EP1434586A1 - Preparation d'association estrogene-progestatif et son utilisation - Google Patents

Preparation d'association estrogene-progestatif et son utilisation

Info

Publication number
EP1434586A1
EP1434586A1 EP02785133A EP02785133A EP1434586A1 EP 1434586 A1 EP1434586 A1 EP 1434586A1 EP 02785133 A EP02785133 A EP 02785133A EP 02785133 A EP02785133 A EP 02785133A EP 1434586 A1 EP1434586 A1 EP 1434586A1
Authority
EP
European Patent Office
Prior art keywords
active ingredient
estrogen
daily dosage
progestogen
daily
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Withdrawn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
EP02785133A
Other languages
German (de)
English (en)
Inventor
Diethard Schwanitz
Jutta Rogoll
Bernd Hachmeister
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.)
Abbott Products GmbH
Original Assignee
Solvay Pharmaceuticals GmbH
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 Solvay Pharmaceuticals GmbH filed Critical Solvay Pharmaceuticals GmbH
Priority to EP02785133A priority Critical patent/EP1434586A1/fr
Publication of EP1434586A1 publication Critical patent/EP1434586A1/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Withdrawn legal-status Critical Current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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • 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
    • A61P5/34—Gestagens

Definitions

  • the present invention relates to new estrogen-progestogen combination preparations for use in hormone replacement therapy, for. B. for use in menopausal or climacteric complaints.
  • Typical enopausal or climacteric complaints occur in connection with the menopause of women. With the onset of menopause, the ovaries slowly cease to function. This reduces the formation of the female sex hormones estrogen and progesterone and finally stops. The ability to reproduce goes out. With the decline in hormone formation, numerous changes in the female organism are connected, which z. B. in menopausal symptoms, aging of the skin, decrease in bone mass, increase in the risk of cardiovascular diseases and a gradual decrease in mental performance.
  • hormone replacement therapy is usually prescribed which acts in the organism instead of the hormones no longer provided by the ovary.
  • hormone preparations such. B. in the form of coated tablets with an estrogen active ingredient as monopreparations and as combination preparations with a progestogen as an additional active ingredient.
  • the administration of the estrogen active ingredient and the progestogen active ingredient can be cyclical or continuous, depending on the patient and the type of combination product, by oral means
  • Effective dosage units of the hormone active ingredients are administered, usually in regimens without interruption, but possibly also with interruption phases.
  • dosing with single and daily doses takes place with the cycle still in place from the 1st to the 14th day of the cycle by oral administration of a coated tablet containing estrogen daily and from the 15th to the 28th day of the cycle by oral administration of one dragee daily, which contains a combination of estrogen and progestogen.
  • Another pharmaceutical combination preparation of the prior art is described in the European patent application EP 136011 B1.
  • EP 136011 B1 proposes therapeutic combination preparations with low-dose progestin and estrogen active ingredients for the treatment of post-menopausal complaints in women with an intact uterus, the 20 to 120 combined dosage units of progestogen and estrogen, and, if desired, 3 to 7 separate daily gestagens -Dosing units (without estrogen) included.
  • the administration can take place on the one hand by continuous continuous oral administration of the progestogen and simultaneous continuous continuous oral administration of the estrogen once daily in the form of a single combined dosage unit of the two hormones.
  • the estrogen can also be administered cyclically orally, the progestogen and the estrogen being administered together for the first time for 20 to 120 days in the form of the combined dosage unit and the progestogen without the estrogen once for 3 to 7 days in the form of the progestogen dosage units becomes.
  • Menopausal or climatic complaints are often perceived very differently by the women concerned.
  • the choice of the individual regimen for the prophylaxis, relief and / or treatment of the enopausal or climacteric complaints therefore makes a flexible possibility of variation appear desirable, which if necessary also allow alternative application regimes with one and the same preparation.
  • the present invention therefore proposes a new estrogen-progestogen combination preparation with an alternating regime.
  • the invention therefore relates to the use of an estrogen and a progestogen for the production of an oral pharmaceutical preparation, each of which has separate 14 or a whole multiple thereof daily dosage units of an estrogen active ingredient and, in a corresponding number, a combination of an estrogen active ingredient and a Gesta - Contains gene active ingredient in combined daily dosage units, for the prophylaxis, relief and / or treatment of endopausal or climacteric complaints in women, especially in women with an intact uterus, if no menstrual cycle is desired, by daily alternating, uninterrupted administration of the daily dosage units
  • the estrogen active ingredient and the combined daily dosage units of the combination of the estrogen active ingredient with the gestagen active ingredient over a period of at least 28 days (28-day cycle).
  • the pharmaceutical preparation according to the invention is suitable for the prophylaxis, relief and / or treatment of endopausal, including pre-, peri- and post-menopausal or climacteric complaints in women with an intact uterus, for whom a menstrual cycle is no longer desired.
  • Menopausal or climacteric complaints include a number of undesirable complaints or pathological changes due to the changing hormonal balance.
  • Perimenopausal e.g. over the age of 40
