca3(PO4)2, abbreviated as β-TCP, is mainly composed of calcium (Ca) and phosphorus (P), with a Ca / P ratio of 1.5. 10 (PO4)6(OH)2), therefore, β-tricalcium phosphate has high biocompatibility, bioactivity and biodegradability. A large number of literature and biological experiments show that when β-tricalcium phosphate is implanted in the body as a bone repair material, due to its high compatibility in the body, β-tricalcium phosphate produces calcium and phosphorus products during the degradation process, while participating in the metabolism in the body and promoting bone growth in the body. In addition, a large number of clinical experiments have shown that β-tricalcium phosphate has no local or systemic toxic side effects or rejection reactions in the body. Taking into account the excellent biological properties of β-tricalcium phosphate, it is also widely used in drug carriers, medical cosmetology and bone repair materials.
[0003] There are many methods for synthesizing β-tricalcium phosphate, mainly including solid phase reaction method, coprecipitation method, hydrothermal method, etc. The common solid phase reaction method uses CaHPO4 and CaCl2 powders to mix and ball mill, and then calcined at 900℃ for 2 hours to obtain β-tricalcium phosphate powder. Studies have found that amorphous calcium phosphate can be used to prepare β-tricalcium phosphate powder with high purity through low-temperature calcination, but this method has high process requirements, and the instability of amorphous calcium phosphate makes it difficult to control β-tricalcium phosphate during the crystallization process. Coprecipitation method is a common wet process with advantages such as simple operation and no special requirements for equipment. The β-tricalcium phosphate powder prepared by this method has uniform particles and regular morphology. The more common method is to mix Ca(NO3)2 and Na2HPO4 solutions and prepare β-tricalcium phosphate powder by adjusting the pH value of the mixed solution. The hydrothermal method for preparing β-tricalcium phosphate has the advantages of controllable morphology and uniform particle size, but it is difficult to produce on a large scale. Although researchers have prepared β-tricalcium phosphate powder by different methods, the prepared β-tricalcium phosphate powder still has problems such as low purity, difficult particle size control, and complex preparation process. Therefore, preparing high-purity, uniform-sized, and morphology-controllable β-tricalcium phosphate by simple process is of great significance for expanding the clinical application of β-tricalcium phosphate. Summary of the invention
[0004] The invention synthesizes spherical CaCO3 and uses the spherical CaCO3 as a template to prepare spherical beta-tricalcium phosphate powder with different particle sizes by chemical precipitation method.
[0005] To achieve the above object, the technical solution adopted by the present invention is: a method for preparing spherical β-tricalcium phosphate, which is characterized by comprising the following steps: S1: dropping a NaHCO3 solution into a soluble calcium salt solution containing an amide gemini quaternary ammonium salt, continuing to stir the reaction after the addition is completed, and obtaining a spherical CaCO3 template by suction filtration, washing, and drying after the reaction is completed; S2: Weigh the spherical CaCO3 prepared above and place it in a dilute phosphoric acid solution, stir it evenly and then carry out a hydrothermal reaction. After the reaction is completed, cool it, centrifuge it, wash it, dry it, and calcine it to obtain spherical β-tricalcium phosphate.
[0006] The soluble calcium salt is calcium nitrate tetrahydrate, anhydrous calcium chloride or a mixture of the two.
[0007] The concentration of the amide gemini quaternary ammonium salt is 0.001%-5%.
[0008] The concentration of the NaHCO3 solution in step (1) is 0.1-1 mol / L; the dropping speed of the NaHCO3 solution is 2 ml / min-10 ml / min.
[0009] The concentration of the dilute phosphoric acid solution in step (1) is 0.005-0.05 mol / L; the stirring speed is 380r / min-500r / min.
[0010] The hydrothermal reaction temperature in step (2) is 100-120° C., and the reaction time is 10-15 h.
[0011] The calcination temperature in step (2) is 900-1000°C and the calcination time is 1-3h.
