WO2001026603A2 - Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives - Google Patents

Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives Download PDF

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Publication number
WO2001026603A2
WO2001026603A2 PCT/IB2000/002053 IB0002053W WO0126603A2 WO 2001026603 A2 WO2001026603 A2 WO 2001026603A2 IB 0002053 W IB0002053 W IB 0002053W WO 0126603 A2 WO0126603 A2 WO 0126603A2
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WO
WIPO (PCT)
Prior art keywords
mesoprogestin
estrogen
use according
administration
dosage units
Prior art date
Application number
PCT/IB2000/002053
Other languages
English (en)
French (fr)
Other versions
WO2001026603A3 (en
Inventor
Kristof Chwalisz
Walter Elger
Gerd Schubert
Original Assignee
Jenapharm Gmbh & Co. Kg
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
Priority to BR0013711-1A priority Critical patent/BR0013711A/pt
Priority to AU32150/01A priority patent/AU781835B2/en
Priority to MXPA02002186A priority patent/MXPA02002186A/es
Priority to IL14841500A priority patent/IL148415A0/xx
Priority to JP2001529395A priority patent/JP2003511399A/ja
Priority to CA002383650A priority patent/CA2383650A1/en
Priority to HU0202515A priority patent/HUP0202515A3/hu
Priority to SK298-2002A priority patent/SK2982002A3/sk
Priority to EEP200200103A priority patent/EE200200103A/xx
Priority to EA200200284A priority patent/EA006805B1/ru
Application filed by Jenapharm Gmbh & Co. Kg filed Critical Jenapharm Gmbh & Co. Kg
Priority to NZ517470A priority patent/NZ517470A/en
Priority to SI200020043A priority patent/SI20853A/sl
Priority to PL00353994A priority patent/PL353994A1/xx
Priority to EP00991299A priority patent/EP1605949A2/en
Priority to KR1020027002785A priority patent/KR20020038745A/ko
Priority to UA2002032429A priority patent/UA77150C2/uk
Publication of WO2001026603A2 publication Critical patent/WO2001026603A2/en
Publication of WO2001026603A3 publication Critical patent/WO2001026603A3/en
Priority to BG06441A priority patent/BG106441A/bg
Priority to NO20020998A priority patent/NO20020998L/no
Priority to HR20020265A priority patent/HRP20020265A2/hr

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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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens

Definitions

  • the present invention relates to the field of contraception. More particularly it relates to the use of mesoprogestins for the production of a pharmaceutical for female contraception, to a pharmaceutical preparation for female contraception and to a method of female contraception administering effective amounts of a mesoprogestin to a female desiring contraception.
  • oral contraception is a pill that combines both an estrogen and a progestin, a so-called combined oral contraceptive preparation.
  • the progestin acts to block gonadotropin releases (inhibition of ovulation); the estrogen component provides endomethal control to diminish breakthrough bleeding.
  • the combined preparations are the preferred oral contraceptives in use today (Sheth et al., Contraception, 25:243, (1982)).
  • Antiprogestins are a class of compounds that block the progesterone receptor.
  • RU 486 is a progesterone receptor antagonist. RU 486 binds to the progesterone receptor and produces a blockade of the binding of progesterone to ist receptor. When administered in the luteal phase of the menstrual cycle, RU 486 induces vaginal bleeding.
  • a contraception method using competitive progesterone antagonists is disclosed in WO 93/23020. Below their ovulation inhibiting dose and the abortive dose progesterone antagonist, preferably after oral administration, achieve contraception in females, by inhibition of implantation. The method does not adversely affect the female's menstrual cycle and is without risk of aborting a previous implanted fertilized egg or a fetus.
  • the application of the progesterone antagonist occurs at least once in the follicular phase of the female's menstrual cycle (i.e. before ovulation).
  • the preferred frequency of administration is daily or it follows in regular intervals of some days, e.g. weekly or with a distance of 3 or 4 days between the single administrations of active compound.
  • WO 94/18982 teaches a method of inhibiting fertilization of an oocyte which comprises administering a fertilizing inhibitory amount of an antiprogestin to an ovulatory mammal.
  • the amount is insufficient either to prevent ovulation or to interfere with the regularity of the ovarian menstrual cycle of the mammal.
  • the preferred frequency of administration is daily.
  • mesoprogestins are used as a component for the production of a pharmaceutical for female contraception.
  • They can be used either as single pharmaceutically active principle in female contraceptives or they can be used together with an estrogen.
  • the mesoprogestins are used in a regular, cyclical administration regime. This shall mean that the mesoprogestins are administered in identical and repeating administration cycles as long as contraception is desired.
  • a cycle starts with the administration of a mesoprogestin or mesoprogestin / estrogen containing dosage unit followed daily by further dosage units thereof. Each cycle is completed by a period in which no active dosage units mecanicpill-free" days) or in which placebos are administered.
  • the administration cycle can be completed by further administration of estrogen only containing dosage units.
  • a new application cycle starts on the first day after completion of theticianpill free" or placebo phase, respectively or after the phase in which estrogen only containing dosage units have been administered.
  • day 1 in the first administration cycle is the first day of bleeding in the female's menstrual cycle in which the contraceptive treatment starts.
  • One embodiment of the mesoprogestin only administration provides for administering the mesoprogestin containing dosage units up to day 180 at the maximum.
  • a reversible amenorrhoea is induced and maintained.
  • the contraceptive effect is due to endometrial effects (endometrial suppression) of the mesoprogestin. Consequently the endometrium is not prepared for implantation of a fertilized egg.
  • the dose of the mesoprogestin can also be ovulation inhibiting but this is not essential to achieve the contraceptive effect and to induce and maintain amenorrhoea.
  • mesoprogestin only administration takes place for 3 months at the maximum (this allows to check the contraceptive reliability of the method).
  • progesterone only pill and to subcutaneous implants loaded with a progestin (Norplant) less breakthrough bleedings are observed.
  • a next embodiment of the mesoprogestin only administration takes place continuously for more than 3 months, for example, 1-3 years. Since a mesoprogestin suppresses endometrial growth and prevents endometrial vessel fragility it can be used chronically. In addition a condition of chronic but reversible amenorrhea is achieved.
  • a next embodiment of the mesoprogestin only administration provides for administering the mesoprogestin containing dosage units up to day 21 , 22, 23, 24 or 25 either followed by a period of 7, 6, 5, 4 or 3 days during which no active compound is administered or followed by the administration of 7, 6, 5, 4 or 3 placebo pills so as to complete a 28 day long cycle.
  • the next cycle starts with the administration of a mesoprogestin containing dosage unit, etc.
  • the mesoprogestin acts like a progestin by blocking the ovulation and inducing amenorrhoea and triggering withdrawal bleeding. Breakthrough bleedings are not induced. The withdrawal bleeding is due to endometrial transformation induced by the mesoprogestin. Consequently, in this embodiment the mesoprogestin has to be administered, at least in the luteal phase of the female's menstrual cycle, in an ovulation-inhibiting dose.
  • a variant of the last mentioned embodiment is to administer dosage units containing mesoprogestin in an ovulation inhibiting dose exclusively during the luteal phase of the female's menstrual cycle (no administration in the follicular phase).
  • Amenorrhoea inducing doses of mesoprogestins can be determined by methods known to a person skilled in the art for example in clinical studies.
  • the daily dose of the mesoprogestin will be in the range of 1 to 25 mg.
