Preparation method of metal-doped hydroxyapatite nanoflower

Abstract

The invention discloses a preparation method of a metal doped type hydroxyapatite nanoflower. The method specifically comprises the following steps: dispersing a calcium source and soluble metal salt into water, adding acid phosphate, urea and L-histidine, uniformly mixing, carrying out a hydrothermal reaction, mechanically stirring, filtering, washing, and drying a hydrothermal system precipitate to obtain the corresponding metal-doped hydroxyapatite nanoflower. Compared with the prior art, the metal-doped hydroxyapatite nanoflower prepared by the preparation method disclosed by the invention is directly assembled by nanosheets, and a single metal type can be doped in a customized manner. According to the method, water is used as a unique solvent, the use of an organic solvent is avoided, the pH does not need to be adjusted in advance, the technological process is simple, operation is convenient, equipment investment is small, and the method is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of inorganic functional materials, and particularly relates to a preparation method of metal-doped hydroxyapatite nanoflower. BACKGROUND

[0002] Hydroxyapatite (HAP) is a calcium phosphate salt with a hexagonal crystal structure, and its chemical formula is Ca 10 (PO4)6(OH)2. It is widely present in nature and living organisms and has good biocompatibility. It is widely used in biomedical, oral medicine, environmental protection and other fields. Metal ion doping can further optimize the performance of hydroxyapatite to meet complex application requirements. In biomedical applications, Mg doping optimizes degradation and osteogenic activity, which is suitable for bone repair scaffolds and drug release carriers; Cu doping imparts antibacterial properties, which is used in antibacterial bone cement and wound dressings to reduce the risk of infection. In the field of oral medicine, Zn doping promotes osteoblast proliferation and immune regulation, which can be used in enamel repair materials and orthopedic implants. In the field of environmental protection, Fe doping facilitates material recycling and reuse due to its magnetic properties, and Fe and Cu doping can enhance its catalytic activity, which is used in organic pollutant degradation reactions to exhibit high-efficiency catalytic effects and significant environmental governance value.

[0003] HAP nanoflower is a three-dimensional flower-like architecture formed by self-assembly of nanosheets or nanorods. The nanoflower structure imparts the material with high specific surface area and multi-level pores, higher surface energy and active site density, and also enhances the mechanical toughness of the material, avoiding problems such as easy agglomeration of nanoparticles and poor dispersibility of nanorods. Patent CN102556993A dissolves calcium nitrate tetrahydrate and diammonium hydrogen phosphate in a dilute nitric acid solution, and then simultaneously drops into a urea solution, controls the pH to be 3-6, and obtains a three-dimensional nanoflower HAP composed of one-dimensional nanorods and two-dimensional nanobands through hydrothermal reaction. Patent CN108004527A adds a calcium source, a phosphorus source and a zinc source into water, adjusts the pH value to 9-11, and obtains zinc-doped HAP nanoflower through hydrothermal reaction in the presence of EDTA-2Na. The above two nanoflower synthesis methods both need to control the pH range in advance, and are not suitable for synthesizing other metal-doped HAP nanoflowers, so the application range is limited. SUMMARY

[0004] In view of the problems in the prior art, the present application discloses a preparation method of metal-doped hydroxyapatite nanoflower. Not only can the nanoflower HAP composed of nanosheets directly assembled be synthesized, but also the type of doped metal can be customized. In the present application, the calcium source and the soluble metal salt are dispersed into water, then the acid phosphate, urea and L-histidine are added, the mixture is uniformly mixed, and then the hydrothermal reaction is carried out with the aid of mechanical stirring to synthesize the nanoflower HAP, and the type of soluble metal salt is changed to realize the customization of metal-doped nanoflower HAP. The specific steps are as follows: (1) dispersing a calcium source and a soluble metal salt into water and stirring uniformly; (2) sequentially adding an acid phosphate, urea and L-histidine, and stirring for a period of time; (3) placing the mixture obtained in step (2) into a hydrothermal reaction kettle, and performing hydrothermal reaction at high temperature and with mechanical stirring; (4) after the hydrothermal reaction is completed, centrifuging and collecting the precipitate in the system, and washing and drying to obtain the metal-doped hydroxyapatite nanoflower.

[0005] Further, in step (1), the calcium source is one or more of calcium chloride, calcium nitrate, calcium sulfate, etc., and can also be phosphogypsum with calcium sulfate as the main component, and the theoretical [Ca 2+ ] ion concentration in the system is 0.01 - 0.35 M.

