ZA200602338B - Improved stability of progrestogen formulations - Google Patents
Improved stability of progrestogen formulations Download PDFInfo
- Publication number
- ZA200602338B ZA200602338B ZA200602338A ZA200602338A ZA200602338B ZA 200602338 B ZA200602338 B ZA 200602338B ZA 200602338 A ZA200602338 A ZA 200602338A ZA 200602338 A ZA200602338 A ZA 200602338A ZA 200602338 B ZA200602338 B ZA 200602338B
- Authority
- ZA
- South Africa
- Prior art keywords
- formulation according
- range
- formulation
- progestogen
- neta
- Prior art date
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- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
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- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
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Landscapes
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- Reproductive Health (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200301408 | 2003-09-29 |
Publications (1)
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|---|---|
| ZA200602338B true ZA200602338B (en) | 2007-04-25 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200602339A ZA200602339B (en) | 2003-09-29 | 2006-03-22 | HRT Formulations |
| ZA200602338A ZA200602338B (en) | 2003-09-29 | 2006-03-22 | Improved stability of progrestogen formulations |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200602339A ZA200602339B (en) | 2003-09-29 | 2006-03-22 | HRT Formulations |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20060257472A1 (ja) |
| EP (2) | EP1673071A1 (ja) |
| JP (1) | JP4880465B2 (ja) |
| AU (1) | AU2004275470B2 (ja) |
| ES (1) | ES2933479T3 (ja) |
| IL (1) | IL175844A0 (ja) |
| WO (1) | WO2005030176A1 (ja) |
| ZA (2) | ZA200602339B (ja) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8475838B2 (en) * | 2005-06-03 | 2013-07-02 | Sandoz Ag | Rapidly-dissolving pharmaceutical composition for inhibiting ovulation |
| DE202007019049U1 (de) | 2007-11-05 | 2010-05-12 | Bayer Schering Pharma Aktiengesellschaft | Verwendung eines Gestagens in Kombination mit einem Estrogen zur Prophylaxe der Laktoseintoleranz bei der oralen Kontrazeption |
| ES2915698T3 (es) * | 2009-04-01 | 2022-06-24 | Bial Portela & Ca Sa | Formulaciones farmacéuticas que comprenden derivados de nitrocatecol y métodos para preparar las mismas |
| ES2730678T3 (es) | 2009-04-01 | 2019-11-12 | Bial Portela & Ca Sa | Formulaciones farmacéuticas que comprenden derivados de nitrocatecol y métodos para fabricarlas |
| WO2010117873A2 (en) * | 2009-04-06 | 2010-10-14 | Banner Pharmacaps, Inc. | Progesterone solutions for increased bioavailability |
| WO2011128336A1 (en) | 2010-04-15 | 2011-10-20 | Bayer Pharma Aktiengesellschaft | Very low-dosed solid oral dosage forms for hrt |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| LT2782584T (lt) | 2011-11-23 | 2021-09-10 | Therapeuticsmd, Inc. | Natūralios kombinuotos pakaitinės hormonų terapijos kompozicijos ir gydymas |
| US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
| US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
| US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
| AU2015264003A1 (en) | 2014-05-22 | 2016-11-17 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| CA2988485A1 (en) | 2015-06-18 | 2016-12-22 | Mithra Pharmaceuticals S.A. | Orodispersible tablet containing estetrol |
| KR102664563B1 (ko) | 2015-06-18 | 2024-05-09 | 에스테트라, 소시에떼 아 레스폰서빌리떼 리미떼 | 에스테트롤 성분을 함유하는 구강분해성 투여 단위 |
| EP3310346B1 (en) | 2015-06-18 | 2021-03-24 | Estetra SPRL | Orodispersible tablet containing estetrol |
| SI3310333T1 (sl) | 2015-06-18 | 2020-08-31 | Estetra Sprl | Orodisperzibilna enota odmerka, ki vsebuje komponento estetrola |
| US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
| US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
| WO2017173071A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
| CA3178291A1 (en) | 2016-08-05 | 2018-04-12 | Estetra Srl | Method for the management of dysmenorrhea and menstrual pain |
| TWI801561B (zh) | 2018-04-19 | 2023-05-11 | 比利時商依思特拉私人有限責任公司 | 化合物及其用於緩解絕經相關症狀的用途 |
| JOP20200260A1 (ar) | 2018-04-19 | 2019-10-19 | Estetra Sprl | مركبات واستخداماتها للتخفيف من الأعراض المصاحبة لانقطاع الطمث |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4390531A (en) * | 1981-08-10 | 1983-06-28 | Syntex Pharmaceuticals International Ltd. | Method of contraception using peak progestogen dosage |
| US4826831A (en) * | 1983-08-05 | 1989-05-02 | Pre Jay Holdings Limited | Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens |
| US4530839A (en) * | 1983-09-26 | 1985-07-23 | Ortho Pharmaceutical Corporation | Triphasic oral contraceptive |
