DE60127457T2 - Fibrat-statin kombinationen mit verminderten von der nahrungsaufnahme abhängigen auswirkungen - Google Patents
Fibrat-statin kombinationen mit verminderten von der nahrungsaufnahme abhängigen auswirkungen Download PDFInfo
- Publication number
- DE60127457T2 DE60127457T2 DE60127457T DE60127457T DE60127457T2 DE 60127457 T2 DE60127457 T2 DE 60127457T2 DE 60127457 T DE60127457 T DE 60127457T DE 60127457 T DE60127457 T DE 60127457T DE 60127457 T2 DE60127457 T2 DE 60127457T2
- Authority
- DE
- Germany
- Prior art keywords
- fenofibrate
- statin
- dosage form
- drug
- microparticles
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
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Classifications
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- 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
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- A61P3/06—Antihyperlipidemics
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- 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
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- 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
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- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/902—Specified use of nanostructure
- Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
- Y10S977/906—Drug delivery
Landscapes
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Meat, Egg Or Seafood Products (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US27015701P | 2001-02-22 | 2001-02-22 | |
| US270157P | 2001-02-22 | ||
| PCT/US2001/012747 WO2002067901A1 (en) | 2001-02-22 | 2001-04-20 | Fibrate-statin combinations with reduced fed-fasted effects |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60127457D1 DE60127457D1 (de) | 2007-05-03 |
| DE60127457T2 true DE60127457T2 (de) | 2007-11-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| DE60127457T Expired - Lifetime DE60127457T2 (de) | 2001-02-22 | 2001-04-20 | Fibrat-statin kombinationen mit verminderten von der nahrungsaufnahme abhängigen auswirkungen |
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|---|---|
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| EP (1) | EP1361867B1 (enExample) |
| JP (1) | JP2004523552A (enExample) |
| CN (1) | CN1273112C (enExample) |
| AT (1) | ATE357216T1 (enExample) |
| AU (1) | AU2001259099B2 (enExample) |
| CA (1) | CA2440355C (enExample) |
| DE (1) | DE60127457T2 (enExample) |
| ES (1) | ES2284646T3 (enExample) |
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| PL (1) | PL202778B1 (enExample) |
| TW (1) | TWI288000B (enExample) |
| WO (1) | WO2002067901A1 (enExample) |
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| US8236352B2 (en) | 1998-10-01 | 2012-08-07 | Alkermes Pharma Ireland Limited | Glipizide compositions |
| US8293277B2 (en) | 1998-10-01 | 2012-10-23 | Alkermes Pharma Ireland Limited | Controlled-release nanoparticulate compositions |
| US7521068B2 (en) | 1998-11-12 | 2009-04-21 | Elan Pharma International Ltd. | Dry powder aerosols of nanoparticulate drugs |
| HK1042856B (zh) * | 1998-11-20 | 2007-07-27 | Skyepharma Canada Inc. | 可分散的磷脂稳定的微粒 |
