JP5518282B2 - 安定なペプチドの製剤 - Google Patents
安定なペプチドの製剤 Download PDFInfo
- Publication number
- JP5518282B2 JP5518282B2 JP2006525045A JP2006525045A JP5518282B2 JP 5518282 B2 JP5518282 B2 JP 5518282B2 JP 2006525045 A JP2006525045 A JP 2006525045A JP 2006525045 A JP2006525045 A JP 2006525045A JP 5518282 B2 JP5518282 B2 JP 5518282B2
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- Prior art keywords
- glp
- peptide
- val
- formulation
- pharmaceutical composition
- 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 - Fee Related
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- 239000000203 mixture Substances 0.000 title claims description 57
- 238000009472 formulation Methods 0.000 title claims description 50
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
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- Diabetes (AREA)
- Endocrinology (AREA)
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- Organic Chemistry (AREA)
- Obesity (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200301239 | 2003-09-01 | ||
| DKPA200301239 | 2003-09-01 | ||
| US50115703P | 2003-09-08 | 2003-09-08 | |
| US60/501,157 | 2003-09-08 | ||
| PCT/DK2004/000576 WO2005021022A2 (en) | 2003-09-01 | 2004-08-31 | Stable formulations of peptides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007504178A JP2007504178A (ja) | 2007-03-01 |
| JP2007504178A5 JP2007504178A5 (https=) | 2011-03-03 |
| JP5518282B2 true JP5518282B2 (ja) | 2014-06-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006525045A Expired - Fee Related JP5518282B2 (ja) | 2003-09-01 | 2004-08-31 | 安定なペプチドの製剤 |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1663295A2 (https=) |
| JP (1) | JP5518282B2 (https=) |
| WO (1) | WO2005021022A2 (https=) |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA06001283A (es) | 2003-08-05 | 2006-04-11 | Novo Nordisk As | Derivados de insulina novedosos. |
| US9649382B2 (en) | 2005-01-14 | 2017-05-16 | Camurus Ab | Topical bioadhesive formulations |
| US9757461B2 (en) | 2005-01-14 | 2017-09-12 | Camurus Ab | GnRH analogue formulations |
| ATE501710T1 (de) | 2005-01-14 | 2011-04-15 | Camurus Ab | Somatostatin-analog-formulierungen |
| KR101245022B1 (ko) | 2005-01-21 | 2013-03-19 | 카무러스 에이비 | 약제학적 지질 조성물 |
| CA2609810C (en) | 2005-06-06 | 2012-05-22 | Camurus Ab | Glp-1 analogue formulations |
| JP4808785B2 (ja) | 2005-12-28 | 2011-11-02 | ノボ・ノルデイスク・エー／エス | インスリン組成物および組成物の製造方法 |
| US9034818B2 (en) | 2007-06-13 | 2015-05-19 | Novo Nordisk A/S | Pharmaceutical formulations comprising an insulin derivative |
| GB0711656D0 (en) | 2007-06-15 | 2007-07-25 | Camurus Ab | Formulations |
| GB0716385D0 (en) | 2007-08-22 | 2007-10-03 | Camurus Ab | Formulations |
| GB0815435D0 (en) | 2008-08-22 | 2008-10-01 | Camurus Ab | Formulations |
| CN102256618A (zh) | 2008-10-17 | 2011-11-23 | 赛诺菲-安万特德国有限公司 | 胰岛素和glp-1激动剂的组合 |
| AU2009309623B9 (en) | 2008-10-30 | 2014-10-02 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| US8903364B2 (en) | 2009-01-16 | 2014-12-02 | Broadcom Corporation | Method and system for processing and delivery of multimedia content by an integrated femtocell and set-top-box device |
| US9060098B2 (en) | 2009-01-16 | 2015-06-16 | Broadcom Corporation | Method and system for data processing in a device with integrated set-top-box and femtocell functionality |
| US20100210239A1 (en) | 2009-02-17 | 2010-08-19 | Jeyhan Karaoguz | Service mobility via a femtocell infrastructure |
| US9049652B2 (en) | 2009-02-27 | 2015-06-02 | Broadcom Corporation | Method and system for controlling access and utilization of femtocells via a network based service |
| US8855048B2 (en) | 2009-02-27 | 2014-10-07 | Broadcom Corporation | Method and system for peer-to-peer cellular communications |
| US8259617B2 (en) | 2009-03-18 | 2012-09-04 | Broadcom Corporation | Method and system for timely delivery of multimedia content via a femtocell |
| EP2435061A4 (en) | 2009-05-28 | 2013-03-27 | Amylin Pharmaceuticals Inc | DAMPING GLP-1 RECEPTOR AGONIST COMPOUNDS |
| PL2451437T3 (pl) | 2009-07-06 | 2017-05-31 | Sanofi-Aventis Deutschland Gmbh | Wodne preparaty insuliny zawierające metioninę |
| EP2496249B1 (en) | 2009-11-03 | 2016-03-09 | Amylin Pharmaceuticals, LLC | Glp-1 receptor agonist for use in treating obstructive sleep apnea |
| DE102010011919A1 (de) | 2010-03-18 | 2011-09-22 | Sanofi-Aventis Deutschland Gmbh | Pharmazeutische Zusammensetzung umfassend einen GLP-1-Agonisten und Methionin |
| TR201809460T4 (tr) | 2009-11-13 | 2018-07-23 | Sanofi Aventis Deutschland | Bir GLP- 1-agonisti, bir insülin ve metiyonin içeren farmasötik bileşim. |
| NZ599847A (en) | 2009-11-13 | 2013-09-27 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a glp-1 agonist and methionine |
