JP2010518091A5 - - Google Patents
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- JP2010518091A5 JP2010518091A5 JP2009549130A JP2009549130A JP2010518091A5 JP 2010518091 A5 JP2010518091 A5 JP 2010518091A5 JP 2009549130 A JP2009549130 A JP 2009549130A JP 2009549130 A JP2009549130 A JP 2009549130A JP 2010518091 A5 JP2010518091 A5 JP 2010518091A5
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- Japan
- Prior art keywords
- pharmaceutical composition
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- bryologs
- pharmaceutical
- activator
- Prior art date
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- 239000012190 activator Substances 0.000 claims description 6
- OYHQOLUKZRVURQ-IXWMQOLASA-N (9E,12Z)-octadeca-9,12-dienoic acid Chemical class CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims description 3
- 150000001982 diacylglycerols Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 37
- -1 bicyclic triterpenoids Chemical class 0.000 claims 5
- 208000008208 Craniocerebral Trauma Diseases 0.000 claims 3
- 150000004141 diterpene derivatives Chemical class 0.000 claims 3
- ZFIFHAKCBWOSRN-UHFFFAOYSA-N naphthalene-1-sulfonamide Chemical class C1=CC=C2C(S(=O)(=O)N)=CC=CC2=C1 ZFIFHAKCBWOSRN-UHFFFAOYSA-N 0.000 claims 3
- ZBCATMYQYDCTIZ-UHFFFAOYSA-N 4-Methylcatechol Chemical compound CC1=CC=C(O)C(O)=C1 ZBCATMYQYDCTIZ-UHFFFAOYSA-N 0.000 claims 2
- CGPFADLKIPZYRE-OWLUANBVSA-N daphnane Chemical compound C([C@]12CCC[C@H]1[C@]13CCC)C[C@H]4[C@]3(C)CC[C@H](C(C)C)[C@@H]1N2C4 CGPFADLKIPZYRE-OWLUANBVSA-N 0.000 claims 2
- 239000003047 diacylglycerol kinase inhibitor Substances 0.000 claims 2
- 229930004069 diterpenes Natural products 0.000 claims 2
- 239000003102 growth factor Substances 0.000 claims 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- MJMJERJFCHYXEM-UHFFFAOYSA-N 5-chloro-N-heptylnaphthalene-1-sulfonamide Chemical group C1=CC=C2C(S(=O)(=O)NCCCCCCC)=CC=CC2=C1Cl MJMJERJFCHYXEM-UHFFFAOYSA-N 0.000 claims 1
- 208000008581 Brain Disease Diseases 0.000 claims 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N Guaiacol Chemical class COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 claims 1
- 206010019196 Head injury Diseases 0.000 claims 1
- GIMKEHNOTHXONN-NXBFFCPZSA-N Ingenol 3,20-dibenzoate Chemical compound C([C@H]1[C@H]2[C@H](C2(C)C)C[C@H]([C@@]2(C=C(C)[C@H](OC(=O)C=3C=CC=CC=3)[C@@]2(O)[C@@H]2O)C1=O)C)=C2COC(=O)C1=CC=CC=C1 GIMKEHNOTHXONN-NXBFFCPZSA-N 0.000 claims 1
- GIMKEHNOTHXONN-QBZCICILSA-N Ingenol 3,20-dibenzoate Natural products O=C(OCC=1[C@@H](O)[C@]2(O)[C@@H](OC(=O)c3ccccc3)C(C)=C[C@@]32[C@@H](C)C[C@H]2C(C)(C)[C@@H]2[C@H](C3=O)C=1)c1ccccc1 GIMKEHNOTHXONN-QBZCICILSA-N 0.000 claims 1
- VDJHFHXMUKFKET-WDUFCVPESA-N Ingenol mebutate Chemical compound C[C@@H]1C[C@H]2C(C)(C)[C@H]2[C@@H]2C=C(CO)[C@@H](O)[C@]3(O)[C@@H](OC(=O)C(\C)=C/C)C(C)=C[C@]31C2=O VDJHFHXMUKFKET-WDUFCVPESA-N 0.000 claims 1
- 208000001652 Memory Disorders Diseases 0.000 claims 1
- 102000003923 Protein Kinase C Human genes 0.000 claims 1
- 108090000315 Protein Kinase C Proteins 0.000 claims 1
