US20110172197A1 - Dosace Form For Hormonal Contraceptive - Google Patents

Dosace Form For Hormonal Contraceptive Download PDF

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Publication number
US20110172197A1
US20110172197A1 US13/070,205 US201113070205A US2011172197A1 US 20110172197 A1 US20110172197 A1 US 20110172197A1 US 201113070205 A US201113070205 A US 201113070205A US 2011172197 A1 US2011172197 A1 US 2011172197A1
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Prior art keywords
hormone
daily units
dosage form
folic acid
form according
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US13/070,205
Inventor
Georg Schramm
Eric-Paul Paques
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Gruenenthal GmbH
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Gruenenthal GmbH
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Priority claimed from DE102004026670A external-priority patent/DE102004026670A1/en
Application filed by Gruenenthal GmbH filed Critical Gruenenthal GmbH
Priority to US13/070,205 priority Critical patent/US20110172197A1/en
Publication of US20110172197A1 publication Critical patent/US20110172197A1/en
Abandoned legal-status Critical Current

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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
    • 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 a dosage form for hormonal contraception containing a given number of hormone-containing daily units and a given number of hormone-free daily units for uninterrupted daily oral administration to women, characterized in that the hormone-containing daily units contain folic acid in a daily amount of at most 200 ⁇ g and the hormone-free daily units in each case contain folic acid in a daily amount of >200 ⁇ g up to the maximum permissible amount of folic acid for women.
  • the combination of hormonal contraceptives and folic acid is already known from WO 99/53910.
  • the amount of folic acid per daily dose of hormones merely matches the changes in a woman's folic acid requirements as she ages, and does not take account of the changes in folic acid requirements over a contraceptive-taking cycle.
  • the dosage form according to the invention for hormonal contraception containing a given number of hormone-containing daily units and a given number of hormone-free daily units for uninterrupted daily oral administration to women, characterized in that the hormone-containing daily units contain folic acid in a daily amount of at most 200 ⁇ g and the hormone-free daily units in each case contain folic acid in a daily amount of >200 ⁇ g up to the maximum permissible amount for women of folic acid.
  • hormone-containing daily units of the dosage form according to the invention may each comprise a daily amount of folic acid corresponding to this minimum effective daily amount of folic acid.
  • the hormone-containing daily units of the dosage form according to the invention contain 0 to 200 ⁇ g of folic acid, particularly preferably 5 to 200 ⁇ g of folic acid.
  • the hormone-containing daily units of the dosage form according to the invention may also not contain any additional folic acid, however.
  • the hormone-free daily units of the folic acid dosage form according to the invention contain folic in an amount of more that 200 ⁇ g up to the maximum permissible daily amount of folic acid for women, preferably up to 5 mg of folic acid per daily unit, particularly preferably of more than 200 ⁇ g to 5 mg folic acid, very particularly preferably up to the maximum permissible daily amount of folic add for women of reproductive age.
  • folic acid By adding folic acid to the hormone-free daily units of the dosage form according to the invention in amounts of up to the maximum permissible amount, it is possible to increase the folic acid concentration in a woman's body while she is taking the hormone-free daily units to the extent that the her body's increased folic acid requirement is met as quickly as possible if she stops taking a hormone-containing contraceptive and then falls pregnant.
  • the hormone-containing daily units of the dosage form according to the invention preferably each contain the same amount of folic acid. This also applies to the hormone-free daily units, which likewise each contain the same amount of folic acid, this being greater than the amount contained in the hormone-containing daily units however.
  • the folic acid may also be present in the dosage form according to the invention as a pharmaceutically safe salt, preferably as sodium, potassium or magnesium salt, or as a corresponding derivative.
  • Suitable derivatives of folic acid are mono- or diesters, wherein the diesters may be differently or identically esterified.
  • Suitable ester groups are preferably C 1 -C 8 low alkyl groups, such as methyl, ethyl, propyl or butyl, branched C 1 -C 8 low alkyl groups, such as isopropyl, isobutyl or sec.-butyl, cycloalkyl groups, such as cyclopentyl or cyclohexyl, aryl groups, such as phenyl or substituted phenyl with 1-2 substituents, such as low alkyl or haloalkoxyl groups, or arylalkyl groups with C 1 -C 8 alkyl and aryl groups, such as phenyl or substituted phenyl.
  • hormone-free daily units and optionally the hormone-containing daily units may contain further vitamins or minerals in addition to the folic acid.
  • the number of daily units of a dosage form according to the invention may correspond to a natural, monthly menstrual cycle.
  • the dosage form according to the invention contains 21 to 25 hormone-containing daily units and 7 to 3 hormone-free daily units.
  • a dosage form according to the invention may contain hormone-containing daily units to be taken without interruption for up to 2 years, preferably up to 1 year, and 7 to 3 hormone-free daily units.
  • the dosage form according to the invention may comprise 42 to 52 or 77 to 193 hormone-containing daily units alongside 7 to 3 hormone-free daily units.
  • the hormone-containing daily units of the dosage form according to the invention may each contain at least one contraceptively acting hormone component, preferably a combination of hormone components such as an oestrogen and a gestagen.
