CA2758029A1 - Clavulanate formulation for neuroprotection and treatment of neurodegenerative disorders - Google Patents
Clavulanate formulation for neuroprotection and treatment of neurodegenerative disorders Download PDFInfo
- Publication number
- CA2758029A1 CA2758029A1 CA2758029A CA2758029A CA2758029A1 CA 2758029 A1 CA2758029 A1 CA 2758029A1 CA 2758029 A CA2758029 A CA 2758029A CA 2758029 A CA2758029 A CA 2758029A CA 2758029 A1 CA2758029 A1 CA 2758029A1
- Authority
- CA
- Canada
- Prior art keywords
- clavulanate
- formulation
- clavulanic acid
- tablet
- group
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
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Landscapes
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
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| US17384109P | 2009-04-29 | 2009-04-29 | |
| US61/173,841 | 2009-04-29 | ||
| PCT/US2010/032983 WO2010127125A1 (en) | 2009-04-29 | 2010-04-29 | Clavulanate formulation for neuroprotection and treatment of neurodegenerative disorders |
Publications (1)
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| CA2758029A1 true CA2758029A1 (en) | 2011-11-04 |
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| Country | Link |
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| US (1) | US20100255099A1 (enExample) |
| EP (1) | EP2424498A1 (enExample) |
| JP (1) | JP2012525427A (enExample) |
| KR (1) | KR20120012823A (enExample) |
| CN (1) | CN102413814A (enExample) |
| AU (1) | AU2010242948A1 (enExample) |
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| CA (1) | CA2758029A1 (enExample) |
| IL (1) | IL215940A0 (enExample) |
| MX (1) | MX2011011459A (enExample) |
| WO (1) | WO2010127125A1 (enExample) |
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| BR0013366A (pt) * | 1999-08-16 | 2002-07-23 | Revaax Pharmaceuticals Llc | Métodos para tratar um distúrbio comportamental, um paciente humano, doença de próstata, distúrbios de ansiedade e cognitivos em um paciente humano afligido com uma condição ou disposto ao desenvolvimento de uma condição distinguida pelo menos em parte pela concentração de glutamato extracelular anormal no cérebro ou em outro tecido nervoso, distúrbio comportamental nas espécies humana, canina, felina e equina e um paciente afligido com ou disposto a desenvolver uma doença compreendendo concentrações de glutamato anormalmente elevadas em tecido neuronal ou nìveis de naaladase elevados em tecido prostático e com esclerose múltipla e para realçar a função cognitiva, formulação farmacêutica e usos de um inibidor da atividade de peptidase de uma dipeptidase ácida ligada em alfa n-acetilada e de um composto de beta-lactama |
| US6426342B2 (en) * | 1999-08-16 | 2002-07-30 | Revaax Pharmaceuticals, Llc | Use of β-lactamase inhibitors as neuroprotectants |
| MX2010004556A (es) * | 2007-10-26 | 2010-07-01 | Rexahn Pharmaceuticals Inc | Formulacion farmaceutica de acido clavulanico. |
| WO2013006808A2 (en) * | 2011-07-06 | 2013-01-10 | Rexahn Pharmaceuticals, Inc. | Clavulanic acid for treatment of restless legs syndrome |
| US8978166B2 (en) * | 2012-08-27 | 2015-03-17 | Well & David Corp. | Multi-function garment |
