DE69838789T2 - Verfahren zur behandlung oder prävention der alzheimerischen krankheit - Google Patents
Verfahren zur behandlung oder prävention der alzheimerischen krankheit Download PDFInfo
- Publication number
- DE69838789T2 DE69838789T2 DE69838789T DE69838789T DE69838789T2 DE 69838789 T2 DE69838789 T2 DE 69838789T2 DE 69838789 T DE69838789 T DE 69838789T DE 69838789 T DE69838789 T DE 69838789T DE 69838789 T2 DE69838789 T2 DE 69838789T2
- Authority
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- Germany
- Prior art keywords
- dione
- benzyl
- insulin
- ethoxy
- methyl
- 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.)
- Expired - Lifetime
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- 238000000034 method Methods 0.000 title description 3
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Classifications
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Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998039967A1 (en) * | 1997-03-12 | 1998-09-17 | The General Hospital Corporation | A method for treating or preventing alzheimer's disease |
| NZ505761A (en) * | 1998-01-28 | 2003-08-29 | Warner Lambert Co | Method for treating alzheimer's disease using plasma-triglceride level-lowering agents or agents that interfer with cholesterol ester synthesis |
| US6191154B1 (en) * | 1998-11-27 | 2001-02-20 | Case Western Reserve University | Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases |
| WO2000043006A1 (en) * | 1999-01-19 | 2000-07-27 | Sankyo Company, Limited | Inhibitor for nerve cell death due to glutamic acid cytotoxicity |
| US6835750B1 (en) | 2000-05-01 | 2004-12-28 | Accera, Inc. | Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II |
| US20020006959A1 (en) * | 2000-05-01 | 2002-01-17 | Henderson Samuel T. | Use of medium chain triglycerides for the treatment and prevention of Alzheimer's Disease and other diseases resulting from reduced Neuronal Metabolism |
| US20070179197A1 (en) * | 2000-05-01 | 2007-08-02 | Accera, Inc. | Compositions and methods for improving or preserving brain function |
| US6770797B2 (en) | 2001-06-01 | 2004-08-03 | Rhode Island Hospital | Non-Transgenic nonhuman model for Alzheimer's Disease using a AD7c-NTP nucleic acid |
| ATE476188T1 (de) | 2002-05-14 | 2010-08-15 | Nipro Corp | Medikament zur prävention und behandlung von familiärer amyloid polyneuropathie |
| JP2004043443A (ja) * | 2002-05-14 | 2004-02-12 | Kumamoto Technology & Industry Foundation | アミロイドーシスの予防及び治療のための医薬 |
| ES2271640T3 (es) * | 2002-11-12 | 2007-04-16 | L'oreal | Uso de microperlas de celulosa para hacer la piel mate. |
| EP1605950A4 (en) * | 2003-03-06 | 2008-01-09 | Accera Inc | NOVEL CHEMICAL ENTITIES AND METHODS OF USE IN THE TREATMENT OF METABOLIC DISORDERS |
| US20090088367A1 (en) * | 2004-05-10 | 2009-04-02 | Burnham Institute For Medical Research | Treatment of Insulin Resistance/Metabolic Syndrome to Alleviate the Risks of Dementia |
| US7833513B2 (en) * | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
| WO2008147454A1 (en) | 2006-11-16 | 2008-12-04 | Case Western Reserve University | Selective inhibitors of translesion dna replication |
| US8114847B2 (en) | 2005-03-16 | 2012-02-14 | Case Western Reserve University | Selective inhibitors of translesion DNA replication |
| US20060252775A1 (en) * | 2005-05-03 | 2006-11-09 | Henderson Samuel T | Methods for reducing levels of disease associated proteins |
| WO2007001883A2 (en) * | 2005-06-20 | 2007-01-04 | Accera, Inc. | Method to reduce oxidative damage and improve mitochondrial efficiency |
