Estrogenic substances combined with cruciferous indole compounds

• US 20020058648A1
• Filed: 11/10/2001
• Published: 05/16/2002
• Est. Priority Date: 11/13/2000
• Status: Active Grant

• Current Assignee: Milton Hammerly
• Original Assignee: Milton Hammerly
• Inventors: Hammerly, Milton
• Granted Patent: US 6,605,605 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Provided herein are medicinal compositions of matter that comprise an estrogenic medication component and a cruciferous indole component (indole 3-carbinol, diindolylmethane, or any derivative thereof. Through use of the compositions of the invention a heretofore unobserved synergy is observed in the treatment of perimenopause, menopause or any other cause of ovarian failure. The invention also provides procedures for administering the composition to a patient who is afflicted with perimenopause, menopause or any other cause of ovarian failure.

Claims

1. A medicinal composition useful in estrogen replacement therapy comprising:

a) an estrogenic substance; and

b) a cruciferous indole compound component.

2. A composition as set forth in claim 1 wherein said estrogenic substance is selected from the group consisting of:

estrogen, conjugated estrogens, dienestrol, estrone, esterified estrogens, estradiol, estriol, estropipate, ethinyl estradiol, or any estrogenic derivatives of the foregoing.

3. A composition as set forth in claim 1 wherein said cruciferous indole compound is selected from the group consisting of:

indole 3-carbinol, diindolylmethane, 5-methyl-indole-3-carbinol, 5-ethyl-indole-3-carbinol, 5-propyl-indole-3-carbinol, 5-butyl-indole-3-carbinol, 5-pentyl-indole-3-carbinol, 5-methoxy-indole-3-carbinol, 5-ethoxy-indole-3-carbinol, 5-propyloxy-indole-3-carbinol, 5-butyloxy-indole-3-carbinol, 5-amyloxy-indole-3-carbinol, N-methyl-indole-3-carbinol, N-ethyl-indole-3-carbinol, N-propyl-indole-3-carbinol, N-butyl-indole-3-carbinol, N-pentyl-indole-3-carbinol, 2-methyl-indole-3-carbinol, 2-ethyl-indole-3-carbinol, 2-propyl-indole-3-carbinol, 2-butyl-indole-3-carbinol and 2-pentyl-indole-3-carbinol.

4. A composition according to claim 1 wherein said estrogenic substance component is present in any amount between 0.005% and 99.5% by weight based upon total weight of the composition, including every hundredth percentage therebetween.

5. A composition according to claim 1 wherein said cruciferous indole compound component is present in any amount between 0.05% and 99.5% by weight based upon total weight of the composition, including every hundredth percentage therebetween.

6. A single-dose medicament useful in estrogen replacement therapy comprising a composition according claim 1, wherein said estrogenic substance is selected from the group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing, and wherein the quantity said cruciferous indole compound component is at least 0.5 milligrams.

7. A single-dose medicament according to claim 6 wherein said cruciferous indole compound is indole 3-carbinol.

8. A single-dose medicament according to claim 6 wherein said cruciferous indole compound is diindolylmethane.

9. A single-dose medicament useful in estrogen replacement therapy comprising a composition according claim 1, wherein said estrogenic substance is selected from the group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing, said estrogenic substance being present in a quantity of between 0.10 milligrams and 50 milligrams, including every milligram therebetween, and wherein the quantity said cruciferous indole compound component is selected from the group consisting of;

indole 3-carbinol and diindolylmethane, and wherein said cruciferous indole compound component is present in an amount of between 0.5 and 300 milligrams, including every milligram therebetween.

10. A single-dose medicament useful in estrogen replacement therapy comprising a composition according claim 1, wherein said estrogenic substance is selected from the group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing, and wherein said estrogenic substance is present in a quantity of between 0.10 and 50 milligrams, including every hundredth milligram therebetween, and wherein the quantity of said cruciferous indole compound component is present in an amount of at least 0.5 milligrams.

11. A medicinal composition useful in the treatment of estrogen replacement therapy comprising an estrogenic substance selected from the group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing; and

further comprising indole 3-carbinol.

14. A method according to claim 13 wherein the administration is oral.

15. A method according to claim 13 wherein the administration is parenteral.

16. A method according to claim 13, wherein the estrogen replacement therapy medication is selected from a group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing.

17. A method according to claim 13, wherein the estrogenic substance is compounded into a single oral unit with the cruciferous indole compound.

18. A method according to claim 17, wherein the single oral unit is a tablet.

19. A method according to claim 17, wherein the single oral unit is a capsule.

20. A method according to claim 13, wherein the estrogenic substance and the cruciferous indole compound are dissolved or suspended in oil to provide an oil suspension.

21. A method according to claim 20 wherein said oil suspension is placed in a single oral softgelatin capsule.

22. A method according to claim 13, wherein the estrogenic substance is formed into a first single oral unit, and the cruciferous indole compound is formed into a second single oral unit,

23. A method according to claim 22, wherein a number of first single oral units are placed in a first container, and a number of the second single oral units are placed in a second container.

24. The method of claim 23, wherein the first and second containers are packaged together.

25. The method of claim 22, wherein the first and second single oral units are a tablet.

26. The method of claim 22, wherein the first and second single oral units are a capsule.

27. The method of claim 22, wherein the second single oral unit is a softgelatin capsule.

28. The method of claim 13, wherein the estrogenic substance is administered orally to the patient in one daily dose of at least 0.03 milligrams per day.

29. The method of claim 13, wherein the cruciferous indole compound is administered orally to the patient in one daily dose containing at least 0.5 milligrams of any compound selected from the group consisting of indole 3-carbinol and diindolyl methane.

30. The method of claim 22, wherein binders and carriers are used in the first and second oral units to facilitate the administration of the estrogenic substance component and the cruciferous indole compound component.

31. A method according to claim 13 wherein said derivatives include a compound selected from the group consisting of 5-methyl-indole-3-carbinol, 5-ethyl-indole-3-carbinol, 5-propyl-indole-3-carbinol, 5-butyl-indole-3-carbinol, 5-pentyl-indole-3-carbinol, 5-methoxy-indole-3-carbinol, 5-ethoxy-indole-3-carbinol, 5-propyloxy-indole-3-carbinol, 5-butyloxy-indole-3-carbinol, 5-amyloxy-indole-3-carbinol, N-methyl-indole-3-carbinol, N-ethyl-indole-3-carbinol, N-propyl-indole-3-carbinol, N-butyl-indole-3-carbinol, N-pentyl-indole-3-carbinol, 2-methyl-indole-3-carbinol, 2-ethyl-indole-3-carbinol, 2-propyl-indole-3-carbinol, 2-butyl-indole-3-carbinol and 2-pentyl-indole-3-carbinol.

12. A medicinal composition useful in the treatment of estrogen replacement therapy comprising an estrogenic substance selected from the group consisting of:

estrogen;

conjugated estrogens;

dienestrol;

estrone;

esterified estrogens;

estradiol;

estriol; and

estropipate;

ethinyl estradiol;

or any estrogenic derivative of the foregoing; and

further comprising diindolylmethane.

13. A method of providing estrogen replacement therapy to a patient needing same, the method comprising:

administration of a therapeutically-effective amount of a estrogenic substance in synergistic combination with a therapeutically effective amount of a cruciferous indole compound selected from the group consisting of;

indole 3-carbinol; and

diindolylmethane, and derivatives thereof,

wherein the estrogenic substance is administered to alleviate symptoms of estrogen deficiency, and the cruciferous indole compound is administered to increase 2-hydroxyestrogen metabolites and to decrease 16-hydroxyestrogen metabolites in said patient.

32. A process in estrogen replacement therapy comprising the steps of:

a) providing a combination comprising;

i) an estrogenic substance component; and

ii) a cruciferous indole compound component, and

b) introducing said composition into a human body that is afflicted with an deficiency of an estrogenic substance.

33. A process according to claim 32 wherein the total mass of the combination introduced into said body from step b) is in the range of 0.1 milligrams and 1,000 milligrams, including every hundredth of a milligram therebetween, per introduction.

34. The process according to claim 32 wherein said introducing is undertaken orally, buccally, dermally, enterally, parenterally, or by means of a patch.