NO322514B1 - Stabile, ikke-vandige formuleringer av en LHRH-beslektet peptidforbindelse og fremgangsmater for fremstilling av disse. - Google Patents
Stabile, ikke-vandige formuleringer av en LHRH-beslektet peptidforbindelse og fremgangsmater for fremstilling av disse. Download PDFInfo
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- NO322514B1 NO322514B1 NO19986207A NO986207A NO322514B1 NO 322514 B1 NO322514 B1 NO 322514B1 NO 19986207 A NO19986207 A NO 19986207A NO 986207 A NO986207 A NO 986207A NO 322514 B1 NO322514 B1 NO 322514B1
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- Norway
- Prior art keywords
- formulations
- leuprolide
- lhrh
- dmso
- stable
- Prior art date
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- BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
- 229960004309 nafarelin acetate Drugs 0.000 description 1
- 229910052757 nitrogen Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
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- 239000002798 polar solvent Substances 0.000 description 1
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- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 208000006155 precocious puberty Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Reproductive Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2269996P | 1996-07-03 | 1996-07-03 | |
| PCT/US1997/011450 WO1998000158A1 (en) | 1996-07-03 | 1997-07-01 | Non-aqueous polar aprotic peptide formulations |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO986207D0 NO986207D0 (no) | 1998-12-30 |
| NO986207L NO986207L (no) | 1999-03-03 |
| NO322514B1 true NO322514B1 (no) | 2006-10-16 |
Family
ID=21810971
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19986207A NO322514B1 (no) | 1996-07-03 | 1998-12-30 | Stabile, ikke-vandige formuleringer av en LHRH-beslektet peptidforbindelse og fremgangsmater for fremstilling av disse. |
| NO20063870A NO20063870L (no) | 1996-07-03 | 2006-08-30 | Anvendelse av stabile, ikke-vandige formuleringer av en LHRH-beslektet peptidforbindelse |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20063870A NO20063870L (no) | 1996-07-03 | 2006-08-30 | Anvendelse av stabile, ikke-vandige formuleringer av en LHRH-beslektet peptidforbindelse |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US5932547A (da) |
| EP (2) | EP0921808B1 (da) |
| JP (2) | JP2000515131A (da) |
| CN (4) | CN101116742A (da) |
| AR (1) | AR007714A1 (da) |
| AT (2) | ATE263570T1 (da) |
| AU (1) | AU739169B2 (da) |
| BR (1) | BR9710132A (da) |
| CA (1) | CA2259557A1 (da) |
| CO (1) | CO4870762A1 (da) |
| CY (1) | CY2486B1 (da) |
| CZ (2) | CZ299464B6 (da) |
| DE (2) | DE69715639T2 (da) |
| DK (2) | DK1208846T3 (da) |
| ES (2) | ES2181010T3 (da) |
| HU (1) | HUP9904270A3 (da) |
| ID (2) | ID19718A (da) |
| IL (3) | IL127771A0 (da) |
| MY (1) | MY128850A (da) |
| NO (2) | NO322514B1 (da) |
| NZ (1) | NZ333294A (da) |
| PL (1) | PL189015B1 (da) |
| PT (2) | PT921808E (da) |
| RO (1) | RO119863B1 (da) |
| RU (1) | RU2203084C2 (da) |
| SK (1) | SK283926B6 (da) |
| TW (1) | TW584562B (da) |
| WO (1) | WO1998000158A1 (da) |
| ZA (1) | ZA975941B (da) |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932547A (en) * | 1996-07-03 | 1999-08-03 | Alza Corporation | Non-aqueous polar aprotic peptide formulations |
| MY125870A (en) * | 1997-07-25 | 2006-08-30 | Alza Corp | Osmotic delivery system flow modulator apparatus and method |
| GB2344287A (en) * | 1998-12-03 | 2000-06-07 | Ferring Bv | Controlled release pharmaceutical formulation |
| US7919109B2 (en) | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
| US7258869B1 (en) * | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
| US7658938B2 (en) * | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
| US20070148228A1 (en) * | 1999-02-22 | 2007-06-28 | Merrion Research I Limited | Solid oral dosage form containing an enhancer |