- UEZROEGYRDHMRV-UHFFFAOYSA-N [1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound O=C1C=CN=C2SC=CN12 UEZROEGYRDHMRV-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- VEBVPUXQAPLADL-POYOOMFHSA-N ingenol Chemical compound C1=C(CO)[C@@H](O)[C@]2(O)[C@@H](O)C(C)=C[C@]32[C@H](C)C[C@H]2C(C)(C)[C@H]2[C@H]1C3=O VEBVPUXQAPLADL-POYOOMFHSA-N 0.000 claims 1
- 229960002993 ingenol mebutate Drugs 0.000 claims 1
- 150000003951 lactams Chemical class 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- QGVLYPPODPLXMB-UBTYZVCOSA-N phorbol derivatives Chemical class [H][C@@]12C=C(CO)C[C@]3(O)C(=O)C(C)=C[C@@]3([H])[C@@]1(O)[C@H](C)[C@@H](O)[C@]1(O)[C@@]2([H])C1(C)C QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 claims 1
- 239000002644 phorbol ester Substances 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 150000003505 terpenes Chemical class 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- CONYTTFKIUJZOF-UHFFFAOYSA-N 8-[2-[(2-pentylcyclopropyl)methyl]cyclopropyl]octanoic acid Chemical compound CCCCCC1CC1CC1C(CCCCCCCC(O)=O)C1 CONYTTFKIUJZOF-UHFFFAOYSA-N 0.000 description 4
- UNJJBGNPUUVVFQ-ZJUUUORDSA-N Phosphatidylserine Chemical compound CCCC(=O)O[C@H](COC(=O)CC)COP(O)(=O)OC[C@H](N)C(O)=O UNJJBGNPUUVVFQ-ZJUUUORDSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
Description
リノール酸誘導体DCP-LA (2-[(2-ペンチルシクロプロピル)メチル]シクロプロパンオクタン酸)は既知PKCのほとんど知られていないアイソフォーム特異的なアクチベータの一つである。DCP-LAは、100 nMで最大効果を示し、選択的にPKCεを活性化する(Kanno et al. (2006) J. Lipid Res. 47: 1146)。SC-10と同様に、DCP-LAは、ジアシルグリセロール結合部位の代わりに、PKCのホスファチジルセリン結合部位と相互作用する。
Claims (18)
- 頭部外傷を治療するための医薬組成物であって、有効成分としてのプロテインキナーゼC（PKC）アクチベータ、4-メチルカテコール酢酸（MCBA）、またはメチルカテコールの他の誘導体と、薬学的に許容される担体とを含み、当該PKCアクチベータが、ブリオログ、ホルボールエステル以外のジアシルグリセロール誘導体、イソプレノイド、ダフナン型ジテルペン、二環式トリテルペノイド、ナフタレンスルホンアミド、リノール酸誘導体、ジアシルグリセロールキナーゼインヒビター、成長因子アクチベータ、およびそれらの組み合わせからなる群より選択される医薬組成物。
- 請求項１に記載の医薬組成物であって、当該医薬組成物の投与は前記頭部外傷の１〜３日目の間に開始される医薬組成物。
- 請求項１に記載の医薬組成物であって、当該医薬組成物による治療は１〜６週間の期間継続する医薬組成物。
- 請求項１に記載の医薬組成物であって、当該医薬組成物による治療は頭部外傷誘導性の脳障害または記憶障害を逆転させる医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ブリオログがB環ブリオログまたはA環ブリオログである医薬組成物。
- 請求項５に記載の医薬組成物であって、当該B環またはA環ブリオログが約600から755の分子量および約０．２５ｎＭから１０μＭのPKC親和性を有する医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ブリオログが：
- 請求項５に記載の医薬組成物であって、当該ブリオログが：
- 請求項５に記載の医薬組成物であって、当該ブリオログが：
- 請求項１に記載の医薬組成物であって、当該ジアシルグリセロール誘導体がシス不飽和脂肪酸から構成される医薬組成物。
- 請求項１に記載の医薬組成物であって、当該PKCアクチベータがオクチリンドラクタムVである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ダフナン型ジテルペンがグニジマクリンである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該二環式トリテルペノイドがイリパリダールである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ジテルペノイドがインゲノール、インゲノール3,20-ジベンゾエートまたはインゲノール-3-アンゲレートである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ナフタレンスルホンアミドがN-(n-ヘプチル)-5-クロロ-1-ナフタレンスルホンアミドまたはN-(6-フェニルヘキシル)-5-クロロ-1-ナフタレンスルホンアミドである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該リノール酸誘導体が2-[(2-ペンチルシクロプロピル)メチル]-シクロプロパンオクタン酸である医薬組成物。
- 請求項１に記載の医薬組成物であって、当該ジアシルグリセロールキナーゼインヒビターが、6-(2-(4-[(4-フルオロフェニル)フェニルメチレン]-1-ピペリジニル)エチル)-7-メチル-5H-チアゾロ[3,2-a]ピリミジン-5-オンまたは[3-[2-[4-(ビス-(4-フルオロフェニル)メチレン]ピペリジン-1-イル)エチル]-2,3-ジヒドロ-2-チオキソ-4(1H)-キナゾリノンである医薬組成物。
- 請求項１に記載の医薬組成物であって、当該成長因子アクチベータが4-メチルカテコール酢酸である医薬組成物。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90033807P | 2007-02-09 | 2007-02-09 | |
| US60/900,338 | 2007-02-09 | ||
| US92466307P | 2007-05-24 | 2007-05-24 | |
| US60/924,663 | 2007-05-24 | ||