| CZ20013174A3 (cs) | 1999-03-05 | 2002-02-13 | The Procter & Gamble Company | C16 nenasycené FP-selektivní prostaglandinové analogy |
| US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
| US8586094B2 (en) | 2000-09-20 | 2013-11-19 | Jagotec Ag | Coated tablets |
| US7276249B2 (en) | 2002-05-24 | 2007-10-02 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| US7198795B2 (en) | 2000-09-21 | 2007-04-03 | Elan Pharma International Ltd. | In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate of nanoparticulate active agent compositions |
| US20080241070A1 (en) * | 2000-09-21 | 2008-10-02 | Elan Pharma International Ltd. | Fenofibrate dosage forms |
| WO2003013607A1 (en) * | 2001-08-07 | 2003-02-20 | Galephar M/F | ORAL PHARMACEUTICAL COMPOSITION CONTAINING A COMBINATION OF FENOFIBRATE AND A HMG-CoA REDUCTASE INHIBITOR |
| WO2003055467A1 (en) * | 2001-12-18 | 2003-07-10 | Synthon B.V. | Simvastatin dosage forms |
| DK1471887T3 (da) | 2002-02-04 | 2010-06-07 | Elan Pharma Int Ltd | Nanopartikelkompositioner der har lysozym som overfladestabiliseringsmiddel |
| AU2003225752A1 (en) * | 2002-03-12 | 2003-09-29 | Paul S. Phillips | Method of diagnosing statin myopathy |
| AU2003245313A1 (en) * | 2002-06-10 | 2003-12-22 | Elan Pharma International, Ltd | Nanoparticulate formulations comprising hmg coa reductase inhibitor derivatives (statins), novel combinations thereof as well as manufacturing of these pharmaceutical compositions |
| JP2005531606A (ja) * | 2002-06-10 | 2005-10-20 | エラン ファーマ インターナショナル，リミティド | ナノ粒子ステロール製剤およびステロールの組合せ |
| DE10248619A1 (de) * | 2002-10-18 | 2004-04-29 | Bayer Ag | Verfahren zur Herstellung pulverförmiger Wirkstoff-Formulierungen mit kompressiblen Fluiden |
| FR2851734B1 (fr) * | 2003-02-28 | 2006-06-09 | Galenix Innovations | Procede pour la fabrication d'une composition pharmaceutique sous la forme de comprimes contenant un fibrate et comprimes obtenus selon le procede |
| BRPI0410840A (pt) * | 2003-05-30 | 2006-07-04 | Ranbaxy Lab Ltd | derivados substituìdos de pirrol, composição farmacêutica contendo os mesmos e processo para sua preparação |
| WO2005013940A1 (en) * | 2003-08-06 | 2005-02-17 | Galephar M/F | Stable controlled release pharmaceutical compositions containing fenofibrate and pravastatin |
| US20070014846A1 (en) * | 2003-10-10 | 2007-01-18 | Lifecycle Pharma A/S | Pharmaceutical compositions comprising fenofibrate and atorvastatin |
| US20050096390A1 (en) * | 2003-10-10 | 2005-05-05 | Per Holm | Compositions comprising fenofibrate and pravastatin |
| US9173847B2 (en) * | 2003-10-10 | 2015-11-03 | Veloxis Pharmaceuticals A/S | Tablet comprising a fibrate |
| JP5069001B2 (ja) * | 2003-10-10 | 2012-11-07 | ベロクシス ファーマシューティカルズ エー／エス | フィブラートを含む固体投与形態 |
| US20050096391A1 (en) * | 2003-10-10 | 2005-05-05 | Per Holm | Compositions comprising fenofibrate and rosuvastatin |
| JP2007508249A (ja) * | 2003-10-10 | 2007-04-05 | ライフサイクル ファーマ アクティーゼルスカブ | フィブラートとスタチンを含む固体剤型 |
| US7410978B2 (en) * | 2003-11-04 | 2008-08-12 | Supernus Pharmaceuticals, Inc. | Once daily dosage forms of trospium |
