CN103768658B - Hydroxyapatite-loading polylactic acid porous microsphere and preparation method thereof - Google Patents
Hydroxyapatite-loading polylactic acid porous microsphere and preparation method thereof Download PDFInfo
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- CN103768658B CN103768658B CN201210396694.6A CN201210396694A CN103768658B CN 103768658 B CN103768658 B CN 103768658B CN 201210396694 A CN201210396694 A CN 201210396694A CN 103768658 B CN103768658 B CN 103768658B
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Abstract
The invention provides a hydroxyapatite-loading polylactic acid composite porous microsphere which is characterized in that: the composite porous microsphere has an obvious pore appearance structure, the particle size is 50-500 mum, the pore diameter is 5-20 mum, the inside of the microsphere and external environment are communicated, and the water absorption rate is 900-3200%. The invention also provides a preparation method of the hydroxyapatite-loading polylactic acid composite porous microsphere. The prepared hydroxyapatite-loading polylactic acid composite porous microsphere can be used as an adult cell growth scaffold, also can be used as an attachment scaffold for stem cell growth and differentiation, and can be used in tissue engineering. The preparation method of the composite porous microsphere is simple and convenient in operation, low in cost, safe in use, and is favorable for market promotion.
Description
Technical field
The present invention relates to a kind of porous microsphere and preparation method thereof, particularly relate to porous polylactic acid microball of a kind of load hydroxyapatite and preparation method thereof, belong to field of tissue engineering technology.
Background technology
Porous polymer bead, refers to that material is made up of macromolecular material, and particle size range is between 1-1000 micron, and surface has the microsphere of all vesicular textures.Can be used for the fields such as medicament slow release, cytoskeleton, cell infusion at present.
The macromolecular material preparing porous microsphere at present mainly contains polylactic acid, the polyesters macromolecular materials such as the blend of polylactic acid and polycaprolactone or lactic acid-caprol acton copolymer.Above-mentioned material has good biological degradability and biological safety and is widely used as tissue engineering bracket and pharmaceutical carrier field (Lin Sun, 2009; Hyun Jung Chung, 2006; Stefano Giovagnoli, 2007).But prepared porous microsphere also exists various problem, main cause is that pH value reduces and easily causes inflammation because catabolite is in acid.
The light base apatite of inorganic material, is widely used as organizational project because having good biocompatibility, the research that particularly orthopaedics is relevant.Hydroxyapatite discharges weakly alkaline ion in aqueous, just in time can be used for neutralizing the acid problem of above-mentioned Degradation of Polymer Materials product, can also improve the biological activity of material in addition.
Jointly report less as carrier about polylactic acid and hydroxyapatite at present, both compounds are prepared porous microsphere, and at home and abroad there is not been reported.
Summary of the invention
One of the object of the invention is to provide a kind of polylactic acid composite porous microspheres of load hydroxyapatite, can be used as the support of cell adhesion in organizational project.
A polylactic acid composite porous microspheres for load hydroxyapatite, is characterized in that, the outward appearance of composite porous microspheres has obvious cavernous structure, its particle diameter is 50 ~ 500 μm, aperture is 5 ~ 20 μm, be connected inner for microsphere with external environment, its water absorption rate is 900 ~ 3200%.
The present invention also provides a kind of preparation method of polylactic acid composite porous microspheres of load hydroxyapatite, it is characterized in that comprising the steps:
Macromolecular material and hydroxyapatite are dissolved in organic solvent, heating also condensing reflux is dissolved simultaneously, makes its macromolecular material and hydroxyapatite dispersion in organic solvent, forms organic facies;
(2) ammonium bicarbonate solubility is in water, normal-temperature dissolution, forms aqueous phase I;
(3) polyethylene alcoholysis is in water, during high-temperature digestion, forms aqueous phase II;
(4) take out above-mentioned organic facies and be placed in dry small beaker, add above-mentioned aqueous phase I, carry out homogenized subsequently, form emulsion;
(5) be added drop-wise in aqueous phase II by emulsion even speed at once, magnetic stir bar after 4 hours, by centrifugal for microsphere 5 minutes, then uses ultra-pure water Eddy diffusion with stirring at low speed, repeatedly washes away unnecessary PVA 3 times, then by microsphere lyophilization process.
