DK171300B1 - Polypeptider, fremgangsmåder til deres fremstilling og analgetikum indeholdende et sådant polypeptid - Google Patents

Polypeptider, fremgangsmåder til deres fremstilling og analgetikum indeholdende et sådant polypeptid Download PDF

Info

Publication number: DK171300B1
Authority: DK; Denmark
Prior art keywords: arg; leu; gly; phe; tos
Prior art date: 1984-11-09

Application number

DK513385A

Other languages

Danish (da)

English (en)

Other versions

DK513385A (da

DK513385D0 (da

Inventor

Hiroshi Yoshino

Yutaka Tsuchiya

Takeru Kaneko

Takahiro Nakazawa

Masuhiro Ikeda

Shin Araki

Kiyomi Yamatsu

Shinro Tachibana

Yoshihiro Arakawa

Original Assignee

Eisai Co Ltd

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.)

1984-11-09

Filing date

1985-11-07

Publication date

1996-08-26

1985-11-07 Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd

1985-11-07 Publication of DK513385D0 publication Critical patent/DK513385D0/da

1986-05-10 Publication of DK513385A publication Critical patent/DK513385A/da

1996-08-26 Application granted granted Critical

1996-08-26 Publication of DK171300B1 publication Critical patent/DK171300B1/da

Links

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- C07K14/665—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
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- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/26—Containing cys-cys disulfide bridge between nonadjacent cysteine residues

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Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Gastroenterology & Hepatology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
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Biochemistry (AREA)
Zoology (AREA)
Toxicology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
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Biomedical Technology (AREA)
Pharmacology & Pharmacy (AREA)
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Animal Behavior & Ethology (AREA)
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Pain & Pain Management (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

DK513385A 1984-11-09 1985-11-07 Polypeptider, fremgangsmåder til deres fremstilling og analgetikum indeholdende et sådant polypeptid DK171300B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP59236076A JPH0680079B2 (ja)	1984-11-09	1984-11-09	ポリペプチド
JP23607684		1984-11-09

Publications (3)

Publication Number	Publication Date
DK513385D0 DK513385D0 (da)	1985-11-07
DK513385A DK513385A (da)	1986-05-10
DK171300B1 true DK171300B1 (da)	1996-08-26

Family

ID=16995360

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK513385A DK171300B1 (da)	1984-11-09	1985-11-07	Polypeptider, fremgangsmåder til deres fremstilling og analgetikum indeholdende et sådant polypeptid

Country Status (21)