| US8119159B2 (en) * | 1999-02-22 | 2012-02-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| DE60115005T2 (de) | 2000-04-19 | 2006-07-27 | Genentech Inc., San Francisco | Formulierungen mit verzögerter freisetzung enthaltend wachstumshormon |
| US8470359B2 (en) | 2000-11-13 | 2013-06-25 | Qlt Usa, Inc. | Sustained release polymer |
| IL157531A0 (en) * | 2001-02-23 | 2004-03-28 | Genentech Inc | Erodible polymers for injection |
| ES2554106T3 (es) * | 2001-06-21 | 2015-12-16 | Genentech, Inc. | Formulación de liberación sostenida |
| ES2545090T3 (es) | 2001-12-21 | 2015-09-08 | Human Genome Sciences, Inc. | Proteínas de fusión de albúmina y GCSF |
| CA2472956A1 (en) * | 2002-02-14 | 2003-08-21 | Bayer Pharmaceuticals Corporation | Formulation strategies in stabilizing peptides in organic solvents and in dried states |
| MY135711A (en) * | 2002-06-17 | 2008-06-30 | Alza Corp | Osmotic delivery system with early zero order push power engine |
| RU2342118C2 (ru) * | 2002-12-19 | 2008-12-27 | Алза Корпорейшн | Стабильные неводные однофазные гели и композиции на их основе для доставки из имплантируемого устройства |
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| US8110209B2 (en) | 2002-12-20 | 2012-02-07 | Xeris Pharmaceuticals Inc. | Intracutaneous injection |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| AR043810A1 (es) * | 2003-03-31 | 2005-08-17 | Alza Corp | Sistema osmotico de administracion y metodo para disminuir los tiempos de llegada al regimen de funcionamiento en los sistemas osmoticos de administracion |
| MXPA05010605A (es) * | 2003-03-31 | 2005-11-23 | Alza Corp | Bomba osmotica con medios para disipar la presion interna. |
| WO2004096176A2 (en) * | 2003-04-25 | 2004-11-11 | Boston Scientific Scimed Inc. | Solid drug formulation and device for storage and controlled delivery thereof |
| EP1631308B1 (en) * | 2003-05-30 | 2013-07-31 | Amylin Pharmaceuticals, LLC | Novel methods and compositions for enhanced transmucosal delivery of peptides and proteins |
| CN1905861A (zh) * | 2003-10-31 | 2007-01-31 | 阿尔扎公司 | 具有自保持、快启动薄膜插塞的渗透泵 |
| EP1694310A2 (en) * | 2003-11-06 | 2006-08-30 | Alza Corporation | Modular imbibition rate reducer for use with implantable osmotic pump |
| FI116942B (fi) * | 2004-05-10 | 2006-04-13 | Biohit Oyj | Proteiini- ja peptidistabilointi |
| US20050266087A1 (en) * | 2004-05-25 | 2005-12-01 | Gunjan Junnarkar | Formulations having increased stability during transition from hydrophobic vehicle to hydrophilic medium |
| US20060039949A1 (en) * | 2004-08-20 | 2006-02-23 | Nycz Jeffrey H | Acetabular cup with controlled release of an osteoinductive formulation |
| US20060045902A1 (en) * | 2004-09-01 | 2006-03-02 | Serbousek Jon C | Polymeric wrap for in vivo delivery of osteoinductive formulations |
| US20060057184A1 (en) * | 2004-09-16 | 2006-03-16 | Nycz Jeffrey H | Process to treat avascular necrosis (AVN) with osteoinductive materials |
| US8137664B2 (en) * | 2005-02-02 | 2012-03-20 | Sdgi Holdings, Inc. | Method and kit for repairing a defect in bone |
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| US20060263433A1 (en) * | 2005-02-03 | 2006-11-23 | Ayer Rupal A | Suspension formulation of interferon |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| US7959938B2 (en) * | 2005-03-15 | 2011-06-14 | Intarcia Therapeutics, Inc. | Polyoxaester suspending vehicles for use with implantable delivery systems |
| WO2006110551A2 (en) * | 2005-04-08 | 2006-10-19 | Amylin Pharmaceuticals, Inc. | Pharmaceutical formulations comprising incretin peptide and aprotic polar solvent |
| US20070015689A1 (en) * | 2005-06-23 | 2007-01-18 | Alza Corporation | Complexation of metal ions with polypeptides |
| BRPI0620268B8 (pt) * | 2005-12-22 | 2021-05-25 | Oakwood Laboratories LLC | composição eficaz como sistema de fornecimento para liberação controlada, seu uso, seu método de fabricação, e método para proteger um agente biologicamente ativo |
| MX2008012678A (es) * | 2006-04-07 | 2008-12-17 | Merrion Res Iii Ltd | Forma de dosis oral solida que contiene un mejorador. |
| MX2008014870A (es) | 2006-05-30 | 2009-02-12 | Intarcia Therapeutics Inc | Modulador de flujo para sistema de suministro osmotico con canal interno de dos piezas. |
| CA2654566A1 (en) * | 2006-06-09 | 2007-12-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| EP2363112B8 (en) * | 2006-08-09 | 2018-11-21 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
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| CA2691531C (en) | 2007-06-22 | 2016-11-01 | Board Of Regents,The University Of Texas System | Formation of stable submicron peptide or protein particles by thin film freezing |
| JP2010539015A (ja) * | 2007-09-11 | 2010-12-16 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | 治療剤としての、ＩＬ−１レセプターペプチド単独またはＤ−Ａｌａ−Ｇｌｎ−オクタデシルエステルとの組合せの使用 |
| US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| MX2010012201A (es) * | 2008-05-07 | 2011-05-30 | Merrion Res Iii Ltd | Composiciones de péptidos y procedimientos de preparación de las mismas. |
| US20100015240A1 (en) * | 2008-07-16 | 2010-01-21 | Danielle Biggs | Process for preparing microparticles containing bioactive peptides |
| CN109010254A (zh) | 2008-08-15 | 2018-12-18 | 硬木药品公司 | 适合口服给药的鸟苷酸环化酶-c受体激动剂多肽的稳定的固体制剂 |
| EP2161030A1 (en) * | 2008-09-09 | 2010-03-10 | Rijksuniversiteit te Groningen | Oxytocin formulations and uses thereof |
| CN106880596A (zh) * | 2008-10-15 | 2017-06-23 | 精达制药公司 | 高浓缩药物颗粒、制剂、混悬剂及其应用 |
| CA2743789C (en) | 2008-11-16 | 2017-10-31 | Board Of Regents, The Univesity Of Texas System | Low viscosity highly concentrated suspensions |
| JP2012518686A (ja) * | 2009-02-25 | 2012-08-16 | メリオン・リサーチ・Ｉｉｉ・リミテッド | ビスホスホネート類の組成物および薬物送達 |
| JP2013501071A (ja) | 2009-08-06 | 2013-01-10 | アイロンウッド ファーマシューティカルズ， インコーポレイテッド | リナクロチドを含む処方物 |
| AU2010298733B2 (en) | 2009-09-28 | 2014-10-09 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
| US20110182985A1 (en) * | 2010-01-28 | 2011-07-28 | Coughlan David C | Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof |
| EP2536742B1 (en) | 2010-02-17 | 2017-07-19 | Ironwood Pharmaceuticals, Inc. | Treatments for gastrointestinal disorders |
| US9089484B2 (en) * | 2010-03-26 | 2015-07-28 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor Xa inhibitors for oral administration |
| US20120046225A1 (en) | 2010-07-19 | 2012-02-23 | The Regents Of The University Of Colorado, A Body Corporate | Stable glucagon formulations for the treatment of hypoglycemia |
| ES2919136T3 (es) | 2010-08-11 | 2022-07-22 | Ironwood Pharmaceuticals Inc | Formulaciones estables de linaclotida |
| WO2012094598A2 (en) | 2011-01-07 | 2012-07-12 | Merrion Research Iii Limited | Pharmaceutical compositions of iron for oral administration |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| MX342675B (es) | 2011-03-10 | 2016-10-07 | Xeris Pharmaceuticals Inc | Formulaciones estables para inyeccion parenteral de farmacos de peptido. |
| HUE032237T2 (en) | 2011-08-17 | 2017-09-28 | Ironwood Pharmaceuticals Inc | Treatment of gastrointestinal disorders |
| EA027744B1 (ru) * | 2011-10-31 | 2017-08-31 | Ксерис Фармасьютикалс, Инк. | Лекарственные формы для лечения сахарного диабета |
| WO2013154779A1 (en) * | 2012-04-10 | 2013-10-17 | The Regents Of The University Of California | Nanocrystal-polymer nanocomposite electrochromic device |
| US9125805B2 (en) | 2012-06-27 | 2015-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
| US9018162B2 (en) | 2013-02-06 | 2015-04-28 | Xeris Pharmaceuticals, Inc. | Methods for rapidly treating severe hypoglycemia |
| JP6763777B2 (ja) * | 2014-02-06 | 2020-09-30 | ゼリス ファーマシューティカルズ インコーポレイテッド | 安定なペプチド製剤、および調製のための方法 |
| CN106573106B (zh) | 2014-08-06 | 2021-06-22 | Xeris药物公司 | 用于皮内和/或皮下注射糊剂的注射器、试剂盒和方法 |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| WO2016120378A1 (en) | 2015-01-29 | 2016-08-04 | Novo Nordisk A/S | Tablets comprising glp-1 agonist and enteric coating |
| EP3302354B1 (en) | 2015-06-03 | 2023-10-04 | i2o Therapeutics, Inc. | Implant placement systems |
| US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
| US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
| RU2760007C2 (ru) | 2016-05-16 | 2021-11-22 | Интарсия Терапьютикс, Инк. | Полипептиды, селективные к рецепторам глюкагона, и способы их применения |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods involving continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
| WO2018222922A1 (en) | 2017-06-02 | 2018-12-06 | Xeris Pharmaceuticals, Inc. | Precipitation resistant small molecule drug formulations |
| RS65380B1 (sr) | 2017-08-24 | 2024-04-30 | Novo Nordisk As | Glp-1 kompozicije i njihova upotreba |
| US20230093542A1 (en) | 2020-02-18 | 2023-03-23 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL22493A (en) * | 1963-12-09 | 1968-10-24 | Crown Zellerbach Corp | Membrane penetrant composition containing a dialkyl sulfoxide |
| US3914412A (en) * | 1973-10-11 | 1975-10-21 | Abbott Lab | {8 Des{13 Gly{9 {0 10 -Gn{13 RH nonapeptide amide analogs in position 6 having ovulation-inducing activity |
| GB2008403B (en) * | 1977-11-04 | 1982-07-28 | Christie R B Parsons J A | Pharmaceutical compositions |
| GB2119248A (en) * | 1982-04-28 | 1983-11-16 | John Kenneth Mcmullen | Insulin formulations and method of producing them |
| US4547370A (en) * | 1983-11-29 | 1985-10-15 | The Salk Institute For Biological Studies | GnRH Antagonists |
| US4661472A (en) * | 1985-05-09 | 1987-04-28 | The Salk Institute For Biological Studies | GnRH antagonists IX |
| US4897256A (en) * | 1986-11-25 | 1990-01-30 | Abbott Laboratories | LHRH analog formulations |
| US4851385A (en) * | 1987-07-15 | 1989-07-25 | Indiana University Foundation | LHRH antagonist analogs having low histamine-release activity |
| US4800191A (en) * | 1987-07-17 | 1989-01-24 | Schally Andrew Victor | LHRH antagonists |
| ATE99543T1 (de) * | 1987-10-15 | 1994-01-15 | Syntex Inc | Pulverfoermige zubereitungen zur intranasalen verabreichung von polypeptiden. |
| US5057318A (en) * | 1988-12-13 | 1991-10-15 | Alza Corporation | Delivery system for beneficial agent over a broad range of rates |
| US5110596A (en) * | 1988-12-13 | 1992-05-05 | Alza Corporation | Delivery system comprising means for delivering agent to livestock |
| US5034229A (en) * | 1988-12-13 | 1991-07-23 | Alza Corporation | Dispenser for increasing feed conversion of hog |
| DE4117507A1 (de) * | 1991-05-24 | 1992-11-26 | Schering Ag | Verfahren zur herstellung von n(pfeil hoch)6(pfeil hoch)-substituierten lysin-derivaten |
| DE69312947T2 (de) * | 1992-09-21 | 1998-01-08 | Pharmacia & Upjohn Company Kal | Proteinhaftige arzneimittel mit verzögerter wirkstoffabgabe |
| TW333456B (en) * | 1992-12-07 | 1998-06-11 | Takeda Pharm Ind Co Ltd | A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide. |
| EP0686045B1 (en) * | 1993-02-23 | 2000-11-15 | Genentech, Inc. | Excipient stabilization of polypeptides treated with organic solvents |
| DE4320201A1 (de) * | 1993-06-18 | 1995-01-12 | Asta Medica Ag | Verwendung von Cetrorelix und weiteren Nona- und Dekapeptiden zur Herstellung eines Arzneimittels zur Bekämpfung von Aids und zur Wachstumsstimulation |
| US5413990A (en) * | 1993-08-06 | 1995-05-09 | Tap Pharmaceuticals Inc. | N-terminus modified analogs of LHRH |
| DK1238659T3 (da) * | 1996-02-02 | 2005-01-24 | Alza Corp | Vedvarende frigivelse af et aktivt middel ved anvendelse af et implanterbart system |
| US5932547A (en) * | 1996-07-03 | 1999-08-03 | Alza Corporation | Non-aqueous polar aprotic peptide formulations |
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