CA1292945C - Antigestagens for the inhibition of uterine synthesis of prostaglandin - Google Patents
Antigestagens for the inhibition of uterine synthesis of prostaglandinInfo
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- CA1292945C CA1292945C CA000547805A CA547805A CA1292945C CA 1292945 C CA1292945 C CA 1292945C CA 000547805 A CA000547805 A CA 000547805A CA 547805 A CA547805 A CA 547805A CA 1292945 C CA1292945 C CA 1292945C
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- beta
- alpha
- hydroxy
- dimethylamino
- phenyl
- Prior art date
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Abstract
Abstract of the Disclosure Antigestagens inhibit prostatglandin synthesis by the uterus and thus can be used to treat symptoms of dysmennhorea.
Description
ANTIGESTA~:ENS FOR '1'~; INHIBITION OF
UTERINE SYNT~SIS OF PROSTA&I~NDIN
8ackground of the Invention The invention relates to the use of antigestagens and the production of drugs containing antigestagens for the inhibition of uterine synthesis of prostaglandin, especially for thé treatment and prevention of dysmenorrheic symptoms.
Effective antigestagens are known, for example, ~rom European patent speci~ication 57,115 (Roussel-Uclaf).
Studied especially thoroughly was 11-beta-t4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one designated as RU 486.
Data on the therapeutic mechanism of RU 486 are found in "Human Reproduction," Vol. 1 (1986), 107-110. According to it, antigestagen causes a blocking of progesterone activity and an increase of the formation of prostaglandin, and the prostaglandin stimulates uterine ~- 20 contractility. With RU 486, clinical studies to the end of pregnancy have just been conducted.
Prostaglandins play a key role in normal and pathological menstruation:
They are viewed in relation to changes in the blood supply of the mucous coating o~ the uterus and to the laborlike contractions of the uteru~ during menstruation. Increased release of PG and increased ' . ~ , - ~zszs~s uterine contractions, which can be felt as extremely painful, are the essence of dysmenorrhea.
Summary of the Invention It is an object of the invention, therefore, to provide a method for the inhibition of dysmennorhea and prophalactic treatment of individuals with a history of such smyptons.
It has now been found that, contrary to the previous assumption, antigestagens inhibit uterine - prodction of prostaglandins (PG). These objects therefore have been satisfied by the provision of a method for the use of antigestagens and the production of drugs containing antigestagens used in the inhibition of uterine synthesis of prostaglandin.
The invention further relates to the use of antigestagens ~or treatment and prevention of dysmenorrheic symptoms.
Detailed D~scussion Inhibition of uterine PG through the use of antigestagens eliminates or at least substantially lessens the symptoms which accompany dysmenorrhea.
Since uterine synthesis o~ PG occurs essentially in the endometrium, di~turbances and pains resulting from endometriosis will also be benef~cially af~ected by antigestagens.
The inhibitory effect of antigestageus was observed in nonpregnant guinea pigs.
Luteolysis resulting from uterine PG at the end of the approximately 16-day cycle was blocked by antigestagens. A progression of serum progesterone values resulted which otherwise occurs only during pregnancy. Corresponding ef~ects of inhibited uterine PG production would not be observed in human beings as a result of antigestagens, since in a woman the lifespan of the corpus luteum is not controlled by the uterus.
~29Z945 However, with inhibition of uterine PG release in humans, a calming effect of the uterine motor system in the presence of dysmenorrhea will occur.
The advantage of this treatment course is that a desirable degree of inhibition is attained without affecting the PG function in other organs. A high degree of organ selectivity is achieved through the treatment of dysmenorrhea with antigestagens.
Antigestagens can be used at the onset of dysmenorrheic symptoms, such as "pains in the lower abdomen." It is sometimes appropriate to set the beginning of the treatment at somewhat earlier phases of the luteal phase to achieve a sufficient degree of inhibition. In such prophylactic treatment, typical hosts are those with a prior history of dysmenorrheic symptoms, and treatment is commenced be~ore the onset of estrus or menstruat~on.