[0012] Compared with the prior art, the preparation method of spherical β-tricalcium phosphate described in the present invention has the following advantages: 1. The preparation method of spherical β-tricalcium phosphate of the present invention uses homemade spherical CaCO3 as a template and combines it with a chemical precipitation method, so that the prepared β-tricalcium phosphate nanopowder has high purity, small particle size, good crystallinity, good dispersibility, and its morphology is regular and uniform, and its performance is stable. It can be well used in biomedical fields such as bone transplantation and drug delivery, greatly improving its application prospects in the fields of biomaterials, drug carriers, etc. 2. The preparation method of spherical β-tricalcium phosphate of the present invention adopts a template method combined with a hydrothermal method. The preparation method is simple, the conditions are mild and controllable, the cycle is short, and there is no pollution to the environment. The prepared β-tricalcium phosphate presents a complete spherical morphology and has high crystallinity, purity and dispersibility. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1 The XRD diagram and standard spectrum of the spherical β-tricalcium phosphate prepared in Example 1 of the present invention.
[0014] Figure 2 This is a SEM image of the spherical β-tricalcium phosphate prepared in Example 1 of the present invention.
[0015] Figure 3 This is the SEM image of the spherical β-tricalcium phosphate prepared in Comparative Example 1. DETAILED DESCRIPTION
[0016] The technical solutions in the embodiments of the present invention will be described clearly and completely below. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present invention.
[0017] Example 1 Weigh 2.52g NaHCO3 and 6.67g CaCl2 and dissolve them in 200ml deionized water respectively. Stir well to prepare 0.3 mol / L NaHCO3 solution and 0.3 mol / L CaCl2 solution. Add 2% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly add the prepared 0.3 mol / L NaHCO3 solution to the 0.3 mol / L CaCl2 solution. Stir at room temperature for 0.5h before stopping the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process and place it in 50ml of dilute phosphoric acid solution with a concentration of 0.01 mol / L and put it into a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a blast drying oven at 100℃ for 12h. After the reaction is completed, take out the product, cool it naturally, centrifuge it, wash it and dry it. The dried powder was calcined in a muffle furnace at 900 °C for 2 h and then characterized. Figure 1 Its XRD spectrum shows a purity of 99.68%. Figure 2 Shown is a SEM image of spherical β-tricalcium phosphate.
[0018] Figure 1 The XRD diagram and standard spectrum of the spherical β-tricalcium phosphate prepared in Example 1 of the present invention show that the position of the XRD peak of the prepared spherical β-tricalcium phosphate should be consistent with the interplanar spacing on the standard card, which indicates that the crystal structure matches the known crystal structure. The peak is very sharp, which indicates that the crystal grain size is large and the lattice is neatly arranged. The high intensity of the peak means that the content of crystals in the sample is high and the orientation of the crystals is good.
[0019] Figure 2This is a SEM image of the spherical β-tricalcium phosphate prepared in Example 1 of the present invention. It can be seen from the figure that the powder prepared by the present invention has good dispersibility, no agglomeration, high particle sphericity and uniform size.
[0020] Example 2 Weigh 5.04g NaHCO3 and 28.34g Ca(NO3)2·4H2O and dissolve them in 400ml deionized water respectively. Stir them evenly to prepare 0.3 mol / L NaHCO3 solution and 0.3 mol / L Ca(NO3)2·4H2O solution. Add 0.05% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly add the prepared 0.3 mol / L NaHCO3 solution to the 0.3 mol / L Ca(NO3)2·4H2O solution, stir at room temperature for 1.5h and stop the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of a dilute phosphoric acid solution with a concentration of 0.005 mol / L and place it in a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a 100°C forced air drying oven for 12 hours. After the reaction is completed, take out the product, let it cool naturally, then centrifuge, wash and dry it. After the dried powder is calcined at 900°C in a muffle furnace for 2.5 hours, spherical β-tricalcium phosphate is obtained with a purity of 99.43%.
[0021] Example 3 Weigh 7.65g NaHCO3 and 20.25g CaCl2 and dissolve them in 200ml deionized water respectively. Stir well to prepare 0.9 mol / L NaHCO3 solution and 0.9 mol / L CaCl2 solution. Add 0.005% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly add the prepared 0.9 mol / L NaHCO3 solution to the 0.9 mol / L CaCl2 solution, and stop the reaction after stirring at room temperature for 0.5h. The product is obtained after filtration, washing and drying procedures, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process and place it in 50ml of dilute phosphoric acid solution with a concentration of 0.001 mol / L and put it into a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a blast drying oven at 100℃ for reaction for 12h. After the reaction is completed, the product is taken out, cooled naturally, centrifuged, washed and dried. The dried powder is calcined at 900°C in a muffle furnace for 1 hour to obtain spherical β-tricalcium phosphate with a purity of 99.74%.
