目的 建立苦味药物比苦度(ratio of bitterness,ROB)的测定及计算方法,实现不同苦味药物之间的苦度定量比较,为实现复方制剂中的苦味药物定向掩蔽奠定基础。方法 以0.134 mmol/L的盐酸小檗碱(berberine hydrochloride,BBR)为参比,将其ROB定为1,以穿心莲内酯、葛根素、苦参碱、盐酸青藤碱、芦荟苷、氧化苦参碱6种苦味药物单体为模型药物,基于经典人群口尝法(traditional human taste panel method,THTPM),参照"比甜度"的表示方法,结合课题组前期已建立的苦味化合物标准表观苦度(standard apparent bitterness,SAB)的测定方法,反推出6种模型药物SAB=3时的浓度,并根据公式计算出其ROB。结果 采用THTPM法测得不同浓度模型药物的口尝SAB值,建立了6种模型药物的威布尔模型与对数模型。根据最优模型计算出了6种模型药物的ROB分别为0.017、0.031、0.208、0.250、0.500、0.714。结论 建立了基于THTPM的ROB定量方法,并成功测定了6种苦味药物单体的ROB,为不同苦味药物单体之间的苦度比较提供了新的苦度标尺,丰富了药物苦度比较标尺的研究,为苦度评价与苦味掩蔽评价提供了技术支撑。

Objective To establish a method to predict the ratio of bitterness (ROB) of bitter drugs, in order to compare the quantitative bitterness between different bitter drugs and lay the foundation for achieving targeted masking of bitter drugs in compound formulations. Methods Taking berberine hydrochloride (0.134 mmol/L, BBR) as reference, andrographolide, sinomenine hydrochloride, aloin, matrine, oxymatrine and puerarin were used as model drugs. Based on the traditional human taste panel method (THTPM), the expression method of 'sweetness' was referred. Based on the determination method of standard apparent bitterness (SAB) of bitter compounds based on THTPM previously established by our research group, ROBs of six bitter compounds were calculated (SAB=3). Results The oral taste SAB values of different concentrations of model drugs were measured by the THTPM method, and the Weibull and logarithmic models of six model drugs were established. The ROBs for the six model drugs were calculated as 0.017, 0.031, 0.208, 0.250, 0.500, and 0.714, respectively, based on the optimal model. Conclusion The ROB quantitative method based on THTPM was established, and the ROB of six bitter drug monomers was successfully determined. It provided a new bitterness scale for the comparison of bitterness between different bitter drug monomers, enriched the research of drug bitterness comparison scale, and laid a technical support for bitterness evaluation and bitterness masking evaluation.

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国家重点研发计划中医药现代化重点专项（2017YFC1703400）；国家重点研发计划中医药现代化重点专项（2017YFC1703401）；国家重点研发计划中医药现代化重点专项（2017YFC1703402）；国家自然科学基金资助项目（81774452）；国家自然科学基金资助项目（81001646）；河南省中医药拔尖人才培养项目资助（2019ZYBJ07）；河南省高层次人才特殊支持“中原千人计划”—“中原青年拔尖人才”项目（ZYQR201912158）；河南省卫生健康中青年学科带头人专项（HNSWJW-2020014）；国家中医药管理局青年岐黄学者培养项目（国中医药人教函［2022］256号）