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（第二稿草稿）二OO五年三月2目录一、概述······································································································································3二、撰写格式和要求··············································································3（一）主要研究结果综述································································································31．研发背景······························································································································32．主要药效学试验··············································································································43．一般药理学试验··············································································································44．急性毒性试验···················································································································55．长期毒性试验···················································································································56．过敏性、溶血性、局部刺激性和依赖性试验···························································67．致突变试验·························································································································78．生殖毒性试验····················································································································79．致癌试验·····························································································································810．药代动力学试验············································································································9（二）分析与评价····························································································101．有效性分析及评价········································································································102．安全性分析及评价········································································································103．药代动力学特征分析···································································································104．药理毒理综合分析及评价·························································································115．药理毒理与其它专业间的相关性分析························································115．1与药学专业间的相关性分析···············································································115．2与临床研究的相关性分析····················································································11三、参考文献·······················································································································12四、著者································································································································12附：《中药、天然药物药理毒理研究综述撰写格式和要求》技术指导原则起草说明································································································································133一、概述本指导原则是根据《药品注册管理办法》的有关要求，结合我国中药、天然药物研发的实际情况而制订。本指导原则旨在通过对中药、天然药物药理毒理申报综述资料的格式和内容等方面的要求，规范药理毒理综述资料，引导和提高药品注册申请人对新药研发过程及结果的综合分析能力和自我评价意识。本指导原则根据中药、天然药物注册分类不同类别及药理毒理申报资料的要求对申报临床的药理毒理综述资料统一进行要求。撰写该综述时可根据不同的申报类别，按申报项目的不同要求撰写相应的内容。该指导原则主要内容包括药理毒理主要研究结果综述和分析及评价两大部分。二、撰写格式和要求（一）主要研究结果综述对主要研究结果的综述部分建议按以下内容进行全面、简要的描述，不建议写成对试验结果的简单罗列，不必有具体试验表格及数据等。建议对药效学试验结果或毒理学研究结果以列表的形式进行归纳总结。1．研发背景简要说明文献情况（如果有临床应用史需描述有无不良反应报道及相关的研究进展情况）简要说明前期是否进行过基础研究或筛选研究，若有相关研究，简述主要研究结果。简要说明是否有相关研究成果（奖项、论文、专利等）。42．主要药效学试验2．1试验方法和结果总结简要说明所选择的实验模型及其适用于受试物功能主治的依据，重点描述主要药效学试验结果。试验结果可按照先主要、后次要，先体内、后体外试验的顺序，主要包括：动物、剂量组别（给药途径、时间、频次、剂量，相当于临床人用量的倍数关系等）、阳性组设立及主要试验结果等。建议将试验结果以表格的方式列出，参见表1。表1药效学研究总结试验项目模型选择给药情况剂量/浓度途径时间与临床拟用量的关系主要研究结果123……2．2作用机制的研究若为未在国内上市销售的有效成分，需明确是否进行了有关作用机制的研究，简述其主要研究结果。若有相应的国内、外文献报道，简要描述主要文献结果。3．一般药理研究简要描述动物、剂量组别（给药时间、途径、剂量，相当于药效学剂量的关系）及主要试验结果等。建议将试验结果以表格的方式列出，参见表2。表2一般药理学研究总结试验项目动物给药情况与药效学起效主要研究结果5选择剂量途径时间/频次剂量/临床拟用量的关系精神神经系统一般行为自主活动机能协调催眠协同其他……心血管呼吸系统心血管呼吸其他4．急性毒性试验分别简要描述不同种属动物或不同给药途径下所进行的急性毒性试验，包括动物、给药剂量（与临床拟用剂量的倍数关系）和给药途径。对试验结果的描述应包括：毒性表现（何种毒性反应及程度、是否有毒效关系、出现毒性的最低剂量或毒性出现时间、持续时间及恢复时间）、死亡情况（死亡出现时间，死亡前动物表现，死亡后解剖及病理检查情况）、肉眼及病理检查情况，半数致死量（LD50）或最大耐受量（MTD）。尽量描述性别差异及毒性靶器官。5．长期毒性试验分别描述不同种属动物（如啮齿类及非啮齿类）的长期毒性试验，包括动物种属、剂量组别（相当于临床拟用量的倍数）、给药途径、给药周期、主要观察指标及主要试验结果（如一般表现，体重、进食量，心电图变化，血液学，尿常规，血生化，骨髓象，脏器重量或系数，组织病理学检查；动物死亡情况，包括死亡前表现、死亡动物的检测结果；以及其他需要特殊观察6指标的结果）等。明确无毒剂量、中毒剂量及毒性靶器官，量效及时效关系。6．过敏性、溶血性和局部刺激性、依赖性试验6．1溶血性试验简要描述体外和/或体内试验方法、受试物（是否为拟临床用制剂、批次）、溶剂对照的设立、试验结果（溶血发生的时间及试管号）。若出现红细胞凝聚现象，是否做了进一步观察。简要描述静脉给药的长期毒性试验中是否观察了相关指标的改变，如红细胞、网织红细胞、胆红素、尿蛋白、骨髓象等。6．2刺激性试验6．2．1血管及肌肉刺激性试验简要描述试验动物、剂量组别、给药方式（肌肉注射、静脉注射或滴注，给药速度，浓度，给药次数）、观察时间及试验结果（如给药局部的肉眼观察、评分情况及组织病理学检查结果等）。6．2．2皮肤刺激性试验简要描述完整及破损皮肤的制备方法、给药方式（部位、面积、固定方法、剂量或浓度、时间及频次）及试验结果（肉眼观察、评分、组织病理学检查结果，全身毒性表现，毒性发生时间及消退时间等）。6．3过敏性试验（全身主动/被动皮肤过敏试验）简要描述试验方法，包括动物、剂量组别（含阴性及阳性对照）、致敏方式（途径、剂量、次数、抗血清制备等）、激发方式（途径、剂量）。简要描述试验结果，包括全身过敏反应的发生率和严重程度、持续及恢复时间、死亡率等，以及被动皮肤过敏反应的抗体滴度或蓝斑直径等。76．4依赖性试验简要描述身体依赖性试验方法及试验结果，包括自然戒断试验、替代试验、催促试验、诱导试验等。简要描述精神依赖性试验方法及试验结果，包括自身给药试验等。7．致突变试验7．1微生物回复突变试验简要描述菌株、剂量组别（包括空白对照、溶媒对照、阳性对照、加S9或不加S9及受试物组）、试验方法及试验结果等。7．2染色体畸变试验简要描述细胞、剂量组别（包括空白对照、溶媒对照、阳性对照、加S9或不加S9及受试物组）、试验方法及试验结果等。7．3微核试验简要描述动物、剂量组别（包括空白对照、溶媒对照、阳性对照）、给药途径、试验方法（如骨髓采样等）及试验结果等。8．生殖毒性试验8．1一般生殖毒性试验简要