| KR102541110B1 (ko) | 2014-08-25 | 2023-06-08 | 에이뮨 테라퓨틱스, 인코퍼레이티드 | 난 단백질 제형 및 이의 제조 방법 |
| AU2016278846B2 (en) * | 2015-06-19 | 2021-08-05 | Biotie Therapies, Inc. | Controlled-release tozadenant formulations |
| WO2020212418A1 (en) * | 2019-04-15 | 2020-10-22 | Nanologica Ab | Empty porous particles for use in treatment, prevention and/or postponement of degeneration of neurodegenerative diseases, neurons and glia. |
| TWI739220B (zh) * | 2019-11-26 | 2021-09-11 | 亞瑟瑞智科技管理顧問股份有限公司 | 包含克拉維酸與丙戊酸之組合物及其用途 |
| CN112843034B (zh) * | 2019-11-26 | 2022-08-23 | 亚瑟瑞智科技管理顾问股份有限公司 | 包含克拉维酸与丙戊酸的组合物及其用途 |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4110165A (en) * | 1974-04-20 | 1978-08-29 | Beecham Group Limited | Process for the production of clavulanic acid |
| CA1085392A (en) * | 1976-03-25 | 1980-09-09 | Masayuki Narisada | Arylmalonamido-1-oxadethiacephalosporins |
| US4127118B1 (en) * | 1977-03-16 | 1995-12-19 | Alvaro Latorre | Method of effecting and enhancing an erection |
| US4234579A (en) * | 1977-06-07 | 1980-11-18 | Pfizer Inc. | Penicillanic acid 1,1-dioxides as β-lactamase inhibitors |
| JO984B1 (en) * | 1977-10-11 | 1979-12-01 | بيتشام غروب ليمتد | A dry pharmaceutical compound with a suitable dosage unit for oral administration |
| NZ189022A (en) * | 1977-12-08 | 1981-11-19 | Beecham Group Ltd | Pharmaceutically acceptable particles of clavulanates dispersed in a polymeric binder |
| US4273763A (en) * | 1978-01-23 | 1981-06-16 | Efamol Limited | Pharmaceutical and dietary compositions |
| US4268503A (en) * | 1978-09-14 | 1981-05-19 | Fujisawa Pharmaceutical Co., Ltd. | Antibacterial composition |
| DE3001961C2 (de) * | 1980-01-21 | 1984-08-16 | Didier Engineering Gmbh, 4300 Essen | Anströmboden für einen Wirbelschichtreaktor |
| NZ198241A (en) * | 1980-09-27 | 1983-12-16 | Beecham Group Ltd | Tablet containing amoxycillin and potassium clavulanate |
| US4594247A (en) * | 1981-12-21 | 1986-06-10 | Eli Lilly And Company | Synergistic antibacterial compositions and method of treatment of infections caused by multiple antibiotic-resistant organisms |
| JPS59104389A (ja) * | 1982-12-06 | 1984-06-16 | Shionogi & Co Ltd | オキサセファム誘導体 |
| JPS62106015A (ja) * | 1985-10-31 | 1987-05-16 | Sumitomo Pharmaceut Co Ltd | 抗痴呆薬 |
| US5256652A (en) * | 1987-11-12 | 1993-10-26 | Pharmedic Co. | Topical compositions and methods for treatment of male impotence |
| GB9201639D0 (en) * | 1992-01-25 | 1992-03-11 | Smithkline Beecham Plc | Pharmaceutical formulations |
| GB9215908D0 (en) * | 1992-07-27 | 1992-09-09 | Wellcome Found | Water dispersible tablets |
| US5643909A (en) * | 1993-04-19 | 1997-07-01 | Syntex (U.S.A.) Inc. | 10,11-Methanodibenzosuberane derivatives |
| JP3233407B2 (ja) * | 1993-11-06 | 2001-11-26 | 大鵬薬品工業株式会社 | 結晶性ペニシリン誘導体並びにその製造及び使用 |
| US5827537A (en) * | 1995-05-04 | 1998-10-27 | Smithkline Beecham Corporation | Pharmaceutical thermal infusion process |
| GB9515411D0 (en) * | 1995-07-27 | 1995-09-27 | Pharmacia Spa | N-(4-substituted-benzyl)-2-aminolactam derivatives |
| GB9525697D0 (en) * | 1995-12-15 | 1996-02-14 | Pharmacia Spa | Cephem derivatives |
| ES2248840T3 (es) * | 1996-02-23 | 2006-03-16 | Eli Lilly And Company | Antagonistas de vasopresina v1a no peptidilicos. |
| US5905076A (en) * | 1996-04-10 | 1999-05-18 | National Research Council Of Canada | 6-substituted amino-4-oxa-1-azabicyclo 3,2,0! heptan-7-one derivatives as cysteine protease inhibitors |
| US5795877A (en) * | 1996-12-31 | 1998-08-18 | Guilford Pharmaceuticals Inc. | Inhibitors of NAALADase enzyme activity |
| US5824662A (en) * | 1996-09-27 | 1998-10-20 | Guilford Pharmaceuticals Inc. | Treatment of global and focal ischemia using naaladase inhibitors |
| US5977090A (en) * | 1996-09-27 | 1999-11-02 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating compulsive disorders using NAALADase inhibitors |
| US5863536A (en) * | 1996-12-31 | 1999-01-26 | Guilford Pharmaceuticals Inc. | Phosphoramidate derivatives |
| US6017903A (en) * | 1996-09-27 | 2000-01-25 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating a glutamate abnormality and effecting a neuronal activity in an animal using NAALADase inhibitors |
| US5672592A (en) * | 1996-06-17 | 1997-09-30 | Guilford Pharmaceuticals Inc. | Certain phosphonomethyl-pentanedioic acid derivatives thereof |
| JP2002504122A (ja) * | 1997-06-13 | 2002-02-05 | ノースウエスタン ユニバーシティー | ベータラクタマーゼ阻害剤及びその使用方法 |
| US6015809A (en) * | 1998-08-17 | 2000-01-18 | American Home Products Corporation | Photocyclized rapamycin |
| US6177421B1 (en) * | 1999-05-04 | 2001-01-23 | Fuisz International Ltd. | Amoxicillin and clavulanate composition |
| WO2000045793A1 (en) * | 1999-02-04 | 2000-08-10 | Abbott Laboratories | Ph independent extended release pharmaceutical formulation |
| IE990159A1 (en) * | 1999-02-26 | 2000-09-20 | Fuisz Internat Ltd | Storage Stable Amoxycillin and Clavulanate Suspension Composition. |
| US6472406B1 (en) * | 1999-07-06 | 2002-10-29 | Methylgene, Inc. | Sulfonamidomethyl phosphonate inhibitors of beta-lactamase |
| BR0013366A (pt) * | 1999-08-16 | 2002-07-23 | Revaax Pharmaceuticals Llc | Métodos para tratar um distúrbio comportamental, um paciente humano, doença de próstata, distúrbios de ansiedade e cognitivos em um paciente humano afligido com uma condição ou disposto ao desenvolvimento de uma condição distinguida pelo menos em parte pela concentração de glutamato extracelular anormal no cérebro ou em outro tecido nervoso, distúrbio comportamental nas espécies humana, canina, felina e equina e um paciente afligido com ou disposto a desenvolver uma doença compreendendo concentrações de glutamato anormalmente elevadas em tecido neuronal ou nìveis de naaladase elevados em tecido prostático e com esclerose múltipla e para realçar a função cognitiva, formulação farmacêutica e usos de um inibidor da atividade de peptidase de uma dipeptidase ácida ligada em alfa n-acetilada e de um composto de beta-lactama |
| US6489319B2 (en) * | 1999-08-16 | 2002-12-03 | Revaax Pharmaceuticals, Llc | Neurotherapeutic use of carboxypeptidase inhibitors |
| US6426342B2 (en) * | 1999-08-16 | 2002-07-30 | Revaax Pharmaceuticals, Llc | Use of β-lactamase inhibitors as neuroprotectants |
| NZ519467A (en) * | 1999-12-22 | 2004-02-27 | Pharmacia Corp | Dual-release compositions of a cyclooxygenase-2- inhibitor |
| US20020013270A1 (en) * | 2000-06-05 | 2002-01-31 | Bolte Ellen R. | Method for treating a mental disorder |
| ATE286057T1 (de) * | 2000-10-20 | 2005-01-15 | Sandoz Ag | Pharmazeutische zubereitungen enthaltend clavulansäure |
| US7166626B2 (en) * | 2001-06-18 | 2007-01-23 | Revaax Pharmaceuticals, Llc | Therapeutic treatment for sexual dysfunction |
| PL371407A1 (en) * | 2002-01-10 | 2005-06-13 | Biovail Laboratories Inc. | Sedative non-benzodiazepine formulations |
| IL154370A0 (en) * | 2003-02-10 | 2003-09-17 | Chemagis Ltd | Solid amorphous mixtures, processes for the preparation thereof and pharmaceutical compositions containing the same |
| SI21402A (sl) * | 2003-02-12 | 2004-08-31 | LEK farmacevtska dru�ba d.d. | Obloženi delci in farmacevtske oblike |
| US7833998B2 (en) * | 2003-08-25 | 2010-11-16 | Revaax Pharmaceuticals, Llc | Oral neurotherapeutic cephalosporin sulfoxide and sulfone-containing compositions |
| PE20060489A1 (es) * | 2004-08-13 | 2006-06-19 | Schering Plough Ltd | Formulacion farmaceutica que comprende un antibiotico, un triazol y un corticosteroide |
| US20060088591A1 (en) * | 2004-10-22 | 2006-04-27 | Jinghua Yuan | Tablets from a poorly compressible substance |
| SI21912A (sl) * | 2004-12-24 | 2006-06-30 | Lek Farmacevtska Druzba D.D. | Stabilne farmacevtske oblike, ki vsebujejo amoksicilin in klavulansko kislino |
| DE102006007830A1 (de) * | 2006-02-17 | 2007-08-30 | Grünenthal GmbH | Lagerstabile orale Darreichungsform von Amoxicillin und Clavulansäure |
| CA2644911A1 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Antibiotic compositions of modified release and process of production thereof |
| US20080014257A1 (en) * | 2006-07-14 | 2008-01-17 | Par Pharmaceutical, Inc. | Oral dosage forms |
| MX2010004556A (es) * | 2007-10-26 | 2010-07-01 | Rexahn Pharmaceuticals Inc | Formulacion farmaceutica de acido clavulanico. |
-
2010
- 2010-04-29 US US12/770,304 patent/US20100255099A1/en not_active Abandoned
- 2010-04-29 MX MX2011011459A patent/MX2011011459A/es unknown
- 2010-04-29 WO PCT/US2010/032983 patent/WO2010127125A1/en not_active Ceased
- 2010-04-29 EP EP10717387A patent/EP2424498A1/en not_active Withdrawn
- 2010-04-29 AU AU2010242948A patent/AU2010242948A1/en not_active Abandoned
- 2010-04-29 CA CA2758029A patent/CA2758029A1/en not_active Abandoned
- 2010-04-29 CN CN2010800184471A patent/CN102413814A/zh active Pending
- 2010-04-29 JP JP2012508734A patent/JP2012525427A/ja active Pending
- 2010-04-29 BR BRPI1013901A patent/BRPI1013901A2/pt not_active IP Right Cessation
- 2010-04-29 KR KR1020117028280A patent/KR20120012823A/ko not_active Withdrawn
-
2011
- 2011-10-26 IL IL215940A patent/IL215940A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI1013901A2 (pt) | 2019-09-24 |
| AU2010242948A1 (en) | 2011-11-24 |
| IL215940A0 (en) | 2012-01-31 |
| MX2011011459A (es) | 2011-11-18 |
| EP2424498A1 (en) | 2012-03-07 |
| US20100255099A1 (en) | 2010-10-07 |
| WO2010127125A1 (en) | 2010-11-04 |
| CN102413814A (zh) | 2012-04-11 |
| JP2012525427A (ja) | 2012-10-22 |
| KR20120012823A (ko) | 2012-02-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160429 |