NO324405B1 - Agonistanalog av amylin og preparat omfattende denne. - Google Patents

Agonistanalog av amylin og preparat omfattende denne. Download PDF

Info

Publication number: NO324405B1
Authority: NO; Norway
Prior art keywords: amylin; asn; ser; thr; leu
Prior art date: 1991-11-19

Application number

NO19932603A

Other languages

English (en)

Norwegian (no)

Other versions

NO932603D0 (no

NO932603L (no

Inventor

Elisabeth Albrecht

Howard Jones

Laura S L Gatea

Original Assignee

Amylin Pharmaceuticals Inc

Priority date (The priority date 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 date listed.)

1991-11-19

Filing date

1993-07-19

Publication date

2007-10-08

1993-07-19 Application filed by Amylin Pharmaceuticals Inc filed Critical Amylin Pharmaceuticals Inc

1993-07-19 Publication of NO932603D0 publication Critical patent/NO932603D0/no

1993-09-17 Publication of NO932603L publication Critical patent/NO932603L/no

2007-10-08 Publication of NO324405B1 publication Critical patent/NO324405B1/no

Links

108010041872 Islet Amyloid Polypeptide Proteins 0.000 title claims abstract description 81
102000036770 Islet Amyloid Polypeptide Human genes 0.000 title claims abstract description 81
239000000556 agonist Substances 0.000 title claims abstract description 55
238000002360 preparation method Methods 0.000 title claims description 35
125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 14
125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 13
125000001691 aryl alkyl amino group Chemical group 0.000 claims abstract description 13
125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 13
125000001769 aryl amino group Chemical group 0.000 claims abstract description 13
125000004104 aryloxy group Chemical group 0.000 claims abstract description 13
125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 13
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 53
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230000000694 effects Effects 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 14
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MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 6
150000008574 D-amino acids Chemical group 0.000 claims description 6
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 claims description 6
125000000539 amino acid group Chemical group 0.000 claims description 6
150000003951 lactams Chemical class 0.000 claims description 6
125000000534 N(2)-L-lysino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C([H])([H])C(C([H])([H])N([H])[H])([H])[H] 0.000 claims description 5
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 2
159000000021 acetate salts Chemical class 0.000 claims 2
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims 2
RFCVXVPWSPOMFJ-STQMWFEESA-N Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 RFCVXVPWSPOMFJ-STQMWFEESA-N 0.000 claims 1
108010073101 phenylalanylleucine Proteins 0.000 claims 1
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
150000001413 amino acids Chemical class 0.000 description 24
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 22
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 20
238000000034 method Methods 0.000 description 17
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 16
239000008103 glucose Substances 0.000 description 16
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BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 10
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PSHNNUKOUQCMSG-UHFFFAOYSA-K bis[(2,2,2-trifluoroacetyl)oxy]thallanyl 2,2,2-trifluoroacetate Chemical compound [Tl+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PSHNNUKOUQCMSG-UHFFFAOYSA-K 0.000 description 10
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UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 10
SHDMMLFAFLZUEV-UHFFFAOYSA-N n-methyl-1,1-diphenylmethanamine Chemical compound C=1C=CC=CC=1C(NC)C1=CC=CC=C1 SHDMMLFAFLZUEV-UHFFFAOYSA-N 0.000 description 10
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229960004666 glucagon Drugs 0.000 description 8
238000004007 reversed phase HPLC Methods 0.000 description 8
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125000004432 carbon atom Chemical group C* 0.000 description 6
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
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238000003556 assay Methods 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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238000012360 testing method Methods 0.000 description 5
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JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
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LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
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150000003871 sulfonates Chemical class 0.000 description 1
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
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150000003556 thioamides Chemical class 0.000 description 1
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XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- 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
- 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
- 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
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Emergency Medicine (AREA)
Immunology (AREA)
Biochemistry (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Toxicology (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO19932603A 1991-11-19 1993-07-19 Agonistanalog av amylin og preparat omfattende denne. NO324405B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US79426691A	1991-11-19	1991-11-19
PCT/US1992/009842 WO1993010146A1 (fr)	1991-11-19	1992-11-19	Peptides a action agoniste a base d'amyline et utilisations de ces peptides