[0022] Example 4 Weigh 10.08g NaHCO3 and 26.68g CaCl2 and dissolve them in 400ml deionized water respectively. Stir well to prepare 0.6 mol / L NaHCO3 solution and 0.6 mol / L CaCl2 solution. Add 0.1% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly add the prepared 0.6 mol / L NaHCO3 solution to the 0.6 mol / L CaCl2 solution, and stop the reaction after stirring at room temperature for 1.5h. The product is obtained by filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of dilute phosphoric acid solution with a concentration of 0.03mol / L and put it into a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a blast drying oven at 100℃ for reaction for 12h. After the reaction is completed, take out the product, cool it naturally, centrifuge it, wash it, and dry it. The dried powder was calcined in a muffle furnace at 900°C for 2.5 h to obtain spherical β-tricalcium phosphate with a purity of 99.52%.
[0023] Example 5 Weigh 7.56g NaHCO3 and 42.51g Ca(NO3)2·4H2O and dissolve them in 400ml deionized water respectively. Stir them evenly to prepare 0.45 mol / L NaHCO3 solution and 0.45 mol / L Ca(NO3)2·4H2O solution. Add 0.25% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly add the prepared 0.45 mol / L NaHCO3 solution to the 0.45 mol / L Ca(NO3)2·4H2O solution, stir at room temperature for 1h and stop the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of a dilute phosphoric acid solution with a concentration of 0.01 mol / L and place it in a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a 100°C forced air drying oven for 12 hours. After the reaction is completed, take out the product, let it cool naturally, then centrifuge, wash and dry it. After the dried powder is calcined at 900°C in a muffle furnace for 3 hours, spherical β-tricalcium phosphate is obtained with a purity of 99.83%.
[0024] Example 6 Weigh 5.04g NaHCO3 and 28.34g Ca(NO3)2·4H2O and dissolve them in 200ml deionized water respectively. Stir them evenly to prepare 0.6 mol / L NaHCO3 solution and 0.6 mol / L Ca(NO3)2·4H2O solution. Add 0.5% amide-based gemini quaternary ammonium salt to the NaHCO3 solution and dissolve evenly. At room temperature, slowly drop the prepared 0.6 mol / L NaHCO3 solution into the 0.6 mol / L Ca(NO3)2·4H2O solution, stir at room temperature for 0.5h and stop the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of a dilute phosphoric acid solution with a concentration of 0.02 mol / L and place it in a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a 100°C forced air drying oven for 12 hours. After the reaction is completed, take out the product, let it cool naturally, then centrifuge, wash and dry it. After the dried powder is calcined at 900°C in a muffle furnace for 2 hours, spherical β-tricalcium phosphate is obtained with a purity of 99.37%.
[0025] Example 7 Weigh 10.08g NaHCO3 and dissolve it in 400ml deionized water. Weigh 13.34g CaCl2 and 28.34g Ca(NO3)2·4H2O and mix them and dissolve them in 400ml deionized water. Stir them evenly to prepare 0.6 mol / L NaHCO3 solution and 0.6 mol / L soluble calcium salt mixed solution. Add 1.5% amide gemini quaternary ammonium salt to the NaHCO3 solution and dissolve it evenly. At room temperature, slowly add the prepared 0.6 mol / L NaHCO3 solution to the 0.6 mol / L soluble calcium salt mixed solution. Stir at room temperature for 1.5h and stop the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of a dilute phosphoric acid solution with a concentration of 0.03mol / L and place it in a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a 100°C forced air drying oven to react for 12 hours. After the reaction is completed, take out the product, place it naturally to cool, then centrifuge, wash and dry it. After the dried powder is calcined at 900°C in a muffle furnace for 3 hours, spherical β-tricalcium phosphate is obtained with a purity of 99.61%.
