JP2013516501A - マイボーム腺機能障害を治療する方法 - Google Patents
マイボーム腺機能障害を治療する方法 Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/16—Amides, e.g. hydroxamic acids
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| PCT/US2011/020871 WO2011085385A1 (en) | 2010-01-11 | 2011-01-11 | Methods of treating meibomian gland dysfunction |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090043365A1 (en) | 2005-07-18 | 2009-02-12 | Kolis Scientific, Inc. | Methods, apparatuses, and systems for reducing intraocular pressure as a means of preventing or treating open-angle glaucoma |
| US7981095B2 (en) | 2005-07-18 | 2011-07-19 | Tearscience, Inc. | Methods for treating meibomian gland dysfunction employing fluid jet |
| US8915253B2 (en) | 2005-07-18 | 2014-12-23 | Tearscience, Inc. | Method and apparatus for treating gland dysfunction employing heated medium |
| US7981145B2 (en) | 2005-07-18 | 2011-07-19 | Tearscience Inc. | Treatment of meibomian glands |
| WO2013003594A2 (en) | 2011-06-28 | 2013-01-03 | Tearscience, Inc. | Methods and systems for treating meibomian gland dysfunction using radio-frequency energy |
| US20070060988A1 (en) * | 2005-07-18 | 2007-03-15 | Grenon Stephen M | Melting meibomian gland obstructions |
| US20080114423A1 (en) | 2006-05-15 | 2008-05-15 | Grenon Stephen M | Apparatus for inner eyelid treatment of meibomian gland dysfunction |
| US8950405B2 (en) | 2006-05-15 | 2015-02-10 | Tearscience, Inc. | Treatment of obstructive disorders of the eye or eyelid |
| US8137390B2 (en) | 2006-05-15 | 2012-03-20 | Tearscience, Inc. | System for providing heat treatment and heat loss reduction for treating meibomian gland dysfunction |
| US8128674B2 (en) | 2006-05-15 | 2012-03-06 | Tearscience, Inc. | System for outer eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US8128673B2 (en) | 2006-05-15 | 2012-03-06 | Tearscience, Inc. | System for inner eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US9314369B2 (en) | 2006-05-15 | 2016-04-19 | Tearscience, Inc. | System for inner eyelid treatment of meibomian gland dysfunction |
| KR101264820B1 (ko) * | 2006-08-24 | 2013-05-22 | 유니버시티 오브 테네시 리서치 파운데이션 | 치환된 아실아닐리드 및 그의 사용 방법 |
| US9381183B2 (en) * | 2012-07-18 | 2016-07-05 | Physicians Recommended Nutriceuticals, Llc | Methods for improving the quality of the meibum composition of meibomian glands |
| US10987334B2 (en) | 2012-07-13 | 2021-04-27 | University Of Tennessee Research Foundation | Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs) |
| US10258596B2 (en) | 2012-07-13 | 2019-04-16 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| US9622992B2 (en) | 2012-07-13 | 2017-04-18 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
| US9969683B2 (en) | 2012-07-13 | 2018-05-15 | Gtx, Inc. | Method of treating estrogen receptor (ER)-positive breast cancers with selective androgen receptor modulator (SARMS) |
| US10314807B2 (en) | 2012-07-13 | 2019-06-11 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| JP6226978B2 (ja) | 2012-07-13 | 2017-11-08 | ジーティーエックス・インコーポレイテッド | 選択的アンドロゲン受容体モジュレーター(sarm)によりアンドロゲン受容体(ar)陽性乳癌を処置する方法 |
| US9744149B2 (en) | 2012-07-13 | 2017-08-29 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
| US10842670B2 (en) | 2012-08-22 | 2020-11-24 | Johnson & Johnson Vision Care, Inc. | Apparatuses and methods for diagnosing and/or treating lipid transport deficiency in ocular tear films, and related components and devices |
| US10064818B2 (en) * | 2013-08-28 | 2018-09-04 | Presbyopia Therapies, LLC | Compositions and methods for the treatment of presbyopia |
| US9463201B2 (en) | 2014-10-19 | 2016-10-11 | M.G. Therapeutics Ltd | Compositions and methods for the treatment of meibomian gland dysfunction |
| RU2567829C1 (ru) * | 2014-10-22 | 2015-11-10 | Елизавета Геннадьевна Полунина | Способ оценки морфофункционального состояния мейбомиевых желез - биометрия мейбомиевых желез |
| KR101714710B1 (ko) | 2015-09-17 | 2017-03-10 | 고려대학교 산학협력단 | 마이봄샘 압출기 |
| CA3019349A1 (en) | 2016-04-14 | 2017-10-19 | Azura Ophthalmics Ltd. | Selenium disulfide compositions for use in treating meibomian gland dysfunction |
| US20210251970A1 (en) | 2018-10-10 | 2021-08-19 | Presbyopia Therapies Inc | Compositions and methods for storage stable ophthalmic drugs |
| WO2023091439A1 (en) | 2021-11-17 | 2023-05-25 | Lenz Therapeutics, Inc. | Aceclidine derivatives, compositions thereof and methods of use thereof |
| US20230168157A1 (en) * | 2021-11-29 | 2023-06-01 | Petróleo Brasileiro S.A. - Petrobras | System and method for evaluation of the deposition in tubes of the furnaces of a delayed coking unit |
| US11648247B1 (en) | 2021-12-16 | 2023-05-16 | Lenz Therapeutics, Inc. | Compositions and methods for the treatment of presbyopia |
| US12414942B1 (en) | 2024-03-15 | 2025-09-16 | Lenz Therapeutics Operations, Inc. | Compositions, methods, and systems for treating presbyopia |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008024456A2 (en) * | 2006-08-24 | 2008-02-28 | University Of Tennessee Research Foundation | Substituted acylanilides and methods of use thereof |
| JP2009506119A (ja) * | 2005-08-31 | 2009-02-12 | ユニバーシティ オブ テネシー リサーチ ファウンデーション | 選択的アンドロゲン受容体モジュレーターを用いる腎疾患、熱傷、創傷および脊髄損傷の処置 |
| WO2009137602A1 (en) * | 2008-05-07 | 2009-11-12 | The Regents Of The University Of California | Therapeutic modulation of ocular surface lubrication |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4407791A (en) * | 1981-09-28 | 1983-10-04 | Alcon Laboratories, Inc. | Ophthalmic solutions |
| EP0100172B1 (en) * | 1982-07-23 | 1987-08-12 | Imperial Chemical Industries Plc | Amide derivatives |
| US20050038110A1 (en) * | 2000-08-24 | 2005-02-17 | Steiner Mitchell S. | Selective androgen receptor modulators and methods of use thereof |
| US6492554B2 (en) * | 2000-08-24 | 2002-12-10 | The University Of Tennessee Research Corporation | Selective androgen receptor modulators and methods of use thereof |
| US6838484B2 (en) * | 2000-08-24 | 2005-01-04 | University Of Tennessee Research Foundation | Formulations comprising selective androgen receptor modulators |
| US7026500B2 (en) * | 2000-08-24 | 2006-04-11 | University Of Tennessee Research Foundation | Halogenated selective androgen receptor modulators and methods of use thereof |
| US7622503B2 (en) * | 2000-08-24 | 2009-11-24 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| US8445534B2 (en) * | 2000-08-24 | 2013-05-21 | University Of Tennessee Research Foundation | Treating androgen decline in aging male (ADAM)-associated conditions with SARMs |
| US7855229B2 (en) * | 2000-08-24 | 2010-12-21 | University Of Tennessee Research Foundation | Treating wasting disorders with selective androgen receptor modulators |
| US6998500B2 (en) * | 2000-08-24 | 2006-02-14 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| US7645898B2 (en) * | 2000-08-24 | 2010-01-12 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and method of use thereof |
| US20040260108A1 (en) * | 2001-06-25 | 2004-12-23 | Dalton James T. | Metabolites of selective androgen receptor modulators and methods of use thereof |
| US7919647B2 (en) * | 2000-08-24 | 2011-04-05 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| US20070173546A1 (en) * | 2000-08-24 | 2007-07-26 | Dalton James T | Selective androgen receptor modulators and method of use thereof |
| AU2001286243A1 (en) * | 2000-09-14 | 2002-03-26 | Kaken Pharmaceutical Co., Ltd. | Tetrahydroquinoline compounds |
| US8853266B2 (en) * | 2001-12-06 | 2014-10-07 | University Of Tennessee Research Foundation | Selective androgen receptor modulators for treating diabetes |
| US20070161608A1 (en) * | 2001-12-06 | 2007-07-12 | Dalton James T | Selective androgen receptor modulators for treating muscle wasting |
| US7772433B2 (en) * | 2002-02-28 | 2010-08-10 | University Of Tennessee Research Foundation | SARMS and method of use thereof |
| US7803970B2 (en) * | 2002-02-28 | 2010-09-28 | University Of Tennessee Research Foundation | Multi-substitued selective androgen receptor modulators and methods of use thereof |
| US7214693B2 (en) * | 2002-10-15 | 2007-05-08 | University Of Tennessee Research Foundation | Heterocyclic selective androgen receptor modulators and methods of use thereof |
| CA2477737C (en) | 2002-02-28 | 2012-08-07 | The University Of Tennessee Research Corporation | Multi-substituted selective androgen receptor modulators and methods of use thereof |
| ES2528764T3 (es) * | 2002-02-28 | 2015-02-12 | University Of Tennessee Research Foundation | Moduladores selectivos multisustituidos del receptor de andrógeno y métodos de uso de los mismos |
