CN111467566B

CN111467566B - Preparation method and application of ion co-doped hydroxyapatite transparent ceramic

Info

Publication number: CN111467566B
Application number: CN202010584182.7A
Authority: CN
Inventors: 徐传艳; 朱阳光; 李亚东; 李亚军
Original assignee: Suzhou Dingan Technology Co ltd
Current assignee: Suzhou Dingan Technology Co ltd
Priority date: 2020-06-24
Filing date: 2020-06-24
Publication date: 2020-10-23
Anticipated expiration: 2040-06-24
Also published as: WO2021259043A1; CN111467566A

Abstract

The invention relates to a preparation method and application of ion co-doped hydroxyapatite transparent ceramic, wherein the general formula of the ion co-doped hydroxyapatite transparent ceramic is [ Ca ]_10‑xM_x][(PO₄)_6‑y(SiO₄)_y][(OH)_2‑zN_z]M is selected from one or more of K ions, Na ions, Mg ions, Al ions, Zn ions, Sr ions, Mn ions, Co ions, Ag ions, Cu ions and Fe ions; n is F ion, Cl ion, CO₃ ^2‑One or more of ions; x is more than or equal to 0 and less than 10, y is more than or equal to 0 and less than 6, and z is more than or equal to 0 and less than 2; the preparation method disclosed by the invention adopts a chemical precipitation method to obtain precursor slurry, regulates and controls the solid content of the precursor slurry, and obtains the ion co-doped hydroxyapatite transparent ceramic through molding, microwave or infrared sintering, and the ion co-doped hydroxyapatite transparent ceramic can be used in the field of defect repair of hard tissues such as teeth, jaws, spines, joints and the like.

Description

Preparation method and application of ion co-doped hydroxyapatite transparent ceramic

Technical Field

The invention relates to the technical field of medical instruments, in particular to a preparation method and application of ion co-doped hydroxyapatite transparent ceramic.

Background

Hydroxyapatite (Hydroxyapatite) is used as a main inorganic component of natural bone tissue, has excellent Biocompatibility and osteoconductivity (Osteoconduction), can form chemical bonding with living bone tissue, is a good biological hard tissue filling, repairing and replacing material, and has been widely applied to clinicThe application is as follows. However, simple hydroxyapatite still has defects in Biodegradation (Biodegradation) and new bone growth, matching of elastic modulus and host bone modulus, vascularization, osseointegration ability and ability to induce bone regeneration. Therefore, the clinical application of the hydroxyapatite is restricted in a certain range. The element-doped hydroxyapatite is formed by substituting functional elements for specific positions in a hydroxyapatite crystal lattice, so that the specific functionality of the doped elements is exerted in bone tissue engineering application. There are three types of element-substituted hydroxyapatite: ca²⁺Substituted in position, PO₄ ^3-Substitution and channel ion OH^-And (4) substitution. A large number of studies have shown that the inorganic component of hydroxyapatite in natural bone tissue contains a number of ions, such as F^-、CO₃ ^2-、Sr²⁺、Zn²⁺、Al³⁺、Si⁴⁺And Na⁺And the like. These trace elements play an important role in the biochemical role of bone. Therefore, the artificially synthesized hydroxyapatite can have more excellent bioactivity by doping modification, obtain the same biological performance as natural bone tissues, and have important application value.

S. Pina et al (Brushite-Forming Mg-, Zn-and Sr-subscribed Bone center for Clinical Applications, Materials, 2010, 3: 519 535), U.S. Thormann et al (Bodefect induced by matrix modified calcium center in crystalline-size metallic activity defects in overview induced ratios, Biomaterials, 2013,34: 8589-: supplementation with Sr ions and Ca, Mg and Zn ions is the most effective method for promoting bone formation and reducing bone resorption. IsmatUllah et al (Impact of structural defects of Sr/Fe co-doped HAp on the osteoplastic promotion and osteoplastic differentiation for Materials application as a bonesults, Materials Science & Engineering C, 2020,110: 110-. Furthermore, studies by Susmita Bose et al (underlying and associated osteogenic in calcium phosphate ceramics, Trends in Biotechnology, 2013,31(10): 594) 605 show that trace elements (such as Li, Zn, Mg, Mn, Si, Sr, etc.) can promote osteogenesis as well as neovascularization. Therefore, the vascularization and bone regeneration induction capability of the hydroxyapatite can be improved through the doping of trace elements and the regulation and control of material parameters; the elastic modulus is regulated and controlled to avoid the stress shielding effect; increasing the degradation rate to match the new bone growth.

In order to obtain hydroxyapatite with different biological functions, CN108164263A discloses a bionic ternary ion doped hydroxyapatite biological ceramic powder material, a preparation method and an application thereof, the patent firstly adopts hydrothermal reaction to prepare Sr, Zn and F ion doped hydroxyapatite biological ceramic powder, and then adopts dry pressing or isostatic pressing technology to prepare ternary ion doped hydroxyapatite ceramic, the patent method can not meet the personalized forming requirements, and can not obtain transparent ceramic. CN107161974B discloses a preparation method of a multi-ion co-doped hydroxyapatite powder material, which adopts hydrothermal reaction to dope K, Na, Mg, Al, Zn, Sr, Si, F and C ions in the hydroxyapatite powder material. In the prior art, ion-doped hydroxyapatite powder is mostly prepared by a hydrothermal synthesis method, which has high requirements on equipment, high investment and operation difficulty and long reaction time and cannot be produced in batch and large scale. The existing multi-ion doped hydroxyapatite powder has few doped ion species, but the ceramic sintered by hydroxyapatite with less doped ions has too high crystallinity which can not be regulated, and the transparent ion doped hydroxyapatite ceramic can not be obtained. Therefore, further improving the comprehensive performance of the hydroxyapatite and optimizing the forming technology have become the key direction of the development of the hydroxyapatite in the future.