  • Oestrogens which are suitable for the hormone-containing daily units of the dosage form according to the invention are preferably selected from the group comprising oestradiol, oestradiol valerate, ethinyloestradiol and mestranol. Ethinyloestradiol is particularly preferred as the oestrogen for the dosage form according to the invention.
  • Gestagens which are suitable for the hormone-containing daily units of the dosage form according to the invention are preferably selected from the group comprising norethisterone, norethisterone acetate, norethisterone enantate, norgestimate, norgestrel, levonorgestrel, gestodene, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, lynestrenol, cyproterone acetate, drospirenone, dienogest, desogestrel, progesterone, dydrogesterone, medrogestone, ethynodiol, promegestone, nomegestrol acetate and trimegestone.
  • the hormones are preferably used in the amounts stated below.
  • Oestrogens Oestradiol, oestradiol valerate 0.5 to 4 mg Ethinyloestradiol 5 to 50 ⁇ g Mestranol 8 to 70 ⁇ g
  • Gestagens Norethisterone, norethisterone acetate 0.5 to 1.0 mg Norgestimate 0.1 to 0.25 mg Norgestrel 0.3 to 1.0 mg Levonorgestrel 0.05 to 0.15 mg Gestodene 0.05 to 0.12 mg Hydroxyprogesterone caproate 10 to 800 mg Medroxyprogesterone acetate 2.5 to 40 mg Megestrol acetate 1.0 to 10 mg Chlormadinone acetate 0.5 to 10 mg Lynestrenol 0.4 to 3 mg Cyproterone acetate 0.5 to 10 mg Drospirenone 1.0 to 10 mg Dienogest 1.0 to 10 mg Desogestrel 0.06 to 0.30 mg Progesterone 100 to 1000 mg Dydrogesterone 5 to 50 mg Medrogestone 2 to 30 mg Ethynodiol, ethynodiol diacetate 0.4 to 3 mg Promegestone 0.5 to 10 mg Nomegestrol acetate 0.5 to 10 mg Trimegestone 1
  • the dosage forms according to the invention especially the hormone-containing daily units, preferably comprise the following hormone combinations:
  • the dosage form according to the invention provides a multiphasic hormone combination
  • the hormone-containing daily units be taken without interruption only for a period of 21 to 25 days, followed by 7 to 3 days of taking hormone-free daily units.
  • the dosage form according to the invention preferably comprises at least 21, preferably 21 to 25, hormone-containing daily units which preferably include 5 to 30 ⁇ g of ethinyloestradiol and 0.5 to 5 mg of chlormadinone acetate, and 3 to 7 hormone-free daily units.
  • hormone-containing daily units preferably include 5 to 30 ⁇ g of ethinyloestradiol and 0.5 to 5 mg of chlormadinone acetate, and 3 to 7 hormone-free daily units.
  • the dosage form according to the invention may also comprise hormone-containing daily units for several years, preferably of 42 to 365 units, which contain the stated hormone combination in the stated ranges, wherein the corresponding uninterrupted tablet-taking periods are followed by 7 to 3 hormone-free daily units with an elevated amount of folic acid stated according to the invention.
  • the hormone-containing daily units of the dosage form according to the invention may take the form of a monophasic (one-phase) or multiphasic contraceptive.
  • a multiphasic contraceptive a two-phase or a three-phase pill may be present, which is not usually suitable, however, to be taken for a period longer than a woman's natural cycle.
  • the dosage form according to the invention may also be a constituent of a kit, wherein the kit according to the invention may comprise a plurality of the dosage forms according to the invention, especially if one dosage form comprises only one monthly cycle.
  • the kit may optionally include a calendar or a diary.
  • Ethinyloestradiol (EE) and povidone K30 polyvinylpyrrolidone were dissolved in 600 ml of ethanol.
  • lactose and maize starch were mixed in a mixer/pelletiser (Diosna P25) for 5 mins. and then moistened thoroughly and mixed with the ethanolic EE/PVP solution.
  • the moist composition was forced through a 3 mm screen and dried in a vacuum drying cabinet.
  • the dried granular product was disagglomerated through a 0.6 mm screen, mixed with magnesium stearate and highly disperse silicon dioxide and pressed on a tablet press with 5 mm punches into tablets with a weight of 50 mg.
  • hormone-free, folic acid-containing tablets with a weight of 50 mg were produced, wherein the sodium salt of the folic acid was dissolved in 600 ml of aqueous ethanol.
  • the tablets were coated with a methylhydroxypropylcellulose-based coating (e.g. Opadry YS-1-2184 made by Colorcon), coating composition 2 mg per tablet, and packaged into a dosage form comprising 120 hormone-containing daily units without folic acid and 7 hormone-free daily units with folic acid.
  • a methylhydroxypropylcellulose-based coating e.g. Opadry YS-1-2184 made by Colorcon

Abstract

A dosage form for hormonal contraception containing a given number of hormone-containing daily units and a given number of hormone-free daily units for daily, oral administration, where the hormone-containing daily units each contain at most the minimum effective daily amount of folic acid for women and the hormone-free daily units contain at least a multiple of this amount up to the maximum permissible amount of folic acid for women.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application is a Continuation in Part Application of U.S. patent application Ser. No. 11/009,817, still pending.
