Use of 2,5-dihydroxybenzene sulfonic acid compounds for treating skin photoaging

1. A method for the treatment of skin having wrinkles, the method comprising topically administering, to a subject in need thereof, a 2,5-dihydroxybenzene derivative represented by Formula (I) or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is —(CH 2 ) a Y or —CH═CH—(CH 2 ) p Y;

Y is —SO 3 H, —SO 3 − .X + , or —SO 3 R 3 ;

X + is an organic cation or an inorganic cation, such that the general charge of the compound of Formula (I) is neutral;

R 9 and R 9 ′ are independently selected from —OH and —OR 2 , wherein when R 9 and R 9 ′ are both —OR 2 , then said R 9 and R 9 ′ can be the same or different;

R 2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylsulfonyl group, a substituted or unsubstituted arylsulfonyl group, a substituted or unsubstituted alkylcarbonyl group or a substituted or unsubstituted arylcarbonyl group;

R 3 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;

a is a number selected from 0, 1, 2, 3, 4, 5 and 6; and

p is a number selected from 0, 1, 2, 3, 4, 5 and 6,

wherein the 2,5-dihydroxybenzene derivative is administered in an amount effective to reduce skin wrinkles.

2. The method of claim 1 , wherein Y is —SO 3 H.

3. The method of claim 1 , wherein the compound of Formula (I) is selected from the group consisting of:

2,5-dihydroxybenzenesulfonic acid (Dobesilate);

5-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}benzenesulfonic acid;

2-hydroxy-5-{[(4-methylphenyl)sulfonyl]oxy}benzenesulfonic acid;

2,5-bis{[(4-methylphenyl)sulfonyl]oxy}benzenesulfonic acid;

2-(acetyloxy)-5-hydroxybenzenesulfonic acid;

5-(acetyloxy)-2-hydroxybenzenesulfonic acid;

2,5-bis(acetyloxy)benzenesulfonic acid;

2-(benzyloxy)-5-hydroxybenzenesulfonic acid;

5-(benzyloxy)-2-hydroxybenzenesulfonic acid;

2,5-bis(benzyloxy)benzenesulfonic acid;

2,5-dihydroxybenzene homosulfonic acid (homodobesilate);

5-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}benzenehomosulfonic acid;

2-hydroxy-5-{[(4-methylphenyl)sulfonyl]oxy}benzenehomosulfonic acid;

2,5-bis{[(4-methylphenyl)sulfonyl]oxy}benzenehomosulfonic acid;

2-(acetyloxy)-5-hydroxybenzenehomosulfonic acid;

5-(acetyloxy)-2-hydroxybenzenehomosulfonic acid;

2,5-bis(acetyloxy)benzenehomosulfonic acid;

2-(benzyloxy)-5-hydroxybenzenehomosulfonic acid;

5-(benzyloxy)-2-hydroxybenzenehomosulfonic acid;

2,5-bis(benzyloxy)benzenehomosulfonic acid;

and pharmaceutically acceptable salts thereof.

4. The method of claim 1 , wherein the compound of Formula (I) is selected from: 2-(acetyloxy)-5-hydroxybenzenesulfonic acid; 5-(acetyloxy)-2-hydroxybenzenesulfonic acid; and 2,5-bis(acetyloxy)benzenesulfonic acid; or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the compound of Formula (I) is administered topically.

6. The method of claim 1 , further comprising at least one coadjuvant therapy selected from the group consisting of: photodynamic therapy, cryotherapy, curettage, and surgery.

7. The method of claim 5 , wherein the compound is administered at least once per week.

8. The method of claim 7 , wherein the compound is administered at least once per day.

9. The method of claim 8 , wherein the compound is administered at least twice per day.

10. The method of claim 5 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 1% w/w.

11. The method of claim 10 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 2.5% w/w.

12. The method of claim 11 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 5% w/w.

13. The method of claim 12 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 10% w/w.

14. The method of claim 13 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 15% w/w.

15. The method of claim 5 , wherein the compound is administered over a period of at least about one week.

16. The method of claim 15 , wherein the compound is administered over a period of at least about four weeks.

17. The method of claim 1 , wherein the compound is potassium 2,5-dihydroxybenzenesulfonate and is administered topically.