Preparation method of spherical hollow hydroxyapatite material
The gel ball is formed by gas shearing and the number of coating layers is controlled to prepare spherical hollow hydroxyapatite materials, which solves the problem of difficulty in controlling the scale and shell thickness in the prior art, and realizes the regularity of the morphology and performance optimization of the material, which is suitable for drug delivery, environmental governance and catalysis.
Patent Information
- Application Number
- CN202510493570.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-18
- Publication Date
- 2025-07-18
AI Technical Summary
The prior art is difficult to accurately control the scale and shell thickness of hollow structure HAp materials, affecting their performance in the fields of drug delivery, environmental governance and catalysis.
Gel balls are formed using gas shear as a pioneer template. By reacting calcium and phosphorus sources on the surface of the template, the particle size and number of coated layers of the gel ball are controlled to prepare spherical hollow hydroxyapatite materials.
The prepared spherical hollow hydroxyapatite material has regular morphology, uniform size, good crystallinity, and is suitable for drug sustained release, heavy metal adsorption and catalysis, and does not require high temperature and high pressure, and the amount of chemical reagents is small.
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Figure CN120328503A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of preparation of carrier materials, and particularly relates to a method for preparing spherical hollow hydroxyapatite materials. Background Art
[0002] Hydroxyapatite (HAp), as a biomimetic material with excellent biocompatibility, has attracted much attention in the fields of bone repair, drug delivery, catalytic carriers, and environmental remediation. In recent years, hollow-structured HAp materials have become a research hotspot due to their unique physical and chemical properties. Their internal cavities can significantly improve the drug loading capacity or the density of catalytic active sites. The particle size controls the interfacial area and interaction distance between the material and the outside world, determines the drug loading or release efficiency, hydrodynamic behavior, and the exposure degree of active sites. The porous structure of the shell endows it with a high specific surface area and selective permeation ability, while the shell thickness determines the mass transfer path length and mechanical strength, directly affecting the drug loading capacity, molecular diffusion resistance, and structural stability.
[0003] In the field of drug delivery, hollow HAp microspheres can achieve slow release and targeted release of drugs through the pores of the shell. Jiang et al. synthesized strontium-substituted hydroxyapatite (Sr-HAp) hollow microspheres by hydrothermal method, which have high drug loading efficiency and excellent biocompatibility. The specific surface area of the prepared Sr-HAp microspheres can be as high as 214.69 m 2 / g, and Sr-HAp shows a high DOX loading rate and continuous DOX release behavior. In environmental governance, the synergy between its cavity and shell can efficiently adsorb heavy metal ions or radionuclides. Guo et al. used potassium dodecyl phosphate, which is cheap and easily available, as a micelle template agent to synthesize iron-doped hydroxyapatite nanoparticles for the first time. The obtained iron-doped HAp nanoparticles have a size of 80-100 nm, a mesoporous shell thickness of 12 nm, a specific surface area of 80.1973 m 2 / g, and a pore volume of 0.43298 cm 3 / g, and have high-efficiency and selective adsorption performance for Cd 2+ In the catalytic field, the hollow structure can be used as a highly stable carrier to load nano-catalysts and enhance the mass transfer efficiency. Lei et al. prepared a novel CdS nanoparticles / hollow hydroxyapatite microspheres (CdS / HAp) photocatalyst with excellent photocatalytic performance by low-temperature hydrothermal method. Using tetracycline (TC) as a model pollutant, the photocatalytic ability of the prepared composite catalyst was studied. Compared with pure CdS and HAp, the CdS(10wt.%) / HAp composite material showed higher photocatalytic removal efficiency within 30 minutes.