According to a pre~erred embodiment, the antigestagen treatment is given as a rule over 1 to 6, pre~erably 1 to 4 days, preférably startin~ at thé
beginning o~ the estrual or menstrual period or upon the appearance o~ symptoms, As antigestagens, all compounds which have a strong affinity for the gestagen receptor (progesterone receptor) and at the same time show no gestagenic activity of their own are suitable. As competitive progesterone antagonists, the following steroids, for example, are suitable:
beta-t(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-t(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-18-methyl-17-alpha-propinyl-4,9(10)-estradien-3-one, ll-beta-t(4-N,N-dimethylamino)-phenyl]-17a-beta-hydroxy-17a-alpha-propinyl-D-homo-4,9(10)-16-estratrien-3-one (European Patent Application 82400025.1 - Publication Number 57,115), 11-beta-methoxyphenyl-17-beta-hydroxy-lZ92945 17-alpha-ethinyl-4,9(10)-estradien-3-one, (Steroids 37 (1981) 361-382), 11-beta-~(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-hydroxyprop-l(Z)-enyl)- 4,9(10)-estradien-3-one (European Patent Application 847300147.0 - Publication Number 147,361), 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxyl7-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10-gonadien-3-one (European Patent Application 84730062.1 - Publication Number 129,49g). Other antigestagens which are disclosed in US-4,536,401; US Patent No. 4,814,327 and US
Patent No. 4,829,060 are useful.
The antigestagens can, for example, be administered locally, topically, enterally or parenterally.
For the preferred oral administration, particularly tablets, coated tablets, capsules, pills, suspensions or solutions which can be produced in the standard way with the admixtures and vehicles usual in galenic medicine are suitable. For local or topical use, vaginal suppositories or transdermal systems such as sXin plasters, for example, are suitable.
According to the present invention, the antigestagens are used generally in amounts of about 2 to 50 mg/day, preferably about 5 to 20 mg/day of 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9~10)-gonadien-3-one or in a biologically equivalent amount of another antigestagen. Such amounts can be routinely determined by differential dosage studies using a conventional protocol determining antigestagenic activity;
- e.g. Fertility and Sterility 40,253 (1982), Steroids 37. 361 (1981).
~,~ .c . ~
lZ9Z945 The compounds according to this invention when administered to patients, e.g., humans to inhibit PG formation or treat dysmenorrhea can be used analogously to the known agent Cyclo-Progynova(R). Dosage amounts are analogous when administered to prevent dysmenorrhea.
~ ~1 - 4a -~2~45 Without further elaboration, it is believed that one s~illed in the art can, using the preceding description; utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight.
The entire text of all applications, patents and publications, if any, cited above and below are hereby incorporated by reference.
Example 1 Compo~ition o~ a tablet with 10 mg o~ 11-beta-[(4-N,N-dimethylamino)-phenyl~-11-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one ~or o~al adm~ais~ation.
2010.0 mg 11-beta-t~4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(ioj-gonadien-3-one 140.5 mg lactose 2S69.5 mg corn starch 2.5 mg polyvinylpyrrolidone 25 2.0 mg Aerosil _ O.S mg magnesium stearate 22S.0 mg Total Weight 129Z~S
Example 2 Composition of an oily solution with So mg of 11-beta-1(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one for parente~al administration.
50 mg of the antigestagen is dissolved in 1 ml each of castor oil/benzyl benzoate in a 6:4 ratio by volume.
Example 3 Nonpregnant guinea pigs received daily, from the 8th to the 16th day of the approximately 16-day cycle, 10 mg of 11-beta-~(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one. The test substance was dissolved in 1 ml of benzyl benzoate/castor oil (1:2) and in~ected subcutaneously. The progesterone content of the serum was determined daily.
It can be seen from the following table that the serum progesterone values for the animals treated with ' 20 the antigestagen increase, while the serum progesterone values for the controls treated with solvent fall sharply toward the end of the cycle. Corresponding dose-dependent findings were obtained for this substance and also for other antigestagens in similar test arrangements. The increase of progesterone in the blood of animals treated with the antigestagen reflects an inhibition of uterine release of PG.
i292945 Treatment of Nonpregnant Guinea Pigs with 10 mg of ll-beta-[~4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-qonadien-3-one _ _ Progesterone/nmol/l serum Animal No. do dl d4 d6 d8 Animals6637 1.3 23.2 7.2 10.2 19.9 Treated With 6638 1.9 1.5 8.5 11.9 8.4 Anti-Gestagen 6639 1.6 5.9 13.5 13.6 9.5 6640 0.4 4.8 8.2 17.6 22.2 ________________________________________________________ Controls 6641 0.4 6.1 5.3 7.1 8.0 Treated With 6642 3.7 2.3 11.7 8.7 18.1 Solvent (Table Continued) Animal No. dlo dl2 dl4 d1s dl6 d17 Animals6637 20.5 18.810.2 --- 16.0 26.8 Treated With 6638 14.3 16.117.4 --- 25.6 .Z~r 6 Anti-Gestagen 6639 13.013.0 Z4.2 18.4 --- ---6640 23.6 36.031.4 39.8 --- ---____________ ___________________________________________ Controls 6641 9.5 10.6 5.2 --- 2.8 2.8 Treated With 6642 5.3 1.3 0.8 1.1 --- ---Solvent 129Z9~S
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operation conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
UTERINE SYNT~SIS OF PROSTA&I~NDIN
8ackground of the Invention The invention relates to the use of antigestagens and the production of drugs containing antigestagens for the inhibition of uterine synthesis of prostaglandin, especially for thé treatment and prevention of dysmenorrheic symptoms.
