WO2017080390A1 - 一种Sr和Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料 - Google Patents

一种Sr和Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料 Download PDF

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WO2017080390A1
WO2017080390A1 PCT/CN2016/104286 CN2016104286W WO2017080390A1 WO 2017080390 A1 WO2017080390 A1 WO 2017080390A1 CN 2016104286 W CN2016104286 W CN 2016104286W WO 2017080390 A1 WO2017080390 A1 WO 2017080390A1
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doped
amorphous
apatite material
elements
apatite
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张兴
曹磊
杨锐
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中国科学院金属研究所
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    • C—CHEMISTRY; METALLURGY
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    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B25/00—Phosphorus; Compounds thereof
    • C01B25/16—Oxyacids of phosphorus; Salts thereof
    • C01B25/26—Phosphates
    • C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
    • C01B25/325—Preparation by double decomposition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
    • A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
    • A61K6/838—Phosphorus compounds, e.g. apatite
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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    • A61L27/58—Materials at least partially resorbable by the body
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    • B82—NANOTECHNOLOGY
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    • C01B25/16—Oxyacids of phosphorus; Salts thereof
    • C01B25/26—Phosphates
    • C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
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    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • A—HUMAN NECESSITIES
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    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
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    • C01P2004/60—Particles characterised by their size
    • C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer

Definitions

  • the invention relates to the technical field of biomedical materials, in particular to an amorphous apatite material and a crystalline apatite material doped with Sr and Mg elements.
  • Bone is the body's support, with important functions such as support, protection, and hematopoiesis. It is an important organ of the human body. So far, the materials used for clinical treatment of bone defect repair in the world mainly include metal alloy materials, polymer materials and bioceramic materials. Among them, bioceramic materials mainly include hydroxyapatite (HA), ⁇ -phase tricalcium phosphate ( ⁇ -TCP), and a mixture of the two (two-phase calcium phosphate material).
  • HA hydroxyapatite
  • ⁇ -TCP ⁇ -phase tricalcium phosphate
  • hydroxyapatite ceramics do not degrade in vivo, which is not conducive to new bone regeneration; while ⁇ -phase tricalcium phosphate ceramics can degrade in vivo, however in some applications its degradation is faster than new bone regeneration, which is not conducive to the formation of intact bone. structure.
  • the solubility of amorphous apatite material is between hydroxyapatite and ⁇ -phase tricalcium phosphate, and the degradation rate is moderate.
  • Mg element can increase the phase transition temperature of ⁇ -TCP ceramics, affecting the early stage of bone Growth, regulation of bone growth and remodeling ([2] Ilich JZ, Kerstetter JE.
  • the purpose of the present invention is to distinguish the degradation rate of the existing hydroxyapatite (HA) and tricalcium phosphate ( ⁇ -TCP) artificial bone materials from the new bone formation rate (the HA crystal is difficult to degrade and the ⁇ -TCP degradation is fast), which is not conducive to New bone growth, and the poor biological activity of HA and ⁇ -TCP artificial bone scaffolds, provide a kind of amorphous apatite material and crystalline apatite material doped with Sr and Mg elements, doped with Sr and Mg elements. It can improve the biological activity of apatite materials and has important clinical application value.
  • HA hydroxyapatite
  • ⁇ -TCP tricalcium phosphate
  • An amorphous apatite material doped with Sr and Mg elements which is an amorphous material, and has the chemical formula: (Ca (9-xy) Sr x Mg y ) (HPO 4 )(PO 4 ) 5 (OH) Where: x is the number of atoms of the Sr element, y is the number of atoms of the Mg element, x is in the range of 0 ⁇ x ⁇ 1.8, and y is in the range of 0 ⁇ y ⁇ 1.28.
  • the above-mentioned Sr and Mg element doped amorphous apatite materials are prepared by Ca(NO 3 ) 2 , Mg(NO 3 ) 2 , Sr(NO 3 ) 2 , (NH 4 ) 2 HPO 4 and an aqueous ammonia solution ( NH 3 ⁇ H 2 O) as a raw material, preparing the amorphous apatite material doped with the Sr and Mg elements by chemical precipitation method (including undoped amorphous apatite material and doping different concentrations of Sr, Mg)
  • the amorphous apatite material of the element specifically comprises the following steps:
  • the precipitation reaction equation occurring in the step (3) is represented by the following formula (1).
  • the invention can further prepare a crystalline apatite material doped with Sr and Mg elements by using the amorphous apatite material, that is, the amorphous apatite material doped with the Sr and Mg elements is obtained by heat treatment. It includes nano-calcium-deficient hydroxyapatite crystals doped with Sr and Mg elements and ⁇ -phase tricalcium phosphate ( ⁇ -TCP) crystals doped with Sr and Mg elements. among them:
  • the Sr and Mg element doped amorphous apatite material is heat treated at 120 ° C for 3-24 hours to obtain the Sr and Mg element doped nano calcium-deficient hydroxyapatite crystals (the longer the constant temperature, the material crystal
  • the degree of chemistry is better, where: the atomic percentage of Sr element (calculated as Sr/(Ca+Sr+Mg)) ranges from 0 to 20%, and the molar percentage of Mg element (calculated as Mg/(Ca+Sr+Mg) The range is 0-10%.
