WO1995007081A1 - Preparation for substitution therapy, containing at least one progestogen and at least one extrogen - Google Patents

Preparation for substitution therapy, containing at least one progestogen and at least one extrogen Download PDF

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Publication number
WO1995007081A1
WO1995007081A1 PCT/EP1994/002997 EP9402997W WO9507081A1 WO 1995007081 A1 WO1995007081 A1 WO 1995007081A1 EP 9402997 W EP9402997 W EP 9402997W WO 9507081 A1 WO9507081 A1 WO 9507081A1
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WO
WIPO (PCT)
Prior art keywords
day
preparation
progestogen
estrogen
dose
Prior art date
Application number
PCT/EP1994/002997
Other languages
French (fr)
Inventor
Philippe Robert Marie Wilhelmus Ghislain KONINCKX
Original Assignee
Saturnus 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 Saturnus Ag filed Critical Saturnus Ag
Priority to JP7508461A priority Critical patent/JPH09502194A/en
Priority to KR1019960701195A priority patent/KR960704553A/en
Priority to AU76952/94A priority patent/AU708881B2/en
Priority to DE69432752T priority patent/DE69432752T2/en
Priority to EP94927583A priority patent/EP0717626B1/en
Priority to CA002171460A priority patent/CA2171460C/en
Priority to US08/605,118 priority patent/US5827843A/en
Priority to AT94927583T priority patent/ATE241362T1/en
Priority to HU9600592A priority patent/HU224818B1/en
Publication of WO1995007081A1 publication Critical patent/WO1995007081A1/en
Priority to FI961098A priority patent/FI961098A/en

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    • 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
    • A61P15/18—Feminine contraceptives

Definitions

  • the present invention relates to a preparation for substitution therapy and for oral contraception. More particularly the present invention on the one hand relates to relieving the effects which occur because the ovaries decrease or stop production of female hormones, for instance during the menopause.
  • the substitution therapy is mainly intended to induce amenorrhoea with negligible blood loss.
  • substitution therapy comprising a hormone treatment with one or more oestrogens and one or more progestogens.
  • oestrogens and progestogens are administered, but such a treatment is ineffective in respect of the decalcification and heart and blood vessel disorders.
  • oestrogens and progestogens are administered continuousl y such that the endometrium does not proliferate.
  • This therapy has the drawback however of an unacceptably high incidence of slight, irregular blood loss.
  • the present invention has for its object to provide a substitution therapy wherein the above described drawbacks occur to a much lesser extent, with the objective of inducing amenorrhoea with negligible blood loss over a long period (many months to years).
  • the present invention relates to preparations designed for oral contraception with substantially continuous application.
  • the preparations according to the present invention are designed to induce menstrual bleeding with a regular menstrual bleeding, with an extended cycle or eventually a constant amenorrhoea, but characterized by an optimal (cycle) control and/or by a substantially reduced ocurrence of intermediate bleeding.
  • EP-A-559 240 discloses preparations for substitution therapy and oral contraception in which the estrogen dose is constant and the progestagen dose is periodically alternated. However, the improvement in inhibiting endometrium bleeding is minor. Above that, since the use of higher progestagen doses provided better results than lower doses it appears illogical to use periodically varying estrogen doses.
  • the present invention is based on the finding that suprisingly when using periodically varying estrogen doses the occurence of blood loss and intermediate bleeding is substantially avoided.
  • the estrogen dose is herein oscillated such that estrogen-dominant and progestogen-dominant periods occur alternatingly with a sufficiently short periodicity. This short periodicity in the estrogen dose is necessary to avoid blood loss.
  • the invention therefore relates to a preparation for substitution therapy and for oral contraception comprising at least one progestogen and at least one estrogen in which the estrogen dose varies with a periodicity such that blood loss is substantially avoided.
  • the preparation is formulated such that a substantially constant blood concentration is obtained for progestogen or estrogen, while the estrogen concentration in the blood varies between two blood concentrations.
  • the periodicity must be sufficiently short and is generally less than 10 days.
  • the periodicity is usually less than 7 days.
  • the periodicity generally lies between 2-9 days, preferably between 2-6 days. It will however be apparent that the periodicity is dependent on the estrogens and progestogens used and the applied doses. Both the periodicity and concentrations of estrogen and progestogen are easy to determine by routine experimentation.
  • the preparation contains a constant progestogen dose, while the estrogen dose oscillates between two levels. This preparation is recommended because there is a greater certainty of avoiding blood loss over a longer period.
  • the preparation contains oscillating doses of progestogen and estrogen, in varying ratios however such that blood loss is avoided and amenorrhoea is induced.
  • progestogens such as progesterone 300-900 mg/day norethisterone acetate 2-5 mg/day medroxyprogesterone acetate 1-5 mg/day d-norgestrel 30-150 ⁇ gr/day desogestrel 30-150 ⁇ gr/day norgestimate 30-150 ⁇ gr/day cyproterone acetate 0.2-2 mg/day, gestodene 10-150 ⁇ g/day
  • progestogen and estrogen depends on the person (constitution and age), the progestogen(s) and estrogen(s), anti-progestogen and anti-estrogen for use and the form of administering same.
  • the progestogen and estrogen can each be present in an oral, transdermal, parenteral or implantable application form for substitution therapy.
  • the preparation can for instance comprise an application form which contains the progestogen and estrogen, and a second like application form which contains the progestogen and an increased dose of estrogen.
  • the progestogen and estrogen can of course be present in like but separate forms of application or in mutually differing forms of application.
  • the progestogen can for instance be an implantable application form while the oestrogen is administered orally, transdermally or parenterally in a dose which takes account of the required time period according to the invention.
  • the oral application form to be used comprises tablets, capsules, syrup, solutions.
  • the transdermal forms of application comprise gels, plasters. Strips can for instance be used wherein tablets with progestogen and oestrogen in the desired ratio and periodicity are arranged in time sequence.
  • the parenteral application form comprises injection fluid and the like.
  • the implantable application form comprises for example a known implantable sustained release preparation.
  • the preparations for oral contraceptive comprise estrogens and progestogens in common form.
  • Preparations according to the invention were administered over a period of 3-12 months to 40 women in the menopause.
  • a constant amenorrhoea could be obtained in the case of more than 90% of the women, wherein the clinical tolerance was perceived as optimal, wherein the woman did not discern any subjective difference between a fixed or changing oestrogen dose with a periodicity of about one week.
  • Using the preparations according to the invention as oral contraceptive intermediate bleeding will be substantially reduced.
  • a preparation according to the invention comprised tablets of the type A which contained 10 gamma aethinyl- estradiol, 1 mg estradiol valerianate and 0.5 mg norethisterone, and tablets of the type B which contained 15 gamma instead of 10 gamma aethinyl-estradiol.
  • a preparation according to the invention contained 1 mg norethisterone or 0.5 mg cyproterone acetate and 2 mg estradiol valerianate.
  • the preparation moreover contained tablets of the type B having 3 mg instead of 2 mg estradiol valerianate.
  • Example 3 A preparation according to the invention comprised tablets of the type A which contained 15 gamma aethinyl- estradiol and 1 mg oestradiol valerianate and 1 mg norethisterone.
  • the preparation moreover contained tablets of the type B having 1.5 mg instead of 1 mg norethisterone.
  • a preparation according to the invention for oral contraceptive with optimal cycle control comprises tablets of type A comprising 20 ⁇ g aethinyl-estradiol and 75 ⁇ g gestoden.
  • the preparation contained tablets of type B comprising 30 ⁇ g instead of 20 ⁇ g aethinyl-estradiol. Tablets A and B are used in four alternating periods of six days.
  • Example 5
  • a preparation according to the invention for oral contraceptive with optimal cycle control comprises tablets of type A comprising 15 ⁇ g aethinyl-estradiol and 75 ⁇ g gestoden, and tablets of type B comprising 25 ⁇ g instead of 15 ⁇ g aethinyl-estradiol. Tablets A and B are used in six alternating periods of four days.
  • aethinyl-estradiol is used in order to use a estrogen dose which is as low as possible. However, higher estrogen doses may be used. Instead of using a constant progestogen dose fluctuating doses may be use fluctuating simultaneously and/or progressively in view of the varying estrogen dose.
  • a preparation for oral contraceptive according to the invention comprises tablets of type A comprising 20 ⁇ g aethinyl-estradiol and 75 ⁇ g gestoden, and tablets of type B comprising 30 ⁇ g aethinyl-estradiol and 75 ⁇ g gestoden and 50 ⁇ g onapristone.
  • the tablets A and B are used in four alternating periods of each six days. After four periods the whole cycle is repeated without allowing a free period.
  • a preparation according to the invention for hormone substitution treatment comprises tablets of type A comprising 2 ⁇ g estradiol valerianate and 50 ⁇ g gestoden.
  • the tablets of type B comprised 3 ⁇ g estradiol valerianate and 25-100 ⁇ g onapristone.
  • antiprogestagen is added in a constant dose to the actual and the above mentioned combinations of estrogens and progestagens in products for hormone replacement therapy and for contraception.

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

Abstract

The invention relates to a preparation for substitution therapy and oral contraception comprising at least one progestogen and at least one estrogen in which the estrogen dose varies with a periodicity such that blood loss is substantially avoided, wherein the periodicity is preferably less than 10 days, more preferably less than 7 days, such as preparations containing the progestogen and/or estrogen in an oral, transdermal, parenteral and/or implantable application form.

Description

PREPARATION FOR SUBSTITUTION THERAPY, CONTAINING AT LEAST ONE PROGESTOGEN AND AT LEAST ONE ESTROGEN.
The present invention relates to a preparation for substitution therapy and for oral contraception. More particularly the present invention on the one hand relates to relieving the effects which occur because the ovaries decrease or stop production of female hormones, for instance during the menopause. The substitution therapy is mainly intended to induce amenorrhoea with negligible blood loss.
During and after the menopause these effects comprise hot flushes and nocturnal sweating, atrophy of the vagina which can result in sexual difficulties, bone decalcification, increase in heart and blood vessel disorders and psychic symptoms with a causal connection that is usually difficult to demonstrate.
Up to the present different types of substitution therapy have been applied comprising a hormone treatment with one or more oestrogens and one or more progestogens.
According to a first therapy, low doses of oestrogens and progestogens are administered, but such a treatment is ineffective in respect of the decalcification and heart and blood vessel disorders.
In another therapy the natural cycle of oestrogen and progestogen is followed as closely as possible. This treatment inevitably results in menstruation and has the advantage of a reduced risk of cancer of the uterus. According to yet another therapy only oestrogens are administered in a dose which lies below the threshold for menstrual bleeding. This treatment has the drawback however of an increased risk of cancer of the uterus.
According to a most recently known therapy oestrogens and progestogens are administered continuously such that the endometrium does not proliferate. This therapy has the drawback however of an unacceptably high incidence of slight, irregular blood loss. The present invention has for its object to provide a substitution therapy wherein the above described drawbacks occur to a much lesser extent, with the objective of inducing amenorrhoea with negligible blood loss over a long period (many months to years).
On the other hand, the present invention relates to preparations designed for oral contraception with substantially continuous application.
In continuous application of oral contraceptive frequently intermediate bleedings occur. The preparations according to the present invention are designed to induce menstrual bleeding with a regular menstrual bleeding, with an extended cycle or eventually a constant amenorrhoea, but characterized by an optimal (cycle) control and/or by a substantially reduced ocurrence of intermediate bleeding.
EP-A-559 240 discloses preparations for substitution therapy and oral contraception in which the estrogen dose is constant and the progestagen dose is periodically alternated. However, the improvement in inhibiting endometrium bleeding is minor. Above that, since the use of higher progestagen doses provided better results than lower doses it appears illogical to use periodically varying estrogen doses.
The present invention is based on the finding that suprisingly when using periodically varying estrogen doses the occurence of blood loss and intermediate bleeding is substantially avoided. The estrogen dose is herein oscillated such that estrogen-dominant and progestogen-dominant periods occur alternatingly with a sufficiently short periodicity. This short periodicity in the estrogen dose is necessary to avoid blood loss.
Purely by administering a dose of progestogen or estrogen substantially constant in time and an estrogen or progestogen varying in time between at least two dose levels, it was possible to induce the desired amenorrhoea while no blood loss occurred over a longer period.
The invention therefore relates to a preparation for substitution therapy and for oral contraception comprising at least one progestogen and at least one estrogen in which the estrogen dose varies with a periodicity such that blood loss is substantially avoided.
It is noted that the preparation is formulated such that a substantially constant blood concentration is obtained for progestogen or estrogen, while the estrogen concentration in the blood varies between two blood concentrations. The periodicity must be sufficiently short and is generally less than 10 days. The periodicity is usually less than 7 days. The periodicity generally lies between 2-9 days, preferably between 2-6 days. It will however be apparent that the periodicity is dependent on the estrogens and progestogens used and the applied doses. Both the periodicity and concentrations of estrogen and progestogen are easy to determine by routine experimentation. According to an embodiment of the invention the preparation contains a constant progestogen dose, while the estrogen dose oscillates between two levels. This preparation is recommended because there is a greater certainty of avoiding blood loss over a longer period. According to another embodiment the preparation contains oscillating doses of progestogen and estrogen, in varying ratios however such that blood loss is avoided and amenorrhoea is induced.
Use can be made in general of all known progestogens, such as progesterone 300-900 mg/day norethisterone acetate 2-5 mg/day medroxyprogesterone acetate 1-5 mg/day d-norgestrel 30-150 μgr/day desogestrel 30-150 μgr/day norgestimate 30-150 μgr/day cyproterone acetate 0.2-2 mg/day, gestodene 10-150 μg/day
