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目的:研究喜树碱-七元瓜环固体包合物的溶血反应、过敏反应和急性毒性反应,为其临床用药的安全性提供科学依据。方法:按照化学药物过敏性、溶血性、急性毒性研究技术指导原则的要求,对喜树碱-七元瓜环固体包合物进行了溶血反应、过敏反应和急性毒性实验研究,并用已知喜树碱LD50(26.9 mg/kg),通过预实验得到该包合物对小鼠的Dm=104.60 mg/kg,Dn=26.9 mg/kg,并按相邻两剂量比值k=0.75,分为5分组,剂量分别为:104.60 mg/kg,78.45mg/kg,58.84 mg/kg,44.13 mg/kg,33.10 mg/kg。每组小鼠16只,从而求出该包合物的LD50及LD50的95%可信限。结果:动物实验表明,喜树碱-七元瓜环固体包合物无溶血作用、无致敏作用,在急性毒性实验的14 d内,给药量104.60mg/kg的小鼠死亡16只,给药量78.45 mg/kg的小鼠死亡12只,给药量58.84 mg/kg的小鼠死亡8只,给药量44.13 mg/kg的小鼠死亡4只,给药量33.10 mg/kg的小鼠死亡4只,死亡率随给药剂量浓度的升高而升高,小鼠的LD50经计算为53.39 mg/kg,LD50的可信限为43.65~52.48 mg/kg。结论:喜树碱-七元瓜环固体包合物在0.3 mg/m L浓度时,无溶血作用、无致敏作用。该包合物的LD50为53.39 mg/kg,大于喜树碱的LD50,说明喜树碱通过瓜环包合以后,降低了毒副作用,致使七元瓜环喜树碱包合物的LD50增大了。
Objective: To study the hemolysis reaction, allergic reaction and acute toxicity reaction of camptothecin - seven melon ring solid clathrate, and provide a scientific basis for the safety of its clinical medication. Methods: According to the requirements of technical guidelines for allergic, hemolytic and acute toxicity of chemicals, hemolysis, anaphylaxis and acute toxicity of camptothecin - (26.9 mg / kg), the Dm value of this inclusion compound was 104.60 mg / kg and Dn = 26.9 mg / kg in mice, and divided into 5 Grouping, the doses were: 104.60 mg / kg, 78.45 mg / kg, 58.84 mg / kg, 44.13 mg / kg, 33.10 mg / kg. Sixteen mice per group were used to determine the 95% confidence limits for the LD50 and LD50 of the inclusion compound. Results: Animal experiments showed that the camptothecin-seven melon ring solid inclusion compound had no hemolysis and no sensitization. Within 14 days of the acute toxicity experiment, mice with the dose of 104.60 mg / kg died of 16, Twelve mice died at a dose of 78.45 mg / kg, 8 mice at a dose of 58.84 mg / kg, 4 mice at a dose of 44.13 mg / kg and a dose of 33.10 mg / kg 4 mice died, the mortality rate increased with the increase of the dose concentration, mouse LD50 was calculated as 53.39 mg / kg, LD50 with a confidence limit of 43.65 ~ 52.48 mg / kg. CONCLUSION: The camptothecin-seven-melon ring solid inclusion compound has no hemolysis and no sensitization at a concentration of 0.3 mg / mL. The LD50 of the inclusion compound is 53.39 mg / kg, which is larger than the LD50 of camptothecin, indicating that the camptothecin reduces the toxic side effects after the inclusion of camptothecin, resulting in an increase of the LD50 of the camptothecin clavulanate inclusion complex It’s