Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
2000-08-31
2004-09-07
Hui, San Ming R. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S178000
Reexamination Certificate
active
06787531
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition comprising drospirenone and ethinylestradiol, a method of providing dissolution of drospirenone, methods of inhibiting ovulation by administration of drospirenone and the use of drospirenone and ethinylestradiol for inhibiting ovulation.
BACKGROUND OF THE INVENTION
Oral contraceptives containing a combination of a gestagen and an estrogen component have been used since the 1960's. The earliest contraceptive preparations consisted of 21 tablets containing the combination of active agents and 7 tablets containing no active agent, and the amount of each active agent was the same in each tablet (the so-called one-phase preparations). Subsequently, preparations were developed that consisted of tablets containing different amounts and ratios of the active agents over the cycle of administration (the so-called multiple-phase preparations).
Contraceptive reliability is mainly provided by the gestagen component. The daily dosage should be at least the minimum of what is needed for the gestagen in question to inhibit ovulation effectively. The estrogen component acts to increase the ovulation inhibitory effect of gestagen and to ensure cycle stability. Since the introduction of oral contraceptives, the daily dosage of gestagen has been reduced through the development of new and more efficient gestagens than were present in the earlier contraceptive preparations. It has also been possible to reduce the daily dosage of estrogen.
6&bgr;,7&bgr;;15&bgr;,16&bgr;-dimethylene-3-oxo-17&agr;-pregn-4-ene-21,17-carbolactone (drospirenone) is known from DE 26 52 761 in which its use as a diuretic compound is disclosed.
In DE 30 22 337, the gestagen-like activity of the compound and its consequent utility as a contraceptive agent is described at dosage levels of 0.5-50 mg of drospirenone per day. It is also noted that the mechanism of action of the compound is very similar to that of the natural corpus luteum hormone progesterone, and that it does not give rise to increased blood pressure for which reason it may be administrated to women who have or are at risk of developing increased blood pressure. It is further described that drospirenone may be administered together with ethinylestradiol in an amount of 0.03-0.05 mg per day.
DE 30 51 166 discloses the use of the drospirenone for the treatment of gynaecological irregularities and for contraception at a dosage level of 0.5-50 mg per day.
EP 398 460 discloses the use of drospirenone for the treatment of androgen-induced disorders, aldosterone-induced disorders and hormonal irregularities as well as for contraception at dosage levels of 0.5-50 mg, preferably 1-10 mg per day. Ethinylestradiol may be co-administered at a level of 0.02-0.04 mg per day.
U.S. Pat. No. 5,756,490 discloses pharmaceutical combination preparations comprising 23 or 24 dosage units containing a combination of a gestagen and an estrogen and 4-10 dosage units containing estrogen alone. Drospirenone is mentioned as a possible, but not preferred, gestagenic compound and ethinylestradiol is mentioned as a possible, but not preferred, estrogenic compound.
SUMMARY OF THE INVENTION
Accordingly, in a first aspect, the present invention relates to a pharmaceutical composition comprising, as a first active agent, 6&bgr;,7&bgr;;15&bgr;,16&bgr;-dimethylene-3-oxo-17&agr;-pregn-4-ene-21,17-carbolactone (drospirenone) in an amount corresponding to a daily dosage, on administration of the composition, of from about 2 mg to about 4 mg, and, as a second active agent, 17&agr;-ethinylestradiol (ethinylestradiol) in an amount corresponding to a daily dosage of from about 0.01 mg to about 0.05 mg, together with one or more pharmaceutically acceptable carriers or excipients.
Apart form the active substances themselves, it is envisaged that an ester or prodrug of drospirenone may be employed in the present composition, e.g. an oxyiminopregnane carbolactone as disclosed in WO 98/24801. Likewise, it is envisaged that esters or ethers of ethinylestradiol may be included in the composition.
In a further aspect, the invention relates to a method of inhibiting ovulation in a mammal, in particular a human, comprising administering, to said mammal, drospirenone in an amount in the range of from about 2 mg to about 4 mg of per day, together with ethinylestradiol in an amount of from about 0.01 mg to about 0.05 mg per day, said amounts being effective to inhibit ovulation in said mammal.
In a still further aspect, the invention relates to the use of drospirenone combined with ethinylestradiol for preparing a pharmaceutical preparation for the inhibition of ovulation in a mammal, in particular a human, the composition comprising an amount of drospirenone corresponding to a daily dosage, on administration of the composition, of from about 2 mg to about 4 mg, and comprising an amount of ethinylestradiol corresponding to a daily dosage, on administration of the composition, of from about 0.01 to about 0.05 mg.
