A method for preparing a multicolored hydroxyapatite

Abstract

The application relates to the field of biomedical materials, and discloses a preparation method of multicolor hydroxyapatite. Calcium hydrogen phosphate and calcium hydroxide are mixed in proportion, calcined at 600-1400 DEG C for 2-4 hours to obtain a sintered cake; the sintered cake is ball milled, dried to obtain calcium phosphate powder; the calcium phosphate powder and calcium carbonate are mixed in a mass ratio of 10:1-4.5:1 for ball milling and drying, and then high-temperature calcination is carried out to obtain multicolor hydroxyapatite. Without adding any metal or nonmetal dopant, specific types of intrinsic defects are introduced into a pure HAP crystal lattice by controlling reaction conditions and heat treatment processes, selective absorption in a visible light region is generated, and multicolor is presented.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a method for preparing multicolor hydroxyapatite. Background Technology

[0002] Hydroxyapatite (HAP, chemical formula Ca) 10 (PO4)6(OH)2) is the main inorganic component of vertebrate bones and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, it is widely used as a bone repair material, dental filler, drug carrier, and chromatographic separation medium. Under normal conditions, pure hydroxyapatite with complete stoichiometry and good crystallinity is a white powder. Its optical properties mainly depend on its band structure: pure HAP is a wide bandgap semiconductor (bandgap of about 5 eV or more), absorbing only ultraviolet light and having no characteristic absorption in the visible light range, thus appearing white.

[0003] In existing technologies, to make hydroxyapatite exhibit multiple colors, metal ions (especially Cu) are typically used. 2+ Co 2 + Fe 2+ Doping methods (e.g., copper ions, etc.) can induce absorption at the red end of the visible light region through dd-electron transitions in these transition metal ions, thus giving the material complementary colors. For example, copper ions (Cu... 2+ After partial substitution of calcium ions, the sample color gradually changes from white to a variety of lighter, darker, and even darker colors as the doping concentration increases. However, metal ion doping often brings some potential problems: on the one hand, doped ions (such as Cu) can cause various problems. 2+ Co 2+ High concentrations of HAP may be cytotoxic, limiting its application dosage in the biomedical field. On the other hand, the doping process introduces lattice distortion and additional defects, which may change the long-term stability, degradation behavior and osteoinductive activity of HAP. Furthermore, the preparation process requires high control over the uniformity of doping.

[0004] Besides metal ion doping, non-metal ion doping (such as N and C) or reducing atmosphere treatment can also induce multicolors in certain oxide ceramics, such as multicolor titanium dioxide or multicolor zirconium oxide. The coloring mechanism usually involves the generation of oxygen vacancies or low-valence ions. However, for the complex phosphate system of hydroxyapatite, reports of stable multicolor coloring achieved through defects in the pure phase itself (such as oxygen vacancies, hydroxyl vacancies, calcium vacancies, phosphorus vacancies, and their composite defects) are extremely rare. In existing literature, pure hydroxyapatite often transforms into other calcium-phosphorus phases (such as β-TCP, CaO, etc.) under oxygen-deficient atmospheres or high-temperature treatment, or its color becomes grayish or blackish, rather than uniform and stable. Therefore, obtaining vibrant multicolors solely by controlling the crystal defect structure or morphology of hydroxyapatite without introducing any external dopant ions remains a challenging task. Summary of the Invention

[0005] This invention aims to overcome the shortcomings of existing technologies and provides a method for preparing multicolor hydroxyapatite. This method requires no addition of any metal or non-metal dopants. By controlling reaction conditions, precursor morphology, and heat treatment processes, specific types of intrinsic defects (such as oxygen vacancy-hydroxyl vacancy composite defects) are introduced into the pure HAP lattice, causing selective absorption in the visible light region, thus exhibiting multicolor properties. Compared with existing doped multicolor HAP, the product obtained by this method avoids the biosafety risks associated with dopant ions, maintains the pure phase composition and high crystallinity of HAP, and simultaneously endows it with unique color characteristics, expanding the application potential of hydroxyapatite in fields such as bio-tracing, optical labeling, sunscreen fillers, and visible light photocatalysis.

