Methods and compositions for the treatment of alopecia and other disorders of the pilosebaceous apparatus

• US 7,105,573 B2
• Filed: 02/11/2002
• Issued: 09/12/2006
• Est. Priority Date: 02/23/2000
• Status: Expired due to Fees

• Current Assignee: Orentreich Foundation for the Advancement of Science, Inc.
• Original Assignee: Orentreich Foundation for the Advancement of Science, Inc.
• Inventors: Orentreich, Norman, Krajcik, Rozlyn A.
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): KIM, JENNIFER M
• Application Number:
  US10/073,607
• Publication Number:
  US 20020143039A1
• Time in Patent Office: 1,674 Days
• Field of Search: 514/635
• US Class Current: 514/635
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia

Abstract

Insulin sensitivity increasing substances (ISIS), including but not limited to D-chiro-inositol, thiazolidinedione and derivatives, and biguanides, are useful in the treatment of hair loss and other disorders of the pilosebaceous apparatus (hirsutism, acne, etc.) associated with conditions of excess insulin and/or insulin resistance. The treatment comprises administering to a mammal, such as a human, at least one ISIS either alone or in combination with at least one agent, such as an androgen receptor blocker (ARB) and/or a steroid enzyme inhibitor or inducer (STI). Additionally, an activity enhancing agent may be included for topical administration.

Claims

1. A method of treating alopecia in a mammal comprising administering to the mammal an insulin sensitivity increasing substance (ISIS) in an amount effective to treat the alopecia in the mammal, in a manner so as to reach an affected area of a pilosebaceous apparatus, wherein the ISIS is a biguanide having a formula NH₂C(═

NH)NHC(═

NH)NH₂, an alkyl or aromatic derivative thereof, or a salt thereof.

2. The method of claim 1, wherein treating alopecia comprises at least one of inhibiting, reducing and reversing the loss of hair in the mammal.

3. The method of claim 1, wherein the ISIS is administered topically to the affected site.

4. The method of claim 1, wherein the ISIS is a biguanide having a formula NH₂C(═

NH)NHC(═

NH)NH₂ and its derivatives selected from the group consisting of monomethyl, dimethyl. trimethyl, tetramethyl and phenyl derivatives, and salts thereof.

5. The method of claim 4, wherein the biguanide is metformin hydrochloride.

6. The method of claim 1, wherein the ISIS is administered orally.

7. The method of claim 1, wherein the mammal is a human.

8. The method of claim 1, further comprising administering to the mammal a steroid enzyme inhibitor or inducer (STI) in an amount effective to inhibit or induce the activity of a steroid enzyme in the mammal.

9. The method of claim 1, wherein the steroid enzyme inhibitor or inducer (STI) is selected from the group consisting of a 5-alpha reductase inhibitor (ARI), a 3-alpha hydroxy steroid dehydrogenase inhibitor, and a 17-beta hydroxy steroid dehydrogenase inducer.

10. The method of claim 1, further comprising administering to the mammal an androgen receptor blocking agent (ARB) in an amount effective to block androgen receptor activity in the mammal.

11. The method of claim 1, wherein the androgen receptor blocking agent ARB is a compound selected from the group consisting of cytoproterone acetate, flutamide, bicalutamide, nilutamide, RU-58841, canrenone, spironolactone, progesterone, 4MA, ketoconazole, and cimetidine.

12. The method of claim 1, further comprising administering to the mammal both an androgen receptor blocking agent (ARB) in an amount effective to block androgen receptor activity, and a steroid enzyme inhibitor or inducer (STI) in an amount effective to inhibit or induce the activity of a steroidal enzyme in the mammal.

13. The method of claim 1, further comprising administering to the mammal an activity-enhancing agent where any ISIS alone or in combination with an androgen receptor blocking agent (ARB) or steroid enzyme inhibitor or inducer (STI) is to be administered topically, wherein the activity-enhancing agent is administered to the mammal in an amount effective to enhance the activity of either the ISIS alone or in combination with the androgen receptor blocking agent (ARB) and/or the steroid enzyme inhibitor or inducer (STI).

14. The method of claim 13, wherein the activity-enhancing agent comprises at least one substance selected from the group consisting of a penetration-enhancing agent, a vasodilator compound, an anti-inflammatory agent, a glucose/insulin regulating compound, and an endogenous or exogenous effector.