  • the obtained Sr and Mg element-doped nano-calcium-deficient hydroxyapatite crystals contain undoped nano-calcium-deficient hydroxyapatite crystals (when both Sr and Mg doping amounts are 0), and only doped with Sr Nano-calcium-deficient hydroxyapatite crystals (atomic percentage of Sr (calculated as Sr/(Ca+Sr)) ⁇ 20%, Mg doping amount is 0), Mg-doped nano-calcium-deficient hydroxyapatite crystals ( Sr doping amount is 0, Mg atomic percentage (calculated as Mg / (Ca + Mg) ⁇ 10%), and Sr and Mg co-doped nano calcium-deficient hydroxyapatite crystals (atomic percentage of Sr (by Sr / (Ca + Sr + Mg) is calculated ⁇ 10% and the molar percentage of Mg (calculated as Mg / (Ca + Sr + Mg))
  • Sr element-doped ⁇ -phase tricalcium phosphate ( ⁇ -TCP) crystals after heat-treating the Sr and Mg element-doped amorphous apatite material at 800 ° C for 3 hours, wherein: Sr element The molar percentage (calculated as Sr/(Ca+Sr+Mg)) ranges from 0 to 20%, and the molar percentage of Mg element (calculated as Mg/(Ca+Sr+Mg)) ranges from 0-14.25%.
  • the obtained Sr and Mg element-doped ⁇ -phase tricalcium phosphate ( ⁇ -TCP) crystal contains undoped ⁇ -phase tricalcium phosphate ( ⁇ -TCP) crystal (when both Sr and Mg doping amounts are 0) Sr-doped ⁇ -phase tricalcium phosphate ( ⁇ -TCP) crystal (Sr/(Ca+Sr)) of Sr ⁇ 20%, Mg doping amount is 0), Mg-doped ⁇ phase Tricalcium phosphate ( ⁇ -TCP) crystal (the doping amount of Sr is 0, the atomic percentage of Mg (Mg/(Ca+Mg)) ⁇ 14.25%), and the Sr and Mg co-doped ⁇ -phase tricalcium phosphate ( ⁇ - TCP) crystal (the atomic percentage of Sr (Sr / (Ca + Sr + Mg)) ⁇ 10% and the molar percentage of Mg (Mg / (Ca + Sr + Mg
  • the present invention provides a method for preparing amorphous apatite and doping different concentrations of Sr and Mg elemental amorphous apatite, and simultaneously preparing a nano-calcium deficiency doped with different concentrations of Sr and Mg elements by a certain heat treatment process. Hydroxyphosphorus Gray stone crystals and ⁇ -TCP crystal materials.
  • Sr element can promote new bone formation, reduce bone resorption, regulate calcium metabolism, and reduce osteoclast activity.
  • Mg element can affect early growth of bone and improve ⁇ -TCP ceramic phase. Change the temperature and regulate the growth and remodeling of bone. The doping of the Sr and Mg elements increases the biological activity of the prepared apatite material.
  • the content of hydroxyapatite in human enamel is above 95%. Therefore, considering the characteristics of hydroxyapatite and enamel having the same structure and high affinity, the amorphous phosphorus synthesized by the present invention Gray stone and Sr and Mg doped apatite materials can also be applied in the field of dental restoration and health care materials.
  • Example 1 is a powder X-ray diffraction pattern of the apatite material synthesized in Example 1: (a) freeze-dried amorphous apatite, (b) nano-calcium-deficient hydroxyapatite obtained after heat treatment at 120 ° C for 3 hours. Crystal, (c) ⁇ -TCP crystal material obtained after heat treatment at 800 ° C for 3 hours.
  • Example 2 is an infrared spectrum of the pure phase amorphous apatite material obtained in Example 1.
  • Figure 4 is a powder X-ray diffraction pattern of nano-calcium-deficient hydroxyapatite crystals formed by doping different concentrations of Sr and Mg elemental amorphous apatite materials after heat treatment at 120 °C for 3 hours: (a) Doping mole percentage 20% Sr Nano-calcium-deficient hydroxyapatite, (b) Doping mole percent 9.67% Mg nano-calcium hydroxyapatite, (c) Doping mole percent 5% Mg, 10% Sr calcium-deficient nano-hydroxyapatite.
  • Fig. 5 is a powder X-ray diffraction pattern of ⁇ -TCP crystals formed by doping different concentrations of Sr and Mg elemental amorphous apatite materials after heat treatment at 800 ° C for 3 hours: (a) ⁇ -TCP with a molar percentage of 20% Sr Crystal material, (b) ⁇ -TCP crystal material doped with 15% Sr mole percent, (c) ⁇ -TCP crystal material doped with 5% Sr mole percent, (d) Doping mole percentage 5% Mg, 10% The ⁇ -TCP crystal material of Sr, (e) the ⁇ -TCP crystal material having a molar percentage of 14.25% Mg.