[0006] Further, in step (1), the soluble metal salt is one of a soluble copper salt, a soluble zinc salt, a soluble magnesium salt, a soluble cobalt salt, a soluble iron salt, etc., and the [M n+ ] ion concentration in the system is 0.001 - 0.06 M.

[0007] Further, in step (2), the acid phosphate is one or more of monohydrogen phosphate and dihydrogen phosphate, and the theoretical [PO4 3- ] ion concentration in the system is 0.01 - 0.21 M.

[0008] Further, in steps (1) and (2), the [Ca 2+ ] provided by the calcium source, the [M n+ ] provided by the soluble metal salt and the [PO4 3- ] provided by the acid phosphate satisfy the condition that ([Ca 2+ ]+[M n+ ]) / [PO4 3- ] is 1.50 - 1.67, and [M n+ ] / ([Ca 2+ ]+[M n+ ]) is 0.1 - 20%.

[0009] Further, in step (2), the urea content in the system is 0.05 - 2.10 M.

[0010] Further, in step (2), the L-histidine content in the system is 0.01 - 0.10 mM.

[0011] Further, in step (2), the stirring speed is 100 - 900 rpm, and the reaction time is 5 - 30 min.

[0012] Further, in step (3), the mechanical stirring speed during the hydrothermal reaction is 50 - 150 rpm, the hydrothermal reaction temperature is 60 - 200℃, and the hydrothermal reaction time is 2 - 24 h.

[0013] Further, in step (4), the centrifugal speed is 3000 - 8000 rpm, and the centrifugal time is 2 - 10 min.

[0014] Further, in step (4), the washing liquid is ultrapure water and ethanol.

[0015] Further, in step (4), the drying temperature of the nanoflower HAP is 50 - 100℃, and the drying time is 2 - 24 h.

[0016] Compared with the prior art, the present application has the following advantages: (1) The nanoflower HAP prepared by the present application is directly assembled from nanosheets, and the type of doped metal can be customized. (2) In the present application, calcium salt and metal salt are simultaneously dispersed in water, which is conducive to the uniform embedding of metal ions into the HAP crystal lattice; the acid phosphate salt avoids the precipitation of metal ions due to the sudden change of pH, and realizes the synergistic control of doping and crystallization; urea inhibits the longitudinal growth of crystals along the c-axis, forming sheet-shaped HAP, which is conducive to the direct assembly into nanoflower HAP; L-histidine further induces the formation of sheet-shaped HAP.

[0017] (3) The present application uses water as the only solvent, avoids the use of organic solvents, and does not need to pre-adjust the pH, so the process is simple, easy to operate, and suitable for industrial application. BRIEF DESCRIPTION OF DRAWINGS

[0018] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0019] Figure 1 is a scanning electron microscope (SEM) image of the HAP prepared in Example 1.

[0020] Figure 2 is an X-ray powder diffraction (XRD) pattern of the HAP prepared in Example 1.

[0021] Figure 3is a SEM image of HAP prepared in Example 2.

[0022] Figure 4 is an infrared absorption spectrum (FTIR) image of HAP prepared in Example 2.

[0023] Figure 5 is a SEM image of HAP prepared in Example 3.

[0024] Figure 6 is a SEM image of HAP prepared in Example 4.

[0025] Figure 7 is a SEM image of HAP prepared in Example 5.

[0026] Figure 8 is a SEM image of HAP prepared in Example 6.

[0027] Figure 9 is a SEM image of HAP prepared in Example 7.

[0028] Figure 10 is a SEM image of HAP prepared in Example 8.

[0029] Figure 11 is a SEM image of HAP prepared in Example 9.

[0030] Figure 12 is a SEM image of HAP prepared in Example 10.

[0031] Figure 13 is a SEM image of HAP prepared in Example 11. DETAILED DESCRIPTION

[0032] The application will be described in detail below with specific examples.

[0033] Example 1 0.013 mol of calcium chloride and 0.0016 mol of magnesium chloride were dispersed into 100 mL of water and stirred until uniform; 0.009 mol of potassium dihydrogen phosphate, 0.04 mol of urea, and 0.005 mol of L-histidine were added in sequence, and the reaction was stirred at 500 rpm for 20 min. After the reaction was completed, the mixture was placed in a hydrothermal reaction kettle, and hydrothermal reaction was performed at 180°C for 24 h while being mechanically stirred at 80 rpm. After the reaction was completed, the mixture was centrifuged at 6000 rpm for 5 min, washed with ultrapure water and ethanol, and dried at 100°C for 4 h to obtain magnesium-doped hydroxyapatite nanoflowers. As can be seen from the SEM of Figure 2 , the nanoflowers were directly assembled from nanosheets, and the point scanning magnesium doping amount was 1.72 ± 0.08%. XRD, as shown in , contained a characteristic absorption peak of HAP.