Disclosure of Invention

In order to solve the technical problems, the invention provides a preparation method and an application scheme of ion co-doped hydroxyapatite transparent ceramic.

The technical scheme adopted by the invention is as follows:

the invention provides a preparation method of ion co-doped hydroxyapatite transparent ceramic (as shown in figure 1), which comprises the following steps:

preparing a solution, namely weighing calcium nitrate, adding the calcium nitrate into a reaction kettle, weighing one or more of silicate, a compound containing M and a compound containing N, adding the silicate, the compound containing M and the compound containing N into the reaction kettle, adding distilled water for dissolving to prepare a mixed solution, and adjusting the pH value of the mixed solution to be 8-13; weighing diammonium phosphate to prepare a diammonium phosphate solution;

performing chemical precipitation reaction, namely adding a diammonium hydrogen phosphate solution into a reaction kettle at the speed of 1-100 mL/min, reacting at the temperature of 30-90 ℃ for 1-18 h, and obtaining reaction product slurry after the reaction is finished;

performing suction filtration and/or washing, performing suction filtration on liquid in the reaction product slurry or repeatedly washing and performing suction filtration on the reaction product slurry by using deionized water, and controlling the solid content range of the reaction product slurry to be 20-90% to obtain precursor slurry;

forming, when the solid content of the precursor slurry is 20-50%, preparing microspheres or particle biscuit by adopting a spray granulation process, and sintering the microspheres or particle biscuit at high temperature to obtain transparent ceramic microspheres or particles; when the solid content of the precursor slurry is 50-90%, a biscuit with a specific shape is prepared by adopting the processes of extrusion molding, casting molding, slip casting, injection molding and additive manufacturing molding, and the biscuit with the specific shape is sintered at high temperature to obtain the transparent ceramic with the specific shape.

Further, the M-containing compound is selected from potassium nitrate, potassium carbonate, potassium bicarbonate, potassium acetate, potassium hydroxide, potassium oxide, potassium lactate, potassium citrate, potassium gluconate, sodium nitrate, sodium carbonate, sodium bicarbonate, sodium acetate, sodium hydroxide, sodium oxide, sodium lactate, sodium citrate, sodium gluconate, magnesium nitrate, magnesium acetate, magnesium carbonate, magnesium bicarbonate, magnesium oxide, magnesium lactate, magnesium chloride, magnesium citrate, magnesium gluconate, aluminum nitrate, aluminum carbonate, aluminum chloride, aluminum lactate, aluminum citrate, zinc nitrate, zinc carbonate, zinc chloride, zinc acetate, zinc lactate, zinc citrate, zinc gluconate, strontium nitrate, strontium carbonate, strontium chloride, strontium acetate, strontium lactate, strontium citrate, manganese nitrate, manganese carbonate, manganese chloride, manganese acetate, manganese lactate, manganese gluconate, cobalt nitrate, cobalt carbonate, cobalt chloride, manganese acetate, manganese lactate, manganese nitrate, manganese chloride, manganese acetate, manganese citrate, manganese gluconate, cobalt nitrate, cobalt chloride, manganese acetate, manganese lactate, manganese citrate, manganese nitrate, one or more of cobalt acetate, silver nitrate, silver carbonate, silver chloride, silver acetate, silver lactate, silver citrate, copper nitrate, copper carbonate, copper chloride, copper acetate, cuprous acetate, copper citrate, copper gluconate, ferric nitrate, ferric carbonate, ferric chloride, ferric acetate, ferrous lactate, ferric citrate and ferrous gluconate; the N-containing compound is selected from potassium fluoride, sodium fluoride, calcium fluoride, magnesium fluoride, dimanganese fluoride, zinc fluoride, aluminum fluoride, ferrous fluoride, silver fluoride, cobalt fluoride, copper fluoride, strontium fluoride, sodium fluorosilicate, fluorosilicic acid, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, manganese chloride, zinc chloride, aluminum chloride, ferric chloride, silver chloride, cobalt chloride, copper chloride, strontium chloride; the silicate is selected from one or more of potassium silicate, sodium silicate, magnesium silicate, sodium fluosilicate, fluosilicic acid, methyl orthosilicate, ethyl orthosilicate, propyl orthosilicate and isopropyl orthosilicate.

Further, the molding process is one of spray granulation, extrusion molding, casting molding, slip casting, injection molding and additive manufacturing molding.

Further, the air inlet temperature of the spray granulation process is 250 ℃, the air outlet temperature is 100-180 ℃, the feeding speed is 5-50mL/min, and the rotating speed of the spray head is 180-300 rpm.

Further, microwave sintering or infrared sintering is adopted for high-temperature sintering.

Furthermore, the temperature range of the high-temperature sintering of the microspheres or the particles or the biscuit with the specific shape is 800-1200 ℃, the sintering time is 10-120 min, and the heating rate is 20-9000 ℃/min.

