CA2294155A1 - Analgesic methods using synthetic catalysts for the dismutation of superoxide radicals - Google Patents
Analgesic methods using synthetic catalysts for the dismutation of superoxide radicals Download PDFInfo
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- CA2294155A1 CA2294155A1 CA002294155A CA2294155A CA2294155A1 CA 2294155 A1 CA2294155 A1 CA 2294155A1 CA 002294155 A CA002294155 A CA 002294155A CA 2294155 A CA2294155 A CA 2294155A CA 2294155 A1 CA2294155 A1 CA 2294155A1
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
Landscapes
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- Catalysts (AREA)
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| US5040297P | 1997-06-20 | 1997-06-20 | |
| US60/050,402 | 1997-06-20 | ||
| PCT/US1998/012231 WO1998058636A1 (en) | 1997-06-20 | 1998-06-15 | Analgesic methods using synthetic catalysts for the dismutation of superoxide radicals |
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| CA2294155A1 true CA2294155A1 (en) | 1998-12-30 |
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| PT (1) | PT1001752E (enExample) |
| WO (1) | WO1998058636A1 (enExample) |
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| US6127356A (en) | 1993-10-15 | 2000-10-03 | Duke University | Oxidant scavengers |
| US20060270639A1 (en) * | 1997-06-20 | 2006-11-30 | Daniela Salvemini | Combinations of superoxide dismutase mimetics and nonsteroidal analgesic/anti-inflammatory drugs |
| US20050171198A1 (en) * | 1997-06-20 | 2005-08-04 | Metaphore Pharmaceuticals, Inc. | SODm therapy for treatment, prevention, inhibition and reversal of inflammatory disease |
| US6214817B1 (en) * | 1997-06-20 | 2001-04-10 | Monsanto Company | Substituted pyridino pentaazamacrocyle complexes having superoxide dismutase activity |
| CA2309154C (en) | 1997-11-03 | 2010-02-16 | Duke University | Substituted porphyrins |
| ATE552260T1 (de) * | 1999-01-25 | 2012-04-15 | Nat Jewish Health | Substituierte porphyrine und deren therapeutische verwendung |
| AU5048400A (en) | 1999-05-27 | 2000-12-18 | Monsanto Company | Biomaterials modified with superoxide dismutase mimics |
| US20030069281A1 (en) * | 2000-06-14 | 2003-04-10 | Irwin Fridovich | Tetrapyrroles |
| US20020072512A1 (en) * | 2000-12-08 | 2002-06-13 | Metaphore Pharmaceuticals, Inc | Method of preventing and treating HIV-mediated central nervous system damage |
| US20050175580A1 (en) * | 2001-01-05 | 2005-08-11 | Daniela Salvemini | Compositions and methods for enhancing cytokine activity and treating hypotension associated with the administration of cytokines |
| ATE439134T1 (de) * | 2001-01-19 | 2009-08-15 | Nat Jewish Med & Res Center | Medikament zum schutz in der radiotherapie |
| WO2002058686A2 (en) * | 2001-01-26 | 2002-08-01 | Metaphore Pharmaceuticals, Inc. | Method of treatment of neurodegenerative disorders using pentaaza-macrocyclic ligand complexes |
| EP1405066B1 (en) * | 2001-03-02 | 2015-06-17 | Galera Therapeutics LLC | Chromatography of metal complexes |
| US20040137638A1 (en) * | 2002-03-04 | 2004-07-15 | Slomczynska Urszula J. | Chromatography of metal complexes |
| AU2002312194B8 (en) * | 2001-06-01 | 2008-05-15 | Aeolus Sciences, Inc. | Oxidant scavengers for treatment of diabetes or use in transplantation or induction of immune tolerance |
| AU2002315001A1 (en) * | 2001-06-08 | 2002-12-23 | Metaphore Pharmaceuticals, Inc. | Libraries of conformationally constrained peptides, chiral azacrowns, and peptidomimetics and methods of making the same |
| JP2005519852A (ja) * | 2001-06-26 | 2005-07-07 | メタファー・ファーマシューティカルズ・インコーポレイテッド | 炎症性疾患の予防および／または処置のためのＳＯＤｍとコルチコステロイドの組合せ療養 |
| WO2003039561A1 (en) * | 2001-11-02 | 2003-05-15 | Elan Corporation, Plc | Pharmaceutical composition |
| PT1463563E (pt) * | 2001-12-14 | 2009-03-19 | Alcon Inc | Miméticos de dismutase do superóxido para o tratamento de distúrbios e doenças oculares |
| US6933275B2 (en) * | 2002-05-01 | 2005-08-23 | The Board Of Trustees Of The Leland Stanford Junior University | Protein kinase C peptides for use in withdrawal |
| EP1513537A4 (en) * | 2002-06-07 | 2006-09-06 | Univ Duke | Substituted porphyrins |
| US20030232784A1 (en) * | 2002-06-14 | 2003-12-18 | Benedict James J. | Hyaluronic acid-associated superoxide dismutase mimics and their use in the treatment of joint pain |
| CA2397684A1 (en) * | 2002-08-12 | 2004-02-12 | Michael P. Murphy | Mitochondrially targeted antioxidants |
| CA2499994C (en) * | 2002-09-23 | 2012-07-10 | Verion, Inc. | Abuse-resistant pharmaceutical compositions |
| MXPA05005937A (es) * | 2002-12-06 | 2005-08-18 | Alcon Inc | Imitaciones de superoxido de dismutasa para el tratamiento de trastornos y enfermedades oculares. |
| CN1717234A (zh) * | 2002-12-06 | 2006-01-04 | 爱尔康公司 | 用于治疗眼紊乱和疾病的超氧化物岐化酶模拟物 |
| KR100648618B1 (ko) * | 2003-11-19 | 2006-11-23 | 주식회사 웰스킨 | 활성 산소 억제제 |
| KR20060101501A (ko) * | 2003-12-11 | 2006-09-25 | 알콘, 인코퍼레이티드 | 시신경 및 망막 손상의 치료를 위한 슈퍼옥사이드디스무타제 유사체 |
| US20120301403A1 (en) | 2007-06-21 | 2012-11-29 | Galera Therapeutics, Llc | Polyethylene glycolated superoxide dismutase mimetics |
| US8217166B2 (en) * | 2005-05-05 | 2012-07-10 | Galera Therapeutics, Llc | Polyethylene glycolated superoxide dismutase mimetics |
| WO2006069326A2 (en) * | 2004-12-21 | 2006-06-29 | Metaphore Pharmaceuticals, Inc. | Polyethylene glycolated superoxide dismutase mimetics |
| KR100724586B1 (ko) | 2005-12-09 | 2007-06-04 | 세종대학교산학협력단 | 수퍼옥사이드 디스뮤타아제 활성을 갖는 고리화합물 |
| EP2056675B1 (en) * | 2006-10-12 | 2019-01-09 | Galera Labs, LLC | Methods of treating oral mucositis |
| WO2009065059A2 (en) | 2007-11-14 | 2009-05-22 | Kereos, Inc. | Super-oxide dismutase mimetics |
| ES2530462T3 (es) | 2008-05-22 | 2015-03-03 | Galera Therapeutics Llc | Combinación terapia antitumoral |
| EP2732817B1 (en) | 2008-05-23 | 2016-08-24 | National Jewish Health | A compound for use in treating injury associated with exposure to phosgene or chlorine gas |
| WO2013048965A1 (en) | 2011-09-26 | 2013-04-04 | Galera Therapeutics, Llc | Methods for treatment of diseases |
| UA126788C2 (uk) | 2015-08-11 | 2023-02-08 | Ґалера Лебз, Елелсі | Комплексні сполуки, що містять макроциклічне кільце пентаази, які мають пероральну біодоступність |
| US12220420B2 (en) | 2016-05-03 | 2025-02-11 | Galera Labs, Llc | Combination therapy for cancer treatment |
| AU2017318718B2 (en) | 2016-09-01 | 2023-06-29 | Galera Labs, Llc | Combination cancer therapy with pentaaza macrocyclic ring complex and ascorbate compound |
| CA3053779A1 (en) | 2017-02-15 | 2018-08-23 | Galera Labs, Llc | Pentaaza macrocyclic ring complexes for local intestinal delivery |
| US11246950B2 (en) | 2017-04-13 | 2022-02-15 | Galera Labs, Llc | Combination cancer immunotherapy with pentaaza macrocyclic ring complex |
