摘要
目的筛选和优化奈达铂制备工艺的主要影响因素,寻找最佳工艺条件。方法采用水解法,在单因素实验基础上,利用响应面分析法建立数学模型,预测并验证奈达铂的最佳工艺,并对该工艺条件下制备的奈达铂进行了元素分析、热重、质谱、核磁共振谱等结构表征。结果反应液浓缩体积对产物的收率和纯度影响最大,确定最佳工艺条件:顺式-二碘-二氨合铂(Ⅱ)用量为20 mmol,乙醇酸钠用量为36 mmol,氢氧化钠用量为24 mmol,反应用水量150 mL,反应温度60℃,反应时间7 h,反应液浓缩体积至15 mL,奈达铂的平均收率为75.33%、纯度为98.55%。结论经Box-Behnken响应面法优化后的奈达铂制备工艺稳定,产品收率高、纯度高,适合工业化大批量生产。
The major factors influencing the synthetic processes of nedaplatin were selected and optimized by Box-Behnken response surface methodology.On the basis of hydrolysis method and single factor experiment,response surface analysis were used to screen and verity the optimum preparation process of nedaplatin by establishing mathematical model.Elemental analysis,thermogravimetric analysis,mass spectrometry and NM R were carried out to characterize the final product.The results show ed that the concentrated volume of reaction solution had a major influence on the yield and purity of the product.Under the conditions of the amount of cis-di-iododiammineplatinum (Ⅱ) of 20 mmol,the dosage of sodium glycolate of 36 mmol,the consumption of sodium hydroxide of 24 mmol,the reaction water consumption of150 mL,the reaction temperature of 60℃,the reaction time of 7 h,and the concentrated volume of reaction solution to 15 mL,nedaplatin products were prepared with the average yield of 75.33%,and the purity of98.55%,which was the optimum synthesis process.This optimized synthesis process of nedaplatin by response surface method is stable,with high yield and purity,which is suitable for industrial mass production.
作者
刘其星
丛艳伟
普绍平
谢丽娇
王应飞
张林涛
LIU Qi-xing;CONG Yan-wei;PU Shao-ping;XIE Li-jiao;WANG Ying-fei;ZHANG Lin-tao(Kunming Guiyan Pharmaceutical Co.Ltd.,Kunming 650033,China)
出处
《中国药物化学杂志》
CAS
CSCD
2021年第3期192-202,共11页
Chinese Journal of Medicinal Chemistry
