CA2519980C - Prevention and treatment of breast cancer with 4-hydroxy tamoxifen - Google Patents
Prevention and treatment of breast cancer with 4-hydroxy tamoxifen Download PDFInfo
- Publication number
- CA2519980C CA2519980C CA2519980A CA2519980A CA2519980C CA 2519980 C CA2519980 C CA 2519980C CA 2519980 A CA2519980 A CA 2519980A CA 2519980 A CA2519980 A CA 2519980A CA 2519980 C CA2519980 C CA 2519980C
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- Prior art keywords
- hydroxy tamoxifen
- tamoxifen
- weight
- breast
- hydroxy
- 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
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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
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- A61K9/0012—Galenical forms characterised by the site of application
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| DE60327363D1 (de) * | 2002-12-18 | 2009-06-04 | Besins Int Lab | Verringerung der dichte des brustgewebes durch 4-hydroxy tamoxifen |
| WO2004087123A1 (en) * | 2003-04-01 | 2004-10-14 | Laboratoires Besins International | Prevention and treatment of breast cancer with 4-hydroxy tamoxifen |
| ATE324880T1 (de) * | 2002-12-18 | 2006-06-15 | Besins Int Lab | Behandlung von mastalgie mit4-hydroxy-tamoxifen |
| ES2304610T3 (es) * | 2003-06-09 | 2008-10-16 | Ascend Therapeutics, Inc. | Tratamiento y prevencion de cicatrizacion excesiva con 4-hidroxi-tamoxifeno. |
| US7968532B2 (en) * | 2003-12-15 | 2011-06-28 | Besins Healthcare Luxembourg | Treatment of gynecomastia with 4-hydroxy tamoxifen |
| US7507769B2 (en) * | 2004-03-22 | 2009-03-24 | Laboratoires Besins International | Treatment and prevention of benign breast disease with 4-hydroxy tamoxifen |
| EP1579856A1 (en) * | 2004-03-22 | 2005-09-28 | Laboratoires Besins International | Treatment and prevention of benign breast disease with 4-hydroxy tamoxifen |
| US20050208139A1 (en) * | 2004-03-22 | 2005-09-22 | Ascend Therapeutics, Inc. | Chemically stable compositions of 4-hydroxy tamoxifen |
| MXPA06010914A (es) * | 2004-03-22 | 2006-12-15 | Besins Int Lab | Tratamiento y prevencion de enfermedades de mama benigna con 4-hidroxi tamoxifen. |
| EP1647271A1 (en) * | 2004-10-14 | 2006-04-19 | Laboratoires Besins International | 4-Hydroxy tamoxifen gel formulations |
| GEP20104889B (en) * | 2004-10-14 | 2010-02-10 | Laboratoires Besins Int | 4-hydroxy tamoxifen gel formulations |
| EP2147674A1 (en) * | 2008-07-24 | 2010-01-27 | Besins Healthcare | Transdermal pharmaceutical compositions comprising danazol |
| US10080760B2 (en) * | 2009-10-27 | 2018-09-25 | Besins Healthcare Luxembourg Sarl | Transdermal pharmaceutical compositions comprising active agents |
| EP3143392B1 (en) * | 2014-05-12 | 2023-02-22 | Quest Diagnostics Investments Incorporated | Quantitation of tamoxifen metabolites by mass spectrometry |
| KR101571098B1 (ko) | 2014-07-16 | 2015-11-23 | 건국대학교 산학협력단 | 타목시펜 및 메틸설포닐메탄을 유효성분으로 포함하는 암 질환 예방 또는 치료용 약학 조성물 |
| EP3230478B1 (en) * | 2014-12-12 | 2023-08-02 | Miradx | Methods for treating or preventing cancer in a kras-variant patient and for diagnosing risk of developing multiple primary breast tumors |
| CA3022377A1 (en) | 2016-04-29 | 2017-11-02 | Board Of Regents, The University Of Texas System | Targeted measure of transcriptional activity related to hormone receptors |
