Ultra-small microparticle-sized mesoporous hydroxyapatite nanoparticles and preparation and application thereof
By controlling micelle assembly behavior and high-temperature calcination, the morphology and size of mesoporous hydroxyapatite nanoparticles were precisely controlled, solving the problem of uncontrollable particle uniformity and morphology and size in existing technologies, and preparing highly efficient nanomaterials suitable for biomedicine.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- FUDAN UNIVERSITY
- Filing Date
- 2024-03-25
- Publication Date
- 2026-07-21
AI Technical Summary
Existing technologies make it difficult to precisely control the morphology and size of mesoporous hydroxyapatite nanoparticles, which limits their application in the biomedical field.
By controlling the dispersion and interaction of cationic surfactants in water and ethanol solutions, combined with the reaction of calcium and phosphorus sources, micelles are formed and then calcined at high temperature, achieving precise control over the morphology and size of mesoporous nanoparticles.
Highly uniform, millet-sized mesoporous hydroxyapatite nanoparticles were prepared, possessing an open mesoscopic structure, high specific surface area, and large pore volume, making them suitable as inorganic biomaterials for the biomedical field.
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Figure CN118359175B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of nanomaterial preparation technology, and relates to an ultra-small millet-sized mesoporous hydroxyapatite nanoparticle and its preparation and application. Background Technology
[0002] Hydroxyapatite (HA) contains calcium, phosphorus, and other elements that are the main inorganic phosphate mineral components of human bones and teeth, and can be replaced through normal metabolic pathways in the human body. Compared with other tissue engineering materials, HA ceramics are an ideal material for filling bone tissue defects because of their excellent osteoconductivity, osteoinduction, and biocompatibility, and because they do not cause immune rejection after implantation. The use of synthetic HA as a substitute for bone tissue in the biomedical field has become a new research hotspot. However, the low specific surface area, large particle size, and poor mechanical properties of traditional HA limit its practical application in bone tissue engineering.
[0003] Recently, some researchers have synthesized mesoporous hydroxyapatite (MHA) nanoparticles. Due to their higher surface area, open mesoporous channels, enhanced mechanical properties, and superior bioactivity, they possess enormous application potential in the biomedical field. However, currently reported mesoporous hydroxyapatite materials are mostly limited to bulk materials or irregular micron-sized particles, and the poor uniformity of these particles restricts their further application in biomedicine. Most importantly, due to insufficient understanding of the self-assembly process, the reported preparation methods cannot achieve precise control over their morphology and size.
[0004] For example, Chinese patent CN202010732089.6 discloses a method for preparing modified hydroxyapatite shaping materials, including the preparation of nanorod-shaped hydroxyapatite, the modification of nanorod-shaped hydroxyapatite, and the preparation of fillers. The preparation of the nanorod-shaped hydroxyapatite involves a hydrothermal reaction at relatively high temperature and pressure, and the use of octadecyl dimethyl benzyl ammonium chloride as a cationic surfactant. The nanorod-shaped hydroxyapatite prepared by this patent lacks a clearly visible mesoscopic structure, hindering the ion dissolution process and reducing its bioactivity. The prepared hydroxyapatite has a particle size of approximately 20 μm, which is large, resulting in a low specific surface area. Furthermore, precise control over its morphology and size cannot be achieved, limiting its application scope and direction in the biomedical field.
[0005] Therefore, the precise preparation of mesoporous hydroxyapatite nanoparticles with adjustable morphology and / or size through simple and controllable methods has significant scientific research and application value. Summary of the Invention
[0006] The purpose of this invention is to provide ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, their preparation method, and applications, so as to fill the gap in highly uniform hydroxyapatite nanoparticles and solve the problem of poor controllability of nanoparticle morphology and / or size in the prior art.
[0007] The objective of this invention can be achieved through the following technical solutions:
[0008] On one hand, the present invention provides a method for preparing ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, comprising the following steps:
[0009] (1) Dissolve the cationic surfactant and phosphate in a mixture of water and ethanol to obtain a clear solution A. Adjust the pH of solution A to 10-14. Dissolve the calcium salt in water to obtain a clear solution B.
[0010] (2) Add solution B dropwise to solution A, stir until homogeneous, and then heat under reflux in a water bath.
[0011] (3) After the reaction is completed, the particles are centrifuged, washed, dried, and then heat-treated to obtain ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, which are the target products.
