阅读说明：本技术 微观动力学反应受限的热力学稳定态羟基磷灰石合成方法 (Method for synthesizing thermodynamically stable hydroxyapatite with microscopic kinetic reaction limitation ) 是由 张青前 白著双 于 2019-11-27 设计创作，主要内容包括：本发明涉及羟基磷灰石的制备,属于无机材料制备领域。一种微观动力学反应受限的热力学稳定态羟基磷灰石合成方法,低温下向含钙盐的微观动力学反应限定性溶液中加入磷酸盐溶液,逐步升温完成反应,然后将所获得中间态固体500～750℃下转变为热力学稳态的羟基磷灰石。采用本发明所提供的微观动力学反应受限的热力学稳定态羟基磷灰石合成方法,所制备的羟基磷灰石颗粒大小在纳米级,且分散性比较好,不存在明显的晶粒团聚体,制备的羟基磷灰石样品粒径78.72％低至100nm以下。(The invention relates to preparation of hydroxyapatite, and belongs to the field of inorganic material preparation. A method for synthesizing thermodynamically stable hydroxyapatite with limited micro-kinetic reaction comprises the steps of adding phosphate solution into calcium salt-containing micro-kinetic reaction limiting solution at low temperature, gradually raising the temperature to complete reaction, and converting the obtained intermediate solid into thermodynamically stable hydroxyapatite at 500-750 ℃. By adopting the method for synthesizing the thermodynamically stable hydroxyapatite with the limited micro-kinetic reaction, the particle size of the prepared hydroxyapatite is in a nanometer level, the dispersibility is good, no obvious crystal particle aggregates exist, and the particle size of the prepared hydroxyapatite sample is 78.72 percent and is below 100 nm.)

1. A method for synthesizing thermodynamically stable hydroxyapatite with limited micro-kinetic reaction is characterized in that a phosphate solution in an ice-water mixture state is added into a micro-kinetic reaction limiting solution containing calcium salt, ammonia water is adopted to control the pH of a reaction system to be within 11.0-11.5, and then the obtained intermediate solid is converted into thermodynamically stable hydroxyapatite at 500-750 ℃;

the composition of the micro-kinetic reaction limiting solution containing calcium salt comprises: calcium nitrate, ethanol, sodium dodecyl sulfate;

the phosphate solution comprises the following components: diammonium phosphate and water.

2. The method of synthesizing a thermodynamically stable hydroxyapatite with limited pharmacokinetic response according to claim 1, wherein the step of adding a phosphate solution in an ice-water mixture state dropwise to the pharmacokinetic response limiting solution containing the calcium salt includes:

a. firstly, cooling the phosphate solution to a semi-solid ice-water mixture state under high-speed stirring, and cooling the calcium salt-containing micro-kinetic reaction limiting solution to the temperature of the semi-solid phosphate solution;

b. adding a semi-solid phosphate solution to a micro-kinetic reaction limiting solution containing calcium salts;

c. gradually raising the temperature of the mixed solution to 40-60 ℃ under the stirring state.

3. The method for synthesizing hydroxyapatite with a thermodynamically stable state and limited kinetic reaction according to claim 2, wherein the temperature of the phosphate solution in the semi-solid ice-water mixture state is-15 ℃ to-40 ℃.

4. The method for synthesizing hydroxyapatite in a thermodynamically stable state with limited micro-kinetic reaction according to claim 1, wherein the calcium nitrate tetrahydrate concentration of the solution with limited micro-kinetic reaction containing the calcium salt is 100 to 300g/L, and the sodium dodecyl sulfate concentration is 0.01 to 0.03 Kg/L.

5. The method for synthesizing a thermodynamically stable state hydroxyapatite with limited micro-kinetic reaction according to claim 1, wherein the concentration of the diammonium phosphate solution of the phosphate solution is 100-240 g/L.

6. The method for synthesizing a thermodynamically stable state hydroxyapatite with limited micro-kinetic reaction according to claim 1, wherein the transition time of the intermediate state solid to the thermodynamic stable state at 500 to 750 ℃ is 2 to 5 hours.

7. The method for synthesizing the thermodynamically stable hydroxyapatite with limited micro-kinetic reaction according to claim 1, wherein the intermediate solid is dried at 110-135 ℃ to remove the solvent before being dried.