  • This application claims priority from German Patent Application No. 10 2004 026 671.9 filed May 28, 2004, German Patent Application No. 10 2004 026 670.0 filed May 28, 2004, pending U.S. application Ser. No. 11/009,817 and pending U.S. application Ser. No. 11/009,938.
    • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention
  • The present invention relates to a dosage form for hormonal contraception containing a given number of hormone-containing daily units and a given number of hormone-free daily units for uninterrupted daily oral administration to women, characterized in that the hormone-containing daily units contain folic acid in a daily amount of at most 200 μg and the hormone-free daily units in each case contain folic acid in a daily amount of >200 μg up to the maximum permissible amount of folic acid for women.
  • It is suspected that long-term taking of gestagen-based hormonal contraceptives may lead to a deficiency of folic acid. This deficiency may lead to cardiovascular diseases, for example.
  • It is also known that if pregnancy occurs a short time after stopping taking such hormonal contraceptives, there is a risk that the deficiency of folic acid may lead to neural tube defects in the embryo. Since the neural tube develops in the first weeks of pregnancy, it is particularly advantageous to ensure that folic acid is taken prior to conception.
  • If, therefore, a woman stops taking hormonal contraceptives because she wants to have a child and she falls pregnant in the first cycle after stopping the hormonal contraceptives, it is particularly important to ensure an appropriately high level of folic acid in the period directly after stopping taking the “Pill”, as hormonal contraceptives are known.
  • There is therefore a need to add folic acid to hormonal contraceptives in such a way that the added folic acid is adapted to a woman's varying needs over the period during and after a tablet-taking cycle.
  • 2. Brief Description of Related Developments
  • The combination of hormonal contraceptives and folic acid is already known from WO 99/53910. The amount of folic acid per daily dose of hormones merely matches the changes in a woman's folic acid requirements as she ages, and does not take account of the changes in folic acid requirements over a contraceptive-taking cycle.
    • SUMMARY OF THE INVENTION
  • It was therefore the object of the present invention to provide a dosage form for hormonal contraception which takes account of the changes in folic acid requirements during a hormone-taking cycle and subsequent hormone-free daily units.
  • This object was achieved by providing the dosage form according to the invention for hormonal contraception containing a given number of hormone-containing daily units and a given number of hormone-free daily units for uninterrupted daily oral administration to women, characterized in that the hormone-containing daily units contain folic acid in a daily amount of at most 200 μg and the hormone-free daily units in each case contain folic acid in a daily amount of >200 μg up to the maximum permissible amount for women of folic acid.
  • Women of child-bearing age have a daily folic acid requirement which may be adequately met by a healthy diet. Long term taking of hormonal contraceptives containing gestagens may lead to an additional folic acid requirement, which may likewise be met by a healthy diet. However, it is advisable to provide women with a daily dose of the minimum effective daily amount of folic acid.
  • Accordingly, hormone-containing daily units of the dosage form according to the invention may each comprise a daily amount of folic acid corresponding to this minimum effective daily amount of folic acid. Preferably, the hormone-containing daily units of the dosage form according to the invention contain 0 to 200 μg of folic acid, particularly preferably 5 to 200 μg of folic acid.
  • The hormone-containing daily units of the dosage form according to the invention may also not contain any additional folic acid, however.
  • To ensure that a woman consumes the necessary amount of folic acid or that her increased folic acid requirement at least at the beginning of pregnancy is met as quickly as possible if she decides to try for a baby, so avoiding possible damage to the embryo due to a folic acid deficiency, the hormone-free daily units of the folic acid dosage form according to the invention contain folic in an amount of more that 200 μg up to the maximum permissible daily amount of folic acid for women, preferably up to 5 mg of folic acid per daily unit, particularly preferably of more than 200 μg to 5 mg folic acid, very particularly preferably up to the maximum permissible daily amount of folic add for women of reproductive age.
  • By adding folic acid to the hormone-free daily units of the dosage form according to the invention in amounts of up to the maximum permissible amount, it is possible to increase the folic acid concentration in a woman's body while she is taking the hormone-free daily units to the extent that the her body's increased folic acid requirement is met as quickly as possible if she stops taking a hormone-containing contraceptive and then falls pregnant.
  • The hormone-containing daily units of the dosage form according to the invention preferably each contain the same amount of folic acid. This also applies to the hormone-free daily units, which likewise each contain the same amount of folic acid, this being greater than the amount contained in the hormone-containing daily units however.
  • The folic acid may also be present in the dosage form according to the invention as a pharmaceutically safe salt, preferably as sodium, potassium or magnesium salt, or as a corresponding derivative.