Publications (3)

Publication Number	Publication Date
NO932603D0 NO932603D0 (no)	1993-07-19
NO932603L NO932603L (no)	1993-09-17
NO324405B1 true NO324405B1 (no)	2007-10-08

Family

ID=25162163

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO19932603A NO324405B1 (no)	1991-11-19	1993-07-19	Agonistanalog av amylin og preparat omfattende denne.
NO20073265A NO20073265L (no)	1991-11-19	2007-06-25	Agonistananalog av amylin

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20073265A NO20073265L (no)	1991-11-19	2007-06-25	Agonistananalog av amylin

Country Status (17)

Country	Link
EP (2)	EP0567626B1 (fr)
JP (4)	JP2902115B2 (fr)
AT (1)	ATE205854T1 (fr)
AU (1)	AU714439B2 (fr)
CA (1)	CA2100745C (fr)
CZ (1)	CZ288029B6 (fr)
DE (1)	DE69232064T2 (fr)
DK (1)	DK0567626T3 (fr)
ES (1)	ES2161697T3 (fr)
FI (1)	FI118601B (fr)
GR (1)	GR3036794T3 (fr)
HK (1)	HK1041891A1 (fr)
MD (1)	MD960317A (fr)
NO (2)	NO324405B1 (fr)
RU (1)	RU2130463C1 (fr)
SK (1)	SK88793A3 (fr)
WO (1)	WO1993010146A1 (fr)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
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
US5625032A (en) *	1993-07-21	1997-04-29	Amylin Pharmaceuticals, Inc.	Selective amylin antagonist peptides and uses therefor
CZ69596A3 (en)	1993-09-07	1997-06-11	Amylin Pharmaceuticals Inc	Application of amylin, amylin agonist, amylin analog agonist or amylin antagonist for preparing a pharmaceutical preparation used for the control of gastrointestinal motility
US6143718A (en) *	1995-06-07	2000-11-07	Amylin Pharmaceuticals, Inc.	Treatment of Type II diabetes mellutis with amylin agonists
US5739106A (en) *	1995-06-07	1998-04-14	Rink; Timothy J.	Appetite regulating compositions
US7312196B2 (en)	1997-01-08	2007-12-25	Amylin Pharmaceuticals, Inc.	Formulations for amylin agonist peptides
US6410511B2 (en)	1997-01-08	2002-06-25	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 (fr) *	1998-01-09	2008-10-08	Amylin Pharmaceuticals, Inc.	Formulations de peptides agonistes d'amyline avec d'insuline
ATE366259T1 (de) *	1999-03-04	2007-07-15	Praecis Pharm Inc	Beta-amyloid-peptidaggregation regulierende peptide mit d-aminosäuren
GB0002952D0 (en) *	2000-02-09	2000-03-29	Pharma Mar Sa	Process for producing kahalalide F compounds
RU2228174C2 (ru) *	2000-04-10	2004-05-10	Помыткин Игорь Анатольевич	Янтарнокислый бис(2-гидрокси-n,n,n-триметилэтанаминий) для лечения инсулиновой резистентности, сахарного диабета, гиперлипидемии и дислипидемии
GB0128583D0 (en)	2001-11-28	2002-01-23	Rsr Ltd	Detection of autoantibodies indicative of diabetes
WO2004037168A2 (fr)	2002-10-18	2004-05-06	Amylin Pharmaceuticals, Inc.	Traitement de la pancreatite avec de l'amyline
GB0304367D0 (en) *	2003-02-26	2003-04-02	Pharma Mar Sau	Methods for treating psoriasis
JP2007527365A (ja) *	2003-03-18	2007-09-27	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	アミリン凝集阻害剤およびその使用
