CA2442683A1 - Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism - Google Patents
Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism Download PDFInfo
- Publication number
- CA2442683A1 CA2442683A1 CA002442683A CA2442683A CA2442683A1 CA 2442683 A1 CA2442683 A1 CA 2442683A1 CA 002442683 A CA002442683 A CA 002442683A CA 2442683 A CA2442683 A CA 2442683A CA 2442683 A1 CA2442683 A1 CA 2442683A1
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- Prior art keywords
- fatty acid
- composition
- compounds
- alkyl
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Child & Adolescent Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
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| US60/279,542 | 2001-03-27 | ||
| US33628901P | 2001-10-31 | 2001-10-31 | |
| US60/336,289 | 2001-10-31 | ||
| PCT/US2002/009773 WO2002080860A2 (en) | 2001-03-27 | 2002-03-27 | Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism |
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| CA2442683A1 true CA2442683A1 (en) | 2002-10-17 |
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| CA002442683A Abandoned CA2442683A1 (en) | 2001-03-27 | 2002-03-27 | Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism |
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| DE10129693A1 (de) * | 2001-06-22 | 2003-01-02 | Jan Loock | Verfahren zur extrakorporalen qualitativen und/oder quantitativen Erfassung neurotoxischer Substanzen im Blutplasma eines Individuums |
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| AU2003296895A1 (en) * | 2002-08-20 | 2004-05-04 | The Regents Of The University Of California | Combination therapy for controlling appetites |
| US7765162B2 (en) * | 2002-10-07 | 2010-07-27 | Mastercard International Incorporated | Method and system for conducting off-line and on-line pre-authorized payment transactions |
| AU2003290387A1 (en) * | 2002-11-18 | 2004-06-15 | Natural Asa | Dietry supplements and foods product comprising oleylethanolamide |
| US7083933B1 (en) | 2003-05-09 | 2006-08-01 | Prosidion Limited | Methods for identification of modulators of OSGPR116 activity |
| EP1677780A4 (en) * | 2003-10-16 | 2007-05-02 | Univ California | DIETARY AND OTHER FOODS, COMPOUNDS AND METHOD FOR REDUCING BODY FAT, APPETIZING AND MODULATING THE FATTY ACID CHANGES |
| ATE399474T1 (de) * | 2004-03-06 | 2008-07-15 | Cognis Ip Man Gmbh | Use of unsaturated fatty acids for the reduction of appetite or food intake |
| JP2006061086A (ja) * | 2004-08-27 | 2006-03-09 | Morishita Jintan Kk | 脂肪代謝改善効果を有する被験試料のスクリーニング方法 |
| DOP2006000008A (es) * | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| US20090054526A1 (en) * | 2005-07-14 | 2009-02-26 | Hansen Harald S | Inhibitors of anorexic lipid hydrolysis for the treatment of eating disorders |
| WO2007111806A2 (en) | 2006-03-23 | 2007-10-04 | Massachusetts Eye And Ear Infirmary | Cyclopentane heptanoic acid compounds for reducing body fat |
| PE20071221A1 (es) * | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| ES2354390T3 (es) | 2006-04-11 | 2011-03-14 | Arena Pharmaceuticals, Inc. | Procedimientos de uso del receptor gpr119 para identificar compuestos útiles para aumentar la masa ósea en un individuo. |
| US20090208513A1 (en) * | 2007-09-07 | 2009-08-20 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Diagnostic And Therapeutic Uses Of Augmenter Of Liver Regeneration In Inflammatory Conditions |
