JP6343619B2 - プロゲステロン依存性病態を処置する方法およびその組成物 - Google Patents
プロゲステロン依存性病態を処置する方法およびその組成物 Download PDFInfo
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- JP6343619B2 JP6343619B2 JP2015540700A JP2015540700A JP6343619B2 JP 6343619 B2 JP6343619 B2 JP 6343619B2 JP 2015540700 A JP2015540700 A JP 2015540700A JP 2015540700 A JP2015540700 A JP 2015540700A JP 6343619 B2 JP6343619 B2 JP 6343619B2
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| HK1245118A1 (zh) * | 2015-05-18 | 2018-08-24 | Bayer Pharma Aktiengesellschaft | 选择性孕酮受体调节剂(sprm)方案 |
| WO2017123577A1 (en) * | 2016-01-12 | 2017-07-20 | Repros Therapeutics Inc. | Trans-clomiphene and progesterone receptor antagonist combination therapy for treating hormone-dependent conditions |
| WO2020176738A1 (en) | 2019-02-28 | 2020-09-03 | Janssen Biotech, Inc. | Anti-il-alpha antibody for the treatment of hidradenitis suppurativa |
| CA3179228A1 (en) | 2020-04-16 | 2021-10-21 | Janssen Biotech, Inc. | Treatment of hidradenitis suppurativa |
Family Cites Families (43)
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| FR2377418A1 (fr) | 1977-01-13 | 1978-08-11 | Roussel Uclaf | Nouveaux derives steroides 4,9-dieniques 11b-substitues, leur procede de preparation et leur application comme medicaments |
| FR2521565B1 (fr) | 1982-02-17 | 1985-07-05 | Dior Sa Parfums Christian | Melange pulverulent de constituants lipidiques et de constituants hydrophobes, procede pour le preparer, phases lamellaires lipidiques hydratees et procede de fabrication, compositions pharmaceutiques ou cosmetiques comportant des phases lamellaires lipidiques hydratees |
| FR2522328B1 (fr) | 1982-03-01 | 1986-02-14 | Roussel Uclaf | Nouveaux produits derives de la structure 3-ceto 4,9 19-nor steroides, leur procede de preparation et leur application comme medicaments |
| FR2534487B1 (fr) | 1982-10-15 | 1988-06-10 | Dior Christian Parfums | Procede d'homogeneisation de dispersions de phases lamellaires lipidiques hydratees, et suspensions obtenues par ce procede |
| ATE151286T1 (de) | 1983-11-14 | 1997-04-15 | Columbia Lab Inc | Bioadhäsive mittel |
| FR2598421B1 (fr) | 1986-05-06 | 1988-08-19 | Roussel Uclaf | Nouveaux produits 19-nor ou 19-nor d-homo steroides substitues en position 11b par un radical phenyle portant un radical alkynyle, leur procede de preparation, leur application comme medicaments et les compositions les renfermant |
| US4954490A (en) | 1988-06-23 | 1990-09-04 | Research Triangle Institute | 11 β-substituted progesterone analogs |
| US5077211A (en) | 1988-07-06 | 1991-12-31 | Applied Genetics, Inc. | Purification and administration of dna repair enzymes |
| US5468741A (en) | 1993-05-28 | 1995-11-21 | The Regents Of The University Of California | Use of low levels of mifepristone to treat leiomyomata |
| US5543150A (en) | 1993-09-15 | 1996-08-06 | Columbia Laboratories, Inc. | Method of progesterone delivery and affect thereof |
| DE4426601A1 (de) | 1994-07-27 | 1996-02-01 | Schering Ag | Verwendung eines Kombinationsproduktes enthaltend einen kompetitiven Progesteronantagonisten und ein Gestagen zur Herstellung eines Arzneimittels zur Behandlung der Endometriose oder des Leiomyomata uteri |
| SK282570B6 (sk) | 1995-02-02 | 2002-10-08 | Schering Aktiengesellschaft | Antagonisty progesterónu na výrobu liekov na ošetrenie dysfunkčného maternicového krvácania |
| US6900193B1 (en) | 1996-05-01 | 2005-05-31 | The United States Of America As Represented By The Department Of Health And Human Services | Structural modification of 19-norprogesterone I: 17-α-substituted-11-β-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents |
| DE69702450T2 (de) | 1996-05-01 | 2001-03-08 | The Government Of The United States Of America As Represented By The Secretary Of National Institute Of Health, Office Of Technology Transfer | 21-substituierte progesteron derivate als antigestagene |
| AU2805397A (en) | 1996-08-30 | 1998-03-19 | Population Council, Center For Biomedical Research, The | Vaginal application mifepristone |
| US6682174B2 (en) | 1998-03-25 | 2004-01-27 | Silverbrook Research Pty Ltd | Ink jet nozzle arrangement configuration |
| US6020328A (en) | 1998-03-06 | 2000-02-01 | Research Triangle Institute | 20-keto-11β-arylsteroids and their derivatives having agonist or antagonist hormonal properties |
