探索性毒理试验在临床前安全性评价中的意义

来源 :中国药理学与毒理学杂志 | 被引量 : 0次 | 上传用户:boyanfang
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目的探讨不同给药途径下动物的毒性反应。方法 50只SD大鼠,雌雄各半,随机分为5组,分别为溶媒对照组(组1)、ZY-XXX灌胃100,200和400 mg·kg-1和ZY-XXX局部涂抹组(160 mg/次)。给药浓度分别是,灌胃20,40和80mg.ml-1及局部涂抹组80 mg.ml-1。给药容量分别为5 m.lkg-1(灌胃组)和2 ml/次(局部涂抹组)。重复灌胃和涂抹给予7 d,每天2次,于第8天对所有动物计划实施安乐死。所有动物除全身组织器官检查外,还对动物进行了临床观察、体重、食量、临床病理、血糖的测定,脏器组织采集保存待日后分析。结果临床观察,与溶媒对照组相比,灌胃低、中、高剂量组动物除可见对照组动物相似的症状流涎外,未见其他异常;局部涂抹组可见明显毒性反应,如死亡、呼吸困难、俯卧、精神不振、鼻腔分泌物、颤抖、肛周污秽、自发活动异常、用力呼吸、闭眼、弓背、竖毛、黄绿色尿液等。灌胃高剂量组雄性动物体重增长略低于溶媒对照组,涂抹组动物的体重明显降低。其他指标,除涂抹组动物的血糖明显增高外,未见明显异常。大体观察,灌胃组动物未见明显异常,涂抹组动物可见肝大小不等的白色区域、胃黏膜大小不等的黑色区域、肺暗红色区域和胸腺明显减小等。结论该供试品以灌胃和局部涂抹两种途径给予SD大鼠,灌胃低、中、高剂量组动物未见明显毒性(除高剂量组雄性动物体重增长减慢外),局部涂抹组的动物毒性反应重。 Objective To investigate the toxicity of animals under different route of administration. Methods 50 SD rats were randomly divided into 5 groups: vehicle control group (group 1), ZY-XXX intragastric administration of 100, 200 and 400 mg · kg -1 and ZY-XXX topical application group (160 mg / Second). The administration concentrations were 20, 40 and 80 mg.ml-1 orally, and 80 mg.ml-1 for topical application group. Dosing capacity were 5 m.lkg-1 (gavage group) and 2 ml / time (topical smear group). Repeated gavage and smear given for 7 days, twice a day, on the 8th day for all animal programs euthanasia. All animals in addition to body tissue and organ examination, but also for clinical observation of animals, body weight, food intake, clinical pathology, blood glucose determination, organ tissue collected for future analysis. Results Clinical observation showed that compared with the vehicle control group, there were no other abnormalities in animals in the low, medium and high doses of gavage, except for the similar symptoms of the animals in the control group. The local smear group showed obvious toxic reactions such as death and dyspnea , Prone, sluggish, nasal secretions, trembling, perianal contamination, spontaneous abnormalities, forced breathing, eyes closed, bow, hair, yellow-green urine. The weight gain of male animals in the high dose group was slightly lower than that of the vehicle control group, and the weight of the animals in the smear group was significantly lower. Other indicators, in addition to smear animals significantly increased blood glucose, no obvious abnormalities. In general, no significant abnormalities were found in the animals in the gavage group. In the smear group, white areas with different sizes of liver, black areas with different sizes of gastric mucosa, dark red areas of the lung and thymus were significantly reduced. CONCLUSIONS: The rats were given gavage and topical application of two routes to SD rats, and no obvious toxicity was found in the low, medium and high dose groups (except for the high dose group, the weight gain of the male animals was slowed down), and the local smear group Animal toxicity is heavy.
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