REFERENCES:
patent: 4129564 (1978-12-01), Wiechert et al.
patent: 4217347 (1980-08-01), Horovitz et al.
patent: 4621079 (1986-11-01), Lachnit-Fixson et al.
patent: 5001113 (1991-03-01), Williams et al.
patent: 5534270 (1996-07-01), De Castro
patent: 5569652 (1996-10-01), Beier et al.
patent: 5583129 (1996-12-01), Spona et al.
patent: 5756490 (1998-05-01), Lachnit et al.
patent: 5824667 (1998-10-01), Spona et al.
patent: 5827843 (1998-10-01), Koninckx
patent: 5922349 (1999-07-01), Elliesen et al.
patent: 6083528 (2000-07-01), Elliesen et al.
patent: 6121465 (2000-09-01), Mohr et al.
patent: RE37564 (2002-02-01), Spona et al.
patent: 2188907 (2001-02-01), None
patent: 3022337 (1982-01-01), None
patent: 30 22 337 (1989-10-01), None
patent: 30 51 166 (1990-10-01), None
patent: 0 148 724 (1988-06-01), None
patent: 0 253 607 (1992-04-01), None
patent: 0 398 460 (1997-02-01), None
patent: 0 770 388 (1998-03-01), None
patent: 2192542 (1988-01-01), None
patent: 94/04157 (1994-03-01), None
patent: WO 95/07081 (1995-03-01), None
patent: 95/17194 (1995-06-01), None
patent: 95/26730 (1995-10-01), None
patent: 97/01342 (1997-01-01), None
patent: WO 97/10827 (1997-03-01), None
patent: WO 97/11680 (1997-04-01), None
patent: WO 98/04267 (1998-02-01), None
patent: 98/04267 (1998-02-01), None
patent: WO 98/04269 (1998-02-01), None
patent: 98/04269 (1998-02-01), None
patent: 98/06738 (1998-02-01), None
patent: 98/24801 (1998-06-01), None
patent: WO 98/27929 (1998-07-01), None
An Invitation (one page) for and 21 slides shown in an oral presentation held on Feb. 17, 1988 in Berlin, Germany, entitled “Studies on pH-dependent Isomerization of Pregnene-17,21-Carbolactones.” by Johannes W. Tack. (Original in German with English translation.)
Sattar, et al., J.Clin.Endocrin.&Metab., vol. 82, No. 8, 1483-2491 (1997).
Elstein et al., “Advances in Oral Hormonal Contraception,”Zentralbl Gynakol117 (1995) 559-565.
Oelkers et al., “Effects of the new progestogen and antimineralocortoid dihydrospirorenone,”Acta Endocrinologica1992: 126 Suppl. 4, p. 71.
Oelkers et al., (1991) “Dihydrospirorenone, a New Progestogen with Antimineralocortcoid Activity: Effects on Ovulation, Electrolyte Excretion, and the Renin-Aldosterone System in Normal Women”Journal of Clinical Endocrinology and Metabolism,vol. 73, No. 4, 837-842.
Oelkers, “Effects of oral contraceptives on the renin—aldosterone system: overview and report on a new natriuretic progestogen,”Advances in Contraception,7 Suppl. 3 (1991) 195-206.
Kincl et al., “Increasing Oral Bioavailability of Progesterone by Formulation,”Journal of Steroid Biochemistry,1978, vol. 9, pp. 83-84.
Whitehead et al., “Absorption and metabolism of oral progesterone,”British Medical Journal,Mar. 22, 1980, pp. 825-827.
Maxson et al., “Bioavailability of oral micronized progesterone,”Fertility and Sterility,vol. 44, No. 5, Nov. 1985, pp. 622-626.
Chakmakjian et al., “Bloavailability of Progesterone with Different Modes of Administration,”The Journal of Reproductive Medicine,vol. 32, No. 6, Jun. 1987, pp. 443-448.
Hargrove et al., “
Heil Wolfgang
Heithecker Renate
Hilman Juergen
Huempel Michael
Lipp Ralph
Hui San Ming R.
Millen White Zelano & Branigan P.C.
Schering AG
LandOfFree
Pharmaceutical composition for use as a contraceptive does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical composition for use as a contraceptive, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition for use as a contraceptive will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3209170