3-ketodesogestrel 10-150 μg/day drospirenon 0.2-3.0 mg/day or combinations thereof. It is noted that the preparation can contain one or more progestogens and estrogens.
It will be apparent that the quantity of progestogen and estrogen depends on the person (constitution and age), the progestogen(s) and estrogen(s), anti-progestogen and anti-estrogen for use and the form of administering same.
The progestogen and estrogen can each be present in an oral, transdermal, parenteral or implantable application form for substitution therapy. The preparation can for instance comprise an application form which contains the progestogen and estrogen, and a second like application form which contains the progestogen and an increased dose of estrogen. The progestogen and estrogen can of course be present in like but separate forms of application or in mutually differing forms of application. The progestogen can for instance be an implantable application form while the oestrogen is administered orally, transdermally or parenterally in a dose which takes account of the required time period according to the invention.
The oral application form to be used comprises tablets, capsules, syrup, solutions. The transdermal forms of application comprise gels, plasters. Strips can for instance be used wherein tablets with progestogen and oestrogen in the desired ratio and periodicity are arranged in time sequence. The parenteral application form comprises injection fluid and the like. The implantable application form comprises for example a known implantable sustained release preparation. The preparations for oral contraceptive comprise estrogens and progestogens in common form.
Preparations according to the invention were administered over a period of 3-12 months to 40 women in the menopause. By making use of the combination preparations according to the invention a constant amenorrhoea could be obtained in the case of more than 90% of the women, wherein the clinical tolerance was perceived as optimal, wherein the woman did not discern any subjective difference between a fixed or changing oestrogen dose with a periodicity of about one week. Using the preparations according to the invention as oral contraceptive intermediate bleeding will be substantially reduced. Example 1
A preparation according to the invention comprised tablets of the type A which contained 10 gamma aethinyl- estradiol, 1 mg estradiol valerianate and 0.5 mg norethisterone, and tablets of the type B which contained 15 gamma instead of 10 gamma aethinyl-estradiol. By alternatingly administering the tablets A and B over a time period of 7 days an amenorrhoea could be induced without blood loss for a very long period of time.
Example 2
A preparation according to the invention contained 1 mg norethisterone or 0.5 mg cyproterone acetate and 2 mg estradiol valerianate. The preparation moreover contained tablets of the type B having 3 mg instead of 2 mg estradiol valerianate. By using the preparation with alternate administering (4-5 days) of the tablets A and B or B and A an amenorrhoea could be induced without blood loss for a longer period of time.
Example 3 A preparation according to the invention comprised tablets of the type A which contained 15 gamma aethinyl- estradiol and 1 mg oestradiol valerianate and 1 mg norethisterone. The preparation moreover contained tablets of the type B having 1.5 mg instead of 1 mg norethisterone. By alternatingly administering the tablets A and B with a periodicity of 4-7 days an amenorrhoea could be induced without blood loss for a very long period of time.
Example 4
A preparation according to the invention for oral contraceptive with optimal cycle control comprises tablets of type A comprising 20 μg aethinyl-estradiol and 75 μg gestoden. The preparation contained tablets of type B comprising 30 μg instead of 20 μg aethinyl-estradiol. Tablets A and B are used in four alternating periods of six days. Example 5
A preparation according to the invention for oral contraceptive with optimal cycle control comprises tablets of type A comprising 15 μg aethinyl-estradiol and 75 μg gestoden, and tablets of type B comprising 25 μg instead of 15 μg aethinyl-estradiol. Tablets A and B are used in six alternating periods of four days.
In example 4 and 5 only aethinyl-estradiol is used in order to use a estrogen dose which is as low as possible. However, higher estrogen doses may be used. Instead of using a constant progestogen dose fluctuating doses may be use fluctuating simultaneously and/or progressively in view of the varying estrogen dose.
Example 6
A preparation for oral contraceptive according to the invention comprises tablets of type A comprising 20 μg aethinyl-estradiol and 75 μg gestoden, and tablets of type B comprising 30 μg aethinyl-estradiol and 75 μg gestoden and 50 μg onapristone. The tablets A and B are used in four alternating periods of each six days. After four periods the whole cycle is repeated without allowing a free period.
Example 7
A preparation according to the invention for hormone substitution treatment comprises tablets of type A comprising 2 μg estradiol valerianate and 50 μg gestoden. The tablets of type B comprised 3 μg estradiol valerianate and 25-100 μg onapristone. By alternatingly admininstering the tablets A and B over a time period of seven days amennorrhoea could be induced without blood loss for a very long period of time.
It is obvious for a skilled person in the examples in association with intermittently given antiprogestogen or anti-estrogen can be alternated alone or simultaneous with estrogens and/or progestagens. For instance, the antiprogestagen is added in a constant dose to the actual and the above mentioned combinations of estrogens and progestagens in products for hormone replacement therapy and for contraception.
*****

Claims

1. Preparation for substitution therapy and for oral contraception comprising at least one progestogen and at least one estrogen in which the estrogen dose varies with a periodicity such that blood loss is substantially avoided.
2. Preparation as claimed in claim 1, wherein the periodicity is less than 10 days, preferably less than 7 days.
3. Preparation as claimed in claim 1 or 2, wherein the periodicity amounts to 2-9 days, preferably 2-6 days.
4. Preparation as claimed in claims 1-3, wherein the dose of progestogen is substantially constant and the dose of oestrogen oscillates.
5. Preparation as claimed in claims 1-3, wherein the dose of progestogen and the dose of estrogen oscillate in such a dose ratio, that blood loss is substantially avoided.
6. Preparation as claimed in claims 1-5, wherein the progestogen comprises progesterone 300-900 mg/day norethisterone acetate 0.2-5 mg/day medroxyprogesterone acetate 1-5 mg/day d-norgestrel 30-150 μgr/day desogestrel 30-150 μgr/day norgestimate 30-150 μgr/day cyproterone acetate 0.2-2 mg/day, gestodene 10-150 μg/day
3-ketodesogestrel 10-150 μg/day drospirenon 0.2-3.0 mg/day or combinations thereof.
7. Preparation as claimed in claims 1-6, wherein the oestrogen comprises aethinylestradiol 5-15 gamma/day oestradiol valerianate 1-4 mg/day oestradiol 1-2 mg/day conjugated oestrogen 0.3-1.25 mg/day oestriol 1-4 mg/day, or combinations thereof.
8. Preparation as claimed in claims 1-7, comprising anti-progestogen.
9. Preparation as claimed in claim 1-8, comprising anti-estrogen.
10. Preparation as claimed in claims 1-9, containing the progestogen and/or estrogen in an oral, transdermal, parenteral and/or implantable application form.
*****
PCT/EP1994/002997 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one extrogen WO1995007081A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
JP7508461A JPH09502194A (en) 1993-09-09 1994-09-08 Alternative therapeutic formulation comprising at least one progestogen and at least one estrogen
KR1019960701195A KR960704553A (en) 1993-09-09 1994-09-08 PREPARATION FOR SUBSTITUTION THERAPY CONTAINING AT LEAST ONE PROGESTOGEN AND AT LEAST ONE ESTROGEN
AU76952/94A AU708881B2 (en) 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one estrogen
DE69432752T DE69432752T2 (en) 1993-09-09 1994-09-08 COMPOSITION FOR SUBSTITUTION THERAPY THAT CONTAINS AT LEAST ONE PROGESTOGEN AND AT LEAST ONE OESTROGEN
EP94927583A EP0717626B1 (en) 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one extrogen
CA002171460A CA2171460C (en) 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one extrogen
US08/605,118 US5827843A (en) 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one estrogen
AT94927583T ATE241362T1 (en) 1993-09-09 1994-09-08 COMPOSITION FOR SUBSTITUTION THERAPY CONTAINING AT LEAST ONE PROGESTOGEN AND AT LEAST ONE ESTROGEN
HU9600592A HU224818B1 (en) 1993-09-09 1994-09-08 The use of progestogen and estrogen for manufacturing a pharmaceutical composition for substitution therapy and oral contraception
FI961098A FI961098A (en) 1993-09-09 1996-03-08 A method of making a progestogen and estrogen-containing substitute

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL9301562A NL9301562A (en) 1993-09-09 1993-09-09 Substitution therapy preparation.
NL9301562 1993-09-09

Publications (1)

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WO1995007081A1 true WO1995007081A1 (en) 1995-03-16

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PCT/EP1994/002997 WO1995007081A1 (en) 1993-09-09 1994-09-08 Preparation for substitution therapy, containing at least one progestogen and at least one extrogen

Country Status (12)

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US (1) US5827843A (en)
EP (1) EP0717626B1 (en)
JP (1) JPH09502194A (en)
KR (1) KR960704553A (en)
CN (1) CN1076969C (en)
AT (1) ATE241362T1 (en)
AU (1) AU708881B2 (en)
DE (1) DE69432752T2 (en)
FI (1) FI961098A (en)
HU (1) HU224818B1 (en)
NL (1) NL9301562A (en)
WO (1) WO1995007081A1 (en)

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WO1996032114A1 (en) * 1995-04-08 1996-10-17 Schering Aktiengesellschaft Combined hormonal contraception pharmaceutical preparation
WO1997001342A1 (en) * 1995-06-28 1997-01-16 Schering Aktiengesellschaft Pharmaceutical combined preparation, kit and method for hormonal contraception
WO1998004268A1 (en) * 1996-07-26 1998-02-05 American Home Products Corporation Oral contraceptive
US6133251A (en) * 1995-10-28 2000-10-17 Jenapharm Gmbh & Co. Kg Combination compound for contraception based on natural estrogen
WO2001052857A1 (en) * 2000-01-18 2001-07-26 Schering Aktiengesellschaft Drospirenone for hormone replacement therapy
WO1998004246A3 (en) * 1996-07-26 2002-09-26 American Home Products Corporation Triphasic contraceptive method and kit comprising a combination of a progestin and estrogen
US6787531B1 (en) 1999-08-31 2004-09-07 Schering Ag Pharmaceutical composition for use as a contraceptive
US6869941B2 (en) 2001-07-13 2005-03-22 Schering Ag Combination of drospirenone and an estrogen sulphamate for HRT
HRP20020666B1 (en) * 2000-01-18 2011-07-31 Bayer Schering Pharma Aktiengesellschaft Drospirenone for hormone replacement therapy
US8071577B2 (en) 2004-04-20 2011-12-06 Bayer Pharma Aktiengesellschaft Multi-phase contraceptive preparation based on a natural estrogen
US8153616B2 (en) 2005-10-17 2012-04-10 Bayer Pharma Aktiengesellschaft Combination preparation for oral contraception and oral therapy of dysfunctional uterine bleeding containing estradiol valerate and dienogest and method of using same
US8349820B2 (en) 2006-10-20 2013-01-08 Bayer Pharma Aktiengesellschaft Use of estradiol valerate or 17β-estradiol in combination with dienogest for oral therapy to maintain and/or increase feminine libido

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DE19549264A1 (en) * 1995-12-23 1997-06-26 Schering Ag Contraception procedure and kit
US6506390B2 (en) 1996-06-25 2003-01-14 Akzo Nobel Progestogen-anti-progestogen regimens
US20020132801A1 (en) * 2001-01-11 2002-09-19 Schering Aktiengesellschaft Drospirenone for hormone replacement therapy
US20010034340A1 (en) * 2000-03-20 2001-10-25 American Home Products Corporation Hormone replacement therapy
DE10045380A1 (en) * 2000-09-14 2002-04-04 Schering Ag Contraception procedure and dosage form
EP1857110A3 (en) * 2001-03-16 2008-08-06 Wyeth Hormone replacement therapy
CA2441152A1 (en) * 2001-03-16 2002-09-26 Wyeth Hormone replacement therapy
US20030004145A1 (en) 2001-05-16 2003-01-02 Leonard Thomas W. Treatment of conditions relating to hormone deficiencies by administration of progestins
PT1390040E (en) * 2001-05-18 2007-04-30 Pantarhei Bioscience Bv Pharmaceutical composition for use in hormone replacement therapy
EP1260225A1 (en) * 2001-05-18 2002-11-27 Pantarhei Bioscience B.V. A pharmaceutical composition for use in hormone replacement therapy
DK1390042T3 (en) * 2001-05-23 2008-03-31 Pantarhei Bioscience Bv System for administering a drug comprising tetrahydroxylated estrogen for use in hormonal contraception
US7871995B2 (en) * 2001-05-23 2011-01-18 Pantarhei Bioscience B.V. Drug delivery system comprising a tetrahydroxylated estrogen for use in hormonal contraception
WO2003018026A1 (en) * 2001-08-31 2003-03-06 Pantarhei Bioscience B.V. Use of estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy
US8026228B2 (en) * 2001-11-15 2011-09-27 Pantarhei Bioscience B.V. Estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy
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WO1996032114A1 (en) * 1995-04-08 1996-10-17 Schering Aktiengesellschaft Combined hormonal contraception pharmaceutical preparation
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US6312722B1 (en) 1995-06-28 2001-11-06 Schering Aktiengesellschaft Pharmaceutical combined preparation, kit and method for hormonal contraception
US6133251A (en) * 1995-10-28 2000-10-17 Jenapharm Gmbh & Co. Kg Combination compound for contraception based on natural estrogen
WO1998004268A1 (en) * 1996-07-26 1998-02-05 American Home Products Corporation Oral contraceptive
WO1998004246A3 (en) * 1996-07-26 2002-09-26 American Home Products Corporation Triphasic contraceptive method and kit comprising a combination of a progestin and estrogen
US6787531B1 (en) 1999-08-31 2004-09-07 Schering Ag Pharmaceutical composition for use as a contraceptive
WO2001052857A1 (en) * 2000-01-18 2001-07-26 Schering Aktiengesellschaft Drospirenone for hormone replacement therapy
AU2001225413B2 (en) * 2000-01-18 2005-06-23 Bayer Schering Pharma Aktiengesellschaft Drospirenone for hormone replacement therapy
KR100747965B1 (en) * 2000-01-18 2007-08-08 바이엘 쉐링 파마 악티엔게젤샤프트 Drospirenone for hormone replacement therapy
KR100913910B1 (en) * 2000-01-18 2009-08-26 바이엘 쉐링 파마 악티엔게젤샤프트 Drospirenone for hormone replacement therapy
HRP20020666B1 (en) * 2000-01-18 2011-07-31 Bayer Schering Pharma Aktiengesellschaft Drospirenone for hormone replacement therapy
US6869941B2 (en) 2001-07-13 2005-03-22 Schering Ag Combination of drospirenone and an estrogen sulphamate for HRT
US8071577B2 (en) 2004-04-20 2011-12-06 Bayer Pharma Aktiengesellschaft Multi-phase contraceptive preparation based on a natural estrogen
US8153616B2 (en) 2005-10-17 2012-04-10 Bayer Pharma Aktiengesellschaft Combination preparation for oral contraception and oral therapy of dysfunctional uterine bleeding containing estradiol valerate and dienogest and method of using same
US8349820B2 (en) 2006-10-20 2013-01-08 Bayer Pharma Aktiengesellschaft Use of estradiol valerate or 17β-estradiol in combination with dienogest for oral therapy to maintain and/or increase feminine libido

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EP0717626A1 (en) 1996-06-26
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ATE241362T1 (en) 2003-06-15
HUT74452A (en) 1996-12-30
HU9600592D0 (en) 1996-05-28
AU708881B2 (en) 1999-08-12
FI961098A0 (en) 1996-03-08
FI961098A (en) 1996-04-03
HU224818B1 (en) 2006-02-28
EP0717626B1 (en) 2003-05-28
DE69432752D1 (en) 2003-07-03
US5827843A (en) 1998-10-27
KR960704553A (en) 1996-10-09

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