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Study On The Therapeutic Basis Of Traditional Chinese Medicinal Preparation Ling-Gui-Zhu-Gan Decoction

Posted on:2003-08-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z H SongFull Text:PDF
GTID:1104360092992316Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
Poria cocos is one of the commonly used traditional Chinese medicines (TCM) which is the principal ingredients of the Ling-Gui-Zhu-Gan decoction. 26 samples of Poria of different origins were collected and the quality assessment was developed. Dehydrotumulosic acid, one of the triterpenes was isolated and identified. Pure dehydrotumulosic acid for quantification was prepared. A reversed-phase HPLC method has been developed for the determination of dehydrotumulosic acid in Poria cocos. The determination can be accomplished in less than 50 min using methanol-acetonitrile-2% glacial acetic acid as the mobile phase at a flow rate of 1.0 mL-min-1, with a UV detector setting at 242 run and testosterone propionate used as an internal standard. The linear range for the determination of dehydrotumulosic acid was 0.0152 -0.304 mg-mL-1 with the coefficient of determination r=0.9991. The average recovery was 99.9% (n=6). The repeatability of the assay was 1.4% (n=6). This assay for dehydrotumulosic is simple, rapid and with good reproducibility and provides a quantitative basis for the quality assessment for Poria cocos. Based on the HPLC method, 29 constituents were eluted and the chemical data was obtained and studied by chemical pattern recognition methods. All samples were identified with hierarchical clustering analysis and divided into three grades, the superior, the general and the inferior. According to the result of classification, 8 chemical features were selected by STEPDA, and the similarity analysis method for quality assessment of Poria cocos samples was built. When the 8 chemical features were used to classify all this samples by hierarchical clustering analysis and similarity analysis, the conclusion whether it is superior, general or inferior can be reached. This suggested that the quality of unknown samples could be described and evaluated only based on chemical data. Thus was it possible to assess the quality of Poria cocos only using chemical data. The methodology may well be used to assess the quality of other herbs.The LGZG decoction was reported originally in the Treatise on cold-induced febrile diseases and the Synopsis of the golden chamber, both written by ZhangZhongjing. In the clinical practice of traditional Chinese medical science, the decoction has been used to treat arrhythmia, cardiac failure, angina pectoris and other cardiovascular diseases over a very long period of time and has produced quite a good effect.The compatibility and therapeutic basis of LGZG decoction were studied in this paper. The survival time of mice in normobaric hypoxia, the effect of mice against ventricular fibrillation (VF) induced with chloroform and diuretic efficiency were selected as pharmacological indices. Using water and alcohol of different concentrations as the extracting solvent, the effects on extracting efficiency with 11 kinds of different extracting methods were studied. 95% alcohol was selected as the optimal solvent:The quantitative analysis of the compatibility can be accomplished by means of the orthogonal array experiments. To ascertain the optimal combination of 4 herbs in a composite prescription, the L16(45) orthogonal array, which permits to arrange 16 combinations, 4 levers for each herb, could be adopted. The index by which the therapeutic effect could be assessed was the pharmacologic action assigned. The combination, which produced the largest pharmacologic index, was the best, and the optimal dose was ascertained. That Fuling and Guizhi are principal medicines of the decoction, whereas Baizhu and Gancao are adjuvant of it has been confirmed by the orthogonal array experiments. We have successfully established a valid approach to confirm the reasonability of the compatibility of the TCM LGZG decoction and its optimal dose.Then, a HPLC method for obtaining the chemical fingerprints was established. HPLC analysis of the 16 combinations arranged by the orthogonal array experiment were carried out. Step regression analysis and canonical correlation analysis were ap...
Keywords/Search Tags:Ling-Gui-Zhu-Gan decoction, Poria cocos, compatibility, therapeutic basis, quality indices, extraction process, pharmacodynamics, pharmacokinetic
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