| PCT/US2008/001755 WO2008100449A2 (en) | 2007-02-09 | 2008-02-11 | Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and brain injury |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013261788A Division JP6199176B2 (ja) | 2007-02-09 | 2013-12-18 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010518091A JP2010518091A (ja) | 2010-05-27 |
| JP2010518091A5 true JP2010518091A5 (ja) | 2011-07-28 |
| JP5518489B2 JP5518489B2 (ja) | 2014-06-11 |
Family
ID=39690678
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009549130A Active JP5518489B2 (ja) | 2007-02-09 | 2008-02-11 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
| JP2013261788A Expired - Fee Related JP6199176B2 (ja) | 2007-02-09 | 2013-12-18 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
| JP2016016127A Pending JP2016128486A (ja) | 2007-02-09 | 2016-01-29 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013261788A Expired - Fee Related JP6199176B2 (ja) | 2007-02-09 | 2013-12-18 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
| JP2016016127A Pending JP2016128486A (ja) | 2007-02-09 | 2016-01-29 | 頭部外傷誘導性の記憶障害および脳障害におけるブリオスタチン、ブリオログ、および他の関連物質の治療効果 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9974832B2 (ja) |
| EP (4) | EP2121000B1 (ja) |
| JP (3) | JP5518489B2 (ja) |
| KR (2) | KR20140049054A (ja) |
| CN (1) | CN101848726A (ja) |
| CA (2) | CA2873179A1 (ja) |
| ES (1) | ES2548766T3 (ja) |
| WO (1) | WO2008100449A2 (ja) |
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| KR100960256B1 (ko) | 2001-02-27 | 2010-06-01 | 블랜체트 록펠러 뉴로사이언시즈 인스티튜트 | 유사분열 촉진인자-활성화 단백질 키나제 인산화에 근거한 알쯔하이머병 진단 |
| US6825229B2 (en) | 2002-03-07 | 2004-11-30 | Blanchette Rockefeller Neurosciences Institute | Methods for Alzheimer's Disease treatment and cognitive enhancement |
| US20050065205A1 (en) | 2002-03-07 | 2005-03-24 | Daniel Alkon | Methods for Alzheimer's disease treatment and cognitive enhance |
| TW201207390A (en) | 2004-05-18 | 2012-02-16 | Brni Neurosciences Inst | Method for screening agent for antidepressant activity |
| CA2617003A1 (en) | 2005-07-29 | 2007-02-08 | Blanchette Rockefeller Neurosciences Institute | Use of a pkc activator, alone or combined with a pkc inhibitor to enhance long term memory |
| US20090029873A1 (en) | 2005-10-11 | 2009-01-29 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's Disease-Specific Alterations of the Erk1/Erk2 Phosphorylation Ratio-Alzheimer's Disease-Specific Molecular Biomarkers (Adsmb) |
| CA3006091A1 (en) * | 2007-02-09 | 2008-08-21 | Blanchette Rockefeller Neurosciences Institute | Therapeutic effects of bryostatins, bryologs, and other related substances on ischemia/stroke-induced memory impairment and brain injury |
| EP2121000B1 (en) | 2007-02-09 | 2015-09-23 | Blanchette Rockefeller Neurosciences, Institute | Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and brain injury |
| WO2008143880A2 (en) * | 2007-05-24 | 2008-11-27 | Blanchette Rockefeller Neurosciences Institute | Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and traumatic brain injury |
| US20100168219A1 (en) * | 2008-12-31 | 2010-07-01 | Jonathan Steven Alexander | Chronic inflammation and transplantation |
