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[液体麦角生物碱制剂的稳定性与溶剂极性的关系(作者译)]

[Stability of liquid ergotalkaloid preparations as a function of the solvent polarity (author's transl)].

作者信息

Hartmann V, Schnabel G, Ohlrich H J

出版信息

Arzneimittelforschung. 1977;27(12):2276-83.

PMID:414760
Abstract

The degradation of dihydroergotamine-, dihydroergocornine-, dihydroergocryptine- (both isomers) and dihydroergocristine-mesilate in solution was studied as a function of the temperature and the dielectric constant of the composition. The degradation reactions of the studied hydrogenated ergopeptide alkaloids gave pseudo first-order kinetics. The pseudo first-order rate constants at room temperature were calculated using the Arrhenius equation. It was found that the stability of the studied hydrogenated ergopeptide alkaloids in solution is a function of the dielectric constant of the composition, and that stable solutions can be obtained by the use of water-alcohol mixtures having dielectric constants between 30 and 45. Solutions of the hydrogenated ergot alkaloids in predominantly organic media have the advantage that the degradation to the corresponding aci-forms, hydrolysis products and oxidation products is reduced. For this reason it is not necessary to carry out the filling operation under an inert gas atmosphere in order to protect the hydrogenated ergot alkaloids from oxidation. These results present an important technological advance.

摘要

研究了溶液中二氢麦角胺、二氢麦角柯宁、二氢麦角隐亭(两种异构体)和甲磺酸二氢麦角克碱的降解与温度及组合物介电常数的关系。所研究的氢化麦角肽生物碱的降解反应呈现伪一级动力学。利用阿伦尼乌斯方程计算了室温下的伪一级速率常数。结果发现,所研究的氢化麦角肽生物碱在溶液中的稳定性是组合物介电常数的函数,并且通过使用介电常数在30至45之间的水 - 醇混合物可获得稳定的溶液。氢化麦角生物碱在主要为有机介质中的溶液具有这样的优点,即减少了向相应酸形式、水解产物和氧化产物的降解。因此,为了保护氢化麦角生物碱不被氧化,没有必要在惰性气体气氛下进行灌装操作。这些结果代表了一项重要的技术进步。

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