Effective antigestagens are known, for example, ~rom European patent speci~ication 57,115 (Roussel-Uclaf).
Studied especially thoroughly was 11-beta-t4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one designated as RU 486.
Data on the therapeutic mechanism of RU 486 are found in "Human Reproduction," Vol. 1 (1986), 107-110. According to it, antigestagen causes a blocking of progesterone activity and an increase of the formation of prostaglandin, and the prostaglandin stimulates uterine ~- 20 contractility. With RU 486, clinical studies to the end of pregnancy have just been conducted.
Prostaglandins play a key role in normal and pathological menstruation:
They are viewed in relation to changes in the blood supply of the mucous coating o~ the uterus and to the laborlike contractions of the uteru~ during menstruation. Increased release of PG and increased ' . ~ , - ~zszs~s uterine contractions, which can be felt as extremely painful, are the essence of dysmenorrhea.
Summary of the Invention It is an object of the invention, therefore, to provide a method for the inhibition of dysmennorhea and prophalactic treatment of individuals with a history of such smyptons.
It has now been found that, contrary to the previous assumption, antigestagens inhibit uterine - prodction of prostaglandins (PG). These objects therefore have been satisfied by the provision of a method for the use of antigestagens and the production of drugs containing antigestagens used in the inhibition of uterine synthesis of prostaglandin.
The invention further relates to the use of antigestagens ~or treatment and prevention of dysmenorrheic symptoms.
Detailed D~scussion Inhibition of uterine PG through the use of antigestagens eliminates or at least substantially lessens the symptoms which accompany dysmenorrhea.
Since uterine synthesis o~ PG occurs essentially in the endometrium, di~turbances and pains resulting from endometriosis will also be benef~cially af~ected by antigestagens.
The inhibitory effect of antigestageus was observed in nonpregnant guinea pigs.
Luteolysis resulting from uterine PG at the end of the approximately 16-day cycle was blocked by antigestagens. A progression of serum progesterone values resulted which otherwise occurs only during pregnancy. Corresponding ef~ects of inhibited uterine PG production would not be observed in human beings as a result of antigestagens, since in a woman the lifespan of the corpus luteum is not controlled by the uterus.
~29Z945 However, with inhibition of uterine PG release in humans, a calming effect of the uterine motor system in the presence of dysmenorrhea will occur.
The advantage of this treatment course is that a desirable degree of inhibition is attained without affecting the PG function in other organs. A high degree of organ selectivity is achieved through the treatment of dysmenorrhea with antigestagens.
Antigestagens can be used at the onset of dysmenorrheic symptoms, such as "pains in the lower abdomen." It is sometimes appropriate to set the beginning of the treatment at somewhat earlier phases of the luteal phase to achieve a sufficient degree of inhibition. In such prophylactic treatment, typical hosts are those with a prior history of dysmenorrheic symptoms, and treatment is commenced be~ore the onset of estrus or menstruat~on.
According to a pre~erred embodiment, the antigestagen treatment is given as a rule over 1 to 6, pre~erably 1 to 4 days, preférably startin~ at thé
beginning o~ the estrual or menstrual period or upon the appearance o~ symptoms, As antigestagens, all compounds which have a strong affinity for the gestagen receptor (progesterone receptor) and at the same time show no gestagenic activity of their own are suitable. As competitive progesterone antagonists, the following steroids, for example, are suitable:
beta-t(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-t(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-18-methyl-17-alpha-propinyl-4,9(10)-estradien-3-one, ll-beta-t(4-N,N-dimethylamino)-phenyl]-17a-beta-hydroxy-17a-alpha-propinyl-D-homo-4,9(10)-16-estratrien-3-one (European Patent Application 82400025.1 - Publication Number 57,115), 11-beta-methoxyphenyl-17-beta-hydroxy-lZ92945 17-alpha-ethinyl-4,9(10)-estradien-3-one, (Steroids 37 (1981) 361-382), 11-beta-~(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-hydroxyprop-l(Z)-enyl)- 4,9(10)-estradien-3-one (European Patent Application 847300147.0 - Publication Number 147,361), 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxyl7-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10-gonadien-3-one (European Patent Application 84730062.1 - Publication Number 129,49g). Other antigestagens which are disclosed in US-4,536,401; US Patent No. 4,814,327 and US
Patent No. 4,829,060 are useful.
