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Investigation Of Pharmacokinetics And Electroanalytical Chemistry Of Some Active Components In TCM

Posted on:2012-10-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:F D HuFull Text:PDF
GTID:1114330335966570Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
Researches on analytical method, quality standard, and Pharmacokinetics are hot fields but also challenges in the study of traditional Chinese medicine(TCM).Administration of single active component or extraction of TCM, leads to change of effects. The chromatographic fingerprint analytical technique, emphasized on the overall guiding principle of TCM, inferior the thought about action of single chemical composition in western medicine, is of significance to the improvement in industrial level, modernization and globalization of TCM. Up to now, electrochemical analysis provided new idea and methods in analysis of TCM due to its advantages of high sensitivity, wide range of test concentration, less amount of sample needed and nondestructive for inhere characteristic of analytical sample.Based on the new trends in study of pharmacokinetics, quality control and new analysis methods focusing on TCM, this researches made use of chromatographic technique and elerochemical technique to carry out the several groundbreaking works as follow.1 A simple and sensitive analysis method by HPLC was established and validated to measure costunolide and dehydrocostus lactone in mouse plasma and tissue; The pharmacokinetic of costunolide and lactone dehydrogenase in mice was investigated after administration of single oral ethanol extraction of Muxiang (EEM).2 A simple, rapid, high selective and sensitive method by UPLC-ESI-MS/MS was established and validated to assay costunolide and dehydrocostus lactone in rat plasma and tissue; We studied the pharmacokinetic in rats that were treated with dehydrogenase lactone, mixed of costunolide and dehydrogenase lactone, and EEM respectively, using different ways of administration, and completely compared their pharmacokinetic parameters, which further proved that the efficacy of TCM is played by the overall ingredient rather than a single active component or partitively, and provided evidence for development and rational clinical application of this medicine.3 To further reveal the phatmacokinetic parameters of costunolide and dehydrogenase lactone in human, the binding process of drug and plasma protein was mimic using equilibrium dialysis and measured by HPLC. The plasma protein binding rate was 59.78% of costunolide and 65.69% of dehydrogenase lactone, treated with each component separately. However, the plasma protein binding rate was 51.78% of costunolide and 45.83% of dehydrogenase lactone when treated with the combination of them. There is a significant difference by t test assay. The result demonstrated treated with the combination of them will affect their own absorption, distribution, metabolism, exeretion(ADME).4 A quality evaluation system of multi-wavelength fingerprint similarity and peak-matching between preparation and its raw herbs was established and further valued preparation technology of Xiaochaihu granula. Xiaochahu granula from different companies was classified to four categories with cluster analysis utilizing the results of peak-matching. Exploitation of preparation technology revealed that boiled preparation technology in water tends to alter the structure of Saikosaponin A and D in radix bupleuri chinense. We purposed that the current preparation technology of Xiaochahu granula would have influence on the outcome of Clinical Therapy. Therefore, this system of multi-wavelength fingerprint similarity and peak-matching could be applied to quality control and optimization of TCM preparation technology.5 Chitosan/Graphene/GCE was fabricated using Chitosan solution which involved in Graphene. And electrochemical behavior of rutin on this modified electrochemical electrode was studied. Rutin effectively accumulated on the chitosan/graphene/GCE and caused a pair of redox peaks at around 408 mV and 482 mV in 0.1 M phosphate buffer solution (pH 4.0). And the anodic peak current was linear to the rutin concentration under optimized conditions. The regression equation was:Y=9.9219X-0.0025 (r=0.9918). Furthermore, this new method was successfully applied to the determination of rutin content in tablet samples with satisfactory results.
Keywords/Search Tags:Pharmacokinetics of TCM, The plasma protein binding rate, Chromatography fingerprint of TCM at multiple wavelength-peak matching pattern, Chitosan/graphene/GCE, Sesquiterpene lactone from Muxiang, Xiaochaihu Granula, Rutin
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