  • ⁇ -TCP porous bioceramic prepared by a polyurethane template method with a doping molar percentage of 5% Mg and 10% Sr.
  • the present invention uses Ca(NO 3 ) 2 , Mg(NO 3 ) 2 , Sr(NO 3 ) 2 , (NH 4 ) 2 HPO 4 and NH 3 ⁇ H 2 O (aqueous ammonia solution) as raw materials to regulate the reaction equation.
  • the value of x and y is obtained by chemical precipitation method to obtain amorphous apatite materials doped with different concentrations of Sr and Mg.
  • the amorphous apatite doped with Sr and Mg elements prepared on the one hand can be freeze-dried and sealed and stored in a refrigerator at 4 ° C for a long time. On the other hand, it can be heat-treated at 120 ° C for 3-24 hours to obtain different concentrations of Sr and Mg.
  • Nano-calcium-deficient hydroxyapatite crystals or heat-treated at 800 °C for 3 hours to obtain ⁇ -TCP crystal materials doped with different concentrations of Sr and Mg, and then ⁇ -TCP artificially doped with different concentrations of Sr and Mg elements by sintering method Bone ceramics.
  • the process flow of the invention is: Ca(NO 3 ) 2 , Mg(NO 3 ) 2 , Sr(NO 3 ) 2 , (NH 4 ) 2 HPO 4 and NH 3 ⁇ H 2 O (aqueous ammonia solution) raw materials ⁇ chemical precipitation ⁇ Freeze-drying ⁇ Amorphous apatite doped with different concentrations of Sr and Mg ⁇ heat treatment ⁇ nano-calcium-calcium hydroxyapatite crystals or tricalcium phosphate crystals doped with different concentrations of Sr and Mg elements ⁇ ball milling ⁇ sintering; step:
  • the concentration of Sr and Mg in the amorphous calcium-deficient hydroxyapatite is adjusted by adjusting the values of x and y in the reaction equation (1).
  • the impurity concentration of Sr and Mg doping should be controlled within a certain range to achieve good Biological activity.
  • the method for converting the obtained amorphous apatite material into a nano-calcium-deficient hydroxyapatite crystal and a nano-calcium-calcium hydroxyapatite crystal material doped with different concentrations of Sr and Mg elements by the heat treatment process is as follows:
  • the amorphous calcium-deficient hydroxyapatite and the amorphous calcium-deficient hydroxyapatite material doped with different concentrations of Sr and Mg elements are placed in a heat treatment furnace, heated from room temperature to 120 ° C, and kept at a temperature of 120 ° C. After 24 hours, and then cooled to room temperature with the furnace, nanometer calcium-deficient hydroxyapatite crystal material and nano-calcium-calcium hydroxyapatite crystal material doped with different concentrations of Sr and Mg were obtained.
  • the method for converting the obtained amorphous apatite material into a ⁇ -TCP crystal and a ⁇ -TCP crystal material doped with different concentrations of Sr and Mg elements by a heat treatment process is as follows:
  • the amorphous apatite material is placed in a heat treatment furnace, heated from room temperature to 800 ° C, and kept at 800 ° C for 3 hours, and then cooled to room temperature with a furnace to obtain ⁇ -TCP crystals and doped different concentrations of Sr, Mg. Elemental ⁇ -TCP crystal material.
  • Heat treatment the obtained amorphous apatite is placed in a heat treatment furnace at 120 ° C for heat treatment for 3 hours to obtain undoped nano calcium-deficient hydroxyapatite crystals (Fig. 1 (b)); the obtained amorphous apatite is placed The heat treatment was performed at 800 ° C for 3 hours in a heat treatment furnace to obtain an undoped ⁇ -TCP crystal material (Fig. 1 (c)).
  • the stone material was heat-treated at 120 ° C for 3 hours in a heat treatment furnace to obtain a nanometer calcium-deficient hydroxyapatite crystal material having a doping molar percentage of 20% Sr (Fig. 4(a)), which was heat-treated at 800 ° C for 3 hours in a heat treatment furnace.
  • the heat treatment was carried out at 800 ° C for 3 hours in a heat treatment furnace to obtain a ⁇ -TCP crystal material having a doping molar percentage of 15% Sr ( FIG. 5( b )).
  • the heat treatment was carried out at 800 ° C for 3 hours in a heat treatment furnace to obtain a ⁇ -TCP crystal material having a doping molar percentage of 5% Sr (Fig. 5(c)).
  • the amorphous sample was heat-treated at 120 ° C for 3 hours in a heat treatment furnace to obtain a nanometer calcium-deficient hydroxyapatite crystal material having a doping molar percentage of 10% Sr and 5% Mg ( FIG. 4( c )).
  • the heat treatment was carried out at 800 ° C for 3 hours in a heat treatment furnace to obtain a ⁇ -TCP crystal material having a doping molar percentage of 10% Sr and 5% Mg ( FIG. 5( d )).
