Suppression in Bitterness Intensity of Bitter Basic Drug by Chlorogenic Acid

• Published in: Chemical & pharmaceutical bulletin Vol. 65; no. 2; pp. 151 - 156
• Main Authors: Shiraishi, Sayuko, Haraguchi, Tamami, Nakamura, Saki, Kojima, Honami, Kawasaki, Ikuo, Yoshida, Miyako, Uchida, Takahiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acids; Adult; Bitter taste; Bitterness; bitterness suppression; Caffeic acid; Caffeic Acids - pharmacology; Carboxyl group; Chlorogenic acid; Chlorogenic Acid - chemistry; Chlorogenic Acid - pharmacology; Data processing; Diphenhydramine; Diphenhydramine - chemistry; Diphenhydramine - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Electrostatic properties; Female; gustatory sensation test; Humans; NMR; Nuclear magnetic resonance; Proton Magnetic Resonance Spectroscopy; Quinic acid; Quinic Acid - pharmacology; Spectroscopic analysis; Taste; Taste - drug effects; Taste Perception - drug effects; taste sensor; Young Adult
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c16-00670

The purpose of the study was to evaluate suppression of the bitterness intensity of bitter basic drugs by chlorogenic acid (CGA) using the artificial taste sensor and human gustatory sensation testing and to investigate the mechanism underlying bitterness suppression using 1H-NMR. Diphenhydramine hydrocholoride (DPH) was the bitter basic drug used in the study. Quinic acid (QNA) and caffeic acid (CFA) together form CGA. Although all three acids suppressed the bitterness intensity of DPH in a dose-dependent manner as determined by the taste sensor and in gustatory sensation tests, CFA was less effective than either CGA or QNA. Data from 1H-NMR spectroscopic analysis of mixtures of the three acids with DPH suggest that the carboxyl group, which is present in both QNA and CGA but not CFA, interact with the amine group of DPH. This study showed that the bitterness intensity of DPH was suppressed by QNA and CGA through a direct electrostatic interaction with DPH as confirmed in 1H-NMR spectroscopic analysis. CGA and QNA may therefore be useful bitterness-masking agents for the basic drug DPH.