| PT2001293T (pt) * | 2006-04-03 | 2018-11-28 | Accera Inc | Utilização de compostos cetogénicos para tratamento de comprometimento da memória associado à idade |
| WO2009018478A2 (en) | 2007-07-31 | 2009-02-05 | Accera, Inc. | Use of genomic testing and ketogenic compounds for treatment of reduced cognitive function |
| US20090216178A1 (en) * | 2008-02-26 | 2009-08-27 | Lee Susan J | Method And Apparatus For Preventing Localized Stasis Of Cerebrospinal Fluid |
| US9125881B2 (en) * | 2008-07-03 | 2015-09-08 | Accera, Inc. | Monoglyceride of acetoacetate and derivatives for the treatment of neurological disorders |
| US8105809B2 (en) * | 2008-07-03 | 2012-01-31 | Accera, Inc. | Enzymatic synthesis of acetoacetate esters and derivatives |
| NZ591107A (en) * | 2008-08-12 | 2012-08-31 | Zinfandel Pharmaceuticals Inc | Method of identifying disease risk factors |
| US8846315B2 (en) | 2008-08-12 | 2014-09-30 | Zinfandel Pharmaceuticals, Inc. | Disease risk factors and methods of use |
| WO2011002939A1 (en) * | 2009-07-01 | 2011-01-06 | Nutrition 21, Inc. | Chromium complexes as enhancers of brain glucose transporters |
| US9102666B2 (en) | 2011-01-10 | 2015-08-11 | Zinfandel Pharmaceuticals, Inc. | Methods and drug products for treating Alzheimer's disease |
| WO2013033705A2 (en) | 2011-09-01 | 2013-03-07 | Case Western Reserve University | Non-natural nucleosides as theranostic agents |
| US9821173B2 (en) | 2013-02-08 | 2017-11-21 | Case Western Reserve University | Anti-cancer agents and methods of use |
| KR101642042B1 (ko) * | 2013-10-24 | 2016-07-22 | 건국대학교 글로컬산학협력단 | 티아졸리딘디온의 p35 및 p25 활성 변화에 대한 용도 |
| MX2018009748A (es) | 2016-02-11 | 2019-02-07 | Nutrition 21 Llc | Composiciones que contienen cromo para mejorar la salud y el estado físico. |
| CN110944639A (zh) * | 2017-06-28 | 2020-03-31 | 国立大学法人京都大学 | 用于预防和/或治疗阿尔茨海默病的药剂 |
Family Cites Families (94)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5522636A (en) | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| JPS5697277A (en) | 1980-01-07 | 1981-08-05 | Takeda Chem Ind Ltd | Thiazolidine derivative |
| US4546095A (en) | 1980-07-21 | 1985-10-08 | Markov Angel K | Use of fructose-1,6-diphosphate for treating myocardial infarction |
| US5039665A (en) | 1980-07-21 | 1991-08-13 | Markov Angel K | Use of fructose-1,6-diphosphate for treating myocardial infarction |
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| JPS58118577A (ja) | 1982-01-07 | 1983-07-14 | Takeda Chem Ind Ltd | チアゾリジン誘導体 |
| US4540564A (en) | 1982-05-18 | 1985-09-10 | University Of Florida | Brain-specific drug delivery |
| US4757052A (en) | 1982-09-03 | 1988-07-12 | Markov Angel K | Method of preserving blood |
| US4775665A (en) | 1983-05-16 | 1988-10-04 | Massachusetts Institute Of Technology | Method and composition for treating neurological disorders and aging |
| JPS6051189A (ja) | 1983-08-30 | 1985-03-22 | Sankyo Co Ltd | チアゾリジン誘導体およびその製造法 |
| CN1003445B (zh) | 1984-10-03 | 1989-03-01 | 武田药品工业株式会社 | 噻唑烷二酮衍生物,其制备方法和用途 |
| AR240698A1 (es) | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4703040A (en) | 1985-04-03 | 1987-10-27 | Markov Angel K | Treatment of adult respiratory distress syndrome (ARDS) using fructose diphosphate (FDP) |
| US4703052A (en) | 1985-05-21 | 1987-10-27 | Pfizer Inc. | Hypoglycemic thiazolidinediones |
| US5039794A (en) | 1986-09-19 | 1991-08-13 | Otsuka Pharmaceutical Co., Ltd. | Tumor egress factor and processes for producing the same |
| US4873255A (en) | 1987-02-04 | 1989-10-10 | Sankyo Company Limited | Thiazolidinone derivatives, their preparation and their use |
