Title:
THERAPEUTIC AGENT FOR SENSORINEURAL HEARING LOSS
Document Type and Number:
WIPO Patent Application WO/2016/117431
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a novel apoptosis inhibitor and a therapeutic agent for sensorineural hearing loss. For achieving the purpose, a medicine is provided which contains a biguanide compound represented by structure formula I or a rapamycin derivative represented by structure formula II as an active ingredient.
(In the formula, R1 to R7 are independently selected from a hydrogen atom, a halogen atom, and a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- to 6-membered heteroaryl group or a 5- or 6-membered nonaromatic heterocyclic group each of which may have a substituent selected from a halogen atom, a cyano group, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxycarbonyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group and a phenyl group.)
(In the formula, R1 represents a C1-6 alkyl group or a C3-6 alkynyl group; R2 represents H, -CH2-OH or -CH2-CH2-OH; and X represents =O, (H,H) or (H,OH).)
Inventors:
HOSOYA MAKOTO (JP)
FUJIOKA MASATO (JP)
OKANO HIDEYUKI (JP)
OGAWA KAORU (JP)
MATSUNAGA TATSUO (JP)
FUJIOKA MASATO (JP)
OKANO HIDEYUKI (JP)
OGAWA KAORU (JP)
MATSUNAGA TATSUO (JP)
Application Number:
PCT/JP2016/050861
Publication Date:
July 28, 2016
Filing Date:
January 13, 2016
Export Citation:
Assignee:
UNIV KEIO (JP)
International Classes:
A61K31/155; A61K31/436; A61P27/16; A61P43/00; G01N33/15; G01N33/50
Foreign References:
| JP2004099537A | 2004-04-02 | |||
| JP2004123713A | 2004-04-22 | |||
| JP2010527361A | 2010-08-12 | |||
| JP2003519655A | 2003-06-24 |
Other References:
OISHI, NAOKI ET AL.: "Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo", NEUROSCIENCE LETTERS, vol. 583, 2014, pages 65 - 69, XP029088678
JUNG, HAK HYUN ET AL.: "Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line", HEARING RESEARCH, vol. 282, no. 1-2, 2011, pages 92 - 96, XP028126678
LECLERC, GILLES M. ET AL.: "Metformin induces apoptosis through AMPK-dependent inhibition of UPR signaling in ALL lymphoblasts", PLOS ONE, vol. 8, no. 8, 2013, pages e74420, XP055438583
ROSA, CONDE DE LA ET AL.: "Oxidative stress induced apoptosis is inhibited by metformin via an ERK and Src dependent pathway in rat hepatocytes", EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, vol. 18, no. 1, 2006, pages A50 - A51, XP009502617
HARRIS, KELLY CARNEY ET AL.: "Prevention of noise-induced hearing loss with Src-PTK inhibitors", HEARING RESEARCH, vol. 208, no. 1-2, 2005, pages 14 - 25, XP005105480
GLUTZ, ANDREA ET AL.: "Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro", AUDIOLOGY & NEUROTOLOGY, vol. 20, no. 6, September 2015 (2015-09-01), pages 360 - 369, XP009502616
FANG, BIN ET AL.: "Rapamycin alleviates cisplatin-induced ototoxicity in vivo", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 448, no. 4, 2014, pages 443 - 447, XP055438585
HAYASHI, KEN ET AL.: "Molecular crosstalk between Nrf2/ Keapl signaling pathway, autophagy and necrosis in auditory cells", OTOLARYNGOLOGY - HEAD AND NECK SURGERY, vol. 145, no. 2, August 2011 (2011-08-01), pages 221, XP055438587
WOLTMAN, ANDREA M. ET AL.: "Rapamycin induces apoptosis in monocyte- and CD 34-derived dendritic cells but not in monocytes and macrophages", BLOOD, vol. 98, no. 1, 2001, pages 174 - 180, XP055438588
LEITMEYER, KATHARINA ET AL.: "Inhibition of mTOR by rapamycin results in auditory hair cell damage and decreased spiral ganglion neuron outgrowth and neurite formation In Vitro", BIOMED RESEARCH INTERNATIONAL, vol. 21, no. 2, 31 March 2015 (2015-03-31), pages 1 - 11, XP055438590
See also references of EP 3248597A4
JUNG, HAK HYUN ET AL.: "Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line", HEARING RESEARCH, vol. 282, no. 1-2, 2011, pages 92 - 96, XP028126678
LECLERC, GILLES M. ET AL.: "Metformin induces apoptosis through AMPK-dependent inhibition of UPR signaling in ALL lymphoblasts", PLOS ONE, vol. 8, no. 8, 2013, pages e74420, XP055438583
ROSA, CONDE DE LA ET AL.: "Oxidative stress induced apoptosis is inhibited by metformin via an ERK and Src dependent pathway in rat hepatocytes", EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, vol. 18, no. 1, 2006, pages A50 - A51, XP009502617
HARRIS, KELLY CARNEY ET AL.: "Prevention of noise-induced hearing loss with Src-PTK inhibitors", HEARING RESEARCH, vol. 208, no. 1-2, 2005, pages 14 - 25, XP005105480
GLUTZ, ANDREA ET AL.: "Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro", AUDIOLOGY & NEUROTOLOGY, vol. 20, no. 6, September 2015 (2015-09-01), pages 360 - 369, XP009502616
FANG, BIN ET AL.: "Rapamycin alleviates cisplatin-induced ototoxicity in vivo", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 448, no. 4, 2014, pages 443 - 447, XP055438585
HAYASHI, KEN ET AL.: "Molecular crosstalk between Nrf2/ Keapl signaling pathway, autophagy and necrosis in auditory cells", OTOLARYNGOLOGY - HEAD AND NECK SURGERY, vol. 145, no. 2, August 2011 (2011-08-01), pages 221, XP055438587
WOLTMAN, ANDREA M. ET AL.: "Rapamycin induces apoptosis in monocyte- and CD 34-derived dendritic cells but not in monocytes and macrophages", BLOOD, vol. 98, no. 1, 2001, pages 174 - 180, XP055438588
LEITMEYER, KATHARINA ET AL.: "Inhibition of mTOR by rapamycin results in auditory hair cell damage and decreased spiral ganglion neuron outgrowth and neurite formation In Vitro", BIOMED RESEARCH INTERNATIONAL, vol. 21, no. 2, 31 March 2015 (2015-03-31), pages 1 - 11, XP055438590
See also references of EP 3248597A4
Attorney, Agent or Firm:
ISSHIKI & CO. (JP)
All international patent business corporation (JP)
All international patent business corporation (JP)
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