中药汤剂普遍存在味苦、口感差的共性问题，严重制约服药顺应性与中医临床疗效。这与汤剂混相体系下众多成分与苦味受体之间复杂的多对多时空响应与苦味信号综合叠加密切相关，单一的掩味或矫味方法效果有限，亟需寻找新的研究思路与策略。受咖啡伴侣的启示，首次提出基于“霰弹理论”的中药汤剂伴侣的研制思路，并选择疗效确切、苦味显著的经典名方黄连解毒汤为模型药，研究汤剂伴侣的基本配方。针对黄连解毒汤中黄芩、黄连、黄柏、栀子的呈味特征，采用单因素实验筛选出适宜的矫味剂纽甜、γ-环糊精（γ-cyclodextrin，γ-CD）和mPEG₂₀₀₀-PLLA₂₀₀₀，并采用星点设计-响应面优化法优化矫味伴侣剂配方，得到黄连解毒汤最优伴侣剂配方为纽甜-mPEG₂₀₀₀-PLLA₂₀₀₀-γ-CD-黄连解毒汤的质量比为0.028∶0.15∶1.5∶100。实验结果表明伴侣剂配方中3个矫味剂达到了1＋1＋1>3的协同矫味增甜的效果，对于提高汤剂服药顺应性、提升中药制剂临床疗效具有重要意义。

Bitter and poor taste is the common problem of traditional Chinese medicine (TCM) decoction that seriously restrict the compliance and clinical efficacy of it. This is closely related to the complex many-to-many spatiotemporal response and comprehensive superposition between many components and bitter taste receptors in the decoction miscibility system. The effect of single masking or flavor correction method is limited, thus it is urgent to find new research ideas and strategies. Based on the “grape-shot theory” and learning from success of the coffee companion to develop TCM decoction companion agent, Huanglian Jiedu Decoction (黄连解毒汤), a classic famous prescription with definite curative effect and significant bitter taste, was selected as the model drug to study the basic formula of decoction companion. According to the taste characteristics of Huangqin (Scutellariae Rhizoma), Huanglian (Coptidis Rhizoma), Huangbo (Phellodendri Chinensis Cortex) and Zhizi (Gardeniae Fructus), neotame, γ-cyclodextrin (γ-CD) and mPEG₂₀₀₀-PLLA₂₀₀₀ were selected as corrigents by single factor experiment. And the central point design-response surface optimization was used to optimize the formulation of the chaperone agent. The optimal formula of bitterness suppression agent was optimized as neotame-mPEG₂₀₀₀-PLLA₂₀₀₀-γ-CD-Huanglian Jiedu Decoction with the mass ratio of 0.028∶0.15∶1.5∶100. The experimental results showed that the three taste masking agents in the chaperone formula achieved synergistic effect of 1 + 1 + 1 > 3, which is of great significance for improving the compliance of Chinese medicine and improving the clinical efficacy of TCM preparations.

国家自然科学基金资助项目（81803745）；国家自然科学基金资助项目（81960721）；国家博士后科学基金面上项目（2020M683269）；江西省自然科学基金青年项目（20181BAB215040）；四川省科技厅杰出青年人才项目（2019JDJQ0007）；2019—2021年度中华中医药学会青年人才托举工程项目（2019-QNRC2-B05）