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Preparation method of porous microspheres by carbon dioxide fluid anti-solvent method

A technology of carbon dioxide and porous microspheres, which can be used in pharmaceutical formulations, medical preparations with non-active ingredients, and non-active components of polymer compounds, etc., which can solve the problems of non-porous surface of porous microspheres, non-penetrating holes, and inconspicuous holes.

Active Publication Date: 2012-10-03
HUAQIAO UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] There are few reports on the preparation of porous microspheres by the supercritical carbon dioxide anti-solvent method. Based on the reports that have been seen, practitioners have concluded that there are the following problems: the pores on the surface of porous microspheres are not obvious under the scanning electron microscope, and it is necessary to use instruments to Recognizable; even the problem that the surface of porous microspheres is non-porous, the interior is hollow, or the holes are not connected to each other
These issues are disadvantageous for pulmonary delivery as a drug carrier

Method used

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  • Preparation method of porous microspheres by carbon dioxide fluid anti-solvent method
  • Preparation method of porous microspheres by carbon dioxide fluid anti-solvent method
  • Preparation method of porous microspheres by carbon dioxide fluid anti-solvent method

Examples

Experimental program
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Effect test

Embodiment 1

[0039] Weigh 112.5mg of L-polylactic acid and 37.5mg of surfactant PF-127 and dissolve them in 10mL of dichloromethane and mix well to obtain an oil phase with a mass concentration of 1.5%; The ammonium aqueous solution is the water phase, and 1.0 mL of the water phase is added dropwise to the oil phase with a mass concentration of 1.5% to form a mixed solution, and then the mixed solution is placed in an ice bath for ultrasonic emulsification to produce Obtain a water-in-oil emulsion; pretreat the autoclave, specifically: liquefy the carbon dioxide through the refrigeration system, then pressurize the liquefied carbon dioxide by a high-pressure plunger pump and pump it into the autoclave, and wait until the predetermined temperature is reached in the autoclave. Temperature and pressure, wherein the temperature is 28 ° C, the pressure is 8 MPa, maintain the pumping rate of carbon dioxide, open the vent valve of the autoclave at a distance of 1.8 m 3 Deflate at a rate of / h, an...

Embodiment 2

[0041] The flow rate of the water-in-oil emulsion sprayed into the autoclave becomes 1.0mL / min, and other conditions and operations are the same as in Example 1. The morphology of the obtained porous microspheres observed under a scanning electron microscope is as follows: figure 2 shown.

Embodiment 3

[0043] Weigh 157.5mg of L-polylactic acid and 52.5mg of surfactant PF-127 and dissolve them in 10mL of dichloromethane and mix well to obtain an oil phase with a mass concentration of 2.1%; The ammonium aqueous solution is the water phase, and 1.0 mL of the water phase is added dropwise to the oil phase with a mass concentration of 2.1% to form a mixed solution, and then the mixed solution is placed in an ice bath for ultrasonic emulsification to obtain an oil Water-in-emulsion; pretreatment of the autoclave, specifically: liquefying carbon dioxide through the refrigeration system, and then pressurizing the liquefied carbon dioxide by a high-pressure plunger pump and pumping it into the autoclave until the predetermined temperature and temperature in the autoclave are reached. pressure, wherein the temperature is 28°C and the pressure is 8MPa, maintain the pumping rate of carbon dioxide, open the vent valve of the autoclave at 1.8m 3 Deflate at a rate of / h, and adjust the ext...

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Abstract

The invention provides a preparation method of porous microspheres by carbon dioxide fluid anti-solvent method. The method comprises the steps of sequentially preparing oil phase and water-in-oil emulsion, passing the water-in-oil emulsion through a high-pressure pump, and injecting into a pre-treated high-pressure kettle through a steel needle head, to precipitate out polymer microspheres embedded with ammonium bicarbonate particles; after emulsion injection, maintaining pressure and temperature in the high-pressure kettle, while keeping introduction of carbon dioxide to flush and clear away residual solvent; after flushing, slowly releasing pressure in the high-pressure kettle to atmospheric pressure, and collecting loose powdery product; and performing thermal decomposition on the powdery product at 50 DEG C under vacuum dry condition to obtain the porous microspheres. The method has the advantages of simple operation procedure, low organic solvent residue, large geometrical particle size and small aerodynamic diameter of prepared porous microspheres.

Description

【Technical field】 [0001] The invention relates to a method for preparing a drug carrier, in particular to a method for preparing porous microspheres, in particular to a method for preparing porous microspheres by a carbon dioxide fluid anti-solvent method. 【Background technique】 [0002] Compared with solid polymer microspheres with the same particle size, porous microspheres have a porous network structure, which can not only be used in the fields of adsorption, immobilized enzymes, separation and purification of biological macromolecules, but also in terms of pharmaceutical carriers, by virtue of their own Low density, irregular surface morphology, better aerodynamic properties and lung settlement performance have become the first choice for pulmonary administration dosage forms. [0003] The traditional preparation methods of porous microspheres mainly include spray drying method and emulsification method. The former is easy to operate and has good reproducibility, but w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K47/32A61K47/34A61K47/36A61K47/42
Inventor 陈爱政王士斌赵趁刘源岗
Owner HUAQIAO UNIVERSITY