[go: up one dir, main page]

DE19510861A1 - One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women - Google Patents

One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women

Info

Publication number
DE19510861A1
DE19510861A1 DE19510861A DE19510861A DE19510861A1 DE 19510861 A1 DE19510861 A1 DE 19510861A1 DE 19510861 A DE19510861 A DE 19510861A DE 19510861 A DE19510861 A DE 19510861A DE 19510861 A1 DE19510861 A1 DE 19510861A1
Authority
DE
Germany
Prior art keywords
estradiol
month
peri
replacement therapy
hormone replacement
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Withdrawn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
DE19510861A
Other languages
German (de)
Inventor
Ursula Dr Dr Lachnit-Fixson
Semiramis Aydinlik
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
Schering 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
Application filed by Schering AG filed Critical Schering AG
Priority to DE19510861A priority Critical patent/DE19510861A1/en
Priority to HU9801691A priority patent/HUP9801691A3/en
Priority to CA002215382A priority patent/CA2215382A1/en
Priority to KR1019970706467A priority patent/KR19980703058A/en
Priority to PL96322202A priority patent/PL322202A1/en
Priority to JP8527295A priority patent/JPH11501649A/en
Priority to MX9707009A priority patent/MX9707009A/en
Priority to ARP960101766A priority patent/AR002283A1/en
Priority to EP96907506A priority patent/EP0814811A1/en
Priority to AU51108/96A priority patent/AU713258B2/en
Priority to SK1239-97A priority patent/SK123997A3/en
Priority to PCT/EP1996/001201 priority patent/WO1996028165A1/en
Priority to NZ304027A priority patent/NZ304027A/en
Priority to CZ972896A priority patent/CZ289697A3/en
Priority to IL11751696A priority patent/IL117516A/en
Priority to ZA962177A priority patent/ZA962177B/en
Publication of DE19510861A1 publication Critical patent/DE19510861A1/en
Priority to NO974255A priority patent/NO974255L/en
Priority to US09/348,232 priority patent/US20010006963A1/en
Priority to US10/062,569 priority patent/US20020193358A1/en
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
    • A61K31/565—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
    • 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
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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

Landscapes

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

Abstract

A once-a-month-injectable that contains an oestrogen and a gestagen component as active substances is used to prepare a contraceptive medicament useful at the same time in the hormone replacement therapy for perimenopausal and premenopausal women. A reliable contraceptive effect with a "natural" oestrogen (without ethinyl oestradiol) is achieved with this medicament, as well as an effective therapy of the first oestrogen deficiency symptoms and the prevention of osteoporosis.

Description

Die vorliegende Erfindung betrifft die Verwendung einer Einmonatsspritze (once-a­ month-injectable) enthaltend eine estrogene und gestagene Komponente als Wirkstoffe zur Herstellung eines Arzneimittels für die Kontrazeption und die gleichzeitige Hormonersatztherapie für peri- und praemenopausale Frauen.The present invention relates to the use of a one-month syringe (once-a month-injectable) containing an estrogenic and gestagenic component as active ingredients for the manufacture of a medicinal product for contraception and simultaneous Hormone replacement therapy for peri- and premenopausal women.

Einmonatsspritze im Sinne vorliegender Erfindung bedeutet eine Hormonpräparation, die Frauen im gebärfähigen Alter einmal monatlich zur Empfängnisverhütung injiziert wird. In dieser Hormonpräparation sind als aktive Substanzen eine gestagene sowie estrogene Komponente, jeweils mit einer ausreichend langen Wirkung zur Erzielung eines kontrazeptiven Effekts für einen einmonatigen Zeitraum, enthalten.One-month injection in the sense of the present invention means a hormone preparation, women of childbearing age injected once a month for contraception becomes. In this hormone preparation, gestagen as well as active substances are estrogenic component, each with a sufficiently long effect to achieve a contraceptive effect for a period of one month.

