DE60038097T2 - Feste orale dosierungsform enthaltend einen resorptionsverstärker - Google Patents
Feste orale dosierungsform enthaltend einen resorptionsverstärker Download PDFInfo
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- DE60038097T2 DE60038097T2 DE60038097T DE60038097T DE60038097T2 DE 60038097 T2 DE60038097 T2 DE 60038097T2 DE 60038097 T DE60038097 T DE 60038097T DE 60038097 T DE60038097 T DE 60038097T DE 60038097 T2 DE60038097 T2 DE 60038097T2
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- dosage form
- oral dosage
- solid oral
- enhancer
- form according
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Classifications
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12104899P | 1999-02-22 | 1999-02-22 | |
| US121048P | 1999-02-22 | ||
| PCT/GB2000/000628 WO2000050012A1 (en) | 1999-02-22 | 2000-02-22 | Solid oral dosage form containing an enhancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60038097D1 DE60038097D1 (de) | 2008-04-03 |
| DE60038097T2 true DE60038097T2 (de) | 2009-02-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60038097T Expired - Lifetime DE60038097T2 (de) | 1999-02-22 | 2000-02-22 | Feste orale dosierungsform enthaltend einen resorptionsverstärker |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1154761B1 (https=) |
| JP (2) | JP2002537321A (https=) |
| AT (1) | ATE386508T1 (https=) |
| AU (1) | AU2681300A (https=) |
| CA (1) | CA2363123C (https=) |
| DE (1) | DE60038097T2 (https=) |
| ES (1) | ES2301477T3 (https=) |
| WO (1) | WO2000050012A1 (https=) |
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| JP2002529204A (ja) | 1998-11-13 | 2002-09-10 | エラン・フアルマ・インターナシヨナル・リミテツド | 薬品を給送するシステム及び方法 |
| US7084279B1 (en) | 1999-02-11 | 2006-08-01 | Emisphere Technologies Inc. | Oxadiazole compounds and compositions for delivering active agents |
| US7658938B2 (en) | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
| JP2007016034A (ja) * | 2000-12-26 | 2007-01-25 | Kirin Brewery Co Ltd | 吸収促進剤 |
| WO2002064148A2 (en) * | 2001-02-16 | 2002-08-22 | Shimizu Pharmaceutical Co., Ltd. | Oral formulations containing mucopolysaccharide for small intestine delivery and their use in the treatment circulatory disorders |
| EP1390383B1 (en) | 2001-05-11 | 2012-02-29 | Isis Pharmaceuticals, Inc. | Antisense permeation enhancers |
| US8241670B2 (en) | 2004-04-15 | 2012-08-14 | Chiasma Inc. | Compositions capable of facilitating penetration across a biological barrier |
| BRPI0513508B1 (pt) * | 2004-07-19 | 2021-06-01 | Biocon Limited | Conjugados de insulina-oligômero, formulações e usos desses |
| AU2014200247B2 (en) * | 2004-07-19 | 2015-05-14 | Biocon Limited | Insulin-oligomer conjugates, formulations and uses thereof |
| WO2006124047A2 (en) * | 2004-08-13 | 2006-11-23 | Emisphere Technologies, Inc. | Pharmaceutical formulations containing microparticles or nanoparticles of a delivery agent |
| JP4759289B2 (ja) * | 2005-03-02 | 2011-08-31 | 国立大学法人北海道大学 | カルシウム吸収促進組成物およびその利用 |
| KR101191322B1 (ko) * | 2006-04-07 | 2012-10-16 | 메리온 리서치 Ⅲ 리미티드 | 증진제를 함유하는 고형 경구용 투여 제형 |
| EP2040731A4 (en) * | 2006-06-09 | 2010-05-19 | Merrion Res Iii Ltd | SOLID DOSAGE FORM FOR ORAL ADMINISTRATION CONTAINING AN ACTIVATOR |
| US20090285887A1 (en) * | 2006-09-12 | 2009-11-19 | Omar Abdelfattah Abu-Baker | Pharmaceutical Composition Comprising A Plurality of Mini-Tablets Comprising A Factor XA Inhibitor |
| JP5868594B2 (ja) * | 2007-10-16 | 2016-02-24 | バイオコン・リミテッドＢｉｏｃｏｎ Ｌｉｍｉｔｅｄ | 経口投与可能な固形医薬組成物及びそのプロセス |
| TWI584817B (zh) | 2007-11-05 | 2017-06-01 | 嘉樂懷醫藥股份有限公司 | 用於增強經口投與之極性劑的生物可用性之調配物 |
| CN107096012A (zh) | 2008-05-07 | 2017-08-29 | 诺和诺德股份有限公司 | 肽的组合物及其制备方法 |
| CN102176900B (zh) | 2008-09-17 | 2017-09-26 | 克艾思马有限公司 | 药物组合物和相关的给药方法 |
| GB0904942D0 (en) * | 2009-03-23 | 2009-05-06 | Ntnu Technology Transfer As | Composition |
| US9169279B2 (en) | 2009-07-31 | 2015-10-27 | Thar Pharmaceuticals, Inc. | Crystallization method and bioavailability |
| DK2459176T3 (en) | 2009-07-31 | 2017-12-04 | Gruenenthal Gmbh | Crystallization process and bioavailability |
| US20160016982A1 (en) | 2009-07-31 | 2016-01-21 | Thar Pharmaceuticals, Inc. | Crystallization method and bioavailability |
| AU2010339907A1 (en) | 2009-12-16 | 2012-07-05 | Nod Pharmaceuticals, Inc. | Compositions and methods for oral drug delivery |
| US20110182985A1 (en) * | 2010-01-28 | 2011-07-28 | Coughlan David C | Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof |
| WO2011120033A1 (en) | 2010-03-26 | 2011-09-29 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor xa inhibitors for oral administration |
| US9340565B2 (en) | 2010-11-24 | 2016-05-17 | Thar Pharmaceuticals, Inc. | Crystalline forms |
| CA2819108A1 (en) * | 2010-12-15 | 2012-06-21 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor xa inhibitors for oral administration |
| MX377589B (es) | 2010-12-16 | 2025-03-10 | Novo Nordisk As | Composiciones sólidas que comprenden agonista de glp-1 y sal del ácido n-(8-(2-hidroxibenzoil)amino)caprílico. |
| EP2661273A4 (en) * | 2011-01-07 | 2014-06-04 | Merrion Res Iii Ltd | IRON PHARMACEUTICAL COMPOSITIONS FOR ORAL ADMINISTRATION |
| RU2602601C2 (ru) | 2011-04-12 | 2016-11-20 | Ново Нордиск А/С | Дважды ацилированные производные glp-1 |
| DK2827845T3 (en) | 2012-03-22 | 2019-04-01 | Novo Nordisk As | COMPOSITIONS INCLUDING A PROCEDURE AND PREPARING THEREOF |
| EP3542790B1 (en) | 2012-03-22 | 2023-09-13 | Novo Nordisk A/S | Compositions comprising a delivery agent and preparation thereof |
| CN104203266B (zh) | 2012-03-22 | 2017-12-26 | 诺和诺德股份有限公司 | Glp‑1肽组合物及其制备 |
| 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 |
| JP6672140B2 (ja) | 2013-05-02 | 2020-03-25 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１化合物の経口投薬 |
| US10265384B2 (en) | 2015-01-29 | 2019-04-23 | Novo Nordisk A/S | Tablets comprising GLP-1 agonist and enteric coating |
| HUE071943T2 (hu) | 2015-02-03 | 2025-10-28 | Amryt Endo Inc | Akromegália kezelése oktreotid orális alkalmazásával |
| PL3280447T3 (pl) * | 2015-04-08 | 2019-07-31 | Torrent Pharmaceuticals Limited | Preparaty farmaceutyczne |
| GB201515387D0 (en) * | 2015-08-28 | 2015-10-14 | Amazentis Sa | Compositions |
| WO2017149070A1 (en) | 2016-03-03 | 2017-09-08 | Novo Nordisk A/S | Glp-1 derivatives and uses thereof |
| US10195218B2 (en) | 2016-05-31 | 2019-02-05 | Grunenthal Gmbh | Crystallization method and bioavailability |
| WO2019016300A1 (en) | 2017-07-19 | 2019-01-24 | Novo Nordisk A/S | EGF ANALOGUES (A), PREPARATION, FORMULATIONS AND USES THEREOF |
| PL3746111T3 (pl) | 2018-02-02 | 2024-01-15 | Novo Nordisk A/S | Stałe kompozycje zawierające agonistę glp-1 i sól kwasu n-(8-(2- hydroksybenzoilo)amino kaprylowego i substancję poślizgową |
| US11141457B1 (en) | 2020-12-28 | 2021-10-12 | Amryt Endo, Inc. | Oral octreotide therapy and contraceptive methods |
| JPWO2024143501A1 (https=) * | 2022-12-28 | 2024-07-04 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB953626A (en) * | 1961-04-25 | 1964-03-25 | Meito Sangyo Kk | Enteric-coated tablets of dextran sulphate ester and method of preparation thereof |
| US4525339A (en) * | 1982-10-15 | 1985-06-25 | Hoffmann-La Roche Inc. | Enteric coated oral dosage form |
| JPS5973600A (ja) * | 1982-10-19 | 1984-04-25 | Okayasu Shoten:Kk | 排卵誘発剤 |
| DE3331009A1 (de) * | 1983-08-27 | 1985-03-14 | Basf Ag, 6700 Ludwigshafen | Verfahren zur erhoehung der enteralen resorbierbarkeit von heparin bzw. heparinoiden sowie das so erhaeltliche heparin- bzw. heparinoidpraeparat |
| ZA898331B (en) * | 1988-11-22 | 1990-07-25 | Hoffmann La Roche | Pharmaceutical compositions |
| JPH03275633A (ja) * | 1990-03-23 | 1991-12-06 | Teikoku Seiyaku Co Ltd | 生理活性ポリペプチドの吸収促進剤 |
| JPH04149126A (ja) | 1990-10-09 | 1992-05-22 | Mitsubishi Kasei Corp | 経粘膜投与用医薬組成物 |
| IT1245761B (it) * | 1991-01-30 | 1994-10-14 | Alfa Wassermann Spa | Formulazioni farmaceutiche contenenti glicosaminoglicani assorbibili per via orale. |
| AU653026B2 (en) * | 1991-06-07 | 1994-09-15 | Teikoku Seiyaku Kabushiki Kaisha | Physiologically active polypeptide-containing pharmaceutical composition |
| CZ282760B6 (cs) * | 1991-11-22 | 1997-09-17 | Procter And Gamble Pharmaceuticals, Inc. | Risedronátové prostředky se zpožděným uvolňováním |
| SE501389C2 (sv) * | 1992-04-24 | 1995-01-30 | Leiras Oy | Farmaceutiskt preparat och förfarande för dess framställning |
| RU2068689C1 (ru) * | 1992-09-24 | 1996-11-10 | Товарищество с ограниченной ответственностью "Лекрон" | Способ получения таблеток парацетамола |
| DK0667148T3 (da) * | 1992-11-06 | 2002-07-22 | Hisamitsu Pharmaceutical Co | Peroralt farmaceutisk præparat, der udløses i den nedre del af mavetarmkanalen |
| JPH06192107A (ja) | 1992-12-25 | 1994-07-12 | Sanwa Kagaku Kenkyusho Co Ltd | グリチルリチン経口剤 |
| GB9516268D0 (en) * | 1995-08-08 | 1995-10-11 | Danbiosyst Uk | Compositiion for enhanced uptake of polar drugs from the colon |
| GB9614235D0 (en) * | 1996-07-06 | 1996-09-04 | Danbiosyst Uk | Composition for enhanced uptake of polar drugs from mucosal surfaces |
-
2000
- 2000-02-22 CA CA2363123A patent/CA2363123C/en not_active Expired - Fee Related
- 2000-02-22 AU AU26813/00A patent/AU2681300A/en not_active Abandoned
- 2000-02-22 DE DE60038097T patent/DE60038097T2/de not_active Expired - Lifetime
- 2000-02-22 WO PCT/GB2000/000628 patent/WO2000050012A1/en not_active Ceased
- 2000-02-22 EP EP00905186A patent/EP1154761B1/en not_active Expired - Lifetime
- 2000-02-22 AT AT00905186T patent/ATE386508T1/de not_active IP Right Cessation
- 2000-02-22 ES ES00905186T patent/ES2301477T3/es not_active Expired - Lifetime
- 2000-02-22 JP JP2000600624A patent/JP2002537321A/ja active Pending
-
2011
- 2011-11-07 JP JP2011243450A patent/JP5412491B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60038097D1 (de) | 2008-04-03 |
| JP2002537321A (ja) | 2002-11-05 |
| ES2301477T3 (es) | 2008-07-01 |
| JP5412491B2 (ja) | 2014-02-12 |
| ATE386508T1 (de) | 2008-03-15 |
| CA2363123C (en) | 2011-09-06 |
| CA2363123A1 (en) | 2000-08-31 |
| JP2012067115A (ja) | 2012-04-05 |
| EP1154761B1 (en) | 2008-02-20 |
| AU2681300A (en) | 2000-09-14 |
| EP1154761A1 (en) | 2001-11-21 |
| WO2000050012A1 (en) | 2000-08-31 |
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Owner name: MERRION RESEARCH III LTD., DUBLIN, IE |