HRP20211768T1 - Liječenje postbarijatrijske hipoglikemije s antagonistima glp-1 - Google Patents
Liječenje postbarijatrijske hipoglikemije s antagonistima glp-1 Download PDFInfo
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- HRP20211768T1 HRP20211768T1 HRP20211768TT HRP20211768T HRP20211768T1 HR P20211768 T1 HRP20211768 T1 HR P20211768T1 HR P20211768T T HRP20211768T T HR P20211768TT HR P20211768 T HRP20211768 T HR P20211768T HR P20211768 T1 HRP20211768 T1 HR P20211768T1
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- Prior art keywords
- exendin
- treatment
- prevention
- chronic symptoms
- hyperinsulinemic hypoglycemia
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- 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 title 1
- 208000013016 Hypoglycemia Diseases 0.000 title 1
- 239000005557 antagonist Substances 0.000 title 1
- 230000002218 hypoglycaemic effect Effects 0.000 title 1
- WSEVKKHALHSUMB-RYVRVIGHSA-N (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[2-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-2-oxoethyl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O WSEVKKHALHSUMB-RYVRVIGHSA-N 0.000 claims 19
- 108010024703 exendin (9-39) Proteins 0.000 claims 19
- 230000001154 acute effect Effects 0.000 claims 15
- 230000001684 chronic effect Effects 0.000 claims 15
- 208000033066 hyperinsulinemic hypoglycemia Diseases 0.000 claims 15
- 230000002265 prevention Effects 0.000 claims 15
- 208000024891 symptom Diseases 0.000 claims 15
- 238000002347 injection Methods 0.000 claims 4
- 239000007924 injection Substances 0.000 claims 4
- 238000010254 subcutaneous injection Methods 0.000 claims 4
- 239000007929 subcutaneous injection Substances 0.000 claims 4
- 238000007681 bariatric surgery Methods 0.000 claims 3
- 238000011902 gastrointestinal surgery Methods 0.000 claims 3
- 230000002183 duodenal effect Effects 0.000 claims 2
- 230000002496 gastric effect Effects 0.000 claims 2
- 235000012054 meals Nutrition 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 210000000689 upper leg Anatomy 0.000 claims 2
- 208000000454 Congenital Hyperinsulinism Diseases 0.000 claims 1
- 210000001015 abdomen Anatomy 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 208000033442 familial 1 hyperinsulinemic hypoglycemia Diseases 0.000 claims 1
- 208000033961 familial 2 hyperinsulinemic hypoglycemia Diseases 0.000 claims 1
- 208000011532 familial hyperinsulinism Diseases 0.000 claims 1
- 238000013110 gastrectomy Methods 0.000 claims 1
- 210000004877 mucosa Anatomy 0.000 claims 1
- 238000007682 sleeve gastrectomy Methods 0.000 claims 1
- 210000001186 vagus nerve Anatomy 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (15)
1. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice kod pacijenta ubrizgavanjem terapeutski učinkovite doze koja sadrži 2-100 mg eksendina(9-39).
2. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 1, pri čemu terapeutski učinkovita doza sadrži 10-75 mg eksendina(9-39).
3. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 1 ili 2, pri čemu je pacijent prethodno bio podvrgnut barijatrijskom operativnom zahvatu.
4. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 3, pri čemu je barijatrijski operativni zahvat odabran iz skupine koju čine operativni zahvat želučane premosnice Roux-en-Y, vertikalna gastrektomija rukava, postavljanje endoskopskog uređaja, obnavljanje sluznice duodenuma, djelomična premosnica duodenuma, blokada vagusnog živca, te piloroplastika, prvenstveno gdje je pacijent prethodno bio podvrgnut operativnom zahvatu želučane premosnice Roux-en-Y.
5. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 1 ili 2, pri čemu je pacijent prethodno bio podvrgnut gastrointestinalnom operativnom zahvatu.
6. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 5, pri čemu je gastrointestinalni operativni zahvat odabran iz skupine koju čine gastrektomija, Nissenova fundoplikacija, te ezofagektomija.
7. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 1 ili 2, pri čemu pacijent ima kongenitalni hiperinzulinizam.
8. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih kroničnih simptoma te posljedice prema zahtjevu 1 ili 2, pri čemu je volumen ubrizganog proizvoda u rasponu od 0,25ml do 2ml, po mogućnosti u rasponu od 0,5 ml do 1,5 ml.
9. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema bilo kojem od zahtjeva 1-8, pri čemu se eksendin(9-39) ubrizgava prije prvog ili posljednjeg obroka u danu.
10. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 9, pri čemu se eksendin(9-39) ubrizgava najmanje 60 minuta prije obroka.
11. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema bilo kojem od zahtjeva 1 do 8, pri čemu se eksendin (9-39) ubrizgava u koncentraciji većoj od 20 mg/ml.
12. Eksendin(9-39) za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema bilo kojem od zahtjeva 1 do 8, pri čemu je terapeutski učinkovita doza prikladna za ubrizgavanje u područje bedra, trbuha ili nadlaktice, poželjno u bedro.
13. Šprica ili injekcijska olovka za potkožno ubrizgavanje koja sadrži jednu dozu eksendina(9-39) ili je unaprijed programirana ili označena za isporuku fiksne količine doze eksendina(9-39), pri čemu pojedinačna doza ili fiksna količina doze sadrži 2-100 mg eksendina formuliranog u farmaceutski prihvatljivom razrjeđivaču ili nosaču, spomenuta šprica ili injekcijska olovka za potkožno ubrizgavanje biva prikladna za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedica kod pacijenata.
14. Šprica ili injekcijska olovka za potkožno ubrizgavanje za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 13, pri čemu je pacijent prethodno bio podvrgnut barijatrijskom operativnom zahvatu ili gastrointestinalnom operativnom zahvatu.
15. Šprica ili injekcijska olovka za potkožno ubrizgavanje za uporabu u liječenju i prevenciju hiperinsulinemijske hipoglikemije i povezanih akutnih i kroničnih simptoma te posljedice prema zahtjevu 13 ili 14, pri čemu je volumen pojedinačne doze u rasponu od 0,25 ml do 2 ml, poželjno u rasponu od 0,5 ml do 1,5 ml.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562165743P | 2015-05-22 | 2015-05-22 | |
| US201562254175P | 2015-11-11 | 2015-11-11 | |
| US201662329850P | 2016-04-29 | 2016-04-29 | |
| EP16800620.3A EP3297653B1 (en) | 2015-05-22 | 2016-05-23 | Treatment of post-bariatric hypoglycemia with glp-1 antagonists |
| PCT/US2016/033836 WO2016191394A1 (en) | 2015-05-22 | 2016-05-23 | Treatment of post-bariatric hypoglycemia with glp-1 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20211768T1 true HRP20211768T1 (hr) | 2022-02-18 |
Family
ID=57393681
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20211285TT HRP20211285T1 (hr) | 2015-05-22 | 2016-05-23 | Liječenje postbarijatrijske hipoglikemije eksendinom (9-39) |
| HRP20211768TT HRP20211768T1 (hr) | 2015-05-22 | 2016-05-23 | Liječenje postbarijatrijske hipoglikemije s antagonistima glp-1 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20211285TT HRP20211285T1 (hr) | 2015-05-22 | 2016-05-23 | Liječenje postbarijatrijske hipoglikemije eksendinom (9-39) |
Country Status (17)
| Country | Link |
|---|---|
| US (8) | US10660937B2 (hr) |
| EP (4) | EP3936143A1 (hr) |
| AU (4) | AU2016267057B2 (hr) |
| BR (2) | BR112017024997A2 (hr) |
| CA (2) | CA3024353A1 (hr) |
| CL (2) | CL2017002913A1 (hr) |
| CY (2) | CY1124616T1 (hr) |
| DK (2) | DK3297653T3 (hr) |
| ES (2) | ES2887723T3 (hr) |
| HR (2) | HRP20211285T1 (hr) |
| HU (2) | HUE055728T2 (hr) |
| LT (2) | LT3297653T (hr) |
| PL (2) | PL3297654T3 (hr) |
| PT (2) | PT3297653T (hr) |
| RS (2) | RS62627B1 (hr) |
| SI (2) | SI3297653T1 (hr) |
| WO (2) | WO2016191395A1 (hr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4049673A1 (en) | 2007-01-08 | 2022-08-31 | The Trustees of the University of Pennsylvania | Glp-1 receptor antagonist for use in the treatment of post-prandial hypoglycemia or congenital hyperinsulinism |
| DK3297653T3 (da) | 2015-05-22 | 2021-10-18 | Univ Leland Stanford Junior | Behandling af postbariatrisk hypoglykæmi med glp-1-antagonister |
| US10653753B2 (en) | 2016-03-04 | 2020-05-19 | Eiger Biopharmaceuticals, Inc. | Treatment of hyperinsulinemic hypoglycemia with exendin-4 derivatives |
| BR112019010236A2 (pt) | 2016-11-21 | 2019-08-20 | Eiger Biopharmaceuticals Inc | formulações tamponadas de exendina (9-39) |
| EP3743097A1 (en) * | 2018-01-23 | 2020-12-02 | Xeris Pharmaceuticals, Inc. | Treatment of post-bariatric hypoglycemia using mini-dose stable glucagon |
| GB201816639D0 (en) * | 2018-10-12 | 2018-11-28 | Heptares Therapeutics Ltd | GLP-1 Receptor Antagonist |
| CN112867730A (zh) * | 2018-10-15 | 2021-05-28 | 艾格尔峰生物制药有限公司 | 用于治疗高胰岛素低血糖症的阿维西特 |
| WO2020144378A1 (en) * | 2019-01-11 | 2020-07-16 | Universitätsspital Basel | Sglt-2 inhibitors or il-1r antagonists for reduction of hypoglycaemia after bariatric surgery |
| WO2024042518A1 (en) * | 2022-08-21 | 2024-02-29 | M. Arkin (1999) Ltd | Glp-1 receptor antagonist and methods of use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| BR9306551A (pt) | 1992-06-15 | 1998-09-15 | Pfizer | Derivados de peptídeo do tipo glucagona e de insulinotropina |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US20040092443A1 (en) | 1996-08-06 | 2004-05-13 | Yeda Research And Development Co., Ltd | Long-acting exendins and exendin agonists |
| ES2359031T3 (es) | 1996-08-08 | 2011-05-17 | Amylin Pharmaceuticals, Inc. | Composición farmacéutica que comprende un péptido de exendina-4. |
| US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| US6268343B1 (en) | 1996-08-30 | 2001-07-31 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| US7235627B2 (en) | 1996-08-30 | 2007-06-26 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| CA2277112C (en) | 1997-01-07 | 2008-08-26 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the reduction of food intake |
| UA56256C2 (uk) | 1998-01-30 | 2003-05-15 | Ново Нордіск А/С | Шприц для ін'єкцій |
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| DK1140145T4 (da) | 1999-01-14 | 2019-07-22 | Amylin Pharmaceuticals Llc | Hidtil ukendte exendinagonistformuleringer og fremgangsmåder til indgivelse deraf |
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| SE0004462D0 (sv) | 2000-12-04 | 2000-12-04 | Pharmacia Ab | Novel method and use |
| WO2002066062A2 (en) | 2001-02-01 | 2002-08-29 | Drucker Daniel J | Enhancement of glp-2 activity |
| AU2002257132A1 (en) | 2001-04-06 | 2002-10-21 | The Trustees Of The University Of Pennsylvania | Erbb interface peptidomimetics and methods of use thereof |
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| EP2394656B1 (en) | 2003-11-20 | 2023-12-13 | Novo Nordisk A/S | Pharmaceutical formulations comprising the peptide liraglutide and propylene glycol |
| US8076288B2 (en) | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
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