Es sind auch sogenannte progestogen-only injectables verfügbar, die einen länger anhaltenden kontrazeptiven Schutz, allerdings bei schlechter Zykluskontrolle, gewährleisten.So-called progestogen-only injectables are also available, which take longer persistent contraceptive protection, but with poor cycle control, guarantee.

Bekannteste Vertreter einer derartigen Einmonatsspritze sind Cyclofem (HRP 112; Cycloprovera) und Mesigyna (HRP 102). Erstere enthält 25 mg Medroxyprogeste­ ronacetat als gestagene und 5 mg Estradiolcypionat als estrogene Komponente in Mikrokristallsuspension, letztere 50 mg Norethisteronenanthat als gestagene und 5 mg Estradiolvalerat als estrogene Komponente in öliger Lösung. Obwohl die Frauen, die diese Verhütungsmethode wählen, jeden Monat ein Familienplanungszentrum oder ei­ nen Arzt zur Verabreichung der Injektion aufsuchen müssen, werden diese Einmonatsspritzen zur Kontrazeption gut angenommen. Vaginale Blutungen treten wie die Menstruation ziemlich regulär und vorhersehbar auf, was für eine breite Akzeptanz dieser sicheren Methode in vielen Kulturkreisen von herausragender Bedeutung ist. (Biennial Report 1988-1989, Research in Human Reproduction, WHO).The best-known representatives of such a one-month injection are Cyclofem (HRP 112; Cycloprovera) and Mesigyna (HRP 102). The former contains 25 mg of medroxy progestin ronacetate as gestagenic and 5 mg of estradiol cypionate as estrogenic component in Microcrystalline suspension, the latter 50 mg norethisterone enanthate as gestagen and 5 mg Estradiol valerate as an estrogenic component in an oily solution. Although the women who choose this method of contraception, monthly family planning center or egg If you need to see a doctor to give the injection, they will One month injection for contraception well accepted. Vaginal bleeding occurs like menstruation is fairly regular and predictable on what a wide acceptance this safe method is of paramount importance in many cultures. (Biennial Report 1988-1989, Research in Human Reproduction, WHO).

Aus dem US-Patent 4,826,831 geht bereits eine Methode für die hormonelle Behandlung menopausaler, einschließlich perimenopausaler und postmenopausaler Störungen (disorders) hervor, die insbesondere eine Behandlung unter der kontinuierlichen Anwendung eines Gestagens in Verbindung mit einem Estrogen betrifft. Das Estrogen kann dabei ebenfalls kontinuierlich oder auch zyklisch, d. h. mit Einnahmepausen, angewendet werden. A method for the hormonal is already out of the US patent 4,826,831 Treatment of menopausal, including perimenopausal and postmenopausal Disorders, which in particular treatment under the continuous use of a progestogen in conjunction with an estrogen concerns. The estrogen can also be continuous or cyclical, i.e. H. With Taking breaks should be applied.  

Es ist eine Vielzahl von Estrogenen und Gestagenen genannt, die für die Zwecke dieser Erfindung geeignet sind, u. a. auch Norethisteronacetat und Medroxyprogesteronacetat als Gestagene sowie Estradiolvalerat. Es sollen prinzipiell alle Estrogene und Gestagene verwendbar sein, die auch in oralen Kontrazeptiva denkbar sind. Ausreichender kontrazeptiver Schutz ist durch die beschriebenen Behandlungen ausdrücklich nicht gegeben.There is a wide variety of estrogens and progestogens called for the purpose of this Invention are suitable u. a. also norethisterone acetate and medroxyprogesterone acetate as progestogens and estradiol valerate. In principle, all estrogens and progestogens are said to be be usable, which are also conceivable in oral contraceptives. Adequate contraceptive protection is expressly not given by the treatments described given.

Norethisteronacetat/Estradiolvalerat ist außerdem als eine mögliche Kombination offen­ bart.Norethisterone acetate / estradiol valerate is also open as a possible combination beard.

Die zur Anwendung kommenden Mengen Gestagen und Estrogen sind niedrig: Das Gestagen in einer täglichen Menge, die einer Menge von 0,025 mg bis 0,075 mg Levo­ norgestrel und das Estrogen in einer täglichen Menge, die einer Menge von 0,5 bis 2,0 mg Estradiol entspricht.The amounts of progestogen and estrogen used are low: That Gestagen in a daily amount that is from 0.025 mg to 0.075 mg Levo norgestrel and the estrogen in a daily amount, an amount of 0.5 to 2.0 mg corresponds to estradiol.

Im Falle einer oralen Applikation der Wirkstoffe liegt die täglich zu verabreichende Menge Estradiolvalerat im Bereich 0,5 mg bis 2,0 mg; für Norethisteronacetat ist eine tägliche Menge von 0,1 mg bis 1,0 mg und für Medroxyprogesteronacetat eine solche von 1,0 mg bis 15,0 mg angegeben.In the case of oral administration of the active ingredients, the daily dose is to be administered Amount of estradiol valerate in the range 0.5 mg to 2.0 mg; for norethisterone acetate is one daily amount of 0.1 mg to 1.0 mg and such for medroxyprogesterone acetate from 1.0 mg to 15.0 mg.

Die US-PS 4,826,831 umfaßt auch die nicht-orale Anwendung der angegebenen Wirkstoffe mittels Implantaten oder durch intramuskuläre Injektion. Die benötigten "täglichen" Dosierungen liegen dann etwas niedriger als im Falle der oralen Applikation aufgrund des direkten Übergangs der Wirkstoffe in die Blutbahn.U.S. Patent 4,826,831 also includes the non-oral use of the specified Active substances by means of implants or by intramuscular injection. The necessities "Daily" dosages are then somewhat lower than in the case of oral administration due to the direct transfer of the active ingredients into the bloodstream.

Für ein Estrogenimplant sind 20 mg bis 100 mg Estradiolvalerat angegeben. Eine Gestagendepotformulierung für 3 Monate soll 50 bis 500 mg Medroxyprogesteronacetat bzw. 20 bis 400 Norethisteronenanthat enthalten.For an estrogen implant, 20 mg to 100 mg estradiol valerate are given. A Gestagen depot formulation for 3 months should be 50 to 500 mg medroxyprogesterone acetate or 20 to 400 norethisterone enanthate.

Dieses Patent betrifft auch pharmazeutische Zusammensetzungen zur Durchführung dieser Methode.This patent also relates to pharmaceutical compositions for use this method.

Durch diese Methode werden den mit dem natürlichen Estrogenentzug, der bereits in der Praemenopause beginnt, einsetzenden Beschwerden, wie beispielsweise hot flushes, Trockenheit der Vagina, der Osteoporosegefahr, der zunehmenden Gefahr bei Frauen über 60 Jahren einen Myokardinfarkt zu erleiden (kardiovaskuläre Komplikationen), wirkungsvoll begegnet, wobei aber aufgrund der gestagenen Komponente eine Blu­ tungsinduktion unterdrückt, aber das Risiko für die Ausbildung von Endometrialcarzi­ nomen nicht erhöht wird.Through this method, those with natural estrogen deprivation that are already in the premenopause begins, complaints such as hot flushes, Dryness of the vagina, the risk of osteoporosis, the increasing risk in women have a myocardial infarction for over 60 years (cardiovascular complications), encountered effectively, but due to the gestagen component a Blu induction suppressed, but the risk of developing endometrial carcinoma nomen is not increased.

In der US-PS 4,826,831 wird ausdrücklich darauf hingewiesen, daß es sich im Falle der oralen Applikation nicht um eine Methode der Empfängnisverhütung handelt. In US Pat. No. 4,826,831 it is expressly pointed out that in the case of oral application is not a method of contraception.  