[0012] Furthermore, the cationic surfactant is any one or a combination of several of hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, and tetradecyldimethylbenzylammonium chloride.
[0013] Furthermore, in step (1), the amount of cationic surfactant used satisfies the following condition: its concentration in solution A is 0.1–20 wt%.
[0014] Furthermore, in step (1), the phosphate is any one or a combination of several of dipotassium hydrogen phosphate, potassium dihydrogen phosphate, and potassium phosphate.
[0015] Furthermore, in step (1), the amount of phosphate used satisfies the following condition: its concentration in solution A is 0.1–20 wt%.
[0016] Furthermore, in step (1), the volume ratio of ethanol to water is 1:2 to 1:4.
[0017] Furthermore, in step (1), the calcium salt is any one or a combination of calcium chloride, calcium sulfate, and calcium nitrate.
[0018] Furthermore, in step (1), the amount of calcium salt used satisfies the following condition: its concentration in solution B is 0.1–20 wt%.
[0019] Furthermore, the reagents used to adjust solution A are selected from any one or a combination of several of ammonia, sodium hydroxide, and potassium hydroxide.
[0020] Furthermore, in step (2), solutions B and A maintain Ca 2+ / PO4 3- The molar ratio is 1.67.
[0021] Furthermore, the water bath reflux heating temperature is 100–150℃, and the time is 18–30 hours.
[0022] Furthermore, in step (3), the heat treatment is carried out in an air atmosphere at a temperature of 500–900°C for 2–4 hours.
[0023] In the initial stage of the reaction, the cationic surfactant is fully dispersed and dissolved in a mixed solution of water and ethanol, forming micelles. Subsequently, upon the addition of a phosphorus source, the phosphate anions interact with the cationic surfactant through electrostatic Coulomb forces, altering the charge density of the inorganic layer. This causes the long chains of the surfactant to approach each other, and the interfacial tension between the inorganic and organic species changes the arrangement of the surfactant. After the addition of a calcium source, the phosphorus and calcium sources react at the interface, changing the overall inorganic-organic solid phase composition. The final phase is determined by the assembly interface and the assembly behavior of the micelles. By controlling the water-to-ethanol ratio, the interfacial tension of micelle self-assembly can be altered, and the assembly behavior of the composite micelles can be manipulated, thereby achieving precise control over the particle uniformity, morphology, and size of the prepared mesoporous nanoparticles. Finally, after a high-temperature calcination process, the nanoparticles lose their surfactant, yielding highly uniform, ultra-small millet-sized mesoporous hydroxyapatite nanoparticles.
[0024] In addition, the present invention also limits the process conditions in the reaction process, such as the reaction temperature, the mass ratio of each raw material, and similar process conditions, in order to precisely control the formation and directional assembly of micelles. If the limits are exceeded, the structure, orientation, and size of the nanoparticles will be out of control.
[0025] Secondly, the present invention also provides ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, which are prepared by any of the preparation methods described above. The nanoparticles are uniform in size, with an ultra-small "millet-sized" shape of 15-25 nm in diameter and 70-90 nm in length, and contain mesoporous channels with uniform pore size.
[0026] Thirdly, the present invention also provides the application of ultra-small millet-sized mesoporous hydroxyapatite nanoparticles in the preparation of inorganic biomaterials for the biomedical field.
[0027] Compared with the prior art, the present invention has the following advantages:
[0028] (1) The prepared mesoporous nanoparticles have an open and clear mesoscopic structure, high specific surface area and large pore volume.
[0029] (2) The method provided can precisely control the assembly behavior of micelles, thereby not only obtaining nanoparticles with uniform size, but also controlling the morphology and size of nanoparticles. Attached Figure Description
[0030] Figure 1 Low-magnification scanning electron microscope image of the ultra-small millet-like mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0031] Figure 2 High-magnification scanning electron microscope image of the ultra-small millet-like mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0032] Figure 3 Low-magnification transmission electron microscope image of the ultra-small millet-like mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0033] Figure 4 High-magnification transmission electron microscope image of the ultra-small millet-like mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0034] Figure 5 Scanning electron microscope image of the short rod-shaped mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0035] Figure 6 Low-magnification transmission electron microscope image of the short rod-shaped mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0036] Figure 7 Low-magnification transmission electron microscope image of the short rod-shaped mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0037] Figure 8 Low-magnification scanning electron microscope image of the long rod-shaped mesoporous hydroxyapatite nanoparticles prepared by this invention.
