| Liensinine(Lien) is a double benzyl isoquinoline single ether bond alkaline extracted from louts plumule. It has been found to possess antihypertensive and anriarrhythmic effects. Until now, the report of Lien has been focused on pharmacology, analysis and extraction, but there are few studies about its formulation, phaimacokinetics and biophannaceutics. It was not included either in the pharmacopoeia of China and other countries, or in the Merck Index. In this study, we investigated the extractive method, the analytic method, physicochemical properties, pharmacokinetics and biopharmaceutics of Lien. All kinds of conditions of extraction were exploited in this report and the best extractive method of Lien used in this study at last was that the medicinal material was extracted by methanol, volatilizing the methanol, and then dissolving the resultants by the acid and depositing the active components by the alkali. At last, Lien was purified by the silica column. Two method was developed for the determination of Lien by HPLC. One was the NP-HPLC, the other was the RP-HPLC. In the former method, dextromethmorphan was used as the internal standard. The calibration curve was linear in the range from 0.5 ii gImL, with r=Th9998, and the detection limit was 0.0 16 t gImL. The precision for within-day and between-day were both below 6.1%. In the latter method, dentoxifylline was used as the internal standard. The calibration cure in plasma was 0.25 100 i g/mL, with r0.9999, and the detection limit was 0.042 ii gImL, the precision for within-day and between-day were both below 5.3%. The extraction recoveries of all biosamples were over 80%. The relative standard deviations for with-day and between-day both met the requirements for analysis. The results showed that these method can be used feo the study of Lien. We choosed the RP-HPLC to determine the concentration of Lien in all biosamples. Some physicochemical properties of Lien was studied. The melt point of Lien was 96?8. The solution degree were better in methanol, acetone, chloroform, acid water and alkaline water than in ethyl ether,but it cannot be solved in water. The E$ was 124.1 in water and 175.7 in ethanol. The was increased with the increase of pH. The P~ of the drug was 18.1. The pKa of the drug was 8.22. The mean plasma protein binding ratio of Lien was 36.1%. The stability of the drug was poor and it was sensitive to light and heat. In this research improved intestinal absorption experiments of rat were used to study the absorption of Lien in intestinal tract. It was found that there was not significant difference in absorptive extent (PA%) in rats between without and with bile duct-ligated ( PA% was 16.9 for the former and 15.3 for the latter respectively). It showed that the intestinal absorptive extent of Lien was not influenced by the excretion of bile. The experiment results at three different concentrations indicated that the transport mechanism of Lien was passive diffusion. The pharmacokinetics and bio availability of Lien was investigated using rats. After i.v. administration of 8.54 and 16.9 mg/kg Lien, the concentration-time curves of Lien were better fitted to two compartment open model, and the elimination of Lien was linear kinetics. After oral administration and hepatic port... |
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