Resorcinol derivatives

• US 6,132,740 A
• Filed: 09/15/1998
• Issued: 10/17/2000
• Est. Priority Date: 09/23/1997
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Hu, Lan
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US09/153,479
• Time in Patent Office: 763 Days
• Field of Search: 424/401, 424/59, 424/60, 424/62, 514/730, 514/731, 514/732, 514/733, 514/844
• US Class Current: 424/401
• CPC Class Codes: A61K 2800/782 Enzyme inhibitors; Enzyme antagonists
• CPC Class Codes: A61K 8/347 Phenols
• CPC Class Codes: A61K 8/365 Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/41 Amines
• CPC Class Codes: A61K 8/46 containing sulfur A61K8/44 takes precedence
• CPC Class Codes: A61K 8/671 Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61Q 19/02 for chemically bleaching or whitening the skin
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10S 977/926 Topical chemical, e.g. cosmetic or sunscreen

Abstract

The present invention relates to the use of certain resorcinol derivatives as skin lightening agents.

Claims

1. A topical pharmaceutical composition for lightening skin or reducing the pigmentation of skin in a human, comprising an amount of a compound of the formula I, ##STR3## wherein X is hydrogen;

OR¹, wherein R¹ represents hydrogen, (C₁ -C₆)alkyl or aryl-(C₁ -C₆)alkyl;

OCOR² wherein R² represents (C₁ -C₆)alkyl, aryl-(C₁ -C₆)alkyl or phenyl;

halogen;

(C₁ -C₆)alkyl;

aryl-(C₁ -C₆)alkyl;

SR³ wherein R³ represents hydrogen, (C₁ -C₆)alkyl, or aryl-(C₁ -C₆)alkyl;

or NHR¹ wherein R¹ is defined as above;

n is 0; and

the dashed line represents an optional double bond;

or a pharmaceutically acceptable salt thereof, that is effective in lightening skin or reducing the pigmentation of skin, and a pharmaceutically acceptable carrier.

2. The topical pharmaceutical composition of claim 1, wherein the compound of formula I is 4-cyclopentylresorcinol.

3. The composition of claim 2, which is in the form of a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

4. The composition of claim 2, which is in the form of a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

5. A composition according to claim 1, which further comprises a sunscreen.

6. A composition according to claim 1, further comprising resveratrol or another active agent that is an anti-oxidant.

7. A composition according to claim 1, further comprising retinoic acid or a derivative of retinoic acid.

8. A composition according to claim 1, further comprising glycolic acid, trichloroacetic acid or another skin peeling agent.

9. A composition according to claim 1 in the form of a lotion, cream or ointment.

10. The composition of claim 1, which is in the form of a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

11. The composition of claim 1, which is in the form of a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

12. The composition of claim 1, wherein the amount of the compound of formula I is a tyrosinase-inhibiting effective amount.

13. A method of lightening skin or reducing the pigmentation of skin in a human, in need of said treatment comprising administering to said human an amount of a compound of the formula I, ##STR4## wherein X is hydrogen;

OR¹, wherein R¹ represents hydrogen, (C₁ -C₆)alkyl or aryl-(C₁ -C₆)alkyl;

OCOR² wherein R² represents (C₁ -C₆)alkyl, aryl-(C₁ -C₆)alkyl or phenyl;

halogen;

(C₁ -C₆)alkyl;

aryl-(C₁ -C₆)alkyl;

SR³ wherein R³ represents hydrogen, (C₁ -C₆)alkyl, or aryl-(C₁ -C₆)alkyl;

or NHR¹ wherein R¹ is defined as above;

n is 0 to 3; and

the dashed line represents an optional double bond;

or a pharmaceutically acceptable salt thereof, that is effective in lightening skin or reducing the pigmentation of skin.

