The Study On Pharmacokinetics Of Sustained-Released Preparation Of Breviscapine

Breviscapine were the flavonoids extracted from Erigeron breviscapus (Vant.) Hand-Mazz. Breviscapine were mainly the mixture of 4'-hydroxy- β-D-pyangluconate methyl ester and scutellarin and the content of the latter was about 95 percent. As a new type of Chinese proprietary medicines, which can promote blood circulation to remove blood stasis, breviscapine showed characteristics of good curative effects, wide uses and less side-effects. Breviscapine is efficacious in the treatment of cerebral infraction, coronary heart disease, angina pectoris.In this paper, the study on breviscapine was reported. Ultraviolet spectrophotometry method was established for the study of physic chemical properties and drug content. The physiochemical properties were observed. High performance liquid chromatography with vv detection was established for studying the stability of breviscapine. Results demonstrated that temperature and PH value had significant influence on its stability. A reversed-phase high performance liquid chromatography method was established for determination if scutellarin in animals plasma which was used for the pharmacokinetics study.To meet clinical need for long time use of drugs for prevent and treatment of cardiovascular disease and cerebrovascular disease, to attain the aim of reducing times of administration and side-effects, briviscapine sustained-release capsules dissolved in intestines were prepared through the technique of sustained-release microgranules. The HPLC method was developed to control the quality of sustained-release pellets.The plasma concentrations and pharmacokinetic parameters compared after vein administration of breviscapine and oral administration of normal tablet and sustained-release capsules dissolved in intestines respectively. The results showed that plasma concentration-time profile after coral administration of normal tablet and sustained-released capsules were both fitted in with two compartment model. The absolute bioavailability of sustained-release capsules dissoloved in intestine were calculated to be 76.79% and that ofcommon tablets were 50.38%. Compared with the normal tablet, the eliminative speed of capsules reduced more slowly. The relative bioavailability was 152.95%. The result showed that breviscapine sustained-release capsules dissolved in intestines was not bioequivalent with the reference preparation (normal tablet). At the same time, metabolites of breviscapine were researched. The breviscapine was incubated in dogs' gastric juice and intestinal juice respectively. The sample was examined by means of HPLC/MS and found the main metabolic product. Two-phase hydrolysis method was used to determined the hydrolysates of breviscapine in vitro. The two kind of product got from different method were the same. The decomposed course of breviscapine in vivo was consistent with that in vitro.