CA2716159A1 - Stable non-aqueous pharmaceutical compositions - Google Patents
Stable non-aqueous pharmaceutical compositions Download PDFInfo
- Publication number
- CA2716159A1 CA2716159A1 CA2716159A CA2716159A CA2716159A1 CA 2716159 A1 CA2716159 A1 CA 2716159A1 CA 2716159 A CA2716159 A CA 2716159A CA 2716159 A CA2716159 A CA 2716159A CA 2716159 A1 CA2716159 A1 CA 2716159A1
- Authority
- CA
- Canada
- Prior art keywords
- insulin
- polypeptide
- pharmaceutical composition
- composition according
- organic solvent
- 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.)
- Abandoned
Links
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- 150000001413 amino acids Chemical class 0.000 claims abstract description 77
- 239000003960 organic solvent Substances 0.000 claims abstract description 59
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 15
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Classifications
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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Landscapes
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
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- Cardiology (AREA)
- Obesity (AREA)
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- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07109435 | 2007-06-01 | ||
| EP07109435.3 | 2007-06-01 | ||
| EP07114524 | 2007-08-17 | ||
| EP07114524.7 | 2007-08-17 | ||
| PCT/EP2008/056689 WO2008145730A1 (en) | 2007-06-01 | 2008-05-30 | Stable non-aqueous pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2716159A1 true CA2716159A1 (en) | 2008-12-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2716159A Abandoned CA2716159A1 (en) | 2007-06-01 | 2008-05-30 | Stable non-aqueous pharmaceutical compositions |
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|---|---|
| US (3) | US20100190706A1 (cg-RX-API-DMAC7.html) |
| EP (4) | EP2164458A1 (cg-RX-API-DMAC7.html) |
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| KR (1) | KR20100017667A (cg-RX-API-DMAC7.html) |
| CN (1) | CN101677944A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2008257505B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0812354A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2716159A1 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2009012789A (cg-RX-API-DMAC7.html) |
| RU (1) | RU2472492C2 (cg-RX-API-DMAC7.html) |
| WO (2) | WO2008145732A1 (cg-RX-API-DMAC7.html) |
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| KR101729986B1 (ko) | 2006-09-22 | 2017-04-25 | 노보 노르디스크 에이/에스 | 프로테아제 내성 인슐린 유사체 |
| WO2008132224A2 (en) | 2007-04-30 | 2008-11-06 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
| KR20100017667A (ko) * | 2007-06-01 | 2010-02-16 | 노보 노르디스크 에이/에스 | 안정한 비-수성의 약학 조성물 |
| WO2009112583A2 (en) * | 2008-03-14 | 2009-09-17 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| DK2910570T3 (en) | 2008-03-18 | 2017-01-30 | Novo Nordisk As | Protease-stabilized acylated insulin analogues. |
| WO2011033019A1 (en) * | 2009-09-16 | 2011-03-24 | Novo Nordisk A/S | Stable non-aqueous liquid pharmaceutical compositions comprising an insulin |
| CA2782056C (en) | 2009-11-25 | 2021-03-09 | Arisgen Sa | Mucosal delivery of peptides |
| MX2012007806A (es) * | 2010-01-12 | 2012-08-01 | Novo Nordisk As | Composiciones farmaceuticas para administracion oral de peptidos de insulina. |
| WO2011094632A1 (en) * | 2010-01-29 | 2011-08-04 | The Uab Research Foundation | Method for administration of insulin and pharmaceutical composition thereof |
| US20130157939A1 (en) * | 2010-08-23 | 2013-06-20 | Shmuel Ben-Sasson | Compositions for gastric delivery of active agents |
| EP2526971A1 (en) | 2011-05-25 | 2012-11-28 | ArisGen SA | Mucosal delivery of drugs |
| US9481721B2 (en) | 2012-04-11 | 2016-11-01 | Novo Nordisk A/S | Insulin formulations |
| US8853189B2 (en) | 2012-05-31 | 2014-10-07 | Prima Innovations, Llc | Antispasmodic 1,2-Diols and 1,2,3-triols |
| US9956287B2 (en) | 2013-02-06 | 2018-05-01 | Perosphere Inc. | Stable glucagon formulations |
| MX366636B (es) | 2013-10-07 | 2019-07-17 | Novo Nordisk As | Nuevo derivado de un análogo de insulina. |
| EP2946788A1 (en) | 2014-05-23 | 2015-11-25 | Immundiagnostik AG | Method and composition for treating heart failure with preserved ejection fraction |
| EP3154568A4 (en) * | 2014-06-10 | 2018-01-24 | California Institute of Technology | Non-canonical insulins and their uses |
| ES2841933T3 (es) | 2014-10-31 | 2021-07-12 | Univ Monash | Formulación en polvo |
| TWI700091B (zh) | 2016-12-16 | 2020-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 含胰島素醫藥組成物 |
| US20200155648A1 (en) * | 2017-06-28 | 2020-05-21 | Children's Medical Center Corporation | Promoting lung growth |
| EP3915571A1 (en) * | 2020-05-29 | 2021-12-01 | Adocia | Pharmaceutical composition in the form of an injectable aqueous solution including at least a rapid acting insulin analog and a glucagon suppressor with prandial action |
| CN114432424B (zh) * | 2021-12-27 | 2023-06-27 | 南通联亚药业股份有限公司 | 一种稳定的铝塑包装去氨加压素片剂 |
| CN117045634B (zh) * | 2022-05-06 | 2025-10-10 | 北京康蒂尼药业股份有限公司 | 一种二肽衍生物组合物及其制备方法和用途 |
| EP4628092A1 (en) * | 2022-12-04 | 2025-10-08 | OOO "Geropharm" | Insulin aspart composition (embodiments) |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6074A (en) | 1849-01-30 | Machine fob making suspender-buckles | ||
| US4468A (en) | 1846-04-25 | Improvement in casting spoons | ||
| US3003A (en) * | 1843-03-17 | Improvement in the method of propelling vessels by means of continuous streams of water | ||
| US221A (en) | 1837-06-03 | Steam-boii | ||
| US2832685A (en) * | 1952-05-24 | 1958-04-29 | Crest Foods Co Inc | Solubilization of milk proteins |
| US3528960A (en) * | 1968-10-07 | 1970-09-15 | Lilly Co Eli | N-carboxyaroyl insulins |
| US3869437A (en) * | 1970-05-08 | 1975-03-04 | Nat Res Dev | Mono-, di, and N{HD A1{B , N{HU B1{B , N{HU B29{B -tri-acylated insulin |
| US3950517A (en) * | 1970-05-08 | 1976-04-13 | National Research Development Corporation | Insulin derivatives |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4033941A (en) * | 1975-12-17 | 1977-07-05 | Eli Lilly And Company | Process for purifying glucagon |
| JPS6030650B2 (ja) * | 1979-10-26 | 1985-07-17 | 日本油脂株式会社 | 座薬基剤組成物 |
| US4468221A (en) | 1981-04-10 | 1984-08-28 | Parker-Hannifin Corporation | Medication infusion pump |
| US4839341A (en) * | 1984-05-29 | 1989-06-13 | Eli Lilly And Company | Stabilized insulin formulations |
| PH25772A (en) | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| US4719655A (en) * | 1986-01-21 | 1988-01-19 | Dean S Brooks | Invalid transfer device |
| US4849227A (en) * | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
| US5266310A (en) * | 1987-09-17 | 1993-11-30 | Boehringer Ingelheim International Gmbh | Stabilization of therapeutically active proteins in pharmaceutical preparations |
| DE3837825A1 (de) | 1988-11-08 | 1990-05-10 | Hoechst Ag | Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung |
| HUT56857A (en) | 1988-12-23 | 1991-10-28 | Novo Nordisk As | Human insulin analogues |
| DE3844211A1 (de) * | 1988-12-29 | 1990-07-05 | Hoechst Ag | Neue insulinderivate, verfahren zu deren herstellung, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung |
| IL93282A (en) | 1989-02-09 | 1995-08-31 | Lilly Co Eli | Insulin analogues |
| US5514646A (en) * | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| AU628674B2 (en) * | 1989-10-19 | 1992-09-17 | Nippon Oil And Fats Company, Limited | Polymer complexes of a sugar response type |
