NZ550199A - Treatment of inflammation, abeta-induced cell toxicity, neuronal cell death or neuronal cell loss in subjects suffering from alzheimer's disease - Google Patents
Treatment of inflammation, abeta-induced cell toxicity, neuronal cell death or neuronal cell loss in subjects suffering from alzheimer's diseaseInfo
- Publication number
- NZ550199A NZ550199A NZ550199A NZ55019999A NZ550199A NZ 550199 A NZ550199 A NZ 550199A NZ 550199 A NZ550199 A NZ 550199A NZ 55019999 A NZ55019999 A NZ 55019999A NZ 550199 A NZ550199 A NZ 550199A
- Authority
- NZ
- New Zealand
- Prior art keywords
- use according
- acid
- medicament
- anionic
- disease
- Prior art date
Links
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
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| US7429598P | 1998-02-11 | 1998-02-11 | |
| US24839699A | 1999-02-10 | 1999-02-10 |
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| NZ550199A true NZ550199A (en) | 2008-07-31 |
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| NZ550199A NZ550199A (en) | 1998-02-11 | 1999-02-11 | Treatment of inflammation, abeta-induced cell toxicity, neuronal cell death or neuronal cell loss in subjects suffering from alzheimer's disease |
| NZ568553A NZ568553A (en) | 1998-02-11 | 1999-02-11 | Treatment of inflammation, AB-induced cell toxicity, neuronal cell death or neuronal loss in subjects suffering from AlzheimerÆs disease |
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| NZ568553A NZ568553A (en) | 1998-02-11 | 1999-02-11 | Treatment of inflammation, AB-induced cell toxicity, neuronal cell death or neuronal loss in subjects suffering from AlzheimerÆs disease |
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| JP (1) | JP4574845B2 (https=) |
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| ES (1) | ES2392391T3 (https=) |
| IL (1) | IL137751A0 (https=) |
| MX (2) | MXPA00007815A (https=) |
| NZ (2) | NZ550199A (https=) |
| PT (1) | PT1054664E (https=) |
| WO (1) | WO1999040909A1 (https=) |
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| US5605938A (en) | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| WO1999059571A1 (en) * | 1998-05-15 | 1999-11-25 | Neurochem, Inc. | Use of amyloid inhibitors for modulating neuronal cell death |
| US6310073B1 (en) | 1998-07-28 | 2001-10-30 | Queen's University At Kingston | Methods and compositions to treat glycosaminoglycan-associated molecular interactions |
| CA2369997C (en) * | 1999-04-28 | 2009-11-17 | Queen's University At Kingston | Compositions and methods for treating amyloidosis |
| AU5994900A (en) * | 1999-07-09 | 2001-01-30 | Isis Innovation Limited | Compounds for inhibiting diseases and preparing cells for transplantation |
| IL150374A0 (en) | 1999-12-23 | 2002-12-01 | Neurochem Inc | Compounds and methods for modulating cerebral amyloid angiopathy |
| US7105336B2 (en) * | 2002-10-07 | 2006-09-12 | Biogaia Ab | Selection and use of lactic acid bacteria for reducing inflammation caused by Helicobacter |
| EP1585520A1 (en) * | 2002-12-24 | 2005-10-19 | Neurochem (International) Limited | Therapeutic formulations for the treatment of beta-amyloid related diseases |
| CN100571701C (zh) * | 2002-12-24 | 2009-12-23 | 贝卢斯健康(国际）有限公司 | 治疗β淀粉样蛋白相关疾病的治疗性制品 |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| US7414076B2 (en) | 2003-06-23 | 2008-08-19 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US7244764B2 (en) | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US20050142191A1 (en) | 2003-06-23 | 2005-06-30 | Neurochem (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| EP1646659B1 (en) * | 2003-06-23 | 2014-05-14 | Kiacta Sàrl | Method for the preparation of 1,3-propane disulfonic acid compounds |
| US7253306B2 (en) | 2003-06-23 | 2007-08-07 | Neurochem (International) Limited | Pharmaceutical drug candidates and methods for preparation thereof |
| WO2006085149A2 (en) | 2004-12-22 | 2006-08-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| TW200716088A (en) * | 2005-04-15 | 2007-05-01 | Neurochem Int Ltd | Formulations and methods for treating amyloidosis |
| RU2432362C2 (ru) | 2005-11-30 | 2011-10-27 | Эбботт Лэборетриз | Моноклональные антитела и их применения |
| PL2289909T3 (pl) | 2005-11-30 | 2015-04-30 | Abbvie Inc | Sposób przeszukiwania, proces oczyszczania niedyfundujących oligomerów Abeta, selektywne przeciwciała przeciw niedyfundującym oligomerom Abeta i sposób wytwarzania tych przeciwciał |
| EP1968561B8 (en) | 2005-12-22 | 2010-10-20 | Kiacta Sàrl | Treatment of diabetic nephropathy |
| PT2089417E (pt) | 2006-10-12 | 2015-04-14 | Bhi Ltd Partnership | Métodos, compostos, composições e veículos para administrar o ácido 3-amino-1-propanossulfónico |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| EP2124952A2 (en) | 2007-02-27 | 2009-12-02 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
| US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
| US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
| RS53174B (sr) | 2007-10-05 | 2014-06-30 | Genentech Inc. | Upotreba antiamiloidnog beta antitela u slučaju oboljenja oka |
| JP2012517822A (ja) * | 2009-02-19 | 2012-08-09 | ガラパゴス・ナムローゼ・フェンノートシャップ | 炎症を包含する疾患の診断及び治療に有用な同定方法及び化合物 |
| MY159626A (en) * | 2009-09-17 | 2017-01-13 | Bespoke Bioscience Llc | Role of n-2-hydroxy-ethyl-piperazine-n'-2-ethane sulfonic acid (hepes) in pain control and reversal of demyelinization injury |
| ES2684475T3 (es) | 2010-04-15 | 2018-10-03 | Abbvie Inc. | Proteínas que se unen a beta amiloide |
| RU2607368C2 (ru) | 2010-07-30 | 2017-01-10 | Ац Иммуне С.А. | Безопасные и функциональные гуманизированные антитела |
| CN103298833B (zh) | 2010-08-14 | 2015-12-16 | Abbvie公司 | β淀粉样蛋白结合蛋白 |
| WO2016163886A2 (en) * | 2015-04-10 | 2016-10-13 | Clues2Cure International B.V. | Administration of taurine or an analog thereof for the treatment of nerve cell damage |
| CN109381452A (zh) * | 2017-08-11 | 2019-02-26 | 江西青峰药业有限公司 | 乙基硫酸类化合物的应用及其制备方法 |
| CN109381453A (zh) * | 2017-08-14 | 2019-02-26 | 江西青峰药业有限公司 | 乙基硫酸钾在制备用于预防或治疗炎症性疾病药物中的应用 |
| CN109394746A (zh) * | 2017-08-15 | 2019-03-01 | 江西青峰药业有限公司 | 乙基硫酸铵在制备用于预防或治疗炎症性疾病药物中的应用 |
| US20250345298A1 (en) | 2022-04-28 | 2025-11-13 | Alzheon, Inc. | Apoe4 correctors and methods of use |
| CN120641092A (zh) | 2022-12-02 | 2025-09-12 | 阿尔泽恩股份有限公司 | 用于用曲米沙特治疗神经变性病症的方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1144937A (en) * | 1977-12-22 | 1983-04-19 | Dke J.E. Helgstrand | Aromatic derivatives, pharmaceutical compositions and methods for combatting virus infections |
| US5087618A (en) * | 1982-05-18 | 1992-02-11 | University Of Florida | Redox carriers for brain-specific drug delivery |
| US5463092A (en) * | 1989-11-22 | 1995-10-31 | Vestar, Inc. | Lipid derivatives of phosphonacids for liposomal incorporation and method of use |
| US5276059A (en) * | 1992-07-10 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibition of diseases associated with amyloid formation |
| DE69434571T2 (de) * | 1993-03-29 | 2006-08-03 | Queen's University At Kingston, Kingston | Propan-1,3-disulphonsäure und deren pharmazeutisch akzeptable Salze zur Behandlung von Amyloidosis |
| US5643562A (en) * | 1993-03-29 | 1997-07-01 | Queen's University Of Kingston | Method for treating amyloidosis |
| US5840294A (en) * | 1993-03-29 | 1998-11-24 | Queen's University At Kingston | Method for treating amyloidosis |
| NZ550116A (en) * | 1997-08-18 | 2008-03-28 | Neurochem Int Ltd | Phosphono-carboxylate compounds for treating amyloidosis |
| US5869469A (en) * | 1997-08-18 | 1999-02-09 | Queen's University At Kingston | Phosphonocarboxylate compounds for treating amyloidosis |
-
1999
- 1999-02-11 WO PCT/IB1999/000354 patent/WO1999040909A1/en not_active Ceased
- 1999-02-11 AU AU24378/99A patent/AU2437899A/en not_active Abandoned
- 1999-02-11 JP JP2000531161A patent/JP4574845B2/ja not_active Expired - Lifetime
- 1999-02-11 DK DK99903869.8T patent/DK1054664T3/da active
- 1999-02-11 PT PT99903869T patent/PT1054664E/pt unknown
- 1999-02-11 CA CA002320224A patent/CA2320224C/en not_active Expired - Lifetime
- 1999-02-11 ES ES99903869T patent/ES2392391T3/es not_active Expired - Lifetime
- 1999-02-11 NZ NZ550199A patent/NZ550199A/en not_active IP Right Cessation
- 1999-02-11 NZ NZ568553A patent/NZ568553A/en unknown
- 1999-02-11 IL IL13775199A patent/IL137751A0/xx not_active IP Right Cessation
- 1999-02-11 EP EP99903869A patent/EP1054664B1/en not_active Expired - Lifetime
- 1999-02-11 CA CA002632106A patent/CA2632106A1/en not_active Abandoned
- 1999-02-11 MX MXPA00007815A patent/MXPA00007815A/es active IP Right Grant
- 1999-02-11 MX MX2008014823A patent/MX2008014823A/es active IP Right Grant
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Also Published As
| Publication number | Publication date |
|---|---|
| PT1054664E (pt) | 2012-11-02 |
| DK1054664T3 (da) | 2012-11-05 |
| MXPA00007815A (es) | 2002-04-24 |
| CY1113205T1 (el) | 2016-04-13 |
| CA2320224C (en) | 2008-08-12 |
| AU2437899A (en) | 1999-08-30 |
| WO1999040909A1 (en) | 1999-08-19 |
| EP1054664B1 (en) | 2012-08-08 |
| CA2632106A1 (en) | 1999-08-19 |
| EP1054664A1 (en) | 2000-11-29 |
| NZ568553A (en) | 2010-02-26 |
| ES2392391T3 (es) | 2012-12-10 |
| CA2320224A1 (en) | 1999-08-19 |
| IL137751A0 (en) | 2001-10-31 |
| JP2002502871A (ja) | 2002-01-29 |
| JP4574845B2 (ja) | 2010-11-04 |
| MX2008014823A (es) | 2009-03-06 |
| HK1032915A1 (en) | 2001-08-10 |
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