| EP1487780A4 (en) * | 2002-02-28 | 2005-11-16 | Univ Tennessee Res Foundation | HALOACETAMIDE AND AZID SUBSTITUTED COMPOUNDS AND METHODS OF USE THEREOF |
| US7022870B2 (en) | 2002-06-17 | 2006-04-04 | University Of Tennessee Research Foundation | N-bridged selective androgen receptor modulators and methods of use thereof |
| US20040265916A1 (en) * | 2002-10-15 | 2004-12-30 | Dalton James T. | Method for detecting selective androgen receptor modulators |
| US20040197928A1 (en) * | 2002-10-15 | 2004-10-07 | Dalton James T. | Method for detecting selective androgen receptor modulators |
| AU2003287075A1 (en) * | 2002-10-15 | 2004-05-04 | Gtx, Inc. | Treating obesity with selective androgen receptor modulators |
| CN1726034A (zh) | 2002-10-15 | 2006-01-25 | 田纳西大学研究基金会 | 亚甲基桥连的选择性雄激素受体调节剂及其应用方法 |
| WO2004035739A2 (en) | 2002-10-16 | 2004-04-29 | Gtx, Inc. | Treating androgen decline in aging male (adam)-associated conditions with sarms |
| US20060276539A1 (en) * | 2002-10-16 | 2006-12-07 | Dalton James T | Treating Androgen Decline in Aging Male (ADAM)- associated conditions with SARMS |
| US20040087810A1 (en) * | 2002-10-23 | 2004-05-06 | Dalton James T. | Irreversible selective androgen receptor modulators and methods of use thereof |
| US8309603B2 (en) * | 2004-06-07 | 2012-11-13 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| MXPA05007536A (es) * | 2003-01-13 | 2005-10-20 | Gtx Inc | Sintesis a gran escala de moduladores de receptor de androgeno selectivos. |
| CN1771031A (zh) | 2003-01-22 | 2006-05-10 | Gtx公司 | 用sarms治疗与女性雄激素缺乏(ad if)相关的疾病 |
| EA200501761A1 (ru) * | 2003-12-16 | 2006-04-28 | Джи Ти Икс, ИНК. | Пролекарственные формы селективных модуляторов андрогеновых рецепторов и способы их применения |
| WO2005067892A1 (en) * | 2004-01-10 | 2005-07-28 | Biolipid, Inc. | Lipid compositions and methods of use |
| US20130034562A1 (en) * | 2004-06-07 | 2013-02-07 | Dalton James T | Selective androgen receptor modulators for treating diabetes |
| US20110237664A1 (en) * | 2004-06-07 | 2011-09-29 | Dalton James T | Selective androgen receptor modulators for treating diabetes |
| AU2005251781C1 (en) | 2004-06-07 | 2008-02-21 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| JP4899625B2 (ja) * | 2006-05-12 | 2012-03-21 | スズキ株式会社 | 鞍乗型不整地走行車両 |
| AR061980A1 (es) | 2006-07-12 | 2008-08-10 | Univ Tennessee Res Foundation | Acilanilidas sustituidas y metodos para su utilizacion |
| MX2009000714A (es) * | 2006-07-19 | 2009-07-27 | Osurf | Moduladores de receptor de androgeno selectivos, analogos y derivados de los mismos. |
| US20080312194A1 (en) * | 2007-02-28 | 2008-12-18 | Ousler Iii George W | Methods and compositions for normalizing meibomian gland secretions |
| CA2886501C (en) * | 2007-09-11 | 2018-03-27 | Gtx, Inc. | Solid forms of selective androgen receptor modulators |
| US7968603B2 (en) * | 2007-09-11 | 2011-06-28 | University Of Tennessee Research Foundation | Solid forms of selective androgen receptor modulators |
-
2011
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- 2011-01-11 US US13/004,764 patent/US8791158B2/en active Active
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- 2011-01-11 AU AU2011203832A patent/AU2011203832A1/en not_active Abandoned
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009506119A (ja) * | 2005-08-31 | 2009-02-12 | ユニバーシティ オブ テネシー リサーチ ファウンデーション | 選択的アンドロゲン受容体モジュレーターを用いる腎疾患、熱傷、創傷および脊髄損傷の処置 |
| WO2008024456A2 (en) * | 2006-08-24 | 2008-02-28 | University Of Tennessee Research Foundation | Substituted acylanilides and methods of use thereof |
| WO2009137602A1 (en) * | 2008-05-07 | 2009-11-12 | The Regents Of The University Of California | Therapeutic modulation of ocular surface lubrication |
Also Published As
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| WO2011085385A1 (en) | 2011-07-14 |
| MX2012008110A (es) | 2012-10-03 |
| EP2523556A4 (en) | 2013-08-28 |
| EP2523556A1 (en) | 2012-11-21 |
| CN103002737A (zh) | 2013-03-27 |
| US20110172302A1 (en) | 2011-07-14 |
| CA2787114A1 (en) | 2011-07-14 |
| RU2012134351A (ru) | 2014-02-20 |
| US8791158B2 (en) | 2014-07-29 |
| AU2011203832A1 (en) | 2012-08-23 |
| KR20120115380A (ko) | 2012-10-17 |
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