JP4009319B2 - アミリンアゴニストを用いるｉｉ型糖尿病の治療 - Google Patents
アミリンアゴニストを用いるｉｉ型糖尿病の治療 Download PDFInfo
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- JP4009319B2 JP4009319B2 JP50206197A JP50206197A JP4009319B2 JP 4009319 B2 JP4009319 B2 JP 4009319B2 JP 50206197 A JP50206197 A JP 50206197A JP 50206197 A JP50206197 A JP 50206197A JP 4009319 B2 JP4009319 B2 JP 4009319B2
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- amylin
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- leu
- arg
- insulin
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/483,188 | 1995-06-07 | ||
| US08/483,188 US6143718A (en) | 1995-06-07 | 1995-06-07 | Treatment of Type II diabetes mellutis with amylin agonists |
| PCT/US1996/009875 WO1996040220A1 (en) | 1995-06-07 | 1996-06-07 | Treatment of type ii diabetes mellitus with amylin agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JPH10503785A JPH10503785A (ja) | 1998-04-07 |
| JPH10503785A5 JPH10503785A5 (enExample) | 2004-07-29 |
| JP4009319B2 true JP4009319B2 (ja) | 2007-11-14 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50206197A Expired - Fee Related JP4009319B2 (ja) | 1995-06-07 | 1996-06-07 | アミリンアゴニストを用いるｉｉ型糖尿病の治療 |
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| Country | Link |
|---|---|
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Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU222249B1 (hu) * | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
| HUT73490A (en) * | 1993-09-07 | 1996-08-28 | Amylin Pharmaceuticals Inc | Methods for regulating gastrointestinal mobility |
| US6143718A (en) * | 1995-06-07 | 2000-11-07 | Amylin Pharmaceuticals, Inc. | Treatment of Type II diabetes mellutis with amylin agonists |
| US6410511B2 (en) | 1997-01-08 | 2002-06-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US7312196B2 (en) | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US7101853B2 (en) * | 1997-05-06 | 2006-09-05 | Amylin Pharmaceuticals, Inc. | Method for treating or preventing gastritis using amylin or amylin agonists |
| US7910548B2 (en) * | 1997-06-06 | 2011-03-22 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity |
| EP1044015B1 (en) * | 1998-01-09 | 2008-10-08 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides with insulin |
| US6087334A (en) * | 1998-08-21 | 2000-07-11 | Amylin Pharmaceuticals, Inc. | Anti-diabetic peptides |
| DE60324387D1 (de) * | 2002-01-08 | 2008-12-11 | Amylin Pharmaceuticals Inc | Verwendung von amylin, amylinanaloga und amylin derivaten zur behandlung von dyslipidämie und hypertriglyceridämie |
| WO2004004665A2 (en) * | 2002-07-09 | 2004-01-15 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
| CA2525168A1 (en) * | 2003-05-14 | 2004-12-02 | Emisphere Technologies, Inc. | Compositions for delivering peptide yy and pyy agonists |
| EP1644027B1 (en) * | 2003-07-16 | 2014-04-09 | Evotec International GmbH | Use of pleiotrophin for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome |
| AU2005320351B2 (en) * | 2004-02-11 | 2010-06-03 | Amylin Pharmaceuticals, Llc | Amylin family peptides and methods for making and using them |
| CA2556923A1 (en) * | 2004-02-20 | 2005-09-09 | Rinat Neuroscience Corp. | Methods of treating obesity or diabetes using nt-4/5 |
| US7399744B2 (en) * | 2004-03-04 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition |
| CA2601304C (en) * | 2005-03-11 | 2010-08-17 | Indevus Pharmaceuticals, Inc. | Controlled release formulations of octreotide |
| US7759312B2 (en) * | 2005-03-11 | 2010-07-20 | Endo Pharmaceuticals Solutions Inc. | Delivery of dry formulations of octreotide |