| US9994585B2 (en) | 2007-12-31 | 2018-06-12 | Aphios Corporation | Transplantation therapies |
| ES2683021T3 (es) | 2008-07-28 | 2018-09-24 | Blanchette Rockefeller Neurosciences Institute | Compuestos activadores de la PKC para el tratamiento de enfermedades neurodegenerativas |
| EP2669386A1 (en) | 2008-07-28 | 2013-12-04 | Blanchette Rockefeller Neurosciences Institute | Stimulus-elicited genomic profile markers of alzheimer's disease |
| WO2010073258A1 (en) * | 2008-12-22 | 2010-07-01 | Department Of Biotechnology | Bicyclic triterpenoid iripallidal as a novel antiglioma and antineoplastic therapy in vitro |
| BR112012007557A2 (pt) | 2009-10-02 | 2017-05-02 | Blanchette Rockefeller Neurosciences Inst | alterações anormais de processamento de isozimas de pkc em células periféricas da doença de alzheimer |
| WO2011041761A1 (en) | 2009-10-02 | 2011-04-07 | Blanchette Rockefeller Neurosciences Institute | Fibroblast growth patterns for diagnosis of alzheimer's disease |
| JP6446624B2 (ja) | 2010-07-08 | 2019-01-09 | アルコン、ダニエル・エル． | 脳卒中の治療法におけるｐｋｃ活性化因子および抗凝血剤 |
| KR101467605B1 (ko) * | 2010-11-29 | 2014-12-04 | 충북대학교 산학협력단 | 신규의 다프난 디테르펜계 화합물 및 이를 유효성분으로 포함하는 피부 미백용 조성물 |
| EP2780316B1 (en) | 2011-11-13 | 2020-04-15 | Blanchette Rockefeller Neurosciences Institute | Esters of dcpla and methods of treatment using the same |
| US9034347B2 (en) | 2011-12-19 | 2015-05-19 | Arphios Corporation | Drug delivery system and method for the treatment of neuro-degenerative disease |
| WO2014085494A1 (en) | 2012-11-28 | 2014-06-05 | Aphios Corporation | Combination therapeutics and methods for the treatment of neurodegenerative and other diseases |
| JP2016516201A (ja) | 2013-03-15 | 2016-06-02 | ブランシェット・ロックフェラー・ニューロサイエンスィズ・インスティテュート | 神経保護性ｐｋｃ活性化因子を特定する方法 |
| US11123324B2 (en) | 2016-08-18 | 2021-09-21 | Noster Inc. | Immunomodulator |
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-
2008
- 2008-02-11 EP EP08725395.1A patent/EP2121000B1/en not_active Not-in-force
- 2008-02-11 CN CN200880004009A patent/CN101848726A/zh active Pending
- 2008-02-11 JP JP2009549130A patent/JP5518489B2/ja active Active
- 2008-02-11 CA CA2873179A patent/CA2873179A1/en not_active Abandoned
- 2008-02-11 EP EP15002036.0A patent/EP2959914A1/en not_active Ceased
- 2008-02-11 US US12/068,742 patent/US9974832B2/en active Active
- 2008-02-11 CA CA002674773A patent/CA2674773A1/en not_active Withdrawn
- 2008-02-11 WO PCT/US2008/001755 patent/WO2008100449A2/en active Application Filing
- 2008-02-11 EP EP18153508.9A patent/EP3332797A3/en not_active Withdrawn
- 2008-02-11 KR KR1020147006408A patent/KR20140049054A/ko not_active Application Discontinuation
- 2008-02-11 EP EP14001303.8A patent/EP2754448A3/en not_active Withdrawn
- 2008-02-11 ES ES08725395.1T patent/ES2548766T3/es active Active
- 2008-02-11 KR KR1020097018890A patent/KR20090119894A/ko not_active Application Discontinuation
-
2013
- 2013-12-18 JP JP2013261788A patent/JP6199176B2/ja not_active Expired - Fee Related
-
2016
- 2016-01-29 JP JP2016016127A patent/JP2016128486A/ja active Pending
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2018
- 2018-04-17 US US15/954,693 patent/US20190083575A1/en not_active Abandoned
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