NO20006194D0 - Farmasöytisk sammensetning for behandling av funksjonell dyspepsi og/eller irriterbar innvollssyndrom og ny anvendelse av substanser deri - Google Patents

Farmasöytisk sammensetning for behandling av funksjonell dyspepsi og/eller irriterbar innvollssyndrom og ny anvendelse av substanser deri

Info

Publication number
NO20006194D0
NO20006194D0 NO20006194A NO20006194A NO20006194D0 NO 20006194 D0 NO20006194 D0 NO 20006194D0 NO 20006194 A NO20006194 A NO 20006194A NO 20006194 A NO20006194 A NO 20006194A NO 20006194 D0 NO20006194 D0 NO 20006194D0
Authority
NO
Norway
Prior art keywords
treatment
bowel syndrome
irritable bowel
functional dyspepsia
pharmaceutical composition
Prior art date
Application number
NO20006194A
Other languages
English (en)
Other versions
NO327738B1 (no
NO20006194L (no
Inventor
Per Hellstroem
Suad Efendic
Original Assignee
Per Hellstroem
Suad Efendic
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.)
Filing date
Publication date
Application filed by Per Hellstroem, Suad Efendic filed Critical Per Hellstroem
Publication of NO20006194D0 publication Critical patent/NO20006194D0/no
Publication of NO20006194L publication Critical patent/NO20006194L/no
Publication of NO327738B1 publication Critical patent/NO327738B1/no

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/26Glucagons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/31Somatostatins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
NO20006194A 1998-06-11 2000-12-06 Anvendelse av et gastrointestinalt peptidhormon eller et derivat derav samt farmasoytisk sammensetning NO327738B1 (no)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9802080A SE9802080D0 (sv) 1998-06-11 1998-06-11 Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein
PCT/SE1999/000997 WO1999064060A1 (en) 1998-06-11 1999-06-08 Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein

Publications (3)

Publication Number Publication Date
NO20006194D0 true NO20006194D0 (no) 2000-12-06
NO20006194L NO20006194L (no) 2001-01-25
NO327738B1 NO327738B1 (no) 2009-09-14

Family

ID=20411665

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20006194A NO327738B1 (no) 1998-06-11 2000-12-06 Anvendelse av et gastrointestinalt peptidhormon eller et derivat derav samt farmasoytisk sammensetning

Country Status (19)

Country Link
US (1) US6348447B1 (no)
EP (2) EP1405642A1 (no)
JP (2) JP2002517468A (no)
AT (1) ATE252912T1 (no)
AU (1) AU738994B2 (no)
CA (1) CA2321700C (no)
CZ (1) CZ300873B6 (no)
DE (1) DE69912434T2 (no)
DK (1) DK1094834T3 (no)
ES (1) ES2205845T3 (no)
HU (1) HUP0103147A3 (no)
NO (1) NO327738B1 (no)
NZ (1) NZ506163A (no)
PL (1) PL198802B1 (no)
PT (1) PT1094834E (no)
RU (1) RU2226402C2 (no)
SE (1) SE9802080D0 (no)
WO (1) WO1999064060A1 (no)
ZA (1) ZA200004080B (no)