| EP3388082A1 (en) | 2017-04-13 | 2018-10-17 | Galera Labs, LLC | Combination cancer immunotherapy with pentaaza macrocyclic ring complex |
| AU2019215032A1 (en) | 2018-01-31 | 2020-09-10 | Board Of Regents Of The University Of Texas System | Combination cancer therapy with pentaaza macrocyclic ring complex and platinum-based anticancer agent |
| WO2021163397A1 (en) | 2020-02-13 | 2021-08-19 | Teva Pharmaceuticals International Gmbh | Solid state forms of avasopasem manganese and process for preparation thereof |
| WO2025024390A2 (en) * | 2023-07-21 | 2025-01-30 | Galera Labs, Llc | Carcinogenesis reduction with pentaaza macrocyclic ring complex |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0751496B2 (ja) | 1986-04-02 | 1995-06-05 | 武田薬品工業株式会社 | リポソ−ムの製造法 |
| US4999347A (en) | 1986-08-28 | 1991-03-12 | Sorenson John R J | Analgesic method |
| US5216021A (en) | 1986-08-28 | 1993-06-01 | Sorenson John R J | Analgesic method |
| JPS63313581A (ja) * | 1987-06-16 | 1988-12-21 | Ube Ind Ltd | 修飾ス−パ−オキシドジスムタ−ゼ |
| CA2072934C (en) | 1991-07-19 | 2007-08-28 | Karl William Aston | Manganese complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide |
| DE69224839T2 (de) | 1991-07-19 | 1998-10-08 | Monsanto Co | Mangan-Komplexe mit Stickstoff enthaltenden makrozyklischen Liganden, wirksam als Superoxiddismutasekatalysatoren. |
| CN1088086A (zh) * | 1992-12-14 | 1994-06-22 | 西北大学 | 一种新型的护肤保健品 |
| US6204259B1 (en) | 1993-01-14 | 2001-03-20 | Monsanto Company | Manganese complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide |
| US6525041B1 (en) | 1995-06-06 | 2003-02-25 | Pharmacia Corporation | Manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide |
| IL125889A0 (en) | 1996-03-13 | 1999-04-11 | Monsanto Co | Bioconjugates of manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide |
-
1998
- 1998-04-09 US US09/057,831 patent/US6180620B1/en not_active Expired - Fee Related
- 1998-06-15 AT AT98929022T patent/ATE256467T1/de not_active IP Right Cessation
- 1998-06-15 DE DE69820633T patent/DE69820633T2/de not_active Expired - Fee Related
- 1998-06-15 AU AU80685/98A patent/AU733415B2/en not_active Ceased
- 1998-06-15 WO PCT/US1998/012231 patent/WO1998058636A1/en not_active Ceased
- 1998-06-15 CA CA002294155A patent/CA2294155A1/en not_active Abandoned
- 1998-06-15 DK DK98929022T patent/DK1001752T3/da active
- 1998-06-15 PT PT98929022T patent/PT1001752E/pt unknown
- 1998-06-15 ES ES98929022T patent/ES2215305T3/es not_active Expired - Lifetime
- 1998-06-15 JP JP50459399A patent/JP2002506445A/ja not_active Ceased
- 1998-06-15 EP EP98929022A patent/EP1001752B1/en not_active Expired - Lifetime
- 1998-06-19 ZA ZA985376A patent/ZA985376B/xx unknown
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2000
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| AU733415B2 (en) | 2001-05-17 |
| ATE256467T1 (de) | 2004-01-15 |
| DK1001752T3 (da) | 2004-04-19 |
| DE69820633D1 (de) | 2004-01-29 |
| DE69820633T2 (de) | 2004-09-23 |
| WO1998058636A1 (en) | 1998-12-30 |
| AU8068598A (en) | 1999-01-04 |
| EP1001752A1 (en) | 2000-05-24 |
| EP1001752B1 (en) | 2003-12-17 |
| US6395725B1 (en) | 2002-05-28 |
| ZA985376B (en) | 1999-06-21 |
| ES2215305T3 (es) | 2004-10-01 |
| PT1001752E (pt) | 2004-05-31 |
| JP2002506445A (ja) | 2002-02-26 |
| US6180620B1 (en) | 2001-01-30 |
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Effective date: 20080616 |