| AU2004289222B2 (en) | 2003-11-04 | 2010-01-21 | Supernus Pharmaceuticals Inc. | Compositions of quaternary ammonium containing bioavailability enhancers |
| CA2543596A1 (en) * | 2003-11-07 | 2005-05-26 | Jj Pharma, Inc. | Hdl-boosting combination therapy complexes |
| WO2005053683A1 (en) | 2003-11-26 | 2005-06-16 | Duke University | A method of preventing or treating glaucoma |
| US20050170063A1 (en) * | 2004-01-29 | 2005-08-04 | Lalit Chordia | Production of powder and viscous material |
| EP1563837A1 (en) * | 2004-02-03 | 2005-08-17 | Ferrer Internacional, S.A. | Hypocholesterolemic compositions comprising a statin and an antiflatulent agent |
| JPWO2006011495A1 (ja) * | 2004-07-30 | 2008-05-01 | 興和株式会社 | 高コレステロール血症及び／又は高トリグリセリド血症治療剤 |
| US20090042979A1 (en) * | 2004-08-06 | 2009-02-12 | Transform Pharmaceuticals Inc. | Novel Statin Pharmaceutical Compositions and Related Methods of Treatment |
| KR20070052760A (ko) * | 2004-08-06 | 2007-05-22 | 트렌스폼 파마수티컬스 인코퍼레이티드 | 신규한 페노피브레이트 제제 및 관련된 치료방법 |
| AU2005271413A1 (en) * | 2004-08-06 | 2006-02-16 | Transform Pharmaceuticals, Inc. | Novel statin pharmaceutical compositions and related methods of treatment |
| WO2006037345A1 (en) * | 2004-10-01 | 2006-04-13 | Lifecycle Pharma A/S | Pharmaceutical composition comprising fenofibrate and simvastatin |
| CA2597492A1 (en) * | 2005-02-10 | 2006-08-17 | Lifecycle Pharma A/S | A stable pharmaceutical composition comprising a fixed dose combination of fenofibrate and an hmg-coa reductase inhibitor |
| AU2006228525A1 (en) * | 2005-03-28 | 2006-10-05 | Dexcel Pharma Technologies Ltd. | Controlled absorption of statins in the intestine |
| WO2006084475A2 (en) * | 2005-04-13 | 2006-08-17 | Lifecycle Pharma A/S | A tablet comprising a fibrate |
| CA2623475A1 (en) * | 2005-09-28 | 2007-04-05 | Dnp Canada Inc. | Combination of polychitosamine and fibrate for the prevention and treatment of hyperlipidemia |
| JP2009514851A (ja) * | 2005-11-08 | 2009-04-09 | ランバクシー ラボラトリーズ リミテッド | （３ｒ，５ｒ）−７−［２−（４−フルオロフェニル）−５−イソプロピル−３−フェニル−４−［（４−ヒドロキシメチルフェニルアミノ）カルボニル］−ピロール−１−イル］−３，５−ジヒドロキシ−ヘプタン酸ヘミカルシウム塩の製法 |
| EP1785133A1 (en) | 2005-11-10 | 2007-05-16 | Laboratoires Fournier S.A. | Use of fenofibrate or a derivative thereof for preventing diabetic retinopathy |
| AR059838A1 (es) * | 2006-03-14 | 2008-04-30 | Ranbaxy Lab Ltd | Formulaciones para dosis estabilizantes de estatina |
| MX2009000439A (es) * | 2006-07-14 | 2009-02-04 | Ranbaxy Lab Ltd | Formas polimorficas de un inhibidor de hmg-coa reductasa y usos de las mismas. |
| WO2008015763A1 (fr) | 2006-08-04 | 2008-02-07 | Aska Pharmaceutical Co., Ltd. | Formulation médicamenteuse contenant un médicament fibrate et procédé pour la produire |
| US7569612B1 (en) | 2006-08-21 | 2009-08-04 | Mutual Pharmaceutical Company, Inc. | Methods of use of fenofibric acid |
| MXPA06010973A (es) * | 2006-09-25 | 2009-02-18 | World Trade Imp Export Wtie Ag | Composicion farmaceutica para el tratamiento del sobrepeso y la obesidad que se acompañan la dislipidemia. |
| US7731604B2 (en) * | 2006-10-31 | 2010-06-08 | Taylor Made Golf Company, Inc. | Golf club iron head |
| WO2008057048A1 (en) * | 2006-11-09 | 2008-05-15 | Nanomaterials Technology Pte Ltd | Nano & micro-sized particles of statin compounds and process for forming same |
| WO2008095195A2 (en) * | 2007-02-02 | 2008-08-07 | Nereus Pharmaceuticals, Inc. | Lyophilized formulations of salinosporamide a |
| EP2182925A2 (en) * | 2007-07-27 | 2010-05-12 | Cipla Limited | Pharmaceutical compositions and process for making them |
| US8524280B2 (en) * | 2008-12-15 | 2013-09-03 | Banner Pharmacaps, Inc. | Methods for enhancing the release and absorption of water insoluble active agents |
| US20110293549A1 (en) | 2009-02-03 | 2011-12-01 | Athena Cosmetics, Inc. | Composition, method and kit for enhancing hair |
| JP2012096998A (ja) * | 2009-02-27 | 2012-05-24 | Kowa Co | 安定なカプセル製剤及びその製造方法 |
| WO2011028757A1 (en) * | 2009-09-01 | 2011-03-10 | First Tech International Limited | Tocotrienol compositions |
| US8877221B2 (en) | 2010-10-27 | 2014-11-04 | Warsaw Orthopedic, Inc. | Osteoconductive matrices comprising calcium phosphate particles and statins and methods of using the same |
| US9107983B2 (en) | 2010-10-27 | 2015-08-18 | Warsaw Orthopedic, Inc. | Osteoconductive matrices comprising statins |
| WO2012170417A2 (en) | 2011-06-06 | 2012-12-13 | Warsaw Orthopedic, Inc. | Methods and compositions to enhance bone growth comprising a statin |
| AR087329A1 (es) | 2011-06-17 | 2014-03-19 | Regeneron Pharma | Anticuerpos humanos contra proteina 3 de tipo angiopoietina humana |
| MX2017011469A (es) | 2015-03-10 | 2018-01-23 | Shionogi Inc | Dispersiones sólidas. |
| MA43734A (fr) | 2016-03-03 | 2018-11-28 | Regeneron Pharma | Procédés de traitement de patients atteints d'hyperlipidémie par administration d'un inhibiteur de pcsk9 en combinaison avec un inhibiteur d'angptl3 |
| MA44764B1 (fr) * | 2016-04-28 | 2025-09-30 | Regeneron Pharmaceuticals, Inc. | Méthodes de traitement de patients présentant une hypercholestérolémie familiale |
| KR20230079187A (ko) * | 2020-09-29 | 2023-06-05 | 라보라토리오스 실레인즈, 에스.에이. 드 씨.브이. | 고지혈증 및 심혈관 질환의 치료 및 예방을 위한 스타틴 및 피브레이트의 약학적 병용 |
Family Cites Families (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2803582A (en) * | 1956-07-16 | 1957-08-20 | Leonid S Cherney | Local anesthetic composition |
| NL120093C (enExample) * | 1958-07-24 | |||
| US3137631A (en) * | 1959-12-01 | 1964-06-16 | Faberge Inc | Encapsulation in natural products |
| US3216897A (en) * | 1961-11-02 | 1965-11-09 | Air Reduction | Injectable anesthetic |
| US3594476A (en) * | 1969-05-12 | 1971-07-20 | Massachusetts Inst Technology | Submicron aqueous aerosols containing lecithin |
| US3937668A (en) * | 1970-07-15 | 1976-02-10 | Ilse Zolle | Method for incorporating substances into protein microspheres |
| NL7012832A (enExample) * | 1970-08-29 | 1972-03-02 | ||
| US3715432A (en) * | 1971-01-22 | 1973-02-06 | Massachusetts Inst Technology | Submicron aqueous aerosols containing lecithin |
| US3794476A (en) * | 1972-12-26 | 1974-02-26 | Ppg Industries Inc | Method for thermally tempering glass sheet by liquid quenching |
| GB1413186A (en) * | 1973-06-27 | 1975-11-12 | Toyo Jozo Kk | Process for encapsulation of medicaments |
| GB1472793A (en) * | 1974-03-28 | 1977-05-04 | Ici Ltd | Pharmaceutical compositions |
