Studies On Oral Absorption Of Breviscapus And Prepareation Of Self-microemulsion For Oral Administration

Breviscapine, which is mainly composed of breviscapus (af lavone glucuronide), is a well-known bioactive constituentextracted from the traditional Chinese medicine Erigeron breviscapus (Vant.) Hand.-Mazz. Breviscapine is extensively used to treat ischemic cerebrovascular and cardiovascular diseases in China. However, the oral bioavailability of breviscapine was found to be quite poor in rats. To increase its oral bioavailability, Caco-2eells and in situ perfusion method in rats were applied to study the meehanism of absorption after oral administration of brevescapine, such as time, temperature, pH, concentration, p-glycoprotein inhibitor,excipients and different intestine segments were investigated, and self-microemulsion was prepared to enhance bioavailability of breviscapine.Stability of breviscapus in artificial gastric juice, K-R fluid at different pH value (pH 6,0.6.8,7.4), contents of different parts of intestine, and homogenates of different parts of intestine mucosa were studied. The results showed that scruetallarin degraded significantly in artificial gastric juice, the contents of intestine and homogenates of intestine mucosa. Analysis on influence factors for stability of breviscapus suggested that breviscapus is sensitive to gastrointestinal Enzymes and pH, stability of breviscapus decreases with pH increasing in K-R fluid.0.1% EDTA-2Na is helpful for improving the stability of scretellarin in K-R fluid but 0.1% Vc can improve its stability significantly.The cytotoxicity of several excipients on Caco-2 cells was evaluated by the MTT test. It showed that the toxic order of theses excipients to Caco-2 cells was F68< Ethyl polyenoate duodenum>jejunum>ileum>> colon.In further study, we separately use ethyl oleate, Ethyl polyenoate and medium chain length fatty acid triglyceride as oil phase to prepare breviscapus microemusion. Phospholipid was selected to increase the solubility of breviscapus in these three oil phase. Pseudo-ternary phase diagrams were constructed identifying the efficient micro emulsification region. Nine breviscapus O/W emulsion formulations with different oil pahse, different proportion of oil phase and surfactant were prepared and their effects on the absorption of breviscapus were studied with Caco-2 cells model. The results showed that all of these nine emulsions have absorption enhancement effect and the effect was related to the oil phase and particle size of the emulsions. The absorption enhancement effect order of these three oil phase is medium chain length fatty acid triglyceride