  • both active components are administered from day 1 (see above) to day 21 , 22, 23, 24 or 25 of the female's menstrual cycle either followed by a period of 7, 6, 5, 4 or 3 days during which no active compound is administered or followed by the administration of 7, 6, 5, 4 or 3 only estrogen containing dosage units or followed by the administration of 7, 6, 5, 4 or 3 placebo pills, respectively so as to complete a 28 day long administration cycle.
  • the next cycle starts with the administration of a mesoprogestin/estrogen containing dosage unit, etc.
  • the estrogen is used in a daily amount of 10 to 30 ⁇ g ethinyl estradiol or a bioequivalent amount thereof.
  • Mesoprogestins can be used sequentially with a progestin.
  • the mesoprogestin component prevents breakthrough bleeding which is usually associated with chronic progestin treatment.
  • the progestin component at a dose used in so called "mini pill regimen" is administered for a period of 30-180 days, whereas the mesoprogestin component is administered for a period of 1-30 days.
  • menstrual bleeding may or may not occur.
  • progestin/mesoprogestin treatment the number of unscheduled bleeding is, however, markedly reduced.
  • a mesoprogestin in a discontinuous, non-cyclical administration regime is the use as a so-called demand pill which has to be administered only around the time point of sexual intercourse for which contraception is desired.
  • the administration is before sexual intercourse impartmedicinal condom").
  • a further aspect of the invention refers to a pharmaceutical combination product (composition) containing a mesoprogestin together with an estrogen.
  • a further aspect of the invention refers to a pharmaceutical combination product (composition) containing a mesoprogestin together with a progestin.
  • Yet another aspect of the invention deals with pharmaceutical preparations for female contraception comprising daily dosage units of a mesoprogestin.
  • mesoprogestins i.a. compounds disclosed in DE 43 32 283 and in DE 43 32 284 are suitable for the purposes of the invention. , o
  • mesoprogestins are defined as compounds possessing both agonistic and antagonistic activities at the progesterone receptor (PR) in vivo.
  • PR progesterone receptor
  • mesoprogestins show high binding affinity to PR.
  • mesoprogestins exhibit different pharmacodynamic properties compared to either progestins or antiprogestins.
  • the presence of progesterone agonistic activity in mesoprogestins measured in commonly used biological tests in vivo represents the key property of this novel class of PRMs. This activity remains, however, below that of progesterone in the plateau of the dose response curve.
  • Mesoprogestins fail to maintain pregnancy in ovariectomized pregnant rodents as mice and rats.
  • mesoprogestins to antagonize progesterone function is also tested in the McPhail test using a progesterone dose which induces a McPhail score ranging between 3 and 4.
  • a mesoprogestin inhibits the effect of progesterone to a significant degree, but the maximum inhibition is below that which is inducible with RU 486 or other pure antiprogestins (e.g. onapristone).
  • the mesoprogestins stabilize, therefore, the function of PR at an intermediate activity level providing the rationale for the novel clinical applications in gynecological therapy.
  • Corresponding functional states cannot be achieved with progestins or antiprogestins.
  • mesoprogestin tested J1042, J867, J956 reached the maximum effect of progesterone.
  • J956 showed a biphasic response in this test with a maximum effect of McPhail score 1.5 at 0.3-1 mg/rabbit.
  • the antiprogestagenic activity of J867, J956, J1042 and RU 486 was evaluated in estradiol-p med juvenile rabbits after 4 days of subcutaneous (s.c.) treatment in the presence of progesterone (1 mg/rabbit s.c).
  • the antiprogestagenic activity of mesoprogestins at higher clinically relevant doses doses i.e. 3-30 mg/rabbit was lower that that of RU 486.
  • the guinea pig is considered as relevant model of human gestation and parturition (Elger W, Fahnrich M, Beier S, Quing SS, Chwalisz K (1987). Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs. Am J Obstet Gynecol 157: 1065-1074; Elger W, Neef G, Beier S, Fahnrich M, Gr ⁇ ndel M, Heermann J, Malmendier A, Laurent D, Puri CP, Singh MM, Hasan SH, Becker H (1992). Evaluation of antifertility activities of antigestagens in animal model.
  • Pregnant guinea pigs were treated on days 43 and 44 of pregnancy and observed until day 50 of gestation. For the effects of various treatments see table 1 and figure 3. It is typical for this model that expulsions occur with a delay of several days after treatment. It can be seen that Mesoprogestins have a much reduced abortifacient activity compared to RU486. The following ranking of abortifacient activity was found: RU486>J956>J867, J912>J1042. The differences with respect to abortifacient activity seem qualitative ones. It is not possible to overcome the low abortifacient activity of a Mesoprogestin by the use of a higher dose.
  • the mesoprogestin is preferably selected for this invention from the group of the compounds J867, J912, J956, J1042.
  • the amount per daily dosage is in the range of 1 to 25 mg of mesoprogestin.
  • estrogens all estrogenically active compounds are suitable for the purposes of this invention.
  • Estrogens that can be used within the scope of this invention are, for example, ethinylestradiol, 17 ⁇ -estradiol as well as its esters such as estradiol-3-benzoate, estradiol-17-valerate, -cypionate, -undecylate, -enanthate and/or other estradiol esters (US-PS 2,61 ,773, US-PS 2,990,414, US-PS 2,054,271 , US-PS 2,225,419 and US-PS 2,156,599) and conjugated estrogens.
  • estradiol esters US-PS 2,61 ,773, US-PS 2,990,414, US-PS 2,054,271 , US-PS 2,225,419 and US-PS 2,156,599
  • Estradiol-, ethinylestradiol- and estrone-3-sulfamates for example estrone-N,N- dimethylsulfamate, estrone-N,N-diethylsulfamate, ethinylestradiol-3-N,N- dimethylsulfamate, ethinylestradiol-3-N,N-diethylsulfamate, ethinylestradiol-3-N,N- tetramethylenesulfamate, estrone sulfamate, estradiol-3-sulfamate, estradiol-3-N,N- dimethylsulfamate, estradiol-3-N,N-diethylsulfamate, ethinylestradiol-3-sulfamate, which all represent prodrugs for the corresponding 3-hydroxy compounds (W.
  • progestins useful in the invention all compounds are suitable that are suitable for use in oral contraceptives because of their progestin activity.
