• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
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    • 专利摘要:
    The invention provides a porous nano-hydroxyapatite microsphere with high porosity and a preparation method thereof. The size distribution of hydroxyapatite composite microspheres 5 prepared with the method is uniform, the particle size distribution range is 10-100 um; and the center particle size is 20-60um. Organic phases are added in a mixing process so that the suspension stability of suspension liquid can be improved effectively; the size distribution of the prepared microspheres is uniform, and the particle size is larger than the size of microspheres prepared with a traditional spray drying method; the microspheres can be used as internal support materials of 10 injections; the microspheres are better in sphere and high in porosity so that the inj ectable property of the materials is improved
    公开号:NL2023794A
    申请号:NL2023794
    申请日:2019-09-09
    公开日:2020-10-27
    发明作者:Liu Jia
    申请人:Shanghai Moyang Biotechnology Co Ltd；
    IPC主号:
    专利说明:

    Porous Nano-hydroxyapatite Microsphere with High Porosity and a Preparation Method Thereof Technical Field The invention belongs to the technical field of materials, and particularly relates to a porous nano-hydroxyapatite microsphere with high porosity and a preparation method thereof. Background The structures and components of hydroxyapatite (HAP) are extremely similar to the bone tissues of a human body, so that the HAP receives extensive attention of biological material and medical experts.
    Various methods are provided for preparing the HAP microspheres. such as a hydrothermal method, an emulsion-crosslinking method, a microwave method and a spray drying method. The emulsion-crosslinking method is usually used for preparing organic and inorganic composite hydroxyapatite microspheres, but this method has the problems that the microspheres are liable to agglomerate. crosslinking agents are hard to remove completely and the like. The spray drying method has the advantages of easy operation, no need of toxic reagents, easy industrialization and the like, but the spray drying method also has the shortcomings of irregular shapes of the microspheres, wide distribution of particle sizes and the like. Methods for preparing porous hydroxyapatite include a chemical foaming method, a pore-forming agent method, an organic foam impregnation method and an organic template method. The pore diameter and porosity of porous materials are hard to control during preparation of the porous hydroxyapatite with the chemical foaming method, and most pores of the porous materials prepared with this method are closed, and the penetration rate of the pores is poor. The porosity of the porous hydroxyapatite prepared with the pore-forming agent method is not high, and the pore diameter range distribution is wider. Micro- cracks are easy to form on biological materials in the drying and sintering process of the organic foam impregnation method, and the strength of the porous hydroxyapatite is reduced. Proper surfactants are required in the organic template method; under some conditions, the selected surfactants may be toxic, and should be removed at high temperature; in this way, the biological activity of the porous hydroxyapatite is reduced.
    Summary of the Invention In order to solve the problems in the prior art, the invention provides a preparation method for porous nano-hydroxyapatite microspheres with high porosity, and the preparation method comprises the following steps: Step 1: Adding nano-hydroxyapatite powder to water for preparing 10%-40% (w/v) hydroxyapatite paste; Step 2: Mixing the hydroxyapatite paste, pore-forming agents and oleic acid proportionally, ball-milling the mixtures in a ball mill for 6-24 hours, and obtaining uniform suspension liquid after ball-milling; Step 3: Adding the suspension liquid to organic composite agents, and mixing the suspension liquid and the organic composite agents proportionally; then, putting the mixtures in a water bath kettle with the temperature of 30-80°C, and stirring and dissolving the mixtures; Step 4: Granulating the suspension liquid dissolving uniformly in a spray drying manner, and obtaining solidified microspheres; Step 5: Making high temperature dewaxing treatment to the prepared solidified microspheres, and calcining the microspheres at high temperature to obtain the porous nano-hydroxyapatite microspheres with high porosity.
    Compared with the prior art, the preparation method has the beneficial effects that the size distribution of the hydroxyapatite composite microspheres prepared with the method is uniform, and the particle size distribution range is 10-100um; and the center particle size is 20-60}un. Organic phases are added in a mixing process so that the suspension stability of suspension liquid can be improved effectively; the size distribution of the prepared microspheres is uniform, and the particle size is larger than the size of microspheres prepared with a traditional spray drying method; the microspheres can be used as internal support materials of injections: the microspheres are better in sphere and high in porosity so that the injectable property of the materials can be improved.
