Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives

Patent metadata

Field	Value
Publication number	US-9346837-B2
Application number	US-201314099756-A
Country	US
Kind code	B2
Filing date	Dec 6, 2013
Priority date	Mar 31, 2000
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

A method for treating hair loss in mammals uses compositions containing 2-decarboxy-2-phosphinico prostaglandin derivatives. The compositions can be applied topically to the skin. The compositions can arrest hair loss, reverse hair loss, and promote hair growth. Compositions containing 2-decarboxy-2-phosphinico prostaglandin derivatives can also be used to lower intraocular pressure and treat bone disorders.

First claim

What is claimed is:

1. A method for treating hair loss comprising administering to a mammal suffering from hair loss, a composition comprising:
A) an active ingredient selected from the group consisting of 2-decarboxy-2-phosphinico derivatives of prostaglandins; optical isomers, diastereomers, and enantiomers of the 2-decarboxy-2-phosphinico derivatives; pharmaceutically-acceptable salts of the 2-decarboxy-2-phosphinico derivatives; amides, esters, and imides of the 2-decarboxy-2-phosphinico derivatives; and combinations thereof, wherein the 2-decarboxy-2-phosphinico derivative has a structure selected from the group consisting of:

wherein R 1 is selected from the group consisting of a hydrogen atom, and lower monovalent hydrocarbon groups, and lower heterogeneous groups;
R 2 is selected from the group consisting of a hydrogen atom, 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;
R 3 is selected from the group consisting of an oxygen atom, a sulfur atom, and NH;
R 4 is selected from the group consisting of an oxygen atom and a sulfur atom;
R 5 is a divalent group selected from the group consisting of a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, and a substituted heterogeneous group; with the proviso that when R 5 is a heterogeneous group, R 5 has only one heteroatom, which is selected from the group consisting of oxygen, sulfur, and nitrogen;
bond a is selected from the group consisting of a single bond, a trans double bond, and a triple bond;
R 6 is a divalent group selected from the group consisting of —C(O)— and —C(R 9 )(OR 9 )—;
R 7 is selected from the group consisting of a divalent group having the formula —(CR 9 (R 9 )) p —X—(CR 9 (R 9 )) q , wherein p is an integer from 0 to 3 and q is an integer from 0 to 3, and wherein X is selected from the group consisting of an oxygen atom, a divalent hydrocarbon group, a sulfur atom, SO, SO 2 , and NR 9 ;
R 8 is selected from the group consisting of a methyl group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, aromatic group, a substituted aromatic group, a heteroaromatic group, a substituted heteroaromatic group;
R 9 is selected from the group consisting of a hydrogen atom and a lower monovalent hydrocarbon group; and
R 10 is selected from the group consisting of a hydrogen atom and a lower monovalent hydrocarbon group.

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

3. The method of claim 2 , 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.

4. The method of claim 3 , wherein the composition is a topical composition further comprising B) a topical carrier, wherein the topical carrier comprises an ingredient selected from the group consisting of q) emollients, r) propellants, s) solvents, t) humectants, u) thickeners, v) powders, w) fragrances, 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.

5. 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.

6. The method of claim 5 , 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.

7. The method of claim 5 , 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 sulfoxide, 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.

8. The method of claim 2 , wherein the composition is a topical composition locally administered on the skin once per day.

9. The method of claim 8 , wherein the composition is administered once per day for 6 to 12 weeks.

10. The method of claim 1 , wherein R 2 is selected from the group consisting of H, CH 2 CO 2 H, CH 2 C(O)NHOH, methyl, CF 3 , ethyl, n-propyl, isopropyl, CH 2 CH 2 OH, CH 2 CH(OH)CH 2 OH, benzyl, and t-butyl.

11. The method of claim 1 , wherein R 3 is selected from the group consisting of an oxygen atom and NH.

12. The method of claim 1 , wherein R 4 is an oxygen atom.

13. The method of claim 1 , wherein R 5 has 1 to 5 member atoms.

14. The method of claim 1 , wherein R 6 is —C(H)(OH)—.

15. The method of claim 1 , wherein X is selected from the group consisting of an oxygen atom, a sulfur atom, and NR 9 .

16. The method of claim 1 , wherein R 8 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, aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group.

17. The method of claim 1 , wherein R 9 is a hydrogen atom.

Assignees

• Univ Duke

Inventors

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

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/662

  Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon · CPC title

• A61Q1/10

  for eyes, e.g. eyeliner, mascara · CPC title

• A61Q7/00

  Preparations for affecting hair growth · CPC title

• A61Q5/065

  Preparations for temporary colouring the hair, e.g. direct dyes · CPC title