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

Patent metadata

Field	Value
Publication number	US-9579270-B2
Application number	US-201514958334-A
Country	US
Kind code	B2
Filing date	Dec 3, 2015
Priority date	Mar 31, 2000
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

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.

First claim

What is claimed is:

1. A method of growing hair, wherein the method comprises topically applying to mammalian skin a safe and effective amount of a composition comprising:
A) an active ingredient selected from the group consisting of a prostaglandin F analog of the following structure:

and pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of C(O)NHOH, CH 2 OH, S(O) 2 R 3 , C(O)NHR 3 , and C(O)NHS(O) 2 R 4 ;
R 2 is selected from the group consisting of a hydrogen atom, a lower heterogeneous group, and a lower monovalent hydrocarbon group;
R 3 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;
R 4 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—, —(CH 2 ) n —, wherein n is 2 to 4, —CH 2 NH—, —CH 2 S—, and —CH 2 O—;
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 R 1 is selected from the group consisting of C(O)NHOH, C(O)NHR 3 , and C(O)NHS(O) 2 R 4 .

3. The method of claim 1 , wherein R 2 is a hydrogen atom.

4. The method of claim 1 , wherein R 3 is selected from the group consisting of methyl, ethyl, and isopropyl.

5. The method of claim 1 , wherein Z is an aromatic group.

6. The method of claim 1 , 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.

7. The method of claim 1 , 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.

8. The method of claim 1 , 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.

9. The method of claim 8 , wherein component i) is selected from the group vasodilator, an antiandrogen, a cyclosporin, an antimicrobial, an anti-inflammatory, a thyroid hormone, a non-selective prostaglandin agonist, a non-selective prostaglandin antagonist, a retinoid, a triterpene, and combinations thereof.

10. The method of claim 8 , 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.

11. The method of claim 1 , wherein the composition is a topical composition locally administered on the skin once per day.

12. The method of claim 11 , wherein the composition is administered once per day for 6 to 12 weeks.

13. The method of claim 1 , wherein the composition is topically applied directly to the locus of desired hair growth.

14. The method of claim 1 , wherein the prostaglandin F analog is selective for an FP receptor over an excitatory prostaglandin receptor in a ratio of at least 1:10.

15. The method of claim 1 , wherein the prostaglandin F analog is selective for an FP receptor over an excitatory prostaglandin receptor in a ratio of at least 1:20.

16. The method of claim 1 , wherein the prostaglandin F analog is selective for an FP receptor over an excitatory prostaglandin receptor in a ratio of at least 1:50.

17. A method of growing hair, wherein the method comprises topically applying to mammalian skin a safe and effective amount of a composition comprising:
A) an active ingredient selected from the group consisting of a prostaglandin F analog of the following structure:

and pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of C(O)NHOH, C(O)NHR 3 , and C(O)NHS(O) 2 R 4 ;
R 2 is a hydrogen atom;
R 3 is methyl, ethyl or isopropyl;
R 4 is phenyl or methyl;
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—, and —(CH 2 ) n —, wherein n is 2 to 4;
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.

18. The method of claim 17 , wherein R 1 is selected from the group consisting of C(O)NHOH and C(O)NHS(O) 2 R 4 .

19. The method of claim 17 , wherein R 1 is selected from the group consisting of C(O)NHR 3 and C(O)NHS(O) 2 R 4 .

20. The method of claim 17 , wherein R 1 is selected from the group consisting of C(O)NHOH and C(O)NHR 3 .

21. The method of claim 17 , wherein R 1 is C(O)NHOH.

22. The method of claim 17 , wherein R 1 is C(O)NHR 3 .

Assignees

• Univ Duke

Inventors

• Delong Mitchell A
• Mciver John M
• Youngquist Robert S

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P17/14

  for baldness or alopecia · CPC title

• A61Q7/00

  Preparations for affecting hair growth · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title