[0034] Example 2 0.0159 mol of calcium nitrate and 0.0008 mol of iron nitrate nine hydrate were dispersed into 100 mL of water and stirred uniformly; 0.010 mol of diammonium hydrogen phosphate, 0.06 mol of urea and 0.002 mol of L-histidine were sequentially added, and the reaction was stirred at 400 rpm for 25 min. After the reaction was completed, the mixture was placed into a hydrothermal reaction kettle, and hydrothermal reaction was carried out at 120°C for 5 h while being mechanically stirred at 100 rpm. After the reaction was completed, centrifugation was carried out at 7000 rpm for 3 min, and washing was carried out with ultrapure water and ethanol, and drying was carried out at 80°C for 6 h to obtain iron-doped hydroxyapatite nanoflowers. Figure 3 As can be seen from the SEM of FIG. 1, the nanoflowers are directly assembled from nanosheets. Figure 4 As shown in the FTIR of FIG. 2, the characteristic groups of HAP are contained.

[0035] Example 3 3.718 g of phosphogypsum and 0.0005 mol of anhydrous zinc acetate were dispersed into 100 mL of water and stirred uniformly; 0.010 mol of sodium dihydrogen phosphate, 0.08 mol of urea and 0.004 mol of L-histidine were sequentially added, and the reaction was stirred at 600 rpm for 15 min. After the reaction was completed, the mixture was placed into a hydrothermal reaction kettle, and hydrothermal reaction was carried out at 130°C for 6 h while being mechanically stirred at 120 rpm. After the reaction was completed, centrifugation was carried out at 6500 rpm for 8 min, and washing was carried out with ultrapure water and ethanol, and drying was carried out at 70°C for 10 h to obtain zinc-doped hydroxyapatite nanoflowers. Figure 5 As can be seen from the SEM of FIG. 3, the nanoflowers are directly assembled from nanosheets.

[0036] Example 4 0.009 mol of calcium sulfate and 0.001 mol of copper sulfate five hydrate were dispersed into 100 mL of water and stirred uniformly; 0.015 mol of calcium hydrogen phosphate, 0.02 mol of urea and 0.001 mol of L-histidine were sequentially added, and the reaction was stirred at 700 rpm for 10 min. After the reaction was completed, the mixture was placed into a hydrothermal reaction kettle, and hydrothermal reaction was carried out at 150°C for 3 h while being mechanically stirred at 60 rpm. After the reaction was completed, centrifugation was carried out at 4000 rpm for 8 min, and washing was carried out with ultrapure water and ethanol, and drying was carried out at 60°C for 24 h to obtain copper-doped hydroxyapatite nanoflowers. Figure 6 As can be seen from the SEM of FIG. 4, the synthesized HAP is directly assembled from nanosheets.

[0037] Example 5 Replace 0.015 mol calcium hydrogen phosphate in Example 4 with 0.015 mol trisodium phosphate, and keep other conditions unchanged, the SEM is shown in Figure 7 The product is fine flaky, no nanometer flower morphology appears.

[0038] Example 6 Replace 0.02 mol urea in Example 4 with 0.02 mol sodium hydroxide, and keep other conditions unchanged, the SEM is shown in Figure 8 The product is short flaky, morphology is not one, no nanometer flower formation.

[0039] Example 7 Change the dosage of L-histidine in Example 4 to 0, and keep other conditions unchanged, the SEM is shown in Figure 9 The synthesized HAP is coarse rod-like aggregate, no nanometer flower formation.

[0040] It is found through experiments that when L-histidine is not contained, zinc metal doping can realize the preparation of nanometer flower structure, but when copper ion (such as copper sulfate pentahydrate), iron ion (such as ferric nitrate nonahydrate), cobalt ion (such as cobalt sulfate) is used, nanometer flower structure cannot be prepared, which is not different from Figure 9 The figure is not described here.

[0041] Example 8 Change 0.001 mol L-histidine in Example 4 to 0.001 mol tryptophan, and the SEM is shown in Figure 10 The product is strip aggregate, no nanometer flower formation.

[0042] Example 9 Change 0.001 mol L-histidine in Example 4 to 0.001 mol lysine, and the SEM is shown in Figure 11 The product has no significant morphology.

