甘草含有医薬品による偽 ... - otc-spf.jp

1 20 .. TEL & FAX .. 11 HSD 2 . GA . 3 MGA .. GA 3 MGA .. GL . GA 11 . -1- HSD 2 .. GL GL . 3- 3 MGA GL. GA 3 MGA . ABC . Mrp2 3 MGA Mrp2 . Makino et al. 2008 . GA 3 MGA . 3 MGA . 11 -HSD2 GA 3 MGA GL . 3 MGA .. Wistar/ST SLC .. GL Calbiochem (San Diego, CA) 3 MGA GA . BSA St. Louis MO .. GL 3 MGA GA .. mm Incubation Medium . -2- IM 120 mM NaCl mM KCl 1 mM CaCl2 mM MgSO4 10 mM . pH IM 10 IM . GL 3 MGA GA IM 5% BSA IM . 37 . PBS M pH PBS . BCATM Protein Assay kit Thermo Scientific Rockford IL . GL 3 MGA GA LC/MS/MS . GL 3 MGA GA .. 50 L 1:10 Sigma 10 L 30 37 . 1 g/mL PHB . 150 L -20 30 15,000 rpm . 80 L LC/MS/MS Waters Quattro Premier XE, Milford, MA Inertosil ODS-3 50 x mm 5 m GL . (A) (B) in CH3CN 50:50.

2 (0 min) 30:70 (6 min) 15:85 (8 min) 50:50 ( min) 50:50 (15 min) mL/min ESR(+) MRM GL Cone 70V . Collision 40eV 3 MGA Cone 65V Collision 50eV GA Cone 80V Collision 40eV PHB Cone 14V Collision 10eV GL. min 3 MGA min GA min PHB min PHB . GL 3 MGA GL 12 1000 nM .. -3- GL 3 MGA GA 5% BSA . 5%BSA . 10 1000 M . 100 M . 120 2 .. GL 11 -HSD2 .. 2007 . 11 -HSD2 2008 .. 3 MGA . Kato H et al. 1995 . 3 MGA Mrp2 .. 3 MGA MGA . GA GA Makino T et al 2008 . 11 -HSD2 . GA . GA . GA . -4- .. GA 3 MGA . 3 MGA . 3 MGA. 3 MGA 11 -HSD2 .. GL 3 MGA GA .. 2003 GL 3 MGA . GA . GL 3 MGA . GL 3 MGA GA IM GA . 3 MGA GL . pH .. 5% . GL 3 MGA GA . 1000 M .. 5 . -5- . LC/MS/MS GA 3 MGA . GL . LC/MS/MS .. GA 3 MGA GL .. 5 . GA 3 MGA GL.

3 GA 3 MGA GL 11 -HSD2 .. -6- .. Kato H, Kanaoka M, Yano S, Kobayashi M. 3-Monoglucuronyl- glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism. J Clin Endocrinol Metab 1995;80:1929-33. Makino T, Ohtake N, Watanabe A, Tsuchiya N, Imamura S, Iizuka S, Inoue M, Mizukami H. Down-regulation of a hepatic transporter Mrp2 is involved in alteration of pharmacokinetics of glycyrrhizin and its metabolites in a rat model of chronic liver injury. Drug Metab. Dispos. 36(7): 1438 1443, 2008.. Organic Anion Transporter (OAT) . Drug Metab Pharmacokinet 2003;18:11-4.. 25. 2008;93. , , , , .. 2007;33:687-97. -7- H3C COOH. O. H CH3. CH3. RO. H 3C CH3. GL R = glucUA-glucUA. 3 MGA R = glucUA.

4 GA R=H. GL 3 MGA GA . -8- 1200 GL 200. GL. 3 MGA. 1000 160 3 MGA. GA GA. 800. 120. 600. 80. 400. 40. 200. 0 0. 0 200 400 600 800 1000 0 20 40 60. imin j GL 3 MGA GA . 5%BSA . 10 .. 100 M 5%BSA .. -9- Development of marker compound for pseudoaldosteronism by OTC drug containing licorice Toshiaki Makino Department of Pharmacognosy Graduate School of Pharmaceutical Sciences Nagoya City University 3-1 Tanabe-Dori, Mizuho-ku, 467-8603 Nagoya, Japan Tel & Fax +81 52 836 3416. Abstract The mechanisms of pseudoaldosteronism induced by OTC drug containing licorice was that some compounds containing licorice inhibit 11 -hydroxysteroid dehydrogenase (HSD) II which is in renal tubular epithelial cells. Since glycyrrhetinic acid (GA), the major metabolite of licorice compounds, is not eliminated into urine and is predicted not to be penetrated through tubular epithelial cells, 3-monoglucuronyl glycyrrhetinic acid (3 MGA), which is another metabolite and is eliminated into urine, is estimated to be a true origin for pseudoaldosteronism by licorice.

5 Then, we evaluated the uptake pattern of GA and 3 MGA into rat kiney slice to identify the transporter that transport these compounds from blood into the inside of tubular epithelialil cells. However, these compounds highly adsorbed onto many substances, and we could not measure the true uptake of these compounds in tubular epithelialium. Further experiments are demanded. -10.