| FI91869C (fi) | 1987-03-18 | 1994-08-25 | Tanabe Seiyaku Co | Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi |
| NL8800823A (nl) * | 1987-04-10 | 1988-11-01 | Sandoz Ag | Werkwijze voor het toepassen van dopamine-receptor agonisten en farmaceutische preparaten die deze agonisten bevatten. |
| EP0295828A1 (en) | 1987-06-13 | 1988-12-21 | Beecham Group Plc | Novel compounds |
| US5194443A (en) | 1987-09-04 | 1993-03-16 | Beecham Group P.L.C. | Compounds |
| US5232925A (en) | 1987-09-04 | 1993-08-03 | Beecham Group P.L.C. | Compounds |
| EP0842925A1 (en) | 1987-09-04 | 1998-05-20 | Beecham Group Plc | Substituted thiazolidinedione derivatives |
| US5260445A (en) | 1987-09-04 | 1993-11-09 | Beecham Group P.L.C. | 2,4-thiazolidinediones |
| US4980350A (en) | 1988-02-25 | 1990-12-25 | Merck & Co., Inc. | Piperazinylalkylpyrimidines as hypoglycemic agents |
| US5061717A (en) | 1988-03-08 | 1991-10-29 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| US5120754A (en) | 1988-03-08 | 1992-06-09 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| MX15171A (es) | 1988-03-08 | 1993-05-01 | Pfizer | Derivados de tiazolidinodiona hipoglicemicos |
| US5223522A (en) | 1988-03-08 | 1993-06-29 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| US5468755A (en) | 1988-05-10 | 1995-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of Type II diabetes |
| US5208250A (en) | 1988-05-25 | 1993-05-04 | Warner-Lambert Company | Known and selected novel arylmethylenyl derivatives of thiazolidinones, imidazolidinones and oxazolidinones useful as antiallergy agents and anti-inflammatory agents |
| US5948634A (en) | 1988-12-21 | 1999-09-07 | The General Hospital Coporation | Neural thread protein gene expression and detection of alzheimer's disease |
| GB8901778D0 (en) | 1989-01-27 | 1989-03-15 | Univ Court Of The University O | Manipulatory technique |
| US4897405A (en) | 1989-04-21 | 1990-01-30 | American Home Products Corporation | Novel naphthalenylalkyl-3H-1,2,3,5-oxathiadiazole 2-oxides useful as antihyperglycemic agents |
| GB8919434D0 (en) | 1989-08-25 | 1989-10-11 | Beecham Group Plc | Novel compounds |
| WO1991007107A1 (en) | 1989-11-13 | 1991-05-30 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
| US5143928A (en) | 1990-03-27 | 1992-09-01 | Warner-Lambert Company | 3,5-di-tertiarybutyl-4-hydroxyphenylmethylene derivatives of 2-substituted thiazolidinones, oxazolidinones, and imidazolidinones as antiinflammatory agents |
| PT97507B (pt) | 1990-04-27 | 1998-08-31 | Orion Yhtymae Oy | Processo para apreparacao de novos derivados de catecol farmacologicamente activos |
| GB9017218D0 (en) | 1990-08-06 | 1990-09-19 | Beecham Group Plc | Novel compounds |
| CA2087437A1 (en) | 1990-08-23 | 1992-02-24 | Steven W. Goldstein | Hypoglycemic hydroxyurea derivatives |
| US5364769A (en) | 1990-09-25 | 1994-11-15 | Genentech, Inc. | Nucleic acid encoding neurotrophic factor four (NT-4), vectors, host cells and methods of production |
| US5668117A (en) * | 1991-02-22 | 1997-09-16 | Shapiro; Howard K. | Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments |
| US6746678B1 (en) * | 1991-02-22 | 2004-06-08 | Howard K. Shapiro | Method of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with medicaments |
| US5192753A (en) | 1991-04-23 | 1993-03-09 | Mcgeer Patrick L | Anti-rheumatoid arthritic drugs in the treatment of dementia |
| US5143929A (en) | 1991-05-09 | 1992-09-01 | Warner-Lambert Company | 2-substituted thiazolidinone, oxazolidinone, and imidazolidinone derivatives of fenamates as antiinflammatory agents |
| US5164384A (en) | 1991-06-19 | 1992-11-17 | Metagenics, Inc. | Anabolic mineral formula |