[0043] Example 10 Change the mechanical stirring speed during the hydrothermal reaction in Example 4 to 0, and keep other conditions unchanged, the SEM is shown in Figure 12 The product is flaky assembled flower morphology, but the stacking phenomenon is serious.

[0044] Example 11 Change the mechanical stirring speed during the hydrothermal reaction in Example 4 to 200 rpm, and keep other conditions unchanged, the SEM is shown in Figure 13 The product is fragment, no nanometer flower formation.

[0045] The above is based on the ideal embodiment of the application, through the above description, relevant personnel can make various changes and modifications without deviating from the technical idea of the application. The technical scope of the application is not limited to the content of the specification, and the technical scope must be determined according to the scope of claims.

Claims

1. A method for preparing metal-doped hydroxyapatite nanoflowers, characterized in that, The method comprises the following steps: (1) dispersing a calcium source and a soluble metal salt into water and stirring uniformly; (2) sequentially adding an acid phosphate, urea and L-histidine, and stirring for a period of time; (3) placing the mixture obtained in step (2) into a hydrothermal reaction kettle, and performing a hydrothermal reaction at high temperature with mechanical stirring; (4) after the hydrothermal reaction, centrifuging and collecting the precipitate in the system, and washing and drying to obtain the metal-doped hydroxyapatite nanoflower.

2. The method for preparing metal-doped hydroxyapatite nanoflowers according to claim 1, characterized in that: In step (1), the calcium source is one or more of calcium chloride, calcium nitrate, calcium sulfate and phosphogypsum.

3. The method according to claim 1, wherein the metal-doped hydroxyapatite nanoflower is prepared by the following steps: (1) preparing a metal-doped hydroxyapatite precursor; (2) preparing a metal-doped hydroxyapatite nanoflower by a hydrothermal method. In step (1), the soluble metal salt includes one of a soluble copper salt, a soluble zinc salt, a soluble magnesium salt, a soluble cobalt salt, and a soluble iron salt, and the metal ion [M n+ ] has a concentration of 0.001 - 0.06 M.

4. The method according to claim 1, wherein the metal-doped hydroxyapatite nanoflower is prepared by the following steps: 1) preparing a metal-doped hydroxyapatite precursor; 2) preparing a metal-doped hydroxyapatite nanoflower by a hydrothermal method. In step (2), the acid phosphate salt is one or more of monohydrogen phosphate, dihydrogen phosphate, [PO4 3- ] ion concentration is 0.01 - 0.21 M.

5. The method for preparing metal-doped hydroxyapatite nanoflowers according to claim 1, characterized in that: In the step (1) and the step (2), the [Ca 2+ ] in the calcium source, the [M n+ ] in the soluble metal salt, and the [PO4 3- ] in the acid phosphate satisfy the following conditions: the ion concentration of ([Ca 2+ ]+[M n+ ]) / [PO4 3- ] is 1.50 - 1.67, and the ion concentration of [M n+ ] / ([Ca 2+ ]+[M n+ ]) is 0.1 - 20%.

6. The method according to claim 1, wherein the metal-doped hydroxyapatite nanoflower is prepared by the following steps: (1) preparing a metal-doped hydroxyapatite precursor; (2) preparing a metal-doped hydroxyapatite nanoflower by a hydrothermal method. In step (2), the urea content in the system is 0.05-2.10 M.

7. The method for preparing metal-doped hydroxyapatite nanoflowers according to claim 1, characterized in that: In step (2), the L-histidine content in the system is 0.01-0.10 mM.

8. The method according to claim 1, wherein the metal-doped hydroxyapatite nanoflower is prepared by the following steps: (1) preparing a metal-doped hydroxyapatite precursor; (2) preparing a metal-doped hydroxyapatite nanoflower by a hydrothermal method. In step (2), the stirring speed is 100-900 rpm, and the reaction time is 5-30 min.

9. The method according to claim 1, wherein the metal-doped hydroxyapatite nanoflower is prepared by the following steps: 1) preparing a metal-doped hydroxyapatite precursor; 2) preparing a metal-doped hydroxyapatite nanoflower by a hydrothermal method. In step (3), the mechanical stirring speed during the hydrothermal reaction is 50-150 rpm, the hydrothermal reaction temperature is 60-200℃, and the hydrothermal reaction time is 2-24 h.

10. A metal-doped hydroxyapatite nanoflower, characterized in that: The metal-doped hydroxyapatite obtained by the preparation method according to any one of claims 1-9 has a nanoflower morphology assembled by nanosheets.

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