基于多传感器信息融合与多尺度模拟的中药呈苦规律及抑苦机制研究

Decoctions of traditional Chinese medicine (TCM) are important weaponin the treatment of diseases, but its taste is an important aspect of restricting its application. Nowadays, the taste masking technology of chemical drugscan not suitable for decoctions which have the characteristics of high-dose and multi-component. So it is important to study suitable bitterness inhibitor (BS) and their external taste masking characteristics and intrinsic mechanisms, and futher establish the taste masking system which is given priority to suppression of bitterness,and frag rance and sweetness as supplementary.In our previous project,we have screened some of the decoction-suitable BSs of TCM and mastered their taste masking characteristics,but their taste masking mechanisms were unclear. In this project, on the basis of bitterness scale,we are going toexplor the bitterenss taste present regularity of TCMin a sigle or multiple system. Meanwhile, we will establish the bitterness modle based on information of bitterness scale, and the information of E-tongue, E-nose, NIR and other types of sensors using multisensor information fusion technology, so that to explor the bitterenss taste present regularity deeply. Furthermore, to establish the interaction and multi-scales model of the staticand dynamic between bitterness and BSon basis of the combination of micro-scale simulation of molecular dynamics and mesoscopic scale simulation of mesoscopic dynamics,horizontal and vertical integration, visualization and numerical computation method. Finally, to illuminate the relationship between taste present of bitterness and taste masking and internal taste masking mechanism of BS from multiple perspectives and multiple levels,and lay the foundation of decoctions taste masking precisly technology system for the theoretical construction.

中药汤剂是中医治病的重要武器，但其口感却严重制约其应用。西药的掩味技术无法适应汤剂“大剂量、多成分”特点。研究适宜的且不影响药效的苦味抑制剂(BS)及其外在抑苦特点与内在抑苦机制，藉此建立抑苦为主、增甜和加香为辅的掩味技术体系是关键。课题组前期筛选了部分BS并掌握了其外在抑苦特点，但其内在抑苦机制尚不清楚。本项目拟在建立分子苦度指数等苦度标尺的基础上，首先探讨单一及多元体系下的中药呈苦规律；同时采集电子舌、电子鼻、近红外等多类传感器信息，运用多传感器信息融合技术（MIF）建立苦度模型，再行探讨呈苦规律；基于上述呈苦规律，再采用基于分子动力学的微观尺度模拟与基于介观动力学的介观尺度模拟相结合、横纵向结合、可视化与数值计算结合的方法，建立苦味质与BS之间相互作用的多尺度的静态与动态模型；最终多角度、多层次阐释呈苦与抑苦的关系及各类BS的内在抑苦机制，为构建汤剂精准掩味技术体系奠定理论基础。

中药汤剂是中医治病的重要武器，但其苦味成分多，口感不佳，严重制约了其应用。目前化药的许多掩味技术无法适应汤剂“大剂量、多成分”特点，因此研究汤剂的呈苦规律及其苦味抑制剂（BS）的抑苦机制是改善汤剂口感的关键。.本项目以建立中药的苦味定量方法为切入点，在课题组前期建立苦味化合物标准表观苦度的评价方法的基础上，探讨19种中药单体苦味物质（Mono）水溶液及7种苦味中药水煎液（BDCMM）单一体系下的呈苦规律，建立了基于分子苦度当量测量的多成分中药苦度定量化方法及基于苦味阈值浓度的药物分子苦度定量方法。然后利用口尝和电子舌联合评价的方法，探讨Mono与BDCMM的叠加规律，发现无论是同种叠加或是非同种叠加，叠加的结果都是对苦度的促进作用，但不同种类的叠加较单独的苦味物质苦度变化缓和，叠加后的苦度与添加物质浓度依然呈威布尔或对数关系；同时对不同类型BS作用于龙胆等4种BDCMM的抑苦效能评价及抑苦规律进行研究，发现HP-β-CD与β-CD对不同BDCMM的抑苦效果类似，阿斯巴甜对穿心莲水煎液的抑苦效果不太理想，安赛蜜在较低质量浓度时可使龙胆、苦参水煎液苦度有较大程度降低；最后采用微观尺度模拟与介观尺度模拟相结合的方法，选用黄芩苷（BAI）、穿心莲内酯（AND）、盐酸小檗碱（BBR）与β-CD为研究对象，建立苦味物质与BS之间相互作用的多尺度的动静态模型，发现BBR、BAI与β-CD形成分子间氢键，BBR与AND部分结构进入β-CD空腔内，进而从微观角度对BS掩味机制进行了阐述。总体上本项目在前期标准表观苦度的评价方法的基础上,建立苦度标尺，并对Mono与BDCMM的呈味与叠加规律进行探讨，对多种BS的抑苦规律从多层次多角度进行阐述，为构建汤剂精准掩味体系奠定了基础。.汤剂口感问题是目前亟待解决的问题，也是药学工作者长期面临的课题。未来，可以在本项目基础上，增加相关受体蛋白与中药苦味单体化合物、苦味抑制剂间的模拟研究，以形成更为完整的中药呈苦与抑苦规律体系，进一步为掩味研究构建更为完善的理论体系。