Topical composition for follicular delivery of an ornithine decarboxylase inhibitor
View Patent ↗Polyethylene glycol ethers of alkyl alcohols having the general formula CH 3 (CH 2 ) x CH 2 (OCH 2 CH 2 ) n OH wherein x is 8 to 20 (of which ceteareth-20, steareth-20 and steareth-100 are preferred), poloxamer 185, poloxamer 407, N,N-dimethyl dodecylamine N-oxide, and mixtures thereof, are employed to increase follicular delivery and/or follicular residence time of certain water soluble ornithine decarboxylase inhibitors of which 2(difluoromethyl)-2,5-diamino pentanoic acid and its pharmaceutically acceptable salts, hydrates, optical enantiomers and racemic mixture are preferred.
1. A topical composition for follicular delivery of an ornithine decarboxylase inhibitor to an area of mammalian skin containing hair follicles, the composition comprising:
a) an amount of an ornithine decarboxylase inhibitor selected from the group consisting of 2-(difluoromethyl)-2,5 -diaminopentanoic acid, alpha-ethynyl ornithine, 6heptyne-2,5-diamine,2-methyl-6-heptyne-2,5-diamine, and pharmaceutically acceptable salts, hydrates, optical enantiomers, and racemic mixtures thereof sufficient to deliver 1 to 2000 micrograms of the omithine decarboxylase inhibitor per square centimeter (cm 2 ) of the skin;
b) 1.0 to 25% of a follicular delivery enhancer, which provides a follicular enhancement ratio of at least 1.3 and is selected from the group consisting of poloxamer 185, poloxamer 407, N,N-dimethyl dodecylamine N-oxide, steareth-100, and mixtures thereof; and
c) a pharmaceutically acceptable carrier.
2. The composition, as claimed in claim 1 , wherein the inhibitor is 2-(difluoromethyl)-2,5-diaminopentanoic acid or a pharmaceutically acceptable salt, hydrate, (R) enantiomer, (S) enantiomer, or racemic mixture thereof.
3. The composition, as claimed in claim 1 , wherein the inhibitor is 2-(di fluoromethyl)-2,5-diaminopentanoic acid.
4. The composition, as claimed in claim 1 , wherein the ihhibitor is the R enantiomer of 2-(difluoromethyl)-2,5-diaminopentanoic acid.
5. The composition, as claimed in claim 1 , wherein the composition is a water-in-oil emulsion, an oil-in-water emulsion, a solution, a gel, a cream, a stick, an ointments a paste, a shampoo, a foam, a patch or a mousse.
6. The composition, as claimed in claim 1 , wherein the composition is an oil-in-water emulsion based lotion or cream.
7. The composition, as claimed in claim 1 , wherein the carrier is water and the composition is a solution.
8. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer is present in an amount from 2.5% to 20% w/w based on the total weight of the composition.
9. The composition, as claimed in claim 1 , wherein the follicular delivery enhanceris present in an amount from 4% to 15% w/w based on the total weight of the composition.
10. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer is present in an amount from 5% to 10% w/w based on the total weight of the composition.
11. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer is present in an amount of at least 3% w/w based on the total weight of the composition.
12. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer is present in an amount of at least4% w/w based on the total weight of the composition.
13. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer comprises steareth-100.
14. The composition, as claimed in claim 13 , further comprising steareth-20.
15. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer comprises poloxamer 185.
16. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer comprises poloxamer 407.
17. The composition, as claimed in claim 1 , wherein the follicular delivery enhancer comprises N,N-dimethyl dodecylamine-N-oxide.
18. The composition, as claimed in claim 1 , further comprising an amount of an inhibitor of S-adenosyl methionine decarboxylase effective to reduce the rate and alter the character of mammalian hair growth.
19. The composition, as claimed in claim 18 , wherein the inhibitor of S-adenosyl methionine decarboxylase is selected from the group consisting of methylglyoxal bis (guanylhydrazone), diethylglyoxal bis (guanylhydrazone), and 5 ′-deoxy-5′-{N-methyl-N-}aminoadenosine.
20. The composition, as claimed in claim 14 , wherein 5% w/w steareth-20 and 5% w/w stearelh-100, based on the total weight of the composition, are present.
21. The composition, as claimed in claim 15 , where in the poloxamer 185 is present in an amount of 10% w/w based on the total weight of the composition.
22. The composition, as claimed in claim 16 , wherein poloxamer 407 is present in an amount of 10% w/w based on the total weight of the composition.
23. The composition, as claimed in claim 17 , wherein N,N-dimethyl dodecylamine N-oxide is present in an amount of 0.5% w/w based on the total weight of the composition.
24. The composition, as claimed in claim 14 , further comprising ceteareth-20.
25. The composition, as claimed in claim 24 , wherein 5% w/w steareth-20, 5% w/w steareth-100, and 2.5% w/w cetearyl alcohol and ceteareth-20, based on the total weight of the composition, are present.
26. The composition, as claimed in claim 14 , wherein the steareth-20 and steareth-100are present in a ratio of 1:1.