[0038] Figure 9 Scanning electron microscope image of the irregularly shaped hydroxyapatite nanoparticles prepared by this invention. Detailed Implementation
[0039] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.
[0040] In the following embodiments, unless otherwise specified, the raw materials or processing techniques are conventional commercially available raw materials or conventional processing techniques in the art.
[0041] Example 1:
[0042] Hexadecyltrimethylammonium chloride and dipotassium hydrogen phosphate were fully dissolved in a mixed solution of water and ethanol (volume ratio 3:1) to form a clear solution A, wherein the mass fraction of hexadecyltrimethylammonium chloride was 6%, the mass fraction of dipotassium hydrogen phosphate was 4%, and the pH value was 12. Calcium chloride was then dissolved in water to obtain a clear solution B (calcium chloride mass fraction 6%). Solution B was added dropwise to solution A, maintaining a constant Ca²⁺ concentration between solutions B and A. 2+ / PO4 3- The molar ratio was 1.67. After thorough mixing, the mixture was refluxed in a water bath and heated to 120°C for 24 hours. After the reaction, the sample was washed with alternating centrifugation using ethanol and water, and dried at 100°C. The product was calcined at 700°C for 3 hours to obtain ultra-fine millet-sized mesoporous hydroxyapatite nanoparticles. (When calculating the amount of each raw material added, the mutual reactions between the raw materials during the addition process are not considered.)
[0043] Low-magnification scanning electron microscope image of the particles prepared in Example 1 ( Figure 1 The nanoparticles exhibit a rice-grain-like appearance, with uniform size and consistent morphology. This can be observed through magnified scanning electron microscope images (SEM images). Figure 2 It can be observed that the particles are approximately 80 nm long and 20 nm in diameter. (Transmission electron microscopy image) Figure 3 and Figure 4 This further confirmed its highly uniform, rice-grain-like microstructure, with mesopore diameters of approximately 2.7 nm. Furthermore, its morphology and size can be precisely controlled by adjusting interfacial tension. For example, keeping other precursor concentrations constant and only increasing the water-to-alcohol ratio (e.g., a volume ratio of 6:1) can form mesoporous hydroxyapatite nanorods approximately 160 nm long. Figure 5 ), based on scanning and transmission electron microscopy results ( Figure 6 and Figure 7 Furthermore, it can be clearly observed that the synthesized short rod-shaped hydroxyapatite nanoparticles all possess a clear mesoscopic structure and uniform microstructure, indicating that this method has a high degree of controllability. Further increasing the water-to-alcohol ratio to a volume ratio of 10:1, while keeping the concentrations of other precursors constant, allows the formation of long rod-shaped mesoporous hydroxyapatite nanoparticles approximately 500 nm in length. Figure 8 This method, which precisely controls the morphology and size of precursor solutions by adjusting the water-to-alcohol ratio, demonstrates the feasibility and simplicity of designing and synthesizing mesoporous hydroxyapatite nanoparticles with different microstructures.
[0044] Comparative Example 1:
[0045] Most aspects are the same as in Example 1, except that no cationic surfactant is added. As shown in the scanning electron microscope (SEM) Figure 9The resulting particles have uneven morphology and size, and no obvious mesoporous structure on the surface, thus failing to form mesoporous hydroxyapatite nanoparticles.
[0046] Example 2:
[0047] Unlike Example 1, in this example, the amount of hexadecyltrimethylammonium chloride added is adjusted to have a concentration of 0.1 wt% in the clear solution A.
[0048] Example 3:
[0049] Unlike Example 1, in this example, the amount of hexadecyltrimethylammonium chloride added is adjusted to have a concentration of 20 wt% in the clarified solution A.
[0050] Example 4:
[0051] Unlike Example 1, in this example, the amount of dipotassium hydrogen phosphate is adjusted to a concentration of 0.1 wt% in the clear solution A.
[0052] Example 5:
[0053] Unlike Example 1, in this example, the amount of dipotassium hydrogen phosphate is adjusted to a concentration of 20 wt% in the clear solution A.
[0054] Example 6:
[0055] Unlike Example 1, in this example, the water-to-alcohol ratio is adjusted to a volume ratio of 2:1.
[0056] Example 7:
[0057] Unlike Example 1, in this example, the water-to-alcohol ratio is adjusted to a volume ratio of 4:1.