| CA2637707A1 (en) * | 2006-02-02 | 2007-08-09 | Rinat Neuroscience Corporation | Methods for treating obesity by administering a trkb antagonist |
| CN101400367A (zh) * | 2006-02-02 | 2009-04-01 | 瑞纳神经科学公司 | 施用trkb激动剂治疗不希望的重量减轻或进食障碍的方法 |
| WO2008078179A1 (en) * | 2006-12-20 | 2008-07-03 | Rinat Neuroscience Corporation | Trkb agonists for treating autoimmune disorders |
| CA2705708A1 (en) * | 2007-11-14 | 2009-05-22 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity and obesity related diseases and disorders |
| US8071537B2 (en) * | 2008-06-25 | 2011-12-06 | Endo Pharmaceuticals Solutions Inc. | Implantable device for the sustained release of a polypeptide |
| BRPI0914336A2 (pt) * | 2008-06-25 | 2017-05-30 | Endo Pharmaceuticals Solutions | implante de octreotida com um agente de liberação |
| LT3228320T (lt) | 2008-10-17 | 2020-03-10 | Sanofi-Aventis Deutschland Gmbh | Insulino ir glp-1 agonisto derinys |
| JP2009149684A (ja) * | 2009-03-11 | 2009-07-09 | Amylin Pharmaceut Inc | アミリン作動薬ペプチド用製剤 |
| RU2537181C2 (ru) * | 2009-03-12 | 2014-12-27 | Нордик Байосайенс А/С | Лечение диабета и метаболического синдрома |
| PL2498802T3 (pl) | 2009-11-13 | 2015-06-30 | Sanofi Aventis Deutschland | Kompozycja farmaceutyczna zawierająca agonistę GLP-1, insulinę i metioninę |
| EP2498801B1 (de) | 2009-11-13 | 2018-01-24 | Sanofi-Aventis Deutschland GmbH | HARMAZEUTISCHE ZUSAMMENSETZUNG UMFASSEND desPro36Exendin-4(1-39)-Lys6-NH2 UND METHIONIN |
| US20110118180A1 (en) * | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Method of treatment of diabetes type 2 comprising add-on therapy to metformin |
| US20110118178A1 (en) * | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Method of treatment of diabetes type 2 comprising add-on therapy to insulin glargine and metformin |
| SI2611458T1 (sl) | 2010-08-30 | 2017-01-31 | Sanofi-Aventis Deutschland Gmbh | Uporaba AVE0010 za izdelavo zdravila za zdravljenje sladkorne bolezni tipa 2 |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| HUE027989T2 (en) | 2011-08-29 | 2016-11-28 | Sanofi Aventis Deutschland | A pharmaceutical composition for use in glycemic control in patients with type 2 diabetes |
| AR087744A1 (es) | 2011-09-01 | 2014-04-16 | Sanofi Aventis Deutschland | Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa |
| BR102013017626A2 (pt) * | 2013-06-14 | 2015-02-10 | Univ Rio De Janeiro | Bioconjugados não aglomerantes de amilinomiméticos com polietilenoglicol, uso de bioconjugados não aglomerantes de amilinomiméticos com polietilenoglicol, composições farmacêuticas de baixa toxicidade, adjuvante para a prevenção ou tratamento das doenças, medicamento, método de tratamento ou prevenção de doenças. |
| TW201625671A (zh) * | 2014-09-04 | 2016-07-16 | 諾佛 儂迪克股份有限公司 | 新穎澱粉素及降鈣素受體促效劑 |
| CA2970200A1 (en) | 2014-12-12 | 2016-06-16 | Sanofi-Aventis Deutschland Gmbh | Insulin glargine/lixisenatide fixed ratio formulation |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8720115D0 (en) * | 1987-08-26 | 1987-09-30 | Cooper G J S | Treatment of diabetes mellitus |
| US5367052A (en) * | 1987-04-27 | 1994-11-22 | Amylin Pharmaceuticals, Inc. | Amylin peptides |
| US5266561A (en) * | 1988-01-11 | 1993-11-30 | Amylin Pharmaceuticals, Inc. | Treatment of type 2 diabetes mellitus |
| US5175145A (en) * | 1988-08-26 | 1992-12-29 | Amylin Pharmaceuticals, Inc. | Treatment of diabetes mellitus with amylin agonists |