| US4798846A (en) * | 1974-03-28 | 1989-01-17 | Imperial Chemical Industries Plc | Pharmaceutical compositions |
| US3965255A (en) * | 1974-05-01 | 1976-06-22 | E. E. Eljim Ecology Ltd. | Controlled drug releasing preparations |
| GB1502774A (en) * | 1974-06-25 | 1978-03-01 | Nat Res Dev | Immunological preparations |
| CH588887A5 (enExample) * | 1974-07-19 | 1977-06-15 | Battelle Memorial Institute | |
| US4073943A (en) * | 1974-09-11 | 1978-02-14 | Apoteksvarucentralen Vitrum Ab | Method of enhancing the administration of pharmalogically active agents |
| US4107288A (en) * | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
| JPS5186117A (en) * | 1975-01-27 | 1976-07-28 | Tanabe Seiyaku Co | Johoseibiryushiseizainoseiho |
| JPS5231981A (en) * | 1975-08-18 | 1977-03-10 | Takeda Chem Ind Ltd | Microcapsule preparation method |
| CA1077842A (en) * | 1975-10-09 | 1980-05-20 | Minnesota Mining And Manufacturing Company | Albumin medicament carrier system |
| GB1523965A (en) * | 1976-03-19 | 1978-09-06 | Ici Ltd | Pharmaceutical compositions containing steroids |
| GB1578776A (en) * | 1976-06-10 | 1980-11-12 | Univ Illinois | Hemoglobin liposome and method of making the same |
| US4078052A (en) * | 1976-06-30 | 1978-03-07 | The United States Of America As Represented By The Secretary Of Health, Education And Welfare | Large unilamellar vesicles (LUV) and method of preparing same |
| US4320121A (en) * | 1976-10-12 | 1982-03-16 | Sears Barry D | Method of emulsifying cholesterol, cholesterol esters and triglyceride compounds |
| US4086257A (en) * | 1976-10-12 | 1978-04-25 | Sears Barry D | Phosphatidyl quaternary ammonium compounds |
| US4351831A (en) * | 1977-11-02 | 1982-09-28 | Massachusetts Institute Of Technology | Process and composition for treating disorders by administering isoxsurpine and choline |
| US4356167A (en) * | 1978-01-27 | 1982-10-26 | Sandoz, Inc. | Liposome drug delivery systems |
| US4235871A (en) * | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4529561A (en) * | 1978-03-24 | 1985-07-16 | The Regents Of The University Of California | Method for producing liposomes in selected size range |
| US4186183A (en) * | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
| GB2026340B (en) * | 1978-07-03 | 1982-12-22 | Ash P | Stabilising microvesicles |
| DE2965725D1 (en) * | 1978-07-19 | 1983-07-28 | Patrick Couvreur | Biodegradable nanoparticles, pharmaceutical compositions containing them and process for their preparation |
| US4219548A (en) * | 1978-09-01 | 1980-08-26 | The Procter & Gamble Company | Topical anti-inflammatory composition |
| DE2856333C2 (de) * | 1978-12-27 | 1983-09-22 | A. Nattermann & Cie GmbH, 5000 Köln | Oral einnehmbare Arzneimittel mit entzündungshemmender Wirkung |
| US4369182A (en) * | 1978-09-27 | 1983-01-18 | A. Nattermann & Cie Gmbh | Inflammation-preventing pharmaceutical composition of oral administration |
| US4328222A (en) * | 1978-11-21 | 1982-05-04 | Hoffmann-La Roche Inc. | Pharmaceutical compositions for parenteral or local administration |
| GR73668B (enExample) * | 1978-11-21 | 1984-03-28 | Hoffmann La Roche | |
