EP2841074A1 - Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques - Google Patents

Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques

Info

Publication number
EP2841074A1
EP2841074A1 EP13717289.6A EP13717289A EP2841074A1 EP 2841074 A1 EP2841074 A1 EP 2841074A1 EP 13717289 A EP13717289 A EP 13717289A EP 2841074 A1 EP2841074 A1 EP 2841074A1
Authority
EP
European Patent Office
Prior art keywords
spirox
methyl
methylene
intrauterine
contraception
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP13717289.6A
Other languages
German (de)
English (en)
Inventor
Norbert Schmees
Lars RÖSE
Tuula VALO
Katja Prelle
Reinhard Nubbemeyer
Henriikka Korolainen
Harri Jukarainen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Bayer Pharma AG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=48142002&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2841074(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Pharma AG filed Critical Bayer Pharma AG
Publication of EP2841074A1 publication Critical patent/EP2841074A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A61K9/0039—Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones

Definitions

  • R 6 and R 7 may be a hydrogen atom or together may be an ⁇ -methylene group.
  • the invention thus relates to the intrauterine application of 18-methyl-15 ⁇ , 16 ⁇ -methylene-19-nor-20-spirox-4-en-3-one (compound A) or 18-methyl-6a, 7a, 15 ⁇ , 16 ⁇ -dimethylene-19-nor-20-spirox-4-en-3-one (compound B)
  • Another object of the invention relates to the use of an IUS containing the substance (A) or (B) in contraception and in gynecological therapy.
  • gynecological therapy e.g. the treatment of endometriosis, endometrial hyperplasia, inflammation of the endometrium (endometritis), uterine pain and dysmenorrhea, the use being excluded in the treatment of menorrhagia [also known as hypermenorrhea or heavy enstrual bleeding (HMB)] and other forms of uterine bleeding disorders ,
  • Another object of the invention relates to the use of 18-ethyl-15ß, 16ß-methylene-19-nor-20-spirox-4-en-3-one (compound A) in contraception and gynecological therapy.
  • the inventively employable progestins 18-methyl-15ß, 16ß-methylene-19-nor-20-spirox-4-en-3-one (A) or 18-methyl-6a, 7a, 15ß, 16ß-dimethylene -19-nor-20-spirox-4-en-3-one (B), and their preparation, are described in WO 2008/000521, the first-mentioned compound (A) being disclosed there only as an intermediate.
  • Compound B and other substances described in WO 2008/000521 are used in pharmaceutical preparations for contraception and in therapy for the treatment of premenstrual disorders, such as headache, depressive moods, water retention and astodynia.
  • WO2008 / 000521 also discloses parenteral oily injection solutions.
  • intrauterine use and the use of the compounds in an intrauterine system (IUS) are not described in WO 2008/000521.
  • oral contraceptives are the most widely used contraceptive method in many countries. Nevertheless, hormone-containing, in particular estrogen-containing contraceptives in the public and the literature due to potential risks (such as a slightly increased risk of thrombosis,
  • the basis for the contraceptive effect of Mirena ® is essentially the thickening of the cervical mucus and the local effect of Levonorgestrels, which leads to a strong antiproliferative effect on the endometrium.
  • levonorgestrel alters the utero-tubal milieu and impairs sperm motility and function.
  • Plasma drug levels of on average by 206 pg / ml 2 Although this value is below that of orally administered levonorgestrel-containing contraceptives, it is still so high that it inhibits ovulation in about 20% of users in the first year of application and the known systemic side effects such as acne, depressive moods, May result in chest pain or decreased libido 3 .
  • Contraceptive methods e.g., hormone level measurement or temperature method
  • mechanical methods e.g., condom or diaphragm
  • chemical methods e.g., spermicides
  • the object of the present invention is therefore to provide a contraceptive method which, with comparable high contraceptive safety, as achieved by the known hormone-based contraceptive methods, has even better tolerability.
  • R 6 and R 7 is a hydrogen atom or together an ⁇ -methylene group, namely by the intrauterine application of 18-methyl-15 ⁇ , 16 ⁇ -methylene-19-nor-20-spirox-4-ene-3 or 18-methyl-6a, 7a, 15 ⁇ , 16 ⁇ -dimethylene-19-nor-20-spirox-4-en-3-one.
  • the substances used according to the invention have an at least 10-fold lower androgenic activity compared to LNG.
  • This property compounded with the pronounced dissociation local vs. systemic, shows that no systemic androgenic effects (eg acne) are to be expected even with very high dose local uterine applications compared to levonorgestrel, even if systemic concentrations comparable to levonorgestrel in Mirena ® applications should occur.
  • the substances A and B are excellent for intrauterine use in gynecological therapy but especially in contraception.
  • a polymer system can be used, as used for example in Mirena ® .
  • the active ingredient (A) or (B) is first processed with a polymeric carrier material to a central rod (core).
  • the active ingredient may be in any proportion with the polymeric carrier material, e.g. Polydimethylsiloxane (POMS), mixed.
  • POMS Polydimethylsiloxane
  • Vulcanization is usually surrounded in a second step by a membrane based on a polymer that ensures a uniform dosage over a long period of time.
  • the desired release rate (“release rate”) can be controlled by selecting the polymer and the thickness of the membrane.
  • the polymer used for the membrane are in principle the same polymers as for the core (the central rod) in question. To mention here are e.g. Polydimethylsiloxane, which may optionally be fluorinated or other mixtures of polymers.
  • the membrane thickness is preferably in the range of 0.5 mm.
  • the membrane is applied by a made of the desired polymer tube (membrane) is first brought to swell in a solvent and then pressed into the still swollen tube of drug-containing core.