| KR20200052349A (ko) | 2017-09-11 | 2020-05-14 | 아토사 테라퓨틱스, 인크. | 엔독시펜을 제조 및 사용하는 방법 |
| WO2020023616A1 (en) * | 2018-07-24 | 2020-01-30 | Cornell University | Methods of upregulating tiparp as anticancer strategies |
| US12201591B2 (en) | 2019-07-03 | 2025-01-21 | Atossa Therapeutics, Inc. | Sustained release compositions of endoxifen |
| WO2025019830A1 (en) * | 2023-07-19 | 2025-01-23 | Atossa Therapeutics, Inc. | Anti-tumor compounds and methods of use thereof and synthesis thereof |
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| FR2558373B1 (fr) * | 1984-01-20 | 1987-07-03 | Mauvais Jarvis Pierre | Medicament antioestrogene a base de 4-hydroxytamoxifene pour administration percutanee |
| EP0287690B1 (de) * | 1987-04-21 | 1992-09-02 | HEUMANN PHARMA GMBH & CO | Stabile Lösungsmitteladdukte von Z-1-(p-beta-Dimethylamino-ethoxyphenyl)-1-(p-hydroxyphenyl)-2-phenylbut-1-en |
| US5045553A (en) | 1987-06-24 | 1991-09-03 | Fujisawa Pharmaceutical Company, Ltd. | Pharmaceutical composition for percutaneous drug absorption and percutaneous drug absorption promoter |
| DE3836862A1 (de) | 1988-10-27 | 1990-05-03 | Schering Ag | Mittel zur transdermalen applikation von steroidhormonen |
| US5189212A (en) | 1990-09-07 | 1993-02-23 | University Of Georgia Research Foundation, Inc. | Triarylethylene carboxylic acids with estrogenic activity |
| TW218849B (enExample) * | 1991-05-17 | 1994-01-11 | Bristol Myers Squibb Co | |
| US5613958A (en) | 1993-05-12 | 1997-03-25 | Pp Holdings Inc. | Transdermal delivery systems for the modulated administration of drugs |
| DE4407742C1 (de) | 1994-03-08 | 1995-06-22 | Hexal Pharma Gmbh | Transdermales System in Form eines Pflasters mit einem Tamoxifen-Derivat |
| US5720963A (en) * | 1994-08-26 | 1998-02-24 | Mary Kay Inc. | Barrier disruption treatments for structurally deteriorated skin |
| ATE200978T1 (de) | 1996-03-29 | 2001-05-15 | S W Patentverwertungs Ges M B | KOSMETIKUM BZW. KOSMETIKZUSAMMENSETZUNG ZUR GLÄTTUNG UND STRAFFUNG DER HAUT BEI GESTÖRTEM UNTERHAUT-BINDE-FETTGEWEBE, INSBESONDERE BEI DER ßCELLULITEß |
| JP2001527037A (ja) | 1997-12-23 | 2001-12-25 | ヘキサル アーゲー | Ｚ−４−ヒドロキシタモキシフェン及びシクロデキストリンを含む混合物及び薬剤学的組成 |
| US6013270A (en) * | 1998-04-20 | 2000-01-11 | The Procter & Gamble Company | Skin care kit |
| ATE290856T1 (de) | 1999-12-16 | 2005-04-15 | Dermatrends Inc | Hydroxide freisetzende verbindungen zum verbessern der hautdurchlässigkeit |
| DE10033853A1 (de) | 2000-07-12 | 2002-01-31 | Hexal Ag | Transdermales therapeutisches System mit hochdispersem Siliziumdioxid |
| US20040198706A1 (en) | 2003-03-11 | 2004-10-07 | Carrara Dario Norberto R. | Methods and formulations for transdermal or transmucosal application of active agents |
| US6503894B1 (en) | 2000-08-30 | 2003-01-07 | Unimed Pharmaceuticals, Inc. | Pharmaceutical composition and method for treating hypogonadism |
| AU2002340120A1 (en) | 2001-10-04 | 2003-04-14 | Cellegy Pharmaceuticals, Inc. | Semisolid topical hormonal compositions and methods for treatment |
| PT1317921E (pt) | 2001-12-07 | 2009-11-06 | Besins Mfg Belgium | Composição farmacêutica sob a forma de gel ou de solução à base de di-hidrotestosterona, seu processo de preparação e suas utilizações |
| WO2004087123A1 (en) | 2003-04-01 | 2004-10-14 | Laboratoires Besins International | Prevention and treatment of breast cancer with 4-hydroxy tamoxifen |
