Apatite material and preparation method thereof

Abstract

The invention relates to the technical field of biomedical materials, in particular to an apatite material and a preparation method thereof. The preparation method of the apatite material provided by the embodiment of the invention comprises the following steps: mixing a gallium source, a calcium source and a phosphorus source in water to obtain a precursor suspension; placing the precursor suspension in a hydrothermal reaction kettle for hydrothermal reaction; and after the reaction is completed, obtaining the apatite material containing gallium and calcium. According to the apatite material and the preparation method thereof provided by the embodiment of the invention, bone and meat tumor cells can be effectively targeted, and the dual requirements of tumor inhibition and osteogenesis are met.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to an apatite material and a preparation method thereof. BACKGROUND

[0002] Osteosarcoma is the most common malignant bone tumor with low survival rate, mainly occurring in children and adolescents. Its treatment depends on surgical resection and adjuvant chemotherapy, but the postoperative recurrence rate is high and it is prone to metastasis. Because bone tumor tissue often forms bone-like structure through cartilage stage, it is difficult to completely remove. The treatment of bone tumor not only requires that the drug can actively target bone tumor cells, but also requires bone repair ability. At present, the treatment drugs for osteosarcoma not only lack the ability to actively target osteosarcoma tumor cells, but also cannot meet the dual requirements of "tumor inhibition-osteogenesis". SUMMARY

[0003] The embodiments of the present application provide an apatite material and a preparation method thereof, which can effectively target bone tumor cells and meet the dual requirements of "tumor inhibition-osteogenesis".

[0004] In a first aspect, the embodiments of the present application provide a preparation method of an apatite material, comprising:

[0005] mixing a gallium source, a calcium source and a phosphorus source in water to obtain a precursor suspension;

[0006] placing the precursor suspension in a hydrothermal reaction kettle to perform hydrothermal reaction;

[0007] after the reaction is completed, an apatite material containing gallium and calcium is obtained.

[0008] In a possible design, the gallium source is Ga2O3.

[0009] In a possible design, the calcium source includes one or more combinations of calcium hydroxide, calcium oxide, calcium phosphate, monocalcium phosphate and calcium dihydrogen phosphate.

[0010] In a possible design, the phosphorus source includes one or more combinations of phosphoric acid, calcium phosphate, monocalcium phosphate and calcium dihydrogen phosphate.

[0011] In a possible design, in the gallium source, the calcium source and the phosphorus source, the molar ratio of gallium, calcium and phosphorus is x:(10-x):6, and the chemical formula of the obtained apatite material is Ca 10-x Ga x (PO4)6O x (OH) 2-x , wherein 0 < x ≤ 2.

[0012] In a possible design, the reaction temperature of the hydrothermal reaction is 120-200 DEG C, and the reaction time of the hydrothermal reaction is 2-36 hours.

[0013] In a possible design, the hydrothermal reaction is a dynamic hydrothermal reaction, and the steps of the hydrothermal reaction are as follows:

[0014] The precursor suspension is transferred into a polytetrafluoroethylene container, and the dynamic hydrothermal reaction is carried out in a rotatable homogeneous reactor at a rotating speed of 5-30 revolutions per minute, and the reaction is carried out at 120-200 DEG C for 2-36 hours, and the filling ratio of the dynamic hydrothermal reaction is 50-90%.

[0015] In a possible design, the hydrothermal reaction is carried out in an oven, and the reaction condition is 60-250 DEG C for 10-76 hours.

[0016] In a possible design, the hydrothermal reaction is carried out under stirring, and the temperature is 60-200 DEG C for 10-76 hours.

[0017] In a second aspect, the embodiment of the present application provides an apatite material prepared according to any of the above preparation methods.

[0018] Compared with the prior art, the present application has at least the following beneficial effects:

[0019] The present application prepares the hetero-lattice gallium calcium apatite with uniform distribution of Ga-substituted Ca(2) by slowly releasing the gallium source from the insoluble Ga2O3, thereby generating hetero-electrons and potential redistribution, and precisely regulating the optical band gap, lipophilicity and Zeta potential and other physicochemical properties by controlling the content of Ga.