  • Ball milling and drying The obtained molar percentage of 10% Sr, 5% Mg ⁇ -TCP crystal material was ball milled (200 rpm) for 10 hours, and vacuum dried at 120 ° C for 3 hours.
  • Ceramic sintering Doping molar percentage of 10% Sr, 5% Mg ⁇ -TCP powder and mass percentage Mix 5% polyvinyl alcohol solution, the amount of powder in each milliliter of polyvinyl alcohol solution is 0.8g, obtain a uniform slurry under stirring condition, and squeeze 1ml slurry into 1cm x 1cm x 1cm 60ppi polyurethane porous stent Then, porous ceramics were prepared by sintering at 1200 ° C for 3 hours in an air atmosphere (Fig. 6), and the samples were taken out after cooling to room temperature in the furnace.
  • the porous ceramic has a pore diameter of -200 ⁇ m and a porosity of ⁇ 60%.

Abstract

提供一种Sr和/或Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料，其属于生物医用材料领域。以Ca(NO 3) 2、Mg(NO 3) 2、Sr(NO 3) 2、(NH 4) 2HPO 4和氨水溶液为原材料，快速制备掺杂不同浓度Sr、Mg的非晶磷灰石材料，再经热处理转化为掺杂不同浓度Sr、Mg的纳米缺钙羟基磷灰石或纳米磷酸三钙材料。该非晶材料与传统羟基磷灰石晶体材料相比，溶解度较高。Sr、Mg元素掺杂后，Sr元素可以促进新骨形成，减少骨的再吸收，调节钙代谢，降低破骨细胞活性；Mg元素可以影响骨质的早期生长，调控骨质的生长和重塑。该合成的非晶磷灰石及其晶化产物在骨修复和骨移植领域有着重要的作用。

Description

一种Sr和Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料 技术领域
本发明涉及生物医学材料技术领域，具体涉及一种Sr和Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料。
背景技术
骨骼是人体的支架，具有支持、保护、造血等重要的功能，是人体重要的组织器官。迄今为止，世界范围内用于临床治疗骨缺损修复的材料主要有金属合金材料、高分子材料和生物陶瓷材料。其中，生物陶瓷材料主要包括羟基磷灰石(HA)、β相磷酸三钙(β-TCP)以及两者的混合物(两相磷酸钙材料)。对于骨缺损修复，羟基磷灰石陶瓷体内基本不降解，不利于新骨再生；而β相磷酸三钙陶瓷可以体内降解，然而有些应用中其降解快于新骨再生，不利于形成完整的骨结构。非晶磷灰石材料的溶解度介于羟基磷灰石和β相磷酸三钙之间，降解速度适中。
此外研究表明许多微量元素在骨骼再生中起到关键作用。例如Sr元素可以促进新骨形成，减少骨的再吸收，调节钙代谢，降低破骨细胞活性([1]Braux J,Velard F,Guillaume C,Bouthors S,Jallot E,Nedelec JM,Laurent-Maquin D,Laquerrière P.A new insight into the dissociating effect of strontium on bone resorption and formation.Acta Biomaterialia,2011,7(6):2593-2603.)；Mg元素可以提高β-TCP陶瓷相变温度，影响骨质的早期生长，调控骨质的生长和重塑([2]Ilich JZ,Kerstetter JE.Degradable Biomaterials based on Magnesium Corrosion.J American College of Nutrition,2000,19(6):715-737；[3]Famery R,Richard N,Boch P.Preparation ofα-andβ-tricalcium phosphate ceramics,with and without magnesium addition.Ceramic International,1994,20:327-36.)。因此，研究开发这两种元素掺杂的生物陶瓷材料将具有重要的临床应用价值。