| US5321008A (en) * | 1991-01-10 | 1994-06-14 | Amylin Pharmaceuticals, Inc. | Methods and compositions for treatment of diabetes mellitus, hypoglycemia, and other conditions |
| US5234906A (en) * | 1991-01-10 | 1993-08-10 | Amylin Pharmaceuticals, Inc. | Hyperglycemic compositions |
| US5264372A (en) * | 1991-03-15 | 1993-11-23 | Amylin Pharmaceuticals, Inc. | Receptor-based screening methods for amylin agonists and antagonists |
| HU222249B1 (hu) * | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
| DE69232064T2 (de) * | 1991-11-19 | 2002-03-28 | Amylin Pharmaceuticals, Inc. | Peptide als Amylin-Agonisten und ihre Verwendung |
| US5376638A (en) * | 1992-09-01 | 1994-12-27 | Amylin Pharmaceuticals, Inc. | Methods for treating renin-related disorders with amylin antagonists |
| HUT73490A (en) * | 1993-09-07 | 1996-08-28 | Amylin Pharmaceuticals Inc | Methods for regulating gastrointestinal mobility |
| US6143718A (en) * | 1995-06-07 | 2000-11-07 | Amylin Pharmaceuticals, Inc. | Treatment of Type II diabetes mellutis with amylin agonists |
| US6087334A (en) | 1998-08-21 | 2000-07-11 | Amylin Pharmaceuticals, Inc. | Anti-diabetic peptides |
-
1995
- 1995-06-07 US US08/483,188 patent/US6143718A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 AU AU62685/96A patent/AU721489B2/en not_active Ceased
- 1996-06-07 HU HU9700368A patent/HUP9700368A3/hu unknown
- 1996-06-07 RU RU97104029/14A patent/RU2166958C2/ru not_active IP Right Cessation
- 1996-06-07 DE DE69625157T patent/DE69625157T2/de not_active Expired - Lifetime
- 1996-06-07 CA CA2196999A patent/CA2196999C/en not_active Expired - Fee Related
- 1996-06-07 EP EP96921467A patent/EP0772451B1/en not_active Expired - Lifetime
- 1996-06-07 JP JP50206197A patent/JP4009319B2/ja not_active Expired - Fee Related
- 1996-06-07 ES ES96921467T patent/ES2187659T3/es not_active Expired - Lifetime
- 1996-06-07 DK DK96921467T patent/DK0772451T3/da active
- 1996-06-07 ZA ZA9604838A patent/ZA964838B/xx unknown
- 1996-06-07 AT AT96921467T patent/ATE228849T1/de active
- 1996-06-07 CZ CZ1997337A patent/CZ289043B6/cs not_active IP Right Cessation
- 1996-06-07 IN IN1053CA1996 patent/IN181672B/en unknown
- 1996-06-07 WO PCT/US1996/009875 patent/WO1996040220A1/en not_active Ceased
- 1996-06-07 PT PT96921467T patent/PT772451E/pt unknown
- 1996-06-07 SK SK186-97A patent/SK18697A3/sk unknown
-
1997
- 1997-02-05 NO NO970519A patent/NO970519L/no unknown
- 1997-02-13 BG BG101230A patent/BG101230A/xx unknown
-
2000
- 2000-11-06 US US09/707,370 patent/US6417164B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| PT772451E (pt) | 2003-04-30 |
| US6143718A (en) | 2000-11-07 |
| WO1996040220A1 (en) | 1996-12-19 |
| CZ33797A3 (en) | 1997-07-16 |
| HUP9700368A2 (hu) | 1998-06-29 |
| CZ289043B6 (cs) | 2001-10-17 |
| NO970519L (no) | 1997-04-07 |
| IN181672B (enExample) | 1998-08-29 |
| ZA964838B (en) | 1997-02-24 |
| EP0772451B1 (en) | 2002-12-04 |
| RU2166958C2 (ru) | 2001-05-20 |
| SK18697A3 (en) | 1998-02-04 |
| HU9700368D0 (en) | 1997-04-28 |
| EP0772451A1 (en) | 1997-05-14 |
| ATE228849T1 (de) | 2002-12-15 |
| AU6268596A (en) | 1996-12-30 |
| BG101230A (en) | 1997-10-31 |
| DE69625157D1 (de) | 2003-01-16 |
| JPH10503785A (ja) | 1998-04-07 |
| EP0772451A4 (en) | 1998-09-30 |
| AU721489B2 (en) | 2000-07-06 |
| CA2196999C (en) | 2012-09-04 |
| NO970519D0 (no) | 1997-02-05 |
| CA2196999A1 (en) | 1996-12-19 |
| DE69625157T2 (de) | 2003-04-17 |
| US6417164B1 (en) | 2002-07-09 |
| ES2187659T3 (es) | 2003-06-16 |
| DK0772451T3 (da) | 2003-01-06 |
| HUP9700368A3 (en) | 2001-03-28 |
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