Furthermore, the ion co-doped hydroxyapatite transparent ceramic prepared by the preparation method has a composition general formula of [ Ca_10-xM_x][(PO₄)_6-y(SiO₄)_y][(OH)_2-zN_z]M is selected from one or more of K ions, Na ions, Mg ions, Al ions, Zn ions, Sr ions, Mn ions, Co ions, Ag ions, Cu ions and Fe ions; n is F^-Ions, Cl^-Ion, CO₃ ^2-One or more of ions; x is more than or equal to 0 and less than 10, y is more than or equal to 0 and less than 6, and z is more than or equal to 0 and less than 2; the grain size of the transparent ceramic is not more than 50 μm, and the light transmittance of the transparent ceramic is 5-45%.

Further, the Mn ions in M include Mn³⁺And Mn²⁺The Co ions comprise Co³⁺And Co²⁺The Cu ions comprise Cu⁺And Cu²⁺Said Fe ions comprising Fe³⁺And Fe²⁺。

In another aspect, the invention also provides the application of the ion co-doped hydroxyapatite transparent ceramic, wherein the application comprises the application of the ion co-doped hydroxyapatite transparent ceramic as a tooth repairing material, a jaw repairing material, a spine repairing material, a joint repairing material and other hard tissue repairing materials.

Compared with the prior art, the technical scheme of the invention has the following advantages and beneficial effects:

(1) the invention adopts a liquid-phase chemical precipitation method to synthesize the ion co-doped hydroxyapatite transparent ceramic precursor slurry, can directly meet the process requirements of different molding technologies by controlling the solid content in the precursor slurry, and is convenient for producing biscuit with various forms and structures; the precursor slurry has good rheological property and forming capability, and the preparation process is simple and convenient, has small equipment investment and high production efficiency, is suitable for large-scale production, and has popularization and application values.

(2) The invention adopts microwave or infrared technology to sinter the ion co-doped hydroxyapatite transparent ceramic biscuit, has the advantages of high temperature rise speed and no process pollution, and has the advantages of small crystal grain size, high transparency, controllable degradation speed and the like and excellent mechanical property.

(3) The ion co-doped hydroxyapatite transparent ceramic provided by the invention is subjected to multiple ion co-doping by simulating human mineral elements, so that the ion co-doped hydroxyapatite transparent ceramic not only has good biocompatibility and bioactivity, but also has multiple biological functions of good bone cell conduction, vascularization promotion, osteogenesis performance and the like, and can obtain stronger antibacterial and bacteriostatic functions by adding Ag, Zn and Cu ions.

(4) The ion co-doped hydroxyapatite transparent ceramic prepared by adopting different molding processes has the advantages of individuation customization and can meet the clinical application requirements of tooth repair, jaw repair, spine repair, joint repair, other hard tissue repair and the like.

Drawings

FIG. 1 is a flow chart of a preparation method of ion co-doped hydroxyapatite transparent ceramic;

FIG. 2 is an XRD spectrum of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in example 2;

fig. 3 is an XRD spectrum of the silver-fluoride ion co-doped hydroxyapatite transparent ceramic prepared in example 8;

fig. 4 is an optical photograph of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in example 2;

fig. 5 is an SEM photograph of the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres prepared in example 6;

fig. 6 is an SEM photograph of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic prepared in example 10;

fig. 7 is a histological photograph of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic prepared in example 10 after being implanted for 12 weeks.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

It should be noted that the terms "comprises" and "comprising," and any variations thereof, in the description and claims of the present invention and the above-described drawings, are intended to cover a non-exclusive inclusion, such that a process, method, apparatus, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.

The materials and methods used in the following examples are, unless otherwise specified, conventional in the art.

The simulated body fluid composition used in the following examples was Na⁺：142.0mM·L^-1、K⁺：5.0 mM·L^-1、Mg²⁺：1.5mM·L^-1、Ca²⁺：2.5 mM·L^-1、Cl^-1：147.8 mM·L^-1、HCO₃ ^-：4.2mM·L^-1、HPO₄ ^2-：1.0 mM·L^-1、SO₄ ^2-：0.5 mM·L^-1。

Example 1

[Ca₁₀(PO₄)₆(OH)₂]Transparent ceramic microspheres

Weighing 826.53g of calcium nitrate in a reaction kettle, adding 10L of deionized water to prepare a calcium nitrate solution, and adjusting the pH value of the calcium nitrate solution to 13; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into a reaction kettle at the speed of 5ml/min for reaction, carrying out water bath reaction at the temperature of 30 ℃ for 24 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 40% to obtain precursor slurry; and (2) carrying out a spray granulation process on the precursor slurry (process conditions are that the feeding speed is 10ml/min, the air inlet temperature is 180-200 ℃, the air outlet temperature is 110-120 ℃, and the rotating speed of a spray head is 250 rpm) to obtain a microsphere biscuit, and carrying out high-temperature sintering on the microsphere biscuit by adopting microwaves, wherein the sintering temperature is 1150 ℃, the sintering time is 30min, and the heating rate is 30 ℃/min, so as to obtain the hydroxyapatite transparent ceramic microspheres.

XRD analysis is carried out on the hydroxyapatite transparent ceramic microspheres, and the result shows that the crystallinity of the hydroxyapatite transparent ceramic microspheres is 90%;

the grain size is less than 0.2 μm and the size range of the hydroxyapatite transparent ceramic microspheres is 10-80 μm through the detection of a scanning electron microscope;

carrying out degradation test on the hydroxyapatite transparent ceramic microspheres in simulated body fluid, wherein the maximum degradation rate is more than 30%;

the hydroxyapatite transparent ceramic microspheres and distilled water are prepared into paste which is used for filling root canals of 7 healthy adult male New Zealand white rabbits with pulpitis, the formation of new hard tissues nearby the root canals can be seen through histological observation after 4 weeks, the root canal walls are locked by reparative dentin apical pores, and the effective rate reaches 100%. Therefore, the hydroxyapatite transparent ceramic microspheres can be used for filling the root canal of the tooth.

