WO2008146753A1 - 脳梗塞治療剤 - Google Patents

脳梗塞治療剤 Download PDF

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Publication number
WO2008146753A1
WO2008146753A1 PCT/JP2008/059582 JP2008059582W WO2008146753A1 WO 2008146753 A1 WO2008146753 A1 WO 2008146753A1 JP 2008059582 W JP2008059582 W JP 2008059582W WO 2008146753 A1 WO2008146753 A1 WO 2008146753A1
Authority
WO
WIPO (PCT)
Prior art keywords
therapeutic agent
cerebral infarction
novel therapeutic
brain
mcp
Prior art date
Application number
PCT/JP2008/059582
Other languages
English (en)
French (fr)
Inventor
Haruto Nakagawa
Naoko Ando
Original Assignee
Mitsubishi Tanabe Pharma Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US12/601,609 priority Critical patent/US8835631B2/en
Application filed by Mitsubishi Tanabe Pharma Corporation filed Critical Mitsubishi Tanabe Pharma Corporation
Priority to EP20080764628 priority patent/EP2154135B1/en
Priority to BRPI0811222 priority patent/BRPI0811222A2/pt
Priority to JP2009516304A priority patent/JP5366803B2/ja
Priority to ES08764628T priority patent/ES2405542T3/es
Priority to AU2008255885A priority patent/AU2008255885A1/en
Priority to CA 2687942 priority patent/CA2687942A1/en
Priority to CN200880017326A priority patent/CN101679367A/zh
Publication of WO2008146753A1 publication Critical patent/WO2008146753A1/ja
Priority to US14/457,283 priority patent/US20140350250A1/en
Priority to US14/457,173 priority patent/US20140350249A1/en
Priority to US14/575,489 priority patent/US20150104483A1/en
Priority to US14/575,599 priority patent/US9233969B2/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/18—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

　本発明は、ピペラジン系化合物を有効成分とする新規な脳梗塞治療薬を提供することを課題とする。 　本発明に係る化合物は、ＴＮＦ－α、ＩＬ－１β、ＩＬ－６およびＭＣＰ－１などの脳内に存在する複数の炎症性サイトカインおよびケモカイン産生を抑制することにより、脳傷害体積の抑制や神経症状を改善する効果を有した新規な脳梗塞治療薬とすることができる。
PCT/JP2008/059582 2007-05-24 2008-05-23 脳梗塞治療剤 WO2008146753A1 (ja)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU2008255885A AU2008255885A1 (en) 2007-05-24 2008-05-23 Therapeutic agent for cerebral infarction
EP20080764628 EP2154135B1 (en) 2007-05-24 2008-05-23 Therapeutic agent for cerebral infarction
BRPI0811222 BRPI0811222A2 (pt) 2007-05-24 2008-05-23 Agente terapêutico para infarto cerebral.
JP2009516304A JP5366803B2 (ja) 2007-05-24 2008-05-23 脳梗塞治療剤
ES08764628T ES2405542T3 (es) 2007-05-24 2008-05-23 Agente terapéutico para el infarto cerebral
US12/601,609 US8835631B2 (en) 2007-05-24 2008-05-23 Therapeutic agent for cerebral infarction
CA 2687942 CA2687942A1 (en) 2007-05-24 2008-05-23 Therapeutic agent for cerebral infarction
CN200880017326A CN101679367A (zh) 2007-05-24 2008-05-23 脑梗塞治疗药剂
US14/457,283 US20140350250A1 (en) 2007-05-24 2014-08-12 Therapeutic agent for cerebral infarction
US14/457,173 US20140350249A1 (en) 2007-05-24 2014-08-12 Therapeutic agent for cerebral infarction
US14/575,489 US20150104483A1 (en) 2007-05-24 2014-12-18 Therapeutic agent for cerebral infarction
US14/575,599 US9233969B2 (en) 2007-05-24 2014-12-18 Therapeutic agent for cerebral infarction

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2007-137504 2007-05-24
JP2007137504 2007-05-24

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US12/601,609 A-371-Of-International US8835631B2 (en) 2007-05-24 2008-05-23 Therapeutic agent for cerebral infarction
US14/457,283 Division US20140350250A1 (en) 2007-05-24 2014-08-12 Therapeutic agent for cerebral infarction
US14/457,173 Continuation US20140350249A1 (en) 2007-05-24 2014-08-12 Therapeutic agent for cerebral infarction

Publications (1)

Publication Number Publication Date
WO2008146753A1 true WO2008146753A1 (ja) 2008-12-04

Family

ID=40075000

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2008/059582 WO2008146753A1 (ja) 2007-05-24 2008-05-23 脳梗塞治療剤

Country Status (11)

Country Link
US (5) US8835631B2 (ja)
EP (2) EP2532658A1 (ja)
JP (1) JP5366803B2 (ja)
KR (1) KR20100022080A (ja)
CN (1) CN101679367A (ja)
AU (1) AU2008255885A1 (ja)
BR (1) BRPI0811222A2 (ja)
CA (1) CA2687942A1 (ja)
ES (1) ES2405542T3 (ja)
RU (1) RU2009148049A (ja)
WO (1) WO2008146753A1 (ja)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011524409A (ja) * 2008-06-16 2011-09-01 サノフイ−アベンテイス Ｔｎｆの調節活性を有するフェニル−アルキルピペラジン
US8609672B2 (en) 2010-08-27 2013-12-17 University Of The Pacific Piperazinylpyrimidine analogues as protein kinase inhibitors
WO2014119438A1 (ja) * 2013-01-29 2014-08-07 国立大学法人大阪大学 梗塞性疾患の予防又は治療用医薬

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2008255885A1 (en) * 2007-05-24 2008-12-04 Mitsubishi Tanabe Pharma Corporation Therapeutic agent for cerebral infarction
CN106977500A (zh) * 2017-04-17 2017-07-25 牡丹江医学院 一种用于治疗脑梗塞的药物及其制备方法
ES2822399B2 (es) 2019-10-31 2022-02-16 Univ Murcia Dispositivo de recogida de fluido uterino in vivo

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999019301A1 (fr) 1997-10-14 1999-04-22 Yoshitomi Pharmaceutical Industries, Ltd. Composes de piperazine et utilisation medicale desdits composes
JP2005511698A (ja) * 2001-11-30 2005-04-28 シェーリング　コーポレイション アデノシンＡ２ａレセプターアンタゴニスト
WO2005103013A1 (ja) 2004-04-27 2005-11-03 Mitsubishi Pharma Corporation 非ウイルス性肝炎治療薬

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005110982A2 (en) * 2004-04-07 2005-11-24 Neurogen Corporation Substituted 1-benzyl-4-substituted piperazine analogues
KR101329112B1 (ko) * 2005-11-08 2013-11-14 랜박시 래보러터리스 리미티드 (3ｒ,5ｒ)-7-〔2-(4-플루오로페닐)-5-이소프로필-3-페닐-4-〔(4-히드록시 메틸 페닐 아미노)카르보닐〕-피롤-1-일〕-3,5-디히드록시 헵탄산 헤미 칼슘염의 제조 방법
AU2008255885A1 (en) 2007-05-24 2008-12-04 Mitsubishi Tanabe Pharma Corporation Therapeutic agent for cerebral infarction

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999019301A1 (fr) 1997-10-14 1999-04-22 Yoshitomi Pharmaceutical Industries, Ltd. Composes de piperazine et utilisation medicale desdits composes
JP2005511698A (ja) * 2001-11-30 2005-04-28 シェーリング　コーポレイション アデノシンＡ２ａレセプターアンタゴニスト
WO2005103013A1 (ja) 2004-04-27 2005-11-03 Mitsubishi Pharma Corporation 非ウイルス性肝炎治療薬

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BARONE F.C. ET AL.: "Tumor necrosis factor-alpha: a mediator of focal ischemic brain injury", STORKE, vol. 28, no. 6, 1997, pages 1233 - 1244, XP008123609 *
BARONE, F.C. ET AL., STROKE, vol. 28, 1997, pages 1223 - 1244
BETZ, A.L. ET AL., J. CEREB. BLOOD FLOW METAB., vol. 15, 1995, pages 547 - 551
DIRNAGL, U. ET AL., TRENDS. NEUROSCI., vol. 22, 1999, pages 391 - 397
DIRNAGL, U. ET AL., TRENDS. NEUROSCI., vol. 26, 2003, pages 248 - 254
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HANANO T. ET AL.: "Novel DMARDs on the basis of a new concept of dual cytokine regulation, TNF-alpha suppression and IL-10 augmentation", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 9, 2000, pages 881 - 884, XP004199034 *
HISADOME, M. ET AL., EUR. J. PHARMACOL., vol. 497, 2004, pages 351 - 359
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See also references of EP2154135A4 *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011524409A (ja) * 2008-06-16 2011-09-01 サノフイ−アベンテイス Ｔｎｆの調節活性を有するフェニル−アルキルピペラジン
US8609672B2 (en) 2010-08-27 2013-12-17 University Of The Pacific Piperazinylpyrimidine analogues as protein kinase inhibitors
WO2014119438A1 (ja) * 2013-01-29 2014-08-07 国立大学法人大阪大学 梗塞性疾患の予防又は治療用医薬

Also Published As

Publication number Publication date
JPWO2008146753A1 (ja) 2010-08-19
US20140350250A1 (en) 2014-11-27
CN101679367A (zh) 2010-03-24
US9233969B2 (en) 2016-01-12
ES2405542T3 (es) 2013-05-31
RU2009148049A (ru) 2011-06-27
EP2154135B1 (en) 2013-02-27
US8835631B2 (en) 2014-09-16
US20100179157A1 (en) 2010-07-15
EP2154135A4 (en) 2010-09-01
US20140350249A1 (en) 2014-11-27
KR20100022080A (ko) 2010-02-26
BRPI0811222A2 (pt) 2014-10-29
EP2154135A1 (en) 2010-02-17
CA2687942A1 (en) 2008-12-04
US20150104483A1 (en) 2015-04-16
EP2532658A1 (en) 2012-12-12
US20150105400A1 (en) 2015-04-16
AU2008255885A1 (en) 2008-12-04
JP5366803B2 (ja) 2013-12-11

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