Studies On The Polymorphism And Its Effects On The Pharmcodynamics And Pharmcokinectics Of Emodin-8-O-β-D-glucopyranoside

Emodin-8-O- P -D-glucopyranoside ( PMEG ) is extracted from Polygonum multiflorum Thunb. The curative effect of Polygonum multiflorum Thunb on AD has been confirmed for a long time. It is very important to study on the pharmacodynamics and pharmcokinetics.With the rapid development of the new drug research, more and more attention is being taken to the phenomenon of drug polymorphism. Particularly in the process of pharmaceutics study, as the result of polymorphism, different crystals of the same drug show the differences in physical and chemical characteristics, pharmcodynamics and pharmcokinetics, such as drug absorption, distribution and metabolism. The main aim of this thesis was to study these differences resulting from polymorphism of the new drug PMEG.PMEG was recrystalized with different solvents and two different crystalforms were obtained, which were confirmed and characterized by HPLC, IR, NMR, DTA and X-ray powder diffractometry. We named them a-PMEG and P-PMEG respectively. The enteric absorption, distribution, metabolism and pharmacodynamics of the two crystalforms were studied.PMEG shows the maximum absorption at 267nm by UV spectrophotometry scan. A HPLC method was established to determine the plasma concentration of PMEG. Pharmacokinetics study was carried out in mice which showed that the absorption process correlated the first order equation. The AUC of a-PMEG at low, medium and high dosage of 0.1,0.2,0.4mg/ml were 1146.39+1221.11,3372.051 + 432.67,4708.86 + 400.36 respectively, while the AUC of p-PMEG at the corresponding dose were 2272.82?40.70,3608.60?52.40,5237.28?80.80.There were no significantly difference between the AUC of the two crystals at the corresponding dosage.In the study of the two crystal forms distribution in mice after oral administration PMEG, most of the two crystal forms were distributed into the four organs of the heart, liver, brain and kidney, reaching the maximum concentration at about 4h. There was no significant difference in the distribution of the two crystals.We also found that there are about 50% original PMEG excreted in urine and dejecta.In the study of the absorbance of PMEG in intestines of rats, we found that the absorbance in duodenum, jejunum, ileum, colon is (14.65?.25)%, (12.45?.59)% , (11.37?.77)% and (6.66?.85)% . The total absorbance of PMEG is about 45%.Above all, PMEG can be used to treat AD, and it's preparations should be studied in the future.