Peri- und Praemenopause sollen im Sinne vorliegender Erfindung in ihrer konventionellen Bedeutung, wie sie in "The Controversial Climacteric", P.A. van Keep et al., Ed., MTP Press (1981) auf Seite 9 angegeben ist, verstanden werden.Peri- and premenopause should be in the sense of the present invention in their conventional meaning as described in "The Controversial Climacteric", P.A. van Keep et al., Ed., MTP Press (1981) on page 9.

Aufgabe der vorliegenden Erfindung ist es, ein Depot-Arzneimittel zur Verfügung zu stellen, welches für Frauen in der Peri- und Praemenopause gleichermaßen für die noch nötige Kontrazeption als auch für die bereits in diesem Lebensabschnitt ratsame hormonelle Substitutionstherapie (Hormone Replacement Therapie = HRT) geeignet ist.The object of the present invention is to provide a depot drug which for women in the peri- and premenopause equally for the still necessary contraception as well as for those already advisable in this phase of life hormonal replacement therapy (Hormone Replacement Therapy = HRT) is suitable.

Es wurde nunmehr gefunden, daß ein derartiges Arzneimittel für prae- und perimenopausale Frauen überraschenderweise auf der Basis einer Einmonatsspritze hergestellt werden kann.It has now been found that such a drug for pre- and Perimenopausal women surprisingly on the basis of a one-month injection can be manufactured.

Während durch die in der US-PS 4,826,831 beschriebene Methode Blutungen der behandelten Frauen gerade vermieden werden sollen, tritt bei peri- bzw. praemenopausalen Frauen nach Applikation der erfindungsgemäßen Einmonatsspritze am Ende des Behandlungszeitraumes eine Monatsblutung auf; es wird also keine Amenorrhoe induziert.While bleeding from the method described in U.S. Patent 4,826,831 treated women should be avoided, peri or premenopausal women after application of the one-month injection according to the invention a menstrual period at the end of the treatment period; so it won't be Amenorrhea induced.

Unter Einmonatsspritze im Sinne vorliegender Erfindung sollen sowohl die bereits ein­ gangs erwähnten Produkte als auch alle anderen denkbaren Kombinationen eines natür­ lichen Estrogens mit einem Gestagen verstanden werden. Die beiden Wirkkomponenten müssen dabei in einer Depotformulierung vorliegen, wobei der Depoteffekt entweder durch die besondere Art der galenischen Formulierung (beispielsweise Mikrokristallsuspension) oder aber eher durch den chemischen Aufbau des Gestagens und/oder Estrogens erreicht wird (beispielsweise durch die Veresterung freier Hydroxygruppen).Under one-month injection in the sense of the present invention, both the already one Products mentioned above as well as all other possible combinations of a natural estrogen with a progestogen. The two active components must be in a deposit formulation, with the deposit effect either due to the special nature of the galenic formulation (e.g. Microcrystalline suspension) or rather through the chemical structure of the gestagen and / or estrogen is achieved (for example by the esterification of free Hydroxy groups).

Es kommen dabei prinzipiell alle natürlichen Estrogene und alle Gestagene in Betracht, die zur Verwendung in oralen Kontrazeptiva geeignet sind und die sich in oben erwähnter Weise in eine galenische Formulierung überführen oder chemische Form derivatisieren lassen, die einen Depoteffekt bewirkt und die als intramuskulär zu verabreichende Arzneiform herstellbar ist.In principle, all natural estrogens and all progestogens can be considered, which are suitable for use in oral contraceptives and which are listed above convert into a galenic formulation or chemical form Let derivatize, which causes a depot effect and which as intramuscular administering dosage form can be produced.

Als Estrogene kommen hier in erster Linie 17β-Estradiol, Estradiol-3-benzoat, Estradiol-17-valerat, -cypionat, -undecylat, -enanthat und/oder andere Estradiolester in Frage (US-PS 2,611,773, US-PS 2,990,414, US-PS 2,054,271, US-PS 2,225,419 und US-PS 2,156,599). The primary estrogens here are 17β-estradiol, estradiol-3-benzoate, Estradiol 17 valerate, cypionate, undecylate, enanthate and / or other estradiol esters in question (U.S. Patent 2,611,773, U.S. Patent 2,990,414, U.S. Patent 2,054,271, U.S. Patent 2,225,419 and U.S. Patent 2,156,599).  