| US5208225A (en) * | 1986-02-27 | 1993-05-04 | Warner-Lambert Company | Compositions containing fixed combinations |
| HUT52382A (en) | 1988-03-14 | 1990-07-28 | Sandoz Ag | Process for producing pharmaceutical compositions comprising as active ingredient unsubstituted progestin in 19-position and estrogen in the given case |
| US5200197A (en) * | 1989-11-16 | 1993-04-06 | Alza Corporation | Contraceptive pill |
| US5633011A (en) | 1994-08-04 | 1997-05-27 | Alza Corporation | Progesterone replacement therapy |
| PT782449E (pt) * | 1994-09-22 | 2003-07-31 | Akzo Nobel Nv | Processo de fabrico de unidades de dosagem por granulacao humida |
| WO1996015776A1 (fr) | 1994-11-18 | 1996-05-30 | Hisamitsu Pharmaceutical Co., Inc. | Timbre absorbable par voie percutanee |
| US5547948A (en) * | 1995-01-17 | 1996-08-20 | American Home Products Corporation | Controlled release of steroids from sugar coatings |
| US5759577A (en) * | 1995-01-17 | 1998-06-02 | American Home Products Corporation | Controlled release of steroids from sugar coatings |
| US20010006963A1 (en) * | 1995-03-16 | 2001-07-05 | Ursula Lachnit-Fixson | Once-a-month injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women |
| US5780050A (en) * | 1995-07-20 | 1998-07-14 | Theratech, Inc. | Drug delivery compositions for improved stability of steroids |
| US5897880A (en) | 1995-09-29 | 1999-04-27 | Lam Pharmaceuticals, Llc. | Topical drug preparations |
| US5928666A (en) * | 1996-11-12 | 1999-07-27 | Cygnus Inc. | Crystalline form of estradiol and pharmaceutical formulations comprising same |
| DE19700913C2 (de) | 1997-01-14 | 2001-01-04 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System zur Abgabe von Hormonen |
| JPH1171268A (ja) * | 1997-08-28 | 1999-03-16 | Kayaku:Kk | 性ホルモン含有錠剤 |
| IL128818A0 (en) * | 1998-03-12 | 2000-01-31 | Akzo Nobel Nv | Making dosage units using low shear granulation |
| US6117446A (en) * | 1999-01-26 | 2000-09-12 | Place; Virgil A. | Drug dosage unit for buccal administration of steroidal active agents |
| US7374779B2 (en) | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
| CA2267743C (en) * | 1999-03-30 | 2011-07-26 | Robert F. Casper | Low dose estrogen interrupted hormone replacement therapy |
| US6667050B1 (en) * | 1999-04-06 | 2003-12-23 | Galen (Chemicals) Limited | Chewable oral contraceptive |
| WO2002032431A1 (fr) | 2000-10-16 | 2002-04-25 | Hisamitsu Pharmaceutical Co., Inc. | Compositions pour preparations externes |
| DE10146541A1 (de) | 2001-09-21 | 2003-04-17 | Kade Pharma Fab Gmbh | Arzneimittel auf Basis von Gestagenen zur dermalen Anwendung |
| US6962908B2 (en) * | 2001-12-21 | 2005-11-08 | Warner Chilcott Company Inc. | Oral pharmaceutical products containing 17 β-estradiol-3-lower alkanoate, method of administering the same and process of preparation |
| TW200306846A (en) * | 2002-04-03 | 2003-12-01 | Wyeth Corp | Hormone replacement therapy |
| TW200400040A (en) * | 2002-05-17 | 2004-01-01 | Wyeth Corp | Hormone replacement therapy |
| US20040185093A1 (en) * | 2003-03-18 | 2004-09-23 | Szymczak Christopher E. | Compositions containing sucralose |
| US20040265373A1 (en) * | 2003-06-27 | 2004-12-30 | David Wynn | Soft tablet containing high molecular weight cellulosics |
-
2004
- 2004-09-21 EP EP04762859A patent/EP1673071A1/en not_active Ceased
- 2004-09-21 ES ES11175793T patent/ES2933479T3/es not_active Expired - Lifetime
- 2004-09-21 JP JP2006529643A patent/JP4880465B2/ja not_active Expired - Fee Related
- 2004-09-21 WO PCT/DK2004/000639 patent/WO2005030176A1/en active Application Filing
- 2004-09-21 EP EP11175793.6A patent/EP2409690B1/en not_active Expired - Lifetime
- 2004-09-21 AU AU2004275470A patent/AU2004275470B2/en not_active Ceased
-
2006
- 2006-03-17 US US11/378,977 patent/US20060257472A1/en not_active Abandoned
- 2006-03-22 ZA ZA200602339A patent/ZA200602339B/xx unknown
- 2006-03-22 ZA ZA200602338A patent/ZA200602338B/en unknown
- 2006-05-23 IL IL175844A patent/IL175844A0/en unknown
-
2015
- 2015-12-10 US US14/964,645 patent/US20160089381A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007506797A (ja) | 2007-03-22 |
| EP2409690B1 (en) | 2022-11-09 |
| EP2409690A3 (en) | 2012-07-18 |
| EP1673071A1 (en) | 2006-06-28 |
| US20060257472A1 (en) | 2006-11-16 |
| JP4880465B2 (ja) | 2012-02-22 |
| AU2004275470B2 (en) | 2010-12-02 |
| AU2004275470A1 (en) | 2005-04-07 |
| ES2933479T3 (es) | 2023-02-09 |
| ZA200602339B (en) | 2007-08-29 |
| WO2005030176A1 (en) | 2005-04-07 |
| IL175844A0 (en) | 2006-10-05 |
| EP2409690A2 (en) | 2012-01-25 |
| US20160089381A1 (en) | 2016-03-31 |
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