Inhibitors of melanocyte tyrosinase as topical skin lighteners

Abstract

Methods and formulations are provided to reduce pigmentation in skin, using an array of compounds selected from benzimidazoles, phenylthioureas, phenyltiols, phenylamines, bi- and multicyclic phenols, thiopheneamines, and benzothiamides. The compounds preferably inhibit pigment systhesis in melanocytes through the tyrosinase pathway. The methods can be used for lightening skin, and for treating uneven skin complexions which result from hyperpigmentation-related medical conditions such as melasma, age spots, freckles, ochronosis, and lentigo. The compounds can be used medically or cosmetically.

Description

CROSS REFERENCE TO PRIOR APPLICATIONS [0001] This application is a continuation of U.S. Ser. No. 09 / 795,683, filed Feb. 28, 2001, now abandoned and further claims priority to U.S. provisional patent application No. 60 / 185,610, filed Feb. 29, 2000. This application incorporates the entire disclosure of U.S. Ser. No. 09 / 795,683 and 60 / 185,610 as if fully set forth herein.FIELD OF THE INVENTION [0002] The present invention relates to compounds and methods for inhibiting the activity of melanocyte tyrosinase in mammalian skin, in order to reduce the expression and production of skin pigmentation, and thereby lighten the color of mammalian skin. BACKGROUND OF THE INVENTION [0003] Melanogenesis is the process of production and subsequent distribution of melanin by melanocytes within the skin and hair follicles [1, 2]. Melanocytes have specialized lysosome-like organelles, termed melanosomes, which contain several enzymes that mediate the production of melanin. The copper-containing enzyme...

AI Technical Summary

Benefits of technology

[0028] 2. To lessen the hue of pigmented skin blemishes such as freckles and age spots;

[0033] 7. To reduce skin pigmentation in normal skin adjacent to areas affected by vitiligo, thereby diminishing the contrast in color between normal and vitiligo affected skin.

[0035] The compounds are typically applied topically to the skin wherein tyrosinase activity is sought to be reduced through a lotion or occlusive patch. The compounds can be spread over a larger area to produce an even skin tone fade, or they can be applied locally to skin blemishes and other localized conditions to minimize skin irregularities. Moreover, because most of the compounds are selective against melanocyte tyrosinase, the compounds can also be administered systemically by methods including oral, intradermal, transdermal, intraveneous, and parenteral administrations. The product works by inhibiting the production of melanin in cells beneath the skin surface. Because the skin naturally renews itself every ca. 28 days, when the compounds of the present invention are administered old (differentiated) pigmented keratinocytes cells are gradually sloughed off and keratinocytes with less melanin are eventually brought to the surface giving the skin a lighter, more even toned complexion.

Problems solved by technology

However, acute or persistent UVB exposure can result in the formation of hyperpigmented lesions or regions of skin, including malignant melanoma skin cancer.

[17, 18, 20] Although it would be desirable to restore lost pigmentation in vitiligo-affected skin with topical therapies, this has proven to be quite difficult to accomplish in a high proportion of subjects.

Although it has been repeatedly asserted in the dermatologic literature for many years, without substantiation, that HQ is an inhibitor of tyrosinase, this compound is not an effective inhibitor of the mammalian enzyme [5, 6, 25].

MG has not been developed as a commercially available topical skin lightener product to date.

The compounds are various benzimidazolethiols, but have not been developed as commercially available topical skin lightener products to date.

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