Die gestagene Komponente wird vorzugsweise aus der Gruppe der Verbindungen Norethisteronacetat, Norethisteronenenthat, Medroxyprogesteronacetat und Cyproteronacetat ausgewählt.The gestagen component is preferably selected from the group of compounds Norethisterone acetate, norethisterone acetate, medroxyprogesterone acetate and Cyproterone acetate selected.

In den folgenden Tabellen 1A und 2A sind ausgewählte, gemäß vorliegender Erfindung zu verwendende Estrogene bzw. Gestagene mit Angabe des bevorzugten Mengenbereiches aufgelistet.Tables 1A and 2A below are selected according to the present invention Estrogens or progestogens to be used, stating the preferred one Quantity range listed.

Aus den Tabellen 1B und 2B gehen die besonders bevorzugten Mengen des jeweiligen Estrogens bzw. Gestagens, die in einer Einmonatsspritze gemäß vorliegender Erfindung enthalten sein sollen, hervor.Tables 1B and 2B show the particularly preferred amounts of each Estrogen or progestogen in a one-month syringe according to the present invention should be included.

Tabelle 1A Table 1A

Tabelle 1B Table 1B

Tabelle 2A Table 2A

Tabelle 2B Table 2B

Erfindungsgemäß bevorzugt zur Herstellung einer Einmonatsspritze für die peri- und praemenopausale Kontrazeption ist die Kombination Medroxyprogesteronacetat/ Estradiolcypionat; die Kombination Norethisteronenanthat/Estradiolvalerat ist besonders bevorzugt.According to the invention preferably for the production of a one-month syringe for the peri- and premenopausal contraception is the combination of medroxyprogesterone acetate / Estradiol cypionate; the combination is norethisterone enanthate / estradiol valerate particularly preferred.

Als besondere Vorteile der erfindungsgemäß hergestellten Einmonatsspritze, die im Falle praemenopausaler Frauen überraschenderweise sowohl der Kontrazeption als auch der Hormonersatztherapie dienen kann, sind in erster Linie zu erwähnen:As special advantages of the one-month syringe manufactured according to the invention, which in Cases of premenopausal women surprisingly both contraceptively as well Hormone replacement therapy can primarily be mentioned:

  • - sicherer kontrazeptiver Effekt ohne Ethinylestradiol mit "natürlichem" Estrogen;- safe contraceptive effect without ethinyl estradiol with "natural" estrogen;
  • - damit einhergehende wirksame Therapie der beginnenden Estrogen-Ausfallerschei­ nungen (Beseitigung der menopausalen Symptome);- Associated effective therapy of the beginning estrogen deficiency (elimination of menopausal symptoms);
  • - gleichzeitig optimale Osteoporose-Prävention;- optimal osteoporosis prevention at the same time;
  • - hervorragende Toleranz und Zykluskontrolle;- excellent tolerance and cycle control;
  • - praktisch keine Veränderung des Blutdrucks;- practically no change in blood pressure;
  • - sehr niedrige, fast nicht vorhandene unerwünschte Nebenwirkungen und Einflüsse auf metabolische und haemostatische Parameter;- very low, almost nonexistent undesirable side effects and influences on metabolic and haemostatic parameters;
  • - Vermeidung einer Leberbelastung sowie gastrointestinaler Störungen aufgrund des parenteralen Anwendungsweges;- Avoid liver stress and gastrointestinal disorders due to the parenteral route of application;
  • - Beibehaltung der vorteilhaften Nebenwirkungen oraler Kontrazeptiva (Schutz vor Ovarial- und Endometriumkarzinom und Pelviic Inflammatory Desease [PID]).- Maintaining the beneficial side effects of oral contraceptives (protection against Ovarian and endometrial cancer and Pelviic Inflammatory Desease [PID]).

