矿物药雄黄增效减毒新技术的相关基础理论研究

Realgar occupies a unique and important position in traditional Chinese medicine (TCM), as most of TCM formulae containing realgar. However, its clinical application is seriously restricted due to the fact that it is water insoluble and only can be oral administration on a large dose, thus leading to high toxicity from excessive arsenic intake. In our lab, a kind of microbiological leaching technique is used to dissolve realgar. We have demonstrated that realgar bioleaching solution (RBS) exhibits high therapeutic efficacy and low toxicity. In this proposal we intend to build on these exciting preliminary findings to elucidate the mechanism of the action of RBS. Specifically we will employ surface microzone, cell biological, molecular biological and chemical analysis and chemical and computer molecular design approaches to identify and characterize the active components in RBS and to determine the molecular basis for their efficacy in both mammalian cell lines and animal models. The toxicity of the RBS will be compared in detail with that of the traditional realgar in order to understand the basis for the reduced toxicity of RBS. The knowledge will be useful for developing future guidelines in using realgar in TCM formulae, and finally lead to their good quality control and guarantee their clinical use in TCM formulae.

雄黄在中成药中具有举足轻重的地位。但由于其在使用中常遇到砷等重金属含量超标问题，严重阻碍了含雄黄中成药的应用和发展。本实验室将微生物浸矿技术应用于中药领域，发明了一种温和的雄黄生物法减毒新工艺，从而大大提高了雄黄的生物利用度和药理活性，降低其在中药复方中的使用量。本项目拟在上述研究基础上，运用现代表面微区、分子生物学、现代分析化学以及计算机分子对接等技术方法分析雄黄生物法减毒新工艺的生物、化学过程，系统阐述雄黄溶解液的毒效相关性及其相对于传统雄黄炮制方法的有效性和安全性，并从元素化学形态及微量元素角度探讨雄黄溶解液的药效物质基础，进而奠定这种矿物药创新性减毒工艺的理论基础。本项目的突破对于指导和改进创新性减毒工艺，阐明雄黄溶解液的药理、药效及毒理学机理，有效控制其质量和安全性，使多种确有疗效的雄黄类中药能够重新恢复应有的价值。

雄黄在中成药中具有举足轻重的地位。但由于其在使用中常遇到砷等重金属含量超标问题，严重阻碍了含雄黄中成药的应用和发展。本实验室将微生物浸矿技术应用于中药领域，发明了一种温和的雄黄生物法减毒新工艺，大大提高了雄黄的生物利用度和药理活性，并能够通过这种替代方式，降低雄黄在中药复方中的使用量。本项目运用现代分子生物学、现代分析化学等新技术方法分析雄黄生物法减毒新工艺的生物、化学过程，系统阐述雄黄溶解液的毒效相关性及其相对于传统雄黄炮制方法的有效性和安全性，探讨雄黄溶解液的药效物质基础，进而奠定这种矿物药创新性减毒工艺的理论基础，应用于传统雄黄复方的替代研究。本项目的突破对于指导和改进创新性减毒工艺，阐明雄黄溶解液的药理、药效及毒理学机理，有效控制其质量和安全性，使多种确有疗效的雄黄类中药能够重新恢复应有的价值。