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Method for preparing surface-closed medicine-carrying porous polymer microsphere based on supercritical fluid technology

A porous polymer, supercritical fluid technology, applied in pharmaceutical formulations, medical preparations containing active ingredients, and devices that make medicines into special physical or oral forms, etc., can solve the problem of excessive organic solvent content and organic solvent dosage Large, inactivation and denaturation problems, to achieve the effect of low solvent residue, mild operating conditions, and less drug loss

Inactive Publication Date: 2013-03-13
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method is simple to operate, there are some shortcomings and deficiencies, such as a large amount of organic solvent, excessive residual organic solvent content in the product, and the most important thing is that it will cause the loss and inactivation of the drug encapsulated in the porous microspheres.
With the improvement of living standards, people's requirements for drug efficacy and safety are getting higher and higher. This method is obviously difficult to meet the needs of society.

Method used

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  • Method for preparing surface-closed medicine-carrying porous polymer microsphere based on supercritical fluid technology
  • Method for preparing surface-closed medicine-carrying porous polymer microsphere based on supercritical fluid technology
  • Method for preparing surface-closed medicine-carrying porous polymer microsphere based on supercritical fluid technology

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preparation example Construction

[0018] The method for preparing the surface-sealed drug-loaded porous polymer microspheres based on supercritical fluid technology comprises the following steps:

[0019] 1) Dissolve the mixture of polymer and poloxamer with a mass ratio of 7:3 in 30ml of dichloromethane to prepare a solution with a mass volume concentration of the mixture of 3-5%. Dissolve 2mg of the drug in this solution, and polymerize the obtained Add the mixed solution of drug and drug to 450ml of polyvinyl alcohol aqueous solution with a mass volume concentration of 1%, stir for 3min at 3000rpm using a homogenizer, and place the obtained emulsion in a water bath at 30°C for 5h, then centrifuge at 8000rpm, wash and dry Obtain drug-loaded interconnected porous polymer microspheres;

[0020] 2) Place 50 mg of the prepared drug-loaded interconnected porous polymer microspheres in the autoclave of the supercritical fluid porous polymer microsphere sealing system;

[0021] 3) Carbon dioxide is introduced into...

Embodiment 1

[0025] Example 1: Preparation of Polylactic Acid Loaded Dexamethasone Closed Porous Microspheres

[0026] First, dissolve the mixture of polylactic acid (molecular weight 22000) and poloxamer f-127 with a mass ratio of 7:3 in 30ml of dichloromethane to prepare a solution with a concentration of 3%, and dissolve 2mg of dexamethasone in this solution , Pour the obtained polymer and drug mixed solution into 450ml of 1% (w / v) polyvinyl alcohol aqueous solution, use a homogenizer to stir at 3000rpm for 3min, and the obtained emulsion is placed in a water bath at 30°C for 5h, and then at 8000rpm After centrifugation, washing and drying, the drug-loaded connected porous polylactic acid microspheres are obtained, and the particle diameter of the obtained microspheres is 14.69±4.48 μm. Put 50 mg of drug-loaded interconnected porous polylactic acid microspheres into filter paper and place them in an autoclave, and use a cooling tank to cool the carbon dioxide gas flowing out of the carb...

Embodiment 2

[0027] Example 2: Preparation of polylactic acid-glycolic acid copolymer loaded roxithromycin closed porous microspheres

[0028] First, a mixture of polylactic acid-glycolic acid copolymer (LA:GA, 85:15; molecular weight 50,000,) with a mass ratio of 7:3 and poloxamer f-127 was dissolved in 30ml of dichloromethane to prepare a concentration of 3 % solution, take 2mg roxithromycin and dissolve in this solution, pour the resulting polymer and drug mixed solution into 450ml concentration of 1% (w / v) polyvinyl alcohol aqueous solution, use a homogenizer to stir at 3000rpm After 3 minutes, the obtained emulsion was placed in a water bath at 30°C for 5 hours, then centrifuged at 8000rpm, washed and dried to obtain drug-loaded interconnected porous polylactic acid-glycolic acid copolymer microspheres with a particle size of 15.32±5.48 μm. Put 50 mg of drug-loaded connected porous polylactic acid-glycolic acid copolymer microspheres into filter paper and place them in an autoclave, a...

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Abstract

The invention discloses a method for preparing surface-closed medicine-carrying porous polymer microsphere based on a supercritical fluid technology. The method comprises the following steps of: dispersing a dichloromethane solution of a polymer, poloxamer serving as a pore-foaming agent and a medicinal mixture in a polyvinyl alcohol aqueous solution to form emulsion, performing water bath and drying to obtain a medicine-carrying communication porous polymer microsphere; putting the medicine-carrying communication porous polymer microsphere into a high-pressure autoclave; and introducing supercritical carbon dioxide to contact the medicine-carrying communication porous polymer microsphere fully, closing communication holes on the surface of polymer microsphere under the plasticizing action of the supercritical carbon dioxide on a polymer, and releasing pressure to form the surface-closed medicine-carrying porous polymer microsphere. The method has a simple operating process, is mild in operating conditions and stable in process; and by the method, solvent residues can be removed in the process for preparing the medicine-carrying communication porous polymer microsphere, the burst release of medicines is avoided, and the method can be applied to sustained and controlled release administration systems.

Description

technical field [0001] The invention relates to a method for preparing surface-sealed drug-loaded porous polymer microspheres based on supercritical fluid technology. Background technique [0002] In recent years, polymer porous microspheres have been used more and more widely as drug carriers for sustained and controlled release. Compared with solid microspheres, porous microspheres have low density and small aerodynamic particle size and are suitable for blood administration and lung administration. Medicines and other aspects have great advantages. For example, pulmonary drug delivery requires the aerodynamic particle size of the drug particles to be between 1-5 μm (Journal of Supercritical Fluids, 2003, 26:243-252), but solid particles with an aerodynamic particle size between 1-5 μm Microspheres can be specifically cleared by lung macrophages (Advances in Polymer Science, 1990, 90:107-141), so porous microspheres with larger geometric diameter and aerodynamic particle ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/34A61K31/5383A61K31/573A61K31/7048A61J3/00
Inventor 关怡新唐川余金鹏刘倩倩姚善泾朱自强
Owner ZHEJIANG UNIV
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