[0006] As a first aspect of the present invention, the present invention provides a method for preparing polychromatic hydroxyapatite, comprising the following steps: (1) Dicalcium phosphate and calcium hydroxide were ball-milled in a molar ratio of 2:1 and dried to obtain a mixed powder; (2) Place the mixed powder obtained in step (1) in a muffle furnace and calcine it at 600~1400℃ for 2~4 h to obtain a sintered cake; (3) The sintered cake obtained in step (2) is ball-milled and dried to obtain calcium phosphate powder; (4) The calcium phosphate powder obtained in step (3) and calcium carbonate are ball-milled at a mass ratio of 10:1 to 4.5:1 to obtain the dried product; (5) Place the dried material obtained in step (4) in a muffle furnace and calcine it at 900~1400℃ for 2~4 h to obtain polychromatic hydroxyapatite.

[0007] In a preferred embodiment, in step (1), the mixture is ball-milled at 300 rpm for 2 h and then dried at 60°C.

[0008] As a preferred embodiment, the calcination temperature in step (2) is 800~1200℃ and the calcination time is 2~4 h.

[0009] In a preferred embodiment, in step (3), the ball mill is performed at 400 rpm for 4 h and then dried at 60°C.

[0010] In a preferred embodiment, the mass ratio of calcium phosphate powder to calcium carbonate in step (4) is 9:1 to 5.5:1.

[0011] As a preferred embodiment, the ball milling speed in step (4) is 250~400 rpm, the ball milling mixing time is 2~4 h, and the drying is carried out at 60℃.

[0012] As a preferred embodiment, the calcination temperature in step (5) is 1100~1400℃ and the calcination time is 2~4 h.

[0013] In a preferred embodiment, ball milling is performed in an ethanol medium in steps (2) and (3).

[0014] In a preferred embodiment, the media used in the ball milling of step (4) include water, ethanol, n-hexane and cyclohexane.

[0015] As a second aspect of the present invention, the present invention provides a polychromatic hydroxyapatite prepared by the above-described preparation method.

[0016] In a preferred embodiment, the polychromatic hydroxyapatite has a purity greater than 99.5% and a specific surface area of ​​15.8~22.4 m². 2 / g.

[0017] The beneficial effects of this invention are: 1. This invention eliminates the need for the addition of transition metal ions such as copper, cobalt, and iron, or other exogenous dopants, completely avoiding potential cytotoxicity or inflammatory reactions caused by doping elements. The high-temperature calcination process effectively removes organic impurities and residual reaction byproducts from the precursor, further improving product purity. The resulting polychromatic hydroxyapatite maintains a pure phase composition, exhibits excellent biocompatibility and biodegradability, and is suitable for use in biomedical fields such as bone repair, dental materials, and drug carriers.

[0018] 2. High-temperature calcination promotes the full growth of hydroxyapatite grains, resulting in a pure-phase product with high crystallinity and uniform lattice defect distribution. This invention achieves stable multicolor coloring by precisely controlling the calcination temperature and time to introduce specific types of intrinsic defects into the crystal lattice. Compared to low-temperature synthesized or doped products, the multicolors obtained through high-temperature calcination are less prone to fading, exhibit significantly improved color uniformity and batch stability, and pose no risk of ion leaching in physiological environments, demonstrating excellent long-term stability.

[0019] 3. Since the basic chemical composition of the material remains unchanged, it retains a single hydroxyapatite phase after high-temperature calcination. The product retains the excellent osteoconductivity, osteoinductive capacity, protein adsorption capacity, and bioactivity of pure-phase HAP. Compared with metal ion doping methods, this invention avoids the risk of foreign ions interfering with osteoblast proliferation and differentiation, ensuring that its core function in bone tissue engineering remains unaffected.

[0020] 4. This invention employs a conventional muffle furnace or tube furnace for high-temperature calcination, requiring no special atmosphere protection or complex steps such as high pressure, hydrothermal treatment, or sol-gel processes. Effective control of color depth can be achieved by adjusting the calcination temperature, holding time, and heating rate. The process exhibits good reproducibility, low equipment requirements, and a wide availability of raw materials, making it suitable for large-scale mass production. Attached Figure Description

