【作者】 徐凌云； 陈华兵； 肖峰； 徐辉碧； 潘经媛； 陈其友； 余启枝； 周诗其； 杨祥良；

【Author】 Lingyun Xu~1 Huabing Chen~1 Xiangliang Yang~1 Huibi Xu~1 Feng Xiao~1 Jingyuan Pan~2 Qiyou Chen~2 Qizhi Yu~2 Shiqi Zhou~2 (1.College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China; 2.Hubei center for safety evaluation of drugs,Wuhan 430061,China)

【机构】 华中科技大学生命科学与技术学院药物研究所； 湖北省药物安全性评价中心；

【摘要】 目的研究雷公藤内酯微乳凝胶皮肤用药的抗炎、镇痛作用和临床前安全性。方法通过急性和慢性炎症动物模型观察本品的抗炎作用,扭体法和热板法观察本品的镇痛作用。通过兔急性毒性实验(1.2 mg/kg,单次)、兔长期毒性实验(0.06、0.18、0.54 mg/kg,6 mon)、小鼠和犬的安全性药理实验(0.03,0.09,0.27 mg/kg,5 d)、兔皮肤刺激性实验和豚鼠皮肤过敏实验评价本品的安全性。结果雷公藤内酯微乳凝胶在20～120μg/kg剂量范围内(以雷公藤内酯计)能抑制二甲苯致小鼠的耳廓肿胀、棉球致大鼠的肉芽组织增生和角叉菜胶致大鼠的足趾肿胀,对佐剂性关节炎大鼠的继发性病变具有明显的治疗作用,能抑制醋酸所致小鼠扭体反应,延长热板致痛的潜伏期。在上述安全性评价实验中,除发现雷公藤内酯微乳凝胶组和空白微乳凝胶组出现轻度、可逆的红斑、皮屑外,未发现现其他毒性反应。结论雷公藤内酯微乳凝胶具有良好的抗炎和镇痛作用,在本实验条件下,本品具有较好的安全性。更多还原

【Abstract】 Triptolide (TP) is a major active component of Tripterygium wilfordii Hook F (TWHF), which is used to treat rheumatoid arthritis (RA).TWHF has a narrow therapeutic window.To increase the therapeutic index of TP,a novel TP loaded transdermal delivery system,named TP loaded hydrogel- thickened microemulsion (TP-MTH),has been developed to treat RA.This paper evaluated the efficacy and safety of TP-MTH in vivo.Results demonstrated that TP-MTH (0.003%) possessed good anti-in- flammatory and analgesic activities at the 0.02～0.12 mg/kg dose levels in rats and mice.No obvious toxicities were observed in a series of toxicity tests:acute toxicity study of TP-MTH (1.2 mg/kg) in rab- bits,6-month long-term toxicity study of TP-MTH (0.06,0.18,0.54 mg/kg) in rabbits,safety pharma- cology study of TP-MTH (0.03,0.09,0.27 mg/kg,for 5 days) in mice and beagle dogs,skin irritation study in rabbits and skin allergic reaction test in guinea pigs.Only mild reversible skin irritation signs were observed on the skin of animals.These studies suggest that topical TP-MTH is a promising drug for the treatment of RA.更多还原