发明内容
本发明目的是针对现有羟基磷灰石(HA)和磷酸三钙(β-TCP)人工骨材料降解速度与新骨形成速度不一致(HA晶体难于降解、β-TCP降解较快)，不利于新骨生长，同时HA和β-TCP人工骨支架的生物活性较差等问题，提供一种Sr和Mg元素掺杂的非晶磷灰石材料和晶体磷灰石材料，Sr、Mg元素掺杂可以提高磷灰石材料的生物活性，具有重要的临床应用价值。
为实现上述目的，本发明的技术方案如下：
一种Sr和Mg元素掺杂的非晶磷灰石材料，其为非晶态材料，化学式为：(Ca(9-x-y)SrxMgy)(HPO4)(PO4)5(OH)；其中：x为Sr元素的原子个数，y为Mg元素的原子个数，x取值范围为：0≤x≤1.8，y取值范围为：0≤y≤1.28。
该非晶磷灰石材料中，当x与y均为0时，为无掺杂的非晶态磷灰石材料；当x与y中之一为0时，为仅掺杂Sr元素的非晶磷灰石材料(0<x≤1.8，y＝0)或仅掺杂Mg的非晶磷灰石材料(x＝0，0<y≤1.28)；当x与y都不为0时，为同时掺杂Sr和Mg元素的非晶磷灰石材料(0<x≤0.9，0<y≤0.45)。
上述Sr和Mg元素掺杂的非晶磷灰石材料的制备是以Ca(NO3)2、Mg(NO3)2、Sr(NO3)2、(NH4)2HPO4和氨水溶液(NH3·H2O)作为原材料，通过化学沉淀法制备获得 所述Sr和Mg元素掺杂的非晶磷灰石材料(包括无掺杂非晶磷灰石材料和掺杂不同浓度Sr、Mg元素的非晶磷灰石材料)；其制备具体包括如下步骤：
(1)将Ca(NO3)2、Mg(NO3)2和Sr(NO3)2按照所需的非晶磷灰石材料中Ca、Sr和Mg元素原子比例进行配比(通过调节x和y的值，调节非晶缺钙羟基磷灰石中Sr、Mg元素的浓度)，然后溶于去离子水中形成混合溶液，用25wt.％的氨水溶液将所述混合溶液的pH值调节至9-10，得到溶液A；
(2)将(NH4)2HPO4按照所需的非晶磷灰石材料中P元素的摩尔比例配比，并溶于去离子水中，用25wt.％的氨水溶液将其pH值调节至9-10，得到溶液B；
(3)将溶液A迅速倒入溶液B中，磁力搅拌均匀后用抽滤瓶进行抽滤，并用去离子水和酒精分别清洗三遍，得到乳白色Sr和Mg元素掺杂的非晶磷灰石沉淀；冷冻干燥24小时后，获得粉末状所述Sr和Mg元素掺杂的非晶磷灰石材料。
步骤(3)中发生的沉淀反应方程式如下式(1)。
(9-x-y)Ca(NO3)2+xSr(NO3)2+yMg(NO3)2+6(NH4)2HPO4+6NH3·H2O→(Ca(9-x-y)SrxMgy)(HPO4)(PO4)5(OH)+18NH4NO3+5H2O     (1)
本发明利用所述非晶磷灰石材料可以进一步制备获得Sr和Mg元素掺杂的晶体磷灰石材料，即，将所述Sr和Mg元素掺杂的非晶磷灰石材料经热处理后获得，包括Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体和Sr和Mg元素掺杂的β相磷酸三钙(β-TCP)晶体。其中：
将所述Sr和Mg元素掺杂的非晶磷灰石材料在120℃热处理3-24小时后获得所述Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体(恒温时间越长材料晶化程度越好)，其中：Sr元素的原子百分比(按Sr/(Ca+Sr+Mg)计算)范围为0-20％，Mg元素的摩尔百分比(按Mg/(Ca+Sr+Mg)计算)范围为0-10％。
所得Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体中，包含无掺杂的纳米缺钙羟基磷灰石晶体(Sr和Mg元素掺杂量都为0时)、仅掺杂Sr的纳米缺钙羟基磷灰石晶体(Sr的原子百分比(按Sr/(Ca+Sr)计算)≤20％，Mg掺杂量为0)、仅掺杂Mg的纳米缺钙羟基磷灰石晶体(Sr的掺杂量为0，Mg的原子百分比(按Mg/(Ca+Mg)计算)≤10％)、以及Sr和Mg共掺杂纳米缺钙羟基磷灰石晶体(Sr的原子百分比(按Sr/(Ca+Sr+Mg)计算)≤10％且Mg的摩尔百分比(按Mg/(Ca+Sr+Mg)计算)≤5％)。
将所述Sr和Mg元素掺杂的非晶磷灰石材料在800℃热处理3小时后获得所述Sr和Mg元素掺杂的β相磷酸三钙(β-TCP)晶体，其中：Sr元素的摩尔百分比(按Sr/(Ca+Sr+Mg)计算)范围在0-20％，Mg元素的摩尔百分比(按Mg/(Ca+Sr+Mg)计算)范围在0-14.25％。
所得Sr和Mg元素掺杂的β相磷酸三钙(β-TCP)晶体中，包含无掺杂的β相磷酸三钙(β-TCP)晶体(Sr和Mg元素掺杂量都为0时)、仅掺杂Sr的β相磷酸三钙(β-TCP)晶体(Sr的原子百分比(Sr/(Ca+Sr))≤20％，Mg掺杂量为0)、仅掺杂Mg的β相磷酸三钙(β-TCP)晶体(Sr的掺杂量为0，Mg的原子百分比(Mg/(Ca+Mg))≤14.25％)、以及Sr和Mg共掺杂β相磷酸三钙(β-TCP)晶体(Sr的原子百分比(Sr/(Ca+Sr+Mg))≤10％且Mg的摩尔百分比(Mg/(Ca+Sr+Mg))≤5％)。