[0004] However, the existing preparation technologies face the problem that it is difficult to accurately control the scale and shell thickness of the hollow structure. Therefore, there is an urgent need for a new preparation method to achieve the controllable preparation and performance optimization of hollow-structured HAp materials. Summary of the Invention
[0005] In order to solve the problems existing in the prior art, the object of the present invention is to provide a preparation method of spherical hollow hydroxyapatite materials with a simple preparation process, mild conditions, and capable of accurately controlling the material size and shell thickness. The present invention uses the gel beads obtained by gas shearing as the precursor template, and then uses a calcium source and a phosphorus source to react on the surface of the template and dry to prepare spherical hollow hydroxyapatite materials.
[0006] In order to achieve the above object, the technical solution of the present invention is as follows:
[0007] On the one hand, the present invention provides a spherical hollow hydroxyapatite material, the diameter of the spherical hollow hydroxyapatite material is 10 nm - 10 cm, the shell thickness is 2 nm - 1 cm, and it has a hollow spherical structure.
[0008] On the other hand, the present invention provides a preparation method of the above spherical hollow hydroxyapatite material, the method comprising the following steps:
[0009] (1) Preparation of gel beads
[0010] Inject the gel aqueous solution into the inner layer of the coaxial needle, and introduce nitrogen into the outer layer of the coaxial needle, so that the gel aqueous solution is pumped out through the coaxial needle and is cut by nitrogen and dropped into the calcium ion solution to obtain gel beads;
[0011] (2) Synthesis of spherical hollow hydroxyapatite materials by coating method
[0012] Transfer the gel beads obtained in step (1) to a beaker, add the phosphate ion solution to the beaker to react with the gel beads, then suck out the remaining phosphate ion solution, and then leave the gel beads in the bottle, and then add the calcium ion solution to the beaker to react with the gel beads. Repeat the above operations several times to coat on the gel beads until a hydroxyapatite shell is formed. Finally, dry the coated spherical hydroxyapatite to obtain spherical hollow hydroxyapatite materials.
[0013] Further, in the above technical solution, in step (1), the gel in the gel aqueous solution is one or more of hyaluronic acid, sodium alginate, pectin, heparin, sodium polyacrylate, polymaleic acid, sodium carboxymethyl cellulose, polyacrylamide sulfonate, polyphosphate, polyglutamic acid, polyacrylic acid, carboxymethyl cellulose, sodium polystyrene sulfonate, sulfonated chitosan, chondroitin sulfate, carrageenan, and the mass concentration of the gel aqueous solution is 0.01% - 20%.
[0014] Further, in the above technical solution, in step (1), the particle size of the gel beads is 8.0 nm - 9.9 cm.
[0015] Further, in the above technical solution, in step (1), the flow rate of the gel aqueous solution is 1 - 1000 μL / min.
[0016] Further, in the above technical solution, in step (1), the flow rate of the nitrogen is 0.1 - 10 L / min.
[0017] Further, in the above technical solution, in step (1), the calcium ion solution is one or more of calcium chloride solution, calcium nitrate solution, calcium acetate solution, calcium gluconate solution, calcium lactate solution, calcium bromide solution, calcium iodide solution, calcium citrate solution, calcium ascorbate solution, calcium propionate solution, calcium formate solution, calcium glutarate solution, calcium malate solution, calcium tartrate solution, calcium fumarate solution.
[0018] Further, in the above technical solution, in step (1), the concentration of the calcium ion solution is 0.001 - 10 mol / L.
[0019] Further, in the above technical solution, in step (2), the phosphate ion solution is one or more of sodium phosphate solution, potassium phosphate solution, ammonium phosphate solution, disodium hydrogen phosphate solution, sodium dihydrogen phosphate solution, dipotassium hydrogen phosphate solution, potassium dihydrogen phosphate solution, diammonium hydrogen phosphate solution, ammonium dihydrogen phosphate solution, phosphoric acid solution, sodium pyrophosphate solution, sodium tripolyphosphate solution, sodium hexametaphosphate solution, triethyl phosphate solution, glyphosate solution, ammonium phosphomolybdate solution.
[0020] Further, in the above technical solution, in step (2), the concentration range of the phosphate ion solution is 0.001 - 10 mol / L.
[0021] Further, in the above technical solution, in step (2), the calcium ion solution is one or more of calcium chloride solution, calcium nitrate solution, calcium acetate solution, calcium gluconate solution, calcium lactate solution, calcium bromide solution, calcium iodide solution, calcium citrate solution, calcium ascorbate solution, calcium propionate solution, calcium formate solution, calcium glutarate solution, calcium malate solution, calcium tartrate solution, calcium fumarate solution.
[0022] Further, in the above technical solution, in step (2), the concentration range of the calcium ion solution is 0.001 - 10 mol / L.
[0023] Further, in the above technical solution, in step (2), the coating times are 1 - 1000 times.
[0024] Further, in the above technical solution, in step (2), the drying method is one or more of normal temperature drying, freeze drying, heat drying, supercritical drying, spray drying, microwave drying, vacuum drying, electric field assisted drying, infrared drying, and air drying, and the drying temperature is -100°C to 900°C.
[0025] The beneficial effects of the present invention are as follows:
[0026] The spherical hollow hydroxyapatite material prepared by the present invention has regular morphology, uniform size, and good crystallinity.
[0027] The spherical hollow hydroxyapatite material prepared by the present invention uses the gel spheres formed by gas shear as the precursor template, and coats the gel spheres. The particle size of the hydroxyapatite material can be controlled by controlling the particle size of the gel spheres, and the thickness of the hydroxyapatite shell layer can be controlled by controlling the number of coating layers.
[0028] The spherical hollow hydroxyapatite material prepared by the present invention does not require drastic reactions such as high temperature or high pressure, and will not affect the stability of the structure of the drug to be loaded.
[0029] The spherical hollow hydroxyapatite material prepared by the present invention uses fewer chemical reagents and has a wide selection range. The phosphorus source and calcium source reagents required can be selected according to needs. Description of the Drawings
[0030] Figure 1 Microscopic picture of the gel spheres prepared in Example 1;
[0031] Figure 2 Microscopic pictures of hydroxyapatite with different coating times in Example 1, where A, B, C, D, and E are optical pictures of coating 100, 200, 300, 400, and 500 times respectively;
[0032] Figure 3 Scanning electron microscope picture of the spherical hollow hydroxyapatite material prepared in Example 5, where Figure A is the overall picture of the hydroxyapatite sample, Figures B and C are the surface morphology pictures of the sample after magnification, Figure D is the morphology picture of the sample after magnification, and Figure E is the cross-section and internal picture observed after the sample is magnified;
[0033] Figure 4 FTIR spectrum of the spherical hollow hydroxyapatite material prepared in Example 7;
[0034] Figure 5 XRD spectrum of the spherical hollow hydroxyapatite material prepared in Example 8. Detailed Embodiments
[0035] The method of the present invention will be further described below in conjunction with embodiments, but it is not a limitation to the present invention.
[0036] Unless otherwise specified, the materials used in the embodiments of the present invention can be obtained through commercial channels or prepared by conventional methods well-known to those skilled in the art.
[0037] Example 1
[0038] (1) Preparation of gel beads
[0039] A mixed aqueous solution of carboxymethyl cellulose and sodium alginate with a mass concentration of 5% was sucked into a syringe. A coaxial needle was tightly connected to the syringe through a rubber tube. The inner layer of the coaxial needle was a channel for the mixed solution of carboxymethyl cellulose and sodium alginate with a flow rate of 300 μL / min, and the outer layer of the coaxial needle was a nitrogen channel with a flow rate of 8 L / min, so that the mixed solution of carboxymethyl cellulose and sodium alginate was cut into balls with uniform size and regular shape by nitrogen. A calcium propionate solution was placed below the needle, so that the small balls could fall into the calcium propionate solution and crosslink with calcium propionate to form gel beads with a diameter of 780 μm;
[0040] As Figure 1 shown, the pore size of the gel beads in the solution is uniform.
