口含片中多酚类物质与唾液蛋白形成疏水性络合物，是产生强烈涩味的根源，严重影响服用的顺应性。基于涩味形成分子机制的理论推导与实践，提出“调控多酚-唾液蛋白络合反应是掩味的核心思路，延缓多酚的溶出释放、降低多酚与唾液蛋白的结合能力是有效途径”。.依据假说，以EGCG为标准物质，运用志愿者口尝试验、脑功能成像、多酚-β-酪蛋白反应模型及理化分析，构建“浊度-浓度-脑成像信号”的涩味体内外关联表征方法。通过多酚单体与β-酪蛋白模拟结合，研究探寻关键因素与调控原理。系统考察HPMC对三果汤含片多酚总量释放规律及浊度的影响，pH对多酚与β-酪蛋白结合能力及浊度的影响，确定主要调控因素及水平；进而优化制剂处方与质量评价，并在3种口含片中进行规律验证；最终解决含多酚口含片的涩味问题，形成适宜于中药口含片特点的涩味掩蔽技术，从理论与实践上推动中药掩味技术的发展，指导口含片制剂设计与生产实践能力的提高。

Hydrophobic complex formation between salivary protein and polyphenols in the buccal tablets is found to be the root of strong astringency, which seriously affected the compliance of patients. Based on the theoretical derivation and pre-preparation, the research team puts forward a hypothesis” Regulation on the complex formation between salivary protein and polyphenols is the key of taste masking. Retard the dissolution of polyphenols, lower the binding capacity of polyphenols and salivary protein are the effective way”..In this experiment, EGCG is selected as the standard material, taste test of volunteers, functional brain imaging, polyphenols-β-casein reaction model ,physical and chemical analysis are used to construct the characterization method related in vivo and in vitro astringency perception.Then,simulation experiment between several polyphenols with β- casein is designed to find the critical factor and regulating principle.Furmore,the effect of HPMC on the total polyphenols releasing regularity and turbidity of Sanguotang buccal tablets, and the effect of pH on the binding capacity with β-casein and turbidity are systematically studied, so as to identify key regulatory factors and their levels.On this basis, optimize pharmaceutical formulations, conduct quality evaluation, and validation in three kinds of law in buccal tablets.The results of this project will solve the astringency problem in buccal tablets, form the masking technology suitable for traditional Chinese buccal tablets, promote the development of Chinese medicine taste masking technology from theory and practice and improve buccal tablets formulation research and production capacity.

本课题以三果汤含片涩味的掩蔽与评价为核心目标，从文献梳理-涩味表征-控涩因素-掩蔽工艺4个方面开展研究，完成了标书的主要内容。梳理国内外文献，述评8种志愿者感官评价方法、5种生物检测方法、及砂粒感、黏附感、刺激性3种口感评价方法，首次在学科内提出脑功能成像评价口感新方法。同时，分析涩味形成分子机制，并从呈味物质相互作用、释药速率控制、小分子淬灭剂方面报道了最新掩味技术。从标准物质、方法参数、定量表征研究动物偏好实验与电子舌仿生评价的方法学条件。结果表明，电子舌能显著区分酸、苦、甜、咸、鲜、涩6种味觉；以鞣酸为标准物质，建立鞣酸浓度-空间位置相关关系，能准确表征中药材与中成药涩味，该结果与VAS志愿者感官实验结果相关性高，符合人体的真实感知。基于人工唾液环境，研究多酚与β-酪蛋白相互作用规律。结果表明，以蛋白吸光度为评价指标，多酚浓度越低、羟基越少、反应环境温度越高（10-37℃范围内）、pH越高，络合程度越低。基于上述结果，确定以pH为调控手段研究三果汤含片的涩味控制。通过正交实验确定常压、减压和超声提取三果汤的最佳工艺参数。采用UPLC-Q-TOF-MS结合多元统计方法及生物评价，对比三种工艺的提取效果。共鉴定化学成分52种，常压提取在众多成分及抗氧化、抑菌活性占有明显优势。研究不同pH条件下三果汤浸膏与β-酪蛋白的结合规律，荧光淬灭试验表明在pH4.5与pH6.5时，结合力最弱，结合位点最少。β-酪蛋白的二级结构红外分析发现，随pH升高，特征波数比例明显变化，蛋白结构发生改变。但当pH＞6时，化学指纹图谱相似度降低，化学成分明显变化。将上述结论在三果汤含片中进行验证，志愿者VAS评分发现，升高pH至4.5或去掉辅料中柠檬酸均能降低含片涩味，但pH调节效果更优，且不影响对金黄色葡萄球菌和白色念珠菌的抑制活性。该项目为中药口含片及其他口服剂型的涩味控制提供了可靠的技术参考，累计发表科研论文14篇（含SCI 3篇），申请发明专利2项，培养直博生1名（2019年6月毕业）。