SK88793A3 - Amylin agonising peptides and their using - Google Patents

Amylin agonising peptides and their using Download PDF

Info

Publication number: SK88793A3
Authority: SK; Slovakia
Prior art keywords: amylin; pro; ser; lys; effective amount
Prior art date: 1991-11-19

Application number

SK887-93A

Other languages

English (en)

Slovak (sk)

Inventor

Laura S L Gaeta

Howard Jones

Elisabeth Albrecht

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

1992-11-19

Publication date

1994-12-07

1992-11-19 Application filed by Amylin Pharmaceuticals Inc filed Critical Amylin Pharmaceuticals Inc

1994-12-07 Publication of SK88793A3 publication Critical patent/SK88793A3/sk

Links

108010041872 Islet Amyloid Polypeptide Proteins 0.000 title claims abstract description 84
102000036770 Islet Amyloid Polypeptide Human genes 0.000 title claims abstract description 83
108090000765 processed proteins & peptides Proteins 0.000 title description 49
102000004196 processed proteins & peptides Human genes 0.000 title description 7
239000000556 agonist Substances 0.000 claims abstract description 33
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 16
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 68
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238000000034 method Methods 0.000 claims description 36
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125000000217 alkyl group Chemical group 0.000 claims description 14
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 14
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101000952234 Homo sapiens Sphingolipid delta(4)-desaturase DES1 Proteins 0.000 claims description 4
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102100037416 Sphingolipid delta(4)-desaturase DES1 Human genes 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
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RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000001769 aryl amino group Chemical group 0.000 claims description 3
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150000008575 L-amino acids Chemical class 0.000 claims description 2
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239000004927 clay Substances 0.000 claims 3
RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 claims 3
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
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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 1
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 claims 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 1
125000004663 dialkyl amino group Chemical group 0.000 claims 1
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QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 40
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ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 33
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 32
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 32
238000004458 analytical method Methods 0.000 description 31
235000001014 amino acid Nutrition 0.000 description 30
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 30
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
238000002360 preparation method Methods 0.000 description 27
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210000003205 muscle Anatomy 0.000 description 23
125000006239 protecting group Chemical group 0.000 description 21
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238000007363 ring formation reaction Methods 0.000 description 19
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239000000047 product Substances 0.000 description 17
150000003839 salts Chemical class 0.000 description 17
238000010532 solid phase synthesis reaction Methods 0.000 description 17
238000010647 peptide synthesis reaction Methods 0.000 description 16
238000012300 Sequence Analysis Methods 0.000 description 15
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150000002500 ions Chemical class 0.000 description 15
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 13
235000018417 cysteine Nutrition 0.000 description 13
150000001945 cysteines Chemical class 0.000 description 13
229910052716 thallium Inorganic materials 0.000 description 13
BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 13
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
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 12
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 11
239000007853 buffer solution Substances 0.000 description 11
238000005859 coupling reaction Methods 0.000 description 11
-1 diabetes mellitus Chemical compound 0.000 description 11
239000008103 glucose Substances 0.000 description 11
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101001081479 Homo sapiens Islet amyloid polypeptide Proteins 0.000 description 9
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UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 9
230000008878 coupling Effects 0.000 description 9
238000010168 coupling process Methods 0.000 description 9
229940096919 glycogen Drugs 0.000 description 9
238000001819 mass spectrum Methods 0.000 description 9
229940127438 Amylin Agonists Drugs 0.000 description 8
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 8
208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
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244000309466 calf Species 0.000 description 7
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
201000001421 hyperglycemia Diseases 0.000 description 6
238000004007 reversed phase HPLC Methods 0.000 description 6
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
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150000001412 amines Chemical class 0.000 description 5
238000003556 assay Methods 0.000 description 5
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238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
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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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 3
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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)
Organic Chemistry (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Emergency Medicine (AREA)
Immunology (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (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)

SK887-93A 1991-11-19 1992-11-19 Amylin agonising peptides and their using SK88793A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US79426691A	1991-11-19	1991-11-19
PCT/US1992/009842 WO1993010146A1 (en)	1991-11-19	1992-11-19	Amylin agonist peptides and uses therefor

Publications (1)

Publication Number	Publication Date
SK88793A3 true SK88793A3 (en)	1994-12-07

Family

ID=25162163

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK887-93A SK88793A3 (en)	1991-11-19	1992-11-19	Amylin agonising peptides and their using

Country Status (17)

