Compositions and methods for treating hair loss using non-naturally occurring prostaglandins

• US 20050222232A1
• Filed: 05/26/2005
• Published: 10/06/2005
• Est. Priority Date: 03/31/2000
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Youngquist, Robert Scott, McIver, John McMillan, DeLong, Mitchell Anthony
• Granted Patent: US 7,388,029 B2
• Time in Patent Office: Days
• US Class Current: 514/381
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/558 having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
• CPC Class Codes: A61K 31/559 having heterocyclic rings containing hetero atoms other than oxygen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/365 Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/49 containing heterocyclic compounds
• CPC Class Codes: A61K 8/4986 with sulfur as the only hetero atom
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 7/00 Preparations for affecting hair growth

Abstract

A method for treating hair loss in mammals uses compositions containing prostaglandin F analogs. The compositions can be applied topically to the skin. The compositions can arrest hair loss, reverse hair loss, and promote hair growth.

Claims

1. A method of treating hair loss comprising administering to a mammal a composition comprising:

A) an active ingredient selected from the group consisting of a prostaglandin F analog having a structure selected from the group consisting of

pharmaceutically acceptable salts and hydrates of the structures above;

biohydrolyzable amides, esters, and imides of the structures above;

optical isomers, diastereomers, and enantiomers of the structures above; and

combinations thereof;

wherein R¹ is selected from the group consisting of C(O)OH, C(O)NHOH, C(O)OR³, CH₂OH, S(O)₂R³, C(O)NHR³, C(O)NHS(O)₂R⁴, tetrazole, a cationic salt moiety, a pharmaceutically acceptable amine or ester comprising 2 to 13 carbon atoms, and a biometabolizable amine or ester comprising 2 to 13 atoms;

R² is selected from the group consisting of a hydrogen atom, a lower heterogenous group, and a lower monovalent hydrocarbon group;

R³ is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group;

R⁴ is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group;

X is selected from the group consisting of —

C≡

C—

, a covalent bond, —

CH═

C═

CH—

, —

CH═

CH—

, —

CH═

N—

, —

C(O)—

, —

C(O)Y—

, —

(CH₂)n—

, wherein n is 2 to 4, —

CH₂NH—

, —

CH₂S—

, and —

CH₂O—

;

Y is selected from the group consisting of a sulfur atom, an oxygen atom, and NH; and

Z is selected from the group consisting of a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group.

2. The method of claim 1, wherein R¹ is selected from the group consisting of CO₂H, C(O)NHOH, CO₂R³, C(O)NHS(O)₂R⁴, and tetrazole.

3. The method of claim 1, wherein R² is a hydrogen atom.

4. The method of claim 1, wherein R³ is selected from the group consisting of methyl, ethyl, and isopropyl.

5. The method of claim 1, wherein R⁴ is a phenyl group.

6. The method of claim 1, wherein X is a covalent bond and Z is selected from the group consisting of an aromatic ring, a heteroaromatic ring, a substituted aromatic ring, and a substituted heteroaromatic ring.

7. The method of claim 1, wherein X is —

C≡

C—

, and Z is a monocyclic aromatic ring.

8. The method of claim 1, wherein the composition is administered by a route selected from the group consisting of systemic and topical routes.

9. The method of claim 8, wherein the composition is a topical composition in a form selected from the group consisting of solutions, oils, creams, ointments, gels, lotions, shampoos, leave-on and rinse-out hair conditioners, milks, cleansers, moisturizers, sprays, and skin patches.

10. The method of claim 8, wherein the composition is a topical composition further comprising B) a carrier, wherein the carrier is selected from the group consisting of water, alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, propylene glycol, dimethyl isosorbide, polypropylene glycol-2 myristyl propionate, and combinations thereof.

11. The method of claim 8, wherein the composition further comprises C) an activity enhancer selected from the group consisting of i) a hair growth stimulant, ii) a penetration enhancer, and combinations thereof.

12. The method of claim 11, wherein component i) is selected from the group vasodilator, an antiandrogen, a cyclosporin, a cyclosporin analog, an antimicrobial, an anti-inflammatory, a thyroid hormone, a thyroid hormone derivative, and a thyroid hormone analog, a non-selective prostaglandin agonist, a non-selective prostaglandin antagonist, a retinoid, a triterpene, and combinations thereof.

13. The method of claim 11, wherein component ii) is selected from the group consisting of 2-methyl propan-2-ol, propan-2-ol, ethyl-2-hydroxypropanoate, hexan-2,5-diol, polyoxyethylene(2) ethyl ether, di(2-hydroxypropyl) ether, pentan-2,4-diol, acetone, polyoxyethylene(2) methyl ether, 2-hydroxypropionic acid, 2-hydroxyoctanoic acid, propan-l-ol, 1,4-dioxane, tetrahydrofuran, butan-1,4-diol, propylene glycol dipelargonate, polyoxypropylene 15 stearyl ether, octyl alcohol, polyoxyethylene ester of oleyl alcohol, oleyl alcohol, lauryl alcohol, dioctyl adipate, dicapryl adipate, di-isopropyl adipate, di-isopropyl sebacate, dibutyl sebacate, diethyl sebacate, dimethyl sebacate, dioctyl sebacate, dibutyl suberate, dioctyl azelate, dibenzyl sebacate, dibutyl phthalate, dibutyl azelate, ethyl myristate, dimethyl azelate, butyl myristate, dibutyl succinate, didecyl phthalate, decyl oleate, ethyl caproate, ethyl salicylate, isopropyl palmitate, ethyl laurate, 2-ethyl-hexyl pelargonate, isopropyl isostearate, butyl laurate, benzyl benzoate, butyl benzoate, hexyl laurate, ethyl caprate, ethyl caprylate, butyl stearate, benzyl salicylate, 2-hydroxypropanoic acid, 2-hydroxyoctanoic acid, dimethyl sulphoxide, N,N-dimethyl acetamide, N,N-dimethyl formamide, 2-pyrrolidone, 1-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, phosphine oxides, sugar esters, tetrahydrofurfural alcohol, urea, diethyl-m-toluamide, 1-dodecylazacyloheptan-2-one, and combinations thereof.

14. The method of claim 8, wherein the composition is a topical composition locally administered on the skin once per day.

15. The method of claim 14, wherein the composition is administered once per day for 6 to 12 weeks.