  • the tube ends are then still closed with a plug, which preferably consists of the same material as the tube / membrane, in order to counteract "bleeding" of the active substance at the tube ends, which can lead to a "burst effect" in the application ,
  • the tube can also be glued with silicone.
  • Systems which can be used according to the invention are those which release a daily dose in the range from 1 to 500 ⁇ g of the respective active ingredient (A) or (B).
  • the release rate of active ingredient (A) may be chosen half as high as that of active ingredient (B) due to its higher efficacy.
  • Active ingredient (A) thus results in a preferred dose range of 1- 200 g / day, more preferably 1-100 g / day, in particular from 2-50 g / day.
  • Active ingredient (B) is preferably in the range between 2-500pg / day, more preferably from 2-200pg / day, in particular from 5-100 g / day, dosed.
  • Another object of the invention thus relates to an intrauterine system containing the active ingredient (A) or (B), as well as the application of the intrauterine system in the contraception.
  • the rat experiment described below was carried out analogously to the preparation of the drug reservoirs, as described, for example, for a human-suitable IUS (see, for example, EP 0 652 738 B1).
  • polysiloxanes and modified polysiloxane polymers can be used (for example, see EP 0652738 B1, WO 00/29464 and WO 00/00550).
  • a drug-loaded core was first prepared by using a mixture of polyethylene oxide block polydimethylsiloxane copolymer (PEO -b-PDMS), polydimethylsiloxane and 10 weight percent of the active ingredient (here the respective progestin A or B) using a Pt (O) -divinyltetramethyldisiloxane catalyst was vulcanized.
  • PEO -b-PDMS polyethylene oxide block polydimethylsiloxane copolymer
  • Pt (O) -divinyltetramethyldisiloxane catalyst was vulcanized.
  • PEO-b-PDMS polydimethylsiloxane (PDMS) can be used, was used as the catalyst for vulcanization bis (2,4-dichlorobenzoyl) peroxide.
  • PDMS polydimethylsiloxane
  • a vertical piston unit was used with a corresponding nozzle head.
  • the nozzle head was dimensioned so that the active substance-containing core has an outer diameter of about 1 mm.
  • the active ingredient-containing core prepared in this way is subsequently treated with a membrane which consists of PDMS, polytrifluoropropylmethylsiloxanes (PTFPMS) or a PTFPMS / PDMS elastomeric mixture (75% of PTFPMS, 25% PDMS), jacketed.
  • the membrane material had an inner diameter of ⁇ 1 mm and a
  • the sheathing was carried out by cutting the core and the membrane to the length of 10-15 mm, the membrane being slightly longer (about 1 mm at each end) than the core, so that the ends of the membrane after the insertion of the core can be closed with a small stopper.
  • the core In order to allow the introduction of the core into the membrane, it was first swelled in a cyclohexane or acetone-hexane mixture. In the swollen membrane then the active substance-containing core was inserted. The ends of the tubes are either glued with silicone or closed with a small stopper made of PTFPMS.
  • Serum levels of luteinizing hormone (LH) serve to detect systemic effects of locally applied progestin.
  • Basal serum LH levels of ovariectomized rats are elevated compared to levels of intact control animals.
  • Unwanted systemic efficacy of uterine-administered progestin can be demonstrated by a decrease in LH levels.
  • the E2 applications were continued at a daily dose of 0.1 g / animal to increase the responsiveness of the uterus (preservation of progesterone). Receptor expression) to ensure progestins. On days 4, 10 and 17, blood was drawn for LH level determinations.
  • progestins can be dosed with local activity so without the side effects described for levonorgestrel occur in women.
  • very rapid degradation rates were also found in vitro (liver). Rapid in vitro degradation in the liver can also be implicated in rapid in vivo degradation, resulting in a very low systemic exposure of 18-methyl-15 ⁇ , 16 ⁇ -methylene-19-nor-20-spirox-4-ene 3-one and 18-methyl-6a, 7a, 15 ⁇ , 16 ⁇ -dimethylene-19-nor-20-spirox-4-en-3-one is calculated after application by an IUS.
  • PC3 human prostate carcinoma
  • Culture medium was RPMI medium (without L-glutamine; without phenol red) # E15-49 PAA L-glutamine 200mM # 25030-024 Gibco BRL 100U / 100g / ml penicillin
  • FCS fetal calf serum
  • the cultivation of the cells was carried out at 37 ° C and 5% C0 2 .
  • the test medium was the same as the culture medium except that the 10% FCS was replaced by 5% activated charcoal-treated FCS (CCS).
  • CCS activated charcoal-treated FCS
  • Cells were seeded in wells of a 96 well plate ("CulturPlate" from Packard # 6005180) with 2x104 cells / well / 200 ⁇ assay medium The cells were incubated with different concentrations of the test substances and 80 ⁇ substrate with the "steadylite HTS Reporter Gene Assay System" of Measure Perkin Elmer. Results:
  • Drug levels should occur as they are observed for levonorgestrel in Mirena ® applications.
  • the amount of active ingredient (A) or (B) released was determined by reversed-phase liquid chromatography with UV detection in a 1% 2-hydroxypropyl- ⁇ -cyclodextrin (2-HPBCD) solution.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Reproductive Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Pregnancy & Childbirth (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne l'utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones de la formule générale (1) pour la contraception et les traitements gynécologiques. L'invention concerne également un système intra-utérin contenant les composés de la formule (1).
EP13717289.6A 2012-04-23 2013-04-19 Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques Withdrawn EP2841074A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102012206652 2012-04-23
PCT/EP2013/058220 WO2013160213A1 (fr) 2012-04-23 2013-04-19 Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques

Publications (1)

Publication Number Publication Date
EP2841074A1 true EP2841074A1 (fr) 2015-03-04

Family

ID=48142002

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13717289.6A Withdrawn EP2841074A1 (fr) 2012-04-23 2013-04-19 Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques

Country Status (28)

Country Link
US (1) US20150065472A1 (fr)
EP (1) EP2841074A1 (fr)
JP (1) JP2015514791A (fr)
KR (1) KR20150004807A (fr)
CN (1) CN104254333A (fr)
AR (1) AR090799A1 (fr)
AU (1) AU2013254840A1 (fr)
BR (1) BR112014026193A2 (fr)
CA (1) CA2871003A1 (fr)
CL (1) CL2014002836A1 (fr)
CO (1) CO7111255A2 (fr)
CR (1) CR20140490A (fr)
CU (1) CU20140121A7 (fr)
DO (1) DOP2014000241A (fr)
EA (1) EA201491922A1 (fr)
EC (1) ECSP14024250A (fr)
HK (1) HK1205000A1 (fr)
IL (1) IL235095A0 (fr)
IN (1) IN2014DN07839A (fr)
MA (1) MA37444A1 (fr)
MX (1) MX2014012849A (fr)
PE (1) PE20142438A1 (fr)
PH (1) PH12014502372A1 (fr)
SG (1) SG11201406582XA (fr)
TN (1) TN2014000444A1 (fr)
TW (1) TW201350122A (fr)
UY (1) UY34758A (fr)
WO (1) WO2013160213A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015055789A1 (fr) * 2013-10-17 2015-04-23 Bayer Pharma Aktiengesellschaft Utilisation intra-vaginale de 18-méthyl-15ss,16ss-méthylène-19-nor-20-spirox-4-en-3-ones, anneaux intra-vaginaux comprenant des 18-méthyl-15ss,16ss-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation de ceux-ci pour la contraception