  • An exemplary list of such compounds is found in B. Runnebaum et al., "Female Contraception: Update and Trends," Springer-Verlag, Berlin, 1988, pages 64-90, 109-121 , 122-128 and 129-140.
  • progestins within the scope of this invention are gestodene, progesterone, levonorgestrel, cyproterone acetate, chlormadinone acetate, drospirenone (dihydrospirorenone), norethisterone, norethisterone acetate, norgestimate, desogestrel or 3-ketodesogestrel.
  • the progestin is present in a dosage form that is suitable for oral administration, namely as a tablet, coated tablet, capsule or pill.
  • the formulation of the progestin is done in a way analogous to preparing progestins for hormonal contraception with use of the adjuvants that are commonly used for this purpose.
  • a daily dosage unit of the progestin contains the latter at a dose of 0.6-6.0 mg of levonorgestrel, 2-20 mg of cyproterone acetate, 0.3-3.0 mg of gestodene or 0.2-2.0 mg of desogestrel or an amount of another progestin that is equivalent in action to these dosages.
  • mesoprogestin can be present in dosage units that are intended for daily oral administration.
  • the estrogen can also be present in daily oral dosage units.
  • the dosage units of the mesoprogestin are provided for administration over a period of 7 days, these dosage units can advantageously be present in the form of a dosage unit that can be administered once a week.
  • the mesoprogestin should preferably be prepared in a formulation that results in a delayed release of the active ingredient.
  • a delayed release of the mesoprogestin can be achieved, for example, by formulating the dosage unit that is to be administered orally as a composite tablet or by providing the dosage unit that is to be administered orally with a timed-disintegration coating, as is readily known to one skilled in the art.
  • the mesoprogestin that is used for the production of the pharmaceutical agent according to the invention can also have a longer half-life than this precursor. As a result, a longer-lasting action is also achieved.
  • the formulation of the mesoprogestin and optionally the estrogen is done in a completely conventional manner, as is already known for the formulation of these compounds for their individual use as described for J867 in DE 43 32 283 and for estrogen therapy, for example Cyclo-Progynova.
  • administration can be done using an intrauterine release system (c.f. Mirena), but this variant is not preferred within the scope of this invention.
  • an intrauterine release system c.f. Mirena
  • the estrogen can be administered transdermally with a skin patch, and the progesterone antagonist can be administered daily orally or one or more times as a depot formulation.
  • the estrogen is contained per daily dosage unit according to the invention in an amount of 10 to 30 ⁇ g of ethinylestradiol or a bioequivalent amount of another estrogen.
  • the mesoprogestin is contained in each dosage unit preferably in an amount such that, when used over the intended length of time, it is sufficient for amenorrhea to occur.
  • the mesoprogestin is contained in each daily dosage unit in an amount that is equivalent to 1 to 25 mg of J 867.
  • the bioequivalent doses of a mesoprogestin can be assessed in the McPhail test.
  • the packaging that contains the pharmaceutical preparation according to the invention is prepared in such a way that, in addition to the one or two components mesoprogestin and estrogen in the respectively intended form of administration (orally in the form of pills, coated tablets, etc. in a blister pack, as may be appropriate for mesoprogestin and/or estrogen, or the estrogen as a skin patch and the mesoprogestin in the form of pills, coated tablets, etc. in a blister or in a capsule as a depot that is to be administered once), said packaging also contains instructions for the use of the pharmaceutical agent (package insert).
PCT/IB2000/002053 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives WO2001026603A2 (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
NZ517470A NZ517470A (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
AU32150/01A AU781835B2 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
IL14841500A IL148415A0 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
JP2001529395A JP2003511399A (ja) 1999-08-31 2000-08-31 女性避妊薬の成分としてのメソプロゲスチン（プロゲステロン受容体モジュレーター）
CA002383650A CA2383650A1 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
HU0202515A HUP0202515A3 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
SK298-2002A SK2982002A3 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
SI200020043A SI20853A (sl) 1999-08-31 2000-08-31 Mezoprogestini (modulatorji receptorja progesterona) kot sestavina ženskih kontraceptivov
EA200200284A EA006805B1 (ru) 1999-08-31 2000-08-31 Мезопрогестины (модуляторы рецептора прогестерона) в качестве компонента женских контрацептивов
BR0013711-1A BR0013711A (pt) 1999-08-31 2000-08-31 Mesoprogestinas (moduladores de receptores de progesterona) como um componente de contraceptivos femininos
MXPA02002186A MXPA02002186A (es) 1999-08-31 2000-08-31 Mesoprogestinas (moduladores del receptor de progesterona) como un componente de los anticonceptivos femeninos.
EEP200200103A EE200200103A (et) 1999-08-31 2000-08-31 Mesoprogestiinid (progesterooniretseptori modulaatorid) naise kontratseptiivide komponendina
PL00353994A PL353994A1 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
EP00991299A EP1605949A2 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives
KR1020027002785A KR20020038745A (ko) 1999-08-31 2000-08-31 여성 피임제 성분으로서의 메조프로게스틴 (프로게스테론수용체 조절물질)
UA2002032429A UA77150C2 (en) 1999-08-31 2000-08-31 Use of mesoprogestins j867, j912, or j1042 for female contraception, pharmaceutical composition and kit (variants)
BG06441A BG106441A (bg) 1999-08-31 2002-02-26 Мезопрогестини (модулатори на прогестероновия рецептор) като компоненти на женски контрацептиви
NO20020998A NO20020998L (no) 1999-08-31 2002-02-28 Mesoprogestiner (progesteronreseptormodulater) som en komponent i svangerskapsforebyggelse for kvinner
HR20020265A HRP20020265A2 (en) 1999-08-31 2002-03-28 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US38613399A 1999-08-31 1999-08-31
US09/386,133 1999-08-31

