Rahman A, Cradock J C, Davignon J P
J Pharm Sci. 1978 May;67(5):611-4. doi: 10.1002/jps.2600670509.
Ellipticine, a poorly water-soluble alkaloid, is active in several experimental tumor systems. Marked solubility increases were produced by polyvinylpyrrolidone of varying molecular weights (10,000--160,000) and were optimal (approximately 13 mg/ml at 25 degrees) with polyvinylpyrrolidone mol. wt 10,000. Dissolution of ellipticine--polyvinylpyrrlidone (1:22 w/w) tablets in simulated gastric juice was superior to that of ellipticine hydrochloride polymers without affecting maximum dissolution at 37 degrees. Physiological disposition of ellipticine--polyvinylpyrrolidone was compared with that of the hydrochloride salt and ellipticine in suspension following oral administration at 250 mg/kg in fasted mice. In comparison to the suspension, ellipticine tissue levels were about threefold higher with polyvinylpyrrolidone or hydrochloride preparations. Antitumor activity of the three preparations was evaluated intraperitonneally and orally versus L-1210 leukemia. The optimal dose of ellipticine--polyvinylpyrrolidone and ellipticine hydrochloride was lower than that of the suspension and suggested improved absorption.
玫瑰树碱是一种水溶性较差的生物碱，在多个实验肿瘤系统中具有活性。不同分子量（10,000 - 160,000）的聚乙烯吡咯烷酮可显著提高其溶解度，其中分子量为10,000的聚乙烯吡咯烷酮效果最佳（25℃时约为13 mg/ml）。玫瑰树碱 - 聚乙烯吡咯烷酮（1:22 w/w）片剂在模拟胃液中的溶出度优于盐酸玫瑰树碱聚合物，且在37℃时不影响最大溶出度。在禁食小鼠中口服给予250 mg/kg后，比较了玫瑰树碱 - 聚乙烯吡咯烷酮与盐酸盐及悬浮液形式的玫瑰树碱的生理处置情况。与悬浮液相比，聚乙烯吡咯烷酮或盐酸盐制剂的玫瑰树碱组织水平高出约三倍。通过腹腔注射和口服给药，对这三种制剂针对L - 1210白血病的抗肿瘤活性进行了评估。玫瑰树碱 - 聚乙烯吡咯烷酮和盐酸玫瑰树碱的最佳剂量低于悬浮液，表明吸收有所改善。
