WO2021259043A1 - Method for preparing ion co-doped hydroxyapatite transparent ceramic and use thereof - Google Patents

Method for preparing ion co-doped hydroxyapatite transparent ceramic and use thereof Download PDF

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Publication number
WO2021259043A1
WO2021259043A1 PCT/CN2021/098347 CN2021098347W WO2021259043A1 WO 2021259043 A1 WO2021259043 A1 WO 2021259043A1 CN 2021098347 W CN2021098347 W CN 2021098347W WO 2021259043 A1 WO2021259043 A1 WO 2021259043A1
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Prior art keywords
ion
chloride
doped hydroxyapatite
sodium
nitrate
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PCT/CN2021/098347
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French (fr)
Chinese (zh)
Inventor
徐传艳
朱阳光
李亚东
李亚军
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苏州鼎安科技有限公司
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Publication of WO2021259043A1 publication Critical patent/WO2021259043A1/en

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    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
    • C04B2235/70—Aspects relating to sintered or melt-casted ceramic products
    • C04B2235/96—Properties of ceramic products, e.g. mechanical properties such as strength, toughness, wear resistance
    • C04B2235/9646—Optical properties
    • C04B2235/9653—Translucent or transparent ceramics other than alumina

Definitions

  • the invention relates to the technical field of medical devices, in particular to a preparation method and application of ion co-doped hydroxyapatite transparent ceramics.
  • Hydroxyaptite As the main inorganic component of natural bone tissue, has excellent biocompatibility and osteoconduction. It can form chemical bonds with living bone tissue and is a good Bio-hard tissue filling, repair and replacement materials have been widely used in clinical practice.
  • pure hydroxyapatite still has shortcomings in terms of biodegradation and new bone growth, elastic modulus matching with host bone modulus, vascularization, osseointegration ability, and bone regeneration ability. Therefore, the clinical application of hydroxyapatite is restricted within a certain range.
  • Element-doped hydroxyapatite is the use of functional elements to replace specific positions in the hydroxyapatite lattice to form functional element-doped hydroxyapatite, thereby exerting the specific function of doping elements in bone tissue engineering applications sex.
  • Numerous studies have shown hydroxyapatite inorganic component of natural bone tissue containing a variety of ions, such as F -, CO 3 2-, Sr 2+, Zn 2+, Al 3+, Si 4+ Na + and the like. These trace elements play an important role in the biochemical effects of bones. Therefore, the doping modification can make the synthetic hydroxyapatite have more excellent biological activity and obtain the same biological properties as the natural bone tissue, which has important application value.
  • CN 108164263 A discloses a bionic ternary ion-doped hydroxyapatite bioceramic powder material and its preparation method and application. The patent first adopts hydrothermal reaction Prepared Sr, Zn, F ion-doped hydroxyapatite bioceramic powders, and then used dry pressing or isostatic pressing to prepare ternary ion-doped hydroxyapatite ceramics. The above-mentioned patented method cannot meet individualized molding. Request, but also unable to obtain transparent ceramics.
  • CN107161974 B discloses a method for preparing a hydroxyapatite powder material co-doped with multiple ions.
  • the patent uses hydrothermal reaction to dope hydroxyapatite powder material with K, Na, Mg, Al, Zn, Sr, Si, F and C ions.
  • ion-doped hydroxyapatite powder is mostly prepared by a hydrothermal synthesis method, which requires high equipment, is difficult to invest and operates, and has a long reaction time, and cannot be mass-produced.
  • the existing multi-ion-doped hydroxyapatite powder has a small number of doping ions, and the hydroxyapatite sintered ceramics with less doped ions have too high crystallinity, and the crystallinity cannot be controlled, and transparent ions cannot be obtained. Doped with hydroxyapatite ceramics. Therefore, further improving the overall performance of hydroxyapatite and optimizing the molding technology have become the focus of future research and development of hydroxyapatite.
  • the present invention provides a preparation method of ion co-doped hydroxyapatite transparent ceramics and an application scheme thereof.
  • the present invention provides a method for preparing ion co-doped hydroxyapatite transparent ceramics (as shown in Figure 1), which includes the following steps:
  • reaction kettle For chemical precipitation reaction, add the diammonium hydrogen phosphate solution to the reaction kettle at a rate of 1-100 mL/min, the reaction temperature is 30-90°C, and the reaction time is 1-18h. After the reaction is completed, a reaction product slurry is obtained;
  • 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, hydrogen carbonate Sodium, 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, chlorinated Strontium, strontium acetate, strontium lactate, strontium citrate, manganese nitrate, manganese carbonate, manganese chloride, manganese
  • the molding process is one of spray granulation, extrusion molding, pouring molding, grouting molding, injection molding, and additive manufacturing molding process.
  • microwave sintering or infrared sintering is used for high-temperature sintering.
  • the temperature range for high-temperature sintering of microspheres or particles or green bodies of specific shapes is 800-1200°C, the sintering time is 10-120 minutes, and the heating rate is 20-9000°C/min.
  • the general formula of the composition of an ion co-doped hydroxyapatite transparent ceramic prepared by the preparation method is [Ca 10-x M x ][(PO 4 ) 6-y (SiO 4 ) y ] [( OH) 2-z N z ],
  • M is selected from one or more of K ion, Na ion, Mg ion, Al ion, Zn ion, Sr ion, Mn ion, Co ion, Ag ion, Cu ion, Fe ion Species;
  • N is one or more of F- ions, Cl - ions, and CO 3 2- ions; 0 ⁇ x ⁇ 10, 0 ⁇ y ⁇ 6, 0 ⁇ z ⁇ 2; crystal grains of the transparent ceramic The size is not more than 50 ⁇ m, and the light transmittance of the transparent ceramic is 5-45%.
  • Mn ions in M include Mn 3+ and Mn 2+
  • the Co ions include Co 3+ and Co 2+
  • the Cu ions include Cu + and Cu 2+
  • the Fe ions include Fe 3 + And Fe 2+
  • the present invention also provides the application of ion co-doped hydroxyapatite transparent ceramics.
  • the applications include tooth restoration materials, jaw bone restoration materials, spine restoration materials, joint restoration materials and other hard tissue restoration materials.
  • the present invention adopts liquid phase chemical precipitation method to synthesize ion co-doped hydroxyapatite transparent ceramic precursor slurry.
  • the process requirements of different molding technologies can be directly met, which is convenient for production Various shapes and structures of blanks; precursor slurry not only has good rheological properties and forming ability, but also has simple and convenient preparation process, small equipment investment and high production efficiency. It is suitable for large-scale production and has the value of popularization and application.
  • the present invention uses microwave or infrared technology to sinter the ion-co-doped hydroxyapatite transparent ceramic green body, which has the advantages of fast heating speed and no process pollution.
  • the obtained ion-co-doped hydroxyapatite transparent ceramic The advantages of small grain size, high transparency, controllable transparency and controllable degradation rate, and excellent mechanical properties.
  • the ion co-doped hydroxyapatite transparent ceramic of the present invention is co-doped with various ions by simulating the mineral elements of the human body, which not only has good biocompatibility and biological activity, but also has good bone cells Conduct, promote vascularization and osteogenic properties and other biological functions, adding Ag, Zn and Cu ions can obtain strong antibacterial and antibacterial functions.
  • Figure 1 is a flow chart of the preparation method of ion co-doped hydroxyapatite transparent ceramics
  • Example 2 is the XRD spectrum of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in Example 2;
  • Figure 3 is an XRD spectrum of the silver-fluorate ion co-doped hydroxyapatite transparent ceramic prepared in Example 8;
  • Example 4 is an optical photograph of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in Example 2;
  • Example 5 is an SEM photograph of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres prepared in Example 6;
  • the degradation test of hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate is greater than 30%;
  • the degradation test of potassium-fluorine co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 60%;
  • a paste of potassium-fluorine co-doped hydroxyapatite transparent ceramics and distilled water was used to repair the mandibular defect of 6 healthy adult male New Zealand white rabbits. After 12 weeks, a histological observation revealed a large amount of mandibular defect. New bone formation accounts for 98%; the bone defect area detected by imaging completely disappears. It can be seen that potassium-fluorine co-doped hydroxyapatite transparent ceramics can be used to repair jaw defects.
  • Potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for pulpitis root canal filling in 6 healthy adult male New Zealand white rabbits. After 3 weeks, the histological observation revealed that there was new growth near the root canal. Bone tissue is formed, and the apical foramen of dentin is blocked, and the effective rate is 100%. It can be seen that potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics can be used for tooth root canal filling.
  • the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 70% to obtain the precursor slurry; the precursor slurry is made into a sheet blank (3 ⁇ 8 ⁇ 12mm), microwave sintering the flake ceramic greenware (sintering at 1120°C for 55min, heating rate 80°C/min) to obtain sodium-chloride co-doped hydroxyapatite transparent ceramic;
  • the degradation test of sodium-chloride co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 35%;
  • the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction and the solid content of the reactant slurry is controlled to 75% to obtain the precursor slurry; the precursor slurry is made into cylindrical element by injection molding process
  • infrared sintering the cylindrical blank sining at 1140°C for 50 min, heating rate 1300°C/min, to obtain the magnesium-silicate ion co-doped hydroxyapatite transparent ceramics (diameter 6mm, length 15mm).
  • the degradation test of magnesium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
  • Magnesium-silicate ion co-doped hydroxyapatite transparent ceramics were used to make a 15 mm long bone defect model of the middle radius of healthy adult male New Zealand white rabbits. Gross, histological and X-ray observations were performed at 4, 8, and 12 weeks after implantation. 4 New bone has begun to form at week 8 and the bone defect was partially repaired at 8 weeks. At 12 weeks, some new bone tissue formed lamellar bone, bone trabecula formed, and a large number of osteoblasts were seen; bone defect was detected by imaging at 12 weeks after implantation The area is completely repaired, the cortex is continuous, and the shape is complete. It can be seen that the magnesium-silicate ion co-doped hydroxyapatite transparent ceramics can be used for joint defect repair.
  • the diameter of the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres is 20-50 ⁇ m;
  • the degradation test of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 15%;
  • the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres and distilled water were made into a filling paste and implanted into the iliac defect of a beagle dog. After 24 weeks, it was found that 75% of it was absorbed, and a large number of microvessels and autologous bodies appeared inside. Trabecular bone-like new bone tissue, the bone defect area completely disappeared by imaging examination. It can be seen that aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres can be used for bone defect repair.
  • the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 20% to obtain the precursor slurry; the precursor slurry is sprayed and granulated (feeding speed 50ml/min, The inlet air temperature is 220 ⁇ 250°C, the outlet air temperature is 150 ⁇ 180°C, and the nozzle speed is 260rpm) to obtain the microsphere green body; the microsphere green body is sintered in the microwave oven (heating speed 50°C/min, 1150°C heat preservation 30min ) To obtain zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres.
  • the diameter of zinc-chloride co-doped hydroxyapatite transparent ceramic microspheres is 10 ⁇ 50um
  • the degradation test of zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 65%;
  • the zinc-chloride co-doped hydroxyapatite transparent ceramic microspheres and distilled water were made into a filling paste and implanted into the femoral defect of a beagle dog. Histological observation revealed that 90% of it was absorbed and fused by the surrounding normal bone after 1 year. There are many blood vessels formed in the internal space, and a large amount of new bone tissue like autologous trabecular bone grows into the implant. The bone defect area is completely disappeared in the imaging test. It can be seen that the zinc-chloride co-doped hydroxyapatite is transparent Ceramic microspheres can be used for bone defect repair;
  • the antibacterial performance test showed (according to SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the antibacterial rate of zinc-chlorine co-doped hydroxyapatite transparent ceramic microsphere particles against Escherichia coli, Staphylococcus aureus and Candida albicans were respectively Reach 90.9, 95.95 and 90.5%, with broad-spectrum antibacterial properties.
  • the three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramic has a pore size of 200 ⁇ 500 ⁇ m and a porosity of 75%;
  • the degradation test of the three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 65%;
  • the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 78% to obtain the precursor slurry; the precursor slurry is made into a cylindrical blank by injection molding process,
  • the cylindrical green body was sintered in an infrared furnace (1190°C for 90 min, heating rate 2200°C/min) to obtain silver-fluorate ion co-doped hydroxyapatite transparent ceramics.