[0020] The calcium apatite prepared by the present application realizes the significant lipophilicity and positive / negative Zeta potential switching, and can be applied to cancer tissue and membrane-containing sub-organ targeted delivery for effective tumor treatment. BRIEF DESCRIPTION OF DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the following embodiment or prior art description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0022] Fig. 1 The transmission electron microscopy (TEM) of the gallium calcium apatite material is shown in the following figure:

[0023] Fig. 2 The charge density distribution and the differential charge density of the gallium calcium apatite material are shown in the following figure:

[0024] Fig. 3 Transmission electron microscopy (TEM) image of the gallium calcium apatite material targeted to mitochondria of osteosarcoma cell mitochondria-targeted delivery. DETAILED DESCRIPTION

[0025] To make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are some but not all of the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the present application.

[0026] The embodiments of the present application provide a preparation method of an apatite material, comprising:

[0027] Mixing a gallium source, a calcium source and a phosphorus source in water to obtain a precursor suspension;

[0028] Placing the precursor suspension in a hydrothermal reaction kettle to perform hydrothermal reaction;

[0029] After the reaction is completed, an apatite material containing gallium and calcium is obtained.

[0030] In the present embodiment, a gallium calcium apatite (GaCa-APT) with a hetero-lattice and a controllable stoichiometric ratio of high purity is prepared by a dynamic hydrothermal synthesis method with a stoichiometrically determined amount of a gallium source. The material realizes positive and negative flipping of Zeta potential under a narrow pH change in a physiological environment through hetero-structure design, has lipophilicity, is endocytosed by tumor cells under a tumor micro-acidic environment, and is targeted to mitochondria, thereby synergistically exerting excellent biological activities such as anti-tumor and antibacterial activities and bone repair. A hetero-lattice gallium calcium apatite with uniform distribution of Ga substitution Ca(2) is prepared by slowly controlling the release of the gallium source through the insoluble Ga2O3, the doping concentration range is significantly widened, and the material has anti-tumor activity, antibacterial activity and bone formation promoting performance, thereby providing an efficient and safe breakthrough strategy for osteosarcoma treatment and postoperative bone regeneration.

[0031] In some embodiments of the present application, the gallium source is Ga2O3.

[0032] In the present embodiment, gallium oxide is selected as the gallium source, which can not only quantitatively provide gallium atoms but also participate in the reaction as a reactant to control the slow release of gallium ions and prepare a hetero-lattice product with uniform distribution of Ga substitution Ca(2).

[0033] In some embodiments of the present application, the calcium source includes one or more combinations of calcium hydroxide, calcium oxide, calcium phosphate, monocalcium phosphate and calcium phosphate.

[0034] In some embodiments of the present application, the phosphorus source comprises one or more combinations of phosphoric acid, calcium phosphate, monocalcium phosphate, and calcium dihydrogen phosphate.

[0035] In some embodiments of the present application, the molar ratio of gallium, calcium, and phosphorus in the gallium source, the calcium source, and the phosphorus source is x:(10-x):6, and the chemical formula of the apatite material obtained is Ca 10-x Ga x (PO4)6O x (OH) 2-x , wherein 0 < x ≤ 2.

[0036] In the present embodiment, by controlling the molar ratio of each raw material, the content of each element in the product can be controlled, and precise control of the composition of the apatite material can be achieved. When each element composition of the material is within the above range, a product with good properties can be obtained.

[0037] Specifically, the gallium-calcium apatite material structure is a hetero-crystal structure composed of two different crystal sublattice periodic arrangements of a gallium-containing layer and a gallium-free layer. The crystal sublattice between the gallium-containing layer and the gallium-free layer has increased interfacial spacing due to the presence of a large number of voids, and there are hydrogen vacancies and lattice distortions in the crystal structure, with a variation rate of the a-axis of 0.01-2.6% and a variation rate of the c-axis of 0.05%-3.5%.

[0038] The covalent bond trims the ionic bond lattice unit, the gallium ion dopes the calcium ion at the Ca(2) site of the hydroxyapatite by unequal substitution, the gallium ion forms a strong covalent bond with the oxygen remaining after the dehydrogenation of the hydroxyl group, and hydrogen vacancies appear in the hydroxyapatite structure. According to the theoretical calculation results, there is a high potential energy zone near the gallium atom, and the introduction of the covalent bond produces hetero-electrons and potential redistribution and the specific chemical properties that follow. The atomic percentage of Ga element is 0.05%-5.2%, and there is a large difference in the bond length between Ga and the coordinated O atoms, ranging from 1.3 to 3.4 .