  • Suitable derivatives of folic acid are mono- or diesters, wherein the diesters may be differently or identically esterified. Suitable ester groups are preferably C1-C8 low alkyl groups, such as methyl, ethyl, propyl or butyl, branched C1-C8 low alkyl groups, such as isopropyl, isobutyl or sec.-butyl, cycloalkyl groups, such as cyclopentyl or cyclohexyl, aryl groups, such as phenyl or substituted phenyl with 1-2 substituents, such as low alkyl or haloalkoxyl groups, or arylalkyl groups with C1-C8 alkyl and aryl groups, such as phenyl or substituted phenyl.
  • In addition, the hormone-free daily units and optionally the hormone-containing daily units may contain further vitamins or minerals in addition to the folic acid.
  • The number of daily units of a dosage form according to the invention may correspond to a natural, monthly menstrual cycle. In this case, the dosage form according to the invention contains 21 to 25 hormone-containing daily units and 7 to 3 hormone-free daily units.
  • However, it is also possible for the total number of hormone-containing daily units to correspond to more than a woman's natural monthly cycle, such that a dosage form according to the invention may contain hormone-containing daily units to be taken without interruption for up to 2 years, preferably up to 1 year, and 7 to 3 hormone-free daily units. However, it is also possible for the dosage form according to the invention to comprise 42 to 52 or 77 to 193 hormone-containing daily units alongside 7 to 3 hormone-free daily units.
  • The hormone-containing daily units of the dosage form according to the invention may each contain at least one contraceptively acting hormone component, preferably a combination of hormone components such as an oestrogen and a gestagen.
  • Oestrogens which are suitable for the hormone-containing daily units of the dosage form according to the invention are preferably selected from the group comprising oestradiol, oestradiol valerate, ethinyloestradiol and mestranol. Ethinyloestradiol is particularly preferred as the oestrogen for the dosage form according to the invention.
  • Gestagens which are suitable for the hormone-containing daily units of the dosage form according to the invention are preferably selected from the group comprising norethisterone, norethisterone acetate, norethisterone enantate, norgestimate, norgestrel, levonorgestrel, gestodene, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, lynestrenol, cyproterone acetate, drospirenone, dienogest, desogestrel, progesterone, dydrogesterone, medrogestone, ethynodiol, promegestone, nomegestrol acetate and trimegestone.
  • The hormones are preferably used in the amounts stated below.
  • Oestrogens:
    Oestradiol, oestradiol valerate 0.5 to 4 mg
    Ethinyloestradiol 5 to 50 μg
    Mestranol 8 to 70 μg
  • Gestagens:
    Norethisterone, norethisterone acetate 0.5 to 1.0 mg
    Norgestimate 0.1 to 0.25 mg
    Norgestrel 0.3 to 1.0 mg
    Levonorgestrel 0.05 to 0.15 mg
    Gestodene 0.05 to 0.12 mg
    Hydroxyprogesterone caproate 10 to 800 mg
    Medroxyprogesterone acetate 2.5 to 40 mg
    Megestrol acetate 1.0 to 10 mg
    Chlormadinone acetate 0.5 to 10 mg
    Lynestrenol 0.4 to 3 mg
    Cyproterone acetate 0.5 to 10 mg
    Drospirenone 1.0 to 10 mg
    Dienogest 1.0 to 10 mg
    Desogestrel 0.06 to 0.30 mg
    Progesterone 100 to 1000 mg
    Dydrogesterone 5 to 50 mg
    Medrogestone 2 to 30 mg
    Ethynodiol, ethynodiol diacetate 0.4 to 3 mg
    Promegestone 0.5 to 10 mg
    Nomegestrol acetate 0.5 to 10 mg
    Trimegestone 1 to 10 mg
    Etonogestrel 0.1 to 1 mg
    Norelgestromin 0.1 to 2 mg
    Norethynodrel 0.3 to 3 mg
    Tibolone 1 to 10 mg
  • The dosage forms according to the invention, especially the hormone-containing daily units, preferably comprise the following hormone combinations:
  • 1. 0.015 mg ethinyloestradiol+0.06 mg gestodene
    2. 0.02 mg ethinyloestradiol+0.15 mg desogestrel
    3. 0.02 mg ethinyloestradiol+0.5 mg norethisterone
    4. 0.02 mg ethinyloestradiol+1 mg chlormadinone acetate or 2 mg or 3 mg chlormadinone acetate
    5. 0.02 mg ethinyloestradiol+1 mg norethisterone
    6. 0.03 mg ethinyloestradiol+1 mg norethisterone
    7. 0.02 mg ethinyloestradiol+4 mg chlormadinone acetate
    8. 0.02 mg ethinyloestradiol+5 mg chlormadinone acetate
    9. 0.02 mg ethinyloestradiol+0.1 mg levonorgestrel
    10. 0.02 mg ethinyloestradiol+0.15 mg desogestrel
    11. 0.02 mg ethinyloestradiol+0.1 mg levonorgestrel
    12. 0.03 mg ethinyloestradiol+3 mg drospirenone
    13. 0.02 mg ethinyloestradiol+3 mg drospirenone
    14. 0.03 mg ethinyloestradiol+2 mg chlormadinone acetate
    15. 0.035 mg ethinyloestradiol+0.25 mg norgestimate
    16. 0.03 mg ethinyloestradiol+0.5 mg norethisterone
