AU730216B2 - Solid coprecipitates for enhanced bioavailability of lipophilic substances - Google Patents
Solid coprecipitates for enhanced bioavailability of lipophilic substances Download PDFInfo
- Publication number
- AU730216B2 AU730216B2 AU42373/97A AU4237397A AU730216B2 AU 730216 B2 AU730216 B2 AU 730216B2 AU 42373/97 A AU42373/97 A AU 42373/97A AU 4237397 A AU4237397 A AU 4237397A AU 730216 B2 AU730216 B2 AU 730216B2
- Authority
- AU
- Australia
- Prior art keywords
- composition
- tpgs
- solid
- coprecipitate
- lipophilic substance
- 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.)
- Ceased
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Classifications
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL119176 | 1996-09-01 | ||
| IL11917696A IL119176A (en) | 1996-09-01 | 1996-09-01 | Soluble coprecipitates for enhanced oral bioavailability of lipophilic substances |
| US08/833,076 US5891469A (en) | 1997-04-02 | 1997-04-02 | Solid Coprecipitates for enhanced bioavailability of lipophilic substances |
| US08/833076 | 1997-04-02 | ||
| PCT/US1997/015072 WO1998008490A1 (en) | 1996-09-01 | 1997-08-27 | Solid coprecipitates for enhanced bioavailability of lipophilic substances |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU4237397A AU4237397A (en) | 1998-03-19 |
| AU730216B2 true AU730216B2 (en) | 2001-03-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU42373/97A Ceased AU730216B2 (en) | 1996-09-01 | 1997-08-27 | Solid coprecipitates for enhanced bioavailability of lipophilic substances |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1017366A4 (enExample) |
| JP (1) | JP2001523221A (enExample) |
| AU (1) | AU730216B2 (enExample) |
| CA (1) | CA2264718C (enExample) |
| WO (1) | WO1998008490A1 (enExample) |
Families Citing this family (56)
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|---|---|---|---|---|
| US20030220234A1 (en) | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
| US5891845A (en) * | 1997-11-21 | 1999-04-06 | Fuisz Technologies Ltd. | Drug delivery systems utilizing liquid crystal structures |
| IT1298731B1 (it) * | 1998-03-13 | 2000-02-02 | Recordati Chem Pharm | Composizioni farmaceutiche contenenti complessi di inclusione con melatonina |
| US6241969B1 (en) * | 1998-06-26 | 2001-06-05 | Elan Corporation Plc | Aqueous compositions containing corticosteroids for nasal and pulmonary delivery |
| US6200550B1 (en) * | 1998-12-11 | 2001-03-13 | Q-Pharma, Inc. | Oral care compositions comprising coenzyme Q10 |
| US20080070981A1 (en) | 2000-02-23 | 2008-03-20 | Henryk Borowy-Borowski | Water-soluble compositions of bioactive lipophilic compounds |
| US6632443B2 (en) | 2000-02-23 | 2003-10-14 | National Research Council Of Canada | Water-soluble compositions of bioactive lipophilic compounds |
| US6045826A (en) * | 1999-04-02 | 2000-04-04 | National Research Council Of Canada | Water-soluble compositions of bioactive lipophilic compounds |
| AR025587A1 (es) | 1999-09-13 | 2002-12-04 | Hoffmann La Roche | Formulaciones en dispersion que contienen inhibidores de lipasa |
| WO2001039836A1 (en) * | 1999-12-01 | 2001-06-07 | Natco Pharma Limited | A rapid acting freeze dired oral pharmaceutical composition for treating migraine |
| CA2397871A1 (en) * | 2000-01-20 | 2001-07-26 | Supratek Pharma Inc. | Novel podophyllotoxin compositions |
| DE10046541A1 (de) | 2000-09-19 | 2002-03-28 | Knoll Ag | Mechanisch stabile darreichungsformen, enthaltend Ubichinone |
| AR033711A1 (es) * | 2001-05-09 | 2004-01-07 | Novartis Ag | Composiciones farmaceuticas |
| US7141648B2 (en) | 2001-10-19 | 2006-11-28 | Isotechnika Inc. | Synthesis of cyclosporin analogs |
| FR2840614B1 (fr) * | 2002-06-07 | 2004-08-27 | Flamel Tech Sa | Polyaminoacides fonctionnalises par de l'alpha-tocopherol et leurs applications notamment therapeutiques |
| WO2004050068A1 (en) | 2002-11-29 | 2004-06-17 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base |
| EP1592760A4 (en) | 2003-01-31 | 2009-08-12 | Smithkline Beecham Corp | AS FIXED DISPERSIONS, COMPOSITIONS |
| EP1596835A1 (en) * | 2003-02-19 | 2005-11-23 | H. Lundbeck A/S | Method for preparation of an agglomerate using melt agglomeration |
| US20050096365A1 (en) * | 2003-11-03 | 2005-05-05 | David Fikstad | Pharmaceutical compositions with synchronized solubilizer release |
| CN101056630A (zh) * | 2003-12-18 | 2007-10-17 | 帝斯曼知识产权资产管理有限公司 | 用于促进生理节奏同步的维生素e |
| CA2578356C (en) * | 2004-09-24 | 2013-05-28 | Boehringer Ingelheim Pharmaceuticals, Inc. | A new class of surfactant-like materials |
| JP2008514714A (ja) * | 2004-09-30 | 2008-05-08 | イーストマン ケミカル カンパニー | 有意な流出阻害を示さない、親油性薬物を可溶化するビタミンｅｔｐｇｓ分子を含む医薬製剤及びこのような医薬製剤の使用 |
| US20060088591A1 (en) * | 2004-10-22 | 2006-04-27 | Jinghua Yuan | Tablets from a poorly compressible substance |
| US8067380B2 (en) | 2005-12-19 | 2011-11-29 | Industrial Technology Research Institute | Glutathione-based delivery system |
| US7446096B2 (en) * | 2005-12-19 | 2008-11-04 | Industrial Technology Research Institute | Glutathione based delivery system |
| WO2008007728A1 (fr) * | 2006-07-13 | 2008-01-17 | Kaneka Corporation | Préparation orale contenue dans une structure à membrane lipidique, et agent contre la fatigue comprenant une coenzyme comme ingrédient actif |
| PE20081506A1 (es) | 2006-12-12 | 2008-12-09 | Infinity Discovery Inc | Formulaciones de ansamicina |
| WO2009113522A1 (ja) * | 2008-03-11 | 2009-09-17 | あすか製薬株式会社 | 固体分散体とその医薬組成物、並びにそれらの製造方法 |
| EP2268274B1 (en) | 2008-03-20 | 2012-05-16 | Virun, Inc. | Vitamin e derivatives and their uses |
| DK2268160T3 (da) | 2008-03-20 | 2013-01-07 | Virun Inc | Emulsioner omfattende et PEG-derivat af tokoferol |
| AR075180A1 (es) * | 2009-01-29 | 2011-03-16 | Novartis Ag | Formulaciones orales solidas de una pirido-pirimidinona |
| JPWO2010092925A1 (ja) * | 2009-02-12 | 2012-08-16 | あすか製薬株式会社 | 固体分散体とその医薬組成物、並びにそれらの製造方法 |
| US8252821B2 (en) * | 2009-04-14 | 2012-08-28 | Bristol-Myers Squibb Company | Bioavailable capsule compositions of amorphous alpha-(N-sulfonamido)acetamide compound |
| EP2563164B1 (en) | 2010-03-23 | 2016-06-29 | Virun, Inc. | Nanoemulsion including sucrose fatty acid ester |
| US8741373B2 (en) | 2010-06-21 | 2014-06-03 | Virun, Inc. | Compositions containing non-polar compounds |
| ITMI20112042A1 (it) * | 2011-11-10 | 2013-05-11 | Eratech S R L | Polvere da ricostituire prima dell'uso comprendente melatonina e preparazione iniettabile ottenibile da tale polvere. |
| ITRM20120331A1 (it) | 2012-07-12 | 2014-01-13 | Guidotti & C Spa Labor | Composizioni pediatriche orali liquide contenenti nepadutant. |
| FR2999081B1 (fr) * | 2012-12-06 | 2015-02-27 | Hra Pharma Lab | Dispersion solide d'un modulateur selectif du recepteur a la progesterone |
| US9351517B2 (en) | 2013-03-15 | 2016-05-31 | Virun, Inc. | Formulations of water-soluble derivatives of vitamin E and compositions containing same |
| US9693574B2 (en) | 2013-08-08 | 2017-07-04 | Virun, Inc. | Compositions containing water-soluble derivatives of vitamin E mixtures and modified food starch |
| HUP1300647A2 (hu) * | 2013-11-12 | 2015-05-28 | Druggability Technologies Ip Holdco Jersey Ltd | Ciklosporin A és származékainak komplexei, elõállításuk és gyógyszerészeti kompozícióik |
| US11911361B2 (en) | 2014-05-29 | 2024-02-27 | Radius Pharmaceuticals, Inc. | Stable cannabinoid formulations |
| US11331279B2 (en) | 2014-05-29 | 2022-05-17 | Radius Pharmaceuticals, Inc. | Stable cannabinoid formulations |
| GB201410869D0 (en) * | 2014-06-18 | 2014-07-30 | Perioc Ltd | Novel pharmaceutical formulations and their use in the treatment of periodontal disease |
| US9861611B2 (en) | 2014-09-18 | 2018-01-09 | Virun, Inc. | Formulations of water-soluble derivatives of vitamin E and soft gel compositions, concentrates and powders containing same |
| US10016363B2 (en) | 2014-09-18 | 2018-07-10 | Virun, Inc. | Pre-spray emulsions and powders containing non-polar compounds |
| CA2986268C (en) * | 2015-05-28 | 2024-01-02 | Insys Development Company, Inc. | Stable cannabinoid formulations |
| EA201892396A1 (ru) | 2016-12-02 | 2019-04-30 | Ресептор Лайф Сайенсиз, Инк. | Быстродействующие растительные лекарственные соединения и биологически активные добавки |
| CN110121337A (zh) * | 2017-01-03 | 2019-08-13 | 受体控股公司 | 药用化合物和营养补充剂 |
| CN110636834A (zh) * | 2017-02-15 | 2019-12-31 | 分子浸剂有限公司 | 制剂 |
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| UY38480A (es) | 2018-11-19 | 2020-06-30 | Receptor Holdings Inc | Aminoácidos grasos n-acilados para reducir la variabilidad de absorción en composiciones a base de cannabinoides |
| EP4282475A3 (en) * | 2019-12-20 | 2024-02-28 | Intervet International B.V. | A pyrazole pharmaceutical composition |
| CN115103668A (zh) * | 2019-12-20 | 2022-09-23 | 爱杜西亚药品有限公司 | 包含n-[1-(5-氰基-吡啶-2-基甲基)-1h-吡唑-3-基]-2-[4-(1-三氟甲基-环丙基)-苯基]-乙酰胺的药物组合物 |
| WO2021186001A1 (en) * | 2020-03-19 | 2021-09-23 | Ac Immune Sa | Dose treatments of tauopathies |
| IT202200002528A1 (it) * | 2022-02-11 | 2023-08-11 | Pierpaoli Exelyas S R L | Composizione comprendente melatonina ad alta biodisponibilità |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3102078A (en) * | 1961-01-13 | 1963-08-27 | Eastman Kodak Co | Water-dispersible vitamin preparations |
| US5179122A (en) * | 1991-02-11 | 1993-01-12 | Eastman Kodak Company | Nutritional supplement containing vitamin e |
| US5430021A (en) * | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3673163A (en) * | 1970-06-16 | 1972-06-27 | Lilly Co Eli | Pharmacological preparation containing an acronycine-polyvinylprrolidone coprecipitate |
| GB1579818A (en) * | 1977-06-07 | 1980-11-26 | Yamanouchi Pharma Co Ltd | Nifedipine-containing solid preparation composition |
| US4327080A (en) * | 1981-07-13 | 1982-04-27 | E. R. Squibb & Sons, Inc. | Novel Bendroflumethiazide formulations and method |
| US4758427A (en) * | 1985-08-08 | 1988-07-19 | Ciba-Geigy Corporation | Enhanced absorption of psychoactive 2-aryl-pyrazolo quinolines as a solid molecular dispersion in polyvinylpyrrolidone |
| US5234696A (en) * | 1991-12-27 | 1993-08-10 | Abbott Laboratories | Method of producing tablets, tablets produced thereby, and method of treatment using same |
| IT1255792B (it) * | 1992-08-05 | 1995-11-16 | Bayer Italia Spa | Composizioni farmaceutiche per la somministrazione orale di diidropiridine in forma di bevanda |
| HU215966B (hu) * | 1994-11-21 | 1999-07-28 | BIOGAL Gyógyszergyár Rt. | Orálisan alkalmazható, ciklosporint tartalmazó, összetett emulzió-előkoncentrátum |
| CA2221145A1 (en) * | 1995-05-19 | 1996-11-21 | Abbott Laboratories | Self-emulsifying formulations of lipophilic drugs |
| MY126358A (en) * | 1996-03-22 | 2006-09-29 | Glaxo Group Ltd | Compositions comprising vx478 and a water soluble tocopherol derivative such as vitamin e-tpgs |
-
1997
- 1997-08-27 CA CA002264718A patent/CA2264718C/en not_active Expired - Fee Related
- 1997-08-27 AU AU42373/97A patent/AU730216B2/en not_active Ceased
- 1997-08-27 EP EP97940639A patent/EP1017366A4/en not_active Withdrawn
- 1997-08-27 JP JP51187998A patent/JP2001523221A/ja not_active Ceased
- 1997-08-27 WO PCT/US1997/015072 patent/WO1998008490A1/en not_active Ceased
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3102078A (en) * | 1961-01-13 | 1963-08-27 | Eastman Kodak Co | Water-dispersible vitamin preparations |
| US5179122A (en) * | 1991-02-11 | 1993-01-12 | Eastman Kodak Company | Nutritional supplement containing vitamin e |
| US5430021A (en) * | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4237397A (en) | 1998-03-19 |
| WO1998008490A1 (en) | 1998-03-05 |
| EP1017366A1 (en) | 2000-07-12 |
| JP2001523221A (ja) | 2001-11-20 |
| EP1017366A4 (en) | 2006-03-22 |
| CA2264718A1 (en) | 1998-03-05 |
| CA2264718C (en) | 2006-05-30 |
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