Use of equol for treating androgen mediated diseases

• US 10,111,855 B2
• Filed: 01/03/2018
• Issued: 10/30/2018
• Est. Priority Date: 10/29/2002
• Status: Expired due to Term

• Current Assignee: Colorado State University Research Foundation (Colorado State University System), Brigham Young University (The Church of Jesus Christ of Latter-Day Saints)
• Original Assignee: Colorado State University Research Foundation (Colorado State University System), Brigham Young University (The Church of Jesus Christ of Latter-Day Saints)
• Inventors: Lephart, Edwin Douglas, Lund, Trent D., Handa, Robert J.
• Primary Examiner(s): McMillian, Kara R
• Application Number:
  US15/861,386
• Publication Number:
  US 20180185326A1
• Time in Patent Office: 300 Days
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 8/498 having 6-membered rings or their condensed derivatives, e.g. coumarin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/28 : Antiandrogens
• CPC Class Codes: A61P 5/30 : Oestrogens
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 7/00 : Preparations for affecting hair growth

Abstract

Equol (7-hydroxy-3(4′hydroxyphenyl)-chroman), or metabolite of the phytoestrogen daidzein, specifically binds and blocks the hormonal action of 5α-dihydrotestosterone (DHT) in vitro and in vivo. Equol can bind circulating free DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol'"'"'s biological properties. The significance of equol'"'"'s ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment and prevention of androgen-mediated pathologies. Thus, equol can specifically bind DHT and prevent DHT'"'"'s biological actions in physiological and pathophysiological processes.

Claims

1. A method of modulating androgen hormone action to ameliorate or enhance at least one condition of the skin or hair of a subject, comprising administering a composition composing racemic equol, wherein the racemic equol binds free 5α

-dihydrotestosterone and inhibits its binding with the androgen receptor, and wherein ameliorating or enhancing at least one condition of the skin or hair of the subject comprises at least one of;

a) enhancing antioxidant content of the skin;

b) reducing skin inflammation;

c) improving skin thickness;

d) reducing skin adipose tissue (fat) and cellulite formation;

e) enhancing skin blood flow;

f) enhancing collagen and elastin;

g) improving skin abrasions and the appearance of scars;

h) enhancing wound healing;

i) diminishing skin pigmentation or dermal age spots;

j) enhancing skin lightening;

k) diminishing facial hair (hirsutism) or body hair; and

l) reducing skin oil production.

2. The method of claim 1, wherein the composition is for oral administration at a dose sufficient to produce a concentration of the racemic equol in the bloodstream of the subject of at least about 0.2 mg equol per kg weight of the subject.

3. The method of claim 1, wherein the composition is for oral administration and comprises at least 1 mg of racemic equol in a food, bar, drink, tablet or capsule.

4. The method of claim 1, wherein the composition is for topical administration and comprises from about 0.1% to about 10% racemic equol.

5. The method of claim 1, wherein the composition is for a topical or subdermal administration and comprises from about 0.1% to about 10% racemic equol for diminishing facial or body hair.

6. The method of claim 1, wherein the composition comprises a pharmaceutical active or an excipient.

7. The method of claim 1, wherein the administering is topically, transdermally, or subdermally.

8. The method of claim 1, wherein the composition is a delayed or sustained release formulation.

9. The method of claim 1, wherein the administration is via a lotion, a spray solution, a foam solution, a pad, a bandage, or a transdermal patch.

10. A method of modulating estrogenic hormone action to ameliorate or enhance at least one condition of the skin or hair of a subject, comprising administering a composition comprising racemic equol, wherein the racemic equol binds estrogen receptor subtypes, and wherein ameliorating or enhancing at least one condition of the skin or hair of the subject comprises at least one of:

a) enhancing antioxidant content of the skin;

b) reducing skin inflammation;

c) improving skin thickness;

d) reducing skin adipose tissue (fat) and cellulite formation;

e) enhancing skin blood flow;

f) enhancing collagen and elastin;

g) improving skin abrasions and the appearance of scars;

h) enhancing wound healing;

i) diminishing skin pigmentation or dermal age spots;

j) enhancing skin lightening;

k) diminishing facial hair (hirsutism) or body hair; and

l) reducing skin oil production.

11. The method of claim 10, wherein the composition is for oral administration and comprises a dose sufficient to produce a concentration of the racemic equol in the bloodstream of the subject of at least about 0.2 mg equol per kg weight of the subject.

12. The method of claim 10, wherein the composition is for oral administration and comprises at least 1 mg of racemic equol in a food, bar, drink, tablet or capsule.

13. The method of claim 10, wherein the composition is for topical administration and comprises from about 0.1% to about 10% racemic equol.

14. The method of claim 10, wherein the composition is for topical or subdermal administration and comprises from about 0.1% to about 10% racemic equol for diminishing facial or body hair.

15. The method of claim 10, wherein the composition comprises a pharmaceutical active or an excipient.

16. The method of claim 10, wherein the administering is topically, transdermally, or subdermally.

17. The method of claim 10, wherein the composition is a delayed or sustained release formulation.

18. The method of claim 10, wherein the administration is via a lotion, a spray solution, a foam solution, a pad, a bandage, or a transdermal patch.