与现有技术相比，本发明的有益效果体现在：
1、本发明提供了一种制备非晶磷灰石及掺杂不同浓度Sr、Mg元素非晶磷灰石的方法，同时通过一定热处理工艺制备出掺杂不同浓度Sr、Mg元素的纳米缺钙羟基磷 灰石晶体和β-TCP晶体材料。
2、Sr、Mg元素掺杂后，Sr元素可以促进新骨形成，减少骨的再吸收，调节钙代谢，降低破骨细胞活性，Mg元素可以影响骨质的早期生长，提高β-TCP陶瓷相变温度，调控骨质的生长和重塑。Sr、Mg元素的掺杂提高了制备的磷灰石材料的生物活性。
3、与骨组成相似，人的牙釉质中羟基磷灰石的含量在95％以上，因此，考虑到羟基磷灰石与牙釉质具有相同结构和高亲和力的特点，本发明合成的非晶磷灰石及Sr、Mg元素掺杂的磷灰石材料也可以应用于牙齿修复和保健材料领域。
附图说明
图1为实施例1合成的磷灰石材料的粉末X光衍射图谱：(a)冷冻干燥的非晶磷灰石，(b)经120℃热处理3小时后得到的纳米缺钙羟基磷灰石晶体，(c)800℃热处理3小时后得到的β-TCP晶体材料。
图2为实施例1所得纯相非晶磷灰石材料的红外谱图。
图3为实施例2冷冻干燥后掺杂摩尔百分比14.25％Mg(Mg/(Ca+Mg)＝14.25％)的非晶磷灰石的透射电镜照片。
图4为掺杂不同浓度Sr、Mg元素非晶磷灰石材料经120℃热处理3小时后生成纳米缺钙羟基磷灰石晶体的粉末X光衍射图：(a)掺杂摩尔百分比20％Sr纳米缺钙羟基磷灰石，(b)掺杂摩尔百分比9.67％Mg纳米缺钙羟基磷灰石，(c)掺杂摩尔百分比5％Mg、10％Sr缺钙纳米羟基磷灰石。
图5为掺杂不同浓度Sr、Mg元素非晶磷灰石材料经800℃热处理3小时后生成β-TCP晶体的粉末X光衍射图：(a)掺杂摩尔百分比20％Sr的β-TCP晶体材料，(b)掺杂摩尔百分比15％Sr的β-TCP晶体材料，(c)掺杂摩尔百分比5％Sr的β-TCP晶体材料，(d)掺杂摩尔百分比5％Mg、10％Sr的β-TCP晶体材料，(e)掺杂摩尔百分比14.25％Mg的β-TCP晶体材料。
图6为利用聚氨酯模板法制备的掺杂摩尔百分比5％Mg、10％Sr的β-TCP多孔生物陶瓷。
具体实施方式
下面结合实施例和附图对本发明的技术方案做进一步说明。
本发明是以Ca(NO3)2、Mg(NO3)2、Sr(NO3)2、(NH4)2HPO4和NH3·H2O(氨水溶液)作为原材料，通过调控反应方程式(1)中x、y值，经化学沉淀法制得掺杂不同浓度Sr、Mg元素的非晶磷灰石材料。一方面制备的掺杂Sr、Mg元素的非晶磷灰石可以冷冻干燥密封后于4℃冰箱长期保存，另一方面可以其120℃热处理3-24小时获得掺杂不同浓度Sr、Mg元素的纳米缺钙羟基磷灰石晶体，或进行800℃热处理3小时得到掺杂不同浓度Sr、Mg元素的β-TCP晶体材料，然后利用烧结法制备掺杂不同浓度Sr、Mg元素的β-TCP人工骨陶瓷。
本发明工艺流程为：Ca(NO3)2、Mg(NO3)2、Sr(NO3)2、(NH4)2HPO4和NH3·H2O(氨水溶液)原材料→化学沉淀→冷冻干燥→掺杂不同浓度Sr、Mg元素的非晶磷灰石→热处理→掺杂不同浓度Sr、Mg元素的纳米缺钙羟基磷灰石晶体或磷酸三钙晶体→球磨 →烧结；具体包括如下步骤：
1)将Ca(NO3)2、Mg(NO3)2和Sr(NO3)2按照方程(1)中的Ca、Mg和Sr摩尔比例配比(通过调节x和y的值，调节非晶缺钙羟基磷灰石中Sr、Mg元素的浓度)并溶于去离子水中，用质量百分比25％的氨水溶液将上述混合溶液的pH值调节至9-10，得到溶液A；
2)将(NH4)2HPO4按照方程(1)中的P元素的摩尔比例配比，并溶于去离子水中，用质量百分比30％的氨水溶液将其pH值调节至9-10，得到溶液B；
3)将溶液A迅速倒入溶液B中，磁力搅拌均匀后用抽滤瓶进行抽滤，并用去离子水和酒精分别清洗三遍，得到乳白色无掺杂非晶磷灰石或掺杂不同浓度Sr和/或Mg元素的非晶磷灰石沉淀。冷冻干燥24小时，得到相应的非晶磷灰石粉末。
反应方程式：
(9-x-y)Ca(NO3)2+xSr(NO3)2+yMg(NO3)2+6(NH4)2HPO4+6NH3·H2O→(Ca(9-x-y)SrxMgy)(HPO4)(PO4)5(OH)+18NH4NO3+5H2O      (1)
通过调控反应方程(1)中x、y的值，来调节非晶缺钙羟基磷灰石中Sr、Mg元素掺杂的浓度，Sr、Mg掺的杂浓度应控制在一定范围以达到良好的生物活性。
将获得的非晶磷灰石材料通过热处理工艺转化为纳米缺钙羟基磷灰石晶体和掺杂不同浓度Sr、Mg元素的纳米缺钙羟基磷灰石晶体材料的方法如下：
将所述非晶缺钙羟基磷灰石及掺杂不同浓度Sr、Mg元素的非晶缺钙羟基磷灰石材料放入热处理炉内，从室温加热至120℃，在120℃下恒温3-24小时，然后随炉冷却至室温，得到纳米缺钙羟基磷灰石晶体材料和掺杂不同浓度Sr、Mg元素的纳米缺钙羟基磷灰石晶体材料。
将获得的非晶磷灰石材料通过热处理工艺转化为β-TCP晶体及掺杂不同浓度Sr、Mg元素的β-TCP晶体材料的方法如下：