    17. 0.03 mg ethinyloestradiol+0.15 mg desogestrel
    18. 0.03 mg ethinyloestradiol+0.075 mg gestodene
    19. 0.03 mg ethinyloestradiol+0.15 mg levonorgestrel
    20. 0.03 mg ethinyloestradiol+0.15 mg desogestrel
    21. 0.03 mg ethinyloestradiol+0.15 mg levonorgestrel
    22. 0.03 mg ethinyloestradiol+0.125 mg levonorgestrel
    23. 0.0375 mg ethinyloestradiol+0.75 mg lynestrenol
    24. 0.03 mg ethinyloestradiol+1 mg norethisterone
    25. 0.03 mg ethinyloestradiol+0.5 mg norethisterone
    26. 0.03 mg ethinyloestradiol+0.15 mg levonorgestrel
    27. 0.04 mg ethinyloestradiol+2 mg lynestrenol
    28. 1st phase=7 days
      • 0.050 mg desogestrel+0.035 ethinyloestradiol
      • 2nd phase=7 days
      • 0.100 mg desogestrel+0.030 ethinyloestradiol
      • 3rd phase=7 days
      • 0.150 mg desogestrel+0.030 ethinyloestradiol
        29. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=5 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=10 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        30. 1st phase=7 days
      • 0.035 mg EE+0.180 mg norgestimate
      • 2nd phase=7 days
      • 0.035 mg EE+0.215 mg norgestimate
      • 3rd phase=7 days
      • 0.035 mg EE+0.250 mg norgestimate
        31. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=5 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=10 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        32. 1st phase=7 days
      • 0.035 mg EE+0.5 mg norethisterone
      • 2nd phase=9 days
      • 0.035 mg EE+1 mg norethisterone
      • 3rd phase=5 days
      • 0.035 mg EE+0.5 mg norethisterone
        33. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=5 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=10 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        34. 1st phase=7 days
      • 0.035 mg-EE+0.5 mg norethisterone
      • 2nd phase=7 days
      • 0.035 mg EE+0.75 mg norethisterone
      • 3rd phase=7 days
      • 0.035 mg EE+1 mg norethisterone
        35. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd chase=5 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=10 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        36. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=6 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=9 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        37. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=5 days
      • 0.05 mg EE+0.05 mg levonorgestrel
      • 3rd phase=10 days
      • 0.04 mg EE+0.125 mg levonorgestrel
        38. 1st phase=6 days
      • 0.03 mg EE+0.05 mg levonorgestrel
      • 2nd phase=5 days
      • 0.04 mg EE+0.075 mg levonorgestrel
      • 3rd phase=10 days
      • 0.03 mg EE+0.125 mg levonorgestrel
        39. 0.035 mg ethinyloestradiol+2 mg cyproterone acetate
        40. 0.05 mg mestranol+2 mg chlormadinone acetate
        41. 1st phase=11 days
      • 0.05 mg ethinyloestradiol+1 mg chlormadinone acetate
      • 2nd phase=11 days
      • 0.05 mg ethinyloestradiol+2 mg chlormadinone acetate
        42. 0.08 mg mestranol+2 mg chlormadinone acetate
        43. 0.03 mg ethinyloestradiol+2 mg dienogest
        44. 0.05 mg ethinyloestradiol+0.5 mg norgestrel
        45. 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel
        46. 0.05 mg ethinyloestradiol+0.25 mg levonorgestrel
        47. 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel
        48. 0.05 mg ethinyloestradiol+1 mg norethisterone acetate
        49. 0.05 mg ethinyloestradiol+0.25 mg levonorgestrel
        50. 1st phase=7 days
      • 0.04 mg ethinyloestradiol+0.025 mg desogestrel
      • 2nd phase=15 days
      • 0.03 mg ethinyloestradiol+0.125 mg desogestrel
        51. 1st phase=11 days
      • 0.05 mg ethinyloestradiol+0.05 mg levonorgestrel
      • 2nd phase=10 days
      • 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel
        52. 1st phase=11 days
      • 0.05 mg ethinyloestradiol+0.05 mg levonorgestrel
      • 2nd phase=10 days
      • 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel
        53. 1st phase=7 days
      • 0.05 mg ethinyloestradiol+
      • 2nd phase=15 days
      • 0.05 mg ethinyloestradiol+2.5 mg lynestrenol
        54. 1st phase=7 days
      • 0.05 mg ethinyloestradiol+
      • 2nd phase=15 days
      • 0.05 mg ethinyloestradiol+0.125 mg desogestrel
        55. 1st phase=6 days
      • 0.05 mg ethinyloestradiol+
      • 2nd phase=15 days
      • 0.05 mg ethinyloestradiol+1 mg norethisterone acetate
  • Where the dosage form according to the invention provides a multiphasic hormone combination, it is recommended that the hormone-containing daily units be taken without interruption only for a period of 21 to 25 days, followed by 7 to 3 days of taking hormone-free daily units.
