JP5108304B2 - 炎症性腸疾患の治療用製剤及び方法 - Google Patents
炎症性腸疾患の治療用製剤及び方法 Download PDFInfo
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Description
実施例3:膜調節錠剤を用いる4−アミノサリチル酸ナトリウムの調節放出製剤
多粒子及び/又は錠剤製剤
Claims (14)
- 4−アミノサリチル酸、5−アミノサリチル酸、それらの製薬的に受容される塩及びエステル、並びにそれらのプロドラッグから選択されるサリチレート及び/又はサリチル酸と、少なくとも1種類の製薬的に受容される賦形剤と、(a)エチルセルロースと組み合わせた、メチルセルロース及びヒドロキシプロピルメチルセルロースの少なくとも1種、または(b)少なくとも2種のアンモニオメタクリレート・コポリマーのいずれかから選択されるポリマー系を含み、調節放出薬剤組成物として製剤化される薬剤組成物であって、周囲pHに依存しない薬剤放出を示す薬剤組成物であって、
該組成物が、試験のために米国薬局方II型装置(パドル)において37℃及び50rpm、pH6.8緩衝剤中で試験した場合に、下記溶解プロフィル:
1時間:10%以下の薬物放出;
2時間:0〜35%薬物放出;
3時間:10〜60%薬物放出;
4時間:20〜60%薬物放出;
6時間:40〜80%薬物放出;及び
12時間:75〜100%薬物放出
を示す、薬剤組成物。 - 該組成物が、試験のために米国薬局方II型装置(パドル)において37℃及び50rpm、pH6.8緩衝剤中で試験した場合に、下記溶解プロフィル:
1時間:5%以下の薬物放出;
2時間:0〜25%薬物放出;
3時間:15〜30%薬物放出;
4時間:40〜50%薬物放出;
6時間:60〜75%薬物放出;及び
12時間:90〜100%薬物放出
を示す、請求項1記載の薬剤組成物。 - 該調節放出組成物が、即時放出コアと半透性膜を含む、請求項1記載の薬剤組成物。
- 該調節放出組成物が、調節放出マトリックス・コアと半透性膜を含む、請求項1記載の薬剤組成物。
- 該サリチレート及び/又はサリチル酸が、4−アミノサリチル酸及び5−アミノサリチル酸、並びにそれらの製薬的に受容される塩若しくはエステルから選択される、請求項1記載の組成物。
- 4−アミノサリチル酸、5−アミノサリチル酸、又はそれらの製薬的に受容される塩若しくはエステルを含む、請求項1記載の組成物。
- 該サリチレート及び/又はサリチル酸が、5,5’−アゾ−ビスサリチル酸、4,5’−アゾ−ビスサリチル酸、4,4’−アゾ−ビスサリチル酸、及びそれらの製薬的に受容される塩から選択される、請求項1記載の組成物。
- 該ポリマー系が、ヒドロキシプロピルメチルセルロースとエチルセルロースとを含む、請求項1記載の組成物。
- 該少なくとも1種類の製薬的に受容される賦形剤が、ヒドロキシプロピルメチルセルロースを含む、請求項8記載の組成物。
- 該ポリマー系が、少なくとも2種のアンモニオメタクリレート・コポリマーを含む、請求項1記載の組成物。
- 該ポリマー系が、機能性被膜及びシーラントを含む、請求項1記載の組成物。
- 機能性被膜がエチルセルロースを含み、シーラントがヒドロキシプロピルメチルセルロースを含む、請求項11記載の組成物。
- 該サリチレート及び/又はサリチル酸が、4,4’−アゾ−ビスサリチル酸である、炎症性腸疾患の治療用の請求項1記載の組成物。
- 該調節放出製剤が、遅延放出性及び持続放出性を有する放出プロフィルを示す、請求項13記載の組成物。
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PCT/IB2004/003059 WO2005021009A2 (en) | 2003-09-03 | 2004-09-02 | Formulations and methods of treating inflammatory bowel disease |
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Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004112756A1 (en) | 2003-06-26 | 2004-12-29 | Isa Odidi | Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient |
US7825106B2 (en) * | 2003-09-03 | 2010-11-02 | Agi Therapeutics Ltd. | Modified release formulations and methods of treating inflammatory bowel disease |
US7737133B2 (en) | 2003-09-03 | 2010-06-15 | Agi Therapeutics Ltd. | Formulations and methods of treating inflammatory bowel disease |
EP1720536B1 (en) | 2004-02-06 | 2012-04-25 | PHARMATEL (R&D) PTY LIMITED as Trustee for the PHARMATEL (R & D) TRUST | Use of aminosalicylates in diarrhoea-predominent irritable bowel syndrome |
JP5009152B2 (ja) * | 2004-05-28 | 2012-08-22 | サリックス ファーマシューティカルズ, インコーポレイテッド | 放射線誘発性腸炎の予防、処置、および回復 |
US8394409B2 (en) | 2004-07-01 | 2013-03-12 | Intellipharmaceutics Corp. | Controlled extended drug release technology |
US10624858B2 (en) | 2004-08-23 | 2020-04-21 | Intellipharmaceutics Corp | Controlled release composition using transition coating, and method of preparing same |