    Brief Description of the Drawings Embodiment 1 A preparation method for porous nano-hydroxyapatite microspheres with high porosity of the embodiment comprises the following steps: Step 1: Adding nano-hydroxy apatite powder to water for preparing 10-40% (w/v) hydroxyapatite paste; Step 2: Mixing the hydroxyapatite paste, pore-forming agents and oleic acid proportionally, wherein the weight ratio of the hydroxyapatite paste to the pore-forming agents is 80:20. Ball-
    milling the mixtures in a ball mill for 6-24 hours, and obtaining uniform suspension liquid after ball-milling; the pore-forming agents are carbon powder.
    Step 3: Adding the suspension liquid to organic composite agents, and mixing the suspension liquid and the organic composite agents proportionally; then, putting the mixtures in a water bath kettle with the temperature of 80°C; the organic composite agents are the combination of gelatin, Arabic gum, chitosan and sodium alginate. The stirring speed of the water bath kettle is 600r/min, and the dissolving time is Sh.
    Step 4: Granulating the suspension liquid dissolving uniformly in a spray drying manner, and obtaining solidified microspheres, wherein the spraying temperature is 250°C, and the feeding speed is 10ml/min; the spraying pressure is 0.05MPa; Step 5: Making high temperature dewaxing treatment to the prepared solidified microspheres at the dewaxing temperature of 800°C for 120min; calcining the microspheres at the high temperature of 1000°C for 120min to obtain the porous nano-hydroxyapatite microspheres with high porosity. The particle size distribution range of the prepared porous nano-hyvdroxyapatite microspheres with high porosity in this embodiment 1 is 20-75pm, and the center particle size is 20- 60pm; the porosity is 78%. Embodiment 2 A preparation method for porous nano-hydroxy apatite microspheres with high porosity of the embodiment comprises the following steps: Step 1: Adding nano-hydroxyapatite powder to water for preparing 10%-40% (w/v) hydroxyapatite paste; Step 2: Mixing the hydroxyapatite paste, pore-forming agents and oleic acid proportionally, wherein the weight ratio of the hydroxyapatite paste to the pore-forming agents 1s 85:15. Ball- milling the mixtures in a ball mill for 6-24 hours, and obtaining uniform suspension liquid after ball-milling; the pore-forming agents are carbon powder.
    Step 3: Adding the suspension liquid to organic composite agents, and mixing the suspension liquid and the organic composite agents proportionally; then, putting the mixtures in a water bath kettle with the temperature of 50°C; the organic composite agents are the combination of gelatin, Arabic gum, chitosan and sodium alginate. The stirring speed of the water bath kettle is 250r/min, and the dissolving time is Sh.
    Step 4: Granulating the suspension liquid dissolving uniformly in a spray drying manner, and obtaining solidified microspheres, wherein the spraying temperature is 250°C, and the feeding speed is 10ml/min; the spraying pressure is 0.05MPa.
    Step 5: Making high temperature dewaxing treatment to the prepared solidified microspheres at the dewaxing temperature of 1,500°C for 60min; calcining the microspheres at the high temperature of 1,000°C for 180min to obtain the porous nano-hydroxyapatite microspheres with high porosity. The particle size distribution range of the prepared porous nano-hydroxyapatite microspheres with high porosity in this embodiment 2 is 60-85um, and the center particle size is 20- 60um; the porosity is 78%. Embodiment 3 A preparation method for porous nano-hydroxy apatite microspheres with high porosity of the embodiment comprises the following steps: Step 1: Adding nano-hydroxyapatite powder to water for preparing 10%-40% (w/v) hydroxyapatite paste; Step 2: Mixing the hydroxyapatite paste, pore-forming agents and oleic acid proportionally, wherein the weight ratio of the hydroxyapatite paste to the pore-forming agents is 93:5. Ball-milling the mixtures in a ball mill for 6-24 hours, and obtaining uniform suspension liquid after ball- milling; the pore-forming agents are carbon powder.
    Step 3: Adding the suspension liquid to organic composite agents, and mixing the suspension liquid and the organic composite agents proportionally; then, putting the mixtures in a water bath kettle with the temperature of 50°C; the organic composite agents are the combination of gelatin, Arabic gum, chitosan and sodium alginate. The stirring speed of the water bath kettle is 250r/min, and the dissolving time is Sh.
    Step 4: Granulating the suspension liquid dissolving uniformly in a spray drying manner, and obtaining solidified microspheres, wherein the spraying temperature is 250°C, and the feeding speed is 10ml/min; the spraving pressure is 0. 1MPa: Step 5: Making high temperature dewaxing treatment to the prepared solidified microspheres at the dewaxing temperature of 1,500°C for 60min; calcining the microspheres at the high temperature of 1,000°C for 180min to obtain the porous nano-hydroxvapatite microspheres with high porosity. The particle size distribution range of the prepared porous nano-hvdroxvapatite microspheres with high porosity in this embodiment 3 is 50-85um, and the center particle size is 20- 60pm; and the porosity is 89%. The porosity of the porous nano-hydroxyapatite microspheres with high porosity prepared with the method provided by this embodiment is high, and the pores almost penetrate completely; and the mechanical strength is moderate.
