Composite microsphere preparation of lactic acid-hydroxyacetic acid copolymer and its preparation process

A technology of composite microspheres and copolymers, applied in the field of pharmacy, can solve the problems of complex preparation method and large particle size, and achieve the effects of simple preparation method, delayed release and reduced burst release.

Active Publication Date: 2010-05-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The drug in this composite microsphere is completely encapsulated into the bilayer alginate-chitosan microsphere, so that the protein drug is protected by double hydrophilic polymers, not only has a suitable hydrophilic microenvironment, It is expected to improve the stability of the protein, and the composite microspheres maintain the high encapsulation efficiency of alginate-chitosan microspheres for BSA, which can make up for the low encapsulation efficiency of single PLGA microspheres, but the preparation method is complicated , the disadvantage of larger particle size (average particle size 30μm)

Method used

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  • Composite microsphere preparation of lactic acid-hydroxyacetic acid copolymer and its preparation process
  • Composite microsphere preparation of lactic acid-hydroxyacetic acid copolymer and its preparation process
  • Composite microsphere preparation of lactic acid-hydroxyacetic acid copolymer and its preparation process

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Effect test

Embodiment 1

[0026] Example 1 A preparation method of PLGA microspheres modified by alginic acid and chitosan of the present invention Weigh about 0.33g PLGA (50:50), dissolve in 4ml of dichloromethane as the organic phase; another weigh 30mg BSA Model drug, dissolved in 100μl distilled water and 100μl 1% sodium alginate as the inner water phase, after the two phases were mixed, the probe was ultrasonicated (50w, 1s×20 times), fully emulsified and injected into 40ml mixed solution (50ml 2%PVA+50ml 2% chitosan solution + 1g CaCl 2 The continuous filtrate of the mixed solution), 12000rpm high-speed stirring for 5min, vacuum rotary evaporation for 1h, centrifugation, washing with water 3 times, and freeze-drying. The alginic acid and chitosan modified PLGA microspheres with a size of 5 μm, a uniform particle size and a rounded shape were obtained.

[0027] The composite microsphere prepared by the method of the invention can obviously reduce the burst release phenomenon, and can adjust the r...

Embodiment 2

[0032] The same as Example 1, but the ratio of PLGA is 70:30, to obtain PLGA (70:30) microspheres modified by alginic acid and chitosan.

Embodiment 3

[0034] Same as Example 1, but the amount of PLGA weighed is 0.2g, dissolved in 2ml of dichloromethane as the organic phase, mixed with the water phase, then installed with a probe-type ultrasonic instrument, ultrasonicated at 200w, 40s, and injected with 20ml of the mixed solution after forming colostrum In the process, stirring at 800rpm for 3min, the encapsulation efficiency and particle size of PLGA microspheres modified by alginic acid and chitosan were not statistically different.

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Abstract

The composite microsphere preparation of lactic acid-hydroxyacetic acid copolymer consists of medicine, calcium alginate, chitosan, glycolide-lactide copolymer, emulsifier and medicine supplementary material. It is prepared through adding low concentration sodium alginate solution to inner water phase containing medicine, forming initial emulsion with PLGA-containing organic phase, injecting PVA solution with chitosan and calcium chloride to form complex emulsion, decompression rotary evaporation to cure, water washing and freeze drying. The process is simple and feasible, and has no influenceon the size of microsphere and no change in protein encapsulating rate, capacity of forming one hydrophilic micro environment to protect protein medicine, and capacity of reducing the release of medicine.

Description

technical field [0001] The invention belongs to the field of pharmacy, relates to a biodegradable microsphere preparation and a preparation method thereof, in particular to a hydrophobic biodegradable lactic acid-glycolic acid copolymer modified with natural hydrophilic biodegradable materials alginic acid and chitosan ( PLGA) composite microsphere preparation and preparation method thereof. This new type of compound preparation is of great significance for solving the phenomenon of sudden release of drugs encapsulated in sustained-release PLGA microspheres, especially for those drugs with strong potency, whose effective dose is close to the toxic dose, that is, with a small therapeutic window. Background technique [0002] Lactic acid-glycolic acid copolymer (PLGA) is also known as lactide-glycolide copolymer, polyethylene lactide, etc. It is polymerized from glycolic acid (or glycolic acid) and lactic acid, and is a biodegradable polymer material. Due to its easy synthes...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61K47/34A61K9/00
Inventor 郑彩虹梁文权
Owner ZHEJIANG UNIV
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