US20090017110A1 (en) * | 2005-05-31 | 2009-01-15 | Capricorn Pharma Inc. | Modified release formulations of anti-irritability drugs |
US20070015689A1 (en) * | 2005-06-23 | 2007-01-18 | Alza Corporation | Complexation of metal ions with polypeptides |
US7452872B2 (en) | 2005-08-24 | 2008-11-18 | Salix Pharmaceuticals, Inc. | Formulations and uses of 2-hydroxy-5-phenylazobenzoic acid derivatives |
US8921344B2 (en) * | 2006-11-03 | 2014-12-30 | Salix Pharmaceuticals, Inc. | Formulations and uses of 2-hydroxy-5-phenylazobenzoic acid derivatives |
EP2586427A3 (en) * | 2005-08-24 | 2013-05-29 | Salix Pharmaceuticals, Inc. | Balsalazide formulations and manufacture thereof |
US8679545B2 (en) | 2005-11-12 | 2014-03-25 | The Regents Of The University Of California | Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract |
US10064828B1 (en) | 2005-12-23 | 2018-09-04 | Intellipharmaceutics Corp. | Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems |
US9561188B2 (en) | 2006-04-03 | 2017-02-07 | Intellipharmaceutics Corporation | Controlled release delivery device comprising an organosol coat |
US10960077B2 (en) | 2006-05-12 | 2021-03-30 | Intellipharmaceutics Corp. | Abuse and alcohol resistant drug composition |
US9095512B2 (en) * | 2006-08-11 | 2015-08-04 | Asahi Kasei Chemicals Corporation | Method for producing spherical base granules comprising hardly water-soluble drug |
US9744137B2 (en) * | 2006-08-31 | 2017-08-29 | Supernus Pharmaceuticals, Inc. | Topiramate compositions and methods of enhancing its bioavailability |
WO2008043107A2 (en) * | 2006-10-06 | 2008-04-10 | Alba Therapeutics Corporation | Use of tight junction antagonists to treat inflammatory bowel disease |
ES2312308T3 (es) | 2006-11-17 | 2013-03-26 | Supernus Pharmaceuticals, Inc. | Formulaciones de liberación sostenida de topiramato |
AU2007329373B2 (en) * | 2006-12-04 | 2013-06-20 | Supernus Pharmaceuticals, Inc. | Enhanced immediate release formulations of topiramate |
WO2008085484A2 (en) * | 2006-12-28 | 2008-07-17 | Jacobus Pharmaceutical Company, Inc. | Treatment of inflammatory bowel disease with enteric coated formulations comprising 5-aminosalicylic acid or 4-aminosalicylic acid |
WO2008115979A2 (en) * | 2007-03-20 | 2008-09-25 | Isp Investments Inc. | Meltable binder for melt granulation and/or pelletization |
US20090036414A1 (en) * | 2007-08-02 | 2009-02-05 | Mutual Pharmaceutical Company, Inc. | Mesalamine Formulations |
WO2009047802A2 (en) * | 2007-10-10 | 2009-04-16 | Lupin Limited | Novel colon targeted modified release bioadhesive formulation of 5-amino salicylic acid or its salts and metabolites thereof |
US20090162434A1 (en) * | 2007-12-21 | 2009-06-25 | Disphar International Bv | Mesalazine tablet |
US20120093939A1 (en) * | 2008-12-17 | 2012-04-19 | Altheus Therapeutics, Inc. | Oral formulations |
MX2019001413A (es) | 2008-12-19 | 2019-08-12 | Supernus Pharmaceuticals Inc | Uso de molindona para el tratamiento de agresion. |
