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CN-122010127-A - Phosphosilicate based bioactive materials and methods of making same

CN122010127ACN 122010127 ACN122010127 ACN 122010127ACN-122010127-A

Abstract

The invention belongs to the technical field of biomedical materials. Specifically, the invention discloses a phosphosilicate-based bioactive material and a preparation method thereof. The preparation method is based on the regulation and control of an emulsifying system and a double-promotion reaction mechanism strategy, and is a preparation technology with simple process and low cost. The preparation method disclosed by the invention can be used for realizing the application of the calcium source raw material with smaller water solubility in the preparation process of the bioactive material by promoting the interface contact reaction through emulsification, reducing the dependence on a water-soluble calcium source which is easy to cause environmental pollution, realizing the greenization of the preparation process, and the phosphosilicate-based bioactive material prepared by adopting the method disclosed by the invention has excellent bioactivity.

Inventors

  • HU FANG
  • GUO CHUANGZHOU
  • ZHOU XUEGANG

Assignees

  • 北京幸福益生再生医学科技有限公司

Dates

Publication Date
20260512
Application Date
20251215

Claims (10)

  1. 1. A method of preparing a phosphosilicate-based bioactive material, the method comprising the steps of: Step 1, providing an aqueous phase solution containing an emulsifier, wherein the concentration of the emulsifier in the aqueous phase solution is in the range of 0.5 to 10 wt%; step 2, providing an oil phase solution containing liquid silicate matters, wherein the concentration of the liquid silicate matters in the oil phase solution is in the range of 15 to 60 volume percent, and the solvent of the oil phase solution is a water-soluble organic solvent; slowly dropwise adding the oil phase solution obtained in the step 2 into the water phase solution obtained in the step 1 at a temperature of 20-30 ℃ under stirring, wherein the ratio of the weight of the water phase solution to the total volume of the dropwise added oil phase solution is in the range of 0.7 g/mL to 3 g/mL, so as to form a stable oil-in-water emulsion system; Step 4, adding a calcium source substance into the emulsifying system obtained in the step 3 under stirring, wherein the calcium source substance comprises calcium hydroxide and optional clean calcium source substances, and adding an organic phosphorus source substance, and continuing stirring until the mixture is uniform, wherein the molar ratio of phosphorus element in the added organic phosphorus source substance to silicon element in the silicate substance is in the range of (0.1-1): 1, and the molar ratio of calcium element in the calcium source substance to silicon element in the silicate substance is in the range of (0.1-2): 1; Step 5, reacting the mixed system obtained from step 4 at a temperature of 20 to 80 ℃ for 2 to 24 hours, thereby forming a suspension comprising phosphosilicate precursor solids; Step 6. The phosphosilicate precursor solid from step 5 is separated from the suspension and, after optional washing and drying, calcined at a calcination temperature of 500 to 900 ℃ for 2 to 6 hours, thereby obtaining the phosphosilicate-based bioactive material.
  2. 2. The method of claim 1, wherein in step 1, the emulsifier comprises one or more of tween 80, span 80, sodium dodecyl sulfate, and polyether F68.
  3. 3. The method according to claim 1, wherein in the step 2, The liquid silicate material comprises one or more of methyl orthosilicate, ethyl orthosilicate and butyl orthosilicate, and/or The water-soluble organic solvent comprises an alcoholic organic solvent, preferably one or more of ethanol, propanol and isopropanol.
  4. 4. The preparation method according to claim 1, wherein step 3 further comprises, after slowly dropping the oil phase solution obtained in step 2 into the aqueous phase solution obtained in step 1, continuing stirring the obtained mixed solution at a stirring speed of 300 to 800 rpm for 10 to 30 minutes, and then homogenizing and emulsifying at a homogenizing speed of 3000 to 6000 rpm for 2 to 5 minutes, thereby forming a stable oil-in-water emulsion system.
  5. 5. The method according to claim 1, wherein in the step 4, The added calcium source material comprises calcium hydroxide and clean calcium source material, and the ratio of calcium element in the calcium hydroxide and clean calcium source material is (2.5-5.5): 1, and/or The clean calcium source material comprises a water-slightly soluble calcium source, and/or The clean calcium source material comprises one or more of calcium dihydrogen phosphate and calcium acetate, and/or The organic phosphorus source substance comprises one or more of triethyl phosphate, inositol hexaphosphate and glycerophosphate.
  6. 6. The method according to claim 1, wherein in step 4, a calcium source and/or an organic phosphorus source is added together with other metal sources to the emulsion system obtained in step 3.
  7. 7. The method according to claim 6, wherein, The other metal source material comprises sodium-containing, magnesium-containing and/or strontium-containing compounds, and/or The molar ratio of the metal cations in the other metal salt species to the silicon element in the silicate species is in the range of (0-0.6): 1.
  8. 8. The method according to any one of claims 1 to 7, wherein in the step 6, The separation process comprises centrifuging the suspension comprising the phosphosilicate precursor solid at a rotational speed of 3000 to 8000 revolutions per minute for 5 to 15 minutes, thereby separating the phosphosilicate precursor solid from the suspension, and/or The washing process comprises alternately washing the separated phosphosilicate precursor solid with deionized water and ethanol 3 to 5 times, and/or The drying process comprises drying the isolated phosphosilicate precursor solid at a temperature of 60 to 100 ℃ for 6 to 24 hours, and/or The phosphosilicate precursor solid is warmed to the calcination temperature at a warming rate of 2 to 10 ℃ per minute prior to the calcination.
  9. 9. Phosphosilicate-based bioactive material prepared by the preparation method according to any one of claims 1 to 8.
  10. 10. The phosphosilicate-based bioactive material of claim 9, wherein the phosphosilicate-based bioactive material has one or more of the following properties: The phosphosilicate-based bioactive material is porous particles stacked from particles having a primary particle size in the range of 50 to 100 nm; The phosphosilicate-based bioactive material has a specific surface area of at least 100m 2 /g; The phosphosilicate-based bioactive material has a particle size of no more than 7 μm D 50 and/or no more than 17 μm D 98 .

Description

Phosphosilicate based bioactive materials and methods of making same Technical Field The invention belongs to the technical field of biomedical materials. Specifically, the invention discloses a phosphosilicate-based bioactive material and a preparation method thereof. Background Phosphosilicate-based bioactive materials have received great attention in the field of bone tissue engineering repair due to their good biocompatibility, bioactivity, and bone conductivity. In the phosphosilicate-based bioactive material, the components of the phosphosilicate material containing phosphorus and calcium are similar to the inorganic components in human bone tissue, so that the phosphosilicate-based bioactive material can better promote proliferation and differentiation of bone cells, accelerate formation of bone-induced new bones, has excellent bone repair performance, and promote cell migration and repair of soft tissue wounds due to the fact that the phosphosilicate-based bioactive material can release active ions to promote cell proliferation and formed scaffolds, so that the phosphosilicate-based bioactive material has a wide application prospect. The phosphosilicate-based bioactive materials of the prior art can be prepared by a variety of preparation methods, however, each preparation method of the prior art still has a number of limitations, particularly in terms of: High temperature fusion process the principle of this process is to effect atomic diffusion reactions by high temperature calcination (typically at about 1300 to about 1700 ℃) of solid raw materials such as silica, calcium carbonate, calcium phosphate, sodium carbonate and the like. The process, although simple and easy to implement, may not be easily performed to be complete, and unreacted original particles are easily remained, thereby causing uneven components of the product. In particular, sodium-containing compounds are required to lower the melting point of the product, which may remain in the product after the end of the reaction, leading to an increase in the pH of the material and severe cytotoxicity. In addition, high temperature sintering may also promote coarsening of the grains of the product (which may typically exceed about 10 μm in size), thereby reducing the specific surface area and surface activity of the material, which is detrimental to its interaction with the biological environment. In addition, the problems of low porosity, high brittleness and the like are easy to generate in the sintering process, so that the cooperative requirement of the bone repair material on the porous structure and the mechanical property is difficult to meet. Sol-gel process the principle of the conventional sol-gel process is to form a sol-gel network by hydrolytic polycondensation of metal alkoxides. Although the method can realize accurate regulation and control of components, the stability of a reaction system is poor and is easily influenced by environmental factors such as humidity, pH value and the like, so that the difference among product batches is easily caused to be obvious. In addition, the hydrolysis process in this method is slow (usually several days to several weeks are required), and particle agglomeration is easily induced by colloid agglomeration in the latter stage of the reaction, so that additional introduction of a dispersing agent or complicated surface modification is required, which increases the complexity of the process and the production cost. In addition, the sol-gel method needs to select soluble calcium salts such as calcium nitrate/calcium chloride, so that strong acid radical ions are required to be removed through heating decomposition, a large amount of strong polluted acid gas is generated, and equipment is corroded and the environment is harmed. Hydrothermal synthesis this method relies on high temperature and high pressure (typically requiring temperatures of about 100 to about 200 ℃ and pressures of about 1 to about 10 MPa) conditions to promote the reaction, and therefore stringent pressure resistance and sealability requirements for the equipment. In addition, the method has high energy consumption and high safety risk when being used for large-scale production, and the temperature and the pressure in the reaction kettle are possibly unevenly distributed, so that the product has wide particle size distribution and imperfect crystal structure, and the product performance is optimized by sieving or grinding for multiple times, thereby further possibly losing the activity of the material. Meanwhile, a phosphorus source (such as diammonium hydrogen phosphate) is easy to volatilize in the hydrothermal reaction, so that the content of phosphorus element in a product can deviate from a design value, and the stability of biological activity is further affected. In addition, the preparation method of phosphosilicate-based bioactive materials in the prior art has the following problems, for example: Inefficiency of