| ES2291147B1 (es) * | 2007-10-15 | 2008-11-01 | Fundacion Instituto Mediterraneo Para La Biotecnologia Y La Investigacion Sanitaria (Imabis) | Derivados pirazolicos de amidas de acidos grasos como activadores especificos de receptores ppar-alfa, procedimiento de preparacion y utilizacion. |
| EP2146210A1 (en) * | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
| US20090264520A1 (en) * | 2008-04-21 | 2009-10-22 | Asha Lipid Sciences, Inc. | Lipid-containing compositions and methods of use thereof |
| CN102036559A (zh) * | 2008-05-19 | 2011-04-27 | 雀巢产品技术援助有限公司 | 降低动物脂质吸收的方法 |
| US20130122147A1 (en) * | 2010-03-24 | 2013-05-16 | Delphine Chaillot Tissot-Favre | Methods for enhancing the palatability of comestible compositions |
| WO2012003176A1 (en) | 2010-07-02 | 2012-01-05 | Helix Biomedix, Inc. | N-acyl amino acid derivatives for treating skin conditions such as cellulite |
| WO2012099942A2 (en) | 2011-01-19 | 2012-07-26 | Terakine Therapeutics, Inc. | Methods and compositions for treating metabolic syndrome |
| US20140193370A1 (en) * | 2011-05-10 | 2014-07-10 | Nestec Sa | Methods and compositions for promoting lean body mass growth |
| BR112013028759A2 (pt) * | 2011-05-10 | 2016-08-09 | Nestec Sa | métodos e composições para conservar a massa magra do corpo durante a perda de peso |
| US8426471B1 (en) * | 2011-12-19 | 2013-04-23 | Topokine Therapeutics, Inc. | Methods and compositions for reducing body fat and adipocytes |
| CN102579414A (zh) * | 2012-01-29 | 2012-07-18 | 厦门大学 | 油酰乙醇胺作为降血脂、防治非酒精性脂肪肝药物的用途 |
| WO2013160492A1 (es) * | 2012-04-24 | 2013-10-31 | Fundación Instituto Mediterráneo Para El Avance De La Biotecnología Y La Investigación Sanitaria (Imabis) | Terapia combinada para el tratamiento de enfermedades metabólicas |
| US9221747B2 (en) | 2012-04-25 | 2015-12-29 | Iowa State University Research Foundation, Inc. | Method of making fatty acid N-acylalkanolamines |
| CN102675141A (zh) * | 2012-05-04 | 2012-09-19 | 庄信修 | N-(2-羟基乙基)芥酰胺及其制备与用途 |
| CN104602536A (zh) | 2012-09-07 | 2015-05-06 | 雀巢产品技术援助有限公司 | 油酰乙醇胺组合物 |
| CN102824338A (zh) * | 2012-09-18 | 2012-12-19 | 厦门大学 | s-油酰丙醇胺在制备降血脂、防治非酒精性脂肪肝药物中的用途 |
| JP5877620B2 (ja) | 2012-11-21 | 2016-03-08 | トポカイン セラピューティックス， インコーポレイテッド | 体脂肪を局所的に増大させるための方法および組成物 |
| CN103113253A (zh) * | 2013-01-28 | 2013-05-22 | 国家海洋局第三海洋研究所 | 一种不饱和脂肪酸醇胺衍生物及其制备方法与应用 |
| ES2498521B1 (es) * | 2013-02-20 | 2015-08-18 | Fundación Pública Andaluza Para La Investigación De Málaga En Biomedicina Y Salud (Fimabis) | Formulaciones basadas en nanoemulsiones y su uso para el tratamiento de la obesidad |
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| WO2014186504A1 (en) | 2013-05-15 | 2014-11-20 | Topokine Therapeutics, Inc. | Methods and compositions for topical delivery of prostaglandins to subcutaneous fat |
| WO2015200425A1 (en) | 2014-06-27 | 2015-12-30 | Topokine Therapeutics, Inc. | Topical dosage regimen |
| MY172113A (en) | 2017-07-05 | 2019-11-14 | Frimline Private Ltd | A pharmaceutical composition for neuropathic pain |
| US10702487B2 (en) | 2017-08-19 | 2020-07-07 | Frimline Private Limited | Pharmaceutical composition for prevention of diet induced obesity |
| MY186286A (en) | 2017-09-05 | 2021-07-05 | Frimline Private Ltd | A pharmaceutical composition for improving or preventing progression of chronic kidney disease |
