L-谷氨酸克拉霉素的安全性评价

目的利用L-谷氨酸和克拉霉素反应,制备可溶性谷氨酸克拉霉素盐,并评价其安全性。方法对谷氨酸克拉霉素盐进行了急性毒性、异常毒性、溶血性、血管刺激性试验研究,以此评价其安全性。结果谷氨酸克拉霉素小鼠静脉注射的LD50为292.15mg·kg-1,LD5095%可信限为276.69~306.90mg·kg-1;异常毒性试验显示注射给药后观察48h,未见死亡;溶血性试验显示无溶血和凝集反应;血管刺激性试验显示该药给药后给药部位可见轻微充血,未见其他明显异常。结论谷氨酸克拉霉素具有较好的安全性,可进一步研究开发为注射用新制剂。

Synthesis and primary study on toxicology of clarithromycin glutamate

Objective To synthesize and to evaluate the toxicity of clarithromycin glutamate.Methods Clarithromycin glutamate was synthesized by reaction of clarithromycin with L-glutamic acid.The clarithromycin glutamate may be a novel form of clarithromycin for injection. To evaluate the reliability of it, the acute toxicity,vascular stimulation and hemoly zation were tested. Results The results showed that the intravenous injection LD_ 50 of clarithromycin glutamate in mice was 292.15 mg·kg~ -1 and with 95% confidence limit was 276.69～306.90 mg·kg~ -1 .The abnormal toxicity test showed that no mice died. The hemolytic test showed that it had no hemolyzation and aggregation. The vascular stimulation test showed it had little congestion,but no evidences of abnormity. Conclusion Clarithromycin glutamate is safety and reliable, and can be further studied and developed for injection.