AU2011235222B2 (en) | 2010-03-31 | 2014-09-25 | Supernus Pharmaceuticals Inc. | Stabilized formulations of CNS compounds |
US8597683B2 (en) * | 2010-11-30 | 2013-12-03 | Watson Pharmaceuticals, Inc. | Modified release tranexamic acid formulation |
EP2822542A1 (en) * | 2012-03-07 | 2015-01-14 | Santarus, Inc. | Controlled-release solid dosage forms of mesalamine |
US20140141075A1 (en) | 2012-11-21 | 2014-05-22 | Warner Chilcott Company, Llc | 5-aminosalicylic acid capsule formulation |
JP5897196B1 (ja) * | 2015-10-05 | 2016-03-30 | 大同化成工業株式会社 | 糖又は糖アルコール、膨潤型結合剤、崩壊剤及び高吸収性賦形剤を含む複合化造粒物及びその製造方法 |
US20170119680A1 (en) | 2015-10-30 | 2017-05-04 | R.P. Scherer Technologies, Llc | Extended release film-coated capsules |
US20210077415A1 (en) * | 2018-01-03 | 2021-03-18 | Ferring B.V. | Oral liquid pharmaceutical compositions of aminosalicylates |
US12053447B2 (en) | 2019-06-25 | 2024-08-06 | NuBioPharma, LLC | Oral solution and powder to liquid compositions of balsalazide |
CN112569915B (zh) * | 2020-12-27 | 2023-06-23 | 王晓玉 | 一种煤矿井水除铀吸附剂、及其制备方法和应用 |
Family Cites Families (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1981002671A1 (en) * | 1980-03-20 | 1981-10-01 | Ferring Farma Lab | Pharmaceutical composition and method for the treatment of colitis ulcerosa and crohn's disease by oral administration |
SE8002322L (sv) * | 1980-03-26 | 1981-09-27 | Pharmacia Ab | Medel for behandling av inflammatoriska tarmsjukdomar |
US4374932A (en) * | 1981-06-08 | 1983-02-22 | G. D. Searle & Co. | 5-ASA Drug delivery system |
ZA825384B (en) * | 1981-07-31 | 1983-05-25 | Tillott J B Ltd | Orally administrable pharmaceutical compositions |
SE8303399D0 (sv) * | 1983-06-15 | 1983-06-15 | Pharmacia Ab | Azo-bis-salicyl syra och salt derav, deras farmaceutiska beredning samt framstellning av syran |
SE8303400D0 (sv) | 1983-06-15 | 1983-06-15 | Pharmacia Ab | Azo-bis-salicylsyra och salt derav samt deras farmaceutiska beredning och anvendning |
US4627851A (en) * | 1984-10-26 | 1986-12-09 | Alza Corporation | Colonic-therapeutic delivery system |
US4705515A (en) * | 1984-10-26 | 1987-11-10 | Alza Corporation | Dosage form for administering drug of the colon |
US4693895A (en) * | 1984-10-26 | 1987-09-15 | Alza Corporation | Colon delivery system |
US4608048A (en) | 1984-12-06 | 1986-08-26 | Alza Corporation | Dispensing device with drug delivery patterns |
US4904474A (en) * | 1988-01-25 | 1990-02-27 | Alza Corporation | Delivery of drug to colon by oral disage form |
US5330998A (en) * | 1988-03-08 | 1994-07-19 | Pfizer Inc. | Thiazolidinedione derivatives as hypoglycemic agents |
US5256675A (en) * | 1989-08-07 | 1993-10-26 | Fujisawa Pharmaceutical Co., Ltd. | Thiazole derivatives, processes for production thereof and pharmaceutical compositions comprising the same |
IE68593B1 (en) * | 1989-12-06 | 1996-06-26 | Sanofi Sa | Heterocyclic substituted acylaminothiazoles their preparation and pharmaceutical compositions containing them |
IT1246382B (it) | 1990-04-17 | 1994-11-18 | Eurand Int | Metodo per la cessione mirata e controllata di farmaci nell'intestino e particolarmente nel colon |
IL98087A (en) * | 1990-05-04 | 1996-11-14 | Perio Prod Ltd | Preparation for dispensing drugs in the colon |
SE9002339L (sv) | 1990-07-04 | 1992-01-05 | Kabi Pharmacia Ab | Terapeutisk komposition och foerfarande foer dess framstaellning |
US5519014A (en) | 1990-10-22 | 1996-05-21 | Borody; Thomas J. | Treatment of non-inflammatory and non-infectious bowel disorders |
WO1995016451A1 (fr) | 1992-06-22 | 1995-06-22 | Franck Arno Gouchet | Comprimes a liberation controlee de 4-asa |
FR2692484B1 (fr) | 1992-06-22 | 1995-06-30 | Gouchet Franck | Nouvelle forme galenique de 4-asa a liberation controlee. |
DE69425453T2 (de) * | 1993-04-23 | 2001-04-12 | Novartis Ag, Basel | Wirkstoffabgabevorrichtung mit gesteuerter Freigabe |
DK66493D0 (da) * | 1993-06-08 | 1993-06-08 | Ferring A S | Praeparater, isaer til brug ved behandling af inflammatoriske tarmsygdomme eller til at opnaa forbedret saarheling |
JPH072650A (ja) * | 1993-06-18 | 1995-01-06 | Tanabe Seiyaku Co Ltd | 放出部位制御型製剤 |
US5482718A (en) | 1994-03-23 | 1996-01-09 | Hoffmann-La Roche Inc. | Colon-targeted delivery system |
EP0759303B1 (en) * | 1994-04-22 | 2002-10-16 | Yamanouchi Pharmaceutical Co. Ltd. | Colon-specific drug release system |
GB9412394D0 (en) | 1994-06-21 | 1994-08-10 | Danbiosyst Uk | Colonic drug delivery composition |
JPH0840941A (ja) * | 1994-07-29 | 1996-02-13 | Kanegafuchi Chem Ind Co Ltd | 炎症性腸疾患治療製剤 |
US5608048A (en) * | 1995-06-05 | 1997-03-04 | Bristol-Myers Squibb Company | d4 T polymorphic Form 1 process |
US6004581A (en) * | 1995-12-21 | 1999-12-21 | Farmaceutisk Laboratorium Ferring A/S | Modified release oral pharmaceutical composition and method for the treatment of bowel diseases |
US5840332A (en) * | 1996-01-18 | 1998-11-24 | Perio Products Ltd. | Gastrointestinal drug delivery system |
DE19732903A1 (de) * | 1997-07-30 | 1999-02-04 | Falk Pharma Gmbh | Pellet-Formulierung zur Behandlung des Intestinaltraktes |
JP2000103732A (ja) * | 1998-07-28 | 2000-04-11 | Tanabe Seiyaku Co Ltd | 腸内適所放出型製剤 |
DE69924735T2 (de) | 1998-07-28 | 2006-01-19 | Tanabe Seiyaku Co., Ltd. | Zur wirkstoffabgabe an zielorten im darm fähige zubereitung |
AU757343B2 (en) | 1998-09-28 | 2003-02-20 | Capsugel Belgium Nv | Enteric and colonic delivery using HPMC capsules |
US6733789B1 (en) * | 1999-01-21 | 2004-05-11 | Biovail Laboratories, Inc. | Multiparticulate bisoprolol formulation |
JP2002535353A (ja) * | 1999-01-29 | 2002-10-22 | ロザン ファルマ ゲゼルシャフトミットベシュレンクテルハフツンク | 医薬品組成物 |
ITMI991316A1 (it) | 1999-06-14 | 2000-12-14 | Cip Ninety Two 92 S A | Composizioni farmaceutiche orali a rilascio modificato di mesalazina |
