JP2009523175A - 目標とされる安定な銅状態を達成及び維持して銅関連中枢神経系疾患を予防及び治療するための医薬組成物及び方法 - Google Patents
目標とされる安定な銅状態を達成及び維持して銅関連中枢神経系疾患を予防及び治療するための医薬組成物及び方法 Download PDFInfo
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- Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Urology & Nephrology (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US75767206P | 2006-01-10 | 2006-01-10 | |
| US76581206P | 2006-02-07 | 2006-02-07 | |
| PCT/US2007/060345 WO2007084818A2 (en) | 2006-01-10 | 2007-01-10 | Pharmaceutical compositions and methods to achieve and maintain a targeted and stable copper status and prevent and treat copper-related central nervous system diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009523175A true JP2009523175A (ja) | 2009-06-18 |
| JP2009523175A5 JP2009523175A5 (enExample) | 2010-02-25 |
Family
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Family Applications (1)
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| JP2008550493A Pending JP2009523175A (ja) | 2006-01-10 | 2007-01-10 | 目標とされる安定な銅状態を達成及び維持して銅関連中枢神経系疾患を予防及び治療するための医薬組成物及び方法 |
Country Status (6)
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| US (1) | US20070207191A1 (enExample) |
| EP (1) | EP1993607A4 (enExample) |
| JP (1) | JP2009523175A (enExample) |
| AU (1) | AU2007205996A1 (enExample) |
| CA (1) | CA2675230A1 (enExample) |
| WO (1) | WO2007084818A2 (enExample) |
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| JP2013509443A (ja) * | 2009-11-01 | 2013-03-14 | シンセティック バイオロジックス，インコーポレイテッド | 胃保持性の経口用高用量亜鉛調製物 |
| JP2013523709A (ja) * | 2010-03-30 | 2013-06-17 | マグナス ティーティーエム アイシー | テトラチオモリブデン酸の治療的使用 |
| JP2022525482A (ja) * | 2019-03-20 | 2022-05-16 | リンドラ セラピューティクス， インコーポレイティド | 胃内滞留剤形用のコーティング |
| JP2022536205A (ja) * | 2019-08-21 | 2022-08-12 | ブレイン ケミストリー ラブズ | 金属及びｌ－セリンを含む組成物、並びにその使用 |
| JP2023517374A (ja) * | 2020-03-16 | 2023-04-25 | 武漢広行科学研究有限公司 | 肝硬変の治療のための銅クラスター及び組成物 |
| WO2025173839A1 (ko) * | 2024-02-14 | 2025-08-21 | 국립부경대학교 산학협력단 | 알부민 고정 셀룰로오스 및 이를 포함하는 알츠하이머 치료용 조성물 |
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| KR102903285B1 (ko) * | 2020-03-16 | 2025-12-23 | 우한 바스트 컨덕트 사이언스 파운데이션 컴퍼니 리미티드 | 간경변증의 치료를 위한 구리 클러스터(CuCs) 및 조성물 |
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| US7164035B2 (en) | 2000-01-07 | 2007-01-16 | Newsome David A | Zinc-monocysteine complex and method of using zinc-cysteine complexes |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002524426A (ja) * | 1998-09-04 | 2002-08-06 | ザ リージェンツ オブ ザ ユニバーシティー オブ ミシガン | 癌の予防または処置のための方法および組成物 |
| US6797283B1 (en) * | 1998-12-23 | 2004-09-28 | Alza Corporation | Gastric retention dosage form having multiple layers |
| JP2005533003A (ja) * | 2002-03-08 | 2005-11-04 | プロテミックス コーポレイション リミティド | 心疾患および／または関連心不全の予防および／または治療 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863898A (en) * | 1986-02-06 | 1989-09-05 | Albion International, Inc. | Amino acid chelated compositions for delivery to specific biological tissue sites |
| US5972328A (en) * | 1993-03-29 | 1999-10-26 | Queen's University At Kingston | Method for treating amyloidosis |
| DE19800523C2 (de) * | 1997-01-14 | 1999-01-21 | Lohmann Therapie Syst Lts | Expandierbares gastroretentives Therapie-System mit kontrollierter Wirkstofffreisetzung im Gastrointestinaltrakt |
| GB9710699D0 (en) * | 1997-05-24 | 1997-07-16 | Danbiosyst Uk | Gastro-retentive controlled release system |
| US6586611B1 (en) * | 2000-01-07 | 2003-07-01 | David A. Newsome | Zinc-monocysteine complex and method of using zinc-cysteine complexes |
| FR2811571B1 (fr) * | 2000-07-11 | 2002-10-11 | Flamel Tech Sa | Composition pharmaceutique orale, permettant la liberation controlee et l'absorption prolongee d'un principe actif |
| WO2002043507A2 (en) * | 2000-11-30 | 2002-06-06 | The Health Research Institute | Nutrient supplements and methods for treating autism and for preventing the onset of autism |
| US20030012824A1 (en) * | 2001-07-03 | 2003-01-16 | Ott Dana Beth | Orally administered anti-stress composition |
| WO2003099223A2 (en) * | 2002-05-24 | 2003-12-04 | The Regents Of The University Of Michigan | Copper lowering treatment of inflammatory and fibrotic diseases |
| JP2006512417A (ja) * | 2002-12-24 | 2006-04-13 | ニューロケム （インターナショナル） リミテッド | β−アミロイド関連疾患の治療のための治療用製剤 |
| US20040191295A1 (en) * | 2003-03-28 | 2004-09-30 | Locniskar Mary Frances | Composition and method for viral inhibition |
| US20060045865A1 (en) * | 2004-08-27 | 2006-03-02 | Spherics, Inc. | Controlled regional oral delivery |
| US8247398B2 (en) * | 2007-02-17 | 2012-08-21 | Ssv Therapeutics, Inc. | Zinc complexes of natural amino acids for treating elevated copper caused toxicities |
-
2007
- 2007-01-10 WO PCT/US2007/060345 patent/WO2007084818A2/en not_active Ceased
- 2007-01-10 EP EP07718298A patent/EP1993607A4/en not_active Withdrawn
- 2007-01-10 AU AU2007205996A patent/AU2007205996A1/en not_active Abandoned
- 2007-01-10 CA CA002675230A patent/CA2675230A1/en not_active Abandoned
- 2007-01-10 JP JP2008550493A patent/JP2009523175A/ja active Pending
- 2007-05-07 US US11/621,962 patent/US20070207191A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002524426A (ja) * | 1998-09-04 | 2002-08-06 | ザ リージェンツ オブ ザ ユニバーシティー オブ ミシガン | 癌の予防または処置のための方法および組成物 |
| US6797283B1 (en) * | 1998-12-23 | 2004-09-28 | Alza Corporation | Gastric retention dosage form having multiple layers |
| JP2005533003A (ja) * | 2002-03-08 | 2005-11-04 | プロテミックス コーポレイション リミティド | 心疾患および／または関連心不全の予防および／または治療 |
Non-Patent Citations (2)
| Title |
|---|
| JPN6012033817; Ｐｅｔｅｒ Ｗ． Ｆ． Ｆｉｓｃｈｅｒ ｅｔ ａｌ: Ｔｈｅ Ａｍｅｒｉｃａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｌｉｎｉｃａｌ Ｎｕｔｒｉｔｉｏｎ ３４（９）, 1981, ｐ．１６７０-１６７５ * |
| JPN6012033826; 香川（田中）聡子 他: 表面（表面談話会・コロイド懇話会） Ｖｏｌ．３４， Ｎｏ．７, 1996, Ｐ．３７１-３８４ * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008106006A (ja) * | 2006-10-26 | 2008-05-08 | Univ Nihon | 筋萎縮性側索硬化症治療薬 |
| JP2013509443A (ja) * | 2009-11-01 | 2013-03-14 | シンセティック バイオロジックス，インコーポレイテッド | 胃保持性の経口用高用量亜鉛調製物 |
| JP2013523709A (ja) * | 2010-03-30 | 2013-06-17 | マグナス ティーティーエム アイシー | テトラチオモリブデン酸の治療的使用 |
| JP2015057450A (ja) * | 2010-03-30 | 2015-03-26 | マグナス ティーティーエム アイシー | テトラチオモリブデン酸の治療的使用 |
| JP2022525482A (ja) * | 2019-03-20 | 2022-05-16 | リンドラ セラピューティクス， インコーポレイティド | 胃内滞留剤形用のコーティング |
| US12447130B2 (en) | 2019-03-20 | 2025-10-21 | Lyndra Therapeutics, Inc. | Capsules and capsule coatings for gastric residence dosage forms |
| JP2022536205A (ja) * | 2019-08-21 | 2022-08-12 | ブレイン ケミストリー ラブズ | 金属及びｌ－セリンを含む組成物、並びにその使用 |
| JP7311086B2 (ja) | 2019-08-21 | 2023-07-19 | ブレイン ケミストリー ラブズ | 金属及びｌ－セリンを含む組成物、並びにその使用 |
| JP2023517374A (ja) * | 2020-03-16 | 2023-04-25 | 武漢広行科学研究有限公司 | 肝硬変の治療のための銅クラスター及び組成物 |
| JP7457827B2 (ja) | 2020-03-16 | 2024-03-28 | 武漢広行科学研究有限公司 | 肝硬変の治療のための銅クラスター及び組成物 |
| KR102903285B1 (ko) * | 2020-03-16 | 2025-12-23 | 우한 바스트 컨덕트 사이언스 파운데이션 컴퍼니 리미티드 | 간경변증의 치료를 위한 구리 클러스터(CuCs) 및 조성물 |
| WO2025173839A1 (ko) * | 2024-02-14 | 2025-08-21 | 국립부경대학교 산학협력단 | 알부민 고정 셀룰로오스 및 이를 포함하는 알츠하이머 치료용 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007205996A1 (en) | 2007-07-26 |
| WO2007084818A3 (en) | 2009-01-08 |
| CA2675230A1 (en) | 2008-07-26 |
| US20070207191A1 (en) | 2007-09-06 |
| WO2007084818A2 (en) | 2007-07-26 |
| EP1993607A2 (en) | 2008-11-26 |
| EP1993607A4 (en) | 2012-03-28 |
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