[0041] (2) Synthesis of spherical hollow hydroxyapatite material by coating method
[0042] The gel beads prepared in step (1) were transferred to a beaker, and the solution in the sample was sucked out, leaving the gel beads in the beaker. Then, a phosphoric acid solution with a concentration of 10 mol / L was added to the beaker, and waited until the reaction between the phosphoric acid solution and the gel beads was complete. The remaining phosphoric acid solution in the sample was sucked out, leaving the gel beads in the beaker. Then, a calcium nitrate solution with a concentration of 7 mol / L was added to the beaker, and waited until the reaction between calcium nitrate and the gel beads was complete. The above steps were recorded as one coating on the surface of the gel beads. The above operation was repeated. According to the standard that one coating with phosphoric acid solution and calcium nitrate solution can form a layer of hydroxyapatite on the surface of the gel beads, the gel beads were coated 500 times. As Figure 2 shown, in the figure, A, B, C, D, and E are the optical pictures of coating 100, 200, 300, 400, and 500 times respectively. Until a hydroxyapatite shell was formed, and finally the coated spherical hydroxyapatite was placed in a vacuum drying oven at 50 °C for drying to obtain a spherical hollow hydroxyapatite material with a diameter of 800 μm and a shell thickness of 20 μm.
[0043] Example 2
[0044] (1) Preparation of gel beads
[0045] The sodium alginate aqueous solution with a mass concentration of 4% was sucked into a syringe. The coaxial needle was tightly connected to the syringe through a rubber tube. The inner layer of the coaxial needle was the sodium alginate solution channel with a flow rate of 200 μL / min, and the outer layer of the coaxial needle was the nitrogen channel with a flow rate of 6 L / min, so that the sodium alginate solution was cut into spheres with uniform size and regular shape by nitrogen. A mixed solution of calcium ascorbate and calcium nitrate was placed below the needle, so that the small spheres could fall into the mixed solution of calcium ascorbate and calcium nitrate and crosslink with calcium ascorbate and calcium nitrate to form gel spheres with a diameter of 1.2 cm;
[0046] (2) Synthesis of spherical hollow hydroxyapatite materials by coating method
[0047] The sodium alginate gel spheres prepared in step (1) were transferred to a beaker, and the solution in the sample was sucked out, leaving the sodium alginate spheres in the beaker. Then, the sodium tripolyphosphate solution with a concentration of 5 mol / L was added to the beaker and waited until the reaction between sodium tripolyphosphate and the gel spheres was complete. The remaining sodium tripolyphosphate solution in the sample was sucked out, leaving the sodium alginate spheres in the beaker. Then, the calcium lactate solution with a concentration of 10 mol / L was added to the beaker and waited until the reaction between calcium lactate and the gel spheres was complete. The above steps were recorded as coating once on the surface of the gel spheres. The above operations were repeated. According to the standard that coating with sodium tripolyphosphate solution and calcium lactate solution once could form a layer of hydroxyapatite on the surface of the gel spheres, the gel spheres were coated 500 times. As the number of coating times increased, the coating thickness of hydroxyapatite continuously increased, and the color of hydroxyapatite on the surface of the gel spheres gradually became darker until a hydroxyapatite shell was formed. Finally, the coated spherical hydroxyapatite was placed in a blast drying oven at 100 °C for drying to obtain spherical hollow hydroxyapatite materials with a diameter of 1.63 cm and a shell thickness of 0.43 cm.
