Puerarin Phospholipid Solid Dispersion

As the main active constituent of Pueraria Lobata Ohwi, Puerarin can widely be used for treatment of cerebro-cardiac vascular diseases. However, for the sake of its low oral absorption and bioavailability, now in clinic Puerarin is administrated only by vein injection, which is inconvenient for patients and limits its clinical use. By the technology of forming phospholipid solid dispersion, the aim of present research is to enhance the bioavailability and to explore a way that can help enlarge the absorption of the active constituents of Chinese Traditional Drugs.The present research focuses on the reaction mechanism of Puerarin-phospholipid solid dispersion and its physicochemical and biological characteristics. In order to provide a scientific basis for the development and application of the study, a series of experiments have been performed in the preparation, the reaction mechanism, the physicochemical properties, the stability, the absorption and tissue distribution characteristics in animals through nasal administration and the biological activity. Up to now, no report about the study of Puerarin-phospholipid solid dispersion at home and abroad is found.Solid dispersions of Puerarin-phospholipid are prepared through co-precipitation, and the effecting factors such as solvent, drug concentration, temperature, reaction time are examined. The technological using alcohol as solvent with a simple reaction condition is determined.The microcosmic form of the solid dispersion of Puerarin-phospholipid is observed under microscope, the results show that compared with the physical mixture, the size of particles of solid dispersion of Puerarin-phospholipid is more even. X-Ray powder diffraction analysis exhibits that the solid dispersion of Puerarin-phospholipid was in an amorphous form in a specific proportion range of the two components, and the crystal diffraction peaks of Puerarin almost completely disappear. The DSC curves prove that after forming the solid dispersion with phospholipid, the thermal characteristic of Puerarin is increasingly sheltered by phospholipid with the increasing proportion of phospholipid. It can be observed with transmission electron microscope that when treated with water the solid dispersion of Puerarin-phospholipid formed into the liposome structure. It is shown that a great improvement of apparent solubility of Puerarin in solid dispersion in water and in chloroformwith the increasing of the proportion of phospholipid, especially significant in chloroform. Study on the solubility in hexane, ether, ethyl acetate, dichloroethane and acetone indicates that with the increasing proportion of phospholipid, solubility of Puerarin in solid dispersion in the low polar solvent raises. The enhancement of apparent oil/water partition coefficient of solid diserison in n-octyl alcohol-water (pH 1.0, 7.0, 9.0) system is found. The experiment results of the dissolution of solid dispersion of Puerarin-phospholipid, Quercetin-phospholipid, Ruting-phospholipid show that phospholipid solid dispersion has an obvious dissolution enhancing effect on the insoluble Quercetin and Rutin, but not obviously for slight soluble Puerarin. Compared with the solid dispersion of polyethylene glycol-Quercetin and polyvinglyrrolidone-Quercetin (l:l,w/w), the solid dispersion of Quercetin-phospholipid in the same proportion has more obvious effect on the dissolution of Quercetin. It shows that compared with polyethylene glycol or polyvinglyrrolidone, phospholipid as a carrier in a small amount could have an obvious dissolution enchancing effect. The research on stability of solid dispersions of Puerarin-phospholipid shows that they should be kept in a low temperature and dry condition.It is the first time to study and conjecture the forming mechanism with ultraviolet spectra, infrared spectra, nuclear magnetic resonance spectra and thin layer chromatogram, and a new idea is put forward. Compared with its physical mixture, the UV absorption spectra in chloroform of solid dispersion of Puerarin-phospholipid i...