Publications (2)

Publication Number Publication Date
WO2001026603A2 true WO2001026603A2 (en) 2001-04-19
WO2001026603A3 WO2001026603A3 (en) 2002-01-17

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PCT/IB2000/002053 WO2001026603A2 (en) 1999-08-31 2000-08-31 Mesoprogestins (progesterone receptor modulators) as a component of female contraceptives

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EP (1) EP1605949A2 (no)
JP (1) JP2003511399A (no)
KR (1) KR20020038745A (no)
CN (1) CN1384748A (no)
AR (1) AR025455A1 (no)
AU (1) AU781835B2 (no)
BG (1) BG106441A (no)
BR (1) BR0013711A (no)
CA (1) CA2383650A1 (no)
CO (1) CO5190694A1 (no)
CZ (1) CZ2002707A3 (no)
EA (1) EA006805B1 (no)
EE (1) EE200200103A (no)
HR (1) HRP20020265A2 (no)
HU (1) HUP0202515A3 (no)
IL (1) IL148415A0 (no)
LT (1) LT5001B (no)
LV (1) LV12940B (no)
MX (1) MXPA02002186A (no)
NO (1) NO20020998L (no)
NZ (1) NZ517470A (no)
PE (1) PE20010579A1 (no)
PL (1) PL353994A1 (no)
SI (1) SI20853A (no)
SK (1) SK2982002A3 (no)
UA (1) UA77150C2 (no)
WO (1) WO2001026603A2 (no)
YU (1) YU13902A (no)

Cited By (5)

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WO2004014935A1 (de) * 2002-08-02 2004-02-19 Schering Aktiengesellschaft Progesteronrezeptormodulatoren mit erhöhter antigonadotroper aktivität für die weibliche fertilitätskontrolle und hormonersatztherapie
WO2005097193A2 (en) * 2004-03-24 2005-10-20 Tap Pharmaceutical Products, Inc. Sequential sprm/progestin treatment
WO2007045513A1 (de) * 2005-10-19 2007-04-26 Bayer Schering Pharma Aktiengesellschaft Verfahren zur präventiven bedarsweisen hormonalen kontrazeption
US7550451B2 (en) 2002-08-02 2009-06-23 Bayer Schering Pharma Ag Progesterone receptor modulators with increased antigonadotropic activity for female birth control and hormone replacement therapy
EP2419108A1 (en) 2009-04-14 2012-02-22 Laboratoire HRA Pharma Method for on-demand contraception

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JP2006525358A (ja) * 2003-05-02 2006-11-09 ドゥラメド ファーマシューティカルズ， インコーポレイテッド 長期周期避妊養生法を利用するホルモン治療の方法
JP5288796B2 (ja) * 2004-07-07 2013-09-11 ワイス・エルエルシー 周期的プロゲスチンレジメン及びキット
CN110548034A (zh) * 2019-07-12 2019-12-10 广州莎蔓生物科技有限公司 一种怀孕阻断药物

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