[0058] Example 8:
[0059] Unlike Example 1, in this example, the amount of calcium chloride used satisfies the following condition: its concentration in solution B is 0.1 wt%.
[0060] Example 9:
[0061] Unlike Example 1, in this example, the amount of calcium chloride used satisfies the following condition: its concentration in solution B is 20 wt%.
[0062] Examples 10-13:
[0063] Unlike Example 1, in this example, hexadecyltrimethylammonium chloride is replaced with equimolar amounts of hexadecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, and tetradecyldimethylbenzylammonium chloride.
[0064] Examples 14-15:
[0065] Unlike Example 1, in this example, calcium chloride is replaced with equimolar amounts of calcium nitrate and calcium sulfate.
[0066] Examples 16-17:
[0067] Unlike Example 1, in this example, dipotassium hydrogen phosphate is replaced with equimolar amounts of monopotassium hydrogen phosphate and potassium phosphate.
[0068] Example 18:
[0069] Unlike Example 1, in this example, the reaction temperature is 100°C and the reaction time is 30 hours.
[0070] Example 19:
[0071] Unlike Example 1, in this example, the reaction temperature is 150°C and the reaction time is 18 hours.
[0072] Example 20:
[0073] Unlike Example 1, in this example, the heat treatment temperature is 500°C and the time is 4 hours.
[0074] Example 21:
[0075] Unlike Example 1, in this example, the heat treatment temperature is 900°C and the time is 2 hours.
[0076] In summary, the method of this invention can control the assembly behavior of micelles, thereby not only obtaining highly uniform ultra-small millet-like microstructures, but also controlling the morphology and size of nanoparticles. This addresses two problems in the preparation of existing mesoporous hydroxyapatite nanoparticles: firstly, the uniformity of the nanoparticles; and secondly, the lack of precise control over parameters such as the morphology and size of the prepared particles in currently reported methods.
[0077] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.
Claims
1. A method for preparing ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, characterized in that, Includes the following steps: (1) Dissolve the cationic surfactant and phosphate in a mixture of water and ethanol to obtain a clear solution A. Adjust the pH of solution A to 10-14. Dissolve the calcium salt in water to obtain a clear solution B. (2) Add solution B dropwise to solution A, stir until homogeneous, and then heat under reflux in a water bath; (3) After the reaction is completed, the particles are centrifuged, washed, dried, and then heat-treated to obtain ultra-small millet-sized mesoporous hydroxyapatite nanoparticles, which are the target products; the cationic surfactant is any one or a combination of several of hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, and tetradecyldimethylbenzylammonium chloride. In step (1), the amount of cationic surfactant used satisfies the following condition: its concentration in solution A is 0.1~20wt%; In step (1), the phosphate is any one or a combination of several of dipotassium hydrogen phosphate, potassium dihydrogen phosphate, and potassium phosphate; In step (1), the amount of phosphate used satisfies the following condition: its concentration in solution A is 0.1~20wt%; In step (1), the volume ratio of ethanol to water is 1:2 to 1:4; In step (1), the calcium salt is any one or a combination of calcium chloride, calcium sulfate, and calcium nitrate; In step (1), the amount of calcium salt used satisfies the following condition: its concentration in solution B is 0.1~20wt%; The reagent used to adjust solution A is selected from any one or a combination of several of ammonia, sodium hydroxide, and potassium hydroxide. In step (2), the amounts of solution B and solution A added satisfy: Ca 2+ / PO4 3− The molar ratio is 1.67; The water bath reflux heating temperature is 100~150 ℃, and the time is 18~30h.
2. The method for preparing ultra-small millet-sized mesoporous hydroxyapatite nanoparticles according to claim 1, characterized in that, In step (3), the heat treatment is carried out in an air atmosphere at a temperature of 500~900℃ for 2~4 hours.
3. A type of ultra-small millet-sized mesoporous hydroxyapatite nanoparticle, prepared by the preparation method described in claim 1 or 2, characterized in that, The nanoparticles are uniform in size, appearing as ultra-small "rice grains" with a diameter of 15-25 nm and a length of 70-90 nm, containing mesoporous channels with uniform pore size.
4. The application of the ultra-small millet-sized mesoporous hydroxyapatite nanoparticles as described in claim 3 in the preparation of inorganic biomaterials for the biomedical field.