KR101545300B1 - 고체 형태의 약제 - Google Patents
고체 형태의 약제 Download PDFInfo
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- KR101545300B1 KR101545300B1 KR1020107024458A KR20107024458A KR101545300B1 KR 101545300 B1 KR101545300 B1 KR 101545300B1 KR 1020107024458 A KR1020107024458 A KR 1020107024458A KR 20107024458 A KR20107024458 A KR 20107024458A KR 101545300 B1 KR101545300 B1 KR 101545300B1
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- KR
- South Korea
- Prior art keywords
- ene
- triol
- ethynyl
- androst
- crystalline
- Prior art date
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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| US8309746B2 (en) | 2008-06-06 | 2012-11-13 | Harbor Therapeutics, Inc | Methods for preparing 17-alkynyl-7-hydroxy steroids and related compounds |
| WO2012083161A1 (en) * | 2010-12-17 | 2012-06-21 | Harbor Biosciences, Inc. | Steroid tetrol solid state forms |
| CN103768071B (zh) * | 2012-10-23 | 2016-08-17 | 中国医药工业研究总院 | 一种治疗糖尿病的口服制剂 |
| WO2019041078A1 (en) * | 2017-08-28 | 2019-03-07 | Zhejiang Jiachi Pharmaceutical Development Ltd. | ASYMMETRIC SYNTHESIS AND USES OF COMPOUNDS IN TREATMENT OF DISEASES |
| JP2024519079A (ja) * | 2021-05-18 | 2024-05-08 | バイオビー・インコーポレイテッド | 神経変性状態の治療のための組成物 |
| WO2024054452A1 (en) * | 2022-09-06 | 2024-03-14 | Biovie Inc. | Methods for the treatment of mild cognitive impairment |
| CN120484042A (zh) * | 2025-05-16 | 2025-08-15 | 中国人民解放军军事科学院军事医学研究院 | 一种he3286的合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070129282A1 (en) * | 1998-11-24 | 2007-06-07 | Ahlem Clarence N | Pharmaceutical treatments and compositions |
| US20080015174A1 (en) * | 1998-11-24 | 2008-01-17 | Reading Christopher L | Metabolic Disease Treatments |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4329366A (en) * | 1979-11-08 | 1982-05-11 | Johnson & Johnson Products, Inc. | Topical acylaminophenols |
| US4898694A (en) * | 1987-11-25 | 1990-02-06 | Schwartz Arthur G | 17-Hydroxy-steroids |
| DE3801229A1 (de) | 1988-01-18 | 1989-07-27 | Krupp Polysius Ag | Mahlverfahren sowie mahlanlage |
| JP2642486B2 (ja) | 1989-08-04 | 1997-08-20 | 田辺製薬株式会社 | 難溶性薬物の超微粒子化法 |
| US5292730A (en) * | 1990-08-29 | 1994-03-08 | Humanetics Corporation | Modulation of immune system with Δ5-androstenes |
| ATE227992T1 (de) * | 1990-08-29 | 2002-12-15 | Humanetics Corp | Behandlungsverfahren zur förderung des gewichtsverlustes unter verwendung eines substituierten delta-5-androstens |
| US5641766A (en) * | 1990-08-29 | 1997-06-24 | Humanetics Corporation | UP-regulation of immune system with Δ 5-Androstenes |
| US5271944A (en) | 1991-04-05 | 1993-12-21 | Biofor, Ltd. | Pharmacologically enhanced formulations |
| US5922701A (en) * | 1992-05-01 | 1999-07-13 | University Of Utah Research Foundation | Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue |
| US5424077A (en) | 1993-07-13 | 1995-06-13 | Church & Dwight Co., Inc. | Co-micronized bicarbonate salt compositions |
| TW369521B (en) | 1993-09-17 | 1999-09-11 | Smithkline Beecham Corp | Androstenone derivative |
| US5455049A (en) | 1995-01-04 | 1995-10-03 | Ascent Pharmaceuticals, Inc. | Terfenadine oral powder |
| US5859000A (en) * | 1995-06-07 | 1999-01-12 | University Of Utah Research Foundation | Method for reducing mast cell mediated allergic reactions |
| US6686486B1 (en) * | 1997-05-07 | 2004-02-03 | Padma Marwah | Process for effecting allylic oxidation |
| US5869709A (en) * | 1997-05-07 | 1999-02-09 | Humanetics Corporation | Process for effecting allylic oxidation |
| ZA986614B (en) * | 1997-07-25 | 1999-01-27 | Gilead Sciences | Nucleotide analog composition |
| AU3088799A (en) * | 1998-03-18 | 1999-10-11 | Humanetics Corporation | Process for effecting allylic oxidation using dicarboxylic acid imides and chromium reagents |
| US20030060425A1 (en) * | 1998-11-24 | 2003-03-27 | Ahlem Clarence N. | Immune modulation method using steroid compounds |