8. The method of synthesizing a thermodynamically stable state hydroxyapatite with limited micro-kinetic reaction according to claim 1, wherein the ammonia content of the ammonia water is 25 wt% to 28 wt%.

9. The method of synthesizing hydroxyapatite in a thermodynamically stable state with limited micro-kinetic reaction according to claim 1, wherein the obtained solid hydroxyapatite is ground into nano-particles by jet milling.

Technical Field

The invention relates to synthesis of thermally stable hydroxyapatite, in particular to a method for synthesizing thermodynamically stable hydroxyapatite with a micro-kinetic reaction limitation.

Background

Hydroxyapatite (HAP) has a molecular formula of Ca ₁₀(PO ₄) ₆(OH) ₂Is the main component of natural bone inorganic matter, has good biocompatibility and bioactivity, can guide the growth of bone, and forms firm osseous combination with bone tissue. HAP is a representative material of bioactive ceramics, and bioactive materials are capable of inducing biological or chemical reactions on the interface between materials and tissues to form strong chemical bonds between the materials and the tissues, thereby achieving the purpose of tissue repair. The similarity of HAP in composition to human bone, which makes HAP to human hard tissueAnd skin, muscular tissue and the like have good biocompatibility, and the material is implanted into a body, is safe and nontoxic, and can guide bone growth, namely, new bone can grow along the surface or the internal through gap of the implanted body from the joint of the HAP implant and the original bone, and the material can form good chemical bond combination with the bone tissue after being implanted into the body.

The preparation method of the nano-grade hydroxyapatite is various and mainly divided into a solid phase method and a liquid phase method. Solid phase synthesis allows phosphate and calcium salt to be fully mixed under certain conditions (high temperature and grinding) to perform solid phase reaction, so as to synthesize HAP powder. The liquid phase synthesis is that phosphate and calcium salt are used as raw materials in water solution, and the raw materials undergo chemical reaction under certain conditions to generate HAP crystal grains with low solubility, and the liquid phase synthesis comprises a chemical precipitation method, a hydrothermal synthesis method, a sol-gel method, a micro-emulsion method, a microwave method and the like.

1. Wet chemical precipitation method

The wet chemical precipitation method comprises adding calcium salt (CaCl) with certain concentration ₂，Ca(NO ₃) ₂，CaO，Ca(OH) ₂，Ca(CH ₃COO) ₂，Ca(OC ₂H ₅) ₂) And phosphates ((NH) ₄) ₂HPO ₄，H ₃P0 ₄。K ₂HPO ₄，NaH ₂PO ₄，(CH ₃O) ₃PO) is mixed and stirred, the solution is subjected to chemical reaction under certain pH value and temperature conditions to generate HAP sediment, and the sediment is calcined at 900-1200 ℃, so that HAP powder which meets certain Ca/P molar ratio and has a good crystal form can be obtained.

In the wet chemical precipitation method, the pH value and the temperature of the solution have great influence on the composition, the structure, the grain size and the like of precipitates, and the control of experimental conditions is particularly important. The method has the advantages of low reaction temperature, high purity of the synthesized powder, fine particles, relatively simple process and relatively low cost of the synthesized powder. However, the process conditions must be strictly controlled, otherwise calcium-deficient apatite with relatively low Ca/P molar ratio is easily formed. In addition, the HAP generated by the wet chemical precipitation method has wide particle size distribution range and low particle dispersity.

2. Sol-gel process

The sol-gel method is a new method developed in recent years, and has attracted a wide attention. The sol-gel method is that alkoxide is dissolved in organic solvent, alkoxide is hydrolyzed and polymerized by adding distilled water to form sol, the sol is changed into gel along with the addition of water after being formed, the gel is dried at low temperature in a vacuum state to obtain loose dry gel, and the dry gel is calcined at high temperature to obtain the nano powder. Compared with the traditional solid phase synthesis method and solid phase sintering method, the synthesis and sintering temperature of the sol-gel method is lower, and the precursors of calcium and phosphorus can be mixed on the molecular level, so that the sol has high chemical uniformity. But the method is restricted in application because of high price of raw materials, high toxicity of organic solvents, environmental pollution, easy rapid agglomeration and the like.