Families Citing this family (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2686899B1 (fr) 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
US9006175B2 (en) * 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
DK1808438T3 (da) 1999-06-29 2014-10-27 Mannkind Corp Rensning og stabilisering af peptid og proteiner i lægemidler
US6528486B1 (en) 1999-07-12 2003-03-04 Zealand Pharma A/S Peptide agonists of GLP-1 activity
CN1487836A (zh) 2000-03-14 2004-04-07 埃米林药品公司 胰高糖素样肽1(7-36)对胃窦幽门十二指肠能动性的影响
EP2213743A1 (en) 2000-04-12 2010-08-04 Human Genome Sciences, Inc. Albumin fusion proteins
CN103356996A (zh) * 2000-05-19 2013-10-23 埃米林药品公司 Glp-1用于制备治疗急性冠脉综合征的药物的用途
WO2005003296A2 (en) 2003-01-22 2005-01-13 Human Genome Sciences, Inc. Albumin fusion proteins
AU2002364586A1 (en) 2001-12-21 2003-07-30 Delta Biotechnology Limited Albumin fusion proteins
PL209734B1 (pl) 2002-02-20 2011-10-31 Emisphere Tech Inc Preparat farmaceutyczny zawierający związek GLP-1 i czynnik dostarczający oraz jego zastosowanie
WO2003080149A2 (en) 2002-03-20 2003-10-02 Mannkind Corporation Inhalation apparatus
US20080260838A1 (en) * 2003-08-01 2008-10-23 Mannkind Corporation Glucagon-like peptide 1 (glp-1) pharmaceutical formulations
DK1641823T3 (da) 2003-06-12 2011-12-12 Lilly Co Eli GLP-1-analog fusionsproteiner
DK1633774T3 (da) 2003-06-18 2010-05-25 Tranzyme Pharma Inc Makrocykliske motilinreceptorantagonister
US20060286129A1 (en) 2003-12-19 2006-12-21 Emisphere Technologies, Inc. Oral GLP-1 formulations
PL1786784T3 (pl) 2004-08-20 2011-04-29 Mannkind Corp Kataliza syntezy diketopiperazyn
KR101644250B1 (ko) 2004-08-23 2016-07-29 맨카인드 코포레이션 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염
US20090305964A1 (en) * 2005-04-21 2009-12-10 Gastrotech Pharma A/S Pharmaceutical preparations of a glp-1 molecule and an anti-emetic drug
CA2608311C (en) 2005-05-13 2012-11-27 Eli Lilly And Company Glp-1 pegylated compounds
CN101258163B (zh) 2005-06-30 2013-08-21 益普生制药股份有限公司 Glp-1药物组合物
JP4994374B2 (ja) * 2005-07-29 2012-08-08 ジオファーム オンコロジー, インコーポレイテッド がんを治療するための化合物および方法
CN104324362B (zh) 2005-09-14 2018-04-24 曼金德公司 以提高活性试剂对结晶微粒表面的亲和力为基础的药物配制方法
IN2015DN00888A (no) 2006-02-22 2015-07-10 Mannkind Corp
MX2009006942A (es) * 2006-12-29 2009-11-09 Ipsen Pharma Sas Composiciones farmaceuticas de glp-1.
WO2008134425A1 (en) * 2007-04-27 2008-11-06 Cedars-Sinai Medical Center Use of glp-1 receptor agonists for the treatment of gastrointestinal disorders
US8785396B2 (en) 2007-10-24 2014-07-22 Mannkind Corporation Method and composition for treating migraines
WO2009055742A2 (en) * 2007-10-24 2009-04-30 Mannkind Corporation Delivery of active agents
JP2011500850A (ja) * 2007-10-24 2011-01-06 マンカインド コーポレイション Glp−1による副作用を防止する方法
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
ES2929343T3 (es) 2008-06-13 2022-11-28 Mannkind Corp Inhalador de polvo seco accionado por aspiración para la administración de fármacos
US8765669B2 (en) 2008-06-17 2014-07-01 Glytech, Inc. Glycosylated GLP-1 peptide
KR101628410B1 (ko) 2008-06-20 2016-06-08 맨카인드 코포레이션 흡입 활동에 관한 실시간 프로파일링을 위한 대화형 장치 및 방법
TWI614024B (zh) 2008-08-11 2018-02-11 曼凱公司 超快起作用胰島素之用途
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
EP2216042A1 (en) 2009-02-09 2010-08-11 Ipsen Pharma S.A.S. GLP-1 analogues pharmaceutical compositions
DK2405963T3 (da) 2009-03-11 2013-12-16 Mannkind Corp Apparat, system og fremgangsmåde til at måle modstand i en inhalator
US8614185B2 (en) 2009-05-04 2013-12-24 Centocor Ortho Biotech Inc. Fusion proteins of alpha-MSH derivatives and Fc
WO2010129248A1 (en) 2009-05-06 2010-11-11 Centocor Ortho Biotech Inc. Melanocortin receptor binding conjugates
CN104721825B (zh) 2009-06-12 2019-04-12 曼金德公司 具有确定比表面积的二酮哌嗪颗粒
SG177592A1 (en) * 2009-07-29 2012-02-28 Daiichi Sankyo Co Ltd Motilin-like peptide compound having transmucosal absorbability imparted thereto
