|
Salvianolic acid (salvianolic acid, sal), also known as Salvia acid, is a water-soluble active ingredient of Salvia (salvia miltiorrhiza) are phenolic compounds. Salvia phenolic compounds include: Salvianolic acid A, B, C, D, E, F, G, H, I, rosmarinic acid, purple acid (lithospermic acid). They all have a very strong anti-lipid peroxidation and scavenging free radicals, in which the highest content of the two components of Salvia strongest acid A and salvianolic acid B activity. Danshensu basic chemical structure, the various Lithospermate the a chemical called β-3, 4 - dihydroxyphenylalanine lactate. Salvianolic acid B the tetramer Danshensu, has strong antioxidant effects, has a protective effect on the heart, brain, liver, and other organ. Salvianolic acid B has a variety of clinical role is constantly attention has been paid to become one of the hot research at home and abroad. Salvia realization acid B the monomer Industrial production, laid the foundation for the development Lithospermate innovative drugs. This study work aims to establish the in vivo analysis of salvianolic acid B, salvianolic acid B in animals drug metabolism dynamics absorption law, the laws of the tissue distribution and excretion law, further salvianolic acid B clinical trials research. In this study, first established rat plasma Chromatography LC-MS, artificial intestinal fluid, rat tissue and bile salvianolic acid B concentration method. Minimum detectable concentration in rat plasma 0.02μg? Ml-1, the linear range of 0.02 ~~ 50 μg? Ml-1; minimum detectable concentration in artificial intestinal fluid 0.02μg? Ml-1, the linear range of of 0.02 ~~ 100μg? ml-1; organizations in the minimum detectable concentration of 0.02μg? ml-1, the linear range of 0.02 ~~ 10μg? ml-1; minimum detectable concentration in the bile 0.02μg? ml-1, the linear range of 0.2 ~~ 50 μg? ml-1; comply with the requirements of the analysis of biological samples in this experiment. Sprague-Dawley (SD) rats by oral gavage and tail vein injection given Salvia acid B, the plasma concentration - time curve are in line with the two-compartment model, the AUC values ??were 37.16 ± 6.02 and 226.11 ± 79.43min · μg? Ml -1, bioavailability was 4.11%. Everted salvianolic acid B in different bowel are transparent, followed by the highest permeability in the duodenum, jejunum, ileum; intestinal fluid were added cyclosporin A (ciclosporin A, and CsA ) and verapamil (Verapamil, Ver), duodenum and ileum transparent salvianolic acid B have increased jejunal permeability of salvianolic acid B does not change. Where CsA make the duodenum and ileum of salvianolic acid B permeability increase is more significant, and Ver only affect the ileum. In rat bile excretion experiments, rifampicin three dose groups could significantly increase salvianolic acid B AUC and salvianolic acid B bile cumulative excretion and biliary clearance rate of inhibition was dose-dependent sex. The Ver three dose groups salvianolic acid B bile cumulative excretion and biliary clearance rate also inhibited in a dose-dependent manner. Borneol salvianolic acid B was found in the study of the absorption and distribution of rats Rats were given Salvia acid B 15min, the first oral administration of borneol make Salvia a significant increase in the absorption acid B, the AUC than individual orally given salvianolic acid B increased by 2.89 times; in everted model, were added to the low concentration of borneol, 5 groups, Salvia acid B permeability rate increased significantly, and there was dose-dependent; administered intravenously salvianolic acid B before 15min, oral administration of borneol found salvianolic acid B in the heart, liver, brain, kidney and other tissues and organs of distribution has increased, which salvianolic acid B in The distribution in the liver and kidney, the amount of increase is more significant, 2.98 and 3 times, respectively.
|