3. Hydrothermal method

The hydrothermal method is a method for preparing HAP crystallization precipitate in aqueous solution under the condition of high temperature, and in a special closed reaction container (high-pressure kettle), the aqueous solution is used as a reaction medium, so that the original insoluble or insoluble substances are dissolved and recrystallized in a high-temperature and high-pressure environment. The method generally uses calcium hydrophosphate or calcium carbonate and the like as raw materials to prepare HAP in an aqueous solution system in an autoclave with the temperature of 200-400 ℃. The method has the advantages of easily controlled conditions, short reaction time, no calcination and grinding steps, high powder purity and low crystal defect density; the synthesis temperature is relatively low, the reaction condition is moderate, the equipment is simple, and the power consumption is low. Therefore, the powder prepared by the hydrothermal method not only has the advantages of complete grain development, small granularity, uniform distribution, light particle agglomeration, cheap raw materials, and easy obtainment of proper stoichiometric ratio and crystal form. The prepared powder does not need calcination treatment, thereby avoiding the problems of grain growth, defect formation, impurity generation and the like in the sintering process, and the prepared powder has higher sintering activity. However, the hydrothermal method has high requirements on the corrosion resistance of equipment, waste liquid needs to be treated, and the pH value, temperature and pressure, reaction time, aging time and the like of reaction raw materials, additives and media have great influence on the growth and properties of products.

4. Ultrasonic synthesis method

Ultrasonic waves cause cavitation in aqueous media, causing microbubbles to form, grow, and collapse in water. This activates the reactivity of the chemical species, thereby effectively accelerating the rate of heterogeneous chemical reactions between the liquid and solid reactants. The HAP powder synthesized by the ultrasonic method is very fine, has a narrow particle size distribution range, and the synthesis method is more effective than other heating methods in some aspects.

5. Microemulsion process

The microemulsion method utilizes two immiscible solvents to form a uniform emulsion under the action of a surfactant, and a solid phase is separated out from the emulsion. The preparation of nano powder by a microemulsion method is widely regarded, and the obtained powder has narrow particle size distribution and is easy to control. The key for synthesizing the nano HAP by using the method is to select proper microemulsion and thoroughly remove the oil phase and the surfactant on the surface of the particles.

6. Solid state synthesis process

Solid calcium phosphate and other compounds are mixed together homogeneously in the presence of water vapor at reaction temperature higher than 1000"C to obtain hydroxyapatite with high crystallization quality. The hydroxyapatite synthesized by the method has high purity and good crystallinity, the lattice constant does not change along with the temperature, and the infrared spectroscopy research of the hydroxyapatite synthesized by the wet method and the solid phase method shows that the HAP prepared by the solid phase method is better than that prepared by the wet method, but the HAP requires higher temperature and heat treatment time, the powder has poor sinterability, large particle size and poor activity, so that the application is limited to a certain extent.

Hydroxyapatite materials belong to thermodynamically stable products, and the existing synthesis processes are classified into two types from the perspective of a microscopic reaction mechanism: a combination method of kinetic synthesis-thermodynamic transformation and a thermodynamic one-step synthesis method.

The combination method of kinetic synthesis and thermodynamic transformation has the defects that under the microscopic kinetic reaction, the product is essentially a product obtained by kinetic drive, and the phosphorus/calcium molar ratio in the crystal of the product does not perfectly accord with the phosphorus/calcium molar ratio of the thermodynamically stable hydroxyapatite, so that the hydroxyapatite prepared by the method cannot avoid the defects of impurities, mixed crystals and the like. In the combined method of kinetic synthesis and thermodynamic transformation, the intermediate product generated by the driving of the micro-kinetics is difficult to obtain a product with uniform components on the micro level due to the influence of the reaction speed, and the hydroxyapatite with perfect phosphorus/calcium molar ratio on the micro level is difficult to obtain through the thermodynamic transformation.

The thermodynamic one-step synthesis method has more obvious defects and is limited by Gibbs free energy limitation on the surface of a material, the raw materials are difficult to realize the reaction of uniform mixing of microscopic molecular layers, the product has wide particle size distribution range and low particle dispersity, the phosphorus/calcium ratio at each part of microscopic particle crystals is not uniform, the crystal form defects of the product are more, and the quality is difficult to improve.

Therefore, a synthesis process of hydroxyapatite is urgently needed at present, a micro-kinetic process and a micro-thermodynamic process are fully blended, the defects of micro-kinetic products are overcome, and the quality of the thermodynamic product hydroxyapatite is improved.