[0048] Example 3
[0049] (1) Preparation of gel spheres
[0050] The aqueous solution of sodium polystyrene sulfonate with a mass concentration of 0.01% was sucked into a syringe. The coaxial needle was tightly connected to the syringe through a rubber tube. The inner layer of the coaxial needle was the sodium polystyrene sulfonate solution channel with a flow rate of 800 μL / min, and the outer layer of the coaxial needle was the nitrogen channel with a flow rate of 0.1 L / min, so that the sodium polystyrene sulfonate solution was cut into spheres with uniform size and regular shape by nitrogen. The calcium formate solution was placed below the needle, so that the small spheres could fall into the calcium formate solution and crosslink with calcium formate to form gel spheres with a diameter of 5.82 cm;
[0051] (2) Synthesis of spherical hollow hydroxyapatite materials by coating method
[0052] Transfer the sodium polystyrene sulfonate gel beads prepared in step (1) to a beaker, suck out the solution in the sample, and leave the sodium polystyrene sulfonate beads in the beaker. Then add the ammonium dihydrogen phosphate solution with a concentration of 1 mol / L to the beaker and wait until the reaction between ammonium dihydrogen phosphate and the gel beads is complete. Suck out the remaining ammonium dihydrogen phosphate solution in the sample and leave the sodium polystyrene sulfonate gel beads in the beaker. Then add the calcium acetate solution with a concentration of 3 mol / L to the beaker and wait until the reaction between calcium acetate and the gel beads is complete. The above steps are recorded as coating the surface of the gel beads once. Repeat the above operations. According to the standard that coating with ammonium dihydrogen phosphate solution and calcium acetate solution once can form a layer of hydroxyapatite on the surface of the gel beads, coat the gel beads 500 times until a hydroxyapatite shell is formed. Finally, after microwave drying the coated spherical hydroxyapatite at 40 °C, put it into a muffle furnace at 400 °C for drying to obtain a spherical hollow hydroxyapatite material with a diameter of 7.86 cm and a shell thickness of 2.25 cm.
[0053] Example 4
[0054] (1) Preparation of gel beads
[0055] Suck the aqueous solution of polyacrylic acid with a mass concentration of 10% into a syringe, tightly connect the coaxial needle to the syringe through a rubber tube. The inner layer of the coaxial needle is the polyacrylic acid solution channel with a flow rate of 800 μL / min, and the outer layer of the coaxial needle is the nitrogen channel with a flow rate of 6 L / min, so that the polyacrylic acid solution is cut into balls with uniform size and regular shape by nitrogen. Place the calcium gluconate solution below the needle so that the small balls can fall into the calcium gluconate solution and crosslink with calcium gluconate to form gel beads with a diameter of 300 nm;
[0056] (2) Synthesis of spherical hollow hydroxyapatite material by coating method
[0057] Transfer the polyacrylic acid gel beads prepared in step (1) to a beaker, suck out the solution in the sample, and leave the polyacrylic acid beads in the beaker. Then add the sodium pyrophosphate solution with a concentration of 1 mol / L to the beaker and wait until the reaction between sodium pyrophosphate and the gel beads is complete. Suck out the remaining sodium pyrophosphate solution in the sample and leave the polyacrylic acid beads in the beaker. Then add the calcium acetate solution with a concentration of 8 mol / L to the beaker and wait until the reaction between calcium acetate and the gel beads is complete. The above steps are recorded as coating the surface of the gel beads once. Repeat the above operations. According to the standard that coating with sodium pyrophosphate solution and calcium acetate solution once can form a layer of hydroxyapatite on the surface of the gel beads, coat the gel beads 800 times until a hydroxyapatite shell is formed. Finally, freeze-dry the coated spherical hydroxyapatite at -40 °C to obtain a spherical hollow hydroxyapatite material with a diameter of 460 nm and a shell thickness of 160 nm.
[0058] Example 5
[0059] (1) Preparation of gel beads
[0060] Inject an aqueous solution of hyaluronic acid with a mass concentration of 20% into a syringe. Connect a coaxial needle tightly to the syringe through a rubber tube. The inner layer of the coaxial needle is a hyaluronic acid solution channel with a flow rate of 100 μL / min, and the outer layer is a nitrogen channel with a flow rate of 10 L / min, so that the hyaluronic acid solution is cut into balls with uniform size and regular shape by nitrogen. Place a calcium malate solution below the needle so that the small balls can fall into the calcium malate solution and crosslink with calcium malate to form gel beads with a diameter of 470 μm;
[0061] (2) Synthesis of spherical hollow hydroxyapatite material by coating method
[0062] Transfer the hyaluronic acid gel beads prepared in step (1) to a beaker, suck out the solution in the sample, and leave the hyaluronic acid beads in the beaker. Then add a glyphosate solution with a concentration of 10 mol / L to the beaker and wait until the reaction between glyphosate and the gel beads is complete. Suck out the remaining glyphosate solution in the sample and leave the hyaluronic acid gel beads in the beaker. Then add a calcium citrate solution with a concentration of 6 mol / L to the beaker and wait until the reaction between calcium citrate and the gel beads is complete. The above steps are recorded as one coating on the surface of the gel beads. Repeat the above operations. According to the standard that one coating with glyphosate solution and calcium citrate solution can form a layer of hydroxyapatite on the surface of the gel beads, coat the gel beads 1000 times until a hydroxyapatite shell is formed. Finally, infrared dry the coated spherical hydroxyapatite at 200 °C to obtain a spherical hollow hydroxyapatite material.
[0063] Perform scanning electron microscopy observation on the sample prepared in Example 5, as Figure 3 shown, where Figure 3 A is the overall view of the hydroxyapatite sample, Figure 3 B, Figure 3 C are the surface morphology diagrams of the sample after magnification, Figure 3 D is the morphology diagram of the sample after magnification, Figure 3 E is the cross-section and internal view of the sample observed after magnification. It can be seen that the obtained hydroxyapatite has uniform pore size, a diameter of 500 μm, a shell thickness of 40 μm, and is a hollow spherical structure.
[0064] Example 6
[0065] (1) Preparation of gel beads
[0066] Draw the aqueous solution of polyglutamic acid with a mass concentration of 15% into a syringe. Connect the coaxial needle tightly to the syringe through a rubber tube. The inner layer of the coaxial needle is the polyglutamic acid solution channel with a flow rate of 400 μL / min, and the outer layer of the coaxial needle is the nitrogen channel with a flow rate of 1 L / min, so that the polyglutamic acid solution is cut into balls with uniform size and regular shape by nitrogen. Place the calcium lactate solution below the needle so that the small balls can fall into the calcium lactate solution and crosslink with calcium lactate to form gel balls with a diameter of 8.18 cm;
[0067] (2) Synthesis of spherical hollow hydroxyapatite materials by coating method
[0068] Transfer the polyglutamic acid gel balls prepared in step (1) to a beaker, suck out the solution in the sample, and leave the polyglutamic acid balls in the beaker. Then add the potassium phosphate solution with a concentration of 2 mol / L to the beaker and wait for the reaction between potassium phosphate and the gel balls to be complete. Suck out the remaining potassium phosphate solution in the sample and leave the polyglutamic acid gel balls in the beaker. Then add the calcium iodide solution with a concentration of 1 mol / L to the beaker and wait for the reaction between calcium iodide and the gel balls to be complete. The above steps are recorded as coating once on the surface of the gel balls. Repeat the above operations. According to the standard that coating with potassium phosphate solution and calcium iodide solution once can form a layer of hydroxyapatite on the surface of the gel balls, coat the gel balls 600 times until a hydroxyapatite shell is formed. Finally, perform supercritical drying on the coated spherical hydroxyapatite to obtain spherical hollow hydroxyapatite materials with a diameter of 10.00 cm and a shell thickness of 1.82 cm.
[0069] Example 7
[0070] (1) Preparation of gel balls
[0071] Draw the aqueous solution of sulfonated chitosan with a mass concentration of 10% into a syringe. Connect the coaxial needle tightly to the syringe through a rubber tube. The inner layer of the coaxial needle is the sulfonated chitosan solution channel with a flow rate of 50 μL / min, and the outer layer of the coaxial needle is the nitrogen channel with a flow rate of 0.8 L / min, so that the sulfonated chitosan solution is cut into balls with uniform size and regular shape by nitrogen. Place the calcium bromide solution below the needle so that the small balls can fall into the calcium bromide solution and crosslink with calcium bromide to form gel balls with a diameter of 2.59 cm;
[0072] (2) Synthesis of spherical hollow hydroxyapatite materials by coating method
[0073] Transfer the sulfonated chitosan gel beads prepared in step (1) to a beaker, suck out the solution in the sample, and leave the hyaluronic acid beads in the beaker. Then add a sodium phosphate solution with a concentration of 7 mol / L to the beaker and wait until the reaction between sodium phosphate and the gel beads is complete. Suck out the remaining sodium phosphate solution in the sample and leave the sulfonated chitosan gel beads in the beaker. Then add a calcium bromide solution with a concentration of 3 mol / L to the beaker and wait until the reaction between calcium bromide and the gel beads is complete. The above steps are recorded as one coating on the surface of the gel beads. Repeat the above operations. According to the standard that one coating with the sodium phosphate solution and the calcium bromide solution can form a layer of hydroxyapatite on the surface of the gel beads, coat the gel beads 30 times until a hydroxyapatite shell is formed. Finally, air-dry the spherical hydroxyapatite after coating to obtain a spherical hollow hydroxyapatite material with a diameter of 2.95 cm and a shell thickness of 0.36 cm.
[0074] Perform Fourier transform infrared spectroscopy scanning on the spherical hollow hydroxyapatite material obtained in Example 7. As Figure 4 shown, it indicates that the obtained hydroxyapatite has the correct structure.
[0075] Example 8
[0076] (1) Preparation of gel beads
[0077] Draw a heparin aqueous solution with a mass concentration of 0.5% into a syringe. Connect a coaxial needle tightly to the syringe through a rubber tube. The inner layer of the coaxial needle is the heparin solution channel with a flow rate of 20 μL / min, and the outer layer is the nitrogen channel with a flow rate of 1 L / min, so that the heparin solution is cut into uniformly sized and regularly shaped balls by nitrogen. Place a calcium formate solution below the needle so that the small balls can fall into the calcium formate solution and crosslink with calcium formate to form gel beads with a diameter of 7.25 cm;
[0078] (2) Synthesis of spherical hollow hydroxyapatite material by coating method
[0079] Transfer the heparin gel beads prepared in step (1) to a beaker, suck out the solution in the sample, and leave the heparin beads in the beaker. Then add a sodium dihydrogen phosphate solution with a concentration of 3 mol / L to the beaker and wait until the reaction between sodium dihydrogen phosphate and the gel beads is complete. Suck out the remaining sodium dihydrogen phosphate solution in the sample and leave the heparin gel beads in the beaker. Then add a calcium citrate solution with a concentration of 8 mol / L to the beaker and wait until the reaction between calcium citrate and the gel beads is complete. The above steps are recorded as coating the surface of the gel beads once. Repeat the above operations. According to the standard that coating with a sodium dihydrogen phosphate solution and a calcium citrate solution once can form a layer of hydroxyapatite on the surface of the gel beads, coat the gel beads 50 times until a hydroxyapatite shell is formed. Finally, subject the spherical hydroxyapatite after coating to electro-assisted drying to obtain a spherical hollow hydroxyapatite material with a diameter of 8.63 cm and a shell thickness of 1.85 cm.
[0080] Perform X-ray diffraction analysis on the spherical hollow hydroxyapatite material obtained in Example 8, as Figure 5 shown, indicating that the obtained hydroxyapatite has the correct structure.