DE10013029A1 (de) * | 2000-03-17 | 2001-09-20 | Roehm Gmbh | Mehrschichtige Arzneiform für die Colonfreigabe |
WO2002009769A2 (en) * | 2000-07-27 | 2002-02-07 | Rutgers, The State University Of New Jersey | Therapeutic azo-compounds for drug delivery |
WO2002017887A1 (de) | 2000-08-29 | 2002-03-07 | Mepha Ag | Arzneimittel zur behandlung von darmerkrankungen |
CA2359812C (en) | 2000-11-20 | 2004-02-10 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures |
ATE380022T1 (de) * | 2001-01-31 | 2007-12-15 | Evonik Roehm Gmbh | Multipartikuläre arzneiform, enthaltend mindestens zwei unterschiedlich überzogene pelletformen |
US7737133B2 (en) | 2003-09-03 | 2010-06-15 | Agi Therapeutics Ltd. | Formulations and methods of treating inflammatory bowel disease |
US7825106B2 (en) * | 2003-09-03 | 2010-11-02 | Agi Therapeutics Ltd. | Modified release formulations and methods of treating inflammatory bowel disease |
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2004
- 2004-09-01 US US10/930,743 patent/US7737133B2/en not_active Expired - Lifetime
- 2004-09-02 AU AU2004267953A patent/AU2004267953A1/en not_active Abandoned
- 2004-09-02 MX MXPA06002048A patent/MXPA06002048A/es not_active Application Discontinuation
- 2004-09-02 AT AT04769427T patent/ATE489956T1/de not_active IP Right Cessation
- 2004-09-02 DE DE602004030353T patent/DE602004030353D1/de not_active Expired - Lifetime
- 2004-09-02 WO PCT/IB2004/003059 patent/WO2005021009A2/en active Application Filing
- 2004-09-02 CA CA002535923A patent/CA2535923A1/en not_active Abandoned
- 2004-09-02 ES ES04769427T patent/ES2353761T3/es not_active Expired - Lifetime
- 2004-09-02 EP EP04769427A patent/EP1663253B1/en not_active Expired - Lifetime
- 2004-09-02 JP JP2006525214A patent/JP5108304B2/ja not_active Expired - Fee Related
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2006
- 2006-02-13 IL IL173684A patent/IL173684A0/en unknown
- 2006-02-15 ZA ZA200601356A patent/ZA200601356B/en unknown
- 2006-04-03 NO NO20061489A patent/NO20061489L/no not_active Application Discontinuation
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Also Published As
Publication number | Publication date |
---|---|
ATE489956T1 (de) | 2010-12-15 |
US7928092B2 (en) | 2011-04-19 |
IL173684A0 (en) | 2006-07-05 |
WO2005021009A2 (en) | 2005-03-10 |
MXPA06002048A (es) | 2006-05-25 |
ES2353761T3 (es) | 2011-03-04 |
NO20061489L (no) | 2006-05-30 |
EP1663253B1 (en) | 2010-12-01 |
CA2535923A1 (en) | 2005-03-10 |
EP1663253A2 (en) | 2006-06-07 |
JP2007504212A (ja) | 2007-03-01 |
US20100278917A1 (en) | 2010-11-04 |
US20050090473A1 (en) | 2005-04-28 |
DE602004030353D1 (de) | 2011-01-13 |
WO2005021009A3 (en) | 2005-07-14 |
AU2004267953A1 (en) | 2005-03-10 |
ZA200601356B (en) | 2007-07-25 |
US7737133B2 (en) | 2010-06-15 |
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