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WO1997041869A1 - Contraceptif oral - Google Patents

Contraceptif oral Download PDF

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Publication number
WO1997041869A1
WO1997041869A1 PCT/US1997/007083 US9707083W WO9741869A1 WO 1997041869 A1 WO1997041869 A1 WO 1997041869A1 US 9707083 W US9707083 W US 9707083W WO 9741869 A1 WO9741869 A1 WO 9741869A1
Authority
WO
WIPO (PCT)
Prior art keywords
phase
estrogen
dosage
days
administered
Prior art date
Application number
PCT/US1997/007083
Other languages
English (en)
Inventor
Michael Jay Gast
Original Assignee
American Home Products Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by American Home Products Corporation filed Critical American Home Products Corporation
Priority to AU29267/97A priority Critical patent/AU2926797A/en
Publication of WO1997041869A1 publication Critical patent/WO1997041869A1/fr

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Classifications

    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • 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

Definitions

  • Lachnit (PCT Publication WO 95/26730) discloses bridged regimens consisting of the administration of a combination of a progestin/estrogen combination (50 - 125 ⁇ g LNg and 10 - 40 ⁇ g EE) for the first 23-24 days of the menstrual cycle followed by the administration of an estrogen (2 - 40 ⁇ g EE) for 4-10 days for a total administration of at least 28 days per cycle.
  • the use of 100 - 300 ⁇ g drospirenone and 10 - 40 ⁇ g EE as the 23-24 day progestin/estrogen combination is disclosed.
  • Upton Upton (EP Patent Specification 253,607 B l) teaches the use of low dose progestin/estrogen combinations for combined hormone replacement therapy and contraception in climacteric women.
  • Climacteric women are defined in Upton as pre- menopausal women around 40 years of age whose hormone levels are waning. The climacteric woman still ovulates (albeit may have irregular ovulation), but she still experiences many of the symptoms of the hypoestrogenic menopausal woman, such as insomnia, hot flushes, and irritability.
  • Upton Based on relative potencies, Upton teaches that a dose of 75 ⁇ g LNg is equivalent to 35 ⁇ g of GTD, 75 ⁇ g of 3-KDSG or DSG, and 250 ⁇ g NE and that a dose of 1000 ⁇ g of 17 ⁇ -estradiol is equivalent to a dose of 15 ⁇ g EE and 30 ⁇ g mestranol. Upton also teaches that NG may be substituted for LNg, but at twice the dose.
  • Specific regimens include (a) 4 mg estradiol for 7 days followed by 21 days of the combination of 1 mg norethisterone acetate and 4 mg estradiol; (b) 2 mg estradiol valerate for 7 days followed by 21 days of the combination of 2 mg chlormadinone acetate and 4 mg estradiol valerate; and (c) 20 ⁇ g EE followed by 18 days of the combination of 150 ⁇ g LNg and 20 ⁇ g EE.
  • Regimen (c) in Erlich provides a total steroidal load of 2.7 mg of LNg and 560 ⁇ g EE per 28 day cycle.
  • Patent 5,418,2278 discloses triphasic regimens which consist of the administration of a combination progestin/estrogen in a 6-8 day phase, a second 6-8 day phase, and a third 6-8 day phase, with it being preferred that the three contraceptive steroid phases be 7 days each.
  • the progestin may be 3-KDSG, DSG, LNg, or GTD.
  • Bergink U.S. Patent 5,262,408 discloses a 24 day triphasic combination regimen in which the first 7-9 day phase consists of the administration of a progestin at a daily dosage equivalent to 100 ⁇ g DSG and an estrogen at a daily dosage equivalent to 25 ⁇ g EE, the second 7-9 day phase consists of the administration of a progestin at a daily dosage equivalent to 125 ⁇ g DSG and an estrogen at a daily dosage equivalent to 20 ⁇ g EE, and the third 7-9 day phase consists of the administration of a progestin at a daily dosage equivalent to 50 ⁇ g DSG and an estrogen at a daily dosage equivalent to 20 ⁇ g EE.
  • the three phases be 8 days each.
  • a placebo may be administered for 4 days, the 4 day interval may be pill free, or a progestin at a dosage equivalent to 25-35 ⁇ g DSG may be administered.
