双氯芬酸赖氨酸盐的研制

Synthesis of diclofenac acid lysine

目的为减轻双氯芬酸钠的刺激性，研制合成氯芬酸赖氨酸盐，以扩大其应用。方法采用均匀设计方法研究从优化双氯芬酸赖氨酸盐的合成条件；采用四大学谱和元素分析法鉴定其结构；采用兔眼结膜法进行刺激性实验。结果：均匀设计法预测出最佳合成条件，并依此对其优化验证，得率为７７．６％（纯度９８％以上）；产品分子式为Ｃ２０Ｈ２５Ｑ４Ｎ３Ｃｌ２，经ＵＶ，ＩＲ，ＭＳ，１ＨＮＭＲ，１３ＣＮＭＲ，ＤＥＰＴ及元素分析确定无疑；刺激性实验结果表明：本品对免眼结膜的刺激性明显低于双氯芬酸钠（Ｐ＜０．０１）。结论：双氯芬酸赖氨酸盐的刺激性明显较双氯芬酸钠小，而且合成工艺简单、快速、得率高、无污染。

OBJECTIVE:To study diclofenac acid lysine for a new diclofenac acid salt with less stimulation than diclofenac sodium salt.METHODS:Uniform design was used to get the best synthetic conditions,and spectral and elementary analyses to identify the product.The rabbit's eyes were used in stimulative experiments.RESULTS:The best synthetic line was obtained through uniform design researches,with a yield up to 77.6%(purity above 98%).The product,with a molecular formula of C 20 H 25 O 4N 3Cl 2,was identified on the basis of spectral data(UV,IR,MS, 1HNMR, 13 CNMR and DEPT).The experiments showed that the stimulation of diclofenac acid lysine to rabbit's eyes was lower than that of diclofenac sodium(P<0.01).CONCLUSION:The irritating of diclofenac acid lysine to rabbit's eyes is less than that of diclofenac sodium salt.Its synthetic line,easy and rapid,has high yield,and no industrial pollution.