Example 2

[Ca₈K₂](PO₄)₆[(OH) F]Transparent ceramics

Weighing 619.89g of calcium nitrate, 70.77g of potassium nitrate and 13.664 g of calcium fluoride in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 12; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 8ml/min for reaction, carrying out water bath reaction at 40 ℃ for 18 hours, and obtaining reaction slurry after the reaction is finished; removing redundant liquid in the reaction slurry through suction filtration, and controlling the solid content of the reaction slurry to be 85% to obtain precursor slurry; preparing the precursor slurry into a cylindrical biscuit (the diameter is 0.5-1.5 mm, the length is 1-3 mm) by adopting an extrusion molding process, and performing microwave sintering on the cylindrical ceramic biscuit (the sintering temperature is 1100 ℃, the sintering time is 45min, and the heating rate is 50 ℃/min) to obtain the potassium-fluorine co-doped hydroxyapatite transparent ceramic in a specific shape.

XRD analysis is carried out on the potassium-fluorine co-doped hydroxyapatite transparent ceramic, and the result is shown in figure 2, and the result shows that the crystallinity is about 65%; from FIG. 2 [ Ca ]₈K₂](PO₄)₆[(OH)F]The XRD spectrum and the hydroxyapatite standard spectrum (JCPDS No. 09-0432) ofIn a comparative example, [ Ca ]₈K₂](PO₄)₆[(OH)F]The transparent ceramic did not have any hetero-phase due to K, F ion doping, however, [ Ca ]₈K₂](PO₄)₆[(OH)F]The diffraction spectrum peak shape of the transparent ceramic is slightly wide, which indicates that the product is not completely crystallized;

the detection result of a scanning electron microscope shows that the grain size is less than 10 mu m; the result of shooting by a digital camera shows that the overall dimension of the ceramic is 0.5-1.5 mm in diameter and 1-3 mm in length (see figure 4);

performing transparency detection on the potassium-fluorine co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is 25-30%, which indicates that a densified structure is formed;

performing degradation test on the potassium-fluorine co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 60%;

preparing paste from potassium-fluorine co-doped hydroxyapatite transparent ceramic and distilled water, and using the paste for repairing the mandible defect of 6 healthy adult male white rabbits in New Zealand for 12 weeks, and observing the histology to find that a large amount of new bones are formed near the mandible defect, and the amount of new bones is 98%; the imaging examined the complete disappearance of the bone defect area. Therefore, the potassium-fluorine co-doped hydroxyapatite transparent ceramic can be used for repairing the jaw defects.

Example 3

[Ca₈KNa](PO₄)₆[(OH) F]Transparent ceramics

Weighing 619.89g of calcium nitrate, 35.77g of potassium nitrate, 36.37g of sodium nitrate and 13.664 g of calcium fluoride in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 12; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 10ml/min for reaction, carrying out water bath reaction at 40 ℃ for 18 hours, and obtaining reaction slurry after the reaction is finished; filtering to remove redundant liquid in the reaction slurry, and controlling the solid content of the reaction slurry to be 85% to obtain precursor slurry; preparing the precursor slurry into a cylindrical biscuit (the diameter is 0.5-1.0 mm, the length is 1-2 mm) by adopting an extrusion molding process, and performing infrared sintering on the cylindrical biscuit (the temperature is 1150 ℃ for 80min, and the heating rate is 300 ℃/min) to obtain the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic.

XRD analysis is carried out on the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 55%, the detection result of a scanning electron microscope shows that the grain size is less than 8.5 mu m, the external dimension of the ceramic is 0.5-1.0 mm in diameter and 1-2 mm in length;

performing transparency detection on the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is 30%;

performing degradation test on the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate is more than 65%;

the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic and distilled water are prepared into paste which is used for filling root canals of 6 healthy adult male New Zealand white rabbits with pulpitis, and histological observation after 3 weeks shows that new bone tissues are formed near the root canals and dentin apical pores are locked, so that the effective rate reaches 100 percent; therefore, the potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramic can be used for filling the root canal of the tooth.

Example 4

[Ca₇Na₃](PO₄)₆[(OH)_1.5Cl_0.5]Transparent ceramics

Weighing 578.57g of calcium nitrate (tetrahydrate), 74.37g of sodium nitrate and 10.227g of sodium chloride in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 11; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 9ml/min for reaction, carrying out water bath reaction at the temperature of 50 ℃ for 20 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 70% to obtain precursor slurry; preparing the precursor slurry into a sheet biscuit (3 multiplied by 8 multiplied by 12 mm) by adopting a casting molding process, and performing microwave sintering on the sheet ceramic biscuit (1120 ℃ for 55min, the heating rate is 80 ℃/min) to obtain the sodium-chlorine co-doped hydroxyapatite transparent ceramic;

XRD analysis is carried out on the sodium-chlorine co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 65 percent, and the scanning electron microscope detection shows that the grain size is less than 20 mu m;

performing transparency detection on the sodium-chlorine co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is more than 5%;

performing degradation test on the sodium-chlorine co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 35%;

carrying out lumbar vertebrae posterior lateral transverse process spinal fusion on 7 healthy adult male New Zealand white rabbits, and implanting sodium-chlorine co-doped hydroxyapatite transparent ceramic plates between the L4/5 transverse processes on two sides; histological examination after 12 weeks revealed that a small amount of cartilage and a large number of continuous trabeculae formed around the implant, forming a large amount of braided bone, and cortical bone surrounding the trabeculae, indicating that bony fusion had been achieved. The method can be used for filling and repairing the defects of the spinal column of the sodium-chlorine co-doped hydroxyapatite transparent ceramic.

Example 5

[Ca₆Mg₄][(PO₄)_5.2(SiO₄)_0.8](OH)₂Transparent ceramics

Weighing 495.92g of calcium nitrate (tetrahydrate), 207.2g of magnesium nitrate and 51.53g of sodium metasilicate in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 10; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 12ml/min for reaction, carrying out water bath reaction at the temperature of 60 ℃ for 18 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 75% to obtain precursor slurry; and preparing the precursor slurry into a cylindrical biscuit by adopting an injection molding process, and performing infrared sintering on the cylindrical biscuit (sintering at 1140 ℃ for 50min, and heating rate of 1300 ℃/min) to obtain the magnesium-silicate ion co-doped hydroxyapatite transparent ceramic (the external dimension is 6mm in diameter and 15mm in length).

XRD analysis is carried out on the magnesium-silicate ion co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 45 percent, and the scanning electron microscope detection shows that the grain size is less than 5 mu m;

performing transparency detection on the magnesium-silicate ion co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is more than 15%;

performing degradation test on the magnesium-silicate ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 55%;

the method is characterized in that a 15mm long bone defect model of the middle section of the radius of a healthy adult male New Zealand white rabbit is made of magnesium-silicate ion co-doped hydroxyapatite transparent ceramic, the model is roughly observed in 4, 8 and 12 weeks after implantation, histology and X-ray observation show that new bones begin to form in 4 weeks, bone defect parts are repaired in 8 weeks, part of new bone tissues form lamellar bones in 12 weeks, trabecular bone forms, and a large number of osteoblasts are visible in the model; imaging detection at 12 weeks after implantation shows that the bone defect area is completely repaired, the cortex is continuous, and the model is complete. Therefore, the magnesium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for repairing joint defects.

Example 6

[Ca₅Al₅](PO₄)₆[(OH)_0.8F_1.2]Transparent ceramic microspheres

Weighing 363.67g of calcium nitrate (tetrahydrate), 656.48g of aluminum nitrate and 16.39g of calcium fluoride in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 13; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 15ml/min for reaction, carrying out water bath reaction at 70 ℃ for 16 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 46% to obtain precursor slurry; carrying out spray granulation on the precursor slurry (the feeding speed is 20ml/min, the air inlet temperature is 180-200 ℃, the air outlet temperature is 110-120 ℃, and the rotating speed of a spray head is 230 rpm) to obtain a microsphere biscuit; and (3) performing microwave sintering on the microsphere biscuit (sintering at 1070 ℃ for 60min, and heating rate of 65 ℃/min) to obtain the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microsphere.

XRD analysis is carried out on the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres, and the result shows that the crystallinity is 90%;

scanning electron microscope detection shows that the result is shown in fig. 5, and the diameter of the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microsphere is 20-50 μm;

performing transparency detection on the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres, wherein the light transmittance is more than 15%;

carrying out degradation test on the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 15%;

the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres and distilled water are prepared into filling paste, the filling paste is implanted into the ilium defect part of a beagle dog, 75% of the filling paste is found to be absorbed after 24 weeks, a large number of microvessels and new bone tissues like autologous trabecular bones appear in the filling paste, and the bone defect area completely disappears through imaging detection. Therefore, the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres can be used for bone defect repair.

Example 7

[Ca_7.2Zn_2.8](PO₄)₆[(OH)_0.6Cl_1.4]Transparent ceramic microspheres

Weighing 537.24g of calcium nitrate (tetrahydrate), 291.54g of zinc nitrate and 27.195g of calcium chloride in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 10; weighing 277.3g of diammonium hydrogen phosphate in a container, adding 2L of deionized water to prepare diammonium hydrogen phosphate solution, adding the diammonium hydrogen phosphate solution into the mixed solution of the reaction kettle at the speed of 25ml/min for reaction, carrying out water bath reaction at 80 ℃ for 15 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 20% to obtain precursor slurry; spraying and granulating the precursor slurry (the feeding speed is 50ml/min, the air inlet temperature is 220-250 ℃, the air outlet temperature is 150-180 ℃, and the rotating speed of a spray head is 260 rpm) to obtain a microsphere biscuit; and (3) sintering the microsphere biscuit in a microwave oven (the temperature rise speed is 50 ℃/min, and the temperature is kept at 1150 ℃ for 30 min) to obtain the zinc-chlorine co-doped hydroxyapatite transparent ceramic microsphere.

XRD analysis is carried out on the zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres, and the result shows that the crystallinity is 90 percent, and the scanning electron microscope detection shows that the average grain size is less than 1 mu m;

the diameter of the zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres is 10-50 mu m by detection of a scanning electron microscope;

performing transparency detection on the zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres, wherein the light transmittance is more than 15%;

performing degradation test on the zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 65%;

preparing a filling paste by using zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres and distilled water, implanting the filling paste into a femoral defect part of a beagle dog, and observing histology after 1 year to find that 90 percent of the filling paste is absorbed and fused by surrounding normal bones, more blood vessels are formed in the internal space of the filling paste, and a large amount of new bone tissues like self-body trabecular bones grow into the implant; the imaging detection shows that the bone defect area completely disappears, so that the zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres can be used for repairing bone defects;

antibacterial property detection shows that (according to an antibacterial property test method of the SNT 3122-.

