Study On The Effective Substance Of Drug Pais Safflower-Licorice In Vivo

The Chinese medicines have a unique advantaged and historic in the treatment ofcardiovascular disease. Due to its own combination complexity and clinical herbalprescription flexibility, Chinese medicine is the hot issues in the fields of chemistry,biology and medicine, which is the research and development of the new drug based on thetheory of traditional Chinese medicine. In this thesis, according to the principle ofcombination prescription, the Safflower as the monarch drug and Licorice as the guidancedrug was selected from Xuefuzhuyetang with the relationship of “xiangshi”, the systemwork was mainly focus on the active compounds groups screening in vivo and the maincontributions are as follows:1. A high performance liquid chromatographic method for the determination ofhydroxy safflower yellow A （HSYA） in rat plasma is established. This method have thegood linear relationship in the range of0.20⁶.25mg·mL^-1and the limit of detection （LOD）for HSYA is0.10mg·mL^-1. The results for the assay of precision, repeatability and stabilityhave met the requirements of methodology for biological samples determination of Foodand Drug Administration in China and United States. The result showed that this methodcould apply to studying the pharmacokinetic of HSYA in vivo and screening bioactivecompounds in a complex prescription.2. The pharmacokinetic process of HSYA in normal rat was studied afteradministration of Safflower and Safflower-Licorice under the proposed method. Theprincipal component analysis （PCA） and the correlation analysis （CA） were performedbased on the theory of Metabolisms. The results showed as follow: The half-life time ofdistribution for HYSA in vivo have obviously decreased after combined with the Licoriceand demonstrated Licorice have the effect on enhancing the distribution of HYSA in vivo; The significant difference between the two treated groups is caused from severalcompounds including HSYA, the endogenous substances of ES16, ES17and ES24.3. The pharmacokinetics process of HSYA in model rat suffered from qi stagnationand blood stasis was studied after administration of Safflower and Safflower-Licoriceunder the proposed method. PCA and CA were performed based on the theory ofMetabolisms. The results showed as follow: The half-life time of distribution, the areasunder drug-time curve and the maximum concentration of HYSA in model group wereincreased and demonstrated that the Licorice have the effect on decelerating thedistribution of HSYA and accelerating its absorption in vivo; The significant differencebetween the two groups of treated animals was achieved mainly due to several compounds,including HSYA, endogenous substances of ES16、ES17and ES24.4. The system of high perform liquids chromatography-quardpole-time of flight massspectral （HPLC-Q-TOF/MS） was employed to analyze the blood sample of blank,Safflower and Safflower-Licorice. The result showed that chromatographic peak, which theretention time （tR） is19,21and24min, is the effective compounds form Licorice and theHYSA, which is the effective compounds in Safflower, is32min.