基于中药复杂成分均衡释放的缓释辅料改良桃胶研究

It is hard for the modern sustained release excipients, such as HPMC and CMC-Na and so on, to realize the balanced release of complex components, and then it cannot reflect the demand of overall effect of traditional Chinese medicine compound complex chemical components. We had to solve the problem of balanced release of complex components on the support by the National Natural Science Foundation of China, with modern science and technology to innovately improve the traditional Chinese medicine accessories. We had combined the improved peach gum and modern preparation technology to develop sustained-release preparations of compound salvia miltiorrhiza, Chuan-ping that could conform balanced release, and the results of pharmacokinetics indicated the goodness in in vivo-in vitro correlation. On the basis of preliminary study, we found that the preparation of compound salvia miltiorrhiza and Chuan-ping developed by peach gums from different regions improved by drafting process have same balanced release effect, but on the contrary with the peach gums improved by different technologies. And sustained-release preparations developed by improved peach gum in the process of the dissolution of surface rendering fall off particles, showing "soluble powder" characteristics of Chinese traditional medicine pills. We would try to study the change laws of material constitution and physicochemical property and deciduous particles and balanced release, and to build the relevance, which would realize the scientific connotation that how improved peach gum could achieve the complex composition balanced release of traditional Chinese medicine sustained-release preparation, which could provide scientific basis for the development and application of novel sustained release excipients of improved peach gum, and also to provide theoretical basis and key technology support for the development of sustained-release formulation of traditional Chinese medicine.

HPMC、CMC-Na等现代缓释辅料难以实现复杂成分均衡释放，无法体现中药复方缓释制剂的整体效应。课题组前期在国家自然基金委资助下，围绕解决中药复杂成分均衡释放问题，利用现代科技对中药传统辅料进行创新改良；将改良桃胶与现代制剂技术相结合，开发出满足复杂成分均衡释放功效需求的复方丹参方、喘平方缓释制剂，药动学研究表明其具有良好的体内外相关性。在前期研究基础上发现，不同产地桃胶经拟订工艺改良后制备中药缓释制剂的均衡释放效果一致，而不同工艺改良桃胶制备的却表现出不同的均衡释放效果；同时缓释制剂在溶出过程中表面呈现脱落颗粒，表现出中药丸剂的“溶散”特征。本课题拟研究改良桃胶的物质构成、理化性质、脱落颗粒、均衡释放之间的变化规律，建立相关性，揭示改良桃胶对中药复杂成分均衡释放的科学内涵，为改良桃胶新型缓释辅料的开发应用提供科学依据，也为中药缓释制剂的发展提供理论依据和关键技术支撑。

本项目通过对原桃胶、不同工艺改良桃胶的化学成分组成分析、理化性质研究，结合喘平方缓释片脱落颗粒及其复杂成分均衡释放的研究，阐明改良桃胶对中药复方缓释复杂成分均衡释放的基本规律。.① 完成原桃胶及不同改良工艺桃胶的多糖成分组成及其多糖含量测定。测得原桃胶及不同工艺改良桃胶的单糖组成中均含有D-甘露糖、D-半乳糖、L-鼠李糖、D-葡萄糖、D-木糖、阿拉伯糖、葡萄糖醛酸，且以阿拉伯糖、D-木糖、D-半乳糖为主。而多糖含量由高至低为改良桃胶3>改良桃胶1>改良桃胶2>原桃胶。.② 完成原桃胶及不同改良工艺桃胶的理化性质研究。测得不同工艺改良桃胶较原桃胶相对分子质量明显降低，在动力黏度、溶解度、溶胀性能等性能方面明显提高，表面形成不规则的孔洞（原桃胶则为紧实光滑）。.③ 完成喘平方缓释制剂脱落颗粒的研究。测得由原桃胶及不同工艺改良喘制备的喘平方缓释片均存在颗粒脱落现象，其中原桃胶颗粒脱落快、粒径大，而改良桃胶1~3则是脱落较为缓慢、粒径较小。此外，由原桃胶及不同工艺改良喘制备的喘平方缓释片在不同时间点脱落的颗粒，其药物含量不同，由高至低依次为改良桃胶3>改良桃胶1>改良桃胶2>原桃胶；同时脱落颗粒药物释放时间由长至短依次为改良桃胶3>改良桃胶1>改良桃胶2>原桃胶。.④ 完成喘平方缓释制剂复杂成分均衡释放的研究。测得原桃胶的缓释效果差，经过改良后，缓释作用更强、均衡释放性更优，其中以改良桃胶3最佳。同时，改良桃胶1~3所制备的喘平方缓释片，在药物释放过程中，均表现出溶胀-扩散与溶蚀-扩散并存，提示其药物释放的特殊性，进一步与本课题组所提出的“溶蚀-溶散-扩散”药物释放模型相佐证。