仔泻康口服液的急性毒性和亚慢性毒性试验研究
详细信息    查看全文 | 推荐本文 |
  • 英文篇名:Study on Acute and Sub-chronic Toxicity Study of Zixiekang Oral Liquid
  • 作者:雒利蓉 ; 王慧 ; 崔东安 ; 王富河 ; 王胜义
  • 英文作者:LUO Lirong;WANG Hui;CUI Dongan;WANG Fuhe;WANG Shengyi;College of Veterinary Medicine,Xinjiang Agricultural University;Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture,Lanzhou Institute of Animal Husbandry and Pharmaceutical Science;
  • 关键词:仔泻康口服液 ; 急性毒性试验 ; 慢性毒性试验
  • 英文关键词:Zixiekang oral liquid;;acute toxicity test;;sub-chronic toxicity test
  • 中文刊名:GWXK
  • 英文刊名:China Animal Husbandry & Veterinary Medicine
  • 机构:新疆农业大学动物医学院;中国农业科学院兰州畜牧与兽药研究所农业部兽药创制重点实验室;
  • 出版日期:2018-09-27 11:19
  • 出版单位:中国畜牧兽医
  • 年:2018
  • 期:v.45;No.346
  • 基金:国家自然基金青年科学基金项目(31502113);; 公益性行业(农业)专项项目(20130304-17);; 中国农业科学院科技创新工程项目(CAAS-ASTIP-2014-LIHPS-03)
  • 语种:中文;
  • 页:GWXK201809031
  • 页数:9
  • CN:09
  • ISSN:11-4843/S
  • 分类号:244-252
摘要
试验旨在通过小鼠急性毒性试验和大鼠亚慢性毒性试验对仔泻康口服液进行安全性评价,为临床安全用药提供理论依据。在急性毒性试验中,采用最大给药剂量对36只昆明小鼠进行灌胃给药。在亚慢性毒性试验中,将80只大鼠,随机均分成高、中、低剂量组和对照组,高、中、低剂量组分别按24、12和6g/kg体重灌胃给药,对照组给予等体积生理盐水,连续给药30d,停药后称量大鼠体重、检测血常规指标、血液生化指标、计算脏器指数并观察组织病理变化等。结果显示,在急性毒性试验中,各剂量组均无小鼠死亡,无法计算LD50,最大耐受量试验也无死亡情况;在亚慢性毒性试验中,该口服液对大鼠生长发育没有影响;经剖检,仅高剂量组可见中央静脉远端的肝细胞有不同程度的肿大,但未见坏死和炎性反应,其他各剂量组的实质器官均未发现异常变化;各剂量组血液学指标、血液生化指标和脏器指数均在正常范围内,与对照组相比均无显著差异(P>0.05)。结果表明,根据外源化学物急性毒性分级(WHO)标准,该制剂属于无毒物质,安全性较高,在合理剂量下,临床使用仔泻康口服液是安全的。
        The aim of this experiment was to evaluate the safety of Zixiekang oral liquid by acute toxicity test in mice and sub-chronic toxicity test in rats,so as to provide theoretical basis for clinical use of drugs.Acute toxicity test was conducted in 36 mice by oral administration with the maximum dose method.In sub-chronic toxicity test,80 rats were randomly divided into high,medium,low dose and control groups,the respective dose of the experimental groups were 24,12 and6 g/(kg·BW)by oral administration,and the control group was given saline at the same volume for 30 days.The weight of the rats was measured after withdrawal.The blood routine index,blood biochemical index,viscera index were calculated.The results showed that no mice died in acute toxicity test,LD50 could not be calculated,and there was no death in maximum tolerance test.In the sub-chronic toxicity test,weight gain of Wistar rats in the treatment group had no significant effect;There were no distinct abnormal changes in parenchymal organs other than the hepatocytesat the distal end of the vein showed swelling of varying degrees while no necrosis or inflammatory reaction in high dose treatment group,and there was no significant difference in hematological,biochemical and visceral indexes compared with control group(P>0.05).According to the acute toxicity of xenobiotics classification standard(WHO),the formulations were no toxic substances,high safety.Thus,the Zixiekang oral liquid was safe in clinical treatment.
