CN101972212A - Method for preparing core-shell type composite microspheres by supercritical fluid technology - Google Patents
Method for preparing core-shell type composite microspheres by supercritical fluid technology Download PDFInfo
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- CN101972212A CN101972212A CN2010105297641A CN201010529764A CN101972212A CN 101972212 A CN101972212 A CN 101972212A CN 2010105297641 A CN2010105297641 A CN 2010105297641A CN 201010529764 A CN201010529764 A CN 201010529764A CN 101972212 A CN101972212 A CN 101972212A
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Abstract
The invention discloses a method for preparing core-shell type composite microspheres by a supercritical fluid technology. The method comprises the following steps of: dissolving a polymer into an organic solvent which cannot be used for dissolving core material particles; dispersing the core material particles into the organic solvent of the polymer to obtain a suspension; then putting the suspension in a suspension conveying device; pumping in supercritical pure fluid through the suspension conveying device to form a solvent resistant effect to ensure that a polymer precipitate is separated out and coated on the surfaces of the core material particles so as to form core-shell type composite microspheres. The invention can improve the drug encapsulation rate and the slow releasing effect.
Description
Technical field
The present invention relates to a kind of method of the novel hud typed complex microsphere of preparation, particularly supercritical fluid technology prepares the method for hud typed complex microsphere.
Background technology
Supercritical carbon dioxide fluid is nontoxic, not flammable, relatively cheap, solvability is higher, capable of circulation, critical point is low, the supercritical carbon dioxide fluid technology is prepared pharmaceutical carrier and has the reaction condition gentleness, temperature is low, technology is simple, do not have or do not have substantially advantages such as dissolvent residual, product cut size are little, controllable size distribution, so the supercritical carbon dioxide fluid technology is used widely in the research of medicine controlled releasing system.
In the supercritical carbon dioxide quick expanding method, can be with medicine and polymer dissolution in supercritical carbon dioxide fluid, make medicine and polymer precipitation separate out through blood pressure lowering fast then and form the drug-polymer complex microsphere; Perhaps earlier with polymer dissolution in supercritical carbon dioxide fluid, the drug particles that will be insoluble to supercritical carbon dioxide fluid then is dispersed in the supercritical carbon dioxide solution of polymer, make polymer overmold on the drug particles surface through quick blood pressure lowering again, form the drug-polymer complex microsphere.Then because most medicine and polymer are insoluble to supercritical carbon dioxide fluid substantially, so the application of supercritical carbon dioxide quick expanding method is greatly limited.
When the material of desiring nucleation is insoluble to supercritical carbon dioxide fluid, can select a kind of this material of dissolution with solvents that can dissolve supercritical carbon dioxide fluid.When the supercritical carbon dioxide fluid as anti-solvent fully contacts with this solution, supercritical carbon dioxide fluid is diffused in the solution rapidly, liquor capacity expands, density descends, solvability descends, solution supersaturation and nucleation is separated out the solute microgranule, the ultimate principle of supercritical carbon dioxide anti-solvent method that Here it is.The supercritical carbon dioxide anti-solvent method has overcome the limitation of supercritical carbon dioxide quick expanding method, in the method, can be with medicine and polymer dissolution in one or more organic solvents, pump into supercritical carbon dioxide fluid through high-pressure pump then and carry out anti-solvent action, medicine and polymer supersaturation co-precipitation are separated out, thereby obtain the drug-polymer complex microsphere.Loosen but the medicine major part that the shortcoming of this method maximum is co-precipitation to be separated out combine attached to polymer microballoon surface or with polymer microballoon, cause that entrapment efficiency is low, the shortcoming of slow release effect difference.
For improving above-mentioned shortcoming, imagination forms uniform suspension if drug particles can be dispersed in the polymer solution, then this suspension is pumped into supercritical carbon dioxide fluid through high-pressure pump and carry out anti-solvent action, be coated on drug particles surface and form hud typed drug-polymer complex microsphere thereby polymer precipitation separated out, then can improve entrapment efficiency and slow release effect.But, cause this method to be difficult to implement because the drug particles in the suspension very easily causes the damage of high-pressure pump check valve.
Summary of the invention
The object of the present invention is to provide a kind of method of the novel hud typed complex microsphere of preparation, it is the method that supercritical fluid technology prepares hud typed complex microsphere, to form hud typed drug-polymer complex microsphere, then can improve entrapment efficiency and slow release effect.
The objective of the invention is to be achieved through the following technical solutions:
Earlier with polymer dissolution in can not dissolving the particulate organic solvent of core material, again the core material Dispersion of Particles is obtained suspension in the organic solvent of polymer, then this suspension is placed the suspension conveyer device, pump into the pure fluid of supercritical through this suspension conveyer device and carry out anti-solvent action, polymer precipitation is separated out be coated on the core material particle surface, form hud typed complex microsphere.
Wherein, the suspension conveyer device includes but not limited to columniform piston container, also comprises the device of any operation principle syringe-like; The thrust source of this device includes but not limited to the fluid pressure of high-pressure pump, also comprises any device that equivalent action is provided.
The pure fluid of supercritical is a CO 2 fluid, can also be other pure fluid.
Anti-solvent action comprises that all are based on the technology of carbon dioxide as anti-solvent principle, promptly act as the technology that the basis derives, comprise the gas anti-solvent method, compress anti-solvent precipitation, the aerosol solvent extraction, strengthen that quality is transmitted the supercritical anti-solvent method, supercritical fluid is forced dispersion method etc. with supercritical carbon dioxide anti-solvent.
The core material granule includes but not limited to drug particles, can also be any material that is insoluble to supercritical carbon dioxide and dissolving coated polymer solvent for use.
Concrete operations of the present invention can be such:
The first, the polymer suspension of preparation core granule: elder generation in the organic solvent that can not dissolve core granule, adds polymer dissolution in this polymer solution then with core granule, ultra-sonic dispersion evenly is placed on piston container front portion;
Second, the supercritical carbon dioxide anti-solvent process: the carbon dioxide in the steel cylinder is after refrigeration system liquefaction, pressurize by high-pressure plunger pump, after heating up by the water bath with thermostatic control in the pipeline again, pump in the autoclave, treat to meet the requirements of in the still pressure, keep carbon dioxide and pump into speed, open vent valve and exit, and regulate outside drying baker of autoclave and pipeline bath temperature, to keep still internal pressure, temperature constant with given pace; Reach experiment temperature required after, supercritical carbon dioxide is by the coaxial two streaming nozzle outer passage in autoclave top, the polymer suspension that contains core granule by the high-pressure pump thrust through the piston container by the nozzle inner channel, pump into autoclave simultaneously; Suspension is kept pressure and temperature-resistant after carrying and finishing, and continues to feed carbon dioxide drip washing a period of time, and slowly release when treating that the still internal pressure is reduced to normal pressure, is collected product.
The present invention has improved entrapment efficiency and slow release effect.
Description of drawings
Fig. 1 is novel shooting flow body device sketch map;
Fig. 2 is a) SiO of SEM shape appearance figure
2, b) SiO
2-PLLA, c) 5-Fu-SiO
2, d) 5-Fu-SiO
2-PLLA;
Fig. 3 is 5-Fu-SiO
2Particle size distribution figure;
Fig. 4 is 5-Fu-SiO
2-PLLA particle size distribution figure.
The specific embodiment
With surface adsorption the nanometer SiO of 5-fluorouracil (5-Fu)
2Be dispersed in the polylactic acid dichloromethane solution of 0.5% (wt/v), ultra-sonic dispersion evenly is placed on piston container front portion as shown in Figure 1.
Carbon dioxide in the steel cylinder is after refrigeration system (condenser) liquefaction, pressurize by high pressure (plunger) pump, after heating up by the water bath with thermostatic control in the pipeline (heat exchanger) again, pump in the autoclave, treat to meet the requirements of pressure in the still, keep carbon dioxide and pump into speed, open vent valve and exit with given pace, and regulate outside drying baker of autoclave and pipeline bath temperature, to keep still internal pressure, temperature constant.Reach experiment temperature required after, supercritical carbon dioxide is by the coaxial two streaming nozzle outer passage in autoclave top, the initial feed liquid of low concentration, high saturation by the nozzle inner channel, pumps into autoclave by high-pressure pump simultaneously.System pressure is that 12MPa, temperature are that 306K, carbon dioxide flow velocity are 25NL/h, and the flow velocity of high-pressure pump is 1.0ml/min.After finishing the pump sample, keep pressure and temperature-resistant, continue to feed carbon dioxide drip washing 30 minutes, slowly release when treating that the still internal pressure is reduced to normal pressure, is collected product.
Fig. 2 is SiO
2And 5-Fu-SiO
2Coat the SEM shape appearance figure of polylactic acid front and back, experimental result shows, thereby utilizes this novel shooting flow body device successfully polymer overmold to be formed hud typed complex microsphere on the surface of core granule.
Fig. 3 and Fig. 4 are respectively 5-Fu-SiO
2Coat the particle size distribution figure of polylactic acid front and back, coating the back mean diameter is 536nm by the 266nm increase, has verified further that also polymer successfully is coated on the core granule surface.
Claims (3)
1. supercritical fluid technology prepares the method for hud typed complex microsphere, it is characterized in that: earlier with polymer dissolution in can not dissolving the particulate organic solvent of core material, again the core material Dispersion of Particles is obtained suspension in the organic solvent of polymer, then this suspension is placed the suspension conveyer device, pump into the pure fluid of supercritical through this suspension conveyer device and carry out anti-solvent action, polymer precipitation is separated out be coated on the core material particle surface, form hud typed complex microsphere.
2. supercritical fluid technology prepares the method for hud typed complex microsphere according to claim 1, and it is characterized in that: the suspension conveyer device is the device of columniform piston container or operation principle syringe-like; The thrust source of this device is the fluid pressure of high-pressure pump.
3. supercritical fluid technology prepares the method for hud typed complex microsphere according to claim 1, and it is characterized in that: the pure fluid of supercritical is a CO 2 fluid.
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Cited By (5)
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|---|---|---|---|---|
| CN103060094A (en) * | 2013-01-14 | 2013-04-24 | 福建正盛无机材料股份有限公司 | Preparation method of menthol/SiO2 as tobacco flavor sustained-release material |
| CN104412432A (en) * | 2012-07-06 | 2015-03-11 | 技术研究院 | Method of preparing a catalytic structure |
| CN104829856A (en) * | 2015-05-14 | 2015-08-12 | 贵州省材料产业技术研究院 | Method for coating surfaces of microspheres with epoxy resin layer by virtue of supercritical carbon dioxide |
| CN108117104A (en) * | 2017-12-01 | 2018-06-05 | 华侨大学 | A kind of method for preparing carbon blended metal oxide nano-particle |
| CN108853498A (en) * | 2018-07-05 | 2018-11-23 | 华侨大学 | A kind of preparation method and applications of indocyanine green polymer nano granules |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104412432A (en) * | 2012-07-06 | 2015-03-11 | 技术研究院 | Method of preparing a catalytic structure |
| CN104412432B (en) * | 2012-07-06 | 2018-04-27 | 技术研究院 | The method for preparing catalytic structure |
| CN103060094A (en) * | 2013-01-14 | 2013-04-24 | 福建正盛无机材料股份有限公司 | Preparation method of menthol/SiO2 as tobacco flavor sustained-release material |
| CN104829856A (en) * | 2015-05-14 | 2015-08-12 | 贵州省材料产业技术研究院 | Method for coating surfaces of microspheres with epoxy resin layer by virtue of supercritical carbon dioxide |
| CN104829856B (en) * | 2015-05-14 | 2018-03-27 | 贵州省材料产业技术研究院 | The method that critical carbon dioxide wraps epoxy resin layer in microsphere surface |
| CN108117104A (en) * | 2017-12-01 | 2018-06-05 | 华侨大学 | A kind of method for preparing carbon blended metal oxide nano-particle |
| CN108117104B (en) * | 2017-12-01 | 2019-11-12 | 华侨大学 | A method of preparing carbon blended metal oxide nanoparticle |
| CN108853498A (en) * | 2018-07-05 | 2018-11-23 | 华侨大学 | A kind of preparation method and applications of indocyanine green polymer nano granules |
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Application publication date: 20110216 |