Title:
THERAPEUTIC AGENT FOR BLOOD-BRAIN BARRIER DISRUPTION SYNDROME
Document Type and Number:
WIPO Patent Application WO/2012/081713
Kind Code:
A1
Abstract:
A medicinal agent or a pharmaceutical composition, each of which comprises a biguanide drug or a pharmaceutically acceptable salt thereof as an active ingredient, and which can potentiate blood-brain barrier functions including tight junction capability and transcellular transport capability of a brain capillary endothelial cell and therefore can treat blood-brain barrier disruption syndrome.
Inventors:
TAKATA FUYUKO (JP)
DOHGU SHINYA (JP)
KATAOKA YASUFUMI (JP)
MATSUMOTO JYUN-ICHI (JP)
KANESHIMA SYUJI (JP)
DOHGU SHINYA (JP)
KATAOKA YASUFUMI (JP)
MATSUMOTO JYUN-ICHI (JP)
KANESHIMA SYUJI (JP)
Application Number:
PCT/JP2011/079266
Publication Date:
June 21, 2012
Filing Date:
December 12, 2011
Export Citation:
Assignee:
UNIV FUKUOKA (JP)
TAKATA FUYUKO (JP)
DOHGU SHINYA (JP)
KATAOKA YASUFUMI (JP)
MATSUMOTO JYUN-ICHI (JP)
KANESHIMA SYUJI (JP)
TAKATA FUYUKO (JP)
DOHGU SHINYA (JP)
KATAOKA YASUFUMI (JP)
MATSUMOTO JYUN-ICHI (JP)
KANESHIMA SYUJI (JP)
International Classes:
A61K31/155; A61K45/00; A61P3/04; A61P3/10; A61P9/12; A61P25/00; A61P25/08; A61P25/18; A61P25/26; A61P25/28; A61P31/04
Domestic Patent References:
| WO2007124308A2 | 2007-11-01 |
Foreign References:
| JP2009221217A | 2009-10-01 |
Other References:
YOKOYAMA, Y. ET AL.: "Regulation of glyceraldehyde 3-phosphate dehydrogenase expression by metformin in HepG2 cells", BIOLOGICAL & PHARMACEUTICAL BULLETIN, vol. 32, no. 7, 2009, pages 1160 - 1165, XP055108915
TAKAYUKI MATSUMOTO: "A Therapeutic Target for Endothelium-derived Hyperpolarizing Factor Signaling in Diabetic Vascular Complication", JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, vol. 130, no. 6, 1 June 2010 (2010-06-01), pages 777 - 784, XP055108916
DOHGU, S. ET AL.: "Cyclosporin A induces hyperpermeability of the blood-brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 644, no. 1-3, 2010, pages 5 - 9, XP027243308
SU, E.J. ET AL.: "Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke", NATURE MEDICINE, vol. 14, no. 7, 2008, NEW YORK, NY, UNITED STATES, pages 731 - 737, XP055108917
SHARMA, R.V. ET AL.: "Metformin attenuates agonist-stimulated calcium transients in vascular smooth muscle cells", CLINICAL AND EXPERIMENTAL HYPERTENSION, vol. 17, no. 6, 1995, pages 913 - 929, XP008168313
LEYBAERT, L. ET AL.: "Inositol-trisphosphate- dependent intercellular calcium signaling in and between astrocytes and endothelial cells", GLIA, vol. 24, no. 4, 1998, pages 398 - 407, XP055108918
CHARLES, M.A. ET AL.: "Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPR01 Study.", BIGUANIDES AND THE PREVENTION OF THE RISK OF OBESITY, DIABETES CARE, vol. 21, no. 11, 1998, pages 1967 - 1972, XP055108920
See also references of EP 2653158A4
NEURON, vol. 57, 2008, pages 178 - 201
NATURE MEDICINE, vol. 14, no. 7, July 2008 (2008-07-01), pages 731 - 737
NICOLAS W.; FLORENCE M.; SYLVIE C.; PIERRE-OLIVIER C.: "The blood-brain barrier in brain hoeostasis and neurological diseases", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1778, 2009, pages 842 - 857
NISHIOKU T.; YAMAUCHI A.; TAKATA F.; WATANABE T.; FURUSHO K.; SHUTO H.; DOHGU S.; KATAOKA Y: "Disruption of the blood-brain barrier in collagen-induced arthritic mice", NEUROSCIENCE LETTERS, vol. 482, no. 3, 4 October 2010 (2010-10-04), pages 208 - 211, XP027234502
YAMAUCHI A.; DOHGU S.; TAKATA F.; WATANABE T.; NISHIOKU T.; MATSUMOTO J.; OHKUBO Y; SHUTO H.; KATAOKA Y: "Partial hepatectomy aggravates cyclosporin A- induced neurotoxicity by lowering the function of the blood-brain barrier in mice", LIFE SCIENCES, vol. 88, no. 11-12, 14 March 2011 (2011-03-14), pages 529 - 534
DOHGU S.; SUMI N.; NISHIOKU T.; TAKATA F.; WATANABE T.; NAITO M.; SHUTO H.; YAMAUCHI A.; KATAOKA Y: "Cyclosporin A induces hyperpermeability of the blood- brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 644, no. 1-3, 10 October 2010 (2010-10-10), pages 5 - 9
DOHGU S.; NISHIOKU T.; SUMI N.; TAKATA F.; NAKAGAWA S.; NAITO M.; TSURUO T.; YAMAUCHI A.; SHUTO H.; KATAOKA Y: "Adverse effect of cyclosporin A on barrier functions of cerebral microvascular endothelial cells after hypoxia-reoxygenation damage in vitro", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 27, no. 7, November 2007 (2007-11-01), pages 889 - 899, XP019570993
TAKATA F.; DOHGU S.; YAMAUCHI A.; SUMI N.; NAKAGAWA S.; NAITO M.; TSURUO T.; SHUTO H.; KATAOKA Y: "Inhibition of transforming growth factor-beta production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-brain barrier", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 27, no. 3, May 2007 (2007-05-01), pages 317 - 328, XP019498985
YAMAUCHI A.; SHUTO H.; DOHGU S.; NAKANO Y; EGAWA T.; KATAOKA Y: "Cyctosporin A aggravates electroshock-induced convulsions in mice with a transient middle cerebral artery occlusion", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 25, no. 5, August 2005 (2005-08-01), pages 923 - 928, XP019275815
DOHGU S.; YAMAUCHI A.; NAKAGAWA S.; TAKATA F.; KAI M.; EGAWA T.; NAITO M.; TSURUO T.; SAWADA Y; NIWA M.: "Nitric oxide mediates cyclosporine- induced impairment of the blood-brain barrier in cocultures of mouse brain endothelial cells and rat astrocytes", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 505, no. 1-3, 28 November 2004 (2004-11-28), pages 51 - 59, XP004649367, DOI: doi:10.1016/j.ejphar.2004.10.027
YAMAUCHI A.; OISHI R.; KATAOKA Y: "HTacrolimus-induced neurotoxicity and nephrotoxicity is ameliorated by administration in the dark phase in rats", CELL MOL NEUROBIOL, vol. 24, no. 5, October 2004 (2004-10-01), pages 695 - 704, XP019275743
FUJISAKI Y; YAMAUCHI A.; DOHGU S.; SUNADA K.; YAMAGUCHI C.; OISHI R.; KATAOKA Y: "Cyclosporine A-increased nitric oxide production in the rat dorsal hippocampus mediates convulsions", LIFE SCIENCES, vol. 72, no. 4-5, 20 December 2002 (2002-12-20), pages 549 - 556
TOMINAGA K.; KAI M.; YAMAUCHI A.; DOHGU S.; TODA K.; OISHI R.; KATAOKA Y: "Subchronic treatment with cyclosporin A decreases the binding properties of the GABAA receptor in ovariectomized rats", LIFE SCIENCES, vol. 72, no. 4-5, 20 December 2002 (2002-12-20), pages 425 - 430
KANOSKI SE; ZHANG Y.; ZHENG W.; DAVIDSON TL: "The effects of a high- energy diet on hippocampal function and blood-brain barrier integrity in the rat", JOURNAL OF ALZHEIMER'S DISEASE, vol. 21, no. 1, January 2010 (2010-01-01), pages 207 - 219
UENO M; SAKAMOTO H; TOMIMOTO H; AKIGUCHI I; ONODERA M; HUANG CL; KANENISHI K.: "Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats.", ACTA NEUROPATHOLOGICA, vol. 107, no. 6, June 2004 (2004-06-01), pages 532 - 538
HONDA M.; NAKAGAWA S.; HAYASHI K.; KITAGAWA N.; TSUTSUMI K.; NAGATA 1.; NIWA M.: "Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 26, no. 2, 2006, pages 109 - 118, XP019392961, DOI: doi:10.1007/s10571-006-9028-x
JIN R.; YANG G.; LI G.: "Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator", NEUROBIOL OF DISEASE, vol. 38, no. 3, June 2010 (2010-06-01), pages 376 - 385, XP027035423
ABU FANNE R.; NASSAR T.; YAROVOI S.; RAYAN A.; LAMENSDORFL.; KARAKOVESKI M.; VADIM P.; JAMMAL M.; CINES D. B.; HIGAZI A. A.: "Blood-brain barrier permeability and tPA-mediated neurotoxicity", NEUROPHARMACOLOGY, vol. 58, no. 7, June 2010 (2010-06-01), pages 972 - 980
ISOBE, I.; WATANABE, T.; HAZEMOTO, N.; YAMAGATA, K.; UEKI, T.; NAKANISHI, K.; ASAI, K.; KATO, T.: "Astrocytic contributions to blood-brain barrier (BBB) formation by endothelial cells: a possible use of aortic endothelial cell for in vitro model", NEUROCHEMISTRY INTERNATIONAL, vol. 28, 1996, pages 523 - 533
DEHOUCK, M.-P.; JOLLIET-RIANT, P.; BREE, F.; FRUCHART J.-C.; CECCHELLI, R.; TILLEMENT, J.-P.: "Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo rnodels", JOURNAL OF NEUROCHEMISTRY, vol. 58, 1992, pages 1790 - 1797
HAYASHI Y; NOMURA M.; YAMAGISHI S.; HARADA S.; YAMASHITA J.; YAMAMOTO H.: "Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes", GLIA, vol. 19, 1997, pages 13 - 26, XP001002756, DOI: doi:10.1002/(SICI)1098-1136(199701)19:1<13::AID-GLIA2>3.0.CO;2-B
TAKATA F; SUMI N; NISHIOKU T; HARADA E; WAKIGAWA T; SHUTO H; YAMAUCHI A; KATAOKA Y: "Oncostatin M induces functional and structural impairment of blood-brain barriers comprised of rat brain capillary endothelial cells", NEUROSCIENCE LETTERS, vol. 441, no. 2, 2008, pages 163 - 166, XP022850178, DOI: doi:10.1016/j.neulet.2008.06.030
TAKAYUKI MATSUMOTO: "A Therapeutic Target for Endothelium-derived Hyperpolarizing Factor Signaling in Diabetic Vascular Complication", JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, vol. 130, no. 6, 1 June 2010 (2010-06-01), pages 777 - 784, XP055108916
DOHGU, S. ET AL.: "Cyclosporin A induces hyperpermeability of the blood-brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 644, no. 1-3, 2010, pages 5 - 9, XP027243308
SU, E.J. ET AL.: "Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke", NATURE MEDICINE, vol. 14, no. 7, 2008, NEW YORK, NY, UNITED STATES, pages 731 - 737, XP055108917
SHARMA, R.V. ET AL.: "Metformin attenuates agonist-stimulated calcium transients in vascular smooth muscle cells", CLINICAL AND EXPERIMENTAL HYPERTENSION, vol. 17, no. 6, 1995, pages 913 - 929, XP008168313
LEYBAERT, L. ET AL.: "Inositol-trisphosphate- dependent intercellular calcium signaling in and between astrocytes and endothelial cells", GLIA, vol. 24, no. 4, 1998, pages 398 - 407, XP055108918
CHARLES, M.A. ET AL.: "Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPR01 Study.", BIGUANIDES AND THE PREVENTION OF THE RISK OF OBESITY, DIABETES CARE, vol. 21, no. 11, 1998, pages 1967 - 1972, XP055108920
See also references of EP 2653158A4
NEURON, vol. 57, 2008, pages 178 - 201
NATURE MEDICINE, vol. 14, no. 7, July 2008 (2008-07-01), pages 731 - 737
NICOLAS W.; FLORENCE M.; SYLVIE C.; PIERRE-OLIVIER C.: "The blood-brain barrier in brain hoeostasis and neurological diseases", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1778, 2009, pages 842 - 857
NISHIOKU T.; YAMAUCHI A.; TAKATA F.; WATANABE T.; FURUSHO K.; SHUTO H.; DOHGU S.; KATAOKA Y: "Disruption of the blood-brain barrier in collagen-induced arthritic mice", NEUROSCIENCE LETTERS, vol. 482, no. 3, 4 October 2010 (2010-10-04), pages 208 - 211, XP027234502
YAMAUCHI A.; DOHGU S.; TAKATA F.; WATANABE T.; NISHIOKU T.; MATSUMOTO J.; OHKUBO Y; SHUTO H.; KATAOKA Y: "Partial hepatectomy aggravates cyclosporin A- induced neurotoxicity by lowering the function of the blood-brain barrier in mice", LIFE SCIENCES, vol. 88, no. 11-12, 14 March 2011 (2011-03-14), pages 529 - 534
DOHGU S.; SUMI N.; NISHIOKU T.; TAKATA F.; WATANABE T.; NAITO M.; SHUTO H.; YAMAUCHI A.; KATAOKA Y: "Cyclosporin A induces hyperpermeability of the blood- brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 644, no. 1-3, 10 October 2010 (2010-10-10), pages 5 - 9
DOHGU S.; NISHIOKU T.; SUMI N.; TAKATA F.; NAKAGAWA S.; NAITO M.; TSURUO T.; YAMAUCHI A.; SHUTO H.; KATAOKA Y: "Adverse effect of cyclosporin A on barrier functions of cerebral microvascular endothelial cells after hypoxia-reoxygenation damage in vitro", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 27, no. 7, November 2007 (2007-11-01), pages 889 - 899, XP019570993
TAKATA F.; DOHGU S.; YAMAUCHI A.; SUMI N.; NAKAGAWA S.; NAITO M.; TSURUO T.; SHUTO H.; KATAOKA Y: "Inhibition of transforming growth factor-beta production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-brain barrier", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 27, no. 3, May 2007 (2007-05-01), pages 317 - 328, XP019498985
YAMAUCHI A.; SHUTO H.; DOHGU S.; NAKANO Y; EGAWA T.; KATAOKA Y: "Cyctosporin A aggravates electroshock-induced convulsions in mice with a transient middle cerebral artery occlusion", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 25, no. 5, August 2005 (2005-08-01), pages 923 - 928, XP019275815
DOHGU S.; YAMAUCHI A.; NAKAGAWA S.; TAKATA F.; KAI M.; EGAWA T.; NAITO M.; TSURUO T.; SAWADA Y; NIWA M.: "Nitric oxide mediates cyclosporine- induced impairment of the blood-brain barrier in cocultures of mouse brain endothelial cells and rat astrocytes", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 505, no. 1-3, 28 November 2004 (2004-11-28), pages 51 - 59, XP004649367, DOI: doi:10.1016/j.ejphar.2004.10.027
YAMAUCHI A.; OISHI R.; KATAOKA Y: "HTacrolimus-induced neurotoxicity and nephrotoxicity is ameliorated by administration in the dark phase in rats", CELL MOL NEUROBIOL, vol. 24, no. 5, October 2004 (2004-10-01), pages 695 - 704, XP019275743
FUJISAKI Y; YAMAUCHI A.; DOHGU S.; SUNADA K.; YAMAGUCHI C.; OISHI R.; KATAOKA Y: "Cyclosporine A-increased nitric oxide production in the rat dorsal hippocampus mediates convulsions", LIFE SCIENCES, vol. 72, no. 4-5, 20 December 2002 (2002-12-20), pages 549 - 556
TOMINAGA K.; KAI M.; YAMAUCHI A.; DOHGU S.; TODA K.; OISHI R.; KATAOKA Y: "Subchronic treatment with cyclosporin A decreases the binding properties of the GABAA receptor in ovariectomized rats", LIFE SCIENCES, vol. 72, no. 4-5, 20 December 2002 (2002-12-20), pages 425 - 430
KANOSKI SE; ZHANG Y.; ZHENG W.; DAVIDSON TL: "The effects of a high- energy diet on hippocampal function and blood-brain barrier integrity in the rat", JOURNAL OF ALZHEIMER'S DISEASE, vol. 21, no. 1, January 2010 (2010-01-01), pages 207 - 219
UENO M; SAKAMOTO H; TOMIMOTO H; AKIGUCHI I; ONODERA M; HUANG CL; KANENISHI K.: "Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats.", ACTA NEUROPATHOLOGICA, vol. 107, no. 6, June 2004 (2004-06-01), pages 532 - 538
HONDA M.; NAKAGAWA S.; HAYASHI K.; KITAGAWA N.; TSUTSUMI K.; NAGATA 1.; NIWA M.: "Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 26, no. 2, 2006, pages 109 - 118, XP019392961, DOI: doi:10.1007/s10571-006-9028-x
JIN R.; YANG G.; LI G.: "Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator", NEUROBIOL OF DISEASE, vol. 38, no. 3, June 2010 (2010-06-01), pages 376 - 385, XP027035423
ABU FANNE R.; NASSAR T.; YAROVOI S.; RAYAN A.; LAMENSDORFL.; KARAKOVESKI M.; VADIM P.; JAMMAL M.; CINES D. B.; HIGAZI A. A.: "Blood-brain barrier permeability and tPA-mediated neurotoxicity", NEUROPHARMACOLOGY, vol. 58, no. 7, June 2010 (2010-06-01), pages 972 - 980
ISOBE, I.; WATANABE, T.; HAZEMOTO, N.; YAMAGATA, K.; UEKI, T.; NAKANISHI, K.; ASAI, K.; KATO, T.: "Astrocytic contributions to blood-brain barrier (BBB) formation by endothelial cells: a possible use of aortic endothelial cell for in vitro model", NEUROCHEMISTRY INTERNATIONAL, vol. 28, 1996, pages 523 - 533
DEHOUCK, M.-P.; JOLLIET-RIANT, P.; BREE, F.; FRUCHART J.-C.; CECCHELLI, R.; TILLEMENT, J.-P.: "Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo rnodels", JOURNAL OF NEUROCHEMISTRY, vol. 58, 1992, pages 1790 - 1797
HAYASHI Y; NOMURA M.; YAMAGISHI S.; HARADA S.; YAMASHITA J.; YAMAMOTO H.: "Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes", GLIA, vol. 19, 1997, pages 13 - 26, XP001002756, DOI: doi:10.1002/(SICI)1098-1136(199701)19:1<13::AID-GLIA2>3.0.CO;2-B
TAKATA F; SUMI N; NISHIOKU T; HARADA E; WAKIGAWA T; SHUTO H; YAMAUCHI A; KATAOKA Y: "Oncostatin M induces functional and structural impairment of blood-brain barriers comprised of rat brain capillary endothelial cells", NEUROSCIENCE LETTERS, vol. 441, no. 2, 2008, pages 163 - 166, XP022850178, DOI: doi:10.1016/j.neulet.2008.06.030
Attorney, Agent or Firm:
ASAMURA, Kiyoshi et al. (JP)
Hiroshi Asamura (JP)
Hiroshi Asamura (JP)
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