Example 8

[Ca_9.2Sr_0.8][ (PO₄)_4.4(SiO₄)_1.6](OH)₂Transparent ceramics

Weighing 760.40g of calcium nitrate (tetrahydrate), 41.34g of strontium carbonate and 159.15g of sodium metasilicate (nonahydrate) in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 13; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 8ml/min for reaction, carrying out water bath reaction at 37 ℃ for 22 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 60% to obtain precursor slurry; and (3) obtaining a sheet biscuit (6.25X 12.5X 15 mm) by adopting the 3D printing and forming process for the precursor slurry, and sintering the sheet biscuit in a microwave oven (1100 ℃ for 60min, and the heating rate of 120 ℃/min) to obtain the strontium-silicate ion co-doped hydroxyapatite transparent ceramic (the external dimension is 5X 10X 12 mm) with the three-dimensional porous structure.

XRD analysis is carried out on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic, and the result is shown in figure 3, and the result shows that the crystallinity is about 90 percent, and the scanning electron microscope detection shows that the average grain size is less than 10 mu m; from FIG. 3 [ Ca_9.2Sr_0.8][(PO₄)_4.4(SiO₄)_1.6](OH)₂Comparing the XRD spectrum with hydroxyapatite standard spectrum (JCPDS No. 09-0432) to determine that [ Ca_9.2Sr_0.8][ (PO₄)_4.4(SiO₄)_1.6](OH)₂Sr is not contained in transparent ceramics²⁺、SiO₄ ^2-Ion doping presents any hetero-phase, however, [ Ca ]_9.2Sr_0.8][ (PO₄)_4.4(SiO₄)_1.6](OH)₂The diffraction pattern is slightly broader, indicating that the product is not completely crystalline.

The detection of a scanning electron microscope shows that the aperture of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic with the three-dimensional porous structure is 200-500 mu m, and the porosity is 75%;

the transparency detection is carried out on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic with the three-dimensional porous structure, the light transmittance is more than 15 percent,

carrying out degradation test on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic with the three-dimensional porous structure in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 65%;

the strontium-silicate ion co-doped hydroxyapatite transparent ceramic with the three-dimensional porous structure is implanted into the epiphyseal bone defect of the tibia of the beagle dog, and is found to be completely fused with normal bone after one year, and the surface of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic is covered by about 72 percent of regenerated cortical bone; the inner space of the bone is provided with a new bone ingrowth which has the same structure with the autologous trabecular bone; at the same time, it was observed that more blood vessels grew from the periosteum adjacent to the implant into the new cortical bone. Therefore, the strontium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for repairing the jaw defects.

Example 9

[Ca_8.4Ag_1.6](PO₄)₆[(OH)_1.5F_0.5]Transparent ceramics

673.62g of calcium nitrate (tetrahydrate), 95.13g of silver nitrate and 6.832g of sodium fluoride are weighed into a reaction kettle, 8L of deionized water is added to prepare a mixed solution, and the pH value of the mixed solution is adjusted to 12; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 6ml/min for reaction, carrying out water bath reaction at 37 ℃ for 24 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 78% to obtain precursor slurry; and preparing the precursor slurry into a cylindrical biscuit by adopting an injection molding process, and sintering the cylindrical biscuit in an infrared furnace (1190 ℃ for 90min, the heating rate of 2200 ℃/min) to obtain the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic.

XRD analysis is carried out on the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic, the result shows that the crystallinity is 85%, and the scanning electron microscope detection shows that the grain size is smaller than 1 mu m;

the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic has the diameter of 0.5-1 mm and the length dimension of 0.5-3 mm through detection of a scanning electron microscope;

the transparency of the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic is detected, the light transmittance is more than 15 percent,

carrying out degradation test on the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 55%;

silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic and distilled water are prepared into paste for filling alveolar bone of healthy adult male New Zealand white rabbits, histological observation is carried out after 3 weeks, a large amount of trabecular bone-like new bone tissues are formed near the implant, more than 70% of cortical bone is covered, and no inflammation appears; the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic can be used for filling alveolar bones;

Example 10

[Ca_9.2Sr_0.8][(PO₄)_4.4(SiO₄)_1.6](OH)₂Transparent ceramics

Weighing 760.40g of calcium nitrate (tetrahydrate), 41.34g of strontium carbonate and 159.15g of sodium metasilicate (nonahydrate) in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to 13; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 8ml/min for reaction, carrying out water bath reaction at 37 ℃ for 22 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 60% to obtain precursor slurry; and (3) obtaining a rectangular cylinder biscuit by adopting a casting molding process for the precursor slurry, freeze-drying the rectangular cylinder biscuit, and sintering in an infrared furnace (the heating rate is 650 ℃/min, and the temperature is 1200 ℃ for 20 min) to obtain the strontium-silicate ion co-doped hydroxyapatite transparent ceramic with the three-dimensional porous structure (the external dimension is 5 multiplied by 10 multiplied by 25 mm).

XRD analysis is carried out on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 92 percent, and the scanning electron microscope detection (shown in figure 6) shows that the average grain size is less than 2 mu m;

carrying out transparency detection on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is more than 45%;

carrying out degradation test on the strontium-silicate ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 45%;

the strontium-silicate ion co-doped hydroxyapatite transparent ceramic is implanted into the radius defect part of a healthy adult male New Zealand white rabbit, and the bone formation condition of the bone defect area is observed by X-ray, histology and scanning electron microscope (see figure 7) at 2, 4, 8 and 12 weeks after the operation, so that the bone formation is better and the new bone grows by more than 85 percent; the strontium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for repairing bone defects.

Example 11

[Ca_8.4Ag_1.6](PO₄)₆[(OH)_1.5F_0.5]Transparent ceramics

673.62g of calcium nitrate (tetrahydrate), 95.13g of silver nitrate and 6.832g of sodium fluoride are weighed into a reaction kettle, 8L of deionized water is added to prepare a mixed solution, and the pH value of the mixed solution is adjusted to be 13; weighing 277.33g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 100ml/min for reaction, carrying out water bath reaction at the temperature of 90 ℃ for 1 hour, and obtaining reactant slurry after the reaction is finished; removing liquid in the reactant slurry by suction filtration, and then repeatedly washing and suction-filtering by deionized water to control the solid content of the reactant slurry to be 90% to obtain precursor slurry; and preparing the precursor slurry into a cylindrical biscuit by adopting an injection molding process, and sintering the cylindrical biscuit in an infrared furnace (sintering at 800 ℃ for 120min, and heating rate of 9000 ℃/min) to obtain the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic.

XRD analysis is carried out on the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic, the result shows that the crystallinity is 45 percent, and the scanning electron microscope detection shows that the grain size is less than 0.1 mu m;

the transparency of the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic is detected, the light transmittance is more than 10 percent,

carrying out degradation test on the silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 65%;

Example 12

[Ca_9.2Sr_0.5Co_0.2Fe_0.1][(PO₄)_4.4(SiO₄)_1.6](OH)₂Transparent ceramics

Weighing 651.77g of calcium nitrate (tetrahydrate), 31.74g of strontium nitrate, 17.46g of cobaltous nitrate (hexahydrate), 7.26g of ferric nitrate and 136.42g of sodium metasilicate (nonahydrate) in a reaction kettle, adding 8L of deionized water to prepare a mixed solution, and adjusting the pH value of the mixed solution to be 11; weighing 174.32g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 12ml/min for reaction, carrying out water bath reaction at 47 ℃ for 12 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 65% to obtain precursor slurry; and (3) obtaining a rectangular cylinder biscuit by adopting a casting molding process for the precursor slurry, freeze-drying the rectangular cylinder biscuit, and sintering in an infrared furnace (the heating rate is 450 ℃/min, and the temperature is 1100 ℃ for 40 min) to obtain the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic (the external dimension is 5 multiplied by 10 multiplied by 25 mm).

XRD analysis is carried out on the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 95 percent, and the scanning electron microscope detection shows that the average grain size is less than 15 um;

carrying out transparency detection on the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is more than 35%;

carrying out degradation test on the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 55%;

implanting the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic into the radius defect part of a healthy adult male New Zealand white rabbit, and observing the bone generation condition of the bone defect area by X-ray and histology at 2, 4, 8 and 12 weeks after the operation, wherein the new bone growth is more than 87 percent; the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic can be used for bone defect repair.

Example 13

[Ca_8.4Mn_1.0Cu_0.5Ag_0.1](PO₄)₆[(OH)_1.5F_0.5]Transparent ceramics

595.10g of calcium nitrate (tetrahydrate), 5.10g of silver nitrate, 53.69g of manganous nitrate, 28.13g of copper nitrate and 6.30g of sodium fluoride are weighed into a reaction kettle, 8L of deionized water is added to prepare a mixed solution, and the pH value of the mixed solution is adjusted to 10; weighing 237.71g of diammonium phosphate in a container, and adding 2L of deionized water to prepare a diammonium phosphate solution; adding a diammonium hydrogen phosphate solution into the mixed solution in the reaction kettle at the speed of 5ml/min for reaction, carrying out water bath reaction at the temperature of 45 ℃ for 20 hours, and obtaining reactant slurry after the reaction is finished; removing redundant liquid in the reactant slurry through suction filtration, and controlling the solid content of the reactant slurry to be 75% to obtain precursor slurry; and preparing the precursor slurry into a cylindrical biscuit by adopting an injection molding process, and sintering the cylindrical biscuit in a microwave oven (sintering at 920 ℃ for 20min, heating rate of 1200 ℃/min) to obtain the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic.

XRD analysis is carried out on the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic, and the result shows that the crystallinity is 95 percent, and the scanning electron microscope detection shows that the grain size is less than 8 um;

the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic has the diameter of 0.2-1 mm and the length dimension of 0.5-1 mm through detection of a scanning electron microscope;

performing transparency detection on the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic, wherein the light transmittance is more than 20%;

performing degradation test on the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic in simulated body fluid, wherein the maximum degradation rate in the simulated body fluid is more than 45%;

manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic, sodium carboxymethylcellulose and distilled water are prepared into paste for filling alveolar bone of healthy adult male New Zealand white rabbits, histological observation is carried out after 5 weeks of sacrifice, a large amount of trabecular bone-like new bone tissues are formed near the implant, more than 80% of cortical bone is covered, and no inflammation occurs; the manganese-copper-silver-fluoric acid radical ion co-doped hydroxyapatite transparent ceramic can be used for filling alveolar bones;