KR20120101037A (ko) 2009-10-30 2012-09-12 오츠카 가가쿠 가부시키가이샤 항원성 glp?1 아날로그의 당쇄 부가체
WO2011056889A1 (en) 2009-11-03 2011-05-12 Mannkind Corporation An apparatus and method for simulating inhalation efforts
WO2011123943A1 (en) 2010-04-09 2011-10-13 Mount Sinai Hospital Methods for treating disorders of the gastrointestinal tract using a glp-1 agonist
CN107129538B (zh) 2010-04-27 2021-07-16 西兰制药公司 Glp-1受体激动剂和胃泌素的肽缀合物及其用途
IL223742A (en) 2010-06-21 2016-06-30 Mannkind Corp A dry powder inhaler and preparation for it
JP2013530993A (ja) 2010-07-02 2013-08-01 アンジオケム インコーポレーテッド 治療用コンジュゲートのための短く且つd−アミノ酸を含有するポリペプチドおよびその使用
SI2651398T1 (en) 2010-12-16 2018-04-30 Novo Nordisk A/S SOLID COMPOSITIONS CONTAINING GLP-1 AGONIST AND SOL N- (8- (2-HYDROXYBENZOIL) AMINO) CAPRICULATE ACIDS
AU2012236150B2 (en) 2011-04-01 2016-03-31 Mannkind Corporation Blister package for pharmaceutical cartridges
PL2696687T3 (pl) 2011-04-12 2017-06-30 Novo Nordisk A/S Pochodne podwójnie acylowanej GLP-1
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
BR112014009686A2 (pt) 2011-10-24 2018-08-07 Mannkind Corp composição analgésica inalável, pó seco e método para tratar dor
TW201326194A (zh) 2011-11-03 2013-07-01 Zealand Pharma As Glp-1胃泌素受體促效劑肽結合物
HRP20181447T1 (hr) 2012-03-22 2018-11-02 Novo Nordisk A/S Pripravci glp-1 peptida i njihova priprava
PT2827845T (pt) 2012-03-22 2019-03-29 Novo Nordisk As Composições compreendendo um agente de entrega e sua preparação
ES2965469T3 (es) 2012-03-22 2024-04-15 Novo Nordisk As Composiciones que comprenden un agente de suministro y preparación de estas
JP6517690B2 (ja) 2012-06-20 2019-05-22 ノヴォ ノルディスク アー/エス ペプチド及び送達剤を含む錠剤製剤
CN104619369B (zh) 2012-07-12 2018-01-30 曼金德公司 干粉药物输送系统和方法
IN2015DN00544A (no) 2012-07-23 2015-06-26 Zealand Pharma As
TWI608013B (zh) 2012-09-17 2017-12-11 西蘭製藥公司 升糖素類似物
US10159644B2 (en) 2012-10-26 2018-12-25 Mannkind Corporation Inhalable vaccine compositions and methods
AU2014228415B2 (en) 2013-03-15 2018-08-09 Mannkind Corporation Microcrystalline diketopiperazine compositions and methods
KR102272671B1 (ko) 2013-05-02 2021-07-06 노보 노르디스크 에이/에스 Glp-1 화합물의 경구 투여
MX375448B (es) 2013-07-18 2025-03-06 Mannkind Corp Composiciones farmacéuticas en polvo seco estables al calor y métodos.
US11446127B2 (en) 2013-08-05 2022-09-20 Mannkind Corporation Insufflation apparatus and methods
CN104371019B (zh) 2013-08-13 2019-09-10 鸿运华宁(杭州)生物医药有限公司 一种能与glp-1r特异性结合的抗体及其与glp-1的融合蛋白质
US9988429B2 (en) 2013-10-17 2018-06-05 Zealand Pharma A/S Glucagon analogues
PL3057984T3 (pl) 2013-10-17 2018-12-31 Zealand Pharma A/S Acylowane analogi glukagonu
CN105829339B (zh) 2013-11-06 2021-03-12 西兰制药公司 胰高血糖素-glp-1-gip三重激动剂化合物
WO2015067715A2 (en) 2013-11-06 2015-05-14 Zealand Pharma A/S Gip-glp-1 dual agonist compounds and methods
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
KR102620911B1 (ko) 2014-10-29 2024-01-05 질랜드 파마 에이/에스 Gip 효능제 화합물 및 방법
KR101825048B1 (ko) 2014-12-31 2018-02-05 주식회사 제넥신 GLP 및 면역글로불린 하이브리드 Fc 융합 폴리펩타이드 및 이의 용도
PT3257524T (pt) 2015-02-11 2020-11-27 Gmax Biopharm Llc Preparação de solução estabilizada de proteína de fusão de anticorpo glp-1r farmacêutica
DK3283507T3 (da) 2015-04-16 2020-01-02 Zealand Pharma As Acyleret glucagonanalog
EP3551651B1 (en) 2016-12-09 2024-03-06 Zealand Pharma A/S Acylated glp-1/glp-2 dual agonists
JP6898518B2 (ja) 2018-02-02 2021-07-07 ノヴォ ノルディスク アー/エス Glp−1アゴニスト、n−(8−(2−ヒドロキシベンゾイル)アミノ)カプリル酸の塩及び滑沢剤を含む固形組成物
CN117126279A (zh) 2018-03-20 2023-11-28 鸿运华宁(杭州)生物医药有限公司 Gipr抗体及其与glp-1的融合蛋白质,以及其药物组合物和应用
CN112521501A (zh) 2019-09-18 2021-03-19 鸿运华宁(杭州)生物医药有限公司 Gipr抗体及其与glp-1的融合蛋白质,以及其药物组合物和应用
CN119744271A (zh) 2022-09-08 2025-04-01 鸿运华宁(杭州)生物医药有限公司 Gipr抗体及其与fgf21的融合蛋白,以及其药物组合物和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY147327A (en) * 1995-06-29 2012-11-30 Novartis Ag Somatostatin peptides
US5994500A (en) * 1996-07-19 1999-11-30 1149336 Ontario Inc. Antagonists of intestinotrophic GLP-2 peptides

