CN104107417B - 用于预防或治疗胰岛素抵抗性的方法 - Google Patents
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Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4879020B2 (ja) * | 2003-05-01 | 2012-02-15 | コーネル リサーチ ファウンデイション インコーポレイテッド | 細胞に分子を送達する方法及び担体複合体 |
| CA2947335A1 (en) * | 2005-09-16 | 2007-03-29 | Cornell Research Foundation, Inc. | Methods for reducing cd36 expression |
| EP3103467A1 (en) * | 2008-02-07 | 2016-12-14 | Cornell University | Methods for preventing or treating insulin resistance |
| EP3563862B1 (en) | 2009-03-20 | 2021-05-05 | The General Hospital Corporation d/b/a Massachusetts General Hospital | D-arg-2'6'-dimethyltyrosine-lys-phe-nh2 for use in the prevention of secondary complications of burn injuries |
| CN105031605A (zh) * | 2009-08-12 | 2015-11-11 | 康奈尔大学 | 预防或治疗代谢综合症的方法 |
| PL2470191T3 (pl) * | 2009-08-24 | 2014-09-30 | Stealth Peptides Int Inc | Sposoby i kompozycje do profilaktyki lub leczenia stanów okulistycznych |
| EP2485749A4 (en) * | 2009-10-05 | 2013-07-24 | Univ Cornell | METHOD FOR THE PREVENTION AND TREATMENT OF HEART FAILURE |
| EP3266462A1 (en) * | 2009-12-31 | 2018-01-10 | Stealth Peptides International, Inc. | Methods for performing a coronary artery bypass graft procedure |
| AU2011207432A1 (en) * | 2010-01-25 | 2012-08-02 | Cornell University | Aromatic-cationic peptides and uses of same |
| US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
| GB201018125D0 (en) * | 2010-10-26 | 2010-12-08 | Marealis As | Peptide |
| EP3009141A1 (en) * | 2011-12-09 | 2016-04-20 | Stealth Peptides International, Inc. | Aromatic-cationic peptides and uses of same |
| HK1204988A1 (en) * | 2012-02-22 | 2015-12-11 | Stealth Peptides International, Inc. | Methods and compositions for preventing or treating ophthalmic conditions |
| JP6317324B2 (ja) * | 2012-03-30 | 2018-04-25 | ステルス ペプチドズ インターナショナル インコーポレイテッド | 神経障害を予防および処置するための方法および組成物 |
| HK1210953A1 (en) * | 2012-08-02 | 2016-05-13 | Stealth Peptides International, Inc. | Methods for treatment of atherosclerosis |
| EP2928562A4 (en) * | 2012-12-06 | 2016-06-22 | Stealth Peptides Int Inc | PEPTIDE THERAPEUTIC PRODUCTS AND METHODS OF USE |
| MX392555B (es) | 2016-09-07 | 2025-03-24 | Univ Temple | Composiciones y métodos para el tratamiento de resistencia a la insulina. |
| BR112020018010A2 (pt) * | 2018-03-07 | 2020-12-29 | Temple University - Of The Commonwealth System Of Higher Education | Métodos de prevenção ou tratamento de diabetes tipo 2, de prevenção ou tratamento de pré-diabetes e de prevenção ou tratamento de uma condição em um indivíduo em necessidade |
| EP3761985A4 (en) * | 2018-03-07 | 2021-12-29 | Temple University - Of The Commonwealth System of Higher Education | Compositions and methods for treatment of insulin resistance |
| TW202206062A (zh) | 2020-04-24 | 2022-02-16 | 美國坦普大學 高等教育聯邦系統 | 治療非酒精性脂肪肝炎的方法 |
| CA3191819A1 (en) | 2020-09-09 | 2022-03-17 | Hazel Szeto | Methods and compositions for delivery of biotin to mitochondria |
| CN117881411A (zh) | 2021-06-01 | 2024-04-12 | 艾迪雅生物有限责任公司 | 用于眼部药物的延长释放药物递送系统和使用方法 |
| US20240122884A1 (en) * | 2022-10-03 | 2024-04-18 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of n-lactoyl-phenylalanine and other n-lactoyl-amino acids |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070129306A1 (en) * | 2005-09-16 | 2007-06-07 | Szeto Hazel H | Methods for Reducing CD36 Expression |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
| US3817837A (en) | 1971-05-14 | 1974-06-18 | Syva Corp | Enzyme amplification assay |
| US3939350A (en) | 1974-04-29 | 1976-02-17 | Board Of Trustees Of The Leland Stanford Junior University | Fluorescent immunoassay employing total reflection for activation |
| US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
| US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
| US4277437A (en) | 1978-04-05 | 1981-07-07 | Syva Company | Kit for carrying out chemically induced fluorescence immunoassay |