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI90627C (fi) 1992-07-31 1994-03-10 Leiras Oy Laitteisto lääkeainesauvan varustamiseksi vaipalla
PH30867A (en) 1992-07-31 1997-12-09 Leiras Oy Method and equipment for installing a medicine capsule on a support.
FI107339B (fi) 1998-06-30 2001-07-13 Leiras Oy Lääkeaineiden läpäisynopeutta säätävä kalvo tai matriisi
US6056976A (en) 1998-11-12 2000-05-02 Leiras Oy Elastomer, its preparation and use
NZ520630A (en) * 2000-01-18 2004-09-24 Schering Ag Drospirenone for hormone replacement therapy
CA2771944A1 (fr) * 2003-07-16 2005-01-27 Teva Women's Health, Inc. Procedes de traitement hormonal utilisant des posologies contraceptives avec administration continue d'oestrogenes
DE102006030416A1 (de) 2006-06-29 2008-01-03 Bayer Schering Pharma Ag 18-Methyl-19-nor-androst-4-en-17,17-spiroether (18-Methyl-19-nor-20-spirox-4-en-3-one) sowie diese enthaltende pharmazeutische Präparate
DE102007011105A1 (de) * 2007-03-02 2008-09-04 Bayer Schering Pharma Aktiengesellschaft Mineralcorticoid-Rezeptor-Antagonisten zur Behandlung von Endometriose
DE102007063495A1 (de) * 2007-12-29 2009-09-17 Bayer Schering Pharma Aktiengesellschaft 19-Nor-Steroidderivate mit einer 15α,16α-Methylengruppe und einem gesättigten 17,17-Spirolactonring, deren Verwendung sowie diese Derivate enthaltende Arzneimittel
DE102007063496A1 (de) * 2007-12-29 2009-07-02 Bayer Schering Pharma Aktiengesellschaft 15,16-Methylen-17-(1'-propenyl)-17-3'-oxidoestra-4-en-3-on-Derivat, dessen Verwendung und das Derivat enthaltende Arzneimittel
EP2140860A1 (fr) * 2008-07-03 2010-01-06 Bayer Schering Pharma Oy Procédé de contraception amélioré
WO2012063262A2 (fr) * 2010-11-08 2012-05-18 Hll Lifecare Limited Nouveau dispositif intra-utérin à libération de cuivre contrôlée

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2013160213A1 *

Also Published As

Publication number Publication date
UY34758A (es) 2013-11-29
HK1205000A1 (en) 2015-12-11
PE20142438A1 (es) 2015-02-01
AU2013254840A1 (en) 2014-11-06
MA37444A1 (fr) 2016-11-30
CU20140121A7 (es) 2014-12-26
CR20140490A (es) 2014-11-17
TW201350122A (zh) 2013-12-16
DOP2014000241A (es) 2014-12-31
IN2014DN07839A (fr) 2015-04-24
CA2871003A1 (fr) 2013-10-31
WO2013160213A1 (fr) 2013-10-31
MX2014012849A (es) 2015-02-05
ECSP14024250A (es) 2015-12-31
IL235095A0 (en) 2014-12-31
KR20150004807A (ko) 2015-01-13
BR112014026193A2 (pt) 2017-06-27
CO7111255A2 (es) 2014-11-10
CN104254333A (zh) 2014-12-31
US20150065472A1 (en) 2015-03-05
TN2014000444A1 (en) 2016-03-30
JP2015514791A (ja) 2015-05-21
SG11201406582XA (en) 2014-11-27
CL2014002836A1 (es) 2015-03-13
AR090799A1 (es) 2014-12-10
EA201491922A1 (ru) 2015-04-30
PH12014502372A1 (en) 2015-01-26

Similar Documents

Publication Publication Date Title
EP2552404B1 (fr) Forme galénique parentérale libérant des inhibiteurs de l'aromatase et des gestagènes, pour le traitement de l'endométriose
DE69736911T2 (de) Kontrazeptives Implantat für Männer
EP2445491B1 (fr) Composition pharmaceutique pour contraception d'urgence
DD269557A5 (de) Verfahren zur herstellung einer zusammensetzung zur wirksamen prephylaxe von brustkrebs bei frauen und zur empfaengnisverhuetung
EP1935423A2 (fr) Composition pour le traitement et/ou la prophylaxie des tumeurs du sein
US20160262923A1 (en) Intrauterine delivery system
CH645545A5 (de) Mikroteilchen zur behandlung der inneren weiblichen geschlechtsorgane.
DE602004008912T2 (de) Retardiertes Freigabesystem mit kontrollierter Initialabgabe
TW200528073A (en) Transdermal delivery of hormones without the need of penetration enhancers
EP2841074A1 (fr) Utilisation intra-utérine de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones, et utilisation desdits composés pour la contraception et les traitements gynécologiques
WO2013160200A1 (fr) Utilisation de 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones pour le traitement des ménorragies, ainsi que système intra-utérin contenant du 18-méthyl-15 bêta, 16-bêta-méthylène-19-nor-20-spirox-4-en-3-ones pour le traitement des hémorragies utérines
EP1978969A1 (fr) Médicament comprenant une association d'hormones
WO2006087173A1 (fr) Preparation pharmaceutique de contraception orale
TW201529058A (zh) 子宮內遞送系統
WO2010015372A1 (fr) Prévention d'une grossesse par utilisation de gestagènes
TW201605457A (zh) １８－甲基－１５β，１６β－亞甲基－１９－降－２０－螺氧－４－烯－３－酮之陰道內用途，包含１８－甲基－１５β，１６β－亞甲基－１９－降－２０－螺氧－４－烯－３－酮之陰道內環及其於避孕之用途

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20141124

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20160720