| ATE324880T1 (de) * | 2002-12-18 | 2006-06-15 | Besins Int Lab | Behandlung von mastalgie mit4-hydroxy-tamoxifen |
| DE60327363D1 (de) | 2002-12-18 | 2009-06-04 | Besins Int Lab | Verringerung der dichte des brustgewebes durch 4-hydroxy tamoxifen |
| ES2304610T3 (es) | 2003-06-09 | 2008-10-16 | Ascend Therapeutics, Inc. | Tratamiento y prevencion de cicatrizacion excesiva con 4-hidroxi-tamoxifeno. |
| US7968532B2 (en) | 2003-12-15 | 2011-06-28 | Besins Healthcare Luxembourg | Treatment of gynecomastia with 4-hydroxy tamoxifen |
| US7507769B2 (en) | 2004-03-22 | 2009-03-24 | Laboratoires Besins International | Treatment and prevention of benign breast disease with 4-hydroxy tamoxifen |
| EP1579856A1 (en) | 2004-03-22 | 2005-09-28 | Laboratoires Besins International | Treatment and prevention of benign breast disease with 4-hydroxy tamoxifen |
| US20050208139A1 (en) | 2004-03-22 | 2005-09-22 | Ascend Therapeutics, Inc. | Chemically stable compositions of 4-hydroxy tamoxifen |
| EP1647271A1 (en) | 2004-10-14 | 2006-04-19 | Laboratoires Besins International | 4-Hydroxy tamoxifen gel formulations |
-
2003
- 2003-12-15 WO PCT/EP2003/015029 patent/WO2004087123A1/en not_active Ceased
- 2003-12-15 CA CA2519980A patent/CA2519980C/en not_active Expired - Lifetime
- 2003-12-15 ES ES03785958.4T patent/ES2483896T3/es not_active Expired - Lifetime
- 2003-12-15 ES ES08103007.4T patent/ES2456957T3/es not_active Expired - Lifetime
- 2003-12-15 AU AU2003294973A patent/AU2003294973B2/en not_active Expired
- 2003-12-15 EP EP03785958.4A patent/EP1608353B1/en not_active Expired - Lifetime
- 2003-12-15 ES ES08103014.0T patent/ES2456958T3/es not_active Expired - Lifetime
- 2003-12-15 MX MXPA05010597A patent/MXPA05010597A/es active IP Right Grant
- 2003-12-15 EP EP08103014.0A patent/EP1941871B1/en not_active Expired - Lifetime
- 2003-12-15 EP EP08103007.4A patent/EP1952810B1/en not_active Expired - Lifetime
- 2003-12-15 NZ NZ542499A patent/NZ542499A/en not_active IP Right Cessation
- 2003-12-15 JP JP2004570040A patent/JP5490346B2/ja not_active Expired - Lifetime
- 2003-12-15 US US10/734,638 patent/US7704516B2/en not_active Expired - Lifetime
-
2005
- 2005-09-12 IL IL170807A patent/IL170807A/en active IP Right Grant
- 2005-09-30 NO NO20054526A patent/NO333805B1/no not_active IP Right Cessation
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2009
- 2009-01-14 US US12/353,890 patent/US8475814B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7704516B2 (en) | 2010-04-27 |
| EP1608353B1 (en) | 2014-04-30 |
| US20090186944A1 (en) | 2009-07-23 |
| EP1952810A1 (en) | 2008-08-06 |
| MXPA05010597A (es) | 2006-03-09 |
| HK1119950A1 (en) | 2009-03-20 |
| AU2003294973B2 (en) | 2010-05-13 |
| US20050031695A1 (en) | 2005-02-10 |
| EP1608353A1 (en) | 2005-12-28 |
| JP2006514967A (ja) | 2006-05-18 |
| EP1941871B1 (en) | 2014-01-08 |
| AU2003294973A1 (en) | 2004-10-25 |
| HK1086193A1 (en) | 2006-09-15 |
| EP1952810B1 (en) | 2014-01-08 |
| NZ542499A (en) | 2008-10-31 |
| IL170807A (en) | 2014-08-31 |
| NO333805B1 (no) | 2013-09-16 |
| US8475814B2 (en) | 2013-07-02 |
| ES2456958T3 (es) | 2014-04-24 |
| ES2456957T3 (es) | 2014-04-24 |
| CA2519980A1 (en) | 2004-10-14 |
| WO2004087123A1 (en) | 2004-10-14 |
| NO20054526L (no) | 2005-09-30 |
| EP1941871A1 (en) | 2008-07-09 |
| JP5490346B2 (ja) | 2014-05-14 |
| ES2483896T3 (es) | 2014-08-08 |
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