    权利要求:
    Claims (5)
    [1]
    1. A preparation method for high porosity porous nanohydroxyapatite microspheres, the preparation method comprising the following steps: Step 1: Adding nanohydroxvapatite powder to water to prepare a 10-40% (w / v) hydroxyapatite paste: Step 2: Evenly mixing the hydroxvapatite paste with pore-forming agent and oleic acid, milling the mixture in a ball mill for 6-24 hours, and obtaining a uniform slurry liquid after the ball milling; Step 3: Add the suspending liquid to organic compounding agents, and mixing the suspending liquid and the compounding agents proportionally, then placing the mixtures in a 30-80 ° C water bath and stirring and dissolving the mixtures; Step 4: Granulating the uniform suspension liquid by spray drying to obtain solidified microspheres; Step 5: Dewashing the obtained solidified microspheres at high temperature, and calcination at high temperature to obtain the porous nano-hydroxyapatite microspheres with high porosity; Step 6: Embedding drugs in the high porosity porous nano-hydroxyapatite microspheres; Step 7: Preparing a mixed suspension liquid with water-soluble alginate and the high porosity porous nano-hydroxyapatite microspheres uniformly dispersed, and water-soluble calcium salt solutions separately; Step 8: Add the water-soluble calcium salt solutions to the mixed suspension liquid by spray drying; after gelation of the mixed suspension liquid, immerse the mixed suspension liquid in the water-soluble calcium salt solutions for 10 minutes to 24 hours to obtain a porous nano-hydroxyapatite sustained release gel.
    [2]
    The method of producing porous high porosity nano-hydroxyapatite microspheres according to claim 1, wherein the weight ratio of the hydroxyapatite suspension to the pore-forming agent is 80-95: 20-5; the organic compounding agents are any combination of one or more of gelatin, gum arabic, chitosan, sodium alginate, polylactic acid and natural cellulose; the pore-forming agents are any combination of one or more of carbon powder, graphite powder and acetylene black: the agitation speed of the water bath is 200-600 rpm and the dissolution takes 2-5 hours; the temperature of the dewaxing treatment is 800-1500 ° C and the dewaxing treatment lasts 30-120 minutes.
    [3]
    The production method for a porous high porosity nano-hydroxyapatite microspheres according to claim 1, wherein the high temperature calcination is at 1000-1500 ° C, and the calcination time is 45-180 min.
    [4]
    The production method for a porous nano-hydroxyapatite sustained release gel according to claim 1, wherein the spraying temperature is 250-500 ° C, the feed rate is 10-30 ml / min and the spray pressure is 0.05-0.1 MPa.
    [5]
    A high porosity porous nanohydroxvapation unicrospheres according to any one of claims 1-4, wherein the particle size distribution of the high porosity nanohydroxvapatite microspheres is 10-100 µm, the median particle size is 20-60 µm, and the porosity factor is 60-9094. .
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    同族专利:
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    CN109529111A|2019-03-29|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CN101343054B|2008-08-19|2011-03-16|华南理工大学|Preparation method of hydroxyapatite microsphere|
    WO2015134469A1|2014-03-03|2015-09-11|Bioway Scientific Llc|Spherical porous hydroxyapatite sorbent and methods thereof|
    CN108178656B|2018-01-11|2020-10-20|江西理工大学|High-porosity porous ceramic microsphere and preparation method thereof|
    CN109529110A|2018-12-10|2019-03-29|上海摩漾生物科技有限公司|Porous nano hydroxyapatite sustained-release gel preparation method|BE1027375B1|2018-12-10|2021-01-26|Shanghai Moyang Biotechnology Co Ltd|High porosity porous nanohydroxyapatite microsphere and its preparation process|
    CN110681323B|2019-08-26|2021-12-21|上海摩漾生物科技有限公司|Golf ball type degradable microsphere with micro-topological structure and preparation method thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    CN201811514912.5A|CN109529111A|2018-12-12|2018-12-12|High porosity porous nano hydroxyapatite micro-sphere and preparation method thereof|
    CN201910324114.4A|CN110538347A|2018-12-12|2019-04-22|High-porosity porous nano hydroxyapatite microspheres and preparation method thereof|
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