| US4378354A (en) * | 1978-12-27 | 1983-03-29 | A. Nattermann & Cie. Gmbh | Inflammation-preventing pharmaceutical composition of oral administration |
| US4316884A (en) * | 1979-01-25 | 1982-02-23 | Adria Laboratories, Inc. | Sustained release pharmaceutical formulation |
| DE2914788A1 (de) * | 1979-04-11 | 1980-10-16 | Nattermann A & Cie | Parenteral applizierbare, stabile arzneimittelloesungen mit entzuendungshemmender wirkung |
| US4345588A (en) * | 1979-04-23 | 1982-08-24 | Northwestern University | Method of delivering a therapeutic agent to a target capillary bed |
| JPS6030652B2 (ja) * | 1979-05-07 | 1985-07-17 | 株式会社ミドリ十字 | 静脈注射用脂肪乳剤 |
| JPS562353A (en) * | 1979-06-20 | 1981-01-12 | Ricoh Co Ltd | Novel disazo compound and its preparation |
| CA1173360A (en) * | 1979-06-22 | 1984-08-28 | Jurg Schrank | Pharmaceutical preparations |
| US4309404A (en) * | 1979-08-09 | 1982-01-05 | American Home Products Corporation | Sustained release pharmaceutical compositions |
| DE3003886A1 (de) * | 1980-02-02 | 1981-08-13 | Olympia Werke Ag, 2940 Wilhelmshaven | Farbbandkassette fuer eine schreib- o.ae. bueromaschine |
| AR220263A1 (es) * | 1980-02-19 | 1980-10-15 | Bago Lab Sa | Procedimiento para obtener una preparacion inyectable de sulfonamida potenciada de baja irritabilidad |
| JPS609726B2 (ja) * | 1980-05-15 | 1985-03-12 | 株式会社 ミドリ十字 | ステロイド製剤 |
| US4331654A (en) * | 1980-06-13 | 1982-05-25 | Eli Lilly And Company | Magnetically-localizable, biodegradable lipid microspheres |
| US4394372A (en) * | 1980-12-22 | 1983-07-19 | The Procter & Gamble Company | Process for making lipid membrane structures |
| US4397846A (en) * | 1981-05-15 | 1983-08-09 | Murray Weiner | Storage-stable lipid vesicles and method of preparation |
| US5030453A (en) * | 1983-03-24 | 1991-07-09 | The Liposome Company, Inc. | Stable plurilamellar vesicles |
| US4515736A (en) * | 1983-05-12 | 1985-05-07 | The Regents Of The University Of California | Method for encapsulating materials into liposomes |
| US4725442A (en) * | 1983-06-17 | 1988-02-16 | Haynes Duncan H | Microdroplets of water-insoluble drugs and injectable formulations containing same |
| JPS601122A (ja) * | 1983-06-20 | 1985-01-07 | Green Cross Corp:The | ビフエニリルプロピオン酸誘導体脂肪乳剤 |
| US4492720A (en) * | 1983-11-15 | 1985-01-08 | Benjamin Mosier | Method of preparing microspheres for intravascular delivery |
| US4532089A (en) * | 1984-01-14 | 1985-07-30 | Northwestern University | Method of preparing giant size liposomes |
| US4610868A (en) * | 1984-03-20 | 1986-09-09 | The Liposome Company, Inc. | Lipid matrix carriers for use in drug delivery systems |
| JPS60208910A (ja) * | 1984-03-31 | 1985-10-21 | Green Cross Corp:The | 水難溶性薬物・リン脂質複合体の製造方法 |
| JPS6176414A (ja) * | 1984-09-21 | 1986-04-18 | Shionogi & Co Ltd | リポソーム製剤の製法 |
| JPS61174940A (ja) * | 1985-01-29 | 1986-08-06 | Oogawara Kakoki Kk | ワックス類コーテイング単核状マイクロカプセルおよびその製造方法 |
| JPH0688911B2 (ja) * | 1985-06-06 | 1994-11-09 | 国立予防衛生研究所長 | インフルエンザワクチン及びその製造方法 |
| US4766046A (en) * | 1985-09-27 | 1988-08-23 | Liposome Technology, Inc. | Stabilized liposome/amphotericin composition and method |
| JPH0617309B2 (ja) * | 1985-11-29 | 1994-03-09 | 株式会社ビタミン研究所 | アドリアマイシン包埋リポソ−ム製剤 |
| US4803070A (en) * | 1986-04-15 | 1989-02-07 | Ribi Immunochem Research Inc. | Immunological emulsion adjuvants for polysaccharide vaccines |
| US4806352A (en) * | 1986-04-15 | 1989-02-21 | Ribi Immunochem Research Inc. | Immunological lipid emulsion adjuvant |
| US4806350A (en) * | 1986-04-18 | 1989-02-21 | Norden Laboratories, Inc. | Vaccine formulation |
| DE3623376A1 (de) * | 1986-07-11 | 1988-01-21 | Behringwerke Ag | Pharmazeutische formulierung und verfahren zu deren herstellung |
| FR2602423B1 (fr) * | 1986-08-08 | 1989-05-05 | Ethypharm Sa | Procede de preparation d'un medicament a base de fenofibrate, medicament obtenu par ce procede |
| US4776991A (en) * | 1986-08-29 | 1988-10-11 | The United States Of America As Represented By The Secretary Of The Navy | Scaled-up production of liposome-encapsulated hemoglobin |
| US5320906A (en) * | 1986-12-15 | 1994-06-14 | Vestar, Inc. | Delivery vehicles with amphiphile-associated active ingredient |
| US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4839111A (en) * | 1987-02-02 | 1989-06-13 | The University Of Tennessee Research Corporation | Preparation of solid core liposomes |
| US5154930A (en) * | 1987-03-05 | 1992-10-13 | The Liposome Company, Inc. | Pharmacological agent-lipid solution preparation |
| FR2627696B1 (fr) * | 1988-02-26 | 1991-09-13 | Fournier Innovation Synergie | Nouvelle forme galenique du fenofibrate |
| US5744477A (en) * | 1988-05-10 | 1998-04-28 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Method for treatment of obesity using prolactin modulators and diet |
| FR2651680B1 (fr) * | 1989-09-14 | 1991-12-27 | Medgenix Group Sa | Nouveau procede de preparation de microparticules lipidiques. |
| JP2785981B2 (ja) * | 1989-11-20 | 1998-08-13 | 株式会社資生堂 | 乳化組成物 |
| US5246707A (en) * | 1990-04-26 | 1993-09-21 | Haynes Duncan H | Sustained release delivery of water-soluble bio-molecules and drugs using phospholipid-coated microcrystals, microdroplets and high-concentration liposomes |
| US5091187A (en) * | 1990-04-26 | 1992-02-25 | Haynes Duncan H | Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs |
| US5091188A (en) * | 1990-04-26 | 1992-02-25 | Haynes Duncan H | Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs |
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5302401A (en) * | 1992-12-09 | 1994-04-12 | Sterling Winthrop Inc. | Method to reduce particle size growth during lyophilization |
| US5336507A (en) * | 1992-12-11 | 1994-08-09 | Sterling Winthrop Inc. | Use of charged phospholipids to reduce nanoparticle aggregation |
| US5785976A (en) * | 1993-03-05 | 1998-07-28 | Pharmacia & Upjohn Ab | Solid lipid particles, particles of bioactive agents and methods for the manufacture and use thereof |
| US5545628A (en) * | 1995-01-10 | 1996-08-13 | Galephar P.R. Inc. | Pharmaceutical composition containing fenofibrate |
| FR2730231B1 (fr) * | 1995-02-02 | 1997-04-04 | Fournier Sca Lab | Association de fenofibrate et de vitamine e, utilisation en therapeutique |
| FR2737121B1 (fr) * | 1995-07-27 | 1997-10-03 | Cl Pharma | Nouvelles formulations galeniques du fenofibrate et leurs applications |
