AU2016351588A1 - Topical formulations and uses thereof - Google Patents
Topical formulations and uses thereof Download PDFInfo
- Publication number
- AU2016351588A1 AU2016351588A1 AU2016351588A AU2016351588A AU2016351588A1 AU 2016351588 A1 AU2016351588 A1 AU 2016351588A1 AU 2016351588 A AU2016351588 A AU 2016351588A AU 2016351588 A AU2016351588 A AU 2016351588A AU 2016351588 A1 AU2016351588 A1 AU 2016351588A1
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- Australia
- Prior art keywords
- formulation
- hco
- alkyl
- polyoxyl
- aryl
- 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.)
- Abandoned
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K9/0012—Galenical forms characterised by the site of application
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- Bioinformatics & Cheminformatics (AREA)
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- Medicinal Preparation (AREA)
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| PCT/US2016/060391 WO2017083167A1 (en) | 2015-11-10 | 2016-11-03 | Topical formulations and uses thereof |
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| EP3373976B1 (en) | 2015-11-10 | 2024-01-03 | Sun Pharmaceutical Industries Limited | Topical formulations and uses thereof |
| US10918694B2 (en) * | 2016-02-29 | 2021-02-16 | Sun Pharma Global Fze | Topical cyclosporine-containing formulations and uses thereof |
| WO2021224901A2 (en) * | 2021-08-20 | 2021-11-11 | Sun Pharmaceutical Industries Limited | Stable cyclosporine ophthalmic formulation and manufacturing process thereof |
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| DE69307505T2 (de) | 1992-05-13 | 1997-07-24 | Sandoz-Patent-Gmbh, 79539 Loerrach | Opthalmische zusammensetzungen enthaltend ein cyclosporin |
| NZ247516A (en) | 1993-04-28 | 1995-02-24 | Bernard Charles Sherman | Water dispersible pharmaceutical compositions comprising drug dissolved in solvent system comprising at least one alcohol and at least one surfactant |
| US5484597A (en) * | 1993-07-30 | 1996-01-16 | Chesebrough-Pond's Usa Co. | Clear hydroalcholic cosmetic microemulsions |
| NZ280689A (en) | 1995-12-15 | 1997-08-22 | Bernard Charles Sherma Sherman | Pharmaceutical composition comprising a cyclosporipharmaceutical composition comprising a cyclosporin; a tocol, tocopherol or tocotrienol; and propylen; a tocol, tocopherol or tocotrienol; and propylene carbonate or polyethylene glycol ne carbonate or polyethylene glycol |
| MX9701946A (es) | 1997-03-14 | 1998-04-30 | Arturo Jimenez Bayardo | Solucion oftalmica transportadora. |
| US7678836B2 (en) | 1999-11-04 | 2010-03-16 | Fxs Ventures, Llc | Method for rendering a contact lens wettable |
| US7732404B2 (en) | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
| JP4932116B2 (ja) | 2000-02-16 | 2012-05-16 | ザ・ブリガーム・アンド・ウーメンズ・ホスピタル・インコーポレーテッド | アスピリン誘発脂質メディエータ |
| US20030176356A1 (en) | 2001-04-24 | 2003-09-18 | University Of North Texas Health Science Center | Endothelin antagonists and endothelin-converting enzyme inhibitors for the treatment of glaucoma |
| HRP20040354B1 (en) | 2001-10-19 | 2012-10-31 | Isotechnika Inc. | Novel cyclosporin analog microemulsion preconcentrates |
| AU2002365167A1 (en) | 2001-12-18 | 2003-07-09 | The Brigham And Women's Hospital | Inhibition or prevention of infection by bacteria with epa, dha or analogs |
| US7582785B2 (en) | 2002-04-01 | 2009-09-01 | University Of Southern California | Trihydroxy polyunsaturated eicosanoid derivatives |
| WO2003084305A2 (en) | 2002-04-01 | 2003-10-16 | University Of Southern California | Trihydroxy polyunsaturated eicosanoids |
| DE60330154D1 (de) | 2002-08-12 | 2009-12-31 | Brigham & Womens Hospital | Resolvine: biotemplate zur durchführung therapeutischer anwendungen |
| US7759395B2 (en) | 2002-08-12 | 2010-07-20 | The Brigham And Women's Hospital, Inc. | Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma |
| WO2004069181A2 (en) | 2003-02-03 | 2004-08-19 | Pharmacia Corporation | Composition for the treatment of intraocular pressure |
| JP2004238346A (ja) | 2003-02-07 | 2004-08-26 | Shiono Chemical Co Ltd | トラニラストの安定な水溶液製剤 |
| WO2004078143A2 (en) | 2003-03-05 | 2004-09-16 | The Brigham And Women's Hospital Inc. | Methods for identification and uses of anti-inflammatory receptors for eicosapentaenoic acid analogs |
| WO2004096261A1 (es) | 2003-05-02 | 2004-11-11 | Arturo Jimenez Bayardo | Metodo para preparar una solucion acuosa de ciclosporina-a y solucion acuosa resultante |
| US7087237B2 (en) | 2003-09-19 | 2006-08-08 | Advanced Ocular Systems Limited | Ocular solutions |
| US20050238589A1 (en) | 2004-04-14 | 2005-10-27 | Van Dyke Thomas E | Methods and compositions for preventing or treating periodontal diseases |
| DE602004017477D1 (de) | 2004-11-09 | 2008-12-11 | Novagali Pharma Sa | Öl-in-Wasser-Emulsion mit niedriger Konzentration des kationischen Mittels und positivem Zetapotential |
| WO2006055965A2 (en) | 2004-11-19 | 2006-05-26 | Martek Biosciences Corporation | Oxylipins from long chain polyunsaturated fatty acids and methods of making and using the same |
| US20090209599A1 (en) | 2005-06-09 | 2009-08-20 | Yoko Endo | Eye drop containing roflumilast |
| EP1890677A4 (en) | 2005-06-16 | 2013-01-30 | Myriad Genetics Inc | PHARMACEUTICAL COMPOSITIONS AND THEIR USE |
| US20070015691A1 (en) | 2005-07-13 | 2007-01-18 | Allergan, Inc. | Cyclosporin compositions |
| AU2006270041B2 (en) | 2005-07-18 | 2011-08-18 | Minu, Llc | Enhanced ocular neuroprotection/neurostimulation |
| EP1983977A4 (en) | 2006-01-31 | 2011-11-30 | Martek Biosciences Corp | OXYLIPINES FROM STEARIDONIC ACID AND GAMMA-LINOLIC ACID AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| US10137083B2 (en) | 2006-03-07 | 2018-11-27 | SGN Nanopharma Inc | Ophthalmic preparations |
| CA2650422A1 (en) | 2006-04-24 | 2007-11-08 | Nanocarrier Co., Ltd. | Process for producing polymer micelles encapsulating low molecular weight drugs |
| WO2007136134A1 (ja) | 2006-05-23 | 2007-11-29 | Nanocarrier Co., Ltd. | 疎水性薬物内包ポリマーミセルの製造方法 |
| CN101489574A (zh) | 2006-07-18 | 2009-07-22 | 那野伽利阿株式会社 | 内包生理活性多肽或蛋白质的高分子聚合物胶束及其制造方法 |
| EP2120920A4 (en) | 2007-02-20 | 2011-06-15 | Martek Biosciences Corp | OXYLIPINES OF LONG-CHAIN MULTIPLE-UNSATURATED FATTY ACIDS AND METHOD FOR THEIR PREPARATION AND USE |
| US20100310462A1 (en) | 2007-04-18 | 2010-12-09 | Biochromix Ab | Binding of pathological forms of proteins using conjugated polyelectrolytes |
| US8512687B2 (en) | 2007-07-09 | 2013-08-20 | Novagali Pharma Sa | Oil in water emulsion comprising NSAIDs and quaternary ammonium halides |
| EP2193795B1 (en) | 2007-08-29 | 2014-10-01 | Wakamoto Pharmaceutical Co., Ltd. | Latanoprost-containing aqueous pharmaceutical composition |
| MX2007011165A (es) | 2007-09-12 | 2009-03-11 | Arturo Jimenez Bayardo | Composición farmacéutica estable de timolol, dorzolamida y brimonidina. |
| ES2667945T3 (es) | 2007-10-08 | 2018-05-16 | Aurinia Pharmaceuticals Inc. | Composiciones oftálmicas que comprenden inhibidores de calcineurina o Inhibidores de mTOR |
| JP2011508776A (ja) | 2008-01-04 | 2011-03-17 | アルコン ファーマシューティカルズ リミテッド | 安定な水性シクロスポリン組成物 |
| TWI544927B (zh) | 2008-03-17 | 2016-08-11 | 愛爾康研究有限公司 | 具有低濃度的表面活性劑以促進治療劑之生物可利用性的藥學組成物 |
| EP2278953B1 (en) | 2008-05-28 | 2016-05-04 | Alcon Research, Ltd | Self-preserved emulsions |
| EP2127638A1 (en) | 2008-05-30 | 2009-12-02 | Santen Pharmaceutical Co., Ltd | Method and composition for treating ocular hypertension and glaucoma |
| AP2012006053A0 (en) | 2009-06-02 | 2012-02-29 | Brian Charles Keller | Pure peg-lipid conjugates. |
| EP2440185B1 (en) | 2009-06-09 | 2015-04-08 | Aurinia Pharmaceuticals Inc. | Topical drug delivery systems for ophthalmic use |
| EP2478906A4 (en) | 2009-09-17 | 2013-02-20 | Senju Pharma Co | AQUEOUS OPHTHALMIC DROPS THAT CONTAIN LATANOPROST, AND A METHOD OF INHIBITING ADSORPTION OF LATANOPROST ON A RESIN |
| US8637569B2 (en) | 2009-10-22 | 2014-01-28 | Api Genesis, Llc | Methods of increasing solubility of poorly soluble compounds and methods of making and using formulations of such compounds |
| EP2538965B1 (en) | 2010-02-25 | 2017-04-12 | Schepens Eye Research Institute | Therapeutic compositions for the treatment of dry eye disease |
| WO2011138801A1 (en) | 2010-05-07 | 2011-11-10 | Sun Pharma Advanced Research Company Ltd. | Novel ophthalmic compositions |
| US20130065888A1 (en) | 2011-08-15 | 2013-03-14 | Biserka Cetina-Cizmek | Ophthalmic formulations and processes for their preparation |
| US9278132B2 (en) | 2012-02-13 | 2016-03-08 | Bausch & Lomb Incorporated | Ophthalmic pharmaceutical compositions and methods of making and using same |
| KR101211902B1 (ko) | 2012-04-30 | 2012-12-13 | 주식회사 휴온스 | 사이클로스포린 함유 무자극성 나노에멀젼 안약 조성물 |
| MX2014013714A (es) | 2012-05-11 | 2015-08-10 | Cipla Ltd | Composicion farmaceutica. |
| PL2887923T3 (pl) * | 2012-08-24 | 2023-08-14 | Sun Pharmaceutical Industries Limited | Preparat okulistyczny polioksylipidu lub polioksylowego kwasu tłuszczowego i leczenie chorób oczu |
| WO2014126997A1 (en) | 2013-02-13 | 2014-08-21 | The Research Foundation For The State University Of New York | Glaucoma treatment |
| AU2015264181A1 (en) | 2014-05-23 | 2016-12-01 | Ocular Technologies Sarl | Topical formulations and uses thereof |
| US20150352176A1 (en) | 2014-06-06 | 2015-12-10 | Newport Research, Inc. | Oil-free and fat-free aqueous suspensions of cyclosporin |
| US9421199B2 (en) | 2014-06-24 | 2016-08-23 | Sydnexis, Inc. | Ophthalmic composition |
| US20180133217A1 (en) | 2015-05-04 | 2018-05-17 | Ocular Technologies Sarl | Topical formulations and uses thereof |
| EP3373976B1 (en) | 2015-11-10 | 2024-01-03 | Sun Pharmaceutical Industries Limited | Topical formulations and uses thereof |
| EP3373924A4 (en) | 2015-11-12 | 2019-06-19 | Sun Pharma Global FZE | Topical formulations and uses thereof |
| US10918694B2 (en) | 2016-02-29 | 2021-02-16 | Sun Pharma Global Fze | Topical cyclosporine-containing formulations and uses thereof |
| WO2017152129A2 (en) | 2016-03-03 | 2017-09-08 | Ocular Technologies Sarl | Treatment of glaucoma and/or retinal diseases and formulations useful therefore |
-
2016
- 2016-11-03 EP EP16864797.2A patent/EP3373976B1/en active Active
- 2016-11-03 WO PCT/US2016/060391 patent/WO2017083167A1/en not_active Ceased
- 2016-11-03 PT PT168647972T patent/PT3373976T/pt unknown
- 2016-11-03 US US15/772,779 patent/US20190231885A1/en not_active Abandoned
- 2016-11-03 PL PL16864797.2T patent/PL3373976T3/pl unknown
- 2016-11-03 EP EP23219654.3A patent/EP4364810A3/en active Pending
- 2016-11-03 FI FIEP16864797.2T patent/FI3373976T3/fi active
- 2016-11-03 ES ES16864797T patent/ES2974821T3/es active Active
- 2016-11-03 DK DK16864797.2T patent/DK3373976T3/da active
- 2016-11-03 JP JP2018543272A patent/JP7793283B2/ja active Active
- 2016-11-03 AU AU2016351588A patent/AU2016351588A1/en not_active Abandoned
-
2021
- 2021-03-12 US US17/200,454 patent/US12053528B2/en active Active
-
2022
- 2022-11-04 JP JP2022177207A patent/JP7669326B2/ja active Active
-
2024
- 2024-07-02 US US18/762,112 patent/US20240358840A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3373976A4 (en) | 2019-05-22 |
| WO2017083167A1 (en) | 2017-05-18 |
| EP3373976A1 (en) | 2018-09-19 |
| PT3373976T (pt) | 2024-04-02 |
| EP4364810A3 (en) | 2024-07-24 |
| JP2023012533A (ja) | 2023-01-25 |
| EP3373976B1 (en) | 2024-01-03 |
| JP7793283B2 (ja) | 2026-01-05 |
| EP4364810A2 (en) | 2024-05-08 |
| DK3373976T3 (da) | 2024-04-02 |
| PL3373976T3 (pl) | 2024-06-24 |
| US20240358840A1 (en) | 2024-10-31 |
| JP2018532809A (ja) | 2018-11-08 |
| ES2974821T3 (es) | 2024-07-01 |
| US20210268114A1 (en) | 2021-09-02 |
| US12053528B2 (en) | 2024-08-06 |
| JP7669326B2 (ja) | 2025-04-28 |
| US20190231885A1 (en) | 2019-08-01 |
| FI3373976T3 (fi) | 2024-03-25 |
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