[0039] In the present application, the gallium-calcium apatite material prepared has lipophilicity, with a logD of 0.5-2.

[0040] In the present application, by controlling the atomic percentage of Ga element to be 0.05%-5.2%, the optical band gap of the gallium-calcium apatite material is 1.5-5.2 eV.

[0041] The content of each element is in the above range, so that the Zeta potential of the gallium calcium apatite material not only has a pH response change, and the Zeta potential value is adjustable in the following range: the surface of the gallium calcium apatite material is negatively charged, and the Zeta potential is negative when the gallium calcium apatite material is in an environment with a pH of 7.4-14; when the pH is 2-6.8, the surface is positively charged, and the Zeta potential is positive. The gallium calcium apatite material realizes a significant positive / negative Zeta potential switching in a narrow physiological pH range (7.4 and 6.8), and the apatite material provided by the application has lipophilicity, is endocytosed by tumor cells under the micro-acidic environment of the tumor, and targets mitochondria, thereby synergistically exerting excellent biological activities such as anti-tumor antibacterial and bone repair.

[0042] In summary, the band gap is regulated by the addition amount of Ga, and the chemical band gap (1.8-5.2 eV) of the gallium calcium apatite material changes with the change of the gallium content (0.05-5.2 at%).

[0043] The lipophilicity is regulated by the addition amount of Ga, and the logD (0.5-2) of the gallium calcium apatite material changes with the change of the gallium content (0.05-5.2 at%).

[0044] The surface charge is regulated by the addition amount of Ga, and with the change of the gallium content (0.05-5.2 at%), the surface of the gallium calcium apatite material is negatively charged in an aqueous solution environment with a pH of 7.4-14, and the Zeta potential is negative; when in an aqueous solution environment with a pH of 2-6.8, the surface is positively charged, and the Zeta potential is positive.

[0045] The product obtained according to the embodiment of the application is tested, please refer to Figs. 1 to 3 , Fig. 1 The transmission electron microscope (TEM) of the gallium calcium apatite material is shown in the figure, and it can be seen from the figure that the gallium doped into the hydroxyapatite lattice makes the hydroxyapatite lattice composed of two different crystal sublattice periodic arrangements. The incorporation of gallium causes vacancies in the crystal lattice, and a large number of voids are generated between the crystal faces;

[0046] Fig. 2 The charge density distribution and differential charge density of the gallium calcium apatite material are shown in the figure, and it can be seen from the figure that a high charge density area and a high potential area are formed around the gallium atom, and a strong covalent bond is formed between the surface gallium and the surrounding oxygen, thereby generating hetero-electrons and potential redistribution;

[0047] Fig. 3From the TEM figure of the transmission electron microscopy (TEM) of the gallium calcium apatite material targeted mitochondria of the osteosarcoma cell mitochondria targeted delivery, it can be seen that the gallium calcium apatite material is adsorbed and endocytosed by the tumor cells, and is targeted to accumulate on the surface and inside the mitochondria, which is due to the significant lipophilicity of the gallium calcium apatite, and the property of carrying a positive charge in an acidic state.

[0048] In some embodiments of the present application, the reaction temperature of the hydrothermal reaction is 120-200℃, and the reaction time of the hydrothermal reaction is 2-36h.

[0049] In some embodiments of the present application, the hydrothermal reaction is a dynamic hydrothermal reaction, and the steps of the hydrothermal reaction are as follows:

[0050] The precursor suspension is transferred into a polytetrafluoroethylene container, and the dynamic hydrothermal reaction is carried out in a rotatable homogeneous reactor at a rotation speed of 5-30 revolutions per minute, at 120-200℃ for 2-36h, and the filling ratio of the dynamic hydrothermal reaction is 50-90%.

[0051] In some embodiments of the present application, the hydrothermal reaction is carried out in an oven, and the reaction conditions are 60-250℃ for 10-76h.

[0052] In some embodiments of the present application, the hydrothermal reaction is carried out under stirring, at a temperature of 60-200℃ for 10-76h.

[0053] The embodiments of the present application provide a kind of apatite material, which is prepared according to any one of the above preparation methods.

[0054] In order to more clearly illustrate the technical solutions and advantages of the present application, the following will be described in detail through several embodiments.