  • menopausal and post-meopausal women often suffer from a variety of different conditions and symptoms that can be attributed to estrogen deprivation due to declining ovarian function. The duration of such complaints can vary widely, and they can e.g. B.
  • estrogen is the most effective agent for controlling hot flashes and vaginal atrophy and prevents or delays the appearance of clinical signs of osteoporosis. From a clinical point of view, it is also necessary not to administer estrogens alone, but preferably in combination with a progestogen in a suitable dosage or therapy regimen. For this purpose, the present invention provides a suitable combination and administration that was not previously known in the prior art.
  • the areas of application according to the present invention include, in particular, early climacteric and menopausal symptoms with bleeding disorders, cycle irregularities (cycle anomalies), absence of the menstrual period (aenorrhea), menstrual periods which are too weak (hypomenorrhea), menstrual periods which are too rare (oligomenorrhea), excessively heavy menstrual periods (hymenorrhea) Intermediate bleeding, under-functioning of the ovaries (ovarian failure).
  • the dosage of the preparation according to the invention is carried out in an alternating therapy scheme with single and daily doses.
  • This alternating therapy scheme is particularly suitable especially for the patient group of women for whom no further cycle is desired.
  • the gestagen is given alternately, such as. B. also from Fig. 1 in an exemplary embodiment of the invention.
  • Is z. B. the estrogen drug in white coated tablets and the estrogen-progestogen combination in a pink coated tablet, the alternate progestogen is given by alternating 1 white and 1 pink coated tablet daily. Ie on the first day a white dragee (1) is taken, on the second day a pink dragee (2), on the third day again a white (3), on the fourth day again a pink dragee (4) etc. until the end of one 28-day cycle.
  • the coated tablets are e.g. B. as shown in Fig. 1 after a printed on the front of a blister strip therapy scheme, in the order of the specified numbers, starting with the number (1). These numbers are not dates, but only indicate the order in which the coated tablets are taken. Further exemplary configurations for the arrangement and labeling of the respective coated tablets in dosage forms according to the invention for the alternating therapy scheme are given in FIGS. 3 and 4. Packaged pharmaceutical preparations according to the invention which are suitable for this purpose are described in more detail below.
  • the next day i.e. without a break, is taken with a new blister pack according to the same alternating pink-white scheme as described above, following the numbers used for orientation.
  • the coated tablets can be used for one. Month (28-day cycle) should always be pre-sorted alternately in pink and white in a pill box.
  • 5A and 5B which illustrate an exemplary geometric configuration of a pill box or storage box, i.e. reproduce a pill box with a round geometry; further geometric configurations, e.g. B. oval shapes or rectangular shapes, e.g. B. analogous to the blister packs are possible.
  • this aspect of the invention is described in more detail below in connection with the packaged pharmaceutical preparations according to the invention.
  • the pharmaceutical preparation comprises 14 daily dosage units of an estrogen active ingredient and 14 daily dosage units of a combination of the estrogen active ingredient with a gestagen active ingredient.
  • This pharmaceutical preparation consisting of 14 daily dosage units, is intended for a 1-month treatment, ie for a 28-day cycle, and is packed accordingly.
  • the pharmaceutical preparation according to the invention can also be intended for a 3-month treatment, ie for three successive 28-day cycles, and be packaged accordingly, ie it becomes 3 times the daily dosage units of estrogen required for a 28-day cycle Active ingredient on the one hand and the combination of the estrogen active ingredient with a progestogen active ingredient.
  • the pharmaceutical preparation then comprises e.g. B.
  • Estrogens which can be used in the context of the invention are estrogen active substances which are selected from the group consisting of estradiol, 17-beta-estradiol, estradiol valerate, natural conjugated estrogens, also of equine origin, estrone, estropipate (piperazinesestrone sulfate), ethinyl estradiol, mestranol and quinestranol are.
  • Natural conjugated estrogen hormones are an amorphous extract, which is a mixture of water-soluble, conjugated estrogens, which are usually from natural sources such as, in particular, e.g. B.
  • the main estrogenic component in this mixture is the sodium salt of estrone sulfate, and to a lesser extent the sodium salt of equiline sulfate.
  • the overall estrogenic activity of pharmaceutical preparations is usually expressed in the form of equivalent amounts of the sodium estrone sulfate salt and, if appropriate, the sodium equiline sulfate salt.
  • Further conjugated estrogenic active ingredient components contained in the mixtures of natural conjugated estrogens are likewise contained in the mixtures as water-soluble sodium sulfate salts and are, for. 17- ⁇ -dihydroequiline, 17- ⁇ -estradiol and 17- ⁇ -dihydroequiline.
  • Tablets for oral administration usually contain the mixtures of the natural conjugated estrogens in strengths of about 0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg and 2.5 mg of the conjugated estrogens.
  • Gestagens which can be used in the context of the invention are progestogens which are selected from the group Laevo-Norgestrel, dl-Norgestrel, Norethindron (Norethistron), Norethindron- (No- rethistrone) acetate ethynodiol diacetate, dydrogesterone, medroxyprogesterone acetate, norethynodrel, allylestrenol, lyonestrestrol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chloromadestrone, chlormadestrone, chloroformadestrone Trimegeston, Dienogest, Drosperinon and Nomegestrol acetate are selected.
  • Gestagens preferred according to the invention are dydrogesterone, medroxyprogesterone acetate, norethistrone acetate, trimegestone, dienogest, drosperinone, and in particular medrogestone.
