Title:
MEDICINAL AGENT AND BEVERAGE/FOOD FOR PREVENTING CEREBRAL DYSFUNCTION AND IMPROVING SAME
Document Type and Number:
WIPO Patent Application WO/2011/132435
Kind Code:
A1
Abstract:
Disclosed is a means for improving the symptoms of a cerebral dysfunction. The present inventors made a new discovery that the activity of brain aromatic monoamines increases when sepiapterin is administered peripherally. Disclosed, therefore, is a medicinal agent, which contains at least sepiapterin or a salt thereof, for preventing or improving cerebral dysfunction. Also disclosed is a beverage/food, which contains at least sepiapterin or a salt thereof, for preventing or improving cerebral dysfunction. Unlike tetrahydrobiopterin and the like, sepiapterin can control reductions in the brain neuron levels of brain aromatic monoamines (serotonin, dopamine, noradrenaline, and the like) and increase the activity thereof even when administered peripherally. Therefore, sepiapterin may be effective for cerebral dysfunctions, which are due to reductions in the brain neuron levels of brain aromatic monamines, such as depression, bulimia, autism, impaired consciousness and concentration, cognitive disorders and other central mental disorders, as well as myotonia, rigidity, tremors, and other central motor disorders.
Inventors:
HASEGAWA HIROYUKI (JP)
AIZAWA SHIN (JP)
AIZAWA SHIN (JP)
Application Number:
PCT/JP2011/002393
Publication Date:
October 27, 2011
Filing Date:
April 22, 2011
Export Citation:
Assignee:
UNIV NIHON (JP)
HASEGAWA HIROYUKI (JP)
AIZAWA SHIN (JP)
HASEGAWA HIROYUKI (JP)
AIZAWA SHIN (JP)
International Classes:
C07D475/04; A23L1/30; A23L2/52; A23L33/00; A61K31/519; A61P25/14; A61P25/16; A61P25/24; A61P25/28
Domestic Patent References:
| WO2009088530A1 | 2009-07-16 | |||
| WO2008089008A2 | 2008-07-24 | |||
| WO1996003989A1 | 1996-02-15 |
Foreign References:
| JPS5925323A | 1984-02-09 | |||
| JPS611688A | 1986-01-07 | |||
| JPS5925323A | 1984-02-09 | |||
| JP2008504295A | 2008-02-14 | |||
| JPH06192100A | 1994-07-12 |
Other References:
VASQUEZ-VIVAR, J. ET AL.: "Tetrahydrobiopterin in the prevention of hypertonia in hypoxic fetal brain", ANNALS OF NEUROLOGY, vol. 66, no. 3, 2009, pages 323 - 331, XP008159437
KAPATOS, G. ET AL.: "Biosynthesis of biopterin by rat brain", JOURNAL OF NEUROCHEMISTRY, vol. 39, no. 4, 1982, pages 1152 - 1162, XP008159436
SAWABE, K. ET AL.: "Tetrahydrobiopterin uptake in supplemental administration: Elevation of tissue tetrahydrobiopterin in mice following uptake of the exogenously oxidized product 7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive process", JOURNAL OF PHARMACOLOGICAL SCIENCES, vol. 96, no. 2, 2004, pages 124 - 133, XP008159439
SAWABE, K. ET AL.: "Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin", MOLECULAR GENETICS AND METABOLISM, vol. 94, 2008, pages 410 - 416, XP022833448
K. SAWABE; K. YAMAMOTO; Y. HARADA; A. OHASHI; Y. SUGAWARA; H. MATSUOKA; H. HASEGAWA: "Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin", MOL GENET METAB, vol. 94, 2008, pages 410 - 416, XP022833448, DOI: doi:10.1016/j.ymgme.2008.04.007
H. HASEGAWA; K. SAWABE; N. NAKANISHI; O.K. WAKASUGI: "Delivery of exogenous tetrahydrobiopterin (BH4) to cells of target organs: role of salvage pathway and uptake of its precursor in effective elevation of tissue BH4", MOL GENET METAB, vol. 86, no. 1, 2005, pages 2 - 10, XP005197866, DOI: doi:10.1016/j.ymgme.2005.09.002
A. NIEDERWIESER; H.-CH. CURTIUS; M. WANG; D.LEUPOLD: "Atypicalphenylketonuria with defective biopterin metabolism. Monotherapy with tetrahydrobiopterin or sepiapterin, screening und study of biosynthesis in man", EUR J PEDIATR, vol. 138, 1982, pages 110 - 112
G. KAPATOS; S. KATOH; S. KAUFMAN: "Biosynthesis of biopterin by rat brain", JOURNAL OF NEUROCHEM, vol. 39, 1982, pages 1152 - 1162, XP008159436, DOI: doi:10.1111/j.1471-4159.1982.tb11509.x
M. P. BRAND; K. HYLAND; T. ENGLE; I. SMITH; S. J. R. HEALES: "Neurochemical effects following peripheral administration of tetrahydropterin derivatives to the hph-1 mouse", JOURNAL OF NEUROCHEM., vol. 66, 1996, pages 1150 - 1156, XP055077605, DOI: doi:10.1046/j.1471-4159.1996.66031150.x