Country	Link
US (1)	US4707468A (de)
EP (2)	EP0614913A3 (de)
JP (1)	JPH0680079B2 (de)
KR (1)	KR880000765B1 (de)
CN (1)	CN1029684C (de)
AT (1)	ATE135712T1 (de)
AU (1)	AU588837B2 (de)
CA (1)	CA1267997A (de)
DE (1)	DE3588095T2 (de)
DK (1)	DK171300B1 (de)
ES (1)	ES8800272A1 (de)
FI (1)	FI92935C (de)
GR (1)	GR852689B (de)
HU (1)	HU203563B (de)
IL (1)	IL76924A (de)
NO (1)	NO169347C (de)
NZ (1)	NZ214122A (de)
PH (1)	PH23847A (de)
PT (1)	PT81441B (de)
SU (1)	SU1433415A3 (de)
ZA (1)	ZA858456B (de)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2673376A1 (fr) *	1991-03-01	1992-09-04	Lefesvre Andre	Composition pharmaceutique pour le traitement des tumeurs de kaposi.
US5817628A (en) *	1992-12-02	1998-10-06	The Rockefeller University	Dynorphin a suppression of natural killer cell activity
SE9401596D0 (sv) *	1994-05-06	1994-05-06	Astra Ab	New compounds
JP3385147B2 (ja) *	1996-01-31	2003-03-10	ユニ・チャーム株式会社	男性用尿とり袋
AU3499997A (en) *	1996-06-24	1998-01-14	Rockefeller University, The	Method of using ligands of the kappa opioid receptor
NZ506839A (en) *	1998-03-09	2003-05-30	Zealand Pharma As	Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis
US6232287B1 (en) *	1998-03-13	2001-05-15	The Burnham Institute	Molecules that home to various selected organs or tissues
IL137820A (en) *	2000-08-10	2009-06-15	S I S Shulov Inst For Science	Pharmaceutical composition for topical administration comprising an analgesic peptide
AU8676301A (en) *	2000-08-25	2002-03-04	Res Corp Technologies Inc	New uses for amino acid anticonvulsants
DK1243262T3 (da) *	2001-03-20	2006-10-02	Sanol Arznei Schwarz Gmbh	Hidtil ukendt anvendelse af en peptidklasse af forbindelser til behandling af ikke-neuropatiske, inflammatoriske smerter
ES2185606T3 (es) *	2001-03-21	2003-05-01	Sanol Arznei Schwarz Gmbh	Nuevo uso de una clase de compuestos peptidicos para tratamiento de la alodinia u otros tipos diferentes de dolor cronico o fantasma.
US7491702B2 (en) *	2001-04-18	2009-02-17	The Open University	Polypeptides related to amyloid precursor protein, pharmaceutical compositions thereof, and methods of treatment using the same
US7622446B2 (en) *	2001-04-18	2009-11-24	The Open University	Polypeptides, derivatives and uses thereof
KR20070007931A (ko)	2004-04-16	2007-01-16	쉬바르츠파르마에이지	만성 두통의 예방 및 치료를 위한 펩티드 화합물의 용도
PL1781276T3 (pl) *	2004-08-27	2010-11-30	Ucb Pharma Gmbh	Zastosowanie związków peptydowych do leczenia bólu związanego z rakiem kości, bólu indukowanego przez chemioterapię oraz nukleozydy
US20070043120A1 (en) *	2005-08-18	2007-02-22	Bettina Beyreuther	Therapeutic combination for painful medical conditions
US20070048372A1 (en) *	2005-08-18	2007-03-01	Srz Properties, Inc.	Method for treating non-inflammatory osteoarthritic pain
EP1754476A1 (de) *	2005-08-18	2007-02-21	Schwarz Pharma Ag	Lacosamid (SPM 927) zur Behandlung von Myalgien, z.B. Fibromyalgie
GB2432586B (en) *	2005-11-25	2010-01-13	Univ Open	Treatment of neurodegenerative disorders
WO2007144195A2 (en)	2006-06-15	2007-12-21	Schwarz Pharma Ag	Pharmaceutical composition with synergistic anticonvulsant effect
US20100204145A1 (en) *	2007-09-11	2010-08-12	Dorian Bevec	Use of a peptide as a therapeutic agent
WO2009033690A1 (en) *	2007-09-11	2009-03-19	Mondobiotech Laboratories Ag	Bfgf (119-126) for therapeutic applications
CN111182887A (zh) *	2017-06-14	2020-05-19	株式会社生物解决方案有限公司	用于改善皮肤皱纹或抗炎活性的包括物质p的化妆品组合物
EP3681900A4 (de)	2017-09-11	2021-09-08	Protagonist Therapeutics, Inc.	Opioidagonistpeptide und verwendungen davon
CA3188556A1 (en) *	2020-07-01	2022-01-06	PreveCeutical Medical Inc.	Peptides and uses thereof
RU2760133C1 (ru) *	2021-04-22	2021-11-22	Федеральное государственное бюджетное учреждение науки "Научный центр биомедицинских технологий Федерального медико-биологического агентства".	Амиды гептапептида для лечения HMGB1-зависимых заболеваний
CA3238696A1 (en) *	2021-11-18	2023-05-25	PreveCeutical Medical Inc.	Peptides and uses thereof

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4254106A (en) *	1976-01-26	1981-03-03	Burroughs Wellcome Co.	Biologically active amides
JPS5291839A (en) *	1976-01-26	1977-08-02	Wellcome Found	Peptide and derivatives
US4123523A (en) *	1976-06-21	1978-10-31	Imperial Chemical Industries Limited	Analgesic and sedative polypeptides
US4371463A (en) *	1977-02-17	1983-02-01	The United States Of America As Represented By The Department Of Health And Human Services	Enzyme-resistant opiate pentapeptides
US4081434A (en) *	1977-03-11	1978-03-28	Hoffmann-La Roche Inc.	Novel analogs of β-endorphin
US4139504A (en) *	1977-06-16	1979-02-13	Coy David Howard	Novel nonapeptides, intermediates therefor, and compositions and methods employing said nonapeptides
US4127533A (en) *	1977-06-16	1978-11-28	Coy David Howard	Novel octapeptides, intermediates therefor, and compositions and methods employing said octapeptides
GB1604850A (en) *	1977-11-24	1981-12-16	Wellcome Found	Biologically active peptides
US4148786A (en) *	1978-06-26	1979-04-10	American Home Products Corporation	Analgesic polypeptide
US4178284A (en) *	1978-12-11	1979-12-11	American Home Products Corporation	Octapeptides
DE2936099A1 (de) *	1979-09-06	1981-04-02	Victor Dipl.- Chem. 8000 München Brantl	Pharmakologisch aktive peptide
EP0044451B1 (de) *	1980-07-17	1984-04-18	Sandoz Ag	Pentapeptide, Verfahren zu deren Herstellung, deren pharmazeutische Zusammensetzungen und deren Anwendung
JPS57134451A (en) *	1981-02-13	1982-08-19	Suntory Ltd	Peptide opioide
EP0076676B1 (de) *	1981-10-05	1986-12-30	Tni Pharmaceuticals, Inc.	Verfahren zur Verwendung von Endorphinen als Antitumormittel
US4462941A (en) *	1982-06-10	1984-07-31	The Regents Of The University Of California	Dynorphin amide analogs
JPS59141547A (ja) *	1983-02-01	1984-08-14	Eisai Co Ltd	鎮痛作用を有する新規ペプタイドおよび製法
US4518711A (en) *	1983-05-16	1985-05-21	Gibson-Stephens Institute	Conformationally constrained cyclic enkephalin analogs with delta receptor specificity

1984
- 1984-11-09 JP JP59236076A patent/JPH0680079B2/ja not_active Expired - Lifetime
1985
- 1985-10-28 FI FI854227A patent/FI92935C/fi not_active IP Right Cessation
- 1985-11-02 CN CN85109722A patent/CN1029684C/zh not_active Expired - Lifetime
- 1985-11-04 KR KR8508213A patent/KR880000765B1/ko not_active Expired
- 1985-11-04 PH PH33004A patent/PH23847A/en unknown
- 1985-11-04 IL IL76924A patent/IL76924A/xx not_active IP Right Cessation
- 1985-11-04 ZA ZA858456A patent/ZA858456B/xx unknown
- 1985-11-06 SU SU3974503A patent/SU1433415A3/ru active
- 1985-11-06 HU HU854270A patent/HU203563B/hu not_active IP Right Cessation
- 1985-11-06 AU AU49389/85A patent/AU588837B2/en not_active Ceased
- 1985-11-06 PT PT81441A patent/PT81441B/pt not_active IP Right Cessation
- 1985-11-07 NO NO854435A patent/NO169347C/no not_active IP Right Cessation
- 1985-11-07 DK DK513385A patent/DK171300B1/da not_active IP Right Cessation
- 1985-11-07 GR GR852689A patent/GR852689B/el unknown
- 1985-11-07 ES ES548667A patent/ES8800272A1/es not_active Expired
- 1985-11-08 CA CA000494974A patent/CA1267997A/en not_active Expired - Fee Related
- 1985-11-08 US US06/796,390 patent/US4707468A/en not_active Expired - Lifetime
- 1985-11-08 EP EP94107769A patent/EP0614913A3/de not_active Withdrawn
- 1985-11-08 NZ NZ214122A patent/NZ214122A/xx unknown
- 1985-11-08 AT AT85114226T patent/ATE135712T1/de not_active IP Right Cessation
- 1985-11-08 EP EP85114226A patent/EP0181001B1/de not_active Expired - Lifetime
- 1985-11-08 DE DE3588095T patent/DE3588095T2/de not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FI92935B (fi)	1994-10-14
HU203563B (en)	1991-08-28
CN85109722A (zh)	1986-10-08
PH23847A (en)	1989-11-23
CA1267997A (en)	1990-04-17
GR852689B (de)	1986-02-21
ZA858456B (en)	1987-07-29
ATE135712T1 (de)	1996-04-15
KR860004081A (ko)	1986-06-16
FI92935C (fi)	1995-01-25
NO169347B (no)	1992-03-02
SU1433415A3 (ru)	1988-10-23
FI854227L (fi)	1986-05-10
IL76924A0 (en)	1986-04-29
US4707468A (en)	1987-11-17
NZ214122A (en)	1988-08-30
DK513385A (da)	1986-05-10
HUT40145A (en)	1986-11-28
ES8800272A1 (es)	1987-10-16
DK513385D0 (da)	1985-11-07
DE3588095T2 (de)	1996-09-19
PT81441B (pt)	1987-11-11
ES548667A0 (es)	1987-10-16
PT81441A (en)	1985-12-01
AU588837B2 (en)	1989-09-28
JPS61115097A (ja)	1986-06-02
NO169347C (no)	1992-06-10
EP0614913A3 (de)	1997-06-04
IL76924A (en)	1990-07-12
EP0614913A2 (de)	1994-09-14
JPH0680079B2 (ja)	1994-10-12
NO854435L (no)	1986-05-12
EP0181001A2 (de)	1986-05-14
KR880000765B1 (en)	1988-05-06
EP0181001A3 (en)	1989-04-19
AU4938985A (en)	1986-05-15
DE3588095D1 (de)	1996-04-25
EP0181001B1 (de)	1996-03-20
CN1029684C (zh)	1995-09-06
FI854227A0 (fi)	1985-10-28