  • the daily estrogen dosage unit contains the estrogen active ingredient, preferably a mixture of natural conjugated equine estrogens, in an amount of 0.05 mg to 10 mg depending on the type of estrone used, and the combined daily dosage unit contains the estrogen active ingredient , preferably also a mixture of natural conjugated equine estrogens, in an amount of 0.05 mg to 10 mg, depending on the type of estrone used, and the gestagen active ingredient in an amount of 0.05 mg to 50 mg, depending on the type of used progestogen.
  • Medrogeston which is preferably used as a gestagen, is contained in an amount of 1 mg to 20 mg, in particular in an amount of 1 mg to 10 mg.
  • the person skilled in the art is familiar with the amounts to be used for the respective individual estrogen or progestogen active ingredients.
  • the daily dosage unit of the estrogen active ingredient contains 14 mg of an extract from the urine of pregnant mares, standardized to 0.33 mg of sodium salt of estrone-3-hydrogen sulfate and 0.17 mg of sodium salt of equiline-3 hydrogen sulfate (equivalent to 0.6 mg conjugated equine estrogens) and the combined daily dosage unit a combination of also 14 mg of an extract from the urine of pregnant mares, standardized to 0.33 mg sodium salt of estrone-3-hydrogen sulfate and 0.17 mg sodium salt from equiline - 3-hydrogen sulfate (equivalent to 0.6 mg conjugated estrogens) as an estrogen drug and 5 mg of medrogestone as a progestogen drug.
  • the active ingredients are in the daily dosage units in a suitable manner with z.
  • B. usual pharmaceutical carriers and excipients as an orally administrable solid pharmaceutical dosage forms, for. B. as a tablet, pill or in particular as a dragee, in any geometric configuration.
  • Conventional galenical preparation methods can be used to produce these solid oral dosage forms, which in addition to tablet or pill production processes also include filming and coating processes if desired. These methods are familiar to the person skilled in the art.
  • pharmaceutical carriers and auxiliaries such. B.
  • the pharmaceutical materials known in the prior art in question such as conventional inorganic and / or organic carriers, such as lactose, talc or starch, and, if required, other pharmaceutically customary auxiliaries, such as, for example, matrix formers, binders, granulating aids, lubricants, lubricants, humectants or desiccants, fillers, dyes or tablet disintegrants. Additional auxiliaries can also be added, such as. B. preservatives, stabilizers, taste corrections, flavorings and the like. Enveloped solid pharmaceutical forms can be in the form of a film tablet (film or lacquer tablet), optionally with an additional coating layer, or as a classic coated tablet.
  • film tablet film or lacquer tablet
  • additional coating layer or as a classic coated tablet.
  • Film-coated tablets are usually coated with a polymer film.
  • Formulations for coating film tablets include, for example, in addition to the polymeric film former, if desired, plasticizers, dispersing or smoothing agents, opacifying agents and dyes; the ingredients are usually applied to the tablet or pill core with a solvent, usually ethanol or acetone.
  • Dragees are usually the solid dosage forms coated with sugar.
  • coating syrups ie highly concentrated sugar solutions with a sugar content of up to 80% by weight, are usually used. Sucrose is predominantly used as the sugar.
  • a core such as, for example: the cover layer consisting of a few portions of cover syrup and cover powder sprinkled in between; the application layer consisting of several portions of application syrup and application powder sprinkled in between; a smoothing layer of pure, possibly colored syrup to give the coated tablet surface brilliance; followed by glossing or polishing with wax or wax solution as a finish.
  • carriers and auxiliaries which can be used include inert inorganic materials such as tribasic calcium phosphate, calcium sulfates or titanium dioxide, or inert organic materials such as carnauba wax, cellulose, glycerol monooleate, lactose, magnesium stearate, methyl cellulose, pharmaceutical glaze, polyethylene glycol, stearic acid and sucrose.
  • Preferred oral pharmaceutical preparations according to the present invention include e.g. B.
  • Materials such as arabic gum, carmellose sodium, carnauba wax, lactose, macrogol 4000 and 6000, magnesium oxide, magnesium stearate, corn starch, polyvidone, sucrose, shellac, talc, bleached wax, dyes E104, E127 and E171.
  • the solid, oral daily dosage units can also be colored, e.g. B. to identify and differentiate the estrogen dosage units and combined estrogen-progestogen dosage units.
  • the labeling and differentiation can alternatively or additionally take place via the packaging material in which the daily dosage units with the estrogen active ingredient on the one hand and the combined estrogen-progestogen active ingredients on the other hand are provided. Labels can e.g. B. color and / or numbers.
  • the invention therefore also relates to packaged pharmaceutical preparations (packaging units) which - A packaging material in which 14 or a whole multiple thereof daily dosage units of an estrogen active ingredient and in a corresponding number a combination of an estrogen active ingredient with a progestogen active ingredient are combined in combined daily dosage units, and the daily doses with the estrogen active ingredient on the one hand and the combined daily doses of estrogen active ingredient and progestogen active ingredient on the other hand are marked in a suitable manner for clear differentiation from one another; and
  • the packaged pharmaceutical preparation according to the invention is characterized in that the daily dose unit with estrogen active ingredient, on the one hand, and the daily combined daily dose unit consisting of estrogen and progestogen active ingredient, on the other hand, are distinguished by optical identification, preferably by different colors, to distinguish them from one another are.