| WO2024124172A1 (en) * | 2022-12-09 | 2024-06-13 | The Trustees Of The University Of Pennsylvania | Compositions and methods for stimulating and/or enhancing exercise motivation and/or physical performance |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US5506224A (en) * | 1991-12-31 | 1996-04-09 | Lifegroup S.P.A. | N-acyl derivatives of aminoalcohols active as local autacoids and useful in the therapy of autoimmune processes |
| US5679667A (en) * | 1992-04-24 | 1997-10-21 | Lifegroup S.P.A. | Aminoalcohols-N-Acyl derivatives as therapeutical agents against the neurogenic endoneural edema of the peripheral nerve |
| US5602164A (en) * | 1992-04-28 | 1997-02-11 | Senyorina Ltd. | Anti-obesity drugs |
| US5554646A (en) * | 1992-04-29 | 1996-09-10 | Wisconsin Alumni Research Foundation | Method for reducing body fat in animals |
| IL103932A (en) | 1992-11-30 | 1997-02-18 | Yissum Res & Dev | Fatty acid and pharmaceutical compositions containing them |
| US5618955A (en) * | 1992-11-30 | 1997-04-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Fatty acid derivatives and pharmaceutical compositions containing same |
| US5631297A (en) * | 1994-07-11 | 1997-05-20 | Pate; David W. | Anandamides useful for the treatment of intraocular hypertension, ophthalmic compositions containing the same and methods of use of the same |
| IT1271266B (it) * | 1994-12-14 | 1997-05-27 | Valle Francesco Della | Impiego terapeutico di ammidi di acidi mono e bicarbossilici con amminoalcoli,selettivamente attive sul recettore periferico dei cannabinoidi |
| IT1274783B (it) * | 1994-12-15 | 1997-07-24 | Antonio Picarelli | Preparato per il trattamento dell'obesita' |
| AU5524896A (en) * | 1995-03-20 | 1996-10-08 | Institut Pasteur De Lille | Modulators of ob gene and screening methods therefor |
| US6271015B1 (en) | 1995-06-12 | 2001-08-07 | The Scripps Research Institute | Fatty-acid amide hydrolase |
| US6090836A (en) | 1996-02-02 | 2000-07-18 | Merck & Co., Inc. | Benzisoxazole-derived antidiabetic compounds |
| WO1997028149A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Method for raising hdl cholesterol levels |
| DE69728267T2 (de) | 1996-02-02 | 2005-02-24 | Merck & Co., Inc. | Antidiabetisches mittel |
| US5847008A (en) | 1996-02-02 | 1998-12-08 | Merck & Co., Inc. | Method of treating diabetes and related disease states |
| US5859051A (en) | 1996-02-02 | 1999-01-12 | Merck & Co., Inc. | Antidiabetic agents |
| US5803916A (en) | 1996-03-19 | 1998-09-08 | Vital-Tech Ltd. | Body and joints massage device |
| GB9606805D0 (en) | 1996-03-30 | 1996-06-05 | Glaxo Wellcome Inc | Medicaments |
| US5830916A (en) * | 1996-05-23 | 1998-11-03 | Duke University | Inhibitor of ceramidase |
| US5856537A (en) | 1996-06-26 | 1999-01-05 | The Scripps Research Institute | Inhibitors of oleamide hydrolase |
| US5925672A (en) | 1996-12-06 | 1999-07-20 | Neurosciences Research Foundation, Inc. | Methods of treating mental diseases, inflammation and pain |
| US6090839A (en) | 1996-12-23 | 2000-07-18 | Merck & Co., Inc. | Antidiabetic agents |
| US6160000A (en) | 1996-12-23 | 2000-12-12 | Merck & Co., Inc. | Antidiabetic agents based on aryl and heteroarylacetic acids |
| US5985282A (en) * | 1997-01-22 | 1999-11-16 | Hpf, L.L.C. | Herbal appetite suppressant and weight loss composition |
| FR2758723B1 (fr) * | 1997-01-28 | 1999-04-23 | Sanofi Sa | Utilisation des antagonistes des recepteurs aux cannabinoides centraux pour la preparation de medicaments |
| TW492882B (en) | 1997-11-28 | 2002-07-01 | Caleb Pharmaceuticals Inc | Cholinergic antagonist plaster composition |
