紫连膏家兔破损皮肤重复给药4周毒性研究  

Toxicity Study of Zilian Cream(紫连膏)on Repeat Administration for 4 Weeks in New Zealand Rabbit of Damaged Skinv

作　　者：杨宏博 杨雪松[3] 杨坤芬 柳启涛 张智诚 廖文平 史新辉 谭莹 王京昆 YANG Hongbo;YANG Xuesong;YANG Kunfen;LIU Qitao;ZHANG Zhicheng;LIAO Wenping;SHI Xinhui;TAN Ying;WANG Jingkun(Yunnan Institute of Materia Medica,Kunming 650111,Yunnan,China;Yunnan Province Company Key Laboratory for Traditional Chinese Medicine and Ethnic Drug of New Drug Creation,Kunming 650111,Yunnan,China;Yunnan Provincial Hospital of Traditional Chinese Medicine,Kunming 650021,Yunnan,China)

机构地区：[1]云南省药物研究所,云南昆明650111 [2]云南省中药和民族药新药创制企业重点实验室,云南昆明650111 [3]云南省中医医院,云南昆明650021

出　　处：《辽宁中医药大学学报》2023年第5期9-17,共9页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：云南省重大科技专项计划-重大科技专项(生物医药)(2017ZF011)。

摘　　要：目的观察紫连膏经破损皮肤家兔重复给药4周的全身毒性反应特征及严重程度,推测其可能作用的靶器官/靶组织,并为临床对破损皮肤用药安全及不良反应监测提供参考。方法选用新西兰家兔40只,随机分为4组,即辅料对照组和紫连膏低、中、高3个剂量组,每组10只,雌雄各半。经1000目砂纸摩擦破损后,各组每次分别以50.0、15.0(临床拟用剂量)、32.5和50.0 mg/cm^(2)(临床最大拟用剂量)单位面积容量给予白凡士林及相应的紫连膏,每天给予2次,间隔(4.0±0.5)h,连续给药4周。每次给药后,即刻连续观察动物症状反应1 h,并于每次擦除受试物0.5 h后,再观察给药局部皮肤刺激性反应情况1次。给药结束,恢复观察4周。实验期间,评价动物摄食,检查动物体质量、体温、心电、血常规、血清生化及电解质等指标变化情况。末次给药后和恢复期结束系统解剖,观察各动物组织、器官的体积、颜色、质地、质量等异常情况,并进行胸骨骨髓象以及组织病理学检查。结果给药期间,紫连膏各剂量组动物均出现红斑或/和水肿刺激反应症状,从动物出现刺激反应症状的数量和严重程度上看,具有随着剂量增加和给药时间的持续随之增加的趋势。各剂量组通过皮肤刺激强度标准进行评价,结果均已达到轻度刺激。同时,与辅料对照组比较,可见GLU表现出明显的升高趋势变化,APTT和LDH表现出明显的下降趋势变化,且有一定的剂量-反应关系,其中紫连膏低、中、高3个剂量组的APTT、LDH,以及紫连膏高剂量组GLU指标均具有显著性差异(P<0.05或P<0.01)。停药4周,可恢复正常。结论紫连膏长期使用对破损的家兔皮肤具有一定刺激性,且同时可导致凝血和LDH、GLU指标的变化,可为破损皮肤的临床用药安全及不良反应监测提供理论依据。Objective To observe the toxicity reaction characteristics and severity of Zilian Cream(紫连膏)on 4 weeks after repeat percutaneous topical administration in rabbits of damaged skin,to conjecture main target organs,and to provide reference for clinical medication safety of damaged skin and adverse drug reaction(ADR)monitoring.Methods 40 New Zealand rabbits were randomly divided into 4 groups,namely excipient control group,and Zilian Cream-low,medium and high dosage groups.Every group was 10 rabbits,female and male in half.After back topical skin of rabbit was demaged with 1000 meshes sandpaper,the medical vaseline and corresponding Zilian Cream were given percutaneously in the per unit area capacity of 50.0,15.0(proposed clinical dosage),32.5 and 50.0 mg/cm^(2)(proposed clinical maximum dosage),twice a day at an interval of(4.0±0.5)h for 4 weeks.General symptoms,signs of rabbits was observed immediately for 1 hour,when the control and test drug had given percutaneously each time.After cleaning off the cream each time,and waiting for more than 0.5 h,irritation response symptom of topical skin was observed.The rabbits had been observing constantly for 4 weeks after the end of dosing period.During the different period of study,the body weight,temperature,ECGⅡ,routine blood test indexes,serum biochemical and electroyltes indexes were evaluated in rabbits of groups.Rabbits of groups were dissected systematically after last administration and the end of recovery period,which observed on volume,colour,texture etc.of organs,if there should be abnormal,and had been examining sternal marrow indexs and histopathologic characteristics.Results During the repeat percutaneous topical administration in rabbits,skin irritation response symptoms observed on erythema or/and edema of different degrees in animals of Zilian Cream-low,medium and high dosage group,which were scored by scoring criteria of skin irritation response.From the number and severity of irritation symptoms in animals,there was a trend of increase with the r

关 键 词：紫连膏 长期毒性 家兔 破损皮肤 经皮给药 

分 类 号：R285.5[医药卫生—中药学]