加减活络效灵丹的临床前安全性评价(英文)

Preclinical safety evaluation of the aqueous acetone extract of Chinese herbal formula Modified Huo Luo Xiao Ling Dan

目的:评估加减活络效灵丹口服应用的安全性。方法:检索TCMlars(www.cintcm.com)、PubMed(MEDLINE)文献和《中华本草》1999年版、《世界卫生组织精选医用植物》(Ⅰ～Ⅲ卷)关于活络效是丹及其组成药物的毒性方面的内容。大鼠单次给予最大剂量活络效灵丹(9.2 g/kg)评价药物急性毒性;给予4.6g/kg活络效灵丹,连续给药9 d,采用运动功能实验和行为学观察等评价药物亚慢性毒性或不良反应;活络效灵丹2.30g/kg灌胃42d,评价药物慢性毒性或不良反应。结果:文献检索提示,活络效灵丹及其11味组成中药在中文中医药文献中没有副作用或不良反应记载。在临床习用剂量下,《中华本草》和《世界卫生组织精选医用植物》中没有发现该方组成药物有毒副作用或不良反应。大鼠实验提示:(1)应用单次口服最大剂量9.2 g/kg,在14 d观察期中没有发现活络效灵丹对大鼠体征、体质量有明显影响,无大鼠死亡;(2)运动实验提示,每日喂服4.6 g/kg,连续9 d,活络效灵丹未造成运动功能的损害;(3)活络效灵丹9 d连续给药,弗氏完全佐剂致炎大鼠没有出现明显的行为改变、不良反应和体征(最大观察剂量4.6 g/kg),正常大鼠连续9日每日喂服活络效灵丹4.6 g/kg,在用药期间以及停药后14 d内,未出现明显的不良反应;(4)每日应用活络效灵丹2.30g/kg连续42 d喂服正常大鼠,未观察到大鼠出现明显的行为改变、不良反应和体征,以及血清生化和组织病理改变。结论:动物实验提示加减活络效灵丹安全,无明显毒副作用,且文献报道中未发现加减活络效灵丹临床试验或动物实验中有副作用。

Objective：To investigate the safety of oral administration of Modified Huo Luo Xiao Ling Dan（HLXLD）,a compound traditional Chinese herbal medicine. Methods：The toxicological information of HLXLD and its individual constituent herbs was searched in cintom or TCMIars（www.cintcm.com）,PubMed（MEDLINE）,Chinese Herbal Medicine（1999） and WHO Monographs on Selected Medicinal Plants（Vol.Ⅰ—Ⅲ）.Single-dose acute toxicity was assessed by using the highest possible dosage.Motor function test was used to determine whether the herbal formula might cause motor impairment.Nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects,and 42-day chronic toxicity/adverse effects in rats were also assessed. Results：The literature searches showed that HLXLD and its eleven ingredient herbs had no side/adverse effects listed in the traditional Chinese medicine literature.Under the dosages proposed in the formula,the HLXLD formula had no side/adverse effects according to MEDLINE,Chinese Herbal Medicine and WHO Monographs on Selected Medicinal Plants.The studies in rats showed：（1） in single-dose acute toxicity assessment,the maximal feasible single oral dose,9.20 g/kg HLXLD,showed no significant effect on clinical signs,or body weight and mortality over a 14-day period in rats;（2） during motor function test,nine-day repeat-dose of daily HLXLD treatment at 4.60 g/kg did not cause motor impairment;（3） in nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects assessment,there were no noticeable abnormal behavioral changes or obvious adverse reactions and signs in complete Freund＇s adjuvant inflamed rats（highest observed dosage：4.60 g/kg）,and no noticeable adverse effects were observed during,or 14 days after nine-day treatment at 4.60 g/kg in non-inflamed rats;（4） during 42-day chronic toxicity/adverse effects assessments,no noticeable abnormal behavioral changes,no obvious adverse reactions and signs were observed in normal rats administered with HLXLD at a dose of 2.30 g/kg and the values of serum biochemistry and histopathology were in normal range. Conclusion：Both existing information and animal data support that Modified HLXLD is a safe herbal product for clinical application.