# US 7,407,987 B2 · Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins

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- Number: US 7,407,987 B2
- Document ID: US7407987B2
- Status: Granted
- Kind: B2
- Application number: 11/565,297
- Filed: 2006-11-30
- Published: 2007-04-26
- Granted: 2008-08-05
- Earliest claimed: 2000-03-31
- Assignees: Duke University
- Inventors: Mitchell Anthony deLong; John McMillan McIver; Robert Scott Youngquist
- Web page: https://patentgrep.com/patent/US7407987B2

## CPC

- A61K 8/365: Hydroxycarboxylic acids; Ketocarboxylic acids
- A61K 8/46: containing sulfur (A61K8/44 takes precedence)
- A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- A61P 17/14: for baldness or alopecia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61Q 7/00: Preparations for affecting hair growth
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## 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

### Claim 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 the structure
and pharmaceutically acceptable salts and hydrates of the prostaglandin F analog; biohydrolyzable amides, esters, and imides of the prostaglandin F analog; optical isomers, diastereomers, and enantiomers of the prostaglandin F analog; and combinations thereof;
wherein R1 is selected from the group consisting of CO2H, C(O)NHOH, CO2R5, CH2OH, S(O)2R5, C(O)NHR5, C(O)NHS(O)2R5, and tetrazole;
R2 is selected from the group consisting of a hydrogen atom and a lower monovalent hydrocarbon group;
R3 and R4 are each independently selected from the group consisting of H, CH3, C2H5, OR10, SR10, and OH; with the proviso that both R3 and R4 are not OH;
R5 is selected from the group consisting of monovalent hydrocarbon groups, substituted monovalent hydrocarbon groups, aromatic groups, substituted aromatic groups, carbocyclic groups, substituted carbocyclic groups, heterogeneous groups, substituted heterogeneous groups, heterocyclic groups, substituted heterocyclic groups, heteroaromatic groups, and substituted heteroaromatic groups;
X is selected from the group consisting of NR6R7, OR8, SR9, S(O)R9, and S(O)2R9;
R6, R7, and R8 are each independently selected from the group consisting of hydrogen atoms, acyl groups, monovalent hydrocarbon groups, substituted monovalent hydrocarbon groups, heterogeneous groups, substituted heterogeneous groups, carbocyclic groups, substituted carbocyclic groups, aromatic groups, substituted aromatic groups, heteroaromatic groups, and substituted heteroaromatic groups;
R9 is selected from the group consisting of monovalent hydrocarbon groups, substituted monovalent hydrocarbon groups, heterogeneous groups, substituted heterogeneous groups, carbocyclic groups, substituted carbocyclic groups, heterocyclic groups, substituted heterocyclic groups, aromatic groups, substituted aromatic groups, heteroaromatic groups, and substituted heteroaromatic groups;
R10 is selected from the group consisting of a monovalent hydrocarbon group, a substituted monovalent hydrocarbon group, a heterogeneous group, substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group; with the proviso that R10 has 1 to 8 member atoms;
Y is selected from the group consisting of an oxygen atom, a divalent hydrocarbon group, a sulfur-containing moiety, and a nitrogen-containing group; and
Z is selected from the group consisting of a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group.

### Claim 2 (depends on 1)

The method of claim 1, wherein R1 is selected from the group consisting of CO2H, CO2CH3, CO2C2H5, CO2C3H7, CO2C4H9, CO2C3H7O2, and C(O)NHS(O)2R5.

### Claim 3 (depends on 1)

The method of claim 1, wherein R5 is selected from the group consisting of CH3, C2H5, and C3H7.

### Claim 4 (depends on 1)

The method of claim 1, wherein R2 is selected from the group consisting of a hydrogen atom and a methyl group.

### Claim 5 (depends on 1)

The method of claim 1, wherein R3 and R4 are both hydrogen atoms.

### Claim 6 (depends on 1)

The method of claim 1, wherein X is selected from the group consisting of NR6R7 and OR8.

### Claim 7 (depends on 1)

The method of claim 1, wherein R6 and R7 are each independently selected from the group consisting of H, CH3, and C2H5.

### Claim 8 (depends on 1)

The method of claim 1, wherein R8 is selected from the group consisting of H, CH3, C2H5, and C3H7.

### Claim 9 (depends on 1)

The method of claim 1, wherein R9 is selected from the group consisting of CH3, and C2H5.

### Claim 10 (depends on 1)

The method of claim 1, wherein Y is a divalent hydrocarbon group having the formula (CH2)n, wherein n is 1.

### Claim 11 (depends on 1)

The method of claim 1, wherein Y is selected from the group consisting of a sulfur atom, an oxygen atom, S(O), and S(O)2.

### Claim 12 (depends on 1)

The method of claim 1, wherein Y is a nitrogen-containing group having the formula NR11; wherein R11 is selected from the group consisting of a hydrogen atom, an acyl group, a monovalent hydrocarbon group, a substituted monovalent hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group.

### Claim 13 (depends on 1)

The method of claim 1, wherein Z is selected from the group consisting of a monocyclic carbocyclic group, a substituted monocyclic carbocyclic group, a monocyclic heterocyclic group, a substituted monocyclic heterocyclic group, a monocyclic aromatic group, a substituted monocyclic aromatic group, a monocyclic heteroaromatic group, and a substituted monocyclic heteroaromatic group.

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 14)

The method of claim 14, 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.

### Claim 16 (depends on 14)

The method of claim 14, wherein the composition is a topical composition further comprising B) a carrier comprising an ingredient 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, q) emollients, r) propellants, s) solvents, t) humectants, u) thickeners, v) powders, w) fragrances, and combinations thereof.

### Claim 17 (depends on 14)

The method of claim 14, 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.

### Claim 18 (depends on 17)

The method of claim 17, 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.

### Claim 19 (depends on 17)

The method of claim 17, 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-1-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.

### Claim 20 (depends on 14)

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

### Claim 21 (depends on 20)

The method of claim 20, wherein the composition is administered once per day for 6 to 12 weeks.