Disclosure of Invention

The invention aims to solve the technical problem of providing a method for synthesizing thermodynamically stable hydroxyapatite with limited micro-kinetic reaction, which solves the problems of low production quality of the existing hydroxyapatite, poor uniformity of hydroxyapatite particles on a micro-level, wide grain distribution and poor dispersibility.

Technical scheme

A method for synthesizing thermodynamically stable hydroxyapatite with limited micro-kinetic reaction is characterized by comprising the following steps: adding a phosphate solution in an ice-water mixture state into a micro-kinetic reaction limiting solution containing calcium salt, controlling the pH of a reaction system to be within 11-11.5 by adopting ammonia water, and converting the obtained intermediate state solid into thermodynamically stable hydroxyapatite at 500-750 ℃;

the composition of the micro-kinetic reaction limiting solution containing calcium salt comprises: calcium nitrate, ethanol, sodium dodecyl sulfate;

the phosphate solution comprises the following components: diammonium phosphate and water.

Further, the step of adding the phosphate solution dropwise to the pharmacokinetic reaction limiting solution containing calcium salt comprises: a. firstly, cooling the phosphate solution to a semi-solid ice-water mixture state under high-speed stirring, and cooling the calcium salt-containing micro-kinetic reaction limiting solution to the temperature of the semi-solid phosphate solution; b. adding a semi-solid phosphate solution to a micro-kinetic reaction limiting solution containing calcium salts; c. gradually raising the temperature of the mixed solution to 40-60 ℃ under the stirring state.

Further, the temperature of the phosphate solution in the semi-solid ice-water mixture state is-15 to-40 ℃.

Furthermore, in the micro-kinetic reaction limiting solution containing the calcium salt, the concentration of calcium nitrate tetrahydrate is 100-300 g/L, and the concentration of sodium dodecyl sulfate is 0.01-0.03 Kg/L.

Further, the concentration of the diammonium hydrogen phosphate in the phosphate solution is 100-240 g/L.

Further, the transition time of the intermediate solid to the thermodynamic steady state at 600 ℃ is 2-5 h.

Further, before drying the intermediate solid, drying the intermediate solid at 110-135 ℃ to remove the solvent.

Further, the ammonia content of the ammonia water is 25 wt% -28 wt%.

Further, the obtained hydroxyapatite solid is ground into nano particles by airflow.

Advantageous effects

The method for synthesizing the thermodynamically stable hydroxyapatite with the limited micro-kinetic reaction has the advantages of nano-scale particle size, uniform particles, good dispersity and no obvious grain aggregate.

According to the technical scheme, under the conditions that ethanol is used as a solvent to prepare a calcium nitrate solution to serve as a water-soluble cosurfactant and dodecyl sulfate is added into the calcium nitrate solution, the cosurfactant can change the surface activity and the hydrophilic-lipophilic balance of the surfactant, participate in forming micelles, adjust the polarity of water and oil, reduce the polarity of water by using water-soluble alcohol, and increase the polarity of oil by using oil-soluble alcohol, so that the phase state and the phase property of a system are influenced, the reaction uniformity is improved, and the subsequent agglomeration of product particles is reduced. And the microscopic thermodynamic reaction speed is limited by low temperature, the microscopic thermodynamic reaction equilibrium point is improved by raising the temperature in the later stage, and the grain diameter of the prepared sample is 78.72 percent and is lower than 100 nm.

Drawings

FIG. 1 is an X-ray powder diffraction pattern of sample 1;

FIG. 2 is a scanning electron micrograph A of sample 1;

FIG. 3 is a scanning electron micrograph B of sample 1;

FIG. 4 is a particle size analysis inspection of sample 5;

FIG. 5 is a particle size analysis inspection of sample 1;

FIG. 6 is a particle size analysis inspection of sample 4;

fig. 7 is a particle size analysis inspection of sample 2.

Detailed Description

The invention will be further elucidated with reference to the specific embodiments and the accompanying drawings.

The invention provides a method for synthesizing thermodynamically stable hydroxyapatite with limited micro-kinetic reaction, which solves the problems of low production quality of the existing hydroxyapatite, poor uniformity of hydroxyapatite particles on a micro-level, wide grain distribution and poor dispersibility. The following examples are specific: