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Comparison of ephedrine and pseudoephedrine contents in 34 Kampo extracts containing Ephedrae Herba used clinically in Japan

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Abstract

Ephedrae Herba is among the important crude drugs prescribed in Kampo medicine for the treatment of cold, flue, rhinitis, nasal congestion, cough, and asthma. The active ingredients of Ephedrae Herba, ephedrine (E) and pseudoephedrine (PE), are potent sympathomimetic compounds that stimulate α-, β1-, and β2-adrenoceptors resulting in dilatation and alleviation of nasal mucosal hyperemia. Hypertension, palpitations, insomnia, and dysuria are the main adverse effects of E and PE, which can be avoided by determining the actual contents of these alkaloids in Kampo extracts containing Ephedrae Herba. However, the extraction efficiencies of E and PE from Ephedrae Herba contained in Kampo formulas in combination with other crude drugs remain unknown. Therefore, we comprehensively determined the E and PE contents of 34 Kampo extracts containing Ephedrae Herba used clinically in Japan. The E and PE contents per daily dosage in Kampo extracts were generally proportional to the compounding amount of Ephedrae Herba. In contrast, the extraction efficiencies of E or PE were not constant and not influenced by the pH of the extracts. We assume that the extraction efficiencies of E and PE may be independently affected by other constituent crude drugs. Thus, it is necessary to investigate the cause and mechanism in the future. In conclusion, these results show that the E and PE content of each Kampo formulation can be estimated from the compounding amount of Ephedrae Herba. Therefore, the amount of Ephedrae Herba should be carefully considered to ensure the safe use of Kampo formulations containing Ephedrae Herba.

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Acknowledgements

We thank Dr. Yasuhiro Nishikawa and Prof. Dr. Osamu Hara for their guidance in the chemical synthesis of (-)-ephedrine hydrochloride from (-)-norephedrine.

Funding

This study was supported by a Health and Labour Sciences Research Grant for ‘Research on Regulatory Science of Pharmaceuticals and Medical Devices’ from the Ministry of Health, Labour, and Welfare.

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Author notes

  1. Takashi Hakamatsuka

    Present address: Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-Machi, Kita-Adachi-Gun, Saitama, 362-0806, Japan

Authors and Affiliations

  1. Department of Pharmacognosy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-Ku, Nagoya, Aichi, 468-8503, Japan

    Mitsuhiko Nose, Risa Kobayashi, Momoka Tada & Shinsuke Hisaka

  2. Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-Ku, Kawasaki, Kanagawa, 210-9501, Japan

    Sayaka Masada & Takashi Hakamatsuka

  3. Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tenno-Dai, Tsukuba, Ibaraki, 305-8575, Japan

    Masato Homma

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  1. Mitsuhiko Nose
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Correspondence to Mitsuhiko Nose.

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Nose, M., Kobayashi, R., Tada, M. et al. Comparison of ephedrine and pseudoephedrine contents in 34 Kampo extracts containing Ephedrae Herba used clinically in Japan. J Nat Med 77, 476–488 (2023). https://doi.org/10.1007/s11418-023-01687-w

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  • DOI: https://doi.org/10.1007/s11418-023-01687-w

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