Method for recrystallizing and refining fluticasone propionate

A fluticasone propionate and recrystallization technology, which is applied in the fields of steroids, respiratory diseases, organic chemistry, etc., can solve the problems of fluticasone propionate impurities, etc., and achieve the effects of guaranteed yield, easy industrialization, and simple operation

Active Publication Date: 2010-03-03
TIANJIN JINYAO GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] The invention provides a recrystallization method of fluticasone propionate, which solves the problem of fluticasone propionate impurities, so that the related substances of fluticasone propionate fully meet the requirements of EP6 of the European Pharmacopoeia 2008 edition, that is, the total related substances are at most 1.2 %, impurities D and G are up to 0.3%, impurities A, B, C, E, F, H and I are up to 0.2%, other unknown impurities are up to 0.1%

Method used

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  • Method for recrystallizing and refining fluticasone propionate
  • Method for recrystallizing and refining fluticasone propionate
  • Method for recrystallizing and refining fluticasone propionate

Examples

Experimental program
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Effect test

Embodiment 1

[0038]Using conventional methods, use bromofluoromethane with 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrost-1,4-diene-17β-thiocarboxylic acid Reaction obtains fluticasone propionate crude product (sample 1), records liquid phase diagram, sees attached figure 1 . It can be seen from the figure that the main content is: 98.617%; impurities C, D, F, and G are 0.2030%, 0.2877%, 0.3729%, and 0.2138% respectively. In addition, A, B, E, H, I impurities and other unknown impurities are not more than 0.2%

Embodiment 2

[0040] Dissolve 10 g of the crude fluticasone propionate obtained in Example 1 in 100 ml of dioxane solution, concentrate under reduced pressure at 65°C, and concentrate until the volume of recrystallization is about 30ml, slowly cool down, and keep warm at 5°C for crystallization 12 hours, filter, obtain 9.03g fluticasone propionate refined product (sample 2), record liquid phase figure, see attached figure 2 . According to the relative retention time, it can be seen that the main content is: 99.1776%; impurities C, D, and G are 0.1571%, 0.2418%, and 0.1635%, respectively. The remaining unknown impurities are all below 0.15%.

Embodiment 3

[0042] Dissolve 10 g of the crude fluticasone propionate obtained in Example 1 in 80 ml of tetrahydrofuran solution, concentrate under reduced pressure at 55°C, and concentrate until the volume of recrystallization is about 25ml, add 1ml of water dropwise, slowly cool down, and Insulated and crystallized for 12 hours, filtered to obtain 9.12g fluticasone propionate elaboration (sample 3), recorded liquid phase diagram, see attached image 3 . According to the relative retention time, it can be seen that the main content is: 99.1706%; impurities C, D, and G are 0.1852%, 0.2613%, and 0.1463%, respectively. The remaining unknown impurities are all below 0.15%.

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Abstract

The invention provides a method for recrystallizing fluticasone propionate. The method is characterized in that the fluticasone propionate is recrystallized in one or more solvents of alkylene oxide organic solvents and amide organic solvents to solve the impurity problem of the fluticasone propionate, so that related substances of the fluticasone propionate completely accord with the requirementof European Pharmacopoeia 2008 Edition EP6, namely total related substances are 1.2 percent maximally, impurities D and G are 0.3 percent maximally, impurities A, B, C, E, F, H and I are 0.2 percent maximally, and other unknown impurities are 0.1 percent maximally.

Description

technical field [0001] The invention relates to a new method for recrystallization of fluticasone propionate, in particular to a method for recrystallization in a cyclic ether organic solvent or an amide organic solvent. Background technique [0002] Fluticasone propionate (1), chemical name S-6α,9α-difluoro-11β-hydroxy-17α-propionyloxy-16α-methyl-3-oxoandrost-1,4-diene-17β - Fluoromethyl thiocarboxylate, the trade names of Fushuliang, Fushudone, Keyanfu and Seretide, was developed by German Glaxo Wellcome Co., Ltd. and first listed in 1993. As a new generation of topical glucocorticoids for the treatment of asthma in adults and children, compared with other glucocorticoids in clinical use, it has the characteristics of long action time, strong local effect and low systemic side effects, and has broad market prospects. See literature: Am Revpespir Dis, 1992, (45): 669-67 and JJ A1 lergy Clin Immunol, 1998, 101: 5434-5439. [0003] There are many reports on the synthesis me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J3/00A61P11/06
Inventor 王淑丽郑彤金玉鑫樊娜
Owner TIANJIN JINYAO GRP
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