| US5179189A (en) * | 1990-01-19 | 1993-01-12 | Nova Pharmaceutical Corporation | Fatty acid terminated polyanhydrides |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
| AU5171293A (en) * | 1992-10-14 | 1994-05-09 | Regents Of The University Of Colorado, The | Ion-pairing of drugs for improved efficacy and delivery |
| US5589167A (en) * | 1993-02-23 | 1996-12-31 | Genentech, Inc. | Excipient stabilization of polypeptides treated with organic solvents |
| US5359030A (en) * | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
| DE69416409T2 (de) | 1993-06-21 | 1999-09-16 | Novo Nordisk A/S, Bagsvaerd | Asp-b28-insulinkristalle |
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| PT792290E (pt) | 1993-09-17 | 2002-01-30 | Novo Nordisk As | Insulina acilada |
| US6869930B1 (en) * | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| US6011007A (en) | 1993-09-17 | 2000-01-04 | Novo Nordisk A/S | Acylated insulin |
| US5504188A (en) | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US6500645B1 (en) * | 1994-06-17 | 2002-12-31 | Novo Nordisk A/S | N-terminally extended proteins expressed in yeast |
| US5693609A (en) * | 1994-11-17 | 1997-12-02 | Eli Lilly And Company | Acylated insulin analogs |
| US6251856B1 (en) * | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| US20030104981A1 (en) * | 1995-11-03 | 2003-06-05 | Jelena Mandic | Human insulin analogues |
| US5858001A (en) | 1995-12-11 | 1999-01-12 | Elan Medical Technologies Limited | Cartridge-based drug delivery device |
| US6451970B1 (en) * | 1996-02-21 | 2002-09-17 | Novo Nordisk A/S | Peptide derivatives |
| US5981489A (en) * | 1996-07-18 | 1999-11-09 | Alza Corporation | Non-aqueous protic peptide formulations |
| EP0821006B1 (de) * | 1996-07-26 | 2004-04-21 | Aventis Pharma Deutschland GmbH | Insulinderivate mit erhöhter Zinkbindung |
| US5898067A (en) * | 1997-02-07 | 1999-04-27 | Novo Nordisk A/S | Crystallization of proteins |
| US5957895A (en) | 1998-02-20 | 1999-09-28 | Becton Dickinson And Company | Low-profile automatic injection device with self-emptying reservoir |
| TW570805B (en) * | 1998-09-01 | 2004-01-11 | Hoffmann La Roche | Water-soluble pharmaceutical composition in an ionic complex |
| US7030083B2 (en) * | 1998-09-09 | 2006-04-18 | University Of Washington | Treatment of eclampsia and preeclampsia |
| US6660715B2 (en) * | 1998-11-19 | 2003-12-09 | Massachusetts Institute Of Technology | Nonaqueous solutions and suspensions of macromolecules for pulmonary delivery |
| US7425541B2 (en) * | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
| WO2000047203A1 (en) * | 1999-02-12 | 2000-08-17 | Mqs, Inc. | Formulation and system for intra-oral delivery of pharmaceutical agents |
| CN1141974C (zh) * | 2000-06-07 | 2004-03-17 | 张昊 | 结肠定位释放的口服生物制剂 |
| US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) * | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| CN1160122C (zh) * | 2001-04-20 | 2004-08-04 | 清华大学 | 一种制备口服胰岛素油相制剂的方法 |
| US6828297B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| EP1423136A4 (en) * | 2001-08-10 | 2007-07-25 | Epix Pharm Inc | POLYPEPTIDE CONJUGATES HAVING INCREASED CIRCULATION HALF-VIES |
| US6770625B2 (en) * | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| AU2002314790A1 (en) * | 2001-12-05 | 2003-06-23 | Dow Global Technologies Inc. | Method for immobilizing a biologic in a polyurethane-hydrogel composition, a composition prepared from the method, and biomedical applications |
| UA46669C2 (uk) * | 2001-12-29 | 2005-12-15 | Товариство З Обмеженою Відповідальністю "Мако" | Спосіб приготування готової лікарської форми інсуліну пролонгованої дії |
| GB2386601B (en) | 2002-03-18 | 2005-12-21 | Bespak Plc | Seal material for a dispensing apparatus |
| WO2003105768A2 (en) * | 2002-06-13 | 2003-12-24 | Nobex Corporation | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| EP1545526A4 (en) * | 2002-09-17 | 2009-09-23 | Merck & Co Inc | REMOVAL OF ALDEHYDE POLLUTION BY REACTIVE POLYSTYRENE RESIN |
