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Pharmacology By Bioanalysis Of Traditional Chinese Medicine Recipe: Primary Studies On Clinical Pharmacokinetics Of Xiaoyao-San Decoction And In Vivo Pharmacodynamics Of Coronary Heart No.Ⅱ Decoction

Posted on:2004-12-21Degree:MasterType:Thesis
Country:ChinaCandidate:Y X YangFull Text:PDF
GTID:2144360092491830Subject:Traditional Chinese Medicine
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Though the research of Traditional Chinese Medicine Recipe(TCMR) has make great progresses in several thousands years, what the effective chemical components absorbed into circulation after administering TCMR are not clear yet. In order to answer the question, at the base of theoretics and practice of Pharmocokinetics of traditional Chinese syndrome and recipe (S&R-PK) , Professor Huang Xi brought forward the idea of Study on Traditional Chinese medicine(TCM) by Bioanalysis of Traditional Chinese medicine recipe (BA-TCMR), which includes study on pharmaceutics, pharmacokinetics, pharmacodynamics, standard of quality and essence of Zheng ( One term of TCM , it means the subject of diagnosis and treatment . ) by BA-TCMR.The idea indicates that it must be study on TCM at the base of biopharmaceutical analysis of TCMR-derived component . In the experiments ,-6-we chose different recipes to provide examples for the primary study on pharmacology by BA-TCMR.Firstly, we observed the pharmacokinetical character of Ferulic Acid (FA) in 10 patients with Liver depression and Spleen deficiency Zheng after oral administration of Jiaweixiaoyao-San decoction. Methods: 1. A new RP-HPLC method was established: At the time of 5,10,15,30,60,90,120min after oral Jiaweixiaoyao-San decoction, the concentration of FA in serum was determined. Stationary phase: Kromasil C18 chromatographic column (250?. 6mm, Sum); mobile phase: methanol-water-acetic acid (40:59. 6:0.4,v/v); flow rate: 1 .OmL/min; detection wavelength:322nm. Hydroxybenzaldehydr was used as internal standard. The serum sample was extracted and deproteinized with acetonitrile. 2. The pharmacokinetical parameters were fitted with software 3P97. Results: 1. FA was linear in the range of 7.82-195.5 ng-mL"1 ( r = 0.99713), the lowest detection limit of FA was 4.692ng-mL'(S/N=3). The intra-assay and inter-assay precisions in different concentration were all less than 10%; the average recovery rate was 99.38%. 2. The concentration-time date of FA in patients with Liver depression and Spleen deficiency Zheng belong to the open two-compartment model, t1/2ka =15.61 ?.77 min , t1/2a=41.54 min, t(1/2?91.01 min. Conclusions: l.This RP-HPLC method is simple, rapid, sensitive, special and accurate, can be used to determine the concentration of FA in serum in patients with Liver depression and Spleen deficiency Zheng following oral Jiaweixiaoyao-San Decoction. 2. The absorption and elemination of FA are all slow in digestive tract following oral Jiawei Xiaoyao San Decoction. 3. It may be provide an example to study on clinical pharmacokinetics by BA-TCMR.Secondly, we observed the influence of Oral Coronary Heart No. II Decoction (CH.II) on the protein expression of apoptosis-related genes Bax , Bcl-2 and Fas in rat hearts with myocardial ischemia/reperfusion injury (M/IRI). In addition, we want to study the relention between pharmacokinetics and pharmacodynamics of CH.II. Methods: MI/RI models were performed by a-7-ligation and release of coronary artery in rats. The SABC immunohistochemistry and medical image analysis were used to measure number and mean grey level of positive cells of Bcl-2 protein, Bax protein and Fas protein in ischemic myocardium. Results: 1 . The heart rate (HR) of MI/RI group got faster during ischemic phase(p<0.01)and slower in reperfusion phases( p<0.01 , p<0.05); Compared with ischemic phase, the HR of different dose CH.II therapy groups all got slower in reperfusion-6hour phase(p<0.05); Compared with the same phase of MI/RI group, the HR of high dose therapy CH.II group all got slower significantly during ischemic phase and reperfusion-5, 6hour phases (p<0.01). 2. Compared with Sham-operated group, the expression of Bax and Fas proteins increased significantly and the expression of Bcl-2 protein decreased significantly in myocytes of MI/R group(p<0.01); Compared with MIRI group, the expression of Bax and Fas proteins decreased and the expression of Bcl-2 protein increased in myocytes in oral CH.II treatme...
Keywords/Search Tags:Study on pharmacology by Bioanalysis of TCM, Xiaoyao-San decoction, clinical pharmacokinetics, Coronary Heart No. II Decoction, in vivo pharmacodynamics
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