  • the degradation test of silver-fluorate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
  • the silver-fluorate ion co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for the alveolar bone filling of healthy adult male New Zealand white rabbits. After 3 weeks, they were sacrificed and histological observation showed that there were a large number of small particles near the implant. Beam bone-like new bone tissue is formed, cortical bone covers more than 70%, and there is no inflammation; it shows that silver-fluorate ion co-doped hydroxyapatite transparent ceramics can be used for alveolar bone filling;
  • the degradation test of strontium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 45%;
  • the strontium-silicate ion co-doped hydroxyapatite transparent ceramic was implanted into the radius defect of healthy adult male New Zealand white rabbits. X-ray, histological observation and 12-week scanning electron microscopy were performed at 2, 4, 8, 12 weeks after surgery Observation of the bone formation in the bone defect area (see Figure 7) shows that the osteogenesis is good, and the new bone grows more than 85%; it shows that the strontium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for bone defect repair.
  • the silver-fluorate ion co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for the alveolar bone filling of healthy adult male New Zealand white rabbits. After 3 weeks, they were sacrificed and histological observation showed that there were a large number of small particles near the implant. Beam bone-like new bone tissue is formed, cortical bone covers more than 70%, and there is no inflammation; it indicates that silver-fluorate ion co-doped hydroxyapatite transparent ceramics can be used for alveolar bone filling;
  • the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction and the solid content of the reactant slurry is controlled to 65%.
  • the precursor slurry is obtained; the precursor slurry is cast and formed to obtain a rectangular cylinder blank, which is freeze-dried and then placed in an infrared furnace for sintering (heating rate 450°C/min, 1100°C heat preservation 40min), Obtained strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics (external size 5 ⁇ 10 ⁇ 25mm).
  • the degradation test of strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
  • the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic was implanted into the radius defect of healthy adult male New Zealand white rabbits. X-rays and histological observations were performed at 2, 4, 8, 12 weeks after the operation. The bone formation in the defect area shows that the new bone has grown in more than 87%; it shows that the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic can be used for bone defect repair.
  • the reactant slurry was obtained; the excess liquid in the reactant slurry was removed by suction and the solid content of the reactant slurry was controlled to 75% to obtain the precursor slurry; the precursor The slurry is made into a cylindrical blank by injection molding process, and the cylindrical blank is placed in a microwave oven for sintering (sintering at 920°C for 20 minutes, heating rate 1200°C/min) to obtain manganese-copper-silver-fluorate ion co-doped hydroxyl Apatite transparent ceramics.
  • the degradation test of manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 45%;
  • Manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics sodium carboxymethyl cellulose, and distilled water were used to make a paste for alveolar bone filling in healthy adult male New Zealand white rabbits. They were sacrificed after 5 weeks. Histological observation revealed that a large amount of trabecular bone-like new bone tissue was formed near the implant, and the cortical bone covered more than 80%, and there was no inflammation; it indicated that manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics Can be used for alveolar bone filling;
  • the antibacterial performance test showed (according to the SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramic particles is effective against Escherichia coli, Staphylococcus aureus and Candida albicans
  • the antibacterial rates of the antibacterial products are respectively 97.9, 98.5 and 99.5%, and they have broad-spectrum antibacterial properties.

Abstract

A method for preparing an ion co-doped hydroxyapatite transparent ceramic and the use thereof. The ion co-doped hydroxyapatite transparent ceramic has a general formula of [Ca10-xMx][(PO4)6-y(SiO4)y][(OH)2-zNz], wherein M is selected from one or more of K, Na, Mg, Al, Zn, Sr, Mn, Co, Ag, Cu and Fe ions, and N is one or more of F-, Cl- and CO3 2- ions, where 0≤x<10, 0≤y<6, and 0≤z<2. According to the preparation method disclosed in the present invention, a chemical precipitation method is used to obtain a precursor slurry, the solid content of which is adjusted and controlled, and the slurry is then subjected to molding and microwave or infrared sintering to obtain the ion co-doped hydroxyapatite transparent ceramic, which can be used in the field of hard tissue defect repairs, for example on teeth, jaw bones, spines and joints.

Description

一种离子共掺杂羟基磷灰石透明陶瓷的制备方法及其应用Preparation method and application of ion co-doped hydroxyapatite transparent ceramic 技术领域Technical field
本发明涉及医疗器械技术领域，特别涉及一种离子共掺杂羟基磷灰石透明陶瓷的制备方法及其应用。The invention relates to the technical field of medical devices, in particular to a preparation method and application of ion co-doped hydroxyapatite transparent ceramics.
背景技术Background technique
羟基磷灰石（Hydroxyaptite）作为天然骨组织的主要无机成分，具有优良的生物相容性（Biocompatibility）和骨传导性（Osteoconduction），能与活体骨组织形成化学性键合，是一种良好的生物硬组织填充、修复和替换材料，在临床中已得到广泛应用。然而，单纯羟基磷灰石在生物降解（Biodegradation）与新生骨生长、弹性模量与宿主骨模量匹配性、以及血管化、骨整合能力和诱导骨再生能力等方面仍存在缺陷。因此，在一定范围内制约了羟基磷灰石的临床应用。元素掺杂羟基磷灰石是利用功能性元素取代羟基磷灰石晶格中的特定位置，形成功能性元素掺杂的羟基磷灰石，从而在骨组织工程应用中发挥掺杂元素的特定功能性。元素取代羟基磷灰石有三种类型：Ca 2+位取代、PO 4 3-取代和通道离子OH -取代。大量研究显示，天然骨组织的无机成分羟基磷灰石中含有多种离子，如F -、CO 3 2-、Sr 2+、Zn 2+、Al 3+、Si 4+和Na +等。这些微量元素在骨骼的生化作用中起着重要作用。因此，通过掺杂改性可以使人工合成的羟基磷灰石具有更加优异的生物活性，获得与天然骨组织相同的生物学性能，具有重要的应用价值。 Hydroxyaptite (Hydroxyaptite), as the main inorganic component of natural bone tissue, has excellent biocompatibility and osteoconduction. It can form chemical bonds with living bone tissue and is a good Bio-hard tissue filling, repair and replacement materials have been widely used in clinical practice. However, pure hydroxyapatite still has shortcomings in terms of biodegradation and new bone growth, elastic modulus matching with host bone modulus, vascularization, osseointegration ability, and bone regeneration ability. Therefore, the clinical application of hydroxyapatite is restricted within a certain range. Element-doped hydroxyapatite is the use of functional elements to replace specific positions in the hydroxyapatite lattice to form functional element-doped hydroxyapatite, thereby exerting the specific function of doping elements in bone tissue engineering applications sex. There are three types of element-substituted hydroxyapatite: Ca 2+ substitution, PO 4 3- substitution and channel ion OH - substitution. Numerous studies have shown hydroxyapatite inorganic component of natural bone tissue containing a variety of ions, such as F -, CO 3 2-, Sr 2+, Zn 2+, Al 3+, Si 4+ Na + and the like. These trace elements play an important role in the biochemical effects of bones. Therefore, the doping modification can make the synthetic hydroxyapatite have more excellent biological activity and obtain the same biological properties as the natural bone tissue, which has important application value.
S. Pina等（Brushite-Forming Mg-, Zn- and Sr-Substituted Bone Cementsfor Clinical Applications，Materials，2010，3，519–535）、U. Thormann等（Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats, Biomaterials，2013，34，8589–8598）、M. Schumacher等（Strontium modified calcium phosphate cements- approaches towards targeted stimulation of bone turnover，Journal of Materials Chemistry B，2015，3，4626–4640、Strontium substitution in apatitic CaP cements effectively attenuates osteoclastic resorption but does not inhibit osteoclastogenesis，Acta Biomaterialia，2016，37, 184-194）的研究表明，补充Sr离子以及Ca、Mg和Zn离子是促进骨形成和减少骨吸收的最有效方法。Ismat Ullah等（Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute，Materials  Science & Engineering C，2020，110，110633）证实Sr/Fe共掺杂羟基磷灰石纳米材料对MC3T3-E1细胞无毒。此外，Susmita Bose等（Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics, Trends in Biotechnology，2013，Vol.31，No.10，594-605）的研究表明，微量元素（如Li、Zn、Mg、Mn、Si、Sr等）能够促进成骨以及新生血管形成。由此可见，通过微量元素的掺杂和材料学参数调控，可以提高羟基磷灰石的血管化、诱导骨再生能力；调控弹性模量来避免应力遮蔽效应；提高降解速度来匹配新生骨生长。S. Pina, etc. (Brushite-Forming Mg-, Zn- and Sr-Substituted Bone Cements for Clinical Applications, Materials, 2010, 3, 519–535), U. Thormann, etc. (Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats, Biomaterials, 2013, 34, 8589–8598), M. Schumacher, etc. (Strontium modified calcium phosphate cements- approaches towards targeted stimulation of bone turnover, Journal of Materials Chemistry B, 2015, 3, 4626-4640, Strontium substitution in apatitic CaP cements effectively attenuates osteoclastic resorption but does not inhibit osteoclastogenesis, Acta Biomaterialia, 2016, 37, 184-194) studies have shown that supplementing Sr ions and Ca, Mg and Zn ions is the most effective way to promote bone formation and reduce bone resorption. Ismat Ullah et al. (Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute, Materials Science & Engineering C, 2020, 110, 110633) confirmed that Sr/Fe co-doped hydroxyapatite nanomaterials are non-toxic to MC3T3-E1 cells. In addition, Susmita Bose et al. (Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics, Trends in Biotechnology, 2013, Vol.31, No.10, 594-605) research shows that trace elements (such as Li, Zn, Mg, Mn, Si, Sr, etc.) can promote bone formation and neovascularization. It can be seen that the doping of trace elements and the adjustment of material parameters can improve the vascularization of hydroxyapatite and induce bone regeneration; adjust the elastic modulus to avoid the stress shielding effect; increase the degradation rate to match the growth of new bone.
为了获得具有不同生物学功能的羟基磷灰石， CN 108164263 A公开了一种仿生三元离子掺杂羟基磷灰石生物陶瓷粉体材料及其制备方法及其应用，该专利首先采用水热反应制备了Sr、Zn、F离子掺杂羟基磷灰石生物陶瓷粉体，随后再采用干压或等静压成型技术制备三元离子掺杂羟基磷灰石陶瓷，上述专利方法无法满足个性化成型要求，也无法获得透明陶瓷。CN107161974 B公开了一种多元离子共掺杂羟基磷灰石粉体材料的制备方法，该专利采用水热反应对羟基磷灰石粉体材料中掺杂K、Na、Mg、Al、Zn、Sr、Si、F和C离子。现有技术中，离子掺杂羟基磷灰石粉体多采用水热合成法制备，该法对设备要求较高，投资和操作难度大、反应时间较长，且无法进行批量化大规模生产。现有多离子掺杂羟基磷灰石粉体中的掺杂离子种类偏少，而采用掺杂离子较少羟基磷灰石烧结的陶瓷结晶度过高，且结晶度不可调控，无法获得透明离子掺杂羟基磷灰石陶瓷。因此，进一步改善羟基磷灰石的综合性能和优化成型技术已成为未来羟基磷灰石研究发展的重点方向。In order to obtain hydroxyapatite with different biological functions, CN 108164263 A discloses a bionic ternary ion-doped hydroxyapatite bioceramic powder material and its preparation method and application. The patent first adopts hydrothermal reaction Prepared Sr, Zn, F ion-doped hydroxyapatite bioceramic powders, and then used dry pressing or isostatic pressing to prepare ternary ion-doped hydroxyapatite ceramics. The above-mentioned patented method cannot meet individualized molding. Request, but also unable to obtain transparent ceramics. CN107161974 B discloses a method for preparing a hydroxyapatite powder material co-doped with multiple ions. The patent uses hydrothermal reaction to dope hydroxyapatite powder material with K, Na, Mg, Al, Zn, Sr, Si, F and C ions. In the prior art, ion-doped hydroxyapatite powder is mostly prepared by a hydrothermal synthesis method, which requires high equipment, is difficult to invest and operates, and has a long reaction time, and cannot be mass-produced. The existing multi-ion-doped hydroxyapatite powder has a small number of doping ions, and the hydroxyapatite sintered ceramics with less doped ions have too high crystallinity, and the crystallinity cannot be controlled, and transparent ions cannot be obtained. Doped with hydroxyapatite ceramics. Therefore, further improving the overall performance of hydroxyapatite and optimizing the molding technology have become the focus of future research and development of hydroxyapatite.
