| Breviscapin were the flavonoids extracted from the Erigeron breviscapus (Vant.) Hand.-Mazz. Breviscapin were mainly the mixture of 4'-hydroxy -7-O-p-D-Pyrangluconate methyl ester and scutellarin and the content of scutellarin was above 95 percent. As a new type of Chinese proprietary medicines breviscapin, which can promote blood circulation to remove blood stasis, showed characteristic of good curative effects, wide uses, less side-effects. Breviscapin is efficacious in the treatment of cerebral infarction, coronary heart disease, angina pectoris. 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 breviscapin sustained release pellets of twice daily administration were prepared using ethylcellulose (EC) and stearic acid (SA) as the basic sustained excipient. The pellets were prepared by extrusion -spheronization method.Ultraviolet spectrophotometry method was developed for assaying during the study of physiochemical properties, content and drug release. High-performance liquid chromatography with UV detection was developed for studying the stability of breviscapin. In order to exclude the interference of the circulating solution and phenol red, dual-wavelength spectrophotometry was developed for in situ absorption.The physicochemical properties of breviscapin were investigated, which were connected closely with pharmaceutic form design. The studies on solubility showed that the equilibrium solubility in distilled water, pH 6.8phosphate buffer, pH 7.4 phosphate buffer were 1.45?.03,31.5?.8, 7946.3?7.1, 19045.1?57.9#g/ml respectively; Apparent oil-water partition coefficient in the system of n-octylalcohol and water was relatively higher in acid environment.The chemical stability of solid breviscapin was observed, the result of which indicated that light and air had little effect on it , but content of scutellarin decreased slightly under high temperature and high humidity. The stability of breviscapin in solution was studied. Results demonstrated that temperature and pH Value had significant influence on its stability, inflating N2 and adding antioxidants could improve the stability of breviscapin. Functions of different antioxidants were investigated, results showed that EDTA-2Na had good function in different medium. To clarify the absorption of breviscapin from intestine, the absorption was studied by utilizing the rat intestinal absorption recirculating method in situ. After perfusing for 6 h, the permeability rate showed that the permeability rate constant (h-1) of deodenum, jejunum, ileum and colon per 10cm were 0.0486, 0.0587, 0.0756, 0.106h-1 increasing accordingly and having significant difference. The bile duct ligated and pH value had no significant influence on it, but significant difference was found between different concentrations.The sustained release pellets were prepared with EC and SA by extrusion-spheronization method. Based on the studies of the influence factors, optimal formulation modified to release drug over 12h was obtained by orthogonal design test. The release profiles of sustained release pellets in vitro complied with Higuchi equation as well as Peppas equation. It suggested that the release of breviscapin could be described as non-Fickian diffusion, which was mainly by diffusion from pellets associated with slight erosion.In this part, the pharmacodynamics of breviscapin was studied in the blood platelet inhibition rate as the pharmacological index. Results showed that the dose-response relationship was linear. This index could be used to study on thepharmacodynamics of breviscapin. Effect-time profiles in healthy rabbits after oral administration of sustained release pellets and normal tablet were determined by pharmacological method and the pharmacodynamics parameters were calculated. The effect maintained for about 12h. The result of stastical analysis showed that breviscapin sustained relea...
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