Skin lightening agents, compositions and methods

• US 20050191250A1
• Filed: 02/27/2004
• Published: 09/01/2005
• Est. Priority Date: 02/27/2004
• Status: Active Grant

• Current Assignee: Unilever Home & Personal Care USA (Unilever PLC)
• Original Assignee: Unilever Home & Personal Care USA (Unilever PLC)
• Inventors: Bosko, Carol Annette, Bajor, John Steven, Barratt, Michael James, Harichian, Bijan, Rosa, Jose
• Granted Patent: US 7,300,646 B2
• Time in Patent Office: Days
• US Class Current: 424/59
• CPC Class Codes: A61K 2800/782 Enzyme inhibitors; Enzyme antagonists
• CPC Class Codes: A61K 8/365 Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61Q 19/02 for chemically bleaching or whitening the skin
• CPC Class Codes: C07C 59/52 a hydroxy or O-metal group being bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/732 of unsaturated hydroxy carboxylic acids

Abstract

Disclosed are coumarin derived compounds of formula I as skin lightening agents alone or in combination with other skin benefit agents and together with a cosmetic vehicle:

• • Where each or both R₁ and/or R₂ represents hydrogen (H); linear or branched, saturated or unsaturated C₁-C₁₂ alkyl, alkenyl, acyl, or heteroalkyl (preferably, alkoxy) groups; and
  • R₃ represents linear or branched, cyclic or acyclic, saturated or unsaturated C₁-C₁₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, or heteroalkyl group; and
  • R₄ represents a hydrogen atom (H); straight or branched, cyclic or acyclic, saturated or unsaturated, containing or not containing a heteroatom C₁-C₂₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, heteroalkyl, aryl, or heteroaryl group. In a most preferred embodiment, each R₁, R₂ and R₄ represent H, while R₃ represents a methyl group, referred to herein as a 4-methyl 7-hydroxy-coumarin derivative, or coumarin derived resorcinol derivative, which may be prepared by catalytic (nickel or paladium catalyst) hydrogenation of 4-methyl 7-hydroxy-coumarin followed by hydrolysis. The inventive compounds, compositions and methods have effective skin lightening properties, may be less irritating to the skin, and are cost-effective and relatively simple to manufacture. Also disclosed are processes for making the inventive compounds of general formula I from 4-substituted-7-hydroxy coumarin derivatives.

Claims

1. A cosmetic method of skin lightening comprising applying to the skin a composition comprising:

a. about 0.000001 to about 50% of a compound of general formula I

Where each or both R₁ and/or R₂ represents hydrogen (H);

linear or branched, saturated or unsaturated C₁-C₁₂ alkyl, alkenyl, acyl, or heteroalkyl groups;

R₃ represents linear or branched, cyclic or acyclic, saturated or unsaturated C₁-C₁₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, or heteroalkyl group;

R₄ represents a hydrogen atom (H);

straight or branched, cyclic or acyclic, saturated or unsaturated, containing or not containing a heteroatom C₁-C₂₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, heteroalkyl, aryl, or heteroaryl group; and

b. a cosmetically acceptable carrier.

2. The method of claim 1, wherein said composition further comprises a sunscreen.

3. The method of claim 2, wherein said sunscreen is a micronized metal oxide.

4. The method of claim 1, wherein said compound is a 4-methyl 7-hydroxy coumarin derived resorcinol derivative.

5. The method of claim 1, wherein said compound is a compound of formula II:

6. The cosmetic method of claim 1, wherein R₁ and R₂ both represent hydrogen.

7. The cosmetic method according to claim 1, wherein said composition further comprises a skin benefit agent selected from the group consisting of alpha-hydroxy acids, beta-hydroxy acids, polyhydroxy acids, hydroquinone, t-butyl hydroquinone, Vitamin C derivatives, dioic acids, retinoids, resorcinol derivatives, and mixtures thereof.

8. The cosmetic method of claim 1, wherein said composition further comprises an organic sunscreen selected from the group consisting of Benzophenone-3, Benzophenone-4, Benzophenone-8, DEA, Methoxycinnamate, Ethyl dihydroxypropyl-PABA,-Glyceryl PABA, Homosalate, Methyl anthranilate, Octocrylene, Octyl dimethyl PABA, Octyl methoxycinnamate (PARSOL MCX), Octyl salicylate, PABA, 2-Phenylbenzimidazole-5-sulphonic acid, TEA salicylate, 3-(4-methylbenzylidene)-camphor, Benzophenone-1, Benzophenone-2, Benzophenone-6, Benzophenone-12, 4-Isopropyl dibenzoyl methane, Butyl methoxy dibenzoyl methane (PARSOL 1789), Etocrylene, and mixtures thereof.

19. The compound of claim 1, wherein said compound is a 4-methyl 7-hydroxy coumarin derived resorcinol derivative.

20. The compound of claim 1, wherein R₁ and R₂ both represent hydrogen.

9. A cosmetic composition comprising:

a. about 0.000001 to about 50% of a compound of general formula I;

wherein each or both R₁ and/or R₂ represents hydrogen (H);

linear or branched, saturated or unsaturated C₁- C₁₂ alkyl, alkenyl, acyl, or heteroalkyl groups;

R₃ represents linear or branched, cyclic or acyclic, saturated or unsaturated C₁-C₁₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, or heteroalkyl group;

R₄ represents a hydrogen atom (H);

straight or branched, cyclic or acyclic, saturated or unsaturated, containing or not containing a heteroatom C₁-C₂₂ alkyl, alkenyl, cycloalkyl, cycloalkenyl, heteroalkyl, aryl, or heteroaryl group; and

b. a cosmetically acceptable carrier.

10. The cosmetic composition of claim 9, wherein said compound is a compound of formula II:

11. The cosmetic composition of claim 9, wherein R₁ and R₂ both represent hydrogen.

12. The cosmetic composition of claim 9, wherein said compound comprises about 0.00001% to about 10% of said composition.

13. The cosmetic composition of claim 9, wherein said compound comprises about 0.001% to about 7% of said composition.

14. The cosmetic composition of claim 9, wherein said compound comprises about 0.01% to about 5% of said composition.

15. A process for making compounds having a general formula selected from the group consisting of B, C, D, and mixtures thereof, comprising:

16. The process of claim 15 further comprising substitution of the 1,3-hydroxy positions of the phenyl ring to yield compound of general formula I:

17. A compound of general formula I

18. The compound of claim 17, wherein said compound is a compound of formula II: