Voriconazole nano-micro composite powder and preparation method thereof

Abstract

The invention discloses voriconazole nano-micro composite powder, wherein a safe and reliable pharmaceutical auxiliary material is adopted to replace cyclodextrin, tween and other auxiliary materials generally-used in the current voriconazole preparations or physiologically toxic organic solvents as a solvent so as to improve product safety, the composite powder can be dispersed in water so as to obtain a transparent dispersion, and the drug has characteristics of high concentration, small particle size and easy absorption by human body. The present invention provides a voriconazole nano-micro composite powder preparation method, which has characteristics of simple operation, easy enlargement and industrial production, and good application prospect.

Description

technical field [0001] The invention relates to a voriconazole micro-composite powder and a preparation method thereof, belonging to the field of pharmaceutical preparations. Background technique [0002] Voriconazole, chemical name: (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4 -Triazol-1-yl)-2-butanol, which is a second-generation triazole broad-spectrum antifungal new drug developed by Pfizer Pharmaceutical Company of the United States, was listed in 2002. Voriconazole is a derivative of fluconazole. Its chemical structure is to add a methyl group to the fluconazole structure and replace the triazole ring with a fluoropyrimidine ring. Its molecular structure is as follows: [0003] [0004] As a new type of broad-spectrum antifungal drug, voriconazole has strong antifungal activity in vivo and in vitro, and is active against a wide range of pathogenic yeasts, filamentous fungi, and dimorphic fungi, and is also effective against drug-resistant fu...

AI Technical Summary

Problems solved by technology

However, sulfonbutane-β-cyclodextrin has certain physiological toxicity

In order to solve the above problems, there are mainly three types of methods in the current public literature: the first type uses auxiliary materials such as cyclodextrin or Tween as a solubilizer, such as CN200410098736, which uses hydroxypropyl-β-cyclodextrin as an auxiliary material to prepare freeze-dried powder Injections; CN200510068033 added auxiliary materials such as cyclodextrin and Tween; CN200510095595 disclosed a method for preparing voriconazole injections with cyclodextrin as auxiliary materials and using organic solvents; the voriconazole inclusion compound prepared by CN200710143810 and CN200910019770 also added cyclodextrin Dextrin auxiliary materials; although the above method has replaced sulfonylbutane-β-cyclodextrin, because auxiliary materials such as cyclodextrin and Tween also have strong physiological toxicity, they cannot be widely used; the second category is to use organic solvents as Solvents, such as patents CN200610085363 and CN200510095595, although these methods do not use cyclodextrin and Tween and other adjuvants with large toxic and side effects, organic solvents also have certain toxic and side effects

The third category uses auxiliary materials such as poloxamers as solubilizers, such as WO2010084505A2, CN200710122140, but poloxamers are not suitable for injections

However, there are no relevant reports on micronization of voriconazole

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