K. BEAUMONT; R. WEBSTER; I. GARDNER; K. DACK: "Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist", CURRENT DRUG METABOLISM, vol. 4, no. 6, 2003, pages 461 - 485, XP008058352, DOI: doi:10.2174/1389200033489253
W. PFLEIDERER: "Pteridine, LXVIII. Uberfuhrung von Biopterin in Sepiapterin und absolute Konfiguration des Sepiapterins (Konfiguration Des Sepiapterins", CHEMISCHE BERICHTE, vol. 112, 1979, pages 2750 - 2755
T. FUKUSHIMA; J.C. NIXON: "Analysis of reduced forms of biopterin in biological tissues and fluids", ANALYTICAL BIOCHEMISTRY, vol. 102, 1980, pages 176 - 188, XP024822538, DOI: doi:10.1016/0003-2697(80)90336-X
F. INOUE; H.HASEGAWA; M.NISHIMURA; M. YANAGISAWA; A.ICHIYAMA: "Distribution of 5-hydroxytryptamine(5HT) in tissue of a mutant mouse deficient in mast cell (W/Wv) . Demonstration of the contribution of mast cells to the 5HT content in various organs", AGENTS ACTIONS, vol. 16, 1985, pages 2950301
KAPATOS, G. ET AL.: "Biosynthesis of biopterin by rat brain", JOURNAL OF NEUROCHEMISTRY, vol. 39, no. 4, 1982, pages 1152 - 1162, XP008159436
SAWABE, K. ET AL.: "Tetrahydrobiopterin uptake in supplemental administration: Elevation of tissue tetrahydrobiopterin in mice following uptake of the exogenously oxidized product 7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive process", JOURNAL OF PHARMACOLOGICAL SCIENCES, vol. 96, no. 2, 2004, pages 124 - 133, XP008159439
SAWABE, K. ET AL.: "Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin", MOLECULAR GENETICS AND METABOLISM, vol. 94, 2008, pages 410 - 416, XP022833448
K. SAWABE; K. YAMAMOTO; Y. HARADA; A. OHASHI; Y. SUGAWARA; H. MATSUOKA; H. HASEGAWA: "Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin", MOL GENET METAB, vol. 94, 2008, pages 410 - 416, XP022833448, DOI: doi:10.1016/j.ymgme.2008.04.007
H. HASEGAWA; K. SAWABE; N. NAKANISHI; O.K. WAKASUGI: "Delivery of exogenous tetrahydrobiopterin (BH4) to cells of target organs: role of salvage pathway and uptake of its precursor in effective elevation of tissue BH4", MOL GENET METAB, vol. 86, no. 1, 2005, pages 2 - 10, XP005197866, DOI: doi:10.1016/j.ymgme.2005.09.002
A. NIEDERWIESER; H.-CH. CURTIUS; M. WANG; D.LEUPOLD: "Atypicalphenylketonuria with defective biopterin metabolism. Monotherapy with tetrahydrobiopterin or sepiapterin, screening und study of biosynthesis in man", EUR J PEDIATR, vol. 138, 1982, pages 110 - 112
G. KAPATOS; S. KATOH; S. KAUFMAN: "Biosynthesis of biopterin by rat brain", JOURNAL OF NEUROCHEM, vol. 39, 1982, pages 1152 - 1162, XP008159436, DOI: doi:10.1111/j.1471-4159.1982.tb11509.x
M. P. BRAND; K. HYLAND; T. ENGLE; I. SMITH; S. J. R. HEALES: "Neurochemical effects following peripheral administration of tetrahydropterin derivatives to the hph-1 mouse", JOURNAL OF NEUROCHEM., vol. 66, 1996, pages 1150 - 1156, XP055077605, DOI: doi:10.1046/j.1471-4159.1996.66031150.x
K. BEAUMONT; R. WEBSTER; I. GARDNER; K. DACK: "Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist", CURRENT DRUG METABOLISM, vol. 4, no. 6, 2003, pages 461 - 485, XP008058352, DOI: doi:10.2174/1389200033489253
W. PFLEIDERER: "Pteridine, LXVIII. Uberfuhrung von Biopterin in Sepiapterin und absolute Konfiguration des Sepiapterins (Konfiguration Des Sepiapterins", CHEMISCHE BERICHTE, vol. 112, 1979, pages 2750 - 2755
T. FUKUSHIMA; J.C. NIXON: "Analysis of reduced forms of biopterin in biological tissues and fluids", ANALYTICAL BIOCHEMISTRY, vol. 102, 1980, pages 176 - 188, XP024822538, DOI: doi:10.1016/0003-2697(80)90336-X
F. INOUE; H.HASEGAWA; M.NISHIMURA; M. YANAGISAWA; A.ICHIYAMA: "Distribution of 5-hydroxytryptamine(5HT) in tissue of a mutant mouse deficient in mast cell (W/Wv) . Demonstration of the contribution of mast cells to the 5HT content in various organs", AGENTS ACTIONS, vol. 16, 1985, pages 2950301
Attorney, Agent or Firm:
NIWA, SHUNSUKE (JP)
Shunsuke Niwa (JP)
Shunsuke Niwa (JP)
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