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. A preparation method of ion co-doped hydroxyapatite transparent ceramic, which is characterized in that,

the composition general formula of the ion co-doped hydroxyapatite transparent ceramic is [ Ca ]_10-xM_x][(PO₄)_6-y(SiO₄)_y][(OH)_2-zN_z]M is selected from one or more of K ions, Na ions, Mg ions, Al ions, Zn ions, Sr ions, Mn ions, Co ions, Ag ions, Cu ions and Fe ions; n is F ion, Cl ion, CO₃ ^2-One or more of ions; x is more than or equal to 0 and less than 10, y is more than or equal to 0 and less than 6, z is more than or equal to 0 and less than 2, and the Mn ions comprise Mn³⁺And Mn²⁺The Co ions comprise Co³⁺And Co²⁺The Cu ions comprise Cu⁺And Cu²⁺The Fe ion includes Fe³⁺And Fe²⁺(ii) a The preparation method of the codoped hydroxyapatite transparent ceramic comprises the following steps:

performing suction filtration, namely performing suction filtration on liquid in the reaction product slurry, and controlling the solid content range of the reaction product slurry to be 20-90% to obtain precursor slurry;

forming, when the solid content of the precursor slurry is 20-50%, preparing microspheres or particle biscuit by adopting a spray granulation process, and sintering the microspheres or particle biscuit at high temperature to obtain transparent ceramic microspheres or particles; when the solid content of the precursor slurry is 50-90%, preparing a biscuit with a specific shape by adopting a forming process, and sintering the biscuit with the specific shape at high temperature to obtain transparent ceramic with the specific shape;

the air inlet temperature of the spray granulation process is 120-250 ℃, the air outlet temperature is 100-180 ℃, the feeding speed is 5-50mL/min, and the rotating speed of a spray head is 180-300 rpm;

the temperature range of high-temperature sintering of the microspheres, the particles or the biscuit with the specific shape is 800-1200 ℃, the sintering time is 10-120 min, and the heating rate is 20-9000 ℃/min.

2. The method for preparing an ion co-doped hydroxyapatite transparent ceramic according to claim 1, wherein the M-containing compound is selected from potassium nitrate, potassium carbonate, potassium bicarbonate, potassium acetate, potassium hydroxide, potassium oxide, potassium lactate, potassium citrate, potassium gluconate, sodium nitrate, sodium carbonate, sodium bicarbonate, sodium acetate, sodium hydroxide, sodium oxide, sodium lactate, sodium citrate, sodium gluconate, magnesium nitrate, magnesium acetate, magnesium carbonate, magnesium bicarbonate, magnesium oxide, magnesium lactate, magnesium chloride, magnesium citrate, magnesium gluconate, aluminum nitrate, aluminum carbonate, aluminum chloride, aluminum lactate, aluminum citrate, zinc nitrate, zinc carbonate, zinc chloride, zinc acetate, zinc lactate, zinc citrate, zinc gluconate, strontium nitrate, strontium carbonate, strontium chloride, strontium acetate, strontium lactate, strontium citrate, manganese nitrate, manganese carbonate, manganese chloride, magnesium acetate, magnesium lactate, magnesium citrate, magnesium nitrate, magnesium carbonate, magnesium acetate, magnesium lactate, magnesium citrate, magnesium nitrate, magnesium carbonate, one or more of manganese acetate, manganese lactate, manganese citrate, manganese gluconate, cobalt nitrate, cobalt carbonate, cobalt chloride, cobalt acetate, silver nitrate, silver carbonate, silver chloride, silver acetate, silver lactate, silver citrate, copper nitrate, copper carbonate, copper chloride, copper acetate, cuprous acetate, copper citrate, copper gluconate, ferric nitrate, ferric carbonate, ferric chloride, ferric acetate, ferrous lactate, ferric citrate and ferrous gluconate; the N-containing compound is selected from potassium fluoride, sodium fluoride, calcium fluoride, magnesium fluoride, dimanganese fluoride, zinc fluoride, aluminum fluoride, ferrous fluoride, silver fluoride, cobalt fluoride, copper fluoride, strontium fluoride, sodium fluorosilicate, fluorosilicic acid, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, manganese chloride, zinc chloride, aluminum chloride, ferric chloride, silver chloride, cobalt chloride, copper chloride, strontium chloride; the silicate is selected from one or more of potassium silicate, sodium silicate, magnesium silicate, sodium fluosilicate, fluosilicic acid, methyl orthosilicate, ethyl orthosilicate, propyl orthosilicate and isopropyl orthosilicate.

3. The method for preparing the ion co-doped hydroxyapatite transparent ceramic according to claim 1, wherein the molding process is one of spray granulation, extrusion molding, casting molding, slip casting, injection molding and additive manufacturing molding.

4. The method for preparing the ion co-doped hydroxyapatite transparent ceramic according to claim 1, wherein the high temperature sintering is microwave sintering or infrared sintering.

5. The method for preparing an ion co-doped hydroxyapatite transparent ceramic according to any one of claims 1 to 4, wherein the crystal grain size of the transparent ceramic prepared by the preparation method is not more than 50 μm, and the light transmittance of the transparent ceramic is 5 to 45%.

6. An application of the ion co-doped hydroxyapatite transparent ceramic prepared by the preparation method according to any one of claims 1 to 4, which comprises a tooth repairing material, a jaw repairing material, a spine repairing material and an articulation repairing material.