TW200637872A (en) *	2004-10-26	2006-11-01	Lonza Ag	Thiol group protection and cyclization in solid-phase peptide synthesis
US8394765B2 (en)	2004-11-01	2013-03-12	Amylin Pharmaceuticals Llc	Methods of treating obesity with two different anti-obesity agents
CN101094689B (zh)	2004-11-01	2013-06-12	安米林药品有限责任公司	治疗肥胖以及肥胖相关疾病和病症的方法
CN102343084A (zh)	2005-03-31	2012-02-08	安米林药品公司	用于治疗精神病和精神障碍的胰淀素和胰淀素激动剂
US8168592B2 (en)	2005-10-21	2012-05-01	Amgen Inc.	CGRP peptide antagonists and conjugates
WO2008028914A1 (fr)	2006-09-07	2008-03-13	Nycomed Gmbh	Polythérapie contre le diabète sucré
US8309522B2 (en)	2007-02-05	2012-11-13	Amylin Pharmaceuticals, Llc	Neuromedin and FN-38 peptides for treating psychiatric diseases
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
CA2755068C (fr)	2009-03-12	2018-11-06	Keybioscience Ag	Traitement du diabete et du syndrome metabolique
AR097701A1 (es) *	2013-09-19	2016-04-13	Zealand Pharma As	Análogos de amilina
MX2016005995A (es)	2013-11-05	2016-08-17	Ben-Gurion Univ Of The Negev Res And Dev Authority	Compuestos para el tratamiento de diabetes y complicaciones de la enfermedad derivadas de la misma.
CA2947587C (fr) *	2014-05-02	2022-10-18	The Research Foundation For The State University Of New York	Polypeptides a ilots amyloides presentant une solubilite amelioree
BR112017019378A2 (pt) *	2015-03-18	2019-02-19	Zealand Pharma A/S	análogos de amilina
US10071140B2 (en)	2016-09-09	2018-09-11	Zealand Pharma A/S	Amylin analogues
WO2018144671A1 (fr)	2017-02-01	2018-08-09	The Research Foundation For The State University Of New York	Polypeptides à îlots amyloïdes mutants présentant une solubilité améliorée et leurs procédés d'utilisation
KR102130354B1 (ko) *	2019-08-14	2020-07-06	엘아이지넥스원 주식회사	코어 제거용 이형장치
TWI880227B (zh)	2022-05-30	2025-04-11	丹麥商西蘭製藥公司	澱粉素類似物之液體調配物
IL319599A (en)	2022-09-19	2025-05-01	Zealand Pharma As	Combination therapy
MX2025015167A (es)	2023-06-21	2026-02-03	Zealand Pharma As	Analogos con propiedades mejoradas
TW202504913A (zh)	2023-06-21	2025-02-01	丹麥商西蘭製藥公司	減重
TW202517291A (zh)	2023-06-30	2025-05-01	丹麥商西蘭製藥公司	組合療法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5120712A (en) *	1986-05-05	1992-06-09	The General Hospital Corporation	Insulinotropic hormone
GB8720115D0 (en) *	1987-08-26	1987-09-30	Cooper G J S	Treatment of diabetes mellitus
AU631112B2 (en) *	1988-01-11	1992-11-19	Amylin Corporation	Treatment of type 2 diabetes mellitus
ES2080802T3 (es) *	1989-07-10	1996-02-16	Amylin Pharmaceuticals Inc	Uso de un antagonista de amilina en la preparacion de un medicamento para el tratamiento de la obesidad e hipertension intrinseca y desordenes asociados.
US5234906A (en) *	1991-01-10	1993-08-10	Amylin Pharmaceuticals, Inc.	Hyperglycemic compositions
WO1992015317A1 (fr) *	1991-03-08	1992-09-17	Amylin Pharmaceuticals, Inc.	Preparation synthetique d'amyline et d'analogues d'amyline

1992
- 1992-11-19 CA CA002100745A patent/CA2100745C/fr not_active Expired - Lifetime
- 1992-11-19 MD MD96-0317A patent/MD960317A/ro unknown
- 1992-11-19 ES ES92924442T patent/ES2161697T3/es not_active Expired - Lifetime
- 1992-11-19 EP EP92924442A patent/EP0567626B1/fr not_active Expired - Lifetime
- 1992-11-19 JP JP5509441A patent/JP2902115B2/ja not_active Expired - Lifetime
- 1992-11-19 SK SK887-93A patent/SK88793A3/sk unknown
- 1992-11-19 DE DE69232064T patent/DE69232064T2/de not_active Expired - Lifetime
- 1992-11-19 RU RU93053497A patent/RU2130463C1/ru active
- 1992-11-19 CZ CZ19931689A patent/CZ288029B6/cs not_active IP Right Cessation
- 1992-11-19 AT AT92924442T patent/ATE205854T1/de active
- 1992-11-19 EP EP01114132A patent/EP1162207A1/fr not_active Ceased
- 1992-11-19 WO PCT/US1992/009842 patent/WO1993010146A1/fr not_active Ceased
- 1992-11-19 DK DK92924442T patent/DK0567626T3/da active
1993
- 1993-07-16 FI FI933252A patent/FI118601B/fi not_active IP Right Cessation
- 1993-07-19 NO NO19932603A patent/NO324405B1/no not_active IP Right Cessation
1997
- 1997-01-31 AU AU12456/97A patent/AU714439B2/en not_active Expired
1998
- 1998-09-30 JP JP10277573A patent/JPH11152299A/ja not_active Withdrawn
2001
- 2001-10-04 GR GR20010401656T patent/GR3036794T3/el unknown
2002
- 2002-05-02 HK HK02103291.8A patent/HK1041891A1/en unknown
2003
- 2003-01-15 JP JP2003007228A patent/JP2003238594A/ja not_active Withdrawn
2006
- 2006-02-03 JP JP2006027334A patent/JP4018116B2/ja not_active Expired - Lifetime
2007
- 2007-06-25 NO NO20073265A patent/NO20073265L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
AU1245697A (en)	1997-03-27
MD960317A (ro)	1998-05-31
WO1993010146A1 (fr)	1993-05-27
NO932603D0 (no)	1993-07-19
DE69232064T2 (de)	2002-03-28
CA2100745C (fr)	2007-07-31
AU3075392A (en)	1993-06-15
EP0567626A1 (fr)	1993-11-03
AU714439B2 (en)	2000-01-06
HK1041891A1 (en)	2002-07-26
JPH06504794A (ja)	1994-06-02
GR3036794T3 (en)	2002-01-31
CA2100745A1 (fr)	1993-05-20
CZ288029B6 (cs)	2001-04-11
NO20073265L (no)	1993-09-17
FI933252A0 (fi)	1993-07-16
JP2006213716A (ja)	2006-08-17
EP1162207A1 (fr)	2001-12-12
ATE205854T1 (de)	2001-10-15
RU2130463C1 (ru)	1999-05-20
JP4018116B2 (ja)	2007-12-05
AU673147B2 (en)	1996-10-31
EP0567626B1 (fr)	2001-09-19
JPH11152299A (ja)	1999-06-08
FI933252L (fi)	1993-08-23
JP2902115B2 (ja)	1999-06-07
DE69232064D1 (de)	2001-10-25
DK0567626T3 (da)	2001-12-17
ES2161697T3 (es)	2001-12-16
NO932603L (no)	1993-09-17
FI118601B (fi)	2008-01-15
JP2003238594A (ja)	2003-08-27
CZ168993A3 (en)	1994-04-13
SK88793A3 (en)	1994-12-07

Legal Events

Date	Code	Title	Description
2012-12-10	MK1K	Patent expired

Publication	Publication Date	Title
NO324405B1 (no)	2007-10-08	Agonistanalog av amylin og preparat omfattende denne.
US7271238B2 (en)	2007-09-18	Amylin agonist peptides and uses therefor
CA2337971C (fr)	2011-04-26	Nouveaux peptides antidiabetiques
HUT64367A (en)	1993-12-28	Method for producing glucagon-like peptides and insulino-tropine derivatives as well as medical preparatives containing said compounds
NZ230549A (en)	1993-03-26	Linear and cyclic growth hormone releasing factor analogues
CA2320962C (fr)	2011-04-19	Nouveaux composes a activite mixte par rapport a l'amyline
AU669636B2 (en)	1996-06-13	Amylin antagonists and agonists
JP3802863B2 (ja)	2006-07-26	ペプチドを有効成分とする糖尿病の治療用医薬
AU673147C (en)	1998-04-23	Amylin agonist peptides and uses therefor
MXPA98010361A (en)	1999-09-20	Exandin analogues, processes for preparation and medications that contains