| US5714470A (en) | 1991-08-22 | 1998-02-03 | Merrell Pharmaceuticals, Inc. | Orally-active elastase inhibitors |
| US5270319A (en) | 1991-09-09 | 1993-12-14 | Warner-Lambert Company | 5-hydroxy-2-pyrimidinylmethylene derivatives useful as antiinflammatory agents |
| US5256697A (en) | 1992-04-16 | 1993-10-26 | Abbott Laboratories | Method of administering pyruvate and methods of synthesizing pyruvate precursors |
| US5326770A (en) | 1992-07-17 | 1994-07-05 | The Du Pont Merck Pharmaceutical Company | Monoamine oxidase-B (MAO-B) inhibitory 5-substituted 2,4-thiazolidinediones useful in treating memory disorders of mammals |
| IT1260155B (it) | 1992-08-03 | 1996-03-28 | Fidia Spa | Uso terapeutico della fosforil-l-serina-n-acil-sfingosina |
| GB2269992A (en) | 1992-08-14 | 1994-03-02 | Rh Ne Poulenc Rorer Limited | Powder inhalation formulations |
| ZA936492B (en) | 1992-09-10 | 1995-03-02 | Lilly Co Eli | Compounds useful as hypoglycemic agents and for treating Alzheimer's disease. |
| US5543297A (en) | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
| AU683043B2 (en) | 1993-01-25 | 1997-10-30 | Beth Israel Hospital Association, The | Method for modifying, diagnosing, and screening for IGF-I sensitive cell barrier properties |
| DE69432217T2 (de) | 1993-04-06 | 2004-04-08 | Abbott Laboratories, Abbott Park | Tetracyclische verbindungen als dopamin-agonisten |
| DK1564293T3 (da) | 1993-04-20 | 2009-01-12 | Gen Hospital Corp | Nervetrådproteingenekspression og detektion af Alzheimers sygdom |
| US5360614A (en) | 1993-04-26 | 1994-11-01 | The Estee Corporation | Method of controlling the release of carbohydrates by encapsulation and composition therefor |
| US5478852C1 (en) | 1993-09-15 | 2001-03-13 | Sankyo Co | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus |
| US5395822A (en) | 1993-09-20 | 1995-03-07 | Izumi; Yukitoshi | Use of pyruvate to prevent neuronal degeneration associated with ischemia |
| EP0729361A4 (en) * | 1993-11-15 | 1996-11-06 | Celtrix Pharma | METHOD FOR TREATING NEUROLOGICAL DISEASES |
| US5935927A (en) | 1994-02-03 | 1999-08-10 | The Picower Institute For Medical Research | Compositions and methods for stimulating amyloid removal in amyloidogenic diseases using advanced glycosylation endproducts |
| JPH07238035A (ja) * | 1994-02-28 | 1995-09-12 | Kyowa Hakko Kogyo Co Ltd | βアミロイド蛋白質分解剤 |
| US6251928B1 (en) * | 1994-03-16 | 2001-06-26 | Eli Lilly And Company | Treatment of alzheimer's disease employing inhibitors of cathepsin D |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5594015A (en) | 1994-06-22 | 1997-01-14 | Regents Of The University Of California | Thiazolidine derivatives for the treatment of psoriasis |
| WO1996003087A1 (en) | 1994-07-22 | 1996-02-08 | University Of Washington | Methods for stereotactic implantation |
| US5483070A (en) * | 1994-08-02 | 1996-01-09 | Packard Instrument Company | Scintillation counter |
| US5607967A (en) | 1994-10-27 | 1997-03-04 | Merck & Co., Inc. | Treatment of alzheimer's disease with 5-(tetradecyloxy)-2-furan carboxylic acid |
| US5641796A (en) | 1994-11-01 | 1997-06-24 | Eli Lilly And Company | Oral hypoglycemic agents |
| US5602121A (en) | 1994-12-12 | 1997-02-11 | Allelix Biopharmaceuticals, Inc. | Alkyl-substituted compounds having dopamine receptor affinity |
| US5602120A (en) | 1994-12-12 | 1997-02-11 | Allelix Biopharmaceuticals, Inc. | Benzyl-substituted compounds having dopamine receptor affinity |
| US5824692A (en) | 1995-01-06 | 1998-10-20 | Lippiello; Patrick Michael | Pharmaceutical compositions for prevention and treatment of central nervous system disorders |