| JP2007524592A (ja) * | 2003-06-03 | 2007-08-30 | ノボ・ノルデイスク・エー／エス | 安定化された薬学的ペプチド組成物 |
| BRPI0413276B8 (pt) * | 2003-08-05 | 2021-05-25 | Novo Nordisk As | derivado de insulina, complexo de zinco do mesmo, e, composição farmacêutica |
| AU2004290862B2 (en) * | 2003-11-20 | 2010-06-03 | Novo Nordisk A/S | Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices |
| AU2004295023A1 (en) | 2003-12-03 | 2005-06-16 | Novo Nordisk A/S | Single-chain insulin |
| WO2005058961A2 (en) * | 2003-12-12 | 2005-06-30 | Amgen Inc. | Antibodies specific for human galanin, and uses thereof |
| KR20070044805A (ko) * | 2004-04-15 | 2007-04-30 | 키아스마, 인코포레이티드 | 생물학적 장벽 투과를 촉진시킬 수 있는 조성물 |
| WO2005115441A2 (en) * | 2004-05-10 | 2005-12-08 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of parathyroid hormone |
| KR101309770B1 (ko) * | 2004-07-19 | 2013-09-30 | 바이오콘 리미티드 | 인슐린―올리고머 접합체，제형 및 이들의 용도 |
| JP2008510692A (ja) | 2004-08-20 | 2008-04-10 | ノボ ノルディスク アクティーゼルスカブ | 薬学的に活性なインスリン受容体調節分子 |
| AU2006235183B2 (en) * | 2005-04-08 | 2011-02-10 | Amylin Pharmaceuticals, Llc | Pharmaceutical formulations comprising incretin peptide and aprotic polar solvent |
| WO2007004948A1 (en) * | 2005-06-30 | 2007-01-11 | Astrazeneca Ab | Environmental detector |
| US20100210506A1 (en) * | 2005-10-20 | 2010-08-19 | Mdrna, Inc. | Intranasal administration of rapid acting insulin |
| KR101729986B1 (ko) | 2006-09-22 | 2017-04-25 | 노보 노르디스크 에이/에스 | 프로테아제 내성 인슐린 유사체 |
| KR20100017667A (ko) * | 2007-06-01 | 2010-02-16 | 노보 노르디스크 에이/에스 | 안정한 비-수성의 약학 조성물 |
| US20090087484A1 (en) * | 2007-09-28 | 2009-04-02 | Alza Corporation | Formulation and dosage form for increasing oral bioavailability of hydrophilic macromolecules |
| US20110293714A1 (en) * | 2008-11-28 | 2011-12-01 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
-
2008
- 2008-05-30 KR KR1020097025474A patent/KR20100017667A/ko not_active Abandoned
- 2008-05-30 EP EP08760278A patent/EP2164458A1/en not_active Withdrawn
- 2008-05-30 BR BRPI0812354-3A2A patent/BRPI0812354A2/pt not_active Application Discontinuation
- 2008-05-30 EP EP08760287A patent/EP2164459A1/en not_active Withdrawn
- 2008-05-30 JP JP2010509834A patent/JP5628026B2/ja not_active Expired - Fee Related
- 2008-05-30 RU RU2009146883/15A patent/RU2472492C2/ru not_active IP Right Cessation
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- 2008-05-30 US US12/601,345 patent/US20100190706A1/en not_active Abandoned
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- 2008-05-30 EP EP12159415A patent/EP2497462A1/en not_active Withdrawn
- 2008-05-30 CA CA2716159A patent/CA2716159A1/en not_active Abandoned
- 2008-05-30 WO PCT/EP2008/056699 patent/WO2008145732A1/en not_active Ceased
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2014
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Also Published As
| Publication number | Publication date |
|---|---|
| JP5675347B2 (ja) | 2015-02-25 |
| BRPI0812354A2 (pt) | 2015-01-27 |
| JP5628026B2 (ja) | 2014-11-19 |
| EP2164459A1 (en) | 2010-03-24 |
| EP2164458A1 (en) | 2010-03-24 |
| AU2008257505B2 (en) | 2013-05-16 |
| EP2514407A1 (en) | 2012-10-24 |
| CN101677944A (zh) | 2010-03-24 |
| JP2010529004A (ja) | 2010-08-26 |
| MX2009012789A (es) | 2009-12-10 |
| EP2497462A1 (en) | 2012-09-12 |
| KR20100017667A (ko) | 2010-02-16 |
| WO2008145732A1 (en) | 2008-12-04 |
| US20100144592A1 (en) | 2010-06-10 |
| US20140349924A1 (en) | 2014-11-27 |
| RU2009146883A (ru) | 2011-07-20 |
| WO2008145730A1 (en) | 2008-12-04 |
| JP2010529956A (ja) | 2010-09-02 |
| RU2472492C2 (ru) | 2013-01-20 |
| AU2008257505A1 (en) | 2008-12-04 |
| US20100190706A1 (en) | 2010-07-29 |
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