将所述非晶磷灰石材料放入热处理炉内，从室温加热至800℃，在800℃下恒温3小时，然后随炉冷却至室温，得到β-TCP晶体和掺杂不同浓度Sr、Mg元素的β-TCP晶体材料。
实施例1
原材料及要求：Ca(NO3)2(分析纯)、(NH4)2HPO4(分析纯)和NH3·H2O(分析纯)。
快速沉淀：将0.09mol的Ca(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.09mol/L)，用磁力搅拌5min(500rpm)，将0.06mol的(NH4)2HPO4溶于1L去离子水，得到溶液B((NH4)2HPO4浓度为0.06mol/L)，用磁力搅拌5min(500rpm)，用质量百分比25％的氨水溶液(分析纯)将这两种溶液的pH值调为9-10，然后将溶液A迅速倒入溶液B中，磁力搅拌30s(500rpm)，用抽滤瓶进行抽滤，并用去离子水和酒精分别清洗三遍，得到乳白色材料。冷冻干燥24小时，得到无掺杂的非晶磷灰石粉末[Ca9(HPO4)(PO4)5(OH)](图1(a)、图2)。
热处理：将所得非晶磷灰石放入热处理炉内120℃进行热处理3小时，得到无掺杂纳米缺钙羟基磷灰石晶体(图1(b))；将所得非晶磷灰石放入热处理炉内800℃进行热处理3小时，得到无掺杂β-TCP晶体材料(图1(c))。
实施例2
本例将0.0772mol的Ca(NO3)2和0.0128mol的Mg(NO3)2溶于1L去离子水，得到 溶液A(Ca(NO3)2浓度为0.0772mol/L、Mg(NO3)2浓度为0.0128mol/L)，其余部分与实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比14.25％Mg的(Mg/(Ca+Mg)＝14.25％)非晶磷灰石粉末(图3)。在热处理炉内800℃进行热处理3小时得到掺杂摩尔百分比14.25％Mg的β-TCP晶体材料(图5(e))。
实施例3
本例将0.0813mol的Ca(NO3)2和0.0087mol的Mg(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.0813mol/L、Mg(NO3)2浓度为0.0087mol/L)，其余部分与实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比9.67％Mg(Mg/(Ca+Mg)＝9.67％)非晶磷灰石粉末。在热处理炉内120℃进行热处理3小时得到掺杂摩尔百分比9.67％Mg的纳米缺钙羟基磷灰石晶体材料(图4(b))。
实施例4
本例将0.072mol的Ca(NO3)2和0.018mol的Sr(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.072mol/L、Sr(NO3)2浓度为0.018mol/L)，其余部分实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比20％Sr(Sr/(Ca+Sr)＝20％)的非晶缺钙羟基磷灰石材料，在热处理炉内120℃进行热处理3小时得到掺杂摩尔百分比20％Sr的纳米缺钙羟基磷灰石晶体材料(图4(a))，在热处理炉内800℃进行热处理3小时得到掺杂摩尔百分比20％Sr的β-TCP晶体材料(图5(a))。
实施例5
本例将0.0765mol的Ca(NO3)2和0.0135mol的Sr(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.0765mol/L、Sr(NO3)2浓度为0.0135mol/L)，其余部分实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比15％Sr(Sr/(Ca+Sr)＝15％)的非晶磷灰石材料。在热处理炉内800℃进行热处理3小时得到掺杂摩尔百分比15％Sr的β-TCP晶体材料(图5(b))。
实施例6
本例将0.0855mol的Ca(NO3)2和0.0045mol的Sr(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.0855mol/L、Sr(NO3)2浓度为0.0045mol/L)，其余部分实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比5％Sr(Sr/(Ca+Sr)＝5％)的非晶磷灰石材料。在热处理炉内800℃进行热处理3小时得到掺杂摩尔百分比5％Sr的β-TCP晶体材料(图5(c))。
实施例7