[0081] The above examples are only the preferred examples of the present invention and do not limit the implementation manner. The protection scope of the present invention should be subject to the scope defined by the claims. Based on the above description, other different forms of changes or modifications can be made. The obvious changes or modifications derived therefrom are still within the protection scope of the present invention.
Claims
1. A spherical hollow hydroxyapatite material, characterized in that, The spherical hollow hydroxyapatite material has a diameter of 10 nm - 10 cm, a shell thickness of 2 nm - 1 cm, and has a hollow spherical structure.
2. The preparation method of the spherical hollow hydroxyapatite material according to claim 1, characterized in that, The method includes the following steps: (1) Prepare gel beads Inject the gel aqueous solution into the inner layer of the coaxial needle, and introduce nitrogen into the outer layer of the coaxial needle, so that the gel aqueous solution is pumped out through the coaxial needle and is cut by nitrogen and dropped into the calcium ion solution to obtain gel beads; (2) Synthesize spherical hollow hydroxyapatite material by coating method Transfer the gel beads obtained in step (1) to a beaker, add the phosphate ion solution to the beaker to react with the gel beads, then suck out the remaining phosphate ion solution, and then leave the gel beads in the bottle. Then add the calcium ion solution to the beaker to react with the gel beads. Repeat the above operations several times to coat the gel beads until a hydroxyapatite shell is formed. Finally, dry the coated spherical hydroxyapatite to obtain the spherical hollow hydroxyapatite material.
3. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, characterized in that, In step (1), the gel in the gel aqueous solution is one or more of hyaluronic acid, sodium alginate, pectin, heparin, sodium polyacrylate, polymaleic acid, sodium carboxymethyl cellulose, polyacrylamide sulfonate, polyphosphate, polyglutamic acid, polyacrylic acid, carboxymethyl cellulose, sodium polystyrene sulfonate, sulfonated chitosan, chondroitin sulfate, carrageenan, and the mass concentration of the gel aqueous solution is 0.01% - 20%.
4. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, characterized in that, In step (1), the particle size of the gel beads is 8.0 nm - 9.9 cm.
5. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, characterized in that, In step (1), the calcium ion solution is one or more of calcium chloride solution, calcium nitrate solution, calcium acetate solution, calcium gluconate solution, calcium lactate solution, calcium bromide solution, calcium iodide solution, calcium citrate solution, calcium ascorbate solution, calcium propionate solution, calcium formate solution, calcium glutarate solution, calcium malate solution, calcium tartrate solution, calcium fumarate solution.
6. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, wherein, In step (2), the phosphate ion solution is one or more of sodium phosphate solution, potassium phosphate solution, ammonium phosphate solution, disodium hydrogen phosphate solution, sodium dihydrogen phosphate solution, dipotassium hydrogen phosphate solution, potassium dihydrogen phosphate solution, diammonium hydrogen phosphate solution, ammonium dihydrogen phosphate solution, phosphoric acid solution, sodium pyrophosphate solution, sodium tripolyphosphate solution, sodium hexametaphosphate solution, triethyl phosphate solution, glyphosate solution, ammonium phosphomolybdate solution; The calcium ion solution is one or more of calcium chloride solution, calcium nitrate solution, calcium acetate solution, calcium gluconate solution, calcium lactate solution, calcium bromide solution, calcium iodide solution, calcium citrate solution, calcium ascorbate solution, calcium propionate solution, calcium formate solution, calcium glutarate solution, calcium malate solution, calcium tartrate solution, calcium fumarate solution.
7. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, characterized in that, In step (2), the number of coating times is 1 - 1000 times.
8. The preparation method of the spherical hollow hydroxyapatite material according to claim 2, characterized in that, In step (2), the drying method is one or more of normal temperature drying, freeze drying, heat drying, supercritical drying, spray drying, microwave drying, vacuum drying, electric field assisted drying, infrared drying, air drying, and the drying temperature is -100 °C to 900 °C.