The antigestagens can, for example, be administered locally, topically, enterally or parenterally.
For the preferred oral administration, particularly tablets, coated tablets, capsules, pills, suspensions or solutions which can be produced in the standard way with the admixtures and vehicles usual in galenic medicine are suitable. For local or topical use, vaginal suppositories or transdermal systems such as sXin plasters, for example, are suitable.
According to the present invention, the antigestagens are used generally in amounts of about 2 to 50 mg/day, preferably about 5 to 20 mg/day of 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9~10)-gonadien-3-one or in a biologically equivalent amount of another antigestagen. Such amounts can be routinely determined by differential dosage studies using a conventional protocol determining antigestagenic activity;
- e.g. Fertility and Sterility 40,253 (1982), Steroids 37. 361 (1981).
~,~ .c . ~
lZ9Z945 The compounds according to this invention when administered to patients, e.g., humans to inhibit PG formation or treat dysmenorrhea can be used analogously to the known agent Cyclo-Progynova(R). Dosage amounts are analogous when administered to prevent dysmenorrhea.
~ ~1 - 4a -~2~45 Without further elaboration, it is believed that one s~illed in the art can, using the preceding description; utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight.
The entire text of all applications, patents and publications, if any, cited above and below are hereby incorporated by reference.
Example 1 Compo~ition o~ a tablet with 10 mg o~ 11-beta-[(4-N,N-dimethylamino)-phenyl~-11-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one ~or o~al adm~ais~ation.
2010.0 mg 11-beta-t~4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(ioj-gonadien-3-one 140.5 mg lactose 2S69.5 mg corn starch 2.5 mg polyvinylpyrrolidone 25 2.0 mg Aerosil _ O.S mg magnesium stearate 22S.0 mg Total Weight 129Z~S
Example 2 Composition of an oily solution with So mg of 11-beta-1(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one for parente~al administration.
50 mg of the antigestagen is dissolved in 1 ml each of castor oil/benzyl benzoate in a 6:4 ratio by volume.
Example 3 Nonpregnant guinea pigs received daily, from the 8th to the 16th day of the approximately 16-day cycle, 10 mg of 11-beta-~(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one. The test substance was dissolved in 1 ml of benzyl benzoate/castor oil (1:2) and in~ected subcutaneously. The progesterone content of the serum was determined daily.
It can be seen from the following table that the serum progesterone values for the animals treated with ' 20 the antigestagen increase, while the serum progesterone values for the controls treated with solvent fall sharply toward the end of the cycle. Corresponding dose-dependent findings were obtained for this substance and also for other antigestagens in similar test arrangements. The increase of progesterone in the blood of animals treated with the antigestagen reflects an inhibition of uterine release of PG.
i292945 Treatment of Nonpregnant Guinea Pigs with 10 mg of ll-beta-[~4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-qonadien-3-one _ _ Progesterone/nmol/l serum Animal No. do dl d4 d6 d8 Animals6637 1.3 23.2 7.2 10.2 19.9 Treated With 6638 1.9 1.5 8.5 11.9 8.4 Anti-Gestagen 6639 1.6 5.9 13.5 13.6 9.5 6640 0.4 4.8 8.2 17.6 22.2 ________________________________________________________ Controls 6641 0.4 6.1 5.3 7.1 8.0 Treated With 6642 3.7 2.3 11.7 8.7 18.1 Solvent (Table Continued) Animal No. dlo dl2 dl4 d1s dl6 d17 Animals6637 20.5 18.810.2 --- 16.0 26.8 Treated With 6638 14.3 16.117.4 --- 25.6 .Z~r 6 Anti-Gestagen 6639 13.013.0 Z4.2 18.4 --- ---6640 23.6 36.031.4 39.8 --- ---____________ ___________________________________________ Controls 6641 9.5 10.6 5.2 --- 2.8 2.8 Treated With 6642 5.3 1.3 0.8 1.1 --- ---Solvent 129Z9~S
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operation conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
Claims (21)
1. The use of an effective amount of a steroidal antigestagen to inhibit uterine synthesis of prostglandin in the treatment of dysmenorrhea in a mammal host.