[0021] Figure 1 The XRD pattern of the blue hydroxyapatite prepared in Example 1; Figure 2 A photograph of the blue hydroxyapatite prepared in Example 1; Figure 3 The image shows the XRD pattern of the green hydroxyapatite prepared in Example 2. Figure 4 A photograph of the green hydroxyapatite prepared in Example 2; Figure 5 The XRD pattern of the brown hydroxyapatite prepared in Example 3; Figure 6 A photograph of the brown hydroxyapatite prepared in Example 3; Figure 7 The XRD pattern of the blue hydroxyapatite prepared in Comparative Example 1; Figure 8 XRD pattern of green hydroxyapatite prepared in Comparative Example 2. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention in any way. It should be noted that, unless otherwise specified, the following embodiments and features can be combined with each other. It should also be understood that the terminology used in the embodiments of this invention is for describing specific implementation schemes and not for limiting the scope of protection of this invention.

[0023] When a range of values ​​is given, it should be understood that, unless otherwise stated in this invention, the two endpoints of each range and any value between the two endpoints may be selected.

[0024] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly used in the field to which this invention pertains. The terminology used to describe this invention is intended only to describe a particular implementation and is not intended to limit the scope of the teachings. This invention can be implemented using any prior art methods, apparatus, and materials similar to or equivalent to those described, used, or made in the embodiments of this invention.

[0025] The term “and / or” as used herein should be understood to mean any one of the options or any combination of two or more of the options.

[0026] As used herein, the term "about" indicates a range of ±20% of the following value. In some embodiments, the term "about" indicates a range of ±10% of the following value. In some embodiments, the term "about" indicates a range of ±5% of the following value.

[0027] This invention provides a method for preparing polychromatic hydroxyapatite, comprising the following steps: (1) Dicalcium phosphate and calcium hydroxide were ball-milled in a molar ratio of 2:1 and dried to obtain a mixed powder.

[0028] In one specific embodiment, ethanol is selected as the ball milling medium, and the mixture is ball milled at 300 rpm for 2 hours and then dried at 60°C.

[0029] (2) Place the mixed powder obtained in step (1) in a muffle furnace and calcine it at 600~1400℃ for 2~4 h to obtain a sintered cake; The core of this invention lies in "precisely controlling the calcium-to-phosphorus ratio and non-stoichiometric defects of the material through a two-step solid-state high-temperature reaction without introducing exogenous transition metal ions, thereby activating the intrinsic non-metallic defect color-causing mechanism of pure-phase hydroxyapatite (HAP)." Pure HAP is a wide-bandgap semiconductor with no absorption of visible light. This invention utilizes a two-step method, firstly sintering to construct a highly active, specific non-stoichiometric amorphous / low-crystallinity calcium phosphate intermediate, and then introducing calcium carbonate in the second sintering to regulate the local microenvironment and lattice restructuring, inducing oxygen vacancy-hydroxyl vacancy recombination defects. These defects form local defect energy levels in the bandgap of HAP, causing intrinsic color center transitions of electrons, resulting in selective absorption in the visible light region, thus exhibiting a stable multicolor effect.

[0030] In this step, during the first sintering at 600~1400℃, the following solid-state reaction occurs: 2CaHPO4 + Ca(OH)2 Ca3(PO4)2 + 2H2O The main purpose of this stage is to achieve complete reaction and dehydration, generating a calcium phosphate precursor powder rich in specific microscopic defects. The high-temperature process allows the phosphate framework to initially recombine with calcium ions. Subsequently, ball milling breaks down the "cake-like" solidified body, forming an activated powder with high surface energy, high internal strain, and lattice distortion, injecting high reactivity into the second stage of in-situ solid-phase recombination with CaCO3.

[0031] (3) The sintered cake obtained in step (2) is ball-milled and dried to obtain calcium phosphate powder.

[0032] In one specific embodiment, ethanol is selected as the ball milling medium, and the mixture is ball milled at 400 rpm for 4 hours and then dried at 60°C.

[0033] (4) The calcium phosphate powder obtained in step (3) and calcium carbonate are ball-milled at a mass ratio of 10:1 to 4.5:1 to obtain dried material.

[0034] In one specific embodiment, the ball milling medium includes, but is not limited to, water, ethanol, and inert organic solvents such as n-hexane and cyclohexane.

[0035] In one specific embodiment, the ball milling speed is 250~400 rpm, the ball milling mixing time is 2~4 h, and the product is dried at 60℃.

[0036] (5) Place the dried material obtained in step (4) in a muffle furnace and calcine it at 900~1400℃ for 2~4 h to obtain polychromatic hydroxyapatite.

[0037] In this step, the calcium phosphate powder obtained from the first sintering is mixed with CaCO3 in a precise ratio. During the second high-temperature sintering at 900~1400℃, CaCO3 decomposes to produce highly reactive in-situ CaO and CO2, which rapidly diffuse and embed into the lattice of the precursor calcium phosphate, undergoing a phase transformation and ultimately completely transforming into a pure-phase hydroxyapatite structure. Furthermore, at extremely high temperatures, the escape of CO2 from the in-situ reaction and the gaseous microenvironment, combined with the rapid lattice reorganization process, forcefully integrate the generated CaO and CO2 into the crystal structure. 10 The (PO4)6(OH)2 crystal lattice contains oxygen and hydroxyl vacancies resulting from non-equilibrium diffusion. With different reactant ratios (10:1 to 4.5:1) and temperature variations, the degree of lattice distortion and vacancy concentration are finely tuned, resulting in different defect energy levels in its band structure. This allows for the selective absorption of different wavelengths of visible light, directly exhibiting stable intrinsic colors such as blue, green, and brown.

[0038] The following embodiments and accompanying drawings are provided to aid in understanding the present invention. However, it should be understood that these embodiments are for illustrative purposes only and do not constitute any limitation. The actual scope of protection of the present invention is set forth in the claims. It should be understood that any modifications and changes can be made without departing from the spirit of the present invention. Unless otherwise specified, the raw materials used in the embodiments are all commercially available products in the art, their specifications are conventional specifications in the art, and the methods used are conventional methods in the art. The instruments and equipment used in the embodiments are conventional instruments and equipment in the art.

[0039] Example 1 This embodiment provides a method for preparing blue hydroxyapatite, including the following steps: 272.12 g of dicalcium phosphate and 74.09 g of calcium hydroxide were ball-milled in ethanol at 300 rpm for 2 h and dried at 60 °C. The mixed powder was calcined in a muffle furnace at 1100 °C for 2 h. The product was ball-milled in ethanol at 400 rpm for 3 h and dried at 60 °C to obtain calcium phosphate powder.

[0040] Weigh 100g of calcium phosphate powder and 10g of calcium carbonate powder, ball mill them in an aqueous medium at 250rpm for 4 hours, and dry them at 60℃. Place the dried material in a muffle furnace and calcine at 1200℃ for 2 hours to obtain blue hydroxyapatite. Figure 1 The XRD pattern of the prepared blue hydroxyapatite is shown, which is in perfect agreement with standard card 009-0432. Figure 2 A picture of the actual object was shown.

[0041] Example 2 This embodiment provides a method for preparing green hydroxyapatite, including the following steps: 45g of calcium phosphate and 10g of calcium carbonate powder prepared in Example 1 were weighed and ball-milled at 400 rpm for 2 hours in hexane medium, and then dried at 60°C. The dried material was placed in a muffle furnace and calcined at 1400°C for 3 hours to obtain green hydroxyapatite. Figure 3 The XRD pattern of the prepared green hydroxyapatite is shown, and it fully conforms to standard card 009-0432. Figure 4 A picture of the actual object was shown.

[0042] Example 3 This embodiment provides a method for preparing brown hydroxyapatite, including the following steps: 60g of calcium phosphate and 10g of calcium carbonate powder prepared in Example 1 were weighed and ball-milled at 300 rpm for 3 hours in cyclohexane medium, and then dried at 60°C. The dried material was placed in a muffle furnace and calcined at 1300°C for 4 hours to obtain brown hydroxyapatite. Figure 5 The XRD pattern of the prepared brown hydroxyapatite was shown, and it fully conformed to standard card 009-0432. Figure 6 A picture of the actual object was shown.

[0043] Comparative Example 1 This comparative example provides a method for preparing blue hydroxyapatite, comprising the following steps: 110 g of calcium phosphate and 10 g of calcium carbonate powder prepared in Example 1 were weighed and ball-milled in an aqueous medium at 300 rpm for 3 h, and then dried at 60 °C. The dried material was placed in a muffle furnace and calcined at 1200 °C for 4 h to obtain blue hydroxyapatite. Figure 7 The XRD pattern of the prepared blue hydroxyapatite is shown, and compared with the standard card, it contains hydroxyapatite and β-TCP complex.

[0044] Comparative Example 2 This comparative example provides a method for preparing green hydroxyapatite, comprising the following steps: 40g of calcium phosphate and 10g of calcium carbonate powder prepared in Example 1 were weighed and ball-milled in an aqueous medium at 400 rpm for 2 hours, and then dried at 60°C. The dried material was placed in a muffle furnace and calcined at 1200°C for 4 hours to form green hydroxyapatite. Figure 8 The XRD pattern of the prepared green hydroxyapatite is shown, and compared with the standard card, it contains hydroxyapatite and CaO.

[0045] Experimental Example The hydroxyapatite powder samples obtained in each embodiment and comparative example were uniaxially pressed into 10mm×12mm cylindrical specimens under a pressure of 100 MPa. Subsequently, they were sintered and densified under the same conditions. Finally, the compressive strength was measured using a universal testing machine, and the hardness was measured using a micro / nano indenter.

[0046]

[0047] The compressive strength values ​​of Examples 1-3 of the present invention reached 85.4, 92.1 and 88.7 respectively, which is 8.8% to 17.3% higher than that of conventional pure phase HAP.

[0048] Cause analysis: This shows that by introducing the intrinsic defects of "oxygen vacancy-hydroxyl vacancy" into the HAP lattice through the two-step calcination process of the present invention to induce polychromaticity, not only is there no lattice instability or microcracks in the material, but also, due to the in-situ recombination and full growth of the crystals at high temperature, the compressive strength and hardness are simultaneously and steadily improved on a macroscopic scale.

[0049] When deviating from the technical solution of this invention, the specific values ​​of its compressive strength dropped drastically to 54.2 MPa and 41.3 MPa, respectively. Analysis of the reasons: In Comparative Example 1, due to the large amount of residual β-TCP impurity phase, the phase boundary expansion between the two phases was mismatched during high-temperature sintering, resulting in micro-strain and causing the compressive strength to decrease by approximately 31% compared to normal HAP; In Comparative Example 2, the residual free CaO impurity phase had a soft lattice and was extremely prone to absorbing moisture and deliquescence in air or the testing environment, leading to microcracks and severe porosity in the overall structure, resulting in a direct "cliff-like" drop in compressive strength of approximately 47.4%.

[0050] The above embodiments merely illustrate several implementation methods of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the present invention should be determined by the appended claims.

Claims

1. A method for preparing polychromatic hydroxyapatite, characterized in that, Includes the following steps: (1) Dicalcium phosphate and calcium hydroxide were ball-milled in a molar ratio of 2:1 and dried to obtain a mixed powder; (2) Place the mixed powder obtained in step (1) in a muffle furnace and calcine it at 600~1400℃ for 2~4 h to obtain a sintered cake; (3) The sintered cake obtained in step (2) is ball-milled and dried to obtain calcium phosphate powder; (4) The calcium phosphate powder obtained in step (3) and calcium carbonate are ball-milled at a mass ratio of 10:1 to 4.5:1 to obtain the dried product; (5) Place the dried material obtained in step (4) in a muffle furnace and calcine it at 900~1400℃ for 2~4 h to obtain polychromatic hydroxyapatite.

2. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, In step (1), the mixture was ball-milled at 300 rpm for 2 h and then dried at 60°C.

3. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, The calcination temperature in step (2) is 800~1200℃ and the calcination time is 2~4 h.

4. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, In step (3), the ball mill was run at 400 rpm for 4 hours and then dried at 60°C.

5. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, The mass ratio of calcium phosphate powder to calcium carbonate in step (4) is 9:1 to 5.5:

1.

6. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, The ball milling speed in step (4) is 250~400 rpm, the ball milling mixing time is 2~4 h, and the drying is carried out at 60℃.

7. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, The calcination temperature in step (5) is 1100~1400℃ and the calcination time is 2~4 h.

8. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, In steps (2) and (3), ball milling is performed in an ethanol medium.

9. The method for preparing polychromatic hydroxyapatite according to claim 1, characterized in that, The media used in the ball milling in step (4) include water, ethanol, n-hexane and cyclohexane.

10. A polychromatic hydroxyapatite prepared by any one of claims 1-9.

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