Pharmaceutical and cosmetic depigmentation compositions with a c

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice

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424 62, A61K 7135

Patent

active

051641852

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a pharmaceutical or cosmetic depigmenting composition which contains, as an active ingredient, caffeic acid or one of its derivatives.
It will be remembered that the mechanism which forms skin pigmentation, i.e., the formation of melanins, is especially complex and involves the triggering of the main steps diagrammed below:
The depigmenting agents currently used in cosmetology are, more specifically, phenolic derivatives, and, most notably, hydroquinone or a hydroquinone ether such as hydroquinone monomethyl ether.
While these compounds have a certain level of effectiveness, they are not, unfortunately, free from side effects that make their use a sensitive, and even dangerous, matter.
Thus, hydroquinone, whose use is restricted, moreover, to a 2% concentration, is especially irritating and cytotoxic for melanocytes. Many authors have contemplated its total or partial replacement.
Thus, French Patent No. 87.08236 (2,616,325) proposed a composition containing a combination of hydroquinone and kojic acid or of its derivatives, in particular its salts and esters.
International Application WO 85/0401 proposes, in addition and for the same purpose, a depigmenting composition containing a combination of hydroquinone or its benzylic monoether and salicylic acid.
Moreover, among the compositions producing a pronounced depigmenting action, mention must also be made of the Kligman trio, generally chosen as the compound of reference, which is based on a combination of acidic Vitamin A, hydroquinone, and a steroid, either dexamethasone or hydrocortisone. The use of this composition has, however, been restricted to the extent that it exhibits a high level of irritation caused by acidic Vitamin A as well as undesirable effects caused by hypervitaminosis A.
It has now been well established that a substance produces a depigmenting action if it acts directly on the vitality of the epidermal melanocytes where melanogenesis normally takes place, and/or if it interferes with one of the stages of melanin biosynthesis, either by inhibiting one of the enzymes involved or by its insertion as a structural analogue in the synthesis pathway, which can thus become blocked, thereby producing the depigmenting effect.
The use of harmless topical depigmenting substances exhibiting a high degree of efficacy is most especially sought in order to treat regional hyperpigmentation caused by melanocytic hyperactivity, such as idiopathic melasmas occurring during pregnancy ("mask of pregnancy" or chloasma) or melasmas secondary to estrogen-progesterone contraception, cases of localized hyperpigmentation caused by hyperactivity and benign melanocytic proliferation, such as senile pigmentary spots, termed actinic lentigos, accidental hyperpigmentation such as photosensitization and post-lesion scarring, as well as certain leucodermas such as vitiligo, in which, because pigmentation cannot be restored to the injured skin, the areas of remaining normal skin are depigmented so as to impart to the total skin area a homogeneous white color.
Following various studies conducted on numerous substances used either singly or in combination, it was found, surprisingly and unexpectedly, that caffeic acid or its derivatives, and especially its esters and amides, produced an especially interesting depigmenting action, their efficacy being mainly the result of an inhibition of tyrosinasic activity leading to the limited formation of dopachrome and thus, of melanins.
This new property of caffeic acid and its derivatives had heretofore never been brought to light, despite the many studies conducted on this acid.
Therefore, the present invention relates to a pharmaceutical or cosmetic depigmenting composition used in a topical application and containing, in a vehicle suitable for such an application, an effective quantity of caffeic acid or of one of its esters or amides.
Among the esters of caffeic acid, mention may be made especially of the compounds corresponding to the formula: ##STR1## R representing an alkyl radical of from 1

REFERENCES:
patent: 3982999 (1976-09-01), Kharasch
patent: 4136166 (1979-01-01), Barnett et al.
patent: 4767750 (1988-08-01), Jacquet et al.
patent: 4824865 (1989-04-01), Bowser et al.
patent: 4990330 (1991-02-01), Oyama
Patent Abstracts of Japan, vol. 11, No. 349 (C-456)(2796), Nov. 14, 1987.
Patent Abstract of Japan, vol. 6, No. 44, (C-95)(922), Mar. 19, 1982.

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