  • The dosage form according to the invention preferably comprises at least 21, preferably 21 to 25, hormone-containing daily units which preferably include 5 to 30 μg of ethinyloestradiol and 0.5 to 5 mg of chlormadinone acetate, and 3 to 7 hormone-free daily units. However, the dosage form according to the invention may also comprise hormone-containing daily units for several years, preferably of 42 to 365 units, which contain the stated hormone combination in the stated ranges, wherein the corresponding uninterrupted tablet-taking periods are followed by 7 to 3 hormone-free daily units with an elevated amount of folic acid stated according to the invention.
  • As already stated, the hormone-containing daily units of the dosage form according to the invention may take the form of a monophasic (one-phase) or multiphasic contraceptive. In the case of a multiphasic contraceptive, a two-phase or a three-phase pill may be present, which is not usually suitable, however, to be taken for a period longer than a woman's natural cycle.
  • The dosage form according to the invention may also be a constituent of a kit, wherein the kit according to the invention may comprise a plurality of the dosage forms according to the invention, especially if one dosage form comprises only one monthly cycle.
  • The kit may optionally include a calendar or a diary.
    • EXAMPLES Example 1 a) Composition
  • Per tablet
    Ethinyloestradiol  0.020 mg
    Chlormadinone acetate  2.000 mg
    Povidone K30  3.000 mg
    Lactose 31.980 mg
    Maize starch 12.000 mg
    Magnesium stearate  0.500 mg
    Highly disperse silicon dioxide  0.500 mg
  • Ethinyloestradiol (EE) and povidone K30 (polyvinylpyrrolidone) were dissolved in 600 ml of ethanol. Chlormadinone acetate (particle size 90%<50 μm), lactose and maize starch were mixed in a mixer/pelletiser (Diosna P25) for 5 mins. and then moistened thoroughly and mixed with the ethanolic EE/PVP solution. The moist composition was forced through a 3 mm screen and dried in a vacuum drying cabinet. The dried granular product was disagglomerated through a 0.6 mm screen, mixed with magnesium stearate and highly disperse silicon dioxide and pressed on a tablet press with 5 mm punches into tablets with a weight of 50 mg.
  • b) As indicated under a), hormone-free, folic acid-containing tablets with a weight of 50 mg were produced, wherein the sodium salt of the folic acid was dissolved in 600 ml of aqueous ethanol.
  • Per tablet
    Sodium folate  3.000 mg
    Povidone K30  3.000 mg
    Lactose 31.000 mg
    Maize starch 12.000 mg
    Magnesium stearate  0.500 mg
    Highly disperse silicon dioxide  0.500 mg
  • The tablets were coated with a methylhydroxypropylcellulose-based coating (e.g. Opadry YS-1-2184 made by Colorcon), coating composition 2 mg per tablet, and packaged into a dosage form comprising 120 hormone-containing daily units without folic acid and 7 hormone-free daily units with folic acid.

Claims (16)

1-15. (canceled)
16. A hormonal contraceptive dosage form for uninterrupted daily oral administration to women, said dosage form comprising hormone-containing daily units and hormone-free daily units, wherein each of the hormone-containing daily units does not comprise any folic acid and each of the hormone-free daily units comprises folic acid in a daily amount of >200 μg up to the maximum permissible amount of folic acid for women.
17. A dosage form according to claim 16, wherein the hormone-free daily units each comprises more than 200 μg and up to 5 mg of folic acid.
18. A dosage form according to claim 16, wherein the hormone-free daily units each comprises the same amount of folic acid.
19. A dosage form according to claim 16, wherein the dosage form comprises at least 21 hormone-containing daily units and 7 to 3 hormone-free daily units.
20. A dosage form according to claim 19, wherein the number of hormone-containing daily units is sufficient for administration for a maximum of 2 years, and the number of hormone-free daily units is sufficient for administration for 7 to 3 days.
21. A dosage form according to claim 19, comprising up to 730-hormone-containing daily units and 7 to 3 hormone-free daily units.
22. A dosage form according to claim 19, which comprises 21 to 25 hormone-containing daily units and 7 to 3 hormone-free daily units.
23. A dosage form according to claim 19, which comprises 42 to 52 hormone-containing daily units and 7 to 3 hormone-free daily units.
24. A dosage form according to claim 19, which comprises 77 to 193 hormone-containing daily units and 7 to 3 hormone-free daily units.
25. A dosage form according to claim 19, wherein the dosage form comprises up to 365 hormone-containing daily units and 7 to 3 hormone-free daily units.
26. A dosage form according to claim 16, wherein the hormone-containing daily units each comprises at least one contraceptive active hormone component.
27. A dosage form according to claim 26, wherein the hormone-containing daily units each comprises a hormone-combination consisting of an oestrogen and a gestagen.
28. A dosage form according to claim 16, wherein the hormone-containing daily units correspond to a monophasic contraceptive.
29. A kit comprising at least one dosage form for hormonal contraception according to claim 16.
30. A kit form according to claim 29, wherein the kit comprises a plurality of dosage forms for hormonal contraception according to claim 16.