Also Published As

Publication number Publication date
HUP0103147A2 (hu) 2002-01-28
CA2321700A1 (en) 1999-12-16
DE69912434D1 (de) 2003-12-04
PL198802B1 (pl) 2008-07-31
PL343104A1 (en) 2001-07-30
AU738994B2 (en) 2001-10-04
NO327738B1 (no) 2009-09-14
US6348447B1 (en) 2002-02-19
DK1094834T3 (da) 2004-01-05
EP1405642A1 (en) 2004-04-07
NZ506163A (en) 2004-10-29
RU2226402C2 (ru) 2004-04-10
CZ20004491A3 (en) 2001-05-16
HUP0103147A3 (en) 2002-02-28
DE69912434T2 (de) 2004-05-06
ATE252912T1 (de) 2003-11-15
CZ300873B6 (cs) 2009-09-02
JP2002517468A (ja) 2002-06-18
WO1999064060A1 (en) 1999-12-16
EP1094834B1 (en) 2003-10-29
JP2010270125A (ja) 2010-12-02
EP1094834A1 (en) 2001-05-02
AU4669799A (en) 1999-12-30
SE9802080D0 (sv) 1998-06-11
PT1094834E (pt) 2004-03-31
ES2205845T3 (es) 2004-05-01
NO20006194L (no) 2001-01-25
ZA200004080B (en) 2001-12-24
CA2321700C (en) 2011-05-03

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