Described macromolecular material is the blend of polylactic acid and polycaprolactone, or lactic acid-caprol acton copolymer.
Described macromolecular material is 2 ~ 8g/100ml at the final concentration of organic facies, and described hydroxyapatite is 2 ~ 4g/100ml at the final concentration of organic facies.
The final concentration that described ammonium bicarbonate is dissolved in aqueous phase I is 5 ~ 20 g/100ml.
Described polyvinyl alcohol is 0.1 ~ 1 g/100ml at the final concentration of aqueous phase II.
The volume ratio of described aqueous phase I and organic facies is 3:1 ~ 5:1.
Polylactic acid composite porous microspheres of load hydroxyapatite disclosed by the invention and preparation method thereof, can be used as the support of cell adhesion in organizational project.The polylactic acid composite porous microspheres particle diameter of prepared load hydroxyapatite is 50-500 μm, its outward appearance has obvious cavernous structure, and aperture is 5-20 μm, is connected inner for microsphere with external environment, increase its hydrophilic by load hydroxyapatite, water absorption rate is 900-3200%.Prepared composite porous microspheres is used for the support of adult cell growth, also can be used as the support of stem cell growth and differentiation phase attachment, is applied to organizational project.In the present invention, the preparation method of composite porous microspheres, simple to operation, with low cost, and use safety is conducive to marketing.
accompanying drawing illustrates:
Fig. 1 is the schematic diagram of the polylactic acid composite porous microspheres of load hydroxyapatite of the present invention.
Wherein 1 polylactic acid component, 2 is hydroxyapatite component, and 3 is cavernous structure.
Fig. 2 is the schematic diagram scanning electron microscope diagram of the polylactic acid composite porous microspheres of load hydroxyapatite of the present invention.
Detailed description of the invention
Embodiment 1:
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 200rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 201.4 ± 51.6 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 23.4 ± 5.2 μm.Water absorption rate is 2045.7%.
Embodiment 2:
Take the polylactic acid of 200 mg, the hydroxyapatite of 400mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 200rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 164.5 ± 31.1 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 11.5 ± 3.1 μm.Water absorption rate is 1743.0%.
Embodiment 3:
Take the polylactic acid of 400 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 5g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 200rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 274.2 ± 52.1 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 14.3 ± 3.1 μm.Water absorption rate is 913.9%.
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 20g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 200rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 300.2 ± 25.7 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 21.5 ± 5.2 μm.Water absorption rate is 2532.2%.
Embodiment 5:
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 0.2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 200rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 321.7 ± 16.4 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 35.3 ± 5.4 μm.Water absorption rate is 3190.5%.
Embodiment 6:
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 100rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 241.9 ± 13.8 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 32.1 ± 6.6 μm.Water absorption rate is 1969.1%.
Embodiment 7:
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 300rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 149.2 ± 8.1 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 12.2 ± 4.1 μm.Water absorption rate is 2285.2%.
Embodiment 8:
Take the polylactic acid of 200 mg, the hydroxyapatite of 200mg is dissolved in 5ml dichloromethane, and heating also condensing reflux dissolves 1 hour, and formation polylactic acid and hydroxyapatite are dispersed in the organic facies of dichloromethane.Take 10g ammonium bicarbonate solubility in 100ml water, normal-temperature dissolution 1 hour, form aqueous phase I.Take the alcoholysis of 2g polyethylene in 200ml water, high-temperature digestion 1 hour, form aqueous phase II.Take out above-mentioned organic facies 4ml and be placed in dry small beaker, add above-mentioned 1ml aqueous phase I, carry out homogenized subsequently, form emulsion.At once emulsion even speed is added drop-wise in the aqueous phase II of 200ml.After 3cm magnetic stir bar stirs 4 hours with the speed of 400rpm, by the centrifugation 5min of microsphere 50 rpm, then use the ultra-pure water Eddy diffusion of 200ml, 3 times repeatedly.By microsphere lyophilization process, both obtained the load hydroxyapatite/polylactic acid porous microsphere of white appearance.
Through sem observation, the mean diameter of hydroxyapatite/polylactic acid porous microsphere is 111.7 ± 6.9 μm, and its outward appearance has obvious cavernous structure, and be connected inner for microsphere with external environment, the average diameter of cavernous structure is 13.8 ± 8.1 μm.Water absorption rate is 1522.9%.
Claims (1)
1. the preparation method of the polylactic acid composite porous microspheres of a load hydroxyapatite, it is characterized in that, the outward appearance of described composite porous microspheres has obvious cavernous structure, its particle diameter is 50 ~ 500 μm, aperture is 5 ~ 20 μm, be connected inner for microsphere with external environment, its water absorption rate is 900 ~ 3200%, comprises the steps:
(1) macromolecular material and hydroxyapatite are dissolved in organic solvent, heating also condensing reflux is dissolved simultaneously, makes its macromolecular material and hydroxyapatite dispersion in organic solvent, forms organic facies;
(2) ammonium bicarbonate solubility is in water, normal-temperature dissolution, forms aqueous phase I;
(3) polyvinyl alcohol dissolution is in water, during high-temperature digestion, forms aqueous phase II;
(4) take out above-mentioned organic facies and be placed in dry small beaker, add above-mentioned aqueous phase I, carry out homogenized subsequently, form emulsion;
(5) be added drop-wise in aqueous phase II by emulsion even speed at once, magnetic stir bar after 4 hours, by centrifugal for microsphere 5 minutes, then uses ultra-pure water Eddy diffusion with stirring at low speed, repeatedly washes away unnecessary PVA 3 times, then by microsphere lyophilization process;
Described macromolecular material is the blend of polylactic acid and polycaprolactone, or lactic acid-caprol acton copolymer;
Described macromolecular material is 2 ~ 8g/100ml at the final concentration of organic facies, and described hydroxyapatite is 2 ~ 4g/100ml at the final concentration of organic facies;
The final concentration that described ammonium bicarbonate is dissolved in aqueous phase I is 5 ~ 20 g/100ml;
Described polyvinyl alcohol is 0.1 ~ 1 g/100ml at the final concentration of aqueous phase II;
The volume ratio of described aqueous phase I and organic facies is 3:1 ~ 5:1.
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| CN107041964A (en) * | 2016-02-05 | 2017-08-15 | 北京化工大学 | Composite, preparation method and use |
| CN105797217A (en) * | 2016-03-15 | 2016-07-27 | 深圳市汉强医用材料有限公司 | Porous micro-sphere bone repair material and preparing method thereof |
| CN107519536B (en) * | 2017-08-04 | 2019-11-26 | 武汉理工大学 | A kind of controllableization preparation method and application of polylactic acid/hydroxy apatite complex microsphere surface porosity |
| CN107670113A (en) * | 2017-09-15 | 2018-02-09 | 大连理工大学 | A kind of preparation method of cell three-dimensional amplification cultivation microcarrier |
| CN108744060B (en) * | 2018-05-29 | 2021-05-07 | 四川大学 | Bone repair material capable of being injected with multiple pore structures and preparation method thereof |
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| CN109265942B (en) * | 2018-08-16 | 2021-10-19 | 张海军 | Polylactic acid microsphere and preparation method and application thereof |
| CN110404115B (en) * | 2019-07-23 | 2022-03-18 | 广东省医疗器械研究所 | Carbonate/degradable polymer microsphere with surface pits and preparation method and application thereof |
| WO2023093532A1 (en) * | 2021-11-29 | 2023-06-01 | 爱美客技术发展股份有限公司 | Composite gel, preparation method, and application |
| CN116617466A (en) * | 2023-07-21 | 2023-08-22 | 北京万洁天元医疗器械股份有限公司 | Injectable gel and preparation method thereof |
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| CN101138651B (en) * | 2007-09-14 | 2012-04-18 | 华中科技大学 | Method of preparing organization bracket performing selectivity laser sintering by using macromolecule microsphere |
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| CN101590388A (en) * | 2009-06-18 | 2009-12-02 | 重庆文理学院 | A kind of preparation method of nano hydroxyapatite/polylactic acid composite microspheres |
| CN101804032B (en) * | 2010-04-09 | 2012-08-08 | 华南理工大学 | Preparation method of 5-fluorouracil-wrapped biodegradable polylactic acid/nano-hydroxyapatite compound microspheres |
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