本例将0.0765mol的Ca(NO3)2、0.009mol的Sr(NO3)2和0.0045mol的Mg(NO3)2溶于1L去离子水，得到溶液A(Ca(NO3)2浓度为0.0765mol/L、Sr(NO3)2浓度为0.009mol/L、Mg(NO3)2浓度为0.0045mol/L)，其余部分实施例1相同，冷冻干燥24小时，得到掺杂摩尔百分比10％Sr(Sr/(Ca+Sr+Mg)＝10％)、5％Mg(Mg/(Ca+Sr+Mg)＝5％)的非晶磷灰石材料。非晶样品在热处理炉内120℃进行热处理3小时得到掺杂摩尔百分比10％Sr、5％Mg的纳米缺钙羟基磷灰石晶体材料(图4(c))。在热处理炉内800℃进行热处理3小时得到掺杂摩尔百分比10％Sr、5％Mg的β-TCP晶体材料(图5(d))。
球磨及烘干：将得到的掺杂摩尔百分比10％Sr、5％Mg的β-TCP晶体材料球磨(200rpm)10小时，在120℃真空烘干3小时。
陶瓷烧结：将烘干后掺杂摩尔百分比10％Sr、5％Mg的β-TCP粉末与质量百分比 5％聚乙烯醇溶液混合，每毫升聚乙烯醇溶液中粉体的量为0.8g，搅拌条件下获得均匀浆料，将1ml浆料挤压填充至1cm x 1cm x 1cm的60ppi聚氨酯多孔支架内，然后在空气氛围中1200℃烧结3小时制得多孔陶瓷(图6)，随炉冷却至室温后取出样品。多孔陶瓷的孔径～200μm，孔隙率为～60％。

Claims (9)

  1. 一种Sr和Mg元素掺杂的非晶磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的非晶磷灰石材料为非晶态，其化学式为：(Ca(9-x-y)SrxMgy)(HPO4)(PO4)5(OH)，其中：x为Sr元素的原子个数，y为Mg元素的原子个数，x取值范围为：0≤x≤1.8，y取值范围为：0≤y≤1.28。
  2. 根据权利要求1所述的Sr和Mg元素掺杂的非晶磷灰石材料，其特征在于：所述非晶磷灰石材料中，当x与y均为0时，为无掺杂的非晶态磷灰石材料；当0<x≤1.8且y＝0时为仅掺杂Sr的非晶磷灰石材料，当x＝0且0<y≤1.28时为仅掺杂Mg的非晶磷灰石材料；当0<x≤0.9且0<y≤0.45时为同时掺杂Sr和Mg元素的非晶磷灰石材料。
  3. 根据权利要求1或2所述的Sr和Mg元素掺杂的非晶磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的非晶磷灰石材料的制备是以Ca(NO3)2、Mg(NO3)2、Sr(NO3)2、(NH4)2HPO4和氨水溶液作为原材料，通过化学沉淀法制备获得所述Sr和Mg元素掺杂的非晶磷灰石材料。
  4. 根据权利要求3所述的Sr和Mg元素掺杂的非晶磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的非晶磷灰石材料的制备按照如下步骤进行：
    (1)将Ca(NO3)2、Mg(NO3)2和Sr(NO3)2按照所需非晶磷灰石材料中Ca、Sr和Mg元素原子比例进行配比，然后溶于去离子水中形成混合溶液，用25wt.％的氨水溶液将所得混合溶液的pH值调节至9-10，得到溶液A；
    (2)将(NH4)2HPO4按照所需非晶磷灰石材料中P元素比例进行配比，并溶于去离子水中，用25wt.％的氨水溶液将其pH值调节至9-10，得到溶液B；
    (3)将溶液A加入溶液B中，磁力搅拌均匀后用抽滤瓶进行抽滤，并用去离子水和酒精分别清洗三遍，得到乳白色Sr和Mg元素掺杂的非晶磷灰石沉淀；冷冻干燥24小时后，获得粉末状所述Sr和Mg元素掺杂的非晶磷灰石材料。
  5. 一种利用权利要求1或2所述的非晶磷灰石材料制备获得的Sr和Mg元素掺杂的晶体磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的晶体磷灰石材料是将所述Sr和Mg元素掺杂的非晶磷灰石材料经热处理后获得，包括Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体和Sr和Mg元素掺杂的β相磷酸三钙晶体。
  6. 根据权利要求5所述的Sr和Mg元素掺杂的晶体磷灰石材料，其特征在于：将所述Sr和Mg元素掺杂的非晶磷灰石材料在120℃热处理3-24小时后获得所述Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体。
  7. 根据权利要求6所述的Sr和Mg元素掺杂的晶体磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的纳米缺钙羟基磷灰石晶体中，Sr元素的原子百分比范围为0-20％，Mg元素的原子百分比范围在0-10％。
  8. 根据权利要求5所述的Sr和Mg元素掺杂的晶体磷灰石材料，其特征在于：将所述Sr和Mg元素掺杂的非晶磷灰石材料在800℃热处理3小时后获得所述Sr和Mg元素掺杂的β相磷酸三钙晶体。
  9. 根据权利要求8所述的Sr和Mg元素掺杂的晶体磷灰石材料，其特征在于：所述Sr和Mg元素掺杂的β相磷酸三钙晶体中，Sr元素的原子百分比范围在0-20％， Mg元素的原子百分比范围在0-14.25％。
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