US13/070,205 2004-05-28 2011-03-23 Dosace Form For Hormonal Contraceptive Abandoned US20110172197A1 (en)

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DE102004026670A DE102004026670A1 (en) 2004-05-28 2004-05-28 Hormonal contraceptive containing a combination of ethinylestradiol and chlormadinone acetate
DE102004026671.0 2004-05-28
DE102004026670.0 2004-05-28
DE102004026671A DE102004026671A1 (en) 2004-05-28 2004-05-28 Dosage form for hormonal contraception
US11/009,817 US20050267083A1 (en) 2004-05-28 2004-12-10 Dosage form for hormonal contraception
US11/244,974 US8580771B2 (en) 2004-05-28 2005-10-06 Dosage form for hormonal contraception
US13/070,205 US20110172197A1 (en) 2004-05-28 2011-03-23 Dosace Form For Hormonal Contraceptive

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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004026671A1 (en) * 2004-05-28 2005-12-15 Grünenthal GmbH Dosage form for hormonal contraception
US20090254132A1 (en) * 2005-07-07 2009-10-08 Scribner Robert M Devices and methods for the treatment of bone fracture
DE102005034498A1 (en) * 2005-07-20 2007-01-25 Grünenthal GmbH Oral contraception with Trimegeston
DE102005053771A1 (en) 2005-11-09 2007-05-10 Grünenthal GmbH Dosage form for hormonal contraception
KR20090029824A (en) * 2006-07-06 2009-03-23 바이엘 쉐링 파마 악티엔게젤샤프트 Pharmaceutical preparations for contraception and for preventing the risk of congenital malformations
DE202007019049U1 (en) * 2007-11-05 2010-05-12 Bayer Schering Pharma Aktiengesellschaft Use of a gestagen in combination with an estrogen for the prophylaxis of lactose intolerance in oral contraception

Citations (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5280023A (en) * 1991-02-09 1994-01-18 Marika Ehrlich Ovulation-inhibiting preparation for hormonal contraception
US5569652A (en) * 1989-05-16 1996-10-29 Schering Aktiengesellschaft Dihydrospirorenone as an antiandrogen
US5898032A (en) * 1997-06-23 1999-04-27 Medical College Of Hampton Roads Ultra low dose oral contraceptives with less menstrual bleeding and sustained efficacy
US6190693B1 (en) * 1998-04-17 2001-02-20 Ortho-Mcneil Pharamceutical, Inc. Pharmaceutical methods of delivering folic acid
US6312722B1 (en) * 1995-06-28 2001-11-06 Schering Aktiengesellschaft Pharmaceutical combined preparation, kit and method for hormonal contraception
US20010044429A1 (en) * 1998-12-23 2001-11-22 Shangold Gary A. Triphasic oral contraceptive
US20020010167A1 (en) * 2000-06-08 2002-01-24 American Home Products Corporation Starter kit for low dose oral contraceptives
US20020061875A1 (en) * 1997-11-06 2002-05-23 American Home Products Corporation Anti-estrogen plus progestin containing oral contraceptives
US6451779B1 (en) * 1997-02-12 2002-09-17 Rolf-Dieter Hesch Composition and method for contraception and treatment of tumors of the mammary glands
US6500814B1 (en) * 1997-09-11 2002-12-31 Wyeth Pharmaceuticals Hormonal contraceptive
US6511970B1 (en) * 1996-09-13 2003-01-28 New Life Pharmaceuticals Inc. Prevention of ovarian cancer by administration of products that induce transforming growth factor-beta and/or apoptosis in the ovarian epithelium
US20030050287A1 (en) * 2001-09-12 2003-03-13 Wright Jonathan V. Hormone replacement formulation
US20040063721A1 (en) * 2002-08-15 2004-04-01 Wyeth Agonism of the 5HT2A receptor for treatment of thermoregulatory dysfunction
US20040198671A1 (en) * 2001-05-18 2004-10-07 Bunschoten Evert Johannes Pharmaceutical composition for use in hormone replacement therapy
US20040219174A1 (en) * 2000-09-14 2004-11-04 Hermann Kulmann Contraception process and administration form for the same
US20040220152A1 (en) * 2003-05-02 2004-11-04 Ben-Maimon Carole S. Methods of hormonal treatment utilizing extended cycle contraceptive regimens
US20040242550A1 (en) * 2001-05-23 2004-12-02 Van Beek Agatha Antonia Magdalena Means and method for hormonal contraception
US20050267081A1 (en) * 2004-05-28 2005-12-01 Janine Klose Use of a combination of ethinyloestradiol and chlormadinone acetate to produce a pharmaceutical preparation
US20050267084A1 (en) * 2004-05-28 2005-12-01 Janine Klose Hormonal contraceptive containing a combination of ethinyloestradiol and chlormadinone acetate
US20050267082A1 (en) * 2004-05-28 2005-12-01 Georg Schramm Hormonal contraceptive containing a combination of ethinyloestradiol and chlormadinone acetate
US20060089338A1 (en) * 2004-05-28 2006-04-27 Georg Schramm Dosage form for hormonal contraception
US20070021396A1 (en) * 2005-07-20 2007-01-25 Oliver Gloger Oral contraception with trimegestone