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

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
BR9407424A (pt)	1993-09-07	1996-04-09	Amylin Pharmaceuticals Inc	Métodos para regular motilidade gastrointestinal
US5739106A (en) *	1995-06-07	1998-04-14	Rink; Timothy J.	Appetite regulating compositions
US6143718A (en) *	1995-06-07	2000-11-07	Amylin Pharmaceuticals, Inc.	Treatment of Type II diabetes mellutis with amylin agonists
US6410511B2 (en)	1997-01-08	2002-06-25	Amylin Pharmaceuticals, Inc.	Formulations for amylin agonist peptides
US7312196B2 (en)	1997-01-08	2007-12-25	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
ES2316161T3 (es) *	1998-01-09	2009-04-01	Amylin Pharmaceuticals, Inc.	Formulaciones para peptidos agonistas de amilina con insulina.
ES2290023T3 (es) *	1999-03-04	2008-02-16	Praecis Pharmaceuticals Incorporated	Moduladores de la agregacion del peptido beta-amiloide que comprenden d-aminoacidos.
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
GB0304367D0 (en) *	2003-02-26	2003-04-02	Pharma Mar Sau	Methods for treating psoriasis
US8168233B2 (en)	2002-10-18	2012-05-01	Amylin Pharmaceuticals, Inc.	Treatment of pancreatitis with amylin
CA2516726A1 (en) *	2003-03-18	2004-09-30	Applied Research Systems Ars Holding N.V.	Amylin aggregation inhibitors and use thereof
JP2008529969A (ja) *	2004-10-26	2008-08-07	ロンザア−ゲ−	固相合成におけるｓ−アルキル−スルフェニル保護基
ES2325773T5 (es)	2004-11-01	2014-02-24	Amylin Pharmaceuticals, Llc.	Tratamiento de la obesidad y de los trastornos relacionados
US8394765B2 (en)	2004-11-01	2013-03-12	Amylin Pharmaceuticals Llc	Methods of treating obesity with two different anti-obesity agents
US7671023B2 (en)	2005-03-31	2010-03-02	Amylin Pharmaceuticals, Inc.	Amylin agonist for treating depression, anxiety disorder and schizophrenia
US8168592B2 (en)	2005-10-21	2012-05-01	Amgen Inc.	CGRP peptide antagonists and conjugates
UA100497C2 (ru)	2006-09-07	2013-01-10	Никомед Гмбх	Комбинированное лечение сахарного диабета
WO2008097536A2 (en)	2007-02-05	2008-08-14	Amylin Pharmaceuticals, Inc.	Compositions and methods for treating psychiatric diseases and disorders
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
KR101673042B1 (ko)	2009-03-12	2016-11-04	키바이오사이언스 아게	당뇨병 및 대사 증후군의 치료
AR097701A1 (es) *	2013-09-19	2016-04-13	Zealand Pharma As	Análogos de amilina
EA201690938A1 (ru)	2013-11-05	2016-11-30	Бен-Гурион Юниверсити Оф Дзе Негев Рисерч Энд Дивелопмент Оторити	Соединения для лечения диабета и осложнений, возникающих из-за этого заболевания
EP3137494B1 (de) *	2014-05-02	2021-08-04	The Research Foundation for The State University of New York	Inselamyloidpolypeptide mit verbesserter löslichkeit
EA035791B1 (ru) *	2015-03-18	2020-08-11	Зилэнд Фарма А/С	Аналоги амилина
AR109514A1 (es)	2016-09-09	2018-12-19	Zealand Pharma As	Análogos de amilina
US11028137B2 (en)	2017-02-01	2021-06-08	The Research Foundation For The State University Of New York	Mutant islet amyloid polypeptides with improved solubility and methods for using the same
KR102130354B1 (ko) *	2019-08-14	2020-07-06	엘아이지넥스원 주식회사	코어 제거용 이형장치
MX2024005969A (es)	2022-05-30	2024-06-11	Zealand Pharma As	Formulaciones liquidas de analogos de amilina.
IL319599A (en)	2022-09-19	2025-05-01	Zealand Pharma As	Combination therapy
TW202504913A (zh)	2023-06-21	2025-02-01	丹麥商西蘭製藥公司	減重
EP4731239A1 (de)	2023-06-21	2026-04-29	Zealand Pharma A/S	Analoga mit verbesserten eigenschaften
KR20260032481A (ko)	2023-06-30	2026-03-09	질랜드 파마 에이/에스	병용 요법

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
ATE128359T1 (de) *	1988-01-11	1995-10-15	Amylin Pharmaceuticals Inc	Behandlung von diabetes mellitus typ 2.
CA2020786A1 (en) *	1989-07-10	1991-01-11	Amylin Pharmaceuticals, Inc.	Treatment of obesity and essential hypertension and related disorders
US5234906A (en) *	1991-01-10	1993-08-10	Amylin Pharmaceuticals, Inc.	Hyperglycemic compositions
WO1992015317A1 (en) *	1991-03-08	1992-09-17	Amylin Pharmaceuticals, Inc.	Synthetic preparation of amylin and amylin analogues