| US4391904A (en) | 1979-12-26 | 1983-07-05 | Syva Company | Test strip kits in immunoassays and compositions therein |
| US4366241A (en) | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US5602100A (en) | 1988-06-30 | 1997-02-11 | Astra Ab | Dermorphin analogs having pharmacological activity |
| EP0350221B1 (en) | 1988-06-30 | 1996-04-17 | Astra Aktiebolag | Dermorphin analogs, their methods of preparation, pharmaceutical compositions, and methods of therapeutic treatment using the same |
| US5670617A (en) | 1989-12-21 | 1997-09-23 | Biogen Inc | Nucleic acid conjugates of tat-derived transport polypeptides |
| US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
| US5716644A (en) | 1992-06-11 | 1998-02-10 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
| US5674534A (en) | 1992-06-11 | 1997-10-07 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
| IS4261A (is) | 1994-02-21 | 1995-08-22 | Astra Aktiebolag | Nýir peptíð-ópíóíðar til meðhöndlunar á verkjum og notkun þeirra |
| ATE255450T1 (de) | 1995-06-09 | 2003-12-15 | Hisamitsu Pharmaceutical Co | Matrix für iontophorese |
| US5849761A (en) | 1995-09-12 | 1998-12-15 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
| US5885958A (en) | 1997-03-25 | 1999-03-23 | Administrators Of The Tulane Educational Fund | Mu-opiate receptor peptides |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| CA2314267A1 (en) | 1997-12-10 | 1999-06-17 | Washington University | Anti-pathogen system and methods of use thereof |
| JP2002512954A (ja) | 1998-04-24 | 2002-05-08 | マイトコー | ミトコンドリア関連疾患を処置するための化合物および方法 |
| AU5142699A (en) * | 1998-07-31 | 2000-02-28 | Mount Sinai Hospital Corporation | Methods and compositions for increasing insulin sensitivity |
| US6245740B1 (en) | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
| SE9900961D0 (sv) | 1999-03-16 | 1999-03-16 | Astra Ab | Novel compounds |
| AU7855900A (en) | 1999-10-04 | 2001-05-10 | University Of Medicine And Dentistry Of New Jersey | Methods for identifying rna binding compounds |
| US6759520B1 (en) | 1999-10-28 | 2004-07-06 | The New England Medical Center Hospitals, Inc. | Chimeric analgesic peptides |
| US20050192215A1 (en) | 2000-01-21 | 2005-09-01 | Malabika Ghosh | Methods and materials relating to novel polypeptides and polynucleotides |
| EP1303186B1 (en) | 2000-07-18 | 2011-01-26 | Cornell Research Foundation, Inc. | Medicinal uses of mu-opioid receptor agonists |
| US6900178B2 (en) | 2000-09-12 | 2005-05-31 | University Of Kentucky Research Foundation | Protection against ischemia and reperfusion injury |
| US20070015146A1 (en) | 2001-05-22 | 2007-01-18 | Gene Logic, Inc. | Molecular nephrotoxicology modeling |
| SI2656854T1 (sl) | 2003-02-04 | 2015-09-30 | Cornell Research Foundation, Inc. | Uporabe aromatsko-kationskega peptida |
| JP4879020B2 (ja) | 2003-05-01 | 2012-02-15 | コーネル リサーチ ファウンデイション インコーポレイテッド | 細胞に分子を送達する方法及び担体複合体 |
| US7232824B2 (en) | 2003-09-30 | 2007-06-19 | Scios, Inc. | Quinazoline derivatives as medicaments |
| CA2851972C (en) | 2004-01-23 | 2015-06-23 | Cornell Research Foundation, Inc. | Methods for reducing oxidative damage |
| US20050272101A1 (en) | 2004-06-07 | 2005-12-08 | Prasad Devarajan | Method for the early detection of renal injury |
| US20070259377A1 (en) * | 2005-10-11 | 2007-11-08 | Mickey Urdea | Diabetes-associated markers and methods of use thereof |
| US20080027082A1 (en) | 2006-06-19 | 2008-01-31 | Berthold Hocher | Use of adenosine a1 antagonists in radiocontrast media induced nephropathy |
| EP3103467A1 (en) * | 2008-02-07 | 2016-12-14 | Cornell University | Methods for preventing or treating insulin resistance |
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| Publication number | Priority date | Publication date | Assignee | Title |
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