[0055] Embodiment 1

[0056] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-xThe stoichiometric ratio of x=0.1 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container and diluted to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 10 revolutions per minute, and the reaction conditions are 120°C for 24 hours. After the reaction is completed, wet powder is obtained by suction filtration and dried to obtain well-dispersed gallium calcium apatite. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 0.23%. The product is characterized by a UV-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 4.98 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 0.5. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the Zeta potential distribution of the gallium calcium apatite powder sample dispersed in PBS (pH=7.4) and acetate buffer solution (pH=5) is negative-20.3 mV and positive 1.25 mV, respectively.

[0057] Example 2

[0058] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-x The stoichiometric ratio of x=0.5 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container and diluted to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 15 revolutions per minute, and the reaction conditions are 150°C for 20 hours. After the reaction is completed, wet powder is obtained by suction filtration and dried to obtain well-dispersed gallium calcium apatite. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 1.1%. The product is characterized by a UV-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 4.82 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 0.6. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the Zeta potential distribution of the gallium calcium apatite powder sample dispersed in pH=8 and pH=3 deionized water is negative-18.5 mV and positive 3.6 mV, respectively.

[0059] Example 3

[0060] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-xThe stoichiometric ratio of x = 1.1 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container, and the volume is fixed to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 20 rpm, and the reaction conditions are 150°C for 20 hours. After the reaction is completed, wet powder is obtained by suction filtration, and the gallium calcium apatite with good dispersibility is obtained by drying. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 2.3%. The product is characterized by an ultraviolet-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 3.87 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 0.7. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the gallium calcium apatite powder sample is dispersed in a pH = 9 and pH = 4 acetate buffer solution, respectively, and the Zeta potential distribution is negative -17.8 mV and positive 6.6 mV.

[0061] Example 4

[0062] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-x The stoichiometric ratio of x = 1.1 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container, and the volume is fixed to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 20 rpm, and the reaction conditions are 150°C for 20 hours. After the reaction is completed, wet powder is obtained by suction filtration, and the gallium calcium apatite with good dispersibility is obtained by drying. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 2.3%. The product is characterized by an ultraviolet-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 3.87 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 0.7. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the gallium calcium apatite powder sample is dispersed in a pH = 9 and pH = 4 acetate buffer solution, respectively, and the Zeta potential distribution is negative -17.8 mV and positive 6.6 mV.

[0063] Example 5

[0064] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-xThe stoichiometric ratio of x = 1.5 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container and diluted to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 10 revolutions per minute, and the reaction conditions are 150°C for 20 hours. After the reaction is completed, wet powder is obtained by suction filtration and dried to obtain well-dispersed gallium calcium apatite. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 3.4%. The product is characterized by a UV-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 2.21 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 1.5. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the Zeta potential distribution of the gallium calcium apatite powder sample dispersed in a pH = 8 and pH = 4 acetate buffer solution is negative -15.5 mV and positive 9.2 mV.

[0065] Example 6

[0066] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-x The stoichiometric ratio of x = 1.5 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring for ten minutes. The reaction liquid is transferred to a 120 ml Teflon container and diluted to 80 ml. A stainless steel container is fixed in the reactor at a rotation speed of 10 revolutions per minute, and the reaction conditions are 150°C for 20 hours. After the reaction is completed, wet powder is obtained by suction filtration and dried to obtain well-dispersed gallium calcium apatite. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 3.4%. The product is characterized by a UV-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 2.21 eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is 1.5. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the Zeta potential distribution of the gallium calcium apatite powder sample dispersed in a pH = 8 and pH = 4 acetate buffer solution is negative -15.5 mV and positive 9.2 mV.

[0067] Example 7

[0068] According to the following chemical formula Ca 10-x Ga x (PO4)6O x (OH) 2-xThe stoichiometric ratio of x=2 is accurately weighed to prepare a phosphorus source precursor suspension of calcium phosphate, a calcium source precursor suspension of calcium hydroxide is weighed, and a gallium source precursor suspension of gallium oxide is added in proportion during stirring. After stirring for ten minutes, the reaction solution is transferred to a 120ml polytetrafluoroethylene container and diluted to 80ml. A stainless steel container is fixed in the reactor at a rotation speed of 20 revolutions per minute, and the reaction conditions are 180℃ for 18 hours. After the reaction is completed, wet powder is obtained by suction filtration, and the gallium calcium apatite with good dispersibility is obtained after drying. The gallium calcium apatite material is characterized by an energy spectrometer, and the atomic percentage of gallium in the product of the application is 4.7%. The product is characterized by a UV-visible absorption spectrometer, and the band gap of the gallium calcium apatite of the application is 1.85eV. The lipophilicity partition coefficient logD of the gallium calcium apatite material is measured to be 2. The gallium calcium apatite material is characterized by a laser Doppler electrophoresis instrument, and the gallium calcium apatite powder sample is dispersed in a pH=10 and pH=3 acetate buffer solution, respectively. The Zeta potential distribution is negative-7.02mV and positive 15.3mV.