1992
- 1992-11-19 MD MD96-0317A patent/MD960317A/ro unknown
- 1992-11-19 SK SK887-93A patent/SK88793A3/sk unknown
- 1992-11-19 AT AT92924442T patent/ATE205854T1/de active
- 1992-11-19 DE DE69232064T patent/DE69232064T2/de not_active Expired - Lifetime
- 1992-11-19 WO PCT/US1992/009842 patent/WO1993010146A1/en not_active Ceased
- 1992-11-19 EP EP92924442A patent/EP0567626B1/de not_active Expired - Lifetime
- 1992-11-19 EP EP01114132A patent/EP1162207A1/de not_active Ceased
- 1992-11-19 RU RU93053497A patent/RU2130463C1/ru active
- 1992-11-19 CA CA002100745A patent/CA2100745C/en not_active Expired - Lifetime
- 1992-11-19 DK DK92924442T patent/DK0567626T3/da active
- 1992-11-19 ES ES92924442T patent/ES2161697T3/es not_active Expired - Lifetime
- 1992-11-19 JP JP5509441A patent/JP2902115B2/ja not_active Expired - Lifetime
- 1992-11-19 CZ CZ19931689A patent/CZ288029B6/cs not_active IP Right Cessation
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
WO1993010146A1 (en)	1993-05-27
RU2130463C1 (ru)	1999-05-20
JP2006213716A (ja)	2006-08-17
FI118601B (fi)	2008-01-15
NO20073265L (no)	1993-09-17
ATE205854T1 (de)	2001-10-15
JP4018116B2 (ja)	2007-12-05
ES2161697T3 (es)	2001-12-16
CA2100745A1 (en)	1993-05-20
FI933252L (fi)	1993-08-23
JP2003238594A (ja)	2003-08-27
MD960317A (ro)	1998-05-31
CZ168993A3 (en)	1994-04-13
AU673147B2 (en)	1996-10-31
AU3075392A (en)	1993-06-15
JPH11152299A (ja)	1999-06-08
NO932603L (no)	1993-09-17
DE69232064D1 (de)	2001-10-25
DK0567626T3 (da)	2001-12-17
CZ288029B6 (cs)	2001-04-11
EP0567626A1 (de)	1993-11-03
FI933252A0 (fi)	1993-07-16
AU1245697A (en)	1997-03-27
EP1162207A1 (de)	2001-12-12
JPH06504794A (ja)	1994-06-02
NO932603D0 (no)	1993-07-19
HK1041891A1 (en)	2002-07-26
CA2100745C (en)	2007-07-31
JP2902115B2 (ja)	1999-06-07
NO324405B1 (no)	2007-10-08
DE69232064T2 (de)	2002-03-28
GR3036794T3 (en)	2002-01-31
EP0567626B1 (de)	2001-09-19
AU714439B2 (en)	2000-01-06

Publication	Publication Date	Title
RU2130463C1 (ru)	1999-05-20	Аналог-агонист амилина, его фармацевтически приемлемые соли, композиция, проявляющая свойства агониста амилина
US7271238B2 (en)	2007-09-18	Amylin agonist peptides and uses therefor
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AU766545B2 (en)	2003-10-16	Novel anti-diabetic peptides
JP2022172128A (ja)	2022-11-15	インスリン抵抗性のための改善されたペプチド医薬品
JP2003501361A (ja)	2003-01-14	妊娠糖尿病の治療のためのエキセンジンおよびそのアゴニストの使用
JP2001513512A (ja)	2001-09-04	新規なエキセンディン作動剤化合物
JP2003522721A (ja)	2003-07-29	新規なエキセンジンアゴニスト化合物
CA3157899A1 (en)	2014-05-30	Improved peptide pharmaceuticals
SK88893A3 (en)	1994-03-09	Novel amylin antagonist peptides and uses therefor
EA038073B1 (ru)	2021-07-01	Ацилированное инсулиновое соединение
JP2002522355A (ja)	2002-07-23	新規な混合アミリン活性化合物
KR20230106481A (ko)	2023-07-13	지속형 지방산-펩타이드 유도체 및 이의 용도
US20040127412A1 (en)	2004-07-01	Modified GLP-1 peptides with increased biological potency
AU673147C (en)	1998-04-23	Amylin agonist peptides and uses therefor
HK1038025B (en)	2007-04-27	Novel anti-diabetic peptides