| US6022897A (en) | 1995-04-25 | 2000-02-08 | The Salk Institute For Biological Studies | Selective modulators of peroxisome proliferator activated receptor-gamma, and methods for the use thereof |
| US5708012A (en) * | 1995-04-28 | 1998-01-13 | Sankyo Company, Limited | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus |
| US5707971A (en) | 1995-06-07 | 1998-01-13 | Life Resuscitation Technologies, Inc. | Modulation of glycolytic ATP production |
| US5618835A (en) | 1996-02-01 | 1997-04-08 | The Procter & Gamble Company | Dihydrobenzofuran and related compounds useful as anti-inflammatory agents |
| IN182496B (enExample) | 1996-02-20 | 1999-04-17 | Reddy Research Foundation | |
| GB9604242D0 (en) | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| US5783556A (en) | 1996-08-13 | 1998-07-21 | Genentech, Inc. | Formulated insulin-containing composition |
| GB9627006D0 (en) | 1996-12-27 | 1997-02-12 | Knoll Ag | Therapeutic agents |
| GB9627005D0 (en) | 1996-12-27 | 1997-02-12 | Knoll Ag | Therapeutic agents |
| US6025157A (en) | 1997-02-18 | 2000-02-15 | Genentech, Inc. | Neurturin receptor |
| US5814647A (en) | 1997-03-04 | 1998-09-29 | Board Of Regents, The University Of Texas System | Use of troglitazone and related compounds for the treatment of the climacteric symptoms |
| WO1998039967A1 (en) * | 1997-03-12 | 1998-09-17 | The General Hospital Corporation | A method for treating or preventing alzheimer's disease |
| WO1998046588A2 (en) | 1997-04-11 | 1998-10-22 | Neorx Corporation | Compounds and therapies for the prevention of vascular and non-vascular pathologies |
| US5925657A (en) | 1997-06-18 | 1999-07-20 | The General Hospital Corporation | Use of PPARγ agonists for inhibition of inflammatory cytokine production |
| US5789401A (en) * | 1997-08-08 | 1998-08-04 | Nutrition 21 | High-dose chromium/biotin treatment of type II diabetes |
| AU1172999A (en) | 1997-11-19 | 1999-06-07 | Takeda Chemical Industries Ltd. | Novel apoptosis inhibitors |
| US20040058873A1 (en) * | 1998-03-12 | 2004-03-25 | Esmond Robert W. | Method for treating or preventing Alzheimer's disease |
| US6028088A (en) | 1998-10-30 | 2000-02-22 | The University Of Mississippi | Flavonoid derivatives |
| US6191154B1 (en) | 1998-11-27 | 2001-02-20 | Case Western Reserve University | Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases |
-
1998
- 1998-03-12 WO PCT/US1998/004731 patent/WO1998039967A1/en not_active Ceased
- 1998-03-12 CA CA002323889A patent/CA2323889A1/en not_active Abandoned
- 1998-03-12 DE DE69838789T patent/DE69838789T2/de not_active Expired - Lifetime
- 1998-03-12 EP EP98909105A patent/EP1006794B1/en not_active Expired - Lifetime
- 1998-03-12 JP JP53974498A patent/JP2001514663A/ja active Pending
-
2003
- 2003-09-23 US US10/669,217 patent/US7300927B2/en not_active Expired - Fee Related
-
2004
- 2004-09-09 US US10/936,709 patent/US20050043242A1/en not_active Abandoned
-
2009
- 2009-06-23 JP JP2009148356A patent/JP2009280586A/ja active Pending
- 2009-07-20 US US12/505,868 patent/US20090280192A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20090280192A1 (en) | 2009-11-12 |
| US20050043242A1 (en) | 2005-02-24 |
| CA2323889A1 (en) | 1998-09-17 |
| EP1006794A1 (en) | 2000-06-14 |
| JP2009280586A (ja) | 2009-12-03 |
| EP1006794A4 (en) | 2004-07-07 |
| US20040060077A1 (en) | 2004-03-25 |
| JP2001514663A (ja) | 2001-09-11 |
| US7300927B2 (en) | 2007-11-27 |
| EP1006794B1 (en) | 2007-11-28 |
| WO1998039967A1 (en) | 1998-09-17 |
| DE69838789D1 (de) | 2008-01-10 |
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