  • the packaged pharmaceutical preparation according to the invention comprises as a packaging material a blister on which a scheme to facilitate the alternating administration of the daily Dosage units of the estrogen active ingredient and the combined daily dosage unit of estrogen active ingredient and progestogen active ingredient, preferably as a scheme of integers from 1 to 28, is printed in order to determine the sequence of the respective daily dosage unit to be administered.
  • these can e.g. B. for a month (28 days) alternately pre-sorted in a pill box divided into compartments or pre-sorted from a blister pack.
  • the invention therefore also relates as packaged units to packaged pharmaceutical preparations which
  • a packaging material in which 14 or a whole multiple thereof daily dosage units of an estrogen active ingredient and in a corresponding number a combination of an estrogen active ingredient with a progestogen active ingredient are combined in combined daily dosage units, and the daily doses with the estrogen active ingredient on the one hand and the combined daily doses of estrogen active ingredient and progestogen active ingredient on the other hand are marked in a suitable manner for clear differentiation from one another;
  • the above packaged pharmaceutical preparation according to the invention is characterized in that the packaging material is a pill box divided into 28 compartments, preferably a pill box divided into 28 compartments with a ring-shaped arrangement of these compartments, > in which a daily dosage unit of an estrogen active ingredient alternates and a combined daily dosage unit of estrogen active ingredient and progestogen active ingredient, and are marked in a suitable manner for clear differentiation from one another.
  • the packaging material is a pill box divided into 28 compartments, preferably a pill box divided into 28 compartments with a ring-shaped arrangement of these compartments, > in which a daily dosage unit of an estrogen active ingredient alternates and a combined daily dosage unit of estrogen active ingredient and progestogen active ingredient, and are marked in a suitable manner for clear differentiation from one another.
  • the individual subjects can be identified by days of the week and thereby complement the color coding of the dosing units.
  • blisters will be produced as packaging material for the distribution of the pharmaceutical preparation, and the above pill boxes will only be given in support.
  • progestogen administration can also take place according to a classic cyclic therapeutic regimen, which if desired is based on e.g. B. can be printed on a front of the blister in addition to the alternating therapy scheme usually indicated on the back of the blister as an option.
  • the packaged pharmaceutical preparations can thus two different therapy schemes on z. B. provide on a blister pack, and you can choose between the two dosing schemes, with the attending doctor deciding at the start of therapy which of the two schemes is suitable for the respective patient.
  • the cyclical therapy scheme which may also be provided as an option, is particularly suitable for the patient group of women who still have a regular cycle and this cycle continues. should be maintained.
  • the gestagen is given cyclically, such as. B. also from -Fig. 2 can be seen in an exemplary embodiment; other configurations are conceivable. Is z. B. the estrogen-active ingredient in white coated tablets and the estrogen-progestogen-active ingredient combination in a pink coated tablet, alternating gestagen is given by 1 white tablet daily and from 15th to 28th cycle day from the 1st to the 14th cycle day 1 pink coated tablet is administered.
  • the coated tablets are e.g. B. as shown in FIG. 2 in an exemplary embodiment according to a therapy scheme printed on the front of a blister strip, starting from the starting point in the order of the arrows.
  • inventive configurations such. B. a blister pack according to FIG. 3 or FIG. 4, the choice of the classic cyclic therapy scheme on the front of the blister z. B. can also be identified by arrows or numbers according to the arrangement of the respective coated tablets.
  • the next day i.e. without a break, is continued with a new blister pack following the same cyclic therapy regimen as described above, following the arrows for orientation.
  • a particular advantage of the invention, in particular of the packaged pharmaceutical preparations, is that by the type of, patient compliance and therapy compliance is significantly increased.
  • the patients affected by a change can therefore continue to take the preparation in the usual and individually proven formulation and with a change, any other intolerance that may occur can be avoided from the outset.
  • Fig. 1 Blister according to the invention with dosing scheme imprint
  • FIG. 2 blister front with alternative dosing scheme, in the event that menstrual bleeding is still desired; Arrows scheme.
  • Fig. 3 Blister according to the invention with dosing scheme imprint
  • FIG. 4 blister front with dosing scheme imprint according to the invention
  • Arrow diagram Fig. 5 (Fig. 5A) pill box without content
  • An exemplary packaging unit contains the combination preparation from the two different hormone coated tablets, white coated tablets with an estrogen active ingredient and pink coated tablets with an estrogen and a progestogen.
  • the estrogen component is obtained as a standardized extract from the urine of pregnant mares.
  • the progestogen component (corpus luteum hormone component) consists of medrogestone.
  • One package contains 14 white and 14 pink coated tablets.
  • 1 white coated tablet contains 14 mg of an extract from the urine of pregnant mares, standardized to 0.33 mg sodium salt of estrone-3-hydrogen sulfate and 0.17 mg sodium salt of equiline-3 hydrogen sulfate (corresponding to 0.6 mg conjugated equine estrogens).
  • 1 pink coated tablet contains 14 mg of an extract from the urine of pregnant mares, standardized to 0.33 mg of sodium salt of estrone-3-hydrogen sulfate and 0.17 mg of sodium salt of equilin-3-hydrogen sulfate (corresponding to 0.6 mg conjugated estrogens) and 5 mg medrogestone.
  • Packaged pharmaceutical preparations can e.g. B. following

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

La présente invention concerne de nouvelles préparations d'association estrogène-progestatif destinées à être utilisées dans le traitement hormonal substitutif, par exemple, dans les plaintes relatives à la ménopause.
EP02785133A 2001-09-29 2002-09-25 Preparation d'association estrogene-progestatif et son utilisation Withdrawn EP1434586A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02785133A EP1434586A1 (fr) 2001-09-29 2002-09-25 Preparation d'association estrogene-progestatif et son utilisation

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP01123511 2001-09-29
EP01123511 2001-09-29
EP02785133A EP1434586A1 (fr) 2001-09-29 2002-09-25 Preparation d'association estrogene-progestatif et son utilisation
PCT/EP2002/010728 WO2003028735A1 (fr) 2001-09-29 2002-09-25 Preparation d'association estrogene-progestatif et son utilisation

Publications (1)

Publication Number Publication Date
EP1434586A1 true EP1434586A1 (fr) 2004-07-07

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EP02785133A Withdrawn EP1434586A1 (fr) 2001-09-29 2002-09-25 Preparation d'association estrogene-progestatif et son utilisation

Country Status (16)

Country Link
US (1) US20040266745A1 (fr)
EP (1) EP1434586A1 (fr)
JP (1) JP2005507394A (fr)
KR (1) KR20040037097A (fr)
CN (1) CN1561217A (fr)
BR (1) BRPI0208558A2 (fr)
CA (1) CA2462075A1 (fr)
DE (1) DE10294402D2 (fr)
HU (1) HUP0402142A2 (fr)
IL (1) IL161105A0 (fr)
MX (1) MXPA04002771A (fr)
NO (1) NO20034159L (fr)
PL (1) PL373494A1 (fr)
RU (1) RU2004113305A (fr)
WO (1) WO2003028735A1 (fr)
ZA (1) ZA200402458B (fr)

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WO2003028735A1 (fr) 2003-04-10
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