2. The use according to claim 1, wherein the antigestagen is a steroid.
3. The use according to claim 1, wherein the antigestagen is 11-beta-[4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-18-methyl-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17a-beta-hydroxy-17a-alpha-propinyl-D-homo-4,9(10)-16-estratrien-3-one, 11-beta-methoxyphenyl-17-beta-hydroxy-17-alpha-ethinyl-
4,9(10)-estradien-3-one, 11-beta-t(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-hydroxyprop-1-(Z)-enyl)-4,9(10)-estradien-3-one, or 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10-gonadien-3-one.
4. The use according to claim 1, wherein the antigestagen is 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one.
4. The use according to claim 1, wherein the antigestagen is 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one.
5. The use according to claim 4, wherein the effective amount is about 2 to 50 mg/day.
6. The use according to claim 1, wherein the antigestagen is to be adminstered in an amount biologically equivalent to 2 to 50 mg/day of 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one.
7. The use according to claim 1, wherein the antigestagen is to be adminstered for a peiod of 1 to 6 days beginning at the onset of the estrual or menstrual period.
8. The use according to claim 1, wherein the host is a human.
9. The use of an amount of a steroidal antigestagen effective to inhibit dysmenorrhea symptoms in a female in need thereof.
10. The use according to claim 9, wherein the antigestagen is to be adminstered for a peiod of 1 to 6 days beginning at the onset of the estrual or menstrual period.
11. The use according to Claim 9, wherein the antigestagen is to be administered for a period of 1 to 4 days beginning at the onset of the estrual or menstrual period.
12. The use according to claim 9, wherein the antigestagen is a steroid.
13. The use according to claim 9, wherein the antigestagen is 11-beta-[4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-18-methyl-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-l(4-N,N-dimethylamino)-phenyl]-17a-beta-hydroxy-17a-alpha-propinyl-D-homo-4,9(10)-16-estratrien-3-one, ll-beta-methoxyphenyl-17-beta-hydroxy-17-alpha-ethinyl-4,9(10)-estradien-3-one, ll-beta-[(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-hydroxyprop-1-(Z)-enyl)-4,9(10)-estradien-3-one, or 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10-gonadien-3-one.
14. The use according to claim 9, wherein the antigestagen is 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alphd-methyl-4,9(10)-gonadien-3-one.
15. The use according to Claim 14, wherein the antigestagen is to be administered in an amount of 2 to 50 mg/day.
16. The use according to claim 9, wherein the female is a human.
17. The use before the onset of estrus or menstruation of an amount of a steroidal antigestagen effective to prevent or lessen dysmenorrheic symptoms in a female in need thereof.
18. The use according to claim 17, wherein the antigestagen is 11-beta-[4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-18-methyl-17-alpha-propinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17a-beta-hydroxy-17a-alpha-propinyl-D-homo-4,9(10)-16-estratrien-3-one, 11-beta-methoxyphenyl-17-beta-hydroxy-17-alpha-ethinyl-4,9(10)-estradien-3-one, 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-beta-hydroxy-17-alpha-hydroxyprop-1-(Z)-enyl)-4,9(10)-estradien-3-one, or 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10-gonadien-3-one.
19. The use according to claim 17, wherein the antigestagen is 11-beta-[(4-N,N-dimethylamino)-phenyl]-17-alpha-hydroxy-17-beta-(3-hydroxypropyl)-13-alpha-methyl-4,9(10)-gonadien-3-one.
20. The use according to claim 17, wherein the female is a human.
21. The use of an effective amount of a steroidal antigestagen to inhibit uterine synthesis of prostglandin in the treatment of endometriosis in a mammal host.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000547805A CA1292945C (en) | 1987-09-25 | 1987-09-25 | Antigestagens for the inhibition of uterine synthesis of prostaglandin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000547805A CA1292945C (en) | 1987-09-25 | 1987-09-25 | Antigestagens for the inhibition of uterine synthesis of prostaglandin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1292945C true CA1292945C (en) | 1991-12-10 |
Family
ID=4136516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000547805A Expired - Lifetime CA1292945C (en) | 1987-09-25 | 1987-09-25 | Antigestagens for the inhibition of uterine synthesis of prostaglandin |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1292945C (en) |
-
1987
- 1987-09-25 CA CA000547805A patent/CA1292945C/en not_active Expired - Lifetime
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