抗癌中药三氧化二砷增效减毒体系与机制研究

Cancer is a major critical incurable diseases. AS2O3 forthe treatment of promyelocytic leukemia and liver cancer asignificant effect of domestic and foreign recognized, but its cardiac toxicity seriously effect it's clinical use. howto minimize their side effects, and give full play to the anti-cancer role to become a hot topic of research at home and abroad. This project on the basis of the preliminary two National Natural Science Foundation"Targeted drug delivery system for anti-cancer traditional Chinese medicine"and "Aconite compatibility toxic and efficacy effects law"，proposed to"Ginseng and Aconite" reduce the cardiac toxicity of "As" as the entry point,the As,Ginseng and Aconite "compatibility - targeted delivery vehicles-route of administration""Reducing Toxicity "overall system concept and technology system for the study of the main line, use the theoriesand techniques of targeted controlled release drug delivery, buildingAs-Ginseng-Aconite multi-component multi-component targeting vector, using a combination of medicine, pharmacology, toxicology, pharmacokinetics, multidisciplinary, explore the As,Ginseng and Aconite "compatibility-targeting vector-the route of administration "on theeffect of com-pharmacokinetic-toxic effects of changes" in law, to reveal the overall mechanism of action and scientific connotations,finalmake As drugs to achieve efficient,safe,drug release controlled" for thepurpose,for building multi-component targeted drug delivery systemto provide a theoretical basis and effectively controlled for the anti-cancer drug safety research to provide ideas and methods.

癌症是重大疑难疾病。三氧化二砷用于治疗早幼粒细胞性白血病和肝癌疗效显著，得到国内外公认，但是其心脏毒性严重影响临床应用，如何最大限度降低其毒副作用，充分发挥抗癌作用成为国内外研究的热点。本项目在前期两项国家自然基金"抗癌中药复方"靶向给药系统研究及"附子配伍毒效规律研究"基础上，提出以"参附"降低"砷"心肌毒性为切入点，以砷-参附"配伍-靶向传递载体-给药途径"整体系统"增效减毒"研究理念和技术体系为研究主线，利用靶向控释给药理论与技术，构建参-附-砷多成分靶向载体，运用药化、药理、毒理、药代动力学等多学科相结合的方法，探索砷-参附"配伍-靶向载体-给药途径"对其效应组分和成分、生物效应"剂量-药效-药代-毒效"的影响及变化规律，揭示其整体作用机理及科学内涵；最终使含砷药物达到"高效、安全、释药可控"为目的，为构建复方靶向给药体系提供理论依据,为抗癌药物达到安全有效可控提供研究思路与方法。

癌症是重大疑难疾病。三氧化二砷用于治疗早幼粒细胞性白血病和肝癌疗效显著，得到国内外公认，但是其心脏毒性严重影响临床应用，如何最大限度降低其毒副作用，是目前研究的重点。. 本项目研究将中医与西医临床配伍或联合用药“增效减毒”理论技术与现代药物靶向传递系统的理论技术相结合，具体开展了以下三方面的研究：. 1.将三氧化二砷(As)砷剂与叶酸（FA）主动靶向受体结合，成功研制As-FA配伍的主动靶向给药载体As-FA微纳米球；并开展该新型载体As-FA配伍微纳米粒的动物体内分布和药效学等实验研究，结果表明其具有主动靶向给药作用，达到了“减毒增效”作用。. 2.将参附中药复方与制剂的新技术和新剂型理论技术相结合，研制成参附微乳新载体，并开展参附微纳米载体动物体内分布和药效学等实验研究，结果表明“参附微乳载体”具有防治肝癌作用。. 3.开展本项目研制的“砷剂微纳米载体”与“参附微乳载体”联合用药对肝癌小鼠药效学的实验研究，实验数据显示As-FA微纳米球对H22荷瘤小鼠的抑瘤率为52.42%、参附微乳的抑瘤率为44.35%，As-FA微纳米球与参附联用的抑瘤率为57.26%；参附微乳能够降低As对心肌细胞的损伤，减少血清中的ALT及AST含量。这些结果表明“砷剂微纳米载体”与“参附微乳载体”联合用药达到了“减毒增效”作用目的。.由于本研究内容和成果可以解决砷剂抗肿瘤药物应用存在的毒性大问题，使含砷药物达到“高效、安全、释药规律可控”目的，也为抗癌药物靶向给药成果转化提供基础，也为构建复方靶向给药体系的应用研究提供理论依据，为其它抗癌药物达到安全有效可控研究提供思路与方法，同时也培养了中医药高科技人才，故本项目研究成果具有重要的社会和经济效益。