Biopharmaceutical Studies Of Silybin-phosphatidylcholine Complex

Through the biopharmaceutical studies of silybin– phosphatidylcholine complex (SPC), valuable results that are both academic and practical were achieved as follows:1. A novel preparative HPLC method separating silybin was developed to meet the need for both silybin A and silybin B standard. After the preparation of silybin A and silybin B standard, a simple and accurate HPLC method was developed to determine silybin A and silybin B, respectively, which supplied a strong support for the accurate determination of silybin A and silybin B in silybin/silymarin or their preparations2. A simple,sensitive, selective and reproducible liquid chromatography–tandem mass spectrometry(LC/MS/MS) method was developed for the quantification of silybin A and silybin B in rat and human plasma, and applied to the stereospecific analysis of silybin in plasma samples from pharmacokinetic studies in rat and human. The absolute bioavailability of silybin A and B in rat were 2.74% and 1.82%, respectively. The dose-independent pharmacokinetics was observed at three different administered doses to rat . In human, pharmacokinetic parameters between silybin A and B were different although those showed no significant difference between silybin A and B in rats.3. A simple, sensitive, selective and reproducible LC/MS/MS method was developed for the quantification of silybin A and silybin B in different tissues of rat, such as brain, heart, lung, liver, spleen, kidney, stomach, intestine, testicle, uterus and ovary. It was found that the most concentrations of silybin A and B were detected in the stomach, intestine and liver at three different times (15min, 1h and 3h).4. Taking silybin as a single entity, a new HPLC-UV method of determining silybin in human plasma was developed, and using the new developed method the pharmacokinetic of SPC was studied in healthy male Chinese volunteers. The dose-independent pharmacokinetics was observed after a single oral administration of SPC at three different doses. Through the study of relative bioavailability of SPC, it was showed that relative bioavailabilities of SPC were 270.4±139.6% and 125.3± 46.4% compared to silymarin and silybin meglumine, respectively.5. The hepatoprotective potential of SPC was evaluated in rat and mice against CCl4-induced liver damage. Through the study, it was found that the hepatoprotective activity of SPC was better than silybin/silymarin or their preparations, and also phosphatidylcholine (PC). The hepatoprotective potential of SPC was improved not only by the improvement of bioavailability of silybin according to complex silybin with PC, also by the synergic action of PC.