  • Boissonneault U.S. Patent 4,962,098 discloses triphasic progestin/estrogen combinations in which the amount of the estrogenic component is increased stepwise over the three phases. Contraceptive steroid combinations are taken for 4-7 days during the first phase (5 days being preferred); for 5-8 days during the second phase (7 days preferred); and for 7-12 days during the third phase (9 days being preferred). Following the administration of 21 -days of the contraceptive steroid combination, placebo is taken for 7 days. For all three phases, 0.5-1.5 mg of norethindrone acetate is used in the progestin, with 1 mg being preferred. 10-30 ⁇ g EE is used in the first phase, 20-40 ⁇ g in the second, and 30-50 ⁇ g in the third phase.
  • a specific triphasic regimen discloses the administration of 35 ⁇ g EE in each of the three 7-day phases in combination with 0.5 mg, 0.75 mg, and 1.0 mg in the first, second, and third phases, respectively.
  • a second specific triphasic regimen discloses the administration of 35 ⁇ g EE in each of the three 7-day phases in combination with 50 ⁇ g, 75 ⁇ g, and 100 ⁇ g in the first, second, and third phases, respectively.
  • a third specific triphasic regimen discloses the administration of 35 ⁇ g EE in each of the three 7-day phases in combination with 25 ⁇ g, 35 ⁇ g, and 50 ⁇ g in the first, second, and third phases, respectively.
  • Edgren U.S. Patent 4,390,531 discloses triphasic 21-day progestin/estrogen combination regimens in which a dose of 20-40 ⁇ g EE (or another estrogen in an equivalent dosage) is administered in all three phases in combination with 0.3-0.8 mg NE (or another progestin in an equivalent dosage) for 5-8 days in the first phase, twice the dose of NE for 7-11 days in the second phase, and the dose of NE being the same as in the first phase for 3-7 days in the third phase. It is preferred that each of the three phases is 7 days. Placebo is administered for 6-8 days following administration of the contraceptive steroid combination.
  • a specific regimen discloses a first phase of 7 days of 0.5 mg NE in combination with 35 ⁇ g EE, a second 7 day phase of 1.0 mg NE in combination with 35 ⁇ g EE, and a third 7 day phase of 0.5 mg NE in combination with 35 ⁇ g EE.
  • Oettel (EP 628,312 Al) discloses combination contraceptive combinations containing the combination of three components: a biogenic estrogen (estradiol, estrone, or esrriol), a synthetic estrogen (EE or mestranol), and a progestin (LNg, desogestrel, progesterone, norethisterone acetate, DSGT, chlormadinone acetate, gestodene, or cyproterone acetate).
  • the combination is administered for 21 days followed by the administration of placebo (or pill free) or an estrogen on days 22-28 of the cycle.
  • a second phase of a combination of a progestin at a daily dosage equivalent in progestational activity to 40-125 ⁇ g levonorgestrel and an estrogen at a daily dosage equivalent in estrogenic activity to 10-20 ⁇ g ethinyl estradiol is administered for 11-15 days beginning on the day immediately following the last day of administration of the first phase, such that the total administration for both phases is 23-25 days.
  • the same daily dosage of the progestin and estrogen is administered for each of the 11-15 days.
  • the daily dosage of the progestin in the second phase is greater that the daily dosage for the first phase, and the daily dosage of the estrogen in the second phase is greater than or equal to the daily dosage of estrogen in the first phase.
  • progestins include, but are not limited to levonorgestrel, norgestrel, desogestrel, 3-ketodesogestrel, norethindrone, gestodene, norethisterone acetate, and norgestimate. It is more preferred that the progestin is levonorgestrel. When levonorgestrel is used as the progestin, it is preferred that the daily dosage of levonorgestrel is 40-75 ⁇ g when administered as the progestin in the first phase and is 50-100 ⁇ g when administered as the progestin in the second phase.
  • Preferred estrogens include, but are not limited to ethinyl estradiol; 17 ⁇ - estradiol; conjugated estrogens, USP; estrone or a salt thereof; and mestranol; with ethinyl estradiol being more preferred.
  • the daily dosage of ethinyl estradiol is 10-15 ⁇ g when ethinyl estradiol is administered as the estrogen in the first phase, is 10-20 ⁇ g when administered as the estrogen in the second phase, and is 10-20 ⁇ g when administered in the estrogen phase.
  • Preferred salts of estrone include, but are not limited to the sodium and piperate salt.
  • levonorgestrel is abbreviated as LNg and ethinyl estradiol is abbreviated as EE. PREFERRED DAILY DOSAGES