[0069] Comparative Example 1

[0070] Comparative Example 1 uses a wet chemical precipitation method to prepare gallium-containing hydroxyapatite using Ga(NO3)3·xH2O as a gallium source. (For specific preparation methods, see Marika Mosina, Ilijana Kovrlija, Liga Stipniece, Janis Locs. Gallium containing calcium phosphates: Potential antibacterial agents or fictitious truth. [J]. Acta Biomaterialia. 2022, 150: 48-57)

[0071] Comparative Example 2

[0072] Comparative Example 2 uses Ga(NO3)3·xH2O and Ca(NO3)2·4H2O to prepare gallium-containing hydroxyapatite microparticles by a wet chemical precipitation method. (For specific preparation methods, see P. Melnikov, A.R. Teixeira, A. Malzac, M. de B. Coelho. Gallium-containing hydroxyapatite for potential use in orthopedics. [J]. Materials Chemistry and Physics. 2009, 117: 86-90)

[0073] Comparative Example 1 and Comparative Example 2 produce products with the same structure as hydroxyapatite by a chemical precipitation method, the structure framework of the hydroxyapatite matrix does not produce distortion, size uneven, easy to introduce impurity ions.

[0074] Finally, it should be noted that: the above examples are used to illustrate the technical solutions of the present application, but not limited to; although the present application is described in detail with reference to the foregoing examples, those skilled in the art should understand that: it can still be modified to the technical solutions recorded in the foregoing examples, or part of the technical features are replaced; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for the preparation of an apatite material, characterized in that, The application relates to a preparation method of a gallium and calcium-containing apatite material. A gallium source, a calcium source and a phosphorus source are mixed in water to obtain a precursor suspension; The precursor suspension is placed in a hydrothermal reaction kettle to perform a hydrothermal reaction; After the reaction is completed, a gallium and calcium-containing apatite material is obtained.

2. The production method according to claim 1, characterized by, The gallium source is Ga2O3.

3. The preparation method according to claim 1, characterized in that, The calcium source comprises one or more combinations of calcium hydroxide, calcium oxide, calcium phosphate, monocalcium phosphate and calcium dihydrogen phosphate.

4. The method of claim 1, wherein, The phosphorus source comprises one or more combinations of phosphoric acid, calcium phosphate, monocalcium phosphate and calcium dihydrogen phosphate.

5. The preparation method according to claim 1, characterized in that, The molar ratio of gallium, calcium and phosphorus in the gallium source, the calcium source and the phosphorus source is x:(10-x):6, and the chemical formula of the apatite material obtained is Ca 10-x Ga x (PO4)6O x (OH) 2-x wherein 0 < x ≤ 2.

6. The method of claim 1, wherein, The reaction temperature of the hydrothermal reaction is 120-200 DEG C, and the reaction time of the hydrothermal reaction is 2-36 h.

7. The production method according to claim 6, characterized by, The hydrothermal reaction is a dynamic hydrothermal reaction, and the steps of the hydrothermal reaction are as follows: The precursor suspension is transferred into a polytetrafluoroethylene container to perform a dynamic hydrothermal reaction in a rotatable homogeneous reactor, the rotating speed is 5-30 rounds per minute, the reaction is performed at 120-200 DEG C for 2-36 hours, and the filling ratio of the dynamic hydrothermal reaction is 50-90%.

8. The method of claim 1, wherein, The hydrothermal reaction is performed in an oven, and the reaction condition is that the reaction is performed at 60-250 DEG C for 10-76 h.

9. The method of claim 1, wherein, The hydrothermal reaction is performed under stirring, the temperature is 60-200 DEG C, and the reaction is performed for 10-76 h.

10. An apatite material characterized in that, The gallium and calcium-containing apatite material is prepared according to any one of the preparation methods in claims 1-9.

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