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Journal of Chinese Integrative Medicine ›› 2007, Vol. 5 ›› Issue (1): 74-77.doi: 10.3736/jcim20070115

• Original Experimental Research • Previous Articles     Next Articles

Comparison of acute toxicity of two preparations of norcantharidin in mice

Bai Li, Li-feng Zhu, Ya-ni Zhang, Wei Gu   

  1. Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Online:2007-01-31 Published:2007-01-21

Objective: To compare the acute toxicity of common injection and sustained-release preparation of norcantharidin for mice so as to identify the attenuation of the sustained-release preparation of norcantharidin. 

Methods: The poloxamer 407 was used as a sustained-release vehicle for topical administration of norcantharidin, and the acute toxicity of mice treated with common injection and sustained-release preparation of norcantharidin was observed. The median lethal dose (LD50) was calculated by Bliss software. 

Results: The symptoms of mice were similar between the two groups, but the appearance of symptoms in norcantharidin/poloxamer 407 group was 4 hours later than that in norcantharidin group. The LD50 of norcantharidin administered through vein injection was 12.6 mg/kg. The LD50 of norcantharidin/poloxamer 407 administered through intraperitoneal injection, intrahepatic injection and intramuscular injection were 19.9, 19.1 and 20.9 mg/kg, respectively, and the LD50 of the common preparation were 13.0, 13.1 and 15.1 mg/kg, respectively. 

Conclusion: The norcantharidin/poloxamer 407 is less toxic than the equivalent dose of norcantharidin, mainly because norcantharidin/poloxamer 407 may release norcantharidin sustainedly, thus reducing norcantharidin concentration in blood.

Key words: sustained-release preparations, poloxamer 407, acute toxicity tests

CLC Number: 

  • R965.3

Table 1

Injected volume and dose of two preparations of norcantharidin in mice"

Table 1

Acute toxicity of two preparations of norcantharidin in mice"

[1] Li JL, Cai YC, Liu XH , et al. Norcantharidin inhibits DNA replication and induces apoptosis with the cleavage of initiation protein Cdc6 in HL-60 cells[J]. Anticancer Drugs, 2006,17(3):307-314
[2] Chen YJ, Shieh CJ, Tsai TH , et al. Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells[J]. Anticancer Drugs, 2005,16(3):293-299
[3] 李琦, 范忠泽, 李先茜 , 等. 去甲斑蝥素微球介入治疗大鼠肝癌疗效及其机制研究[J]. 中西医结合学报, 2006,4(4):378-383
Li Q, Fan ZZ, Li XX , et al. Effects of interventional therapy with norcantharidin microsphere on hepatoma in rats and its mechanism[J]. Zhong Xi Yi Jie He Xue Bao, 2006,4(4):378-383
[4] 董丽华, 曲雅勤, 刘锋 , 等. 复方去甲斑蝥素合并放射治疗中晚期食管癌近期疗效的临床观察[J]. 吉林医学, 2002,23(5):301
Dong LH, Qu YQ, Liu F , et al. Short-term clinical curative effect of norcantharidin compound recipe and radiotherapy on intermediate and advanced esophageal carcinoma[J]. Jilin Yi Xue, 2002,23(5):301
[5] 郑英兰, 史春雷, 贺延新 . 去甲斑蝥素治疗肝癌的临床研究[J]. 河北医学, 2005,11(9):820-821
Zheng YL, Shi CL, He YX . Clinical study of norcantharidin on patients with hepatoma[J]. Hebei Yi Xue, 2005,11(9):820-821
[6] 胡森, 盛志勇, 薛立波 , 等. 去甲斑蝥素致大鼠腹腔炎症与多脏器功能失常综合征[J]. 中国危重病急救医学, 1998,10(10):603-606
Hu S, Sheng ZY, Xue LB , et al. A trial to reproduce multiple organ dysfunction syndrome in animals with intraperitoneal injection of cantharidin[J]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 1998,10(10):603-606
[7] 孙瑞元 . 定量药理学(第1版)[M]. 北京: 人民卫生出版社, 1987,( 第1版):167
Sun RY.Quantitative Pharmacology ( 1st ed)[M]. Beijing: People's Medcial Publishing House, 1987,( 1st ed):167
[8] 邹建军, 张胜强, 冯瑞祥 . 斑蝥素毒性及其药(毒)动力学研究[J]. 中国药科大学学报, 2002,33(5):393-396
Zou JJ, Zhang SQ, Feng RX . The toxicity and pharmacokinetics of cantharidin[J]. Zhongguo Yao Ke Da Xue Xue Bao, 2002,33(5):393-396
[9] 中华人民共和国卫生部药典委员会. 中华人民共和国药典((一部))[M]. 北京: 化学工业出版社,2000,((一部)): 272
Committee of Pharmacopeia , Ministry of Health of the People's Republic of China. Pharmacopoeia of the People's Republic of China(Part Ⅰ)[M]. Beijing: Chemical Industry Press, 2000,( Part Ⅰ):272
[10] 温祥云, 孙骏奇, 王丽娟 , 等. 去甲斑蝥素对肝细胞的急性损伤[J]. 临床与实验病理学杂志, 1990,6(3):203-205
Wen XY, Sun JQ, Wang LJ , et al. The acute hepatocellular damage by norcantharidin[J]. Lin Chuang Yu Shi Yan Bing Li Xue Za Zhi, 1990,6(3):203-205, V3
[11] 国家医药管理局医药工业情报中心站. 新药指南(第1版)[M]. 北京: 中国医药科技出版社,1989,(第1版): 71, 74
Information Centre of Pharmaceutical Industry of State Pharamaceutical Administration. The guide of new drugs(1st ed)[M]. Beijing: Medical Science and Technology Press of China,1989,(1st ed): 71, 74
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