| Objective:Xihuang Pill is a widely used anti-cancer proprietary Chinese medicine.The current research focuses on clinical application and anti-tumor mechanism.It is still unclear about its compatibility mechanism,in vivo process,especially in vivo under pathological conditions.From the perspective of pharmacokinetics,the study on the compatibility of traditional Chinese medicine compound,and compare the differences in the pharmacokinetic behavior of the body under normal state and pathological conditions,and in-depth study of the compatibility of the compound is the basis for guiding the clinical rational drug use and formulation development.In the early stage of the project,according to the dosage,pharmacological action and chemical composition of Xihuang Pill,it was extracted and refined to obtain the active component?XHF?of Xihuang prescription.The subject will pass plasma pharmacokinetics,tissue distribution in vivo and urinary excretion test.To explore the in vivo process of the main active components of XHF,such as cholic acid,deoxycholic acid,?-boswellic acid,11-carbonyl-?-acetyl succinic acid and muscone,in normal rat and breast cancer precancerous model rats.The biopharmaceutical significance of the compatibility of Xihuang prescription compound provides important experimental basis and data support for the later improvement and improvement of bioavailability through pharmaceutics.Method:A rat model of precancerous lesions of breast cancer was established by using the chemical inducer 7,12-dimethylbenzindole?DMBA?combined with estrogen and progesterone.The model was evaluated by body weight,nipple diameter and pathological section..The active components of chrysanthemum,deoxycholic acid,?-boswellic acid,11-carbonyl-?-acetyl succinic acid and muscone in rat kidney plasma were established by UPLC-MS/MS and GC-MS,respectively,tissue homogenate and urine content determination method.The Western medicine was dissected,and the plasma pharmacokinetics,tissue distribution and urinary excretion parameters of the active components in normal rats and precancerous lesions were determined.The compatibility and pathological status of the compound were preliminarily explained from the perspective of biopharmaceutics.The effect of in vivo processes of active ingredients in Xihuang prescription?XHF?.Result:Compared with the normal group,the weight of the model group was lower?P<0.05?,the diameter of the nipple was increased?P<0.05?,the breast tissue proliferated,and the ductal epithelial cells proliferated significantly.Mildly abnormal,but the overall structure does not see the invasive dilatation of the tumor,which belongs to the symptoms of precancerous lesions of breast cancer.The model of precancerous lesions of breast cancer in rats can be successfully established by using DMBA combined with estrogen and progesterone.UPLC-MS/MS and GC-MS were used to establish the plasma and tissue homogenate of chrysanthemum,deoxycholic acid,?-boswellic acid,11-carbonyl-?-acetyl succinic acid and muscone in rats.The in vivo analysis method in urine showed that each sample had good linearity in the test range,precision and stability RSD<15%,recovery rate and matrix effect were basically between 70%and 120%.After compound compatibility,the AUC?0-t?and Cmax of the active components in the normal group and the model group of Xihuang prescription increased,the clearance rate decreased,and the elimination in the body slowed down;the bile acid and deoxycholic acid were mainly distributed in the kidney and lung.In the tissue,?-boswellic acid is mainly distributed in liver and kidney tissues,and 11-carbonyl-?-acetyl succinic acid is mainly distributed in liver and spleen tissues,cholic acid,deoxycholic acid,?-boswellic acid,11-carbonyl-?-acetyl succinic acid.The concentration of?-acetyl succinic acid increased in the tissue,and the total urinary cumulative excretion showed a decreasing trend.The compound compatibility changed the absorption,distribution and excretion process of the active ingredients of Xihuang prescription.From the physiological state of rats,compared with the normal group,the precancerous lesions of breast cancer showed AUC?0-t?,AUC?0-??</sub>,Cmax showed an increasing trend,and the clearance rate decreased;cholic acid,11-The concentration of carbonyl-?-acetyl succinic acid was high in 1h and 3h tissues,the concentration of?-boswellic acid was high in 3h and 8h tissues,and the cumulative excretion of?-boswellic acid and 11-carbonyl-?-acetyl succinate It is reduced,the concentration in the body is high,and the amount discharged in the form of a prototype drug in urine is reduced.Conclusion:The UPLC-MS/MS and GC-MS methods established in this project are fast,accurate and reliable,and are suitable for the analysis of plasma,tissue samples and urine.Compound compatibility can effectively improve the bioavailability of the active components of Xihuang prescription,change the distribution characteristics,increase the residence time of the drug,and play a synergistic role.At the same time,the pathological state can affect the in vivo process of the active ingredients of Xihuang prescription.The research on the new dosage form of yellow multi-dimensional sustained-release microchips laid the experimental foundation and data support. |
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