Alle diese Eigenschaften wurden durch eine 3-jährige, klinische Studie mit Mesigyna belegt, wobei am Patientinnenkollektiv 17 über 35 Jahre alte Frauen beteiligt waren.All of these traits have been demonstrated through a 3 year clinical trial with Mesigyna documented, whereby 17 women over 35 years of age were involved in the patient collective.

Die besonders bevorzugte Ausführungsform auf Basis der Gestagen/Estrogen-Kombina­ tion Norethisteronenanthat/Estradiolvalerat bietet nicht nur einen prophylaktischen Effekt betreffend die Osteoporose sondern es wird bei dieser Kombination über die knochenabbauhemmende Wirkung des Estrogens hinaus sogar ein durch das Norethis­ teronenanthat hervorgerufener Knochenabbaueffekt beobachtet.The particularly preferred embodiment based on the progestogen / estrogen combination tion Norethisterone enanthate / estradiol valerate is not just a prophylactic Effect regarding the osteoporosis but it is with this combination over the the estrogen's anti-bone effect is even increased by the norethis terone enanthate observed bone degradation effect.

FormulierungsbeispieleFormulation examples MesyginaMesygina

Eine Ampulle enthältContains one ampoule

50 mg Norethisteronenanthat +
 5 mg Estradiolvalerat50 mg of norethisterone enanthate +
5 mg estradiol valerate

in 1 ml Rizinusöl/Benzylbenzoat 6/4 (V/V).in 1 ml castor oil / benzyl benzoate 6/4 (V / V).

Formulierung mit CyproteronacetatFormulation with cyproterone acetate

Eine Ampulle enthältContains one ampoule

50 mg Cyproteronacetat +
 5 mg Estradiolvalerat50 mg cyproterone acetate +
5 mg estradiol valerate

in 1 ml Rizinusöl/Benzylbenzoat 6/4 (V/V).in 1 ml castor oil / benzyl benzoate 6/4 (V / V).

Claims (4)

