Effect Of Preparation Process On Quality, In-vitro Release And Toxicology Of Yaotongning Capsule

To study the effect of preparation process on the quality, in-vitro release and toxicology of Yaotongning capsule, in present study the powders of the four herbs (processed Semen Stiychni, Olibanum, Commiphora myrrha and Radix Glycyrrhizae) in the formulation of Yaotongning capsule were prepared by different methods. The particle size, micro-morphology, toxicology of the powders and contents and in-vitro release of the active components in the powders were investigated. The main research contents were as following:(1) HPLC method was applied to test the release performance of brucine and strychnine of the mixed powders in the artificial gastric juice, which were prepared with different proportions of Olibanum, Commiphora myrrha and processed Semen Stiychni by different crushing methods. Scanning Electron Microscope(SEM) was applied to analyze the micro-morphology of the powders;(2) Radix Glycyrrhizae powders with different particle sizes were prepared and HPLC method was used to study the contents and in-vitro release of the active ingredients (glycyrrhizic acid and liquiritin);(3) According to the proportion of Olibanum, Commiphora myrrha and processed Semen Stiychni in the formulation of Yaotongning capsule,Olibanum, Commiphora myrrha and coarse powder of Semen Stiychni were put together to crush and the remaining herbs were crushed as the original mixed proportion of the recipe, and then these two kinds of powders were mixed to prepare new Yaotongning powder. HPLC method was used to compare the contents of brucine and strychnine of new and original Yaotongning powders, then the acute toxicity and drug tolerance of the mice taken the two Yaotongning powders were compared and investigated.The results showed that crushing Olibanum, Commiphora myrrha and coarse powder of Semen Strychni together could slow down the in-vitro dissolution rate of brucine and strychnine. The greater proportion of Olibanum and Commiphora myrrha was, the more slowly the in-vitro release of the two alkaloids. The contents of liquiritin (or glycyrrhizic acid) increased with the decrease of particle sizes of the Radix Glycyrrhizae powder samples. The contents of the active ingredients in100～140mesh sample were higher and stable, and had good in-vitro release performance. The contents of brucine and strychnine of the Yaotongning powders prepared by the two modes were very close and had no significant difference; but the acute toxicity of Yaotongning powder prepared by new crushing mode was higher than that of Yaotongning powder prepared by original crushing mode. The tested mice had a certain tolerance to the two Yaotongning powder after repeated-oral doses for10days.In summary, the original preparation process of Yaotongning powder has better security. In order to ensure the stability of the active ingredients, the particle size of Yaotongning powder should be controlled between100-140mesh. To explore the optimized regimen to improve the efficacy and safety of Yaotongning capsule, it is recommended to implement clinical experiments by increasing the dose of the clinical trial after taking the existing dose of Yaotongning capsule7-10days.