| US20030083231A1 (en) * | 1998-11-24 | 2003-05-01 | Ahlem Clarence N. | Blood cell deficiency treatment method |
| US20060079492A1 (en) * | 1999-10-25 | 2006-04-13 | Ahlem Clarence N | Compositions and treatment methods |
| US6667299B1 (en) * | 2000-03-16 | 2003-12-23 | Hollis-Eden Pharmaceuticals, Inc. | Pharmaceutical compositions and treatment methods |
| US7045513B1 (en) * | 1999-03-18 | 2006-05-16 | Genelabs Technologies, Inc. | DHEA composition and method |
| CA2669753C (en) * | 1999-09-30 | 2012-06-26 | Hollis-Eden Pharmaceuticals, Inc. | Therapeutic treatment of androgen receptor driven conditions |
| CA2388939C (en) | 1999-10-25 | 2009-06-09 | Hollis-Eden Pharmaceuticals, Inc. | Therapeutic treatments for blood cell deficiencies |
| US6274746B1 (en) * | 2000-08-30 | 2001-08-14 | Padma Marwah | Process for allylic oxidation using metal hypochlorite and alkyl hydroperoxide |
| SK288222B6 (sk) * | 2000-12-14 | 2014-09-04 | Ortho-Mcneil Pharmaceutical, Inc. | Steroidné hormonálne prípravky a spôsoby ich prípravy |
| FR2820745A1 (fr) * | 2001-02-14 | 2002-08-16 | Oreal | Procedes de preparation de la 7alpha-hydroxy- dehydroepiandrosterone |
| WO2003043570A2 (en) * | 2001-11-15 | 2003-05-30 | Galileo Laboratories, Inc. | Formulations and methods for treatment or amelioration of inflammatory conditions |
| AU2003261380A1 (en) | 2002-08-06 | 2004-02-23 | Ssci, Inc. | Method of comparing x-ray diffraction patterns using the fundamental parameter method |
| EP1678484A2 (en) | 2003-10-27 | 2006-07-12 | SSCI, Inc. | Method for monte carlo indexing of powder diffraction data |
| US20070243620A1 (en) | 2004-02-24 | 2007-10-18 | Simon Bates | Analysis and Screening of Solid Forms Using the Atomic Pair Distribution Function |
| CA2582231A1 (en) * | 2004-09-29 | 2006-10-19 | Hollis-Eden Pharmaceuticals, Inc. | Steroid analogs and uses |
| US20060073099A1 (en) * | 2004-10-01 | 2006-04-06 | Frincke James M | Treatment screening methods |
| US20060211604A1 (en) * | 2004-11-26 | 2006-09-21 | The Brigham And Women's Hospital, Inc. | Methods for treating inflammatory disorders using regulators of microvessel dilations |
| US7964604B2 (en) * | 2005-02-18 | 2011-06-21 | Solvay Pharmaceuticals B.V. | Bifeprunox mesylate maintenance dose compositions and methods for using the same |
| PL2012773T3 (pl) | 2006-04-22 | 2012-12-31 | Harbor Biosciences Inc | Leki i zastosowania |
| US20080153792A1 (en) * | 2006-11-17 | 2008-06-26 | Frincke James M | Drug Identification and Treatment Method |
| US8354396B2 (en) * | 2006-11-17 | 2013-01-15 | Harbor Therapeutics, Inc. | Drug identification and treatment method |
| US8217025B2 (en) * | 2006-11-17 | 2012-07-10 | Harbor Therapeutics, Inc. | Drug screening and treatment methods |
| US20080221074A1 (en) * | 2006-11-17 | 2008-09-11 | Jaime Flores-Riveros | Drug Screen and Treatment Method |
| DE102007054497B3 (de) * | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
| EP2249838A4 (en) * | 2008-02-05 | 2012-05-02 | Harbor Biosciences Inc | Pharmaceutical solid state forms |
| WO2009124300A2 (en) | 2008-04-03 | 2009-10-08 | Hollis-Eden Pharmaceuticals, Inc. | Solid state forms of a pharmaceutical |
| US8309746B2 (en) * | 2008-06-06 | 2012-11-13 | Harbor Therapeutics, Inc | Methods for preparing 17-alkynyl-7-hydroxy steroids and related compounds |
| US20100075937A1 (en) * | 2008-09-24 | 2010-03-25 | Hollis-Eden Pharmaceuticals, Inc. | Patient populations and treatment methods |
| US9310310B2 (en) | 2011-08-26 | 2016-04-12 | 3M Innovative Properties Company | Flowable dry powder composition |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070129282A1 (en) * | 1998-11-24 | 2007-06-07 | Ahlem Clarence N | Pharmaceutical treatments and compositions |
| US20080015174A1 (en) * | 1998-11-24 | 2008-01-17 | Reading Christopher L | Metabolic Disease Treatments |
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