| WO2012028172A1 (en) | 2010-08-30 | 2012-03-08 | Sanofi-Aventis Deutschland Gmbh | Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2 |
| DK2632478T3 (da) | 2010-10-27 | 2019-10-07 | Novo Nordisk As | Behandling af diabetes melitus under anvendelse af insulinindsprøjtninger indgivet med varierende indsprøjtningsintervaller |
| JP2014504588A (ja) | 2010-12-22 | 2014-02-24 | アミリン・ファーマシューティカルズ，リミテッド・ライアビリティ・カンパニー | 膵島細胞移植のためのｇｌｐ−１受容体アゴニスト |
| 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 |
| AR087693A1 (es) | 2011-08-29 | 2014-04-09 | Sanofi Aventis Deutschland | Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| ES2834318T3 (es) | 2012-05-25 | 2021-06-17 | Camurus Ab | Formulaciones de agonistas de receptores de la somatostatina |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| HK1211232A1 (en) | 2012-12-21 | 2016-05-20 | Sanofi | Exendin-4 derivatives as dual glp1/gip or trigonal glp1/gip/glucagon agonists |
| TWI780236B (zh) | 2013-02-04 | 2022-10-11 | 法商賽諾菲公司 | 胰島素類似物及/或胰島素衍生物之穩定化醫藥調配物 |
| JP2016519127A (ja) | 2013-04-30 | 2016-06-30 | ノヴォ ノルディスク アー／エス | 新規投与レジメン |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| TW201609799A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重ｇｌｐ－１／ｇｉｐ受體促效劑 |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| US9895423B2 (en) | 2014-01-09 | 2018-02-20 | Sanofi | Stabilized pharmaceutical formulations of insulin aspart |
| CN105960249B (zh) | 2014-01-09 | 2021-03-16 | 赛诺菲 | 胰岛素类似物和/或胰岛素衍生物的稳定化药物制剂 |
| JP6723921B2 (ja) | 2014-01-09 | 2020-07-15 | サノフイＳａｎｏｆｉ | インスリンアナログおよび／またはインスリン誘導体の、グリセリンを含まない安定化された医薬製剤 |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| PE20171622A1 (es) | 2014-12-12 | 2017-11-02 | Sanofi Aventis Deutschland | Formulacion de relacion fija de insulina glargina/lixisenatida |
| 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 |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
| KR102844773B1 (ko) | 2015-12-23 | 2025-08-13 | 암젠 인크 | 위 억제 펩티드 수용체 (gipr)에 대한 결합 단백질을 glp-1 효능제와 조합하여 사용하여 대사 장애를 치료하거나 개선시키는 방법 |
| BR112019014588A2 (pt) | 2017-01-17 | 2020-02-18 | Amgen Inc. | Método de tratamento ou amenização de distúrbios metabólicos usando agonistas do receptor de glp-1 conjugados a antagonistas para receptor do peptídeo inibidor gástrico (gipr) |
| CN110831969B (zh) | 2017-06-20 | 2024-06-21 | 安进公司 | 使用抑胃肽受体（gipr）结合蛋白与glp-1激动剂的组合治疗或改善代谢障碍的方法 |
| MX2019015544A (es) | 2017-06-21 | 2020-07-28 | Amgen Inc | Metodo para tratar o mejorar trastornos metabolicos con proteinas de fusion de agonistas del receptor de glp-1/proteinas de union antagonistas para el receptor peptidico inhibidor gastrico (gipr). |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| WO2020026471A1 (ja) * | 2018-07-31 | 2020-02-06 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| JP6612004B1 (ja) * | 2018-07-31 | 2019-11-27 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| US12343383B2 (en) | 2019-07-12 | 2025-07-01 | Novo Nordisk A/S | High concentration insulin formulation |
| GB201917723D0 (en) | 2019-12-04 | 2020-01-15 | Nv Rose Llc | Stable liquid formulations of glucagon-like peptide 1 or analogues thereof |
| US20240336669A1 (en) | 2020-12-11 | 2024-10-10 | Ip21Po Innovations Limteed | Novel compounds |
| TW202241492A (zh) * | 2020-12-16 | 2022-11-01 | 丹麥商西蘭製藥公司 | Ｇｌｐ－１／ｇｌｐ－２雙重促效劑之醫藥組合物 |
| WO2022140373A1 (en) * | 2020-12-22 | 2022-06-30 | Eli Lilly And Company | Therapeutic peptide formulations |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6380357B2 (en) * | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
| NZ512663A (en) * | 1999-01-14 | 2004-05-28 | Amylin Pharmaceuticals Inc | Novel exendin agonist formulations and methods of administration thereof |
| GB9930882D0 (en) * | 1999-12-30 | 2000-02-23 | Nps Allelix Corp | GLP-2 formulations |
| EP1351984A2 (en) * | 2000-12-13 | 2003-10-15 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
| US7259233B2 (en) * | 2000-12-13 | 2007-08-21 | Eli Lilly And Company | Chronic treatment regimen using glucagon-like insulinotropic peptides |
| AU2002316811A1 (en) * | 2001-06-28 | 2003-03-03 | Novo Nordisk A/S | Stable formulation of modified glp-1 |
| EP1631308B1 (en) * | 2003-05-30 | 2013-07-31 | Amylin Pharmaceuticals, LLC | Novel methods and compositions for enhanced transmucosal delivery of peptides and proteins |
-
2004
- 2004-08-31 JP JP2006525045A patent/JP5518282B2/ja not_active Expired - Fee Related
- 2004-08-31 EP EP04762796A patent/EP1663295A2/en not_active Withdrawn
- 2004-08-31 WO PCT/DK2004/000576 patent/WO2005021022A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP1663295A2 (en) | 2006-06-07 |
| WO2005021022A3 (en) | 2005-06-30 |
| JP2007504178A (ja) | 2007-03-01 |
| WO2005021022A2 (en) | 2005-03-10 |
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