Study On Transdermal Preparation Of Bioactive Ingredients Of Radix Gentianae Macrophyllae

The Chinese Pharmacopoeia records four herbs that belong to Gentiana genus as "Radix Gentianae Macrophyllae"("qingjiao" in Chinese),which are widely used for the treatment of rheumatic diseases,various arthromyodynia and other diseases.However,the medicinal materials of Radix Gentianae Macrophyllae(RGM)are various in variety and uneven in quality on the market,and even appear under the same family or genus,false product confusion.Gentiopicroside,the main active ingredient of RGM,is rapidly metabolized in vivo and difficult to exert long-term curative effect,which severely restricts its clinical application.The present work mainly launches the research around these two questions,and proposes the solution mentality:In response to the first question,the quality control of RGM was studied by using its aromatic components with taxonomic significance.A selective extraction method capable of enriching the aromatic compounds in Radix Gentianae Macrophyllae was established,and 12 chemical components with aromatic structures were identified by UPLC-MS.Besides,an HPLC-DAD method was established for the quantitative determination of three characteristic aromatic compounds of Radix Gentianae Macrophyllae.The quality of eleven batches of medicinal materials of Radix Gentianae Macrophyllae sold in the market was investigated,and the appropriate raw materials of Radix Gentianae Macrophyllae were screened out.Aiming at the second problem,a new formulation of cataplasm was developed by applying modern preparation technology and quality evaluation method.First,the in vitro permeability of the active components of Radix Gentianae Macrophyllae was investigated and the optimal penetration enhancer,i.e.,1.5%menthol+1.5%propylene glycol,was screened out.The optimal formulation of cataplasm matrix was obtained by single factor and orthogonal experiments as follows:content of NP-700 was 4.5%,content of glycerol was 30%,content of glycollate was 0.3%,content of carbomer 980 was 0.5%,content of EDTA was 0.03%,content of kaolin was 1.2%.In addition,the quality of RGM cataplasm was evaluated according to the Chinese Pharmacopoeia.The experimental results showed that all evaluation indicators of RGM cataplasm met the requirements and the stability was satisfying.Based upon the preparation,the in vitro release and transdermal pattern of RGM cataplasm were explored.In which,all three RGM cataplasm could release more than 80%within 2 h.In addition,the cumulative permeation amount of gentiopicroside in the cataplasm was relatively high,the transdermal rate was stable,and the permeation time could maintain for more than 12 h.Additionally,in the anti-inflammatory pharmacodynamics research,The RGM cataplasm exhibited significant inhibitory effect on paw edema induced by carrageenin in mice.Finally,the pharmacokinetic s of gentiopicroside cataplasm after administration and oral administration in rats were explored.The experimental results suggested that cataplasm administration could prolong the action time of the drug and achieve sustained and controlled release administration.