熊果酸纳米脂质体Ⅰ期临床单次耐受性试验研究  

A phase Ⅰ clinical trial of ursolic acid nanoliposome for evaluating its single-dose tolerance and safety

作　　者：赵翠翠[1] 钱正子[1] 王华庆[1] 宋拯[1] 孟祥睿[1] 赵静[1] 阎昭[1] 郝希山[1] 

机构地区：[1]天津医科大学附属肿瘤医院内一科,天津市肿瘤防治重点实验室,天津300060

出　　处：《中国新药杂志》2011年第2期148-151,共4页Chinese Journal of New Drugs

摘　　要：目的:观察注射用熊果酸纳米脂质体在肿瘤患者及健康受试者中单次静脉给药的安全性和耐受性,获得其单次给药的最大耐受剂量和剂量限制性毒性。方法:采用先低剂量后高剂量的逐渐递增的探索性研究方法,依次给予11,22,37,56,74,98,130 mg.m-2熊果酸纳米脂质体。给药后第1,2,4,6,8,12,24及72 h观察生命体征和临床症状,24和72 h进行各项理化检查。结果:受试者单次静脉应用熊果酸纳米脂质体的最高剂量为130 mg.m-2,剂量限制性毒性为肝脏毒性、腹泻,其他不良反应包括腹胀、恶心、血脂异常、血钠升高、镜下血尿、皮肤过敏反应和血管刺激性。结论:本研究中注射用熊果酸纳米脂质体单次静脉给药的最大耐受剂量为98 mg.m-2,剂量限制性毒性为肝脏毒性、腹泻。Objective： To evaluate the single-dose tolerance and safety of intravenous ursolic acid nanoliposome.Methods： In 7 dose groups,the doses of ursolic acid nanoliposome were increased from 11mg·m-2 to 22,37,56,74,98 and 130mg·m-2.The tolerance and safety at 1,2,4,6 and 8,12,24 and 72 h after the single-dose administration were assessed based on changes in vital signs and clinical symptoms,and physico-chemical examination at 24 and 72 h after administration.Results： The maximum intravenous single-dose of ursolic acid nanoliposome was up to 130mg·m-2.The main toxic reactions were hepatotoxicity and diarrhea,other reactions included abdominal distension,nausea,dyslipidemia,serum sodium elevation,microscopic hematuria,skin allergy and vascular irritation.Conclusion： The maximum tolerable dose of intravenous ursolic acid nanoliposome is 98mg·m-2,and the dose-limiting toxicity is hepatotoxicity and diarrhea.

关 键 词：熊果酸 纳米脂质体 Ⅰ期临床试验 耐受性 

分 类 号：R93[医药卫生—生药学] R979.1[医药卫生—药学]