Title:
PHARMACEUTICAL COMPOSITION COMPRISING FLUOXETINE AS AN ACTIVE INGREDIENT, FOR PREVENTING OR TREATING BLOOD-BRAIN BARRIER DISORDERS
Document Type and Number:
WIPO Patent Application WO/2013/058605
Kind Code:
A1
Abstract:
The present invention relates to a pharmaceutical composition comprising fluoxetine as an active ingredient for preventing or treating blood-brain barrier disorders. More particularly, it is defined that fluoxetine may inhibit expressions of matrix metalloproteinase (MMP) MMP-2, MMP-9 and MMP-12, which are reported to be related to a blood-brain barrier (BBB) disruption and inflammatory reaction after a spinal cord injury, and specifically may remarkably reduce MMP-2 and MMP-9 activation. It is also defined that fluoxetine may inhibit a decomposition of ZO-1, which is representative tight junction protein, so as to maintain a tight junction between endothelial cells and to thus protect a blood-brain barrier, may inhibit an increase in permeability of the blood-brain barrier, and may inhibit expressions of chemoattractants of blood cells, such as CXCL-1, CXCL-2, CCL-2, CCL-3 and CCL-4 so as to reduce inflow of blood into spinal cord and recover exercise function which has been deteriorated by a spinal cord injury. Therefore, it is known that fluoxetine can be valuably used in the prevention and treatment of central nervous system diseases or blood-brain barrier disorders or blood-spinal cord barrier disorders.
Inventors:
YUNE TAE YOUNG (KR)
OH TAE HWAN (KR)
BAIK HYUNG HWAN (KR)
LEE JEE YOUN (KR)
OH TAE HWAN (KR)
BAIK HYUNG HWAN (KR)
LEE JEE YOUN (KR)
Application Number:
PCT/KR2012/008614
Publication Date:
April 25, 2013
Filing Date:
October 19, 2012
Export Citation:
Assignee:
UNIV KYUNG HEE UNIV IND COOP GROUP (KR)
International Classes:
A61K31/138; A23L33/00; A61K31/135; A61P9/00; A61P25/28
Foreign References:
| KR20080051246A | 2008-06-11 | |||
| JP2009523802A | 2009-06-25 |
Other References:
TAE KYUONG SHIN ET AL.: "Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice", KOREAN JOURNAL OF PHYSIOLOGY & PHARMACEOLOGY, vol. 13, no. 3, 30 June 2009 (2009-06-30), pages 257 - 263, XP055128645
LUCIANA S. BRANCO-DE-ALMEIDA ET AL.: "Fluoxetine inhibitors inflammatory response and bone loss in a rat model of ligature-induced periodontitis.", JOURNAL OF PERIODONTOLOGY., vol. 83, no. 5, 3 October 2011 (2011-10-03), pages 664 - 671, XP008170864
CHEOL HONG PARK ET AL.: "Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice.", KOREAN JOURNAL OF PHYSIOLOGY & PHARMACEOLOGY., vol. 15, no. 2, 30 April 2011 (2011-04-30), pages 115 - 122, XP055128648
BUTTERFIELD ET AL., FREE RADICAL BIOLOGY AND MEDICINE, vol. 32, 2002, pages 1050 - 1060
BUTTERFIELD ET AL., FREE RADICAL BIOLOGY AND MEDICINE, vol. 43, 2007, pages 658 - 677
RISAU, W., NATURE, vol. 386, 1997, pages 671 - 674
MALTEPE, E.; SIMON, M.C., J. MOL. MED., vol. 76, 1998, pages 391 - 401
LEE, Y.M. ET AL., DEV. DYN., vol. 220, 2001, pages 175 - 186
SONG, H.S. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN, vol. 290, 2002, pages 325 - 331
LEANDER, J.D.: "Fluoxetine, a selective serotonin-uptake inhibitor enhances the anticonvulsant effects of phenytoin, carbamzepine, and ameltolide (LY201116", EPILEPSAI, vol. 33, 1992, pages 573 - 576, XP002374917, DOI: doi:10.1111/j.1528-1157.1992.tb01712.x
See also references of EP 2769716A4
LUCIANA S. BRANCO-DE-ALMEIDA ET AL.: "Fluoxetine inhibitors inflammatory response and bone loss in a rat model of ligature-induced periodontitis.", JOURNAL OF PERIODONTOLOGY., vol. 83, no. 5, 3 October 2011 (2011-10-03), pages 664 - 671, XP008170864
CHEOL HONG PARK ET AL.: "Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice.", KOREAN JOURNAL OF PHYSIOLOGY & PHARMACEOLOGY., vol. 15, no. 2, 30 April 2011 (2011-04-30), pages 115 - 122, XP055128648
BUTTERFIELD ET AL., FREE RADICAL BIOLOGY AND MEDICINE, vol. 32, 2002, pages 1050 - 1060
BUTTERFIELD ET AL., FREE RADICAL BIOLOGY AND MEDICINE, vol. 43, 2007, pages 658 - 677
RISAU, W., NATURE, vol. 386, 1997, pages 671 - 674
MALTEPE, E.; SIMON, M.C., J. MOL. MED., vol. 76, 1998, pages 391 - 401
LEE, Y.M. ET AL., DEV. DYN., vol. 220, 2001, pages 175 - 186
SONG, H.S. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN, vol. 290, 2002, pages 325 - 331
LEANDER, J.D.: "Fluoxetine, a selective serotonin-uptake inhibitor enhances the anticonvulsant effects of phenytoin, carbamzepine, and ameltolide (LY201116", EPILEPSAI, vol. 33, 1992, pages 573 - 576, XP002374917, DOI: doi:10.1111/j.1528-1157.1992.tb01712.x
See also references of EP 2769716A4
Attorney, Agent or Firm:
LEE, Won Hee (642-16Yoksam-dong,Kangnam-ku, Seoul 135-080, KR)
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Claims: