4-甲基环十五烷酮单次给药毒性试验研究  

The study of single-dose toxicity of 4-methylcyclopentadecanone

作　　者：刘彬彬 蒋秋涵 李晓宇[3] 马玉奎 靳鹏 LIU Binbin;JIANG Qiuhan;LI Xiaoyu;MA Yukui;JIN Peng(Shandong Chengchuang Blue Sea Pharmaceutical Technology Co.,Ltd.,Jinan 250100,China;Qilu Normal University,Jinan 250200,China;Shandong Academy of Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东诚创蓝海医药科技有限公司,山东济南250100 [2]齐鲁师范学院,山东济南250200 [3]山东省中医药研究院,山东济南250014

出　　处：《药学研究》2023年第3期161-164,共4页Journal of Pharmaceutical Research

基　　金：山东省中医药科技重点项目(No.Z-2022058)。

摘　　要：目的研究单次灌胃给予4-甲基环十五烷酮(4-methylcyclopentadecanone,4-MCPC)对Beagle犬和小鼠产生的毒性。方法采用经典的半数致死量法(LD 50法)和最大给药量法分别进行小鼠和Beagle犬单次给药毒性试验,动物分组后灌胃给予不同剂量的4-甲基环十五烷酮,给药1次,给药后观察动物毒性反应,检测动物体重、死亡率、血液学、血液生化学等指标,药后14 d观察结束剖检,检查主要脏器的病变。结果小鼠单次给予4-甲基环十五烷酮的半数致死量为9.41 g·kg^(-1),死亡鼠急性毒性症状主要为水样便、竖毛、俯卧不动、翻正反应消失继而死亡。Beagle犬单次给予4-甲基环十五烷酮的最大给药量为18.40 g·kg^(-1),最大耐受量为1.56 g·kg^(-1),Beagle犬毒性症状主要为稀便、呕吐、精神萎靡、厌食、活动减少等反应。临床检验结果显示18.40、12.24 g·kg^(-1)剂量下Beagle犬凝血酶时间(TT)明显延长,谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)、肌酐(CR)显著升高。结论4-甲基环十五烷酮对小鼠和Beagle犬的急性毒性较小,安全范围较大。Objective To study the single-dose toxicity of 4-methylcyclopentadecanone(4-MCPC)in mice and Beagle dogs.Methods The single-dose toxicity of 4-MCPC in mice and Beagle dogs was evaluated with classical LD 50 and maximum dosage methods respectively.Animals were divided into different groups and were administered with different dose for one time.The general symptoms were observed and body weight,hematology,blood biochemistry and histopathology were detected after administration.The animals were autopsied and lesion of main organs were observed after continuous observation for 14 days.Results The LD 50 of 4-MCPC in mice was 9.41 g·kg^(-1).The main acute toxicity symptoms of dead rats are watery stool,erect hair,lie prone without moving,righting reaction disappeared and eventually to death.The maximum dosage and maximal tolerance dose(MTD)of 4-MCPC in Beagle dog were 18.40 g·kg^(-1) and 1.56 g·kg^(-1),respectively.The main acute toxicity symptoms of dogs were loose stool,vomiting,mental depression,anorexia,less activity.TT was significantly prolonged and ALT,AST,BUN and CR were significantly increased in Beagle dogs at the doses of 18.40 and 12.24 g·kg^(-1).Conclusion The acute toxicity of 4-MCPC in mice and Beagle dogs is small and the safety range is large.

关 键 词：4-甲基环十五烷酮 半数致死量 单次给药毒性 小鼠 BEAGLE犬 

分 类 号：R285.5[医药卫生—中药学]