Studies On The Procedure Of Breviscapine-β-CD-inclusion Compound

Breviscapine was a kind of flavone,extracted from Erigeron breviscapus (Van.)H.-M. of feverfew. The main active component in Breviscapine was Scutellarin, which was called β -d-Glucopyranosiduronic acid,5,6-dihydroxy-2-4-oxo-4H-1 -benzopyran-7-yl. Pharmacological study showed that breviscapine could significantly reduce the blood viscosity, inhibit the platelet aggregation and thrombosis formation, it can promote blood circulation to remove blood stasis obviously.Breviscapine was insoluble in water nor organic solvent ,soluble in alkaline solution with low oil/water distribution coefficient,short half-life. Breviscapine was a weak acid with low oil/water distribution coefficent, soluble in alkaline solution and insoluble in water nor organic solvent. In this thesis we use the complex of breviscapine- β -cyclodextrin(breviscapine-β-CD) to improve the dissolubility and bioavailability of breviscapine. It showed that Breviscapine was given by i.v.,then it is absorbed quickly in plasma But the absolute bioavailability of brevescapine for oral administration was so low and it was almost not absorbed for oral administration. Therefore, it was necessary to develope an inclusion compound with good bioavailability and stable efficacy to permit reduction in the frequency of breviscapine administration. According to the pharmacokinetics of breviscapine in rats, breviscapine-β -CD inclusion was prepared with the method of saturated solution method, and it was studied by the orthogonal design in two factors: the breviscapine content and recovery in the inclusion. The experimental data showed that the best condition for the inclusion compound should be formed in aqueoussolution containing P ~CD and breviscaipine with molecular ratio of 1:2 for 2hours at 70 °C . And the breviscapine content in the inclusion was determined by HPLC. Structure examination of UV absorption spectrum , differential scanning calorimetric method, X-ray diffraction , IR absorption spectrum and nuclear magnetic resonance proved that the inclusion compound has completed.Let the inclusion compound be tablets. And the dissolubility was promoted when the drug was wrapped by |3 -CD. Method for controlling quality of the inclusion complex has been formed. To establish the methods of the breviscapine and ￡ -CD inclusion compound content and dissolubility by spectrophotography test and HPLC. The results proved that the all methods had good linearity, good accuracy and were stable, convenient.HPLC method was developed for determination of breviscapine in Rat's. Breviscapine conventional tablet was used as a comparison to study the pharmacokinetics. The mean plasma concentration-time protracted and pharmacokinetic parameters were calculated. The results showed that concentration-time curve was explained by compartment model. Compared with conventional tablet, Tmax and MRT were reduced and Cmax was increased, AUC value and dissolubility were increased remarkably. Inclusion compound make breviscapine release quickly in plasma, increase the absorption of breviscapine and the relative bioavailability value was 110.68%.