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte à un procédé de contraception consistant à administrer à une femme en âge de procréer, sur 23 à 25 jours consécutifs, une combinaison de première phase d'une progestérone selon une posologie quotidienne équivalant, s'agissant de l'activité progestative, à 40 à 125 νg de lévonorgestrel, et un oestrogène selon un dosage quotidien équivalant, s'agissant de l'activité oestrogénique, à 10 à 15 νg d'éthinyl estradiol sur 9 à 13 jours à compter du premier jour du cycle menstruel, cette même posologie de la combinaison de progestérone et d'oestrogène étant administrée dans chacune des périodes de 9 à 13 jours; une combinaison de deuxième phase d'une progestérone selon une posologie quotidienne équivalant, s'agissant de l'activité progestative, à 40 à 125 νg de lévonorgestrel, et un oestrogène selon une posologie quotidienne équivalant, s'agissant de l'activité oestrogénique, à 10 à 20 νg d'éthinyl estradiol, sur 11 à 15 jours à compter du jour suivant immédiatement le dernier jour de prise de la combinaison de première phase, cette même posologie de la combinaison de progestérone et d'oestrogène étant administrée dans chacune des périodes de 11 à 15 jours; et un oestrogène d'une phase oestrogène selon une posologie quotidienne équivalant, s'agissant de l'activité oestrogénique, à 10 à 20 νg d'éthinyl estradiol, sur 3 à 5 jours à compter du jour suivant immédiatement le dernier jour de prise de la combinaison de deuxième phase, cette même posologie d'oestrogène étant administrée dans chacune des périodes de 3 à 5 jours, à condition que la posologie quotidienne de la progestérone biphasique soit supérieure à la posologie quotidienne de la progestérone de la première phase, et que la posologie quotidienne de l'oestrogène de la deuxième phase soit supérieure ou égale à la posologie quotidienne de l'oestrogène de la première phase.
PCT/US1997/007083 1996-05-08 1997-04-28 Contraceptif oral WO1997041869A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU29267/97A AU2926797A (en) 1996-05-08 1997-04-28 Oral contraceptive

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US64342996A 1996-05-08 1996-05-08
US08/643,429 1996-05-08

Publications (1)

Publication Number Publication Date
WO1997041869A1 true WO1997041869A1 (fr) 1997-11-13

Family

ID=24580788

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/007083 WO1997041869A1 (fr) 1996-05-08 1997-04-28 Contraceptif oral

Country Status (2)

Country Link
AU (1) AU2926797A (fr)
WO (1) WO1997041869A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7749987B2 (en) 1996-10-08 2010-07-06 Laboratorie Theramek Contraception method

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4313926A1 (de) * 1993-04-28 1994-11-03 Jenapharm Gmbh Pharmazeutisches Mehrphasenpräparat zur hormonalen Kontrazeption

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4313926A1 (de) * 1993-04-28 1994-11-03 Jenapharm Gmbh Pharmazeutisches Mehrphasenpräparat zur hormonalen Kontrazeption

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7749987B2 (en) 1996-10-08 2010-07-06 Laboratorie Theramek Contraception method

Also Published As

Publication number Publication date
AU2926797A (en) 1997-11-26

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