14. The method of claim 13, wherein the compound of formula I is 4-cyclohexylresorcinol.

15. The method of claim 13, wherein the compound of formula I is 4-cyclopentylresorcinol.

16. The method of claim 15, wherein the compound of formula I is formulated in a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

17. The method of claim 15 wherein the compound of formula I is formulated in a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

18. The method of claim 13, wherein the compound of formula I is formulated in a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

19. The method of claim 13, wherein the compound of formula I is formulated in a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

20. The method of claim 13, wherein the amount of the compound of formula I is a tyrosinase-inhibiting effective amount.

21. A method of inhibiting tyrosinase in a human, in need of said treatment comprising administering to said mammal a tyrosinase inhibiting effective amount of a compound of the formula I, ##STR5## wherein X is hydrogen;

OR¹, wherein R¹ represents hydrogen, (C₁ -C₆)alkyl or aryl-(C₁ -C₆)alkyl;

OCOR² wherein R² represents (C₁ -C₆)alkyl, aryl-(C₁ -C₆)alkyl or phenyl;

halogen;

(C₁ -C₆)alkyl;

aryl-(C₁ -C₆)alkyl;

SR³ wherein R³ represents hydrogen, (C₁ -C₆)alkyl, or aryl-(C₁ -C₆)alkyl;

or NHR¹ wherein R¹ is defined as above;

n is 0 to 3; and

the dashed line represents an optional double bond;

or a pharmaceutically acceptable salt thereof.

22. The method of claim 21, wherein the compound of formula I is 4-cyclohexylresorcinol.

23. The method of claim 21, wherein the compound of formula I is 4-cyclopentylresorcinol.

24. The method of claim 23, wherein the compound of formula I is formulated in a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

25. The method of claim 23, wherein the compound of formula I is formulated in a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

26. The method of claim 21, wherein the compound of formula I is formulated in a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

27. The method of claim 21, wherein the compound of formula I is formulated in a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

28. A method of treating an inflammatory disorder in a human, in need of said treatment comprising administering to said human an amount of a compound of the formula I, ##STR6## wherein X is hydrogen;

OR¹, wherein R¹ represents hydrogen, (C₁ -C₆)alkyl or aryl-(C₁ -C₆)alkyl;

OCOR² wherein R² represents (C₁ -C₆)alkyl, aryl-(C₁ -C₆)alkyl or phenyl;

halogen;

(C₁ -C₆)alkyl;

aryl-(C₁ -C₆)alkyl;

SR³ wherein R³ represents hydrogen, (C₁ -C₆)alkyl, or aryl-(C₁ -C₆)alkyl;

or NHR¹ wherein R¹ is defined as above;

n is 0 to 3; and

the dashed line represents an optional double bond;

or a pharmaceutically acceptable salt thereof, that is effective in treating such disorder.

29. The method of claim 28, wherein the compound of formula I is 4-cyclohexylresorcinol.

30. The method of claim 28, wherein the compound of formula I is 4-cyclopentylresorcinol.

31. A method of lightening skin or reducing the pigmentation of skin in a human, comprising administering to said human an amount of a compound of formula I, ##STR7## wherein X is hydrogen;

OR¹, wherein R¹ represents hydrogen, (C₁ -C₆)alkyl or aryl-(C₁ -C₆)alkyl;

OCOR² wherein R² represents (C₁ -C₆)alkyl, aryl-(C₁ -C₆)alkyl or phenyl;

halogen;

(C₁ -C₆)alkyl;

aryl-(C₁ -C₆)alkyl;

SR³ wherein R³ represents hydrogen, (C₁ -C₆)alkyl, or aryl-(C₁ -C₆)alkyl;

or NHR¹ wherein R¹ is defined as above;

n is 0;

and the dashed line represents an optional double bond;

or a pharmaceutically acceptable salt thereof;

which amount of the compound of formula I or pharmaceutically acceptable salt thereof is effective in lightening skin or reducing the pigmentation of skin in said human.

32. The method of claim 31, wherein the compound of formula I is 4-cyclopentylresorcinol.

33. The method of claim 31, wherein the compound of formula I or pharmaceutically acceptable salt thereof is formulated in a water-alcohol solution, an oil-in-water emulsion, a water-in-oil emulsion, an emulsified gel, or a two-phase system.

34. The method of claim 31, wherein the compound of formula I or pharmaceutically acceptable salt thereof is formulated in a lotion, cream, milk, gel, jelly, paste, ointment, salve, mask, microspheres, nanospheres, or a vesicular dispersion.

35. The method of claim 31, wherein the amount of the compound of formula I is a tyrosinase-inhibiting effective amount.