Legal Events

Date	Code	Title	Description
1996-08-26	B1	Patent granted (law 1993)
2003-07-14	PBP	Patent lapsed	Country of ref document: DK

Publication	Publication Date	Title
DK171300B1 (da)	1996-08-26	Polypeptider, fremgangsmåder til deres fremstilling og analgetikum indeholdende et sådant polypeptid
FI91075C (fi)	1994-05-10	Menetelmä uusien terapeuttisesti käyttökelpoisten peptidien valmistamiseksi
JP2795449B2 (ja)	1998-09-10	治療用ペプチド
DK167928B1 (da)	1994-01-03	Enzym-resistente immunomodulatoriske thymopoietin- eller spleninanaloge peptider og deres farmaceutisk acceptable syre- eller baseadditionssalte samt fremgangsmaade til fremstilling deraf
EP0674652B1 (de)	2000-09-13	Dolastatin analog
WO1986007263A1 (en)	1986-12-18	Bradykinin antagonist peptides
NO301015B1 (no)	1997-09-01	Dekapeptid med antiovulatorisk aktivitet
WO1996040751A1 (en)	1996-12-19	Novel dolastatin derivatives, their preparation and use
HU208439B (en)	1993-10-28	Process for producing pharmaceutical peptides
JPH02289599A (ja)	1990-11-29	オクタペプチド
HU211603A9 (en)	1995-12-28	Nonapeptide bombesin antagonists
KR100286242B1 (ko)	2001-04-16	돌라스타틴 유도체
US4128638A (en)	1978-12-05	Nona- and deca-peptide amide derivatives demonstrating high ovulation inducing activity
CN102482323A (zh)	2012-05-30	新型肽及其应用
NO891006L (no)	1989-09-12	Terapeutisk aktivt polypeptid og fremgangsmaate for dets fremstilling.
US4705778A (en)	1987-11-10	Orally active LHRH analogs
US3749703A (en)	1973-07-31	Asn15-bovine thyrocalcitonin
CA2405704C (en)	2010-11-16	Bombesin analogs for treatment of cancer
HU205771B (en)	1992-06-29	Process for producing irreversible peptide ligands for bombesin receptors and process for producing pharmaceutical compositions comprising such peptides as active ingredient
EP0101929B1 (de)	1986-01-22	Diester von Polypeptiden, ihre Herstellung und Verwendung
IE59556B1 (en)	1994-03-09	Therapeutic somatostatin analogs
EP0225746A2 (de)	1987-06-16	Therapeutische Dekapeptide
US6989371B1 (en)	2006-01-24	Bombesin analogs for treatment of cancer
US3328382A (en)	1967-06-27	L-prolyl-l-seryl-l-lysyl-l-alanyl-l-phenylalanyl-l-isoleucyl-glycyl-l-leucyl-l-methionine amide
AU2533988A (en)	1989-05-02	Vasoactive peptides