| EP1008443A1 (de) | 1998-12-08 | 2000-06-14 | Alusuisse Technology & Management AG | Sterilisierbarer Folienverbund für Verpackungszwecke |
| US6740645B1 (en) | 1999-09-03 | 2004-05-25 | Research Triangle Institute | 17β-acyl-17α-propynyl-11β-(cyclic amino) aryl steroids and their derivatives having antagonist hormonal properties |
| UA74168C2 (uk) | 1999-10-05 | 2005-11-15 | Коламбіа Леборетеріс (Бермуда) Лімітед | Лікування ендометріозу або безпліддя, або покращення плідності та застосування бета-адренергічного агоніста для виробництва лікарського засобу |
| DK1265911T3 (da) | 2000-03-17 | 2008-09-29 | Us Gov Health & Human Serv | 17-alfa-substitueret-11-beta-substitueret-4-aryl og 21-substitueret 19-norpregnadiendion som antiprogestationelle midler |
| IN191020B (enExample) | 2000-03-28 | 2003-09-13 | Dabur Res Foundation | |
| US7378406B2 (en) | 2000-10-18 | 2008-05-27 | Schering Ag | Use of antiprogestins for prophylaxis and treatment of hormone-dependent diseases |
| DE60228583D1 (de) | 2001-07-09 | 2008-10-09 | Repros Therapeutics Inc | Verfahren und materialien für die behandlung des testosteron-mangels bei männern |
| US7833545B2 (en) | 2003-04-29 | 2010-11-16 | The General Hospital Corporation | Methods and devices for the sustained release of multiple drugs |
| EP1593376A1 (en) | 2004-05-04 | 2005-11-09 | Warner-Lambert Company LLC | Improved pullulan capsules |
| AU2005265357B2 (en) | 2004-07-09 | 2011-04-07 | Laboratoire Hra Pharma | Sustained release compositions containing progesterone receptor modulators |
| GT200500185A (es) | 2004-08-09 | 2006-04-10 | Moduladores del receptor de progesterona que comprenden derivados de pirrol-oxindol y sus usos | |
| PL383444A1 (pl) | 2005-03-22 | 2008-03-17 | Repros Therapeutics Inc. | Sposoby dawkowania trans-klomifenu |
| EP1874732A1 (en) | 2005-04-20 | 2008-01-09 | Pfizer Limited | Pyrazole derivatives as progesterone receptor antagonists |
| DE102005030294A1 (de) | 2005-06-24 | 2007-01-04 | Schering Ag | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| KR20080055956A (ko) | 2005-09-29 | 2008-06-19 | 레프로스 쎄라피우틱스 아이엔씨. | 향상된 생체이용률을 가지며, 스테로이드 유도체와폴리글리콜리세드 글리세리드를 포함하는 제제 |
| CN1846703A (zh) | 2006-02-13 | 2006-10-18 | 程定超 | 米非司酮阴道给药制剂及其组成和制备方法 |
| US8173626B2 (en) * | 2006-03-08 | 2012-05-08 | Danco Laboratories Llc | Methods, dosing regimens and medications using anti-progestational agents for the treatment of disorders |
| ES2643318T3 (es) | 2006-10-24 | 2017-11-22 | Repros Therapeutics Inc. | Composiciones y métodos para suprimir la proliferación endometrial |
| CA2682752C (en) | 2007-04-05 | 2015-07-07 | University Of Kansas | Rapidly dissolving pharmaceutical compositions comprising pullulan |
| HRP20160689T1 (hr) | 2007-04-20 | 2016-07-15 | Preglem S.A. | Selektivni modulatori progesterona za tretman uterinog krvarenja |
| JP5555631B2 (ja) | 2007-09-20 | 2014-07-23 | ラピドット メディカル インポート アンド マーケティング リミテッド | ミフェプリストンによる子宮平滑筋腫、平滑筋腫、筋腫、子宮類線維腫、子宮内膜症、または腺筋症を治療するための組成物および手段 |
| TWI477276B (zh) * | 2008-04-28 | 2015-03-21 | Repros Therapeutics Inc | 抗黃體素給藥方案 |
| JP5992330B2 (ja) | 2009-09-29 | 2016-09-14 | メディメトリクス ペルソナリズド ドルグ デリヴェリー ベー ヴェ | 物質を投与するための子宮内電子カプセル |
| UA113283C2 (xx) * | 2010-12-23 | 2017-01-10 | 19-норстероїди і їх застосування для лікування прогестеронзалежних станів | |
| DE202011110355U1 (de) * | 2011-03-09 | 2014-01-15 | Arstat, Inc. | Behandlung von Uterusmyomen durch intravaginale Verabreichung einer niedrigen Dosis eines selektiven Progesteronrezeptormodulators, eines Antigestagens oder eines Antigestagen-Wirkstoffes |
| UA113291C2 (xx) | 2011-08-04 | 2017-01-10 | Метаболіти транскломіфену і їх застосування |
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| ES2688821T3 (es) | 2018-11-07 |
| JP2018062530A (ja) | 2018-04-19 |
| WO2014070517A1 (en) | 2014-05-08 |
| CA2888377A1 (en) | 2014-05-08 |
| MX2015004821A (es) | 2015-08-14 |
| AU2013338305B2 (en) | 2018-06-07 |
| US9545411B2 (en) | 2017-01-17 |
| CA2888377C (en) | 2021-02-02 |
| AU2013338305A1 (en) | 2015-05-14 |
| JP2015535282A (ja) | 2015-12-10 |
| EP2914268B1 (en) | 2018-07-04 |
| HK1211852A1 (en) | 2016-06-03 |
| EP2914268A1 (en) | 2015-09-09 |
| US20150297612A1 (en) | 2015-10-22 |
| IL238403A0 (en) | 2015-06-30 |
| CN104755087A (zh) | 2015-07-01 |
| IL238403B (en) | 2019-01-31 |
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