2-甲氧基雌二醇纳米混悬剂的安全性实验

摘要

目的：观察抗癌新药2-甲氧基雌二醇(2-ME)纳米混悬剂的安全性，为其临床试验提供依据。方法分别进行兔耳缘静脉刺激性实验和溶血性实验，豚鼠过敏性实验，小鼠急性毒性实验。结果2-ME 纳米混悬剂对兔静脉血管无明显刺激作用；2-ME 无明显溶血作用；过敏性实验显示，激敏后30 min 内2-ME 纳米混悬剂组豚鼠未出现竖毛、挠鼻、呼吸困难等过敏症状；急性毒性实验显示，静脉注射给药后第14天，2-ME 纳米混悬剂组小鼠心脏、肝脏、肺脏等组织无肉眼可见的黑斑、充血等病理变化。结论2-ME 纳米混悬剂毒性较低，无溶血性、过敏性及刺激性，初步判断该制剂可供静脉注射用。%Objective To evaluate the preclinical safety of 2-methoxyestradiol nanosuspension. Methods The safety of 2-methoxyestradiol nanosuspension for injection was observed through vascular stimulation test of the ear vein on rabbits, hemolytic test using rabbit erythrocytes, active systemic anaphylaxis (ASA) test on guinea pigs and acute toxicity test on mice. Results 2-Methoxyestradiol nanosuspension injection had no irritating effects on vessels, and no haemocytolysis, agglutination and ASA occurred.ASA test showed no allergy symptoms such as piloerection, nose rubbing and dyspnea in guinea pigs 30 min after sensitization.Acute toxicity test revealed that no pathological changes, including black spots and hyperaemia, were visually observed on the heart, liver and lungs after 14 days of intravenous administration. Conclusion 2-Methoxyestradiol nanosuspension injection is relatively safe, with low toxicity, and no hemolytic, anaphylactic and irritating effects. It may be clinically used for injection.