引文
[1]PEARCE G P.Epidemiology of enteric disease in grower-finisher pigs:A postal survey of pig producers in England[J].Veterinary Record,1999,144(13):338-342.
    [2]王红宁.仔猪腹泻成因及综合防治技术措施[J].中国畜牧杂志,2006,42(6):58-60.WANG H N.The cause and integrated control of piglet diarrhea[J].Chinese Journal of Animal Science,2006,42(6):58-60.(in Chinese)
    [3]施仁波,周以华.浅谈中草药饲料添加剂的优势及发展前景[J].畜牧与兽医,2003,35(3):18-19.SHI R B,ZHOU Y H.Advantages and prospects of Chinese herbal feed additives[J].Animal Husbandry&Veterinary Medicine,2003,35(3):18-19.(in Chinese)
    [4]毛景东.中草药的激素样作用在动物生产中应用的优势及问题[J].中国畜牧兽医,2010,37(12):246-248.MAO J D.Advantages and problems of application of hormone-like effects of Chinese herbal medicine in animal production[J].China Animal Husbandry&Veterinary Medicine,2010,37(12):246-248.(in Chinese)
    [5]农业部兽药评审中心.兽药研究技术指导原则汇编[M].北京:化学工业出版社,2012.MINISTRY OF AGRICULTURE VETERINARY MEDICINE APPRAISAL CENTER.Compilation of Technical Guidelines for Veterinary Drug Research[M].Beijing:Chemical Industry Press,2012.(in Chinese)
    [6]郑筱萸.化学药品和治疗用生物制品研究指导原则[M].北京:中国医药科技出版社,2002.ZHENG X Y.Guidelines for the Study of Biological Products for Chemical and Therapeutic Use[M].Beijing:The Medicine Science and Technology Press of China,2002.(in Chinese)
    [7]吴海港,徐光科,胡静,等.硫酸头孢喹肟脂质体的毒理学试验及安全性评价[J].中国畜牧兽医,2017,44(8):2523-2528.WU H G,XU G K,HU J,et al.Toxicology test and safety evaluation of cefquinome sulfate liposomes[J].China Animal Husbandry&Veterinary Medicine,2017,44(8):2523-2528.(in Chinese)
    [8]李旭廷,王斌,李思聪,等.当归补血汤提取物亚慢性毒性试验研究[J].中国畜牧兽医,2017,44(10):3090-3099.LI X T,WANG B,LI S C,et al.Study on subacute toxicity test of the extact of Dangguibuxue Tang[J].China Animal Husbandry&Veterinary Medicine,2017,44(10):3090-3099.(in Chinese)
    [9]李涓,高天,谢子清,等.苍耳子不同提取物的毒性比较实验[J].时珍国医国药,2005,16(6):484-487.LI J,GAO T,XIE Z Q,et al.The toxicity comparison experiment of the extractions fromFructusxanthii[J].Lishizhen Medicine and Materia Medica Research,2005,16(6):484-487.(in Chinese)
    [10]胡庭俊,刘姗姗,赵灵颖,等.木蝴蝶提取物制备及其抗菌抗炎活性的研究[J].中国畜牧兽医,2010,37(3):225-228.HU T J,LIU S S,ZHAO L Y,et al.Preparation of Oroxylum indicum extracts and their anti-bacterial and anti-inflammatory activities[J].China Animal Husbandry&Veterinary Medicine,2010,37(3):225-228.(in Chinese)
    [11]雷宏东,梁剑平,郭志廷,等.常山提取物急性毒性试验研究[J].中国畜牧兽医,2011,38(6):236-238.LEI H D,LIANG J P,GUO Z T,et al.Study on the acute toxicity of Dichroa febrifuga extractive[J].China Animal Husbandry&Veterinary Medicine,2011,38(6):236-238.(in Chinese)
    [12]刘红梅,郑爱华,蔡光先.超微四逆汤对大鼠的长期毒性试验[J].中华中医药学刊,2012,4:776-779.LIU H M,ZHENG A H,CAI G X.Long-term toxicity testing of Chaowei Sini Decoction on rats[J].Chinese Archives of Traditional Chinese Medicine,2012,4:776-779.(in Chinese)
    [13]瞿发林,过伟,孙元琪,等.乳康口服液的急性毒性试验研究[J].海峡药学,2012,24(1):32-34.QU F L,GUO W,SUN Y Q,et al.Study on acute toxicity test of Rukang oral liquid[J].Strait Pharmaceutical Journal,2012,24(1):32-34.(in Chinese)
    [14]石东霞,蒋忠荣,殷中琼,等.印楝油对小鼠的亚慢性经口毒性研究[J].中国兽医科学,2011,41(1):79-84.SHI D X,JIANG Z R,YIN Z Q,et al.Studies on the subchronic oral toxicity of neem oil in mice[J].Chinese Veterinary Science,2011,41(1):79-84.(in Chinese)
    [15]彭文静,辛蕊华,任丽花,等.紫菀不同极性段提取物对SD大鼠亚慢性毒性试验研究[J].中国畜牧兽医,2016,43(1):147-156.PENG W J,XIN R H,REN L H,et al.Study on subchronic toxicity test of different polarity section extracts fromAster tataricus L.f.on SD rats[J].China Animal Husbandry&Veterinary Medicine,2016,43(1):147-156.(in Chinese)
    [16]周宁,张海华,吕智超,等.饲粮锌水平对冬毛期水貂血清生化指标和脏器指数的影响[J].畜牧兽医学报,2014,45(12):1988-1994.ZHOU N,ZHANG H H,LV Z C,et al.Effects of diets with different zinc levels on the selected serum biochemical indexes and organ indexes of minks during the winter hair period[J].Acta Veterinaria Et Zootechnica Sinica,2014,45(12):1988-1994.(in Chinese)
    [17]王琪,齐仁立,王敬,等.从胚胎期到育肥期饲粮添加共轭亚油酸对猪肉品质、脏器指数及脂肪酸组成的影响[J].中国畜牧杂志,2017,53(2):79-84.WANG Q,QI R L,WANG J,et al.Effects of CLA supplementation on meat quality,organ index and fatty acid composition of pigs from embryo to finishing period[J].Chinese Journal of Animal Science,2017,53(2):79-84.(in Chinese)
    [18]张海华,王士勇,南韦肖,等.饲粮铁水平对冬毛期水貂生产性能、血清生化指标和脏器指数的影响[J].畜牧兽医学报,2017,48(8):1557-1564.ZHANG H H,WANG S Y,NAN W X,et al.Effects of dietary iron levels on production performance,blood serum biochemical parameters and organ index of mink[J].Acta Veterinaria Et Zootechnica Sinica,2017,48(8):1557-1564.(in Chinese)
    [19]贺秀媛,张淑芳,林峰,等.醋酸铅对雌性小鼠生长发育及主要内脏器官的影响[J].中国兽医学报,2015,35(7):1153-1158.HE X Y,ZHANG S F,LIN F,et al.Effect of lead acetate on weight gain,development and main organs in female mice[J].Chinese Journal of Veterinary Science,2015,35(7):1153-1158.(in Chinese)
    [20]王姗姗,路浩,荣杰,等.甘肃棘豆对SD大鼠组织损伤的病理学[J].中国兽医学报,2013,33(2):246-249.WANG S S,LU H,RONG J,et al.Pathological study on tissue injury of Oxytropis kansuensis Bunge in SD rats[J].Chinese Journal of Veterinary Science,2013,33(2):246-249.(in Chinese)
    [21]路浩,韦冬梅,赵宝玉,等.氯化汞对SD大鼠组织损伤的病理学研究[J].中国兽医学报,2010,30(8):1091-1094.LU H,WEI D M,ZHAO B Y,et al.Pathological study on tissue injury of mercuric chloride in SD rats[J].Chinese Journal of Veterinary Science,2010,30(8):1091-1094.(in Chinese)
    [22]韩天龙,王敏,红敏,等.Masson三色染色与HE染色在豚鼠牙齿组织石蜡切片中的比较研究及应用[J].中国畜牧兽医,2011,38(3):55-57.HAN T L,WANG M,HONG M,et al.The comparison and application of Masson trichrome and HE staining in histological paraffin sections of teeth in guinea pig[J].China Animal Husbandry&Veterinary Medicine,2011,38(3):55-57.(in Chinese)
    [23]陈忠伟,刘伟,赵武.复方中药制剂对小鼠的急性毒性试验[J].中国畜牧兽医,2007,34(6):112-113.CHEN Z W,LIU W,ZHAO W.Acute toxicity experiments of Chinese herbal compound on mice[J].China Animal Husbandry&Veterinary Medicine,2007,34(6):112-113.(in Chinese)
    [24]刘昌孝.新药安全性评价中的毒代动力学研究[A].全国药物毒理学会议[C].2007.LIU C X.Study on pharmacokinetics in safety evaluation of new drugs[A].National Conference on Drug Toxicology[C].2007.(in Chinese)
    [25]姜玲玲,陈鸿宇,史开志,等.一种新兽用止泻中药复方制剂对大鼠的急性及亚慢性毒性试验[J].中国畜牧兽医,2016,43(11):3073-3079.JIANG L L,CHEN H Y,SHI K Z,et al.Acute and sub-chronic toxicity test on rats of a new kind of antidiarrheal Chinese herbal medicine compound preparation for livestock[J].China Animal Husbandry&Veterinary Medicine,2016,43(11):3073-3079.(in Chinese)
    [26]李胜坤,王胜义,崔东安,等.乌锦颗粒剂的急性毒性与亚慢性毒性试验研究[J].中国畜牧兽医,2015,42(5):1203-1210.LI S K,WANG S Y,CUI D A,et al.Study on acute and sub-chronic toxicity of Wu Jin granules[J].China Animal Husbandry&Veterinary Medicine,2015,42(5):1203-1210.(in Chinese)
    [27]路西明,王建刚.白头翁对利福平异烟肼肝毒性研究[J].中国中医药信息杂志,1998,5(8):21.LU X M,WANG J G.Study on the hepatotoxicity of Pulsatillato rifampicin isoniazid[J].Chinese Journal of Traditional Chinese Medicine Information,1998,5(8):21.(in Chinese)
    [28]NODA A,SENDO T,OHNO K,et al.Effects of rifampicin and phenobarbital on the fate of isoniazid and hydrazine in vivo in rats[J].Toxicology Letters,1985,25(3):313-317.
    [29]ANANDAN R,DEVAKI T.Hepatoprotective effect of Picrorrhiza kurroa on tissue defence system in D-galactosamine-induced hepatitis in rats[J].Fitoterapia,1999,70(1):54-57.
    [30]刘霆,陈玉祥,赵颜忠,等.银杏内酯软胶囊毒理学研究[J].中国现代医学杂志,2003,13(6):24-27.LIU T,CHEN Y X,ZHAO Y Z,et al.Toxicologic study on Ginkgolides capsules[J].China Journal of Modern Medicine,2003,13(6):24-27.(in Chinese)
    [31]唐娇,赵敏,谭剑斌,等.三七的经口急性毒性及亚慢性毒性研究[J].华南预防医学,2015,41(6):521-526.TANG J,ZHAO M,TAN J B,et al.Acute oral toxicity and subchronic toxicity of Panax notoginseng[J].South China Preventive Medicine,2015,41(6):521-526.(in Chinese)
    [32]HOR S Y,AHMAD M,FARSI E,et al.Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats[J].Journal of Ethnopharmacology,2011,137(3):1067-1076.
    [33]IHSAN A,XU W,HUANG X J,et al.Acute and subchronic toxicological evaluation of mequindox in Wistar rats[J].Regulatory Toxicology&Pharmacology,2010,57(2-3):307-314.(in Chinese)
    [34]彭健波,陶卿,李锦辉,等.蟾酥微丸的急性与亚慢性毒性研究[J].中国畜牧兽医,2017,44(5):1508-1517.PENG J B,TAO Q,LI J H,et al.Acute and sub-chronic toxicity study of Chansu pellets[J].China Animal Husbandry&Veterinary Medicine,2017,44(5):1508-1517.(in Chinese)
    [35]詹纯列,肖育华,李新春,等.普通级、SPF级SD、Wistar大鼠血液生化常值的测定与比较[J].中国比较医学杂志,2004,14(2):94-96.ZHAN C L,XIAO Y H,LI X C,et al.Comparison of normal values of blood examination in conventional,SPF SD and Wistar Rats[J].Chinese Journal of Comparative Medicine,2004,14(2):94-96.(in Chinese)

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700