[0026] Comparative Example 1 0.09 mol of calcium carbonate was weighed and added to 300 mL of deionized water, 6% sodium lauryl sulfate, and 40% 2-methyl-1,3-propanediol aqueous solution, and stirred to form a suspension. Another 0.06 mol of phosphoric acid was dissolved in 300 mL of deionized water, 6% sodium lauryl sulfate, and 40% 2-methyl-1,3-propanediol aqueous solution, and stirred evenly. The phosphoric acid solution was dripped into the calcium carbonate solution at a speed of 2 ml / min using a peristaltic pump in an ultrasonic frequency of 40 kHz and an ultrasonic energy of 4423.68 J. The stirring speed was 300 rpm, and the pH value of the solution was adjusted to 8.5 using ammonia water. The ultrasonic time was 4 h. After the dropwise reaction was completed, stirring was continued for 4 h to fully mix the solution, and the solution was allowed to stand for 12 h. The solution was washed with water 3 times and with anhydrous ethanol 3 times by centrifugation to obtain a β-tricalcium phosphate precursor. The obtained β-tricalcium phosphate precursor was placed in a 120°C oven and dried for 12 hours, and then kept in a muffle furnace at 900°C for 3 hours to obtain nano-scale spherical β-tricalcium phosphate powder with a purity of 83.68%. Figure 3 This is the SEM image.
[0027] Comparative Example 2 Weigh 5.04g NaHCO3 and 28.34g Ca(NO3)2·4H2O and dissolve them in 400ml deionized water respectively. Stir well to prepare 0.3 mol / L NaHCO3 solution and 0.3 mol / L Ca(NO3)2·4H2O solution. Add 10% sodium polystyrene sulfonate to the NaHCO3 solution and dissolve it evenly. At room temperature, slowly drop the prepared 0.3 mol / L NaHCO3 solution into the 0.3 mol / L Ca(NO3)2·4H2O solution. Stir at room temperature for 1.5h and stop the reaction. The product is obtained after filtration, washing and drying, which is a spherical CaCO3 template. Weigh 1g of the CaCO3 template prepared in the above experimental process, place it in 50ml of a dilute phosphoric acid solution with a concentration of 0.005 mol / L and place it in a hydrothermal reactor lined with polytetrafluoroethylene. After stirring, place the hydrothermal reactor in a 100°C forced air drying oven for 12 hours. After the reaction is completed, take out the product, let it cool naturally, then centrifuge, wash and dry it. After the dried powder is calcined at 900°C in a muffle furnace for 2.5 hours, spherical β-tricalcium phosphate is obtained with a purity of 92.54%.
[0028] Both the comparative example and the present invention select calcium carbonate and phosphoric acid as the main raw materials for preparing spherical β-tricalcium phosphate. The difference is that the present invention uses self-made spherical CaCO3 as a template and reacts with phosphoric acid in a hydrothermal kettle to prepare the spherical β-tricalcium phosphate, while the comparative example introduces a surfactant to form a sphere and prepares β-tricalcium phosphate by a conventional precipitation method. The results show that the spherical β-tricalcium phosphate prepared by the present invention has a more complete spherical structure and higher purity.
Claims
1. A method for preparing spherical β-tricalcium phosphate, characterized in that it comprises the following steps: S1: Take a certain amount of soluble calcium salt solution, add amide gemini quaternary ammonium salt thereto and dissolve it completely, drop NaHCO3 solution into the soluble calcium salt solution, continue to stir the reaction after the addition is completed, and obtain a spherical CaCO3 template by suction filtration, washing and drying after the reaction is completed; S2: Weigh the spherical CaCO3 prepared above and place it in a dilute phosphoric acid solution, stir it evenly and then carry out a hydrothermal reaction. After the reaction is completed, cool it, centrifuge it, wash it, dry it, and calcine it to obtain spherical β-tricalcium phosphate.
2. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The soluble calcium salt is calcium nitrate tetrahydrate, anhydrous calcium chloride or a mixture of the two.
3. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The concentration of the amide gemini quaternary ammonium salt is 0.001%-5%.
4. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The concentration of the NaHCO3 solution in step (1) is 0.1-1 mol / L; the dropping speed of the NaHCO3 solution is 2 ml / min-10 ml / min.
5. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The concentration of the dilute phosphoric acid solution in step (1) is 0.005-0.05 mol / L.
6. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The stirring speed in step (1) is 380 r / min-500 r / min.
7. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The hydrothermal reaction temperature in step (2) is 100-120° C., and the reaction time is 10-15 h.
8. The method for preparing spherical β-tricalcium phosphate according to claim 1, characterized in that: The calcination temperature of step (2) is 900-1000°C, and the calcination time is 1-3h.