| US5637625A (en) * | 1996-03-19 | 1997-06-10 | Research Triangle Pharmaceuticals Ltd. | Propofol microdroplet formulations |
| JP2000516244A (ja) * | 1996-08-22 | 2000-12-05 | リサーチ・トライアングル・ファーマシューティカルズ | 水不溶性物質の微粒子を含む組成物およびその製造方法 |
| FR2758459B1 (fr) * | 1997-01-17 | 1999-05-07 | Pharma Pass | Composition pharmaceutique de fenofibrate presentant une biodisponibilite elevee et son procede de preparation |
| WO1998035666A1 (en) * | 1997-02-13 | 1998-08-20 | Nanosystems Llc | Formulations of nanoparticle naproxen tablets |
| US6180660B1 (en) * | 1997-08-26 | 2001-01-30 | Merck & Co., Inc. | Cholesterol-lowering therapy |
| HK1042856B (zh) * | 1998-11-20 | 2007-07-27 | Skyepharma Canada Inc. | 可分散的磷脂稳定的微粒 |
| DE19858789A1 (de) * | 1998-12-18 | 2000-06-21 | Bayer Ag | Kombination von Cerivastatin und Fibraten |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| AU5711501A (en) * | 2000-04-20 | 2001-11-07 | Rtp Pharma Inc | Improved water-insoluble drug particle process |
| NZ522896A (en) * | 2000-05-10 | 2004-05-28 | Skyepharma Canada Inc | Media milling |
| US6368628B1 (en) * | 2000-05-26 | 2002-04-09 | Pharma Pass Llc | Sustained release pharmaceutical composition free of food effect |
-
2001
- 2001-04-20 PL PL364174A patent/PL202778B1/pl unknown
- 2001-04-20 EP EP01932584A patent/EP1361867B1/en not_active Expired - Lifetime
- 2001-04-20 CA CA2440355A patent/CA2440355C/en not_active Expired - Fee Related
- 2001-04-20 AU AU2001259099A patent/AU2001259099B2/en not_active Ceased
- 2001-04-20 DE DE60127457T patent/DE60127457T2/de not_active Expired - Lifetime
- 2001-04-20 CN CNB018231640A patent/CN1273112C/zh not_active Expired - Fee Related
- 2001-04-20 JP JP2002567269A patent/JP2004523552A/ja active Pending
- 2001-04-20 WO PCT/US2001/012747 patent/WO2002067901A1/en not_active Ceased
- 2001-04-20 ES ES01932584T patent/ES2284646T3/es not_active Expired - Lifetime
- 2001-04-20 TW TW090109551A patent/TWI288000B/zh not_active IP Right Cessation
- 2001-04-20 US US09/838,583 patent/US6534088B2/en not_active Expired - Lifetime
- 2001-04-20 NZ NZ527408A patent/NZ527408A/xx not_active IP Right Cessation
- 2001-04-20 AT AT01932584T patent/ATE357216T1/de not_active IP Right Cessation
-
2003
- 2003-03-17 US US10/388,597 patent/US20040086571A1/en not_active Abandoned
-
2011
- 2011-11-14 US US13/295,708 patent/US20120064160A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004523552A (ja) | 2004-08-05 |
| CA2440355A1 (en) | 2002-09-06 |
| US20120064160A1 (en) | 2012-03-15 |
| US20020161032A1 (en) | 2002-10-31 |
| CN1273112C (zh) | 2006-09-06 |
| PL364174A1 (en) | 2004-12-13 |
| CA2440355C (en) | 2011-03-08 |
| EP1361867A1 (en) | 2003-11-19 |
| PL202778B1 (pl) | 2009-07-31 |
| TWI288000B (en) | 2007-10-11 |
| NZ527408A (en) | 2005-04-29 |
| EP1361867B1 (en) | 2007-03-21 |
| AU2001259099B2 (en) | 2005-12-22 |
| DE60127457D1 (de) | 2007-05-03 |
| US20040086571A1 (en) | 2004-05-06 |
| HK1061357A1 (en) | 2004-09-17 |
| US6534088B2 (en) | 2003-03-18 |
| ES2284646T3 (es) | 2007-11-16 |
| ATE357216T1 (de) | 2007-04-15 |
| CN1505502A (zh) | 2004-06-16 |
| WO2002067901A1 (en) | 2002-09-06 |
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