| US6008237A (en) | 1997-12-19 | 1999-12-28 | Merck & Co., Inc. | Arylthiazolidinedione derivatives |
| WO1999060987A2 (en) | 1998-05-29 | 1999-12-02 | Neurosciences Research Foundation, Inc. | Control of pain with endogenous cannabinoids |
| US7897598B2 (en) | 1998-06-09 | 2011-03-01 | Alexandros Makriyannis | Inhibitors of the anandamide transporter |
| US6274608B1 (en) | 1999-04-20 | 2001-08-14 | Novo Nordisk A/S | Compounds, their preparation and use |
| GB9923738D0 (en) | 1999-10-07 | 1999-12-08 | Nestle Sa | Nutritional composition |
| US6359010B1 (en) * | 1999-11-23 | 2002-03-19 | Thomas D. Geracioti, Jr. | Methods of treating anxiety and mood disorders with oleamide |
| US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
| EP1294411A4 (en) | 2000-05-23 | 2006-02-01 | Univ California | COUGH TREATMENT |
| KR20030087657A (ko) | 2001-03-27 | 2003-11-14 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 체지방 감소 및 지방산 대사 조절을 위한 방법, 화합물 및조성물 |
| US7048941B2 (en) | 2001-03-30 | 2006-05-23 | New World Enterprizes, Inc. | Chocolate composition as delivery system for nutrients and medications |
| AU2002309548B2 (en) * | 2001-04-06 | 2006-08-10 | The Board Of Trustees Of The University Of Illinois | Functional role for cannabinoids in autonomic stability during sleep |
| US7351874B2 (en) * | 2001-07-31 | 2008-04-01 | The Scripps Research Institute | Mouse model for fatty acid amide-related neurobehaviors |
| WO2003065989A2 (en) | 2002-02-08 | 2003-08-14 | Bristol-Myers Squibb Company | (oxime)carbamoyl fatty acid amide hydrolase inhibitors |
| AU2003290387A1 (en) | 2002-11-18 | 2004-06-15 | Natural Asa | Dietry supplements and foods product comprising oleylethanolamide |
-
2002
- 2002-03-27 KR KR10-2003-7012669A patent/KR20030087657A/ko not_active Abandoned
- 2002-03-27 CA CA002442683A patent/CA2442683A1/en not_active Abandoned
- 2002-03-27 MX MXPA03008823A patent/MXPA03008823A/es active IP Right Grant
- 2002-03-27 EA EA200301057A patent/EA006556B1/ru not_active IP Right Cessation
- 2002-03-27 EP EP02763872A patent/EP1408945A4/en not_active Withdrawn
- 2002-03-27 AU AU2002338329A patent/AU2002338329B2/en not_active Ceased
- 2002-03-27 US US10/112,509 patent/US6911474B2/en not_active Expired - Lifetime
- 2002-03-27 IL IL15813102A patent/IL158131A0/xx unknown
- 2002-03-27 WO PCT/US2002/009773 patent/WO2002080860A2/en not_active Ceased
- 2002-03-27 CN CNA028093410A patent/CN1523982A/zh active Pending
- 2002-03-27 JP JP2002578899A patent/JP2004526745A/ja active Pending
-
2005
- 2005-04-04 US US11/099,134 patent/US7423066B2/en not_active Expired - Lifetime
-
2008
- 2008-06-16 US US12/140,156 patent/US20090005447A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03008823A (es) | 2004-08-12 |
| IL158131A0 (en) | 2004-03-28 |
| EP1408945A2 (en) | 2004-04-21 |
| US6911474B2 (en) | 2005-06-28 |
| EA006556B1 (ru) | 2006-02-24 |
| AU2002338329B2 (en) | 2006-09-07 |
| US7423066B2 (en) | 2008-09-09 |
| EA200301057A1 (ru) | 2004-04-29 |
| AU2002338329C1 (en) | 2002-10-21 |
| CN1523982A (zh) | 2004-08-25 |
| US20090005447A1 (en) | 2009-01-01 |
| WO2002080860A3 (en) | 2004-02-26 |
| US20050187254A1 (en) | 2005-08-25 |
| KR20030087657A (ko) | 2003-11-14 |
| US20030018081A1 (en) | 2003-01-23 |
| JP2004526745A (ja) | 2004-09-02 |
| EP1408945A4 (en) | 2005-07-06 |
| WO2002080860A2 (en) | 2002-10-17 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |