CN-119461283-B - Mesoporous hydroxyapatite microsphere regulated and controlled by malic acid and preparation method thereof

Abstract

The invention provides a mesoporous hydroxyapatite microsphere regulated and controlled by malic acid and a preparation method thereof, wherein the preparation method comprises the steps of sequentially dissolving a calcium source and a phosphorus source in deionized water, uniformly mixing, dropwise adding nitric acid or sodium hydroxide into a reaction solution, and regulating the pH value of the solution to be clear; adding malic acid with different concentrations as morphology regulator into the clarified reaction solution, adding urea, transferring the prepared solution into a hydrothermal reaction kettle, carrying out heat preservation reaction for 15min-12h at a set temperature, cooling the solution to room temperature after the reaction is finished, and centrifugally drying to obtain a hydroxyapatite powder sample. The invention adjusts sphericity, grain diameter, surface micro-nano structure, crystallinity and the like of the hydroxyapatite microsphere by controlling the concentration of the morphology regulator malic acid and adjusting the reaction time and temperature. The hydroxyapatite microsphere prepared by the invention is expected to be applied to the clinical application fields of drug controlled release systems, injectable facial wrinkle removal, hard tissue repair and the like.

Inventors

• WENG JIE
• HAN LULU
• Chang Dongbiao
• Bai Zhenfan
• ZHANG JIAHAO
• Yi Huixing
• LI XIAOHONG

Assignees

• 西南交通大学

Dates

Publication Date

20260505

Application Date

20241112

Claims (4)

1. 1. The preparation method of the mesoporous hydroxyapatite microsphere regulated and controlled by malic acid is characterized by comprising the following steps of: step S1, sequentially dissolving a calcium source and a phosphorus source in deionized water, and uniformly mixing to prepare a reaction solution; Step S2, dropwise adding nitric acid or sodium hydroxide into the reaction solution, and adjusting the pH value of the solution to be clear; step S3, adding malic acid with different concentrations into the clarified reaction solution to serve as a morphology regulator, and then adding urea; S4, transferring the prepared solution into a reaction kettle, and carrying out heat preservation reaction for 3-5h at a set temperature; S5, after the reaction is completed, cooling the solution to room temperature, and centrifugally drying to obtain a hydroxyapatite powder sample; in the step S3, the molar ratio of the urea to the calcium source is 0.56:0.1, the malic acid is L-malic acid, and the molar ratio of the malic acid to the calcium source is (0.1-0.2): 0.1; in step S4, the set temperature is 120 ℃ to 180 ℃.
2. 2. The method for preparing the malic acid controlled mesoporous hydroxyapatite microsphere according to claim 1, wherein in the step S1, calcium nitrate tetrahydrate and disodium hydrogen phosphate dodecahydrate are sequentially added into 50mL of deionized water to make the calcium source concentration be 0.1mol/L and the calcium-phosphorus molar ratio be 1.67, so as to prepare a reaction solution.
3. 3. The method for preparing the malic acid controlled mesoporous hydroxyapatite microsphere according to claim 1, wherein in step S2, the pH of the solution is adjusted by nitric acid or sodium hydroxide until the solution is clear, and the pH value of the solution is measured to be 2-3.
4. 4. A malic acid controlled mesoporous hydroxyapatite microsphere, characterized in that it is obtained by the preparation method according to any one of claims 1 to 3.

Description

Mesoporous hydroxyapatite microsphere regulated and controlled by malic acid and preparation method thereof Technical Field The invention relates to the technical field of inorganic biological materials, in particular to a mesoporous hydroxyapatite microsphere regulated and controlled by malic acid and a preparation method thereof. Background Hydroxyapatite (Hydroxyapatite, HAP) is a main inorganic component of human hard tissue, and is widely applied to biomedical fields such as bone implantation, wound repair, regenerative filling, drug carriers and the like. The biocompatibility and bone conductivity of HAP and bone tissue make it have significant application advantages in bone defect repair. According to the application requirements of different fields, the design of HAP particles with specific morphology structures is important to improving the functionality and application performance of the HAP particles. The morphology and surface nanostructure of HAP particles have a significant impact on their performance in biomedical applications. The porous HAP microsphere has high specific surface area and specific pore structure, and may be used in obviously raised adsorption capacity, protein and cell interaction and bioactivity, and has relatively high application potential in medicine loading and tissue engineering. Therefore, developing HAP microspheres with adjustable pore structure and morphology is important to improving the application performance of the HAP microspheres in the biomedical field. Currently, methods for preparing calcium phosphate microspheres include sol-gel methods, microemulsion methods, spray drying methods, template methods, and the like. The sol-gel method and the microemulsion method have mild synthesis conditions, but have low yield and are difficult to accurately control the morphology and the surface nano structure of the microsphere, and the spray drying method has high production efficiency, but is difficult to control the morphology and the size of the microsphere, so that the uniformity of the obtained particles is poor. In contrast, the template method provides a simpler and effective means for regulating the morphology and surface structure of the calcium phosphate particles. Particularly, the soft template method forms a template with a specific shape by self-assembly in a solution, and controls nucleation and crystal growth by utilizing the interaction of organic molecules and specific sites on the surface of inorganic crystals, thereby realizing the control of the morphology of HAP particles. However, compared with a macromolecular template, the singleness of small molecules in an adsorption mode and the limitation of the coverage of the surface of a crystal make the stability of the small molecules in the aspect of crystal morphology control insufficient. Therefore, how to combine the advantages of small molecule modulators and develop a stable and efficient hydrothermal synthesis method to realize the precise control of the morphology and structure of HAP microspheres is a problem to be solved at present. Disclosure of Invention Aiming at the prior art. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: In a first aspect, the application provides a method for preparing mesoporous hydroxyapatite microspheres regulated and controlled by malic acid, comprising the following steps: step S1, sequentially dissolving a calcium source and a phosphorus source in deionized water, and uniformly mixing to prepare a reaction solution; Step S2, dropwise adding nitric acid or sodium hydroxide into the reaction solution, and adjusting the pH value of the solution to be clear; Step S3, adding malic acid with different concentrations as a morphology regulator into the clarified reaction solution, then adding urea, and continuously stirring for 5 to 15 minutes; S4, transferring the prepared solution into a reaction kettle, and performing heat preservation reaction for 15min-12h at a set temperature; And S5, after the reaction is finished, cooling the solution to room temperature, centrifugally separating the precipitate, repeatedly cleaning the precipitate with deionized water and ethanol, drying at 80 ℃ for 48 hours, and centrifugally drying to finally obtain the hydroxyapatite powder sample with uniform morphology and high specific surface area. The particle size, the pore diameter and the specific surface area of the hydroxyapatite can be regulated and controlled by adopting a specific morphology regulator organic small molecular acid-malic acid and controlling the concentration of the morphology regulator, so that the spherical particle has a good spherical effect. Preferably, in step S1, calcium nitrate tetrahydrate and disodium hydrogen phosphate dodecahydrate are sequentially added to 50mL of deionized water so that the calcium source concentration is 0.1mol/L and the molar ratio of calcium to phosphorus is 1.67, thereby obtainin