1. Verwendung einer Einmonatsspritze (once-a-month-injectable) enthaltend eine estrogene und gestagene Komponente als Wirkstoffe zur Herstellung eines Arzneimittels für die Kontrazeption und die gleichzeitige Hormonersatztherapie für peri- und praemenopausale Frauen.1. Use of a once-a-month-injectable syringe containing one Estrogenic and progestogen component as active ingredients for the production of a Drug for contraception and concurrent hormone replacement therapy for peri- and premenopausal women. 2. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die estrogene Kom­ ponente aus der Gruppe der Verbindungen 17β-Estradiol, Estradiol-3-benzoat, Estradiol-17-valerat, cypionat, -undecylat, -enanthat sowie weiterer Estradiolester ausgewählt ist.2. Use according to claim 1, characterized in that the estrogenic com component from the group of the compounds 17β-estradiol, estradiol-3-benzoate, Estradiol 17-valerate, cypionate, undecylate, enanthate and other estradiol esters is selected. 3. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die gestagene Komponente aus der Gruppe der Verbindungen Norethisteronacetat, Norethisteronenenthat, Medroxyprogesteronacetat, Cyproteronacetat ausgewählt ist.3. Use according to claim 1, characterized in that the gestagene Component from the group of the compounds norethisterone acetate, Norethisterone enthat, medroxyprogesterone acetate, cyproterone acetate is selected. 4. Verwendung der Kombinationen
Norethisteronananthat/Estradiolvalerat,
Medroxyprogesteronacetat/Estradiolcypionat
nach den Ansprüchen 2 und 3.4. Use of the combinations
Norethisterone ananthate / estradiol valerate,
Medroxyprogesterone acetate / estradiol cypionate
according to claims 2 and 3.
DE19510861A 1995-03-16 1995-03-16 One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women Withdrawn DE19510861A1 (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
DE19510861A DE19510861A1 (en) 1995-03-16 1995-03-16 One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women
AU51108/96A AU713258B2 (en) 1995-03-16 1996-03-15 Once-a-month-injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women
SK1239-97A SK123997A3 (en) 1995-03-16 1996-03-15 Once-a-month-injectable useful as depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women
KR1019970706467A KR19980703058A (en) 1995-03-16 1996-03-15 Monthly injections useful as hormone replacement therapy and depot contraception for menopausal and premenopausal women
PL96322202A PL322202A1 (en) 1995-03-16 1996-03-15 Monthly injections as a contraceptive measure for and in substitute hormonal therapy of pre- and in-menopausal female patients
JP8527295A JPH11501649A (en) 1995-03-16 1996-03-15 Injection for January as a sustained release contraceptive for women in peri-menopause and pre-menopause and for hormone replacement therapy
MX9707009A MX9707009A (en) 1995-03-16 1996-03-15 Once-a-month-injectable useful as depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women.
ARP960101766A AR002283A1 (en) 1995-03-16 1996-03-15 COMPOSITIONS FOR INJECTION ONCE A MONTH, WHICH CONSTITUTES A CONTRACEPTIVE MEDICATION OF PROLONGED ACTION, SUITABLE FOR THERAPY OF REPLACEMENT OF HORMONES IN PERIMENOPAUSIC AND PREMONOPAUSIC WOMEN.
EP96907506A EP0814811A1 (en) 1995-03-16 1996-03-15 Once-a-month-injectable useful as depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women
HU9801691A HUP9801691A3 (en) 1995-03-16 1996-03-15 Once-a-month-injectable useful as depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women
CA002215382A CA2215382A1 (en) 1995-03-16 1996-03-15 Once-a-month-injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women
PCT/EP1996/001201 WO1996028165A1 (en) 1995-03-16 1996-03-15 Once-a-month-injectable useful as depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women
NZ304027A NZ304027A (en) 1995-03-16 1996-03-15 Once a month injectable contraceptive comprising an estrogenic and gestagenic component for contraception and simultaneous hormone replacement therapy
CZ972896A CZ289697A3 (en) 1995-03-16 1996-03-15 Injection administered once a month as a depot contraception and for hormonal substitution therapy for women in perimenstrual and premenstrual pause
IL11751696A IL117516A (en) 1995-03-16 1996-03-17 Injectable composition containing an oestrogenic component and a gestagenic component
ZA962177A ZA962177B (en) 1995-03-16 1996-03-18 Once-a-month injectable composition as a depot contraceptive and for hormone replacement therapy for peri- and pre-menopausal women
NO974255A NO974255L (en) 1995-03-16 1997-09-15 Preparation for once-daily injection month and useful as a depot contraceptive and in hormone replacement therapy for perimenopausal and premenopausal women
US09/348,232 US20010006963A1 (en) 1995-03-16 1999-07-06 Once-a-month injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women
US10/062,569 US20020193358A1 (en) 1995-03-16 2002-02-05 Once-a-month injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19510861A DE19510861A1 (en) 1995-03-16 1995-03-16 One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women

Publications (1)

Publication Number Publication Date
DE19510861A1 true DE19510861A1 (en) 1996-09-19

Family

ID=7757668

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19510861A Withdrawn DE19510861A1 (en) 1995-03-16 1995-03-16 One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women

Country Status (17)

Country Link
EP (1) EP0814811A1 (en)
JP (1) JPH11501649A (en)
KR (1) KR19980703058A (en)
AR (1) AR002283A1 (en)
AU (1) AU713258B2 (en)
CA (1) CA2215382A1 (en)
CZ (1) CZ289697A3 (en)
DE (1) DE19510861A1 (en)
HU (1) HUP9801691A3 (en)
IL (1) IL117516A (en)
MX (1) MX9707009A (en)
NO (1) NO974255L (en)
NZ (1) NZ304027A (en)
PL (1) PL322202A1 (en)
SK (1) SK123997A3 (en)
WO (1) WO1996028165A1 (en)
ZA (1) ZA962177B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0000313D0 (en) 2000-01-10 2000-03-01 Astrazeneca Uk Ltd Formulation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4826831A (en) * 1983-08-05 1989-05-02 Pre Jay Holdings Limited Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens

Also Published As

Publication number Publication date
AU5110896A (en) 1996-10-02
WO1996028165A1 (en) 1996-09-19
CZ289697A3 (en) 1997-12-17
HUP9801691A3 (en) 1999-03-01
KR19980703058A (en) 1998-09-05
ZA962177B (en) 1996-07-29
CA2215382A1 (en) 1996-09-19
NO974255L (en) 1997-11-14
MX9707009A (en) 1997-11-29
IL117516A0 (en) 1996-07-23
IL117516A (en) 2000-07-26
AU713258B2 (en) 1999-11-25
JPH11501649A (en) 1999-02-09
SK123997A3 (en) 1998-02-04
NO974255D0 (en) 1997-09-15
EP0814811A1 (en) 1998-01-07
NZ304027A (en) 2000-05-26
PL322202A1 (en) 1998-01-19
HUP9801691A2 (en) 1998-11-30
AR002283A1 (en) 1998-03-11

Similar Documents

Publication Publication Date Title
DE3916112C2 (en)
EP0499348B1 (en) Ovulation-inhibiting agent for hormonal contraception
DE69003015T4 (en) Treatment of postmenopausal disorders.
EP0735881B1 (en) Means and method for hormonal contraception and/or the treatment of acne
DE69118494T2 (en) Contraception procedure and scheme
EP0735883B1 (en) Composition for contraception comprising an estrogen and a gestagen
DE69804918T2 (en) Very low-dose oral contraceptive with less menstrual bleeding and delayed effects
DE69532894T2 (en) CONCEPT PREVENTION PROCEDURE
EP0770388B1 (en) Multiphase contraceptive preparation based on natural estrogens
EP0628312B1 (en) Anti-contraceptive composition
EP0148724B1 (en) Sequential combined multiphase preparation and its use for oral contraception
EP0835114B1 (en) Pharmaceutical combined preparation, kit and method for hormonal contraception
EP0750501B1 (en) Combined hormonal contraception pharmaceutical preparation
EP1310257A2 (en) Hormonal contraceptive combination
DE69729956T2 (en) ORAL, ONE-STEP CONCEPT PREVENTION METHOD AND COMBINATION PRODUCT CONTAINING THE STAGE AND ESTROGEN
DE69327319T2 (en) MINIMIZATION OF BREAST BLEEDING PROGESTERONE BLEED
DE4330234A1 (en) The use of progestogens and competitive progesterone antagonists for the production of pharmaceuticals for female fertility control and compositions comprising a progestogen and a competitive progesterone antagonist
DE69721314T2 (en) HORMONE COMPOSITION WHICH CONTAINS AN ESTROGEN AGENT AND A PROGESTATIVE AGENT
EP0651644A1 (en) Ovulation inhibitor for hormonal contraception
DE19513662A1 (en) Combined pharmaceutical preparation for hormonal contraception
DE602004009288T2 (en) USE OF A COMBINATION OF AN AROMATASE HEATHER, A PROGESTINE AND AN ESTROGEN FOR THE TREATMENT OF ENDOMETRIOSIS
DE3787386T2 (en) Composition to be used in the treatment of estrogen insufficiency.
DE69827017T2 (en) COMBINATIONS OF ENDOMETRICALLY PROTECTED AND ENDOMETRICALLY ATROPHOSED AGENTS WITH ESTROGENIC IN ORAL CONCENTRATION PREVENTION
DE19510861A1 (en) One-month injection as a depot contraceptive and for hormone replacement therapy for peri- and premenopausal women
DE4405591C1 (en) Postmenopausal hormone substitution

Legal Events

Date Code Title Description
8141 Disposal/no request for examination
8110 Request for examination paragraph 44
8170 Reinstatement of the former position
8130 Withdrawal