论文部分内容阅读
浙江临安产三尖杉(Cepbalotaxus fortunei Hook f.)树皮细粉,经常规方法提取后,得总生物硷,并经 pH 梯度分离.结合氧化铝柱层析得 ZJ-C,得率为0.5～0.2‰,经理化鉴定,证明为三尖杉酯碱(horringtonine)与高三尖杉酯硷(Homoharringtonine)的混合物,二者含量比为2:1。ZJ-C 对动物移植性癌及肉瘤(S_(180),WM_(256))均有显著抑制作用。对小鼠急性网状细胞性白血病(L_(615))抑制作用更为显著,在 L_(615)用615纯种鼠或 F_1小鼠结果相同。间歇给药与连续给药均获显著疗效。不论 ZJ-C 游离碱或其盐疗效相近。于游离硷对小鼠的急性毒性显著较其盐的毒性为高,故临床上以用盐的水溶液较为有利。ZJ-C 对家兔及家犬的亚急性毒性主要是恶心,呕吐,消化道出血,心肌损害,心律紊乱及红、白细胞、血小板造血抑制,无明显肝、肾毒性。病理切片所见与临床观察检查结果基本相同。以上毒性的严重程度,出现迟早均与单次剂量及总剂量大小平行。停药后均能自行恢复,在5～7个月的观察期内,无显著迟发毒性反应。鉴于 ZJ-C 化学上属新型结构,动物实验显示肯定的抗癌作用,毒性是可以控制的,可以恢复的,应推荐临床试用,预计限制剂量的毒性反应是造血抑制和心脏毒性。
The Cephalotaxus fortunei Hook f. bark powder from Lin’an, Zhejiang Province was extracted by conventional methods to obtain total biological enthalpies and separated by a pH gradient. ZJ-C was obtained by chromatography on alumina column. The yield was 0.5. ‰0.2 ‰, managerial identification, proved to be a mixture of horringtonine and Homoharringtonine, the ratio of the two being 2:1. ZJ-C had significant inhibitory effects on animal transplanted carcinoma and sarcoma (S_(180), WM_(256)). Inhibition of acute reticulocyte leukemia (L_(615)) was more pronounced in mice, with the same results in 615 purebred mice or F_1 mice in L_(615). Both intermittent and continuous administration have significant effects. Regardless of whether ZJ-C free base or its salt has similar efficacy. Since the acute toxicity of free hydrazine to mice is significantly higher than that of its salt, it is clinically advantageous to use an aqueous solution of salt. The subacute toxicity of ZJ-C to rabbits and domestic dogs is mainly nausea, vomiting, gastrointestinal bleeding, myocardial damage, arrhythmia, and hematopoietic inhibition of red, white blood cells, platelets, and no obvious liver and kidney toxicity. The results of pathological sections and clinical observations were basically the same. The severity of the above toxicity appears sooner or later parallel to the single dose and the total dose size. All recovered spontaneously after discontinuation of the drug, and no significant late toxicities were observed during the observation period of 5 to 7 months. Given that ZJ-C is a chemically novel structure, animal experiments show a definite anti-cancer effect, toxicity is controllable, and recovery is possible, clinical trials should be recommended, and it is expected that the dose-limiting toxicity reaction is hematopoietic suppression and cardiotoxicity.