技术解决方案Technical solutions
为解决上述技术问题，本发明提供一种离子共掺杂羟基磷灰石透明陶瓷的制备方法及其应用方案。In order to solve the above technical problems, the present invention provides a preparation method of ion co-doped hydroxyapatite transparent ceramics and an application scheme thereof.
本发明采用的技术方案如下：The technical scheme adopted by the present invention is as follows:
本发明提供一种离子共掺杂羟基磷灰石透明陶瓷的制备方法（如图1所示），包括如下步骤：The present invention provides a method for preparing ion co-doped hydroxyapatite transparent ceramics (as shown in Figure 1), which includes the following steps:
溶液配制，称取硝酸钙加入反应釜，称取硅酸盐、含M的化合物和含N的化合物中的一种或多种加入反应釜，然后加入蒸馏水进行溶解，配制成混合溶液，调节混合溶液pH值为8~13；称取磷酸氢二铵配制成磷酸氢二铵溶液；To prepare the solution, weigh calcium nitrate into the reactor, weigh one or more of the silicate, M-containing compound and N-containing compound into the reactor, then add distilled water to dissolve, prepare a mixed solution, and adjust the mixing The pH of the solution is 8~13; Weigh diammonium hydrogen phosphate to prepare diammonium hydrogen phosphate solution;
化学沉淀反应，将磷酸氢二铵溶液以1~100mL/min的速度加入反应釜中，反应温度30~90℃，反应时间1~18h，反应结束后，得到反应产物浆料；For chemical precipitation reaction, add the diammonium hydrogen phosphate solution to the reaction kettle at a rate of 1-100 mL/min, the reaction temperature is 30-90°C, and the reaction time is 1-18h. After the reaction is completed, a reaction product slurry is obtained;
抽滤和/或洗涤，抽滤反应产物浆料中的液体或用去离子水反复洗涤和抽滤反应物浆料，控制反应产物浆料固含量范围为20-90%，得到前驱体浆料；Suction filtration and/or washing, suction filtration of the liquid in the reaction product slurry or repeated washing and suction filtration of the reaction product slurry with deionized water, and control the solid content of the reaction product slurry to range from 20-90% to obtain the precursor slurry ；
成型，前驱体浆料固含量为20-50%时，采用喷雾造粒工艺制成微球或颗粒素坯，微球或颗粒素坯经高温烧结得到透明陶瓷微球或颗粒；前驱体浆料固含量为50-90%时，采用挤出成型、浇注成型、注浆成型、注射成型和增材制造成型工艺制成特定形状素坯，特定形状素坯经过高温烧结得到特定形状的透明陶瓷。Forming, when the solid content of the precursor slurry is 20-50%, the spray granulation process is used to make microspheres or pellets, and the microspheres or pellets are sintered at high temperature to obtain transparent ceramic microspheres or particles; precursor slurry When the solid content is 50-90%, extrusion molding, pouring molding, grouting molding, injection molding and additive manufacturing molding processes are used to make a specific shape green body. The specific shape green body is sintered at a high temperature to obtain a specific shape of transparent ceramic.
进一步地，所述含M的化合物选自硝酸钾、碳酸钾、碳酸氢钾、醋酸钾、氢氧化钾、氧化钾、乳酸钾、柠檬酸钾、葡萄糖酸钾、硝酸钠、碳酸钠、碳酸氢钠、醋酸钠、氢氧化钠、氧化钠、乳酸钠、柠檬酸钠、葡萄糖酸钠、硝酸镁、醋酸镁、碳酸镁、碳酸氢镁、氧化镁、乳酸镁、氯化镁、柠檬酸镁、葡萄糖酸镁、硝酸铝、碳酸铝、氯化铝、乳酸铝、柠檬酸铝、硝酸锌、碳酸锌、氯化锌、醋酸锌、乳酸锌、柠檬酸锌、葡萄糖酸锌、硝酸锶、碳酸锶、氯化锶、醋酸锶、乳酸锶、柠檬酸锶、硝酸锰、碳酸锰、氯化锰、醋酸锰、乳酸锰、柠檬酸锰、葡萄糖酸锰、硝酸钴、碳酸钴、氯化钴、醋酸钴、硝酸银、碳酸银、氯化银、醋酸银、乳酸银、柠檬酸银、硝酸铜、碳酸铜、氯化铜、醋酸铜、醋酸亚铜、柠檬酸铜、葡萄糖酸铜、硝酸铁、碳酸铁、氯化铁、醋酸铁、醋酸亚铁、乳酸亚铁、柠檬酸铁、葡萄糖酸亚铁中的一种或多种；所述含N的化合物选自氟化钾、氟化钠、氟化钙、氟化镁、氟化二锰、氟化锌、氟化铝、氟化亚铁、氟化银、氟化钴、氟化铜、氟化锶、氟硅酸钠、氟硅酸、氯化钾、氯化钠、氯化钙、氯化镁、氯化锰、氯化锌、氯化铝、氯化铁、氯化银、氯化钴、氯化铜、氯化锶；所述硅酸盐选自硅酸钾、硅酸钠、硅酸镁、氟硅酸钠、氟硅酸、正硅酸甲酯、正硅酸乙酯、正硅酸丙酯、正硅酸异丙酯中的一种或多种。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, hydrogen carbonate Sodium, 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, chlorinated Strontium, strontium acetate, strontium lactate, strontium citrate, manganese nitrate, manganese carbonate, manganese chloride, manganese acetate, manganese lactate, manganese citrate, manganese gluconate, cobalt nitrate, cobalt carbonate, cobalt chloride, cobalt acetate, nitric acid Silver, silver carbonate, silver chloride, silver acetate, silver lactate, silver citrate, copper nitrate, copper carbonate, copper chloride, copper acetate, cuprous acetate, copper citrate, copper gluconate, iron nitrate, iron carbonate, One or more of ferric chloride, ferric acetate, ferrous acetate, ferrous lactate, ferric citrate, and ferrous gluconate; the N-containing compound is selected from potassium fluoride, sodium fluoride, calcium fluoride , Magnesium fluoride, manganese fluoride, zinc fluoride, aluminum fluoride, ferrous fluoride, silver fluoride, cobalt fluoride, copper fluoride, strontium fluoride, sodium fluorosilicate, fluorosilicic acid, chlorination Potassium, sodium chloride, calcium chloride, magnesium chloride, manganese chloride, zinc chloride, aluminum chloride, iron chloride, silver chloride, cobalt chloride, copper chloride, strontium chloride; the silicate is selected From potassium silicate, sodium silicate, magnesium silicate, sodium fluorosilicate, fluorosilicic acid, methyl orthosilicate, ethyl orthosilicate, propyl orthosilicate, isopropyl orthosilicate Or multiple.
进一步地，成型工艺为喷雾造粒、挤出成型、浇注成型、注浆成型、注射成型和增材制造成型工艺中的一种。Further, the molding process is one of spray granulation, extrusion molding, pouring molding, grouting molding, injection molding, and additive manufacturing molding process.
进一步地，喷雾造粒工艺的进风温度为120-250℃，出风温度100-180℃，加料速度为5-50mL/min，喷头转速为180-300rpm。Further, the air inlet temperature of the spray granulation process is 120-250°C, the outlet air temperature is 100-180°C, the feeding speed is 5-50 mL/min, and the nozzle rotation speed is 180-300 rpm.
进一步地，高温烧结采用微波烧结或红外烧结。Further, microwave sintering or infrared sintering is used for high-temperature sintering.
进一步地，微球或颗粒或特定形状素坯高温烧结的温度范围为800~1200℃，烧结时间10~120min，升温速率为20~9000℃/min。Further, the temperature range for high-temperature sintering of microspheres or particles or green bodies of specific shapes is 800-1200°C, the sintering time is 10-120 minutes, and the heating rate is 20-9000°C/min.
进一步地，所述制备方法制备的一种离子共掺杂羟基磷灰石透明陶瓷的组成通式为[Ca 10-xM x][(PO 4) 6-y(SiO 4) y] [(OH) 2-zN z]， M选自K离子、Na离子、Mg离子、Al离子、Zn离子、Sr离子、Mn离子、Co离子、Ag离子、Cu离子、Fe离子中的一种或多种；N为F -离子、Cl -离子、CO 3 2-离子中的一种或多种；0≤x＜10，0≤y＜6，0≤z＜2；所述透明陶瓷的晶粒尺寸为不大于50μm，所述透明陶瓷的透光率为5-45%。 Further, the general formula of the composition of an ion co-doped hydroxyapatite transparent ceramic prepared by the preparation method is [Ca 10-x M x ][(PO 4 ) 6-y (SiO 4 ) y ] [( OH) 2-z N z ], M is selected from one or more of K ion, Na ion, Mg ion, Al ion, Zn ion, Sr ion, Mn ion, Co ion, Ag ion, Cu ion, Fe ion Species; N is one or more of F- ions, Cl - ions, and CO 3 2- ions; 0≤x＜10, 0≤y＜6, 0≤z＜2; crystal grains of the transparent ceramic The size is not more than 50 μm, and the light transmittance of the transparent ceramic is 5-45%.
进一步地，M中所述Mn离子包括Mn 3+和Mn 2+，所述Co离子包括Co 3+和Co 2+，所述Cu离子包括Cu +和Cu 2+，所述Fe离子包括Fe 3+和Fe 2+ Further, the Mn ions in M include Mn 3+ and Mn 2+ , the Co ions include Co 3+ and Co 2+ , the Cu ions include Cu + and Cu 2+ , and the Fe ions include Fe 3 + And Fe 2+
另外一方面，本发明还提供离子共掺杂羟基磷灰石透明陶瓷的应用，所述应用包括作为牙齿修复材料、颌骨修复材料、脊柱修复材料、关节修复材料和其他硬组织修复材料。On the other hand, the present invention also provides the application of ion co-doped hydroxyapatite transparent ceramics. The applications include tooth restoration materials, jaw bone restoration materials, spine restoration materials, joint restoration materials and other hard tissue restoration materials.
有益效果Beneficial effect
与现有技术相比，本发明的技术方案具有如下优点和有益效果：Compared with the prior art, the technical solution of the present invention has the following advantages and beneficial effects:
（1）本发明采用液相化学沉淀法合成离子共掺杂羟基磷灰石透明陶瓷前驱体浆料，通过控制前驱体浆料中的固含量即可直接满足不同成型技术的工艺要求，便于生产各种形态和结构的素坯；前驱体浆料不仅具有良好的流变性能和成型能力，而且制备工艺简单方便，设备投入小和生产效率高，适用于规模化生产，具有推广应用价值。(1) The present invention adopts liquid phase chemical precipitation method to synthesize ion co-doped hydroxyapatite transparent ceramic precursor slurry. By controlling the solid content in the precursor slurry, the process requirements of different molding technologies can be directly met, which is convenient for production Various shapes and structures of blanks; precursor slurry not only has good rheological properties and forming ability, but also has simple and convenient preparation process, small equipment investment and high production efficiency. It is suitable for large-scale production and has the value of popularization and application.
（2）本发明采用微波或红外技术对离子共掺杂羟基磷灰石透明陶瓷素坯进行烧结，具有升温速度快和无工艺污染的优点，所获得的离子共掺杂羟基磷灰石透明陶瓷晶粒尺寸小、透明度高、透明度可控和降解速度可控等优点，力学性能优异。(2) The present invention uses microwave or infrared technology to sinter the ion-co-doped hydroxyapatite transparent ceramic green body, which has the advantages of fast heating speed and no process pollution. The obtained ion-co-doped hydroxyapatite transparent ceramic The advantages of small grain size, high transparency, controllable transparency and controllable degradation rate, and excellent mechanical properties.
（3）本发明所述的离子共掺杂羟基磷灰石透明陶瓷，通过模拟人体矿物质元素进行多种离子共掺杂，不仅具有良好的生物相容性和生物活性，而且具有良好骨细胞传导、促进血管化和成骨性能等多种生物学功能，添加Ag、Zn和Cu离子可获得较强的抗菌抑菌功能。(3) The ion co-doped hydroxyapatite transparent ceramic of the present invention is co-doped with various ions by simulating the mineral elements of the human body, which not only has good biocompatibility and biological activity, but also has good bone cells Conduct, promote vascularization and osteogenic properties and other biological functions, adding Ag, Zn and Cu ions can obtain strong antibacterial and antibacterial functions.
（4）本发明采用不同成型工艺制备的离子共掺杂羟基磷灰石透明陶瓷，具有个性化订制优点，可满足牙齿修复、颌骨修复、脊柱修复、关节修复及其它硬组织修复等临床应用要求。(4) The ion-co-doped hydroxyapatite transparent ceramic prepared by the present invention adopts different molding processes. It has the advantages of individual customization and can meet the needs of dental restoration, jaw restoration, spine restoration, joint restoration, and other hard tissue restorations. Application requirements.
附图说明Description of the drawings
图1为离子共掺杂羟基磷灰石透明陶瓷制备方法流程图；Figure 1 is a flow chart of the preparation method of ion co-doped hydroxyapatite transparent ceramics;
图2为实施例2制备的钾-氟共掺杂羟基磷灰石透明陶瓷的XRD谱；2 is the XRD spectrum of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in Example 2;
图3为实施例8制备的银-氟酸根离子共掺杂羟基磷灰石透明陶瓷的XRD谱；Figure 3 is an XRD spectrum of the silver-fluorate ion co-doped hydroxyapatite transparent ceramic prepared in Example 8;
图4为实施例2制备的钾-氟共掺杂羟基磷灰石透明陶瓷的光学照片；4 is an optical photograph of the potassium-fluorine co-doped hydroxyapatite transparent ceramic prepared in Example 2;
图5为实施例6制备的铝-氟共掺杂羟基磷灰石透明陶瓷微球的SEM照片；5 is an SEM photograph of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres prepared in Example 6;
图6 为实施例10制备的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷的SEM照片；6 is an SEM photograph of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic prepared in Example 10;
图7为实施例10制备的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷植入12周后的组织学照片。7 is a histological photograph of the strontium-silicate ion co-doped hydroxyapatite transparent ceramic prepared in Example 10 after implantation for 12 weeks.
本发明的实施方式Embodiments of the present invention
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案作进一步的描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The following will further describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.
需要说明的是，本发明的说明书和权利要求书及上述附图中的术语“包括”和“具有”以及他们的任何变形，意图在于覆盖不排他的包含，例如，包含了一系列步骤或单元的过程、方法、装置、产品或设备不必限于清楚地列出的那些步骤或单元，而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其他步骤或单元。It should be noted that the terms "including" and "having" in the description and claims of the present invention and the above-mentioned drawings and any variations of them are intended to cover non-exclusive inclusions, for example, including a series of steps or units. The process, method, device, product, or equipment of is not necessarily limited to those clearly listed steps or units, but may include other steps or units that are not clearly listed or are inherent to these processes, methods, products, or equipment.
以下实施例中使用到的材料和方法，如无特别说明，均为本技术领域的常规材料和常规方法。The materials and methods used in the following embodiments, unless otherwise specified, are conventional materials and conventional methods in the technical field.
以下实施例中使用的模拟体液组成为Na +：142.0mM×L -1、K +：5.0 mM×L -1、Mg 2+：1.5 mM×L -1、Ca 2+：2.5 mM×L -1、Cl -1：147.8 mM×L -1、HCO 3 -：4.2mM×L -1、HPO 4 2-：1.0 mM×L -1、SO 4 2-：0.5 mM×L -1。 Simulated body fluid used in the following Examples consisting of Na +: 142.0mM × L -1, K +: 5.0 mM × L -1, Mg 2+: 1.5 mM × L -1, Ca 2+: 2.5 mM × L - 1, Cl -1: 147.8 mM × L -1, HCO 3 -: 4.2mM × L -1, HPO 4 2-: 1.0 mM × L -1, SO 4 2-: 0.5 mM × L -1.
实施例1  Example 1
[Ca 10 (PO 4) 6(OH) 2]透明陶瓷微球 [Ca 10 (PO 4 ) 6 (OH) 2 ] Transparent ceramic microspheres
称取826.53g硝酸钙于反应釜中，加入10L去离子水配置成硝酸钙溶液，调节硝酸钙溶液pH值为13；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以5ml/min速度将磷酸氢二铵溶液加入到反应釜进行反应，30℃水浴反应24h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为40%，得到前驱体浆料；将前驱体浆料进行喷雾造粒工艺（工艺条件：加料速度10ml/min，进风温度为180~200℃，出风温度110~120℃，喷头转速为250rpm）获得微球素坯，采用微波对微球素坯进行高温烧结，烧结温度为1150℃，烧结时间30min，升温速率30℃/min，得到羟基磷灰石透明陶瓷微球。Weigh 826.53g of calcium nitrate into the reactor, add 10L of deionized water to prepare a calcium nitrate solution, adjust the pH of the calcium nitrate solution to 13; weigh 277.33g of diammonium hydrogen phosphate into the container, add 2L of deionized water to prepare Diammonium hydrogen phosphate solution: Add the diammonium hydrogen phosphate solution to the reaction kettle at a speed of 5ml/min for reaction, and react in a water bath at 30°C for 24 hours. After the reaction, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction , Control the solid content of the reactant slurry to 40% to obtain the precursor slurry; subject the precursor slurry to spray granulation process (process conditions: feeding speed 10ml/min, inlet air temperature 180~200℃, outlet air temperature 110~120℃, the nozzle speed is 250rpm) to obtain the microsphere green body, the microsphere green body is sintered at a high temperature by microwave, the sintering temperature is 1150℃, the sintering time is 30min, the heating rate is 30℃/min, and the transparent hydroxyapatite is obtained. Ceramic microspheres.
对羟基磷灰石透明陶瓷微球进行XRD分析，结果显示，羟基磷灰石透明陶瓷微球的结晶度为90%；XRD analysis of the hydroxyapatite transparent ceramic microspheres showed that the crystallinity of the hydroxyapatite transparent ceramic microspheres was 90%;
通过扫描电镜检测，晶粒尺寸小于0.2μm，羟基磷灰石透明陶瓷微球尺寸范围为10-80μm；Detected by scanning electron microscope, the crystal grain size is less than 0.2μm, and the size range of the hydroxyapatite transparent ceramic microspheres is 10-80μm;
对羟基磷灰石透明陶瓷微球在模拟体液中进行降解测试，最大降解率大于30%；The degradation test of hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate is greater than 30%;
将羟基磷灰石透明陶瓷微球与蒸馏水配成糊剂，用于7只健康成年雄性新西兰大白兔牙髓炎根管填充，4周后行组织学观察可见其附近有新生硬组织形成，根管壁产生修复性牙本质根尖孔闭锁，有效率达100%。由此可知，羟基磷灰石透明陶瓷微球可用于牙齿根管填充。The hydroxyapatite transparent ceramic microspheres and distilled water were mixed to form a paste, which was used to fill the pulpitis root canals of 7 healthy adult male New Zealand white rabbits. After 4 weeks, the histological observation showed the formation of new hard tissues near the root canal walls. Produce restoration dentin apical foramen atresia, with an effective rate of 100%. It can be seen that hydroxyapatite transparent ceramic microspheres can be used for tooth root canal filling.
实施例2 Example 2
[Ca 8K 2](PO 4) 6[(OH) F]透明陶瓷 [Ca 8 K 2 ](PO 4 ) 6 [(OH) F] Transparent ceramic
称取619.89g硝酸钙、70.77g硝酸钾、13.664氟化钙于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为12；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以8ml/min速度将磷酸氢二铵溶液加入反应釜中的混合溶液中进行反应，40℃水浴反应18h，反应结束后，得到反应浆料；抽滤去除反应浆料中多余液体，控制反应浆料固含量为85%，得到前驱体浆料；前驱体浆料采用挤出成型工艺制成圆柱形素坯（直径0.5~1.5mm，长度1~3mm），将圆柱形陶瓷素坯进行微波烧结（烧结温度1100℃，烧结时间45min，升温速率50℃/min），得到特定形状的钾-氟共掺杂羟基磷灰石透明陶瓷。Weigh 619.89g of calcium nitrate, 70.77g of potassium nitrate, and 13.664 of calcium fluoride into the reactor, add 8L of deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 12; weigh 277.33g of diammonium hydrogen phosphate into the container , Add 2L deionized water to configure diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reaction kettle at a speed of 8ml/min to react, react in a 40℃ water bath for 18 hours, after the reaction is over, a reaction slurry is obtained ; Suction filtration to remove excess liquid in the reaction slurry, and control the solid content of the reaction slurry to 85% to obtain the precursor slurry; the precursor slurry is made into a cylindrical blank (diameter 0.5~1.5mm, length 1~3mm), microwave sintering of cylindrical ceramic blanks (sintering temperature 1100℃, sintering time 45min, heating rate 50℃/min) to obtain a specific shape of potassium-fluorine co-doped hydroxyapatite transparent ceramics.
对钾-氟共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果如图2所示，结果显示，结晶度约为65%；从图2中[Ca 8K 2](PO 4) 6[(OH)F]的XRD谱与羟基磷灰石标准谱（JCPDS No.09-0432）对比可知，[Ca 8K 2](PO 4) 6[(OH)F]透明陶瓷中没有因K、F离子掺杂出现任何杂相，但是，[Ca 8K 2](PO 4) 6[(OH)F]透明陶瓷衍射谱峰形稍宽，说明产物没有完全结晶； The XRD analysis of potassium-fluorine co-doped hydroxyapatite transparent ceramics is shown in Figure 2. The results show that the crystallinity is about 65%; from Figure 2 [Ca 8 K 2 ](PO 4 ) 6 [ The comparison between the XRD spectrum of (OH)F] and the standard spectrum of hydroxyapatite (JCPDS No.09-0432) shows that [Ca 8 K 2 ](PO 4 ) 6 [(OH)F] transparent ceramics have no cause K, There are any impurity phases due to F ion doping, but the diffraction spectrum of [Ca 8 K 2 ](PO 4 ) 6 [(OH)F] transparent ceramics has a slightly wider peak shape, indicating that the product is not completely crystallized;
扫描电镜检测结果显示晶粒尺寸小于10μm，经数字相机拍摄，结果显示陶瓷外形尺寸为直径0.5~1.5mm，长度1~3mm（见图4）；Scanning electron microscopy test results show that the crystal grain size is less than 10μm. The result of digital camera shooting shows that the ceramic size is 0.5~1.5mm in diameter and 1~3mm in length (see Figure 4);
对钾-氟共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率为25-30%，说明其已形成致密化结构；The transparency of potassium-fluorine co-doped hydroxyapatite transparent ceramics is tested, and the light transmittance is 25-30%, indicating that it has formed a dense structure;
对钾-氟共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于60%；The degradation test of potassium-fluorine co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 60%;
将钾-氟共掺杂羟基磷灰石透明陶瓷与蒸馏水配成糊剂，用于6只健康成年雄性新西兰大白兔下颌骨缺损修复，12周后，行组织学观察发现下颌骨缺损附近有大量新骨形成，占有达98%；影像学检测骨缺损区完全消失。由此可知，钾-氟共掺杂羟基磷灰石透明陶瓷可用于颌骨缺陷修复。A paste of potassium-fluorine co-doped hydroxyapatite transparent ceramics and distilled water was used to repair the mandibular defect of 6 healthy adult male New Zealand white rabbits. After 12 weeks, a histological observation revealed a large amount of mandibular defect. New bone formation accounts for 98%; the bone defect area detected by imaging completely disappears. It can be seen that potassium-fluorine co-doped hydroxyapatite transparent ceramics can be used to repair jaw defects.
实施例3 Example 3
[Ca 8KNa](PO 4) 6[(OH) F]透明陶瓷 [Ca 8 KNa](PO 4 ) 6 [(OH) F] Transparent ceramic
称取619.89g硝酸钙、35.77g硝酸钾、36.37g硝酸钠、13.664氟化钙于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为12；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以10ml/min速度将磷酸氢二铵溶液加入反应釜中的混合溶液中进行反应，40℃水浴反应18h，反应结束后得到反应浆料；抽滤去除反应浆料中多余液体，控制反应浆料固含量为85%得到前驱体浆料；前驱体浆料采用挤出成型工艺制成圆柱体素坯（直径0.5~1.0mm，长度1~2mm），将圆柱体素坯采用红外烧结（1150℃红外烧结80min，升温速率300℃/min），得到钾-钠-氟共掺杂羟基磷灰石透明陶瓷。Weigh 619.89g calcium nitrate, 35.77g potassium nitrate, 36.37g sodium nitrate, and 13.664 calcium fluoride into the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 12; weigh 277.33g hydrogen phosphate Diammonium was added to the container, and 2L deionized water was added to prepare the diammonium hydrogen phosphate solution; the diammonium hydrogen phosphate solution was added to the mixed solution in the reaction kettle at a rate of 10 ml/min to react, and the reaction was carried out in a 40°C water bath for 18 hours. After the reaction was completed The reaction slurry is obtained; the excess liquid in the reaction slurry is removed by suction filtration, and the solid content of the reaction slurry is controlled to 85% to obtain the precursor slurry; the precursor slurry is formed into a cylindrical blank (diameter 0.5~1.0) by an extrusion molding process mm, length 1~2mm), the cylindrical blank is sintered by infrared (1150℃ infrared sintering for 80min, heating rate 300℃/min) to obtain potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics.
对钾-钠-氟共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为55%，扫描电镜检测结果显示晶粒尺寸小于8.5μm，陶瓷外形尺寸为直径0.5~1.0mm，长度1~2mm；XRD analysis of potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 55%. Scanning electron microscopy results showed that the crystal grain size was less than 8.5μm, and the ceramic size was 0.5~1.0mm in diameter. Length 1~2mm;
对钾-钠-氟共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率为30%；The transparency of potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics was tested, and the light transmittance was 30%;
对钾-钠-氟共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，最大降解率大于65%；The degradation test of potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate is greater than 65%;
将钾-钠-氟共掺杂羟基磷灰石透明陶瓷与蒸馏水配成糊剂，用于6只健康成年雄性新西兰大白兔牙髓炎根管填充，3周后行组织学观察发现根管附近有新生骨组织形成，牙本质根尖孔闭锁，有效率达100%；由此可知，钾-钠-氟共掺杂羟基磷灰石透明陶瓷可用于牙齿根管填充。Potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for pulpitis root canal filling in 6 healthy adult male New Zealand white rabbits. After 3 weeks, the histological observation revealed that there was new growth near the root canal. Bone tissue is formed, and the apical foramen of dentin is blocked, and the effective rate is 100%. It can be seen that potassium-sodium-fluorine co-doped hydroxyapatite transparent ceramics can be used for tooth root canal filling.
实施例4Example 4
[Ca 7Na 3](PO 4) 6[(OH) 1.5Cl 0.5]透明陶瓷 [Ca 7 Na 3 ](PO 4 ) 6 [(OH) 1.5 Cl 0.5 ] transparent ceramic
称取578.57g硝酸钙（四水）、74.37g硝酸钠、10.227g氯化钠于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH为11；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以9ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，50℃水浴反应20h，反应结束后得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为70%，得到前驱体浆料；前驱体浆料采用浇注成型工艺制成片状素坯（3×8×12mm），将片状陶瓷素坯进行微波烧结（1120℃烧结55min，升温速率80℃/min），得到钠-氯共掺杂羟基磷灰石透明陶瓷；Weigh 578.57g of calcium nitrate (tetrahydrate), 74.37g of sodium nitrate, and 10.227g of sodium chloride into the reaction kettle, add 8L of deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 11; weigh 277.33g of hydrogen phosphate dibasic Ammonium in the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reactor at a rate of 9ml/min to react, and react in a water bath at 50°C for 20 hours. After the reaction is complete The reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 70% to obtain the precursor slurry; the precursor slurry is made into a sheet blank (3 ×8×12mm), microwave sintering the flake ceramic greenware (sintering at 1120°C for 55min, heating rate 80°C/min) to obtain sodium-chloride co-doped hydroxyapatite transparent ceramic;
对钠-氯共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为65%，扫描电镜检测显示晶粒尺寸小于20μm；XRD analysis of sodium-chloride co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 65%, and scanning electron microscopy showed that the grain size was less than 20μm;
对钠-氯共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于5%；The transparency of sodium-chloride co-doped hydroxyapatite transparent ceramics is tested, and the light transmittance is greater than 5%;
对钠-氯共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于35%；The degradation test of sodium-chloride co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 35%;
将7只健康成年雄性新西兰大白兔行腰椎后外侧横突间脊柱融合术，将钠-氯共掺杂羟基磷灰石透明陶瓷片植入两侧的L4/5横突间；12周后行组织学检查，发现植入物周围有少量软骨及大量连续骨小梁形成，形成大量编织骨，围绕骨小梁周边结构为皮质骨，说明已达到骨性融合。说明可用于钠-氯共掺杂羟基磷灰石透明陶瓷脊柱缺陷填充修复。Seven healthy adult male New Zealand white rabbits underwent lumbar posterolateral intertransverse spinal fusion, and sodium-chloride co-doped hydroxyapatite transparent ceramic plates were implanted between the L4/5 transverse processes on both sides; histology was performed 12 weeks later Inspection revealed that there was a small amount of cartilage and a large number of continuous bone trabeculae formed around the implant, forming a large amount of woven bone, and the surrounding structure of the bone trabecula was cortical bone, indicating that bone fusion has been achieved. It can be used to fill and repair spinal defects with sodium-chloride co-doped hydroxyapatite transparent ceramics.
实施例5Example 5
[Ca 6Mg 4][(PO 4) 5.2 (SiO 4) 0.8](OH) 2透明陶瓷 [Ca 6 Mg 4 ][(PO 4 ) 5.2 (SiO 4 ) 0.8 ](OH) 2 Transparent ceramic
称取495.92g硝酸钙（四水）、207.2g硝酸镁、51.53g正硅酸钠于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为10；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以12ml/min速度将磷酸氢二铵溶液加入到反应釜中对的混合溶液中进行反应，60℃水浴反应18h，反应结束后得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为75%，得到前驱体浆料；前驱体浆料采用注塑成型工艺制成圆柱形素坯，将圆柱形素坯进行红外烧结（1140℃烧结50min，升温速率1300℃/min），得到镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷（外形尺寸为直径6mm，长15mm）。Weigh 495.92g calcium nitrate (tetrahydrate), 207.2g magnesium nitrate, 51.53g sodium orthosilicate in the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 10; weigh 277.33g phosphoric acid Diammonium hydrogen phosphate was added to the container, and 2L deionized water was added to prepare a diammonium hydrogen phosphate solution; the diammonium hydrogen phosphate solution was added to the mixed solution in the reaction kettle at a rate of 12 ml/min to react, and the reaction was carried out in a water bath at 60°C for 18 hours. After the reaction, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction and the solid content of the reactant slurry is controlled to 75% to obtain the precursor slurry; the precursor slurry is made into cylindrical element by injection molding process For the blank, infrared sintering the cylindrical blank (sintering at 1140°C for 50 min, heating rate 1300°C/min), to obtain the magnesium-silicate ion co-doped hydroxyapatite transparent ceramics (diameter 6mm, length 15mm).
对镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为45%，扫描电镜检测显示晶粒尺寸小于5μm；XRD analysis of magnesium-silicate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 45%, and scanning electron microscopy showed that the grain size was less than 5μm;
对镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于15%；The transparency of the hydroxyapatite transparent ceramics co-doped with magnesium-silicate ions is tested, and the light transmittance is greater than 15%;
对镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于55%；The degradation test of magnesium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
采用镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷制作健康成年雄性新西兰大白兔桡骨中段15 mm长骨缺损模型，植入后4、8、12周行大体、组织学与X射线观察，4周时新骨已开始形成，8周时骨缺损部分修复，12周时有部分新生骨组织形成板层骨，骨小梁形成，内可见大量成骨细胞；植入后第12周影像学检测骨缺损区完全修复，皮质连续，塑型完全。由此可知，镁-硅酸根离子共掺杂羟基磷灰石透明陶瓷可用于关节缺陷修复。Magnesium-silicate ion co-doped hydroxyapatite transparent ceramics were used to make a 15 mm long bone defect model of the middle radius of healthy adult male New Zealand white rabbits. Gross, histological and X-ray observations were performed at 4, 8, and 12 weeks after implantation. 4 New bone has begun to form at week 8 and the bone defect was partially repaired at 8 weeks. At 12 weeks, some new bone tissue formed lamellar bone, bone trabecula formed, and a large number of osteoblasts were seen; bone defect was detected by imaging at 12 weeks after implantation The area is completely repaired, the cortex is continuous, and the shape is complete. It can be seen that the magnesium-silicate ion co-doped hydroxyapatite transparent ceramics can be used for joint defect repair.
实施例6 Example 6
[Ca 5Al 5](PO 4) 6[(OH) 0.8 F 1.2]透明陶瓷微球 [Ca 5 Al 5 ](PO 4 ) 6 [(OH) 0.8 F 1.2 ] transparent ceramic microspheres
称取363.67g硝酸钙（四水）、656.48g硝酸铝、16.39g氟化钙于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为13；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以15ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，70℃水浴反应16h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为46%，得到前驱体浆料；将前驱体浆料经喷雾造粒工艺（加料速度20ml/min，进风温度为180~200℃，出风温度110~120℃，喷头转速为230rpm）得到微球素坯；微球素坯经微波烧结（1070℃烧结60min，升温速率65℃/min）得到铝-氟共掺杂羟基磷灰石透明陶瓷微球。Weigh 363.67g calcium nitrate (tetrahydrate), 656.48g aluminum nitrate, and 16.39g calcium fluoride into the reactor, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 13; weigh 277.33g hydrogen phosphate Diammonium was added to the container, and 2L deionized water was added to prepare the diammonium hydrogen phosphate solution; the diammonium hydrogen phosphate solution was added to the mixed solution in the reactor at a rate of 15 ml/min to react, and the reaction was carried out in a water bath at 70°C for 16 hours, and the reaction was over Then, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 46% to obtain the precursor slurry; the precursor slurry is sprayed and granulated (feeding speed 20ml /min, the inlet air temperature is 180~200℃, the outlet temperature is 110~120℃, the nozzle speed is 230rpm) to obtain the microsphere green body; the microsphere green body is sintered by microwave (1070℃ sintered 60min, the heating rate is 65℃/min ) Obtaining aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres.
对铝-氟共掺杂羟基磷灰石透明陶瓷微球进行XRD分析，结果显示，结晶度为90%；XRD analysis of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres showed that the crystallinity was 90%;
扫描电镜检测，结果如图5所示，铝-氟共掺杂羟基磷灰石透明陶瓷微球直径为20~50μm；Scanning electron microscopy showed that the results are shown in Figure 5. The diameter of the aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres is 20-50μm;
对铝-氟共掺杂羟基磷灰石透明陶瓷微球进行透明度检测，透光率大于15%；The transparency test of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres, the light transmittance is greater than 15%;
对铝-氟共掺杂羟基磷灰石透明陶瓷微球在模拟体液中进行降解测试，在模拟体液中的最大降解率大于15%；The degradation test of aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 15%;
将铝-氟共掺杂羟基磷灰石透明陶瓷微球与蒸馏水配制成填充膏，植入比格犬的髂骨缺损处，24周后发现其75%被吸收，其内部出现大量微血管和自体小梁骨样的新骨组织，影像学检测骨缺损区完全消失。由此可知，铝-氟共掺杂羟基磷灰石透明陶瓷微球可用于骨缺损修复。The aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres and distilled water were made into a filling paste and implanted into the iliac defect of a beagle dog. After 24 weeks, it was found that 75% of it was absorbed, and a large number of microvessels and autologous bodies appeared inside. Trabecular bone-like new bone tissue, the bone defect area completely disappeared by imaging examination. It can be seen that aluminum-fluorine co-doped hydroxyapatite transparent ceramic microspheres can be used for bone defect repair.
实施例7Example 7
 [Ca 7.2Zn 2.8](PO 4) 6[(OH) 0.6 Cl 1.4]透明陶瓷微球 [Ca 7.2 Zn 2.8 ](PO 4 ) 6 [(OH) 0.6 Cl 1.4 ] transparent ceramic microspheres
称取硝537.24g酸钙（四水）、291.54g硝酸锌、27.195g氯化钙于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为10；称取277.3g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液，以25ml/min速度将磷酸氢二铵溶液加入到反应釜混合溶液中进行反应，80℃水浴反应15h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为20%，得到前驱体浆料；前驱体浆料经喷雾造粒（加料速度50ml/min，进风温度为220~250℃，出风温度150~180℃，喷头转速为260rpm）得到微球素坯；将微球素坯放在微波炉内烧结（升温速度50℃/min，1150℃保温30min），得到锌-氯共掺杂羟基磷灰石透明陶瓷微球。Weigh 537.24g of calcium nitrate (tetrahydrate), 291.54g of zinc nitrate, and 27.195g of calcium chloride in the reaction kettle, add 8L of deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 10; weigh 277.3g of phosphoric acid Diammonium hydrogen phosphate is added to the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution, add the diammonium hydrogen phosphate solution to the mixed solution of the reaction kettle at a rate of 25ml/min to react, and react in a water bath at 80°C for 15 hours. After the reaction is over , The reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 20% to obtain the precursor slurry; the precursor slurry is sprayed and granulated (feeding speed 50ml/min, The inlet air temperature is 220~250°C, the outlet air temperature is 150~180°C, and the nozzle speed is 260rpm) to obtain the microsphere green body; the microsphere green body is sintered in the microwave oven (heating speed 50℃/min, 1150℃ heat preservation 30min ) To obtain zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres.
对锌-氯共掺杂羟基磷灰石透明陶瓷微球进行XRD分析，结果显示，结晶度为90%，扫描电镜检测显示平均晶粒尺寸小于1um；XRD analysis of zinc-chloride co-doped hydroxyapatite transparent ceramic microspheres showed that the crystallinity was 90%, and scanning electron microscopy showed that the average grain size was less than 1um;
扫描电镜检测，锌-氯共掺杂羟基磷灰石透明陶瓷微球直径为10~50um；Detected by scanning electron microscope, the diameter of zinc-chloride co-doped hydroxyapatite transparent ceramic microspheres is 10~50um;
对锌-氯共掺杂羟基磷灰石透明陶瓷微球进行透明度检测，透光率大于15%；The transparency of zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres was tested, and the light transmittance was greater than 15%;
对锌-氯共掺杂羟基磷灰石透明陶瓷微球在模拟体液中进行降解测试，在模拟体液中的最大降解率大于65%；The degradation test of zinc-chlorine co-doped hydroxyapatite transparent ceramic microspheres in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 65%;
将锌-氯共掺杂羟基磷灰石透明陶瓷微球与蒸馏水配制成填充膏植入比格犬的股骨缺损处，1年后组织学观察发现其90%被吸收并被周围正常骨融合，其内部空间有较多血管形成，大量自体小梁骨样的新骨组织长入植入物内部；影像学检测骨缺损区完全消失，由此可知，锌-氯共掺杂羟基磷灰石透明陶瓷微球可用于骨缺损修复；The zinc-chloride co-doped hydroxyapatite transparent ceramic microspheres and distilled water were made into a filling paste and implanted into the femoral defect of a beagle dog. Histological observation revealed that 90% of it was absorbed and fused by the surrounding normal bone after 1 year. There are many blood vessels formed in the internal space, and a large amount of new bone tissue like autologous trabecular bone grows into the implant. The bone defect area is completely disappeared in the imaging test. It can be seen that the zinc-chloride co-doped hydroxyapatite is transparent Ceramic microspheres can be used for bone defect repair;
抗菌性能检测表明（根据SNT 3122-2012 无机抗菌材料抗菌性能试验方法），锌-氯共掺杂羟基磷灰石透明陶瓷微球颗粒对大肠杆菌、金黄色葡萄球菌和白色念珠菌的抗菌率分别达到90.9、95.95和90.5%，具有广谱抗菌性能。The antibacterial performance test showed (according to SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the antibacterial rate of zinc-chlorine co-doped hydroxyapatite transparent ceramic microsphere particles against Escherichia coli, Staphylococcus aureus and Candida albicans were respectively Reach 90.9, 95.95 and 90.5%, with broad-spectrum antibacterial properties.
实施例8Example 8
[Ca 9.2Sr 0.8] [ (PO 4) 4.4(SiO 4) 1.6](OH) 2透明陶瓷 [Ca 9.2 Sr 0.8 ] [(PO 4 ) 4.4 (SiO 4 ) 1.6 ](OH) 2 Transparent ceramic
称取760.40g硝酸钙（四水）、41.34g碳酸锶、159.15g偏硅酸钠(九水)于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为13；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以8ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，37℃水浴反应22h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为60%，得到前驱体浆料；前驱体浆料采用3D打印成型工艺得到片状素坯（6.25´12.5´15mm），将片状素坯放在微波炉内烧结（1100℃保温60min，升温速率120℃/min，），得到具有三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷（外形尺寸为5×10×12mm）。Weigh 760.40g calcium nitrate (tetrahydrate), 41.34g strontium carbonate, and 159.15g sodium metasilicate (nonahydrate) into the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 13; Take 277.33g of diammonium hydrogen phosphate into the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reaction kettle at a rate of 8ml/min for reaction, 37℃ water bath After the reaction for 22 hours, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 60% to obtain the precursor slurry; the precursor slurry is formed by a 3D printing process The flake green body (6.25´12.5´15mm) is obtained, and the flake green body is sintered in a microwave oven (at 1100°C for 60 min, and the heating rate is 120°C/min) to obtain a three-dimensional porous structure of strontium-silicate ion. Transparent ceramic doped with hydroxyapatite (external size 5×10×12mm).
对锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果如图3所示，结果显示，结晶度约为90%，扫描电镜检测显示平均晶粒尺寸小于10 μm；从图3中[Ca 9.2Sr 0.8] [ (PO 4) 4.4(SiO 4) 1.6](OH) 2的XRD谱与羟基磷灰石标准谱（JCPDS No.09-0432）对比可知，[Ca 9.2Sr 0.8] [ (PO 4) 4.4(SiO 4) 1.6](OH) 2透明陶瓷中没有因Sr 2+、SiO 4 2-离子掺杂出现任何杂相，但是，[Ca 9.2Sr 0.8] [ (PO 4) 4.4(SiO 4) 1.6](OH) 2衍射谱峰形稍宽，说明产物没有完全结晶。 XRD analysis of strontium-silicate ion co-doped hydroxyapatite transparent ceramics is shown in Figure 3. The results show that the crystallinity is about 90%, and scanning electron microscopy shows that the average grain size is less than 10 μm; In 3 [Ca 9.2 Sr 0.8 ] [(PO 4 ) 4.4 (SiO 4 ) 1.6 ] (OH) 2 XRD spectrum and hydroxyapatite standard spectrum (JCPDS No.09-0432) comparison shows that [Ca 9.2 Sr 0.8 ] [(PO 4 ) 4.4 (SiO 4 ) 1.6 ](OH) 2 There is no impurity phase due to Sr 2+ , SiO 4 2- ion doping in transparent ceramics, but [Ca 9.2 Sr 0.8 ] [(PO 4 ) 4.4 (SiO 4 ) 1.6 ] (OH) 2 diffraction spectrum peak shape is slightly wider, indicating that the product is not completely crystallized.
扫描电镜检测，三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷孔径200~500μm，气孔率75%；Scanning electron microscopy, the three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramic has a pore size of 200~500μm and a porosity of 75%;
对三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于15%，The transparency of the three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramics was tested, and the light transmittance was greater than 15%.
对三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于65%；The degradation test of the three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 65%;
将三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷植入比格犬的胫骨干骺端骨缺损处，一年后发现其与正常骨完全融合，其表面被再生皮质骨所覆盖72%左右；其内部空间则有同自体小梁骨结构一样的新骨长入；同时，还观察到有较多血管从邻近植入物的骨膜中长入新生的皮质骨内。由此可知，锶-硅酸根离子共掺杂羟基磷灰石透明陶可用于颌骨缺损修复。A three-dimensional porous structure of strontium-silicate ion co-doped hydroxyapatite transparent ceramic was implanted into the bone defect of the tibial metaphysis of a Beagle dog. One year later, it was found to be completely fused with normal bone, and its surface was regenerated by cortical bone. It covers about 72%; the internal space has the same new bone ingrowth as the autologous trabecular bone structure; at the same time, more blood vessels are also observed to grow into the new cortical bone from the periosteum adjacent to the implant. It can be seen that strontium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for jaw defect repair.
实施例9Example 9
[Ca 8.4Ag 1.6](PO 4) 6[(OH) 1.5F 0.5]透明陶瓷 [Ca 8.4 Ag 1.6 ](PO 4 ) 6 [(OH) 1.5 F 0.5 ] transparent ceramic
称取673.62g硝酸钙（四水）、95.13g硝酸银、6.832g氟化钠于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH为12；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以6ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，37℃水浴反应24h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为78%，得到前驱体浆料；前驱体浆料采用注塑成型工艺制成圆柱形素坯，将圆柱形素坯放入红外炉烧结（1190℃烧结90min，升温速率2200℃/min），得到银-氟酸根离子共掺杂羟基磷灰石透明陶瓷。Weigh 673.62g calcium nitrate (tetrahydrate), 95.13g silver nitrate, 6.832g sodium fluoride into the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 12; weigh 277.33g dibasic hydrogen phosphate Ammonium in the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reactor at a rate of 6ml/min to react, and react in a water bath at 37°C for 24 hours. After the reaction is complete , The reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 78% to obtain the precursor slurry; the precursor slurry is made into a cylindrical blank by injection molding process, The cylindrical green body was sintered in an infrared furnace (1190°C for 90 min, heating rate 2200°C/min) to obtain silver-fluorate ion co-doped hydroxyapatite transparent ceramics.
对银-氟酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为85%，扫描电镜检测显示晶粒尺寸小于1μm；XRD analysis of silver-fluorate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 85%, and scanning electron microscopy showed that the grain size was less than 1μm;
扫描电镜检测，银-氟酸根离子共掺杂羟基磷灰石透明陶瓷直径为0.5~1mm，长度尺寸为0.5~3mm；Scanning electron microscopy, silver-fluorate ion co-doped hydroxyapatite transparent ceramics have a diameter of 0.5~1mm and a length of 0.5~3mm;
对银-氟酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于15%，The transparency of silver-fluorate ion co-doped hydroxyapatite transparent ceramics is tested, and the light transmittance is greater than 15%.
对银-氟酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于55%；The degradation test of silver-fluorate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
将银-氟酸根离子共掺杂羟基磷灰石透明陶瓷与蒸馏水配成糊剂用于健康成年雄性新西兰大白兔牙槽骨填充，3周后处死行组织学观察发现植入物附近有大量小梁骨样新生骨组织形成，皮质骨覆盖70%以上，并且没有炎症出现；说明银-氟酸根离子共掺杂羟基磷灰石透明陶瓷可用于牙槽骨填充；The silver-fluorate ion co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for the alveolar bone filling of healthy adult male New Zealand white rabbits. After 3 weeks, they were sacrificed and histological observation showed that there were a large number of small particles near the implant. Beam bone-like new bone tissue is formed, cortical bone covers more than 70%, and there is no inflammation; it shows that silver-fluorate ion co-doped hydroxyapatite transparent ceramics can be used for alveolar bone filling;
抗菌性能检测表明（根据SNT 3122-2012 无机抗菌材料抗菌性能试验方法），银-氟酸根离子共掺杂羟基磷灰石透明陶瓷颗粒对大肠杆菌、金黄色葡萄球菌和白色念珠菌的抗菌率分别达到99.9、99.95和99.9%，具有广谱抗菌性能。The antibacterial performance test showed (according to SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the antibacterial rate of silver-fluorate ion co-doped hydroxyapatite transparent ceramic particles against Escherichia coli, Staphylococcus aureus and Candida albicans were respectively Reach 99.9, 99.95 and 99.9%, with broad-spectrum antibacterial properties.
实施例10Example 10
[Ca 9.2Sr 0.8][(PO 4) 4.4(SiO 4) 1.6](OH) 2透明陶瓷 [Ca 9.2 Sr 0.8 ][(PO 4 ) 4.4 (SiO 4 ) 1.6 ](OH) 2 Transparent ceramic
称取760.40g硝酸钙（四水）、41.34g碳酸锶、159.15g偏硅酸钠(九水)于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为13；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以8ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，37℃水浴反应22h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为60%，得到前驱体浆料；前驱体浆料采用浇注成型工艺得到矩形柱体素坯，矩形柱体素坯经冷冻干燥后放入红外炉内烧结（升温速度650℃/min，1200℃保温20min），得到三维多孔结构的锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷（外形尺寸5´10´25mm）。Weigh 760.40g calcium nitrate (tetrahydrate), 41.34g strontium carbonate, and 159.15g sodium metasilicate (nonahydrate) into the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 13; Take 277.33g of diammonium hydrogen phosphate into the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reaction kettle at a rate of 8ml/min for reaction, 37℃ water bath After the reaction for 22h, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction filtration, and the solid content of the reactant slurry is controlled to 60% to obtain the precursor slurry; the precursor slurry is obtained by a casting process Rectangular column blanks, which are freeze-dried and then put into an infrared furnace for sintering (heating rate 650℃/min, 1200°C for 20min) to obtain a three-dimensional porous structure of strontium-silicate ion co-doped with hydroxyphosphorus Greystone transparent ceramics (external size 5´10´25mm).
对锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为92%，扫描电镜检测（见图6）显示平均晶粒尺寸小于2 um；XRD analysis of strontium-silicate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 92%, and scanning electron microscopy (see Figure 6) showed that the average grain size was less than 2 um;
对锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于45%；The transparency of strontium-silicate ion co-doped hydroxyapatite transparent ceramics is tested, and the light transmittance is greater than 45%;
对锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于45%；The degradation test of strontium-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 45%;
将该锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷植入健康成年雄性新西兰大白兔桡骨缺损处，术后2、4、8、12周行X线、组织学观察及12周扫描电镜观察（见图7）骨缺损区骨生成情况，显示成骨较好，新骨长入85%以上；说明锶-硅酸根离子共掺杂羟基磷灰石透明陶瓷可用于骨缺损修复。The strontium-silicate ion co-doped hydroxyapatite transparent ceramic was implanted into the radius defect of healthy adult male New Zealand white rabbits. X-ray, histological observation and 12-week scanning electron microscopy were performed at 2, 4, 8, 12 weeks after surgery Observation of the bone formation in the bone defect area (see Figure 7) shows that the osteogenesis is good, and the new bone grows more than 85%; it shows that the strontium-silicate ion co-doped hydroxyapatite transparent ceramic can be used for bone defect repair.
实施例11Example 11
[Ca 8.4Ag 1.6](PO 4) 6[(OH) 1.5F 0.5] 透明陶瓷 [Ca 8.4 Ag 1.6 ](PO 4 ) 6 [(OH) 1.5 F 0.5 ] Transparent ceramic
称取673.62g硝酸钙（四水）、95.13g硝酸银、6.832g氟化钠于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH为13；称取277.33g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以100 ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，90℃水浴反应1h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中液体，然后再经去离子水反复洗涤和抽滤控制反应物浆料固含量为90%，得到前驱体浆料；前驱体浆料采用注塑成型工艺制成圆柱形素坯，将圆柱形素坯放入红外炉烧结（800℃烧结120min，升温速率9000℃/min），得到银-氟酸根离子共掺杂羟基磷灰石透明陶瓷。Weigh 673.62g calcium nitrate (tetrahydrate), 95.13g silver nitrate, 6.832g sodium fluoride into the reaction kettle, add 8L deionized water to prepare a mixed solution, adjust the pH of the mixed solution to 13; weigh 277.33g dibasic hydrogen phosphate Ammonium in the container, add 2L deionized water to prepare diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reactor at a rate of 100 ml/min to react, and react in a water bath at 90°C for 1 hour, and the reaction is over Afterwards, the reactant slurry is obtained; the liquid in the reactant slurry is removed by suction filtration, and then the solid content of the reactant slurry is controlled to 90% by repeated washing and suction filtration with deionized water to obtain the precursor slurry; the precursor slurry Cylindrical blanks are made by injection molding process, and the cylindrical blanks are sintered in an infrared furnace (sintering at 800°C for 120min, heating rate 9000°C/min) to obtain silver-fluorate ion co-doped hydroxyapatite transparent ceramics .
对银-氟酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为45%，扫描电镜检测显示晶粒尺寸小于0.1μm；XRD analysis of silver-fluorate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 45%, and scanning electron microscopy showed that the grain size was less than 0.1μm;
扫描电镜检测，银-氟酸根离子共掺杂羟基磷灰石透明陶瓷直径为0.5~1mm，长度尺寸为0.5~3mm；Scanning electron microscopy, silver-fluorate ion co-doped hydroxyapatite transparent ceramics have a diameter of 0.5~1mm and a length of 0.5~3mm;
对银-氟酸根离子掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于10%，The transparency of silver-fluorate ion-doped hydroxyapatite transparent ceramics is tested, and the light transmittance is greater than 10%.
对银-氟酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于65%；The degradation test of silver-fluorate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 65%;
将银-氟酸根离子共掺杂羟基磷灰石透明陶瓷与蒸馏水配成糊剂用于健康成年雄性新西兰大白兔牙槽骨填充，3周后处死行组织学观察发现植入物附近有大量小梁骨样新生骨组织形成，皮质骨覆盖70%以上，并且没有炎症出现；说明银-氟酸根离子共掺杂羟基磷灰石透明陶瓷可用于牙槽骨填充；The silver-fluorate ion co-doped hydroxyapatite transparent ceramics and distilled water were used to form a paste for the alveolar bone filling of healthy adult male New Zealand white rabbits. After 3 weeks, they were sacrificed and histological observation showed that there were a large number of small particles near the implant. Beam bone-like new bone tissue is formed, cortical bone covers more than 70%, and there is no inflammation; it indicates that silver-fluorate ion co-doped hydroxyapatite transparent ceramics can be used for alveolar bone filling;
抗菌性能检测表明（根据SNT 3122-2012 无机抗菌材料抗菌性能试验方法），银-氟酸根离子共掺杂羟基磷灰石透明陶瓷颗粒对金黄色葡萄球菌和白色念珠菌的抗菌率分别达到99.90和99.5%，具有广谱抗菌性能。The antibacterial performance test showed (according to the SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the silver-fluorate ion co-doped hydroxyapatite transparent ceramic particles have antibacterial rates of 99.90 and 99.90 against Staphylococcus aureus and Candida albicans, respectively. 99.5%, with broad-spectrum antibacterial properties.
实施例12 Example 12
[Ca 9.2Sr 0.5 Co 0.2Fe 0.1][(PO 4) 4.4(SiO 4) 1.6](OH) 2透明陶瓷 [Ca 9.2 Sr 0.5 Co 0.2 Fe 0.1 ][(PO 4 ) 4.4 (SiO 4 ) 1.6 ](OH) 2 Transparent ceramic
称取651.77g硝酸钙（四水）、31.74g硝酸锶、17.46g硝酸亚钴（六水）、7.26g硝酸铁、136.42g偏硅酸钠(九水)于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH值为11；称取174.32g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以12ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，47℃水浴反应12h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为65%，得到前驱体浆料；前驱体浆料采用浇注成型工艺得到矩形柱体素坯，矩形柱体素坯经冷冻干燥后放入红外炉内烧结（升温速度450℃/min，1100℃保温40min），得到锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷（外形尺寸5´10´25mm）。Weigh 651.77g calcium nitrate (tetrahydrate), 31.74g strontium nitrate, 17.46g cobalt nitrate (hexahydrate), 7.26g ferric nitrate, and 136.42g sodium metasilicate (nonahydrate) into the reaction kettle, add 8L deionized Prepare the water into a mixed solution, adjust the pH of the mixed solution to 11; weigh 174.32g of diammonium hydrogen phosphate into the container, add 2L of deionized water to prepare the diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution at a speed of 12ml/min Add to the mixed solution in the reactor to react, react at 47°C in a water bath for 12 hours. After the reaction, the reactant slurry is obtained; the excess liquid in the reactant slurry is removed by suction and the solid content of the reactant slurry is controlled to 65%. The precursor slurry is obtained; the precursor slurry is cast and formed to obtain a rectangular cylinder blank, which is freeze-dried and then placed in an infrared furnace for sintering (heating rate 450°C/min, 1100°C heat preservation 40min), Obtained strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics (external size 5´10´25mm).
对锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为95%，扫描电镜检测显示平均晶粒尺寸小于15 um；XRD analysis of strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 95%, and scanning electron microscopy showed that the average grain size was less than 15 um;
对锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于35%；The transparency of strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics was tested, and the light transmittance was greater than 35%;
对锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于55%；The degradation test of strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 55%;
将该锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷植入健康成年雄性新西兰大白兔桡骨缺损处，术后2、4、8、12周行X线、组织学观察骨缺损区骨生成情况，显示新骨长入87%以上；说明锶-钴-铁-硅酸根离子共掺杂羟基磷灰石透明陶瓷可用于骨缺损修复。The strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic was implanted into the radius defect of healthy adult male New Zealand white rabbits. X-rays and histological observations were performed at 2, 4, 8, 12 weeks after the operation. The bone formation in the defect area shows that the new bone has grown in more than 87%; it shows that the strontium-cobalt-iron-silicate ion co-doped hydroxyapatite transparent ceramic can be used for bone defect repair.
实施例13Example 13
[Ca 8.4Mn 1.0Cu 0.5Ag 0.1](PO 4) 6[(OH) 1.5F 0.5]透明陶瓷 [Ca 8.4 Mn 1.0 Cu 0.5 Ag 0.1 ](PO 4 ) 6 [(OH) 1.5 F 0.5 ] transparent ceramic
称取595.10g硝酸钙（四水）、5.10g硝酸银、53.69g硝酸亚锰、28.13g硝酸铜、6.30g氟化钠于反应釜中，加入8L去离子水配置成混合溶液，调节混合溶液pH为10；称取237.71g磷酸氢二铵于容器中，加入2L去离子水配置成磷酸氢二铵溶液；以5 ml/min速度将磷酸氢二铵溶液加入到反应釜中的混合溶液中进行反应，45℃水浴反应20 h，反应结束后，得到反应物浆料；抽滤去除反应物浆料中多余液体，控制反应物浆料固含量为75%，得到前驱体浆料；前驱体浆料采用注塑成型工艺制成圆柱形素坯，将圆柱形素坯放入微波炉烧结（920℃烧结20min，升温速率1200℃/min），得到锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷。Weigh 595.10g calcium nitrate (tetrahydrate), 5.10g silver nitrate, 53.69g manganous nitrate, 28.13g copper nitrate, and 6.30g sodium fluoride into the reactor, add 8L deionized water to make a mixed solution, adjust the mixed solution The pH is 10; Weigh 237.71g of diammonium hydrogen phosphate into the container, add 2L of deionized water to prepare the diammonium hydrogen phosphate solution; add the diammonium hydrogen phosphate solution to the mixed solution in the reaction kettle at a rate of 5 ml/min The reaction was carried out and reacted in a water bath at 45°C for 20 hours. After the reaction, the reactant slurry was obtained; the excess liquid in the reactant slurry was removed by suction and the solid content of the reactant slurry was controlled to 75% to obtain the precursor slurry; the precursor The slurry is made into a cylindrical blank by injection molding process, and the cylindrical blank is placed in a microwave oven for sintering (sintering at 920°C for 20 minutes, heating rate 1200°C/min) to obtain manganese-copper-silver-fluorate ion co-doped hydroxyl Apatite transparent ceramics.
对锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷进行XRD分析，结果显示，结晶度为95%，扫描电镜检测显示晶粒尺寸小于8um；XRD analysis of manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics showed that the crystallinity was 95%, and scanning electron microscopy showed that the grain size was less than 8um;
扫描电镜检测，锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷直径为0.2~1mm，长度尺寸为0.5~1 mm；Detected by scanning electron microscope, the diameter of hydroxyapatite transparent ceramic co-doped with manganese-copper-silver-fluorate ion is 0.2~1mm, and the length is 0.5~1mm;
对锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷进行透明度检测，透光率大于20%，The transparency of hydroxyapatite transparent ceramics co-doped with manganese-copper-silver-fluorate ions is tested, and the light transmittance is greater than 20%.
对锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷在模拟体液中进行降解测试，在模拟体液中的最大降解率大于45%；The degradation test of manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics in simulated body fluids shows that the maximum degradation rate in simulated body fluids is greater than 45%;
将锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷与羧甲基纤维素钠、蒸馏水配成糊剂用于健康成年雄性新西兰大白兔牙槽骨填充，5周后处死行组织学观察发现植入物附近有大量小梁骨样新生骨组织形成，皮质骨覆盖80%以上，并且没有炎症出现；说明锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷可用于牙槽骨填充；Manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics, sodium carboxymethyl cellulose, and distilled water were used to make a paste for alveolar bone filling in healthy adult male New Zealand white rabbits. They were sacrificed after 5 weeks. Histological observation revealed that a large amount of trabecular bone-like new bone tissue was formed near the implant, and the cortical bone covered more than 80%, and there was no inflammation; it indicated that manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramics Can be used for alveolar bone filling;
抗菌性能检测表明（根据SNT 3122-2012 无机抗菌材料抗菌性能试验方法），锰-铜-银-氟酸根离子共掺杂羟基磷灰石透明陶瓷颗粒对大肠杆菌、金黄色葡萄球菌和白色念珠菌的抗菌率分别达到97.9、98. 5和99.5%，具有广谱抗菌性能。The antibacterial performance test showed (according to the SNT 3122-2012 inorganic antibacterial material antibacterial performance test method), the manganese-copper-silver-fluorate ion co-doped hydroxyapatite transparent ceramic particles is effective against Escherichia coli, Staphylococcus aureus and Candida albicans The antibacterial rates of the antibacterial products are respectively 97.9, 98.5 and 99.5%, and they have broad-spectrum antibacterial properties.
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The foregoing descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the present invention. Within the scope of protection.

Claims (8)

  1. 一种离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，A preparation method of ion co-doped hydroxyapatite transparent ceramic, which is characterized in that:
    所述离子共掺杂羟基磷灰石透明陶瓷的组成通式为[Ca 10-xM x][(PO 4) 6-y(SiO 4) y] [(OH) 2-zN z]， M选自K离子、Na离子、Mg离子、Al离子、Zn离子、Sr离子、Mn离子、Co离子、Ag离子、Cu离子、Fe离子中的一种或多种；N为F离子、Cl离子、CO 3 2-离子中的一种或多种；0≤x＜10，0≤y＜6，0≤z＜2，所述Mn离子包括Mn 3+和Mn 2+，所述Co离子包括Co 3+和Co 2+，所述Cu离子包括Cu +和Cu 2+，Fe离子包括Fe 3+和Fe 2+；所述共掺杂羟基磷灰石透明陶瓷的制备方法包括如下步骤： The general formula for the composition of the ion co-doped hydroxyapatite transparent ceramic is [Ca 10-x M x ][(PO 4 ) 6-y (SiO 4 ) y ] [(OH) 2-z N z ], M is selected from one or more of K ion, Na ion, Mg ion, Al ion, Zn ion, Sr ion, Mn ion, Co ion, Ag ion, Cu ion, Fe ion; N is F ion, Cl ion One or more of CO 3 2- ions; 0≤x＜10, 0≤y＜6, 0≤z＜2, the Mn ions include Mn 3+ and Mn 2+ , and the Co ions include Co 3+ and Co 2+ , the Cu ions include Cu + and Cu 2+ , and the Fe ions include Fe 3+ and Fe 2+ ; the preparation method of the co-doped hydroxyapatite transparent ceramic includes the following steps:
    溶液配制，称取硝酸钙加入反应釜，称取硅酸盐、含M的化合物和含N的化合物中的一种或多种加入反应釜，然后加入蒸馏水进行溶解，配制成混合溶液，调节混合溶液pH值为8-13；称取磷酸氢二铵配制成磷酸氢二铵溶液；To prepare the solution, weigh calcium nitrate into the reactor, weigh one or more of the silicate, M-containing compound and N-containing compound into the reactor, then add distilled water to dissolve, prepare a mixed solution, adjust the mixing The pH of the solution is 8-13; Weigh diammonium hydrogen phosphate to prepare a diammonium hydrogen phosphate solution;
    化学沉淀反应，将磷酸氢二铵溶液以1~100mL/min的速度加入反应釜中，反应温度30~90℃，反应时间1~18h，反应结束后，得到反应产物浆料；For chemical precipitation reaction, add the diammonium hydrogen phosphate solution to the reaction kettle at a rate of 1-100 mL/min, the reaction temperature is 30-90°C, and the reaction time is 1-18h. After the reaction is completed, a reaction product slurry is obtained;
    抽滤和/或洗涤，抽滤反应产物浆料中的液体或反复用去离子水洗涤和抽滤反应产物浆料，控制反应产物浆料固含量范围为20-90%，得到前驱体浆料；Suction filtration and/or washing, suction filtration of the liquid in the reaction product slurry or repeated washing and suction filtration of the reaction product slurry with deionized water, controlling the solid content of the reaction product slurry to range from 20-90% to obtain the precursor slurry ；
    成型，前驱体浆料固含量为20-50%时，采用喷雾造粒工艺制成微球或颗粒素坯，微球或颗粒素坯经高温烧结得到透明陶瓷微球或颗粒；前驱体浆料固含量为50-90%时，采用成型工艺制成特定形状素坯，特定形状素坯经过高温烧结得到特定形状的透明陶瓷。Forming, when the solid content of the precursor slurry is 20-50%, the spray granulation process is used to make microspheres or pellets, and the microspheres or pellets are sintered at high temperature to obtain transparent ceramic microspheres or particles; precursor slurry When the solid content is 50-90%, a molding process is used to make a specific shape blank, and the specific shape blank is sintered at a high temperature to obtain a specific shape of transparent ceramic.
  2. 根据权利要求1所述的离子掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，所述含M的化合物选自硝酸钾、碳酸钾、碳酸氢钾、醋酸钾、氢氧化钾、氧化钾、乳酸钾、柠檬酸钾、葡萄糖酸钾、硝酸钠、碳酸钠、碳酸氢钠、醋酸钠、氢氧化钠、氧化钠、乳酸钠、柠檬酸钠、葡萄糖酸钠、硝酸镁、醋酸镁、碳酸镁、碳酸氢镁、氧化镁、乳酸镁、氯化镁、柠檬酸镁、葡萄糖酸镁、硝酸铝、碳酸铝、氯化铝、乳酸铝、柠檬酸铝、硝酸锌、碳酸锌、氯化锌、醋酸锌、乳酸锌、柠檬酸锌、葡萄糖酸锌、硝酸锶、碳酸锶、氯化锶、醋酸锶、乳酸锶、柠檬酸锶、硝酸锰、碳酸锰、氯化锰、醋酸锰、乳酸锰、柠檬酸锰、葡萄糖酸锰、硝酸钴、碳酸钴、氯化钴、醋酸钴、硝酸银、碳酸银、氯化银、醋酸银、乳酸银、柠檬酸银、硝酸铜、碳酸铜、氯化铜、醋酸铜、醋酸亚铜、柠檬酸铜、葡萄糖酸铜、硝酸铁、碳酸铁、氯化铁、醋酸铁、醋酸亚铁、乳酸亚铁、柠檬酸铁、葡萄糖酸亚铁中的一种或多种；所述含N的化合物选自氟化钾、氟化钠、氟化钙、氟化镁、氟化二锰、氟化锌、氟化铝、氟化亚铁、氟化银、氟化钴、氟化铜、氟化锶、氟硅酸钠、氟硅酸、氯化钾、氯化钠、氯化钙、氯化镁、氯化锰、氯化锌、氯化铝、氯化铁、氯化银、氯化钴、氯化铜、氯化锶；所述硅酸盐选自硅酸钾、硅酸钠、硅酸镁、氟硅酸钠、氟硅酸、正硅酸甲酯、正硅酸乙酯、正硅酸丙酯、正硅酸异丙酯中的一种或多种。The method for preparing ion-doped hydroxyapatite transparent ceramics according to claim 1, wherein the M-containing compound is selected from potassium nitrate, potassium carbonate, potassium bicarbonate, potassium acetate, potassium hydroxide, oxide Potassium, 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, carbonic acid Magnesium, 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, acetic acid Zinc, 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, lemon Manganese acid, 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, One or more of copper acetate, cuprous acetate, copper citrate, copper gluconate, ferric nitrate, ferric carbonate, ferric chloride, ferric acetate, ferrous acetate, ferrous lactate, ferric citrate, and ferrous gluconate Species; the N-containing compound is selected from potassium fluoride, sodium fluoride, calcium fluoride, magnesium fluoride, manganese fluoride, zinc fluoride, aluminum fluoride, ferrous fluoride, silver fluoride, fluoride Cobalt, copper fluoride, strontium fluoride, sodium fluorosilicate, fluorosilicic acid, potassium chloride, sodium chloride, calcium chloride, magnesium chloride, manganese chloride, zinc chloride, aluminum chloride, iron chloride, chlorine Silver, cobalt chloride, copper chloride, strontium chloride; the silicate is selected from potassium silicate, sodium silicate, magnesium silicate, sodium fluorosilicate, fluorosilicic acid, methyl orthosilicate, ortho One or more of ethyl silicate, propyl orthosilicate, and isopropyl orthosilicate.
  3. 根据权利要求1所述的离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，成型工艺为喷雾造粒、挤出成型、浇注成型、注浆成型、注射成型和增材制造成型工艺中的一种。The method for preparing ion co-doped hydroxyapatite transparent ceramics according to claim 1, wherein the molding process is spray granulation, extrusion molding, casting molding, grouting molding, injection molding, and additive manufacturing molding. A kind of craft.
  4. 根据权利要求1所述的离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，喷雾造粒工艺的进风温度为120~250℃，出风温度100~180℃，加料速度为5~50mL/min，喷头转速为180~300rpm。The method for preparing ion co-doped hydroxyapatite transparent ceramics according to claim 1, wherein the inlet air temperature of the spray granulation process is 120~250°C, the outlet air temperature is 100~180°C, and the feeding speed is 5~50mL/min, the nozzle speed is 180~300rpm.
  5. 根据权利要求1所述的离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，高温烧结采用微波烧结或红外烧结。The method for preparing ion co-doped hydroxyapatite transparent ceramics according to claim 1, wherein the high-temperature sintering adopts microwave sintering or infrared sintering.
  6. 根据权利要求5所述的离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，微球或颗粒或特定形状素坯高温烧结的温度范围为800~1200℃，烧结时间10~120min，升温速率为20~9000℃/min。The method for preparing ion co-doped hydroxyapatite transparent ceramics according to claim 5, characterized in that the high-temperature sintering temperature range of microspheres or particles or green bodies of specific shapes is 800~1200°C, and the sintering time is 10~120min , The heating rate is 20~9000℃/min.
  7. 根据权利要求1-6任一所述的离子共掺杂羟基磷灰石透明陶瓷的制备方法，其特征在于，所述制备方法制备的所述透明陶瓷的晶粒尺寸为不大于50μm，所述透明陶瓷的透光率为5-45%。The method for preparing ion co-doped hydroxyapatite transparent ceramics according to any one of claims 1-6, wherein the crystal grain size of the transparent ceramic prepared by the preparation method is not greater than 50 μm, and the The light transmittance of transparent ceramics is 5-45%.
  8. 一种权利要求1-6任一所述的制备方法制备的离子共掺杂羟基磷灰石透明陶瓷的应用，其特征在于，所述应用包括作为牙齿修复材料、颌骨修复材料、脊柱修复材料和关节修复材料。An application of ion co-doped hydroxyapatite transparent ceramic prepared by the preparation method of any one of claims 1 to 6, characterized in that the application includes as a tooth restoration material, a jaw restoration material, and a spine restoration material And joint repair materials.
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