基于“治疗窗”导向的雪上一枝蒿微乳透皮给药制剂的构建与评价

Abstract: the toxicity of traditional Chinese medicine transdermal drug delivery has a long history, its percutaneous absorption kinetics are closely Contact with treatment effect and toxicity. as folk medicine of Yunnan and Guizhou, Aconitum brachypodum Diels has significant treatment effect in the treatment of traumatic injury and rheumatic pain, but because of its acute toxicity and poisoning, Therapeutic dose is similar to toxic, poisoning incidents have often happened. This research intends to take Aconitum brachypodum as model drug, to investigate the dose influent on inflammatory cells and expression of related genes. On the basis of this, systemly evaluate drugs (bullatine A ) absorption properties and law of skin and dosage and stromal factors on its absorption effect. Study drug-loaded microemulsion in vitro transdermal process, and take microdialysis technology to research the pharmacokinetic process of optimization of the drug-loaded microemulsion in intradermal and subcutaneous tissue and blood based on common properties and dose-effect - absorption characteristics, and the key parameters and the general efficacy and toxicity study results made a comparative study of and data analysis to get the correlation of bullatine A in pharmacology of absorption kinetics and efficacy and toxicity.We will explore the feasibility and design key and its mechanism of action of increased efficacy and reduced toxicity microemulsion for Aconitum brachypodum transdermal delivery, but also provide new research ideas for the toxicity of traditional Chinese medicine microemulsion transdermal drug delivery system studies.The research has the important theory significance and guiding value of new drugs.

毒性中药经皮给药具有悠久的历史，其经皮吸收动力学过程与其疗效和毒性密切相关。雪上一枝蒿作为云南、贵州等地的民间用药，用于治疗跌打损伤，风湿骨痛疗效显著，但因其毒性剧烈，治疗量与中毒量相近，中毒事件时有发生。本研究拟以雪上一枝蒿为模型药，考察剂量对炎症细胞和相关基因蛋白表达的影响，确定其药理毒理量效范围（治疗窗）；同时系统评价药物（蒿甲素）吸收特性及皮肤、剂型、基质等因素对其吸收影响规律。基于上述量效-吸收特性设计"治疗窗"导向的微乳制剂，考察体外透皮过程，进而以微探针透析技术研究普通制剂与优化后载药微乳给药后在皮内、皮下组织及血液中的药动学过程，通过一般药效和毒性研究，分析得到制剂中蒿甲素吸收动力学和药效、毒性的相关性，探讨以"治疗窗"导向和基于量效-吸收特性设计含毒性中药微乳透皮制剂的增效减毒的可行性和关键问题，具有重要的理论意义和新药指导价值。

毒性中药经皮给药具有悠久的历史，其经皮吸收动力学过程与其疗效和毒性密切相关。雪上一枝蒿作为云南、贵州等地的民间用药，用于治疗跌打损伤，风湿骨痛疗效显著。本研究以雪上一枝蒿为模型药，考察了剂量对炎症细胞和相关基因表达的影响，确定药理毒理量效范围（治疗窗）；同时系统评价了药物（蒿甲素）吸收特性及皮肤、剂型、基质等因素对其吸收影响规律。基于量效-吸收特性设计“治疗窗”导向的微乳制剂，考察了体外透皮过程，进而以微探针透析技术研究普通制剂与优化后载药微乳给药后在皮内、皮下组织及血液中的药动学过程，通过一般药效和毒性研究，分析不同制剂中蒿甲素吸收动力学和药效、毒性的相关性，探讨了以“治疗窗”导向和基于量效-吸收特性设计含毒性中药经皮制剂的增效减毒的可行性和关键问题，具有重要的理论意义和新药指导价值。