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4635051A (en) 1983-09-26 1987-01-06 Tektronix, Inc. High-speed electro-optical light gate and field sequential full color display system incorporating same
AU4805085A (en) 1984-09-05 1986-03-24 Schering Aktiengesellschaft Mittel zur behandlung von androgenisierungserscheinungen und verwendung von antiandrogenen zur herstellung des mittels
IE61236B1 (en) 1986-07-15 1994-10-19 American Home Prod Combination dosage form for pre-menopausal women
DE4224534A1 (en) 1992-07-24 1994-01-27 Marika Dr Med Ehrlich Anti-ovulation agent for hormonal contraception
DE4308406C1 (en) 1993-03-12 1994-06-16 Jenapharm Gmbh Contraceptive compsn. with reduced hormone dose and reduced side-effects - contg. synergistic mixt. of biogenic, synthetic oestrogen and gestagen
DE4321957C2 (en) 1993-07-01 1995-09-28 Marika Dr Med Ehrlich Use of a hormonal agent to treat acne
US6265393B1 (en) 1998-08-07 2001-07-24 Heinrichs William Leroy Prevention of endometriosis signs or symptons
HUP9900213A1 (en) * 1999-02-01 2000-12-28 Gábor Bogye Pharmaceutical compositions for diminishing side-effects of gestagene-type hormone-containing compositions

Patent Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5569652A (en) * 1989-05-16 1996-10-29 Schering Aktiengesellschaft Dihydrospirorenone as an antiandrogen
US5280023A (en) * 1991-02-09 1994-01-18 Marika Ehrlich Ovulation-inhibiting preparation for hormonal contraception
US6312722B1 (en) * 1995-06-28 2001-11-06 Schering Aktiengesellschaft Pharmaceutical combined preparation, kit and method for hormonal contraception
US6511970B1 (en) * 1996-09-13 2003-01-28 New Life Pharmaceuticals Inc. Prevention of ovarian cancer by administration of products that induce transforming growth factor-beta and/or apoptosis in the ovarian epithelium
US6451779B1 (en) * 1997-02-12 2002-09-17 Rolf-Dieter Hesch Composition and method for contraception and treatment of tumors of the mammary glands
US5898032A (en) * 1997-06-23 1999-04-27 Medical College Of Hampton Roads Ultra low dose oral contraceptives with less menstrual bleeding and sustained efficacy
US20040243606A1 (en) * 1997-09-11 2004-12-02 Wyeth Pharmaceuticals, Inc. Hormonal contraceptive product
US6500814B1 (en) * 1997-09-11 2002-12-31 Wyeth Pharmaceuticals Hormonal contraceptive
US20020061875A1 (en) * 1997-11-06 2002-05-23 American Home Products Corporation Anti-estrogen plus progestin containing oral contraceptives
US6190693B1 (en) * 1998-04-17 2001-02-20 Ortho-Mcneil Pharamceutical, Inc. Pharmaceutical methods of delivering folic acid
US20010044429A1 (en) * 1998-12-23 2001-11-22 Shangold Gary A. Triphasic oral contraceptive
US20020010167A1 (en) * 2000-06-08 2002-01-24 American Home Products Corporation Starter kit for low dose oral contraceptives
US20040219174A1 (en) * 2000-09-14 2004-11-04 Hermann Kulmann Contraception process and administration form for the same
US20040198671A1 (en) * 2001-05-18 2004-10-07 Bunschoten Evert Johannes Pharmaceutical composition for use in hormone replacement therapy
US20040242550A1 (en) * 2001-05-23 2004-12-02 Van Beek Agatha Antonia Magdalena Means and method for hormonal contraception
US20030050287A1 (en) * 2001-09-12 2003-03-13 Wright Jonathan V. Hormone replacement formulation
US20040063721A1 (en) * 2002-08-15 2004-04-01 Wyeth Agonism of the 5HT2A receptor for treatment of thermoregulatory dysfunction
US20040220152A1 (en) * 2003-05-02 2004-11-04 Ben-Maimon Carole S. Methods of hormonal treatment utilizing extended cycle contraceptive regimens
US20050267081A1 (en) * 2004-05-28 2005-12-01 Janine Klose Use of a combination of ethinyloestradiol and chlormadinone acetate to produce a pharmaceutical preparation
US20050267084A1 (en) * 2004-05-28 2005-12-01 Janine Klose Hormonal contraceptive containing a combination of ethinyloestradiol and chlormadinone acetate
US20050267082A1 (en) * 2004-05-28 2005-12-01 Georg Schramm Hormonal contraceptive containing a combination of ethinyloestradiol and chlormadinone acetate
US20060089338A1 (en) * 2004-05-28 2006-04-27 Georg Schramm Dosage form for hormonal contraception
US20070021396A1 (en) * 2005-07-20 2007-01-25 Oliver Gloger Oral contraception with trimegestone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Sulak et al., "Outcomes of extended oral contraceptive regimens with a shortened hormone-free interval to manage breakthrough bleeding," Contraception, 70 (2004), pgs 281-287. *

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