Use of oxamate derivatives as depigmenting agents

Details Use of oxamate derivatives as depigmenting agents Use of oxamate derivatives as depigmenting agents

2000-05-16

2001-12-04

Page, Thurman K. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Cosmetic, antiperspirant, dentifrice

C424S062000, C424S070100, C260S66500B, C514S575000, C560S043000

Reexamination Certificate

active

06326014

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention:
The present invention relates to the use of oxamate derivatives as depigmenting or bleaching agents in a cosmetic and/or dermatological composition, and to a depigmenting and/or bleaching composition containing oxamate derivatives.
2. Discussion of the Background
The colour of human skin depends on different factors and, in particular, the seasons of the year, race and sex, and it is mainly determined by the nature and concentration of melanin produced by the melanocytes. Melanocytes are specialized cells which synthesize melanin by means of specific organelles, the melanosomes. In addition, at different periods in their life, certain individuals develop darker and/or more coloured blemishes on the skin and more especially on the hands, making the skin non-uniform. These blemishes are also due to a large concentration of melanin in the keratinocytes at the skin surface.
In the same way, the colour of head hair and other hairs is believed to be due to melanin. When head hair or other hairs are dark, certain people wish to have them lighter. This is particularly advantageous for hairs which are less visible when they are light than when they are dark.
The mechanism for the formation of skin pigmentation, and pigmentation of head hair and other hairs, that is to say the formation of melanin, is particularly complex and, schematically, is believed to involve the following main steps:
Tyrosine→Dopa→Dopaquinone→Dopachrome→Melanin
Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this reaction sequence. It is believed to catalyze the reaction for the conversion of tyrosine into dopa (dihydroxyphenylalanine) by virtue of its hydroxylase activity and the reaction for the conversion of dopa into dopaquinone by virtue of its oxidase activity. This tyrosinase is believed to act only when it is in the mature state, under the action of certain biological factors.
A substance is recognized as being depigmenting if it acts directly on the vitality of the epidermal melanocytes in which melanogenesis takes place and/or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis or by becoming intercalated as a structural analogue of one of the chemical compounds in the melanin synthesis chain, whereby this chain may then be blocked and thus ensure the depigmentation.
The substances most commonly used as depigmenting agents are, more particularly, hydroquinone and its derivatives, in particular its ethers such as hydroquinone monomethyl ether and monoethyl ether. Although they have a certain level of efficacy, these compounds are unfortunately not free of side effects on account of their toxicity, which can make them difficult or even hazardous to use. This toxicity arises from the fact that they interfere with fundamental mechanisms of melanogenesis, by killing cells which then risk disrupting their biological environment and which consequently force the skin to eliminate them by producing toxins.
Thus, hydroquinone is a compound which is particularly irritating and cytotoxic to melanocytes, and whose total or partial replacement has been envisaged by many authors.
Substances have thus been sought which are not involved in the mechanism of melanogenesis, but which act upstream on tyrosinase by preventing its activation, and are consequently much less toxic. Kojic acid is commonly used as tyrosinase-activation inhibitor, this acid complexing the copper present in the active site of this enzyme. Unfortunately, this compound can give rise to allergic reactions (“Contact allergy to kojic acid in skin care products”, Nakagawa M. et al., in Contact Dermatitis, January 95, Vol 42 (1), pp. 9-13). In addition, this compound is unstable in solution, which somewhat complicates the manufacture of the composition.
It is most particularly sought to use harmless topical depigmenting substances which are of good efficacy, in order to treat regional hyperpigmentations caused by melanocyte hyperactivity, such as idiopathic melasmas, occurring during pregnancy (“pregnancy mask” or chloasma) or during oestro-progestative contraception, localized hyperpigmentations caused by hyperactivity and proliferation of benign melanocytes, such as senile pigmentation marks known as actinic lentigo, accidental hyperpigmentations or depigmentations, possibly due to photosensitization or to post-lesional cicatrization, as well as certain leukodermias, such as vitiligo. For the latter, in which the cicatrizations can result in a scar which gives the skin a whiter appearance and leukodermias), failing being able to repigment the damaged skin, the regions of residual normal skin are depigmented in order to give the skin as a whole a uniform white complexion.
Thus, there is a need for a novel agent for bleaching human skin, hairs and/or head hair which acts as effectively as the known agents, but which does not have their drawbacks, i.e. which is non-irritant, non-toxic and/or non-allergenic to the skin and which is stable in a composition.
SUMMARY OF THE INVENTION
One object of the present invention is to provide a novel agent for bleaching human skin, hairs and/or head hair which acts as effectively as the known agents, but which does not have their drawbacks, i.e. which is non-irritant, non-toxic and/or non-allergenic to the skin and which is stable in a composition.
The Applicant has found, unexpectedly, that certain oxamate derivatives have depigmenting activity, even at low concentrations, without showing any cytotoxicity.
These oxamate derivatives have the formula(I) below:
in which:
R represents a hydrogen atom, a radical chosen from a hydroxyl radical, a radical —OR′, a radical —COR′, a radical —COOR′, a radical —NR′R″, a radical —CONR′R″, a linear, cyclic or branched, saturated or unsaturated, C
1
to C
30
aliphatic hydrocarbon radical, which is optionally hydroxylated, and a substituted or unsubstituted aryl radical,
R
1
and R
2
, which may be identical or different, represent a hydrogen atom, a radical chosen from a hydroxyl radical, a radical —OR′, a radical —COR′, a radical —COOR′, a radical —NR′R″, a radical —CONR′R″, a radical —SR′, —CH
2
OR′, a linear, cyclic or branched, saturated or unsaturated, C
1
to C
30
aliphatic hydrocarbon radical, which is optionally hydroxylated, and a substituted or unsubstituted aryl radical, with R′ and R″, which may be identical or different, representing a hydrogen atom, a radical chosen from a linear or branched, saturated or unsaturated, C
1
to C
30
aliphatic hydrocarbon radical, which is optionally hydroxylated, and a substituted or unsubstituted aryl radical, an amino acid residue or a sugar residue,
R
3
represents a hydrogen atom or a radical —COOR
4
,
with R
4
representing a linear, cyclic or branched, saturated or unsaturated, C
1
to C
30
aliphatic hydrocarbon or alkoxyl radical,
X represents a radical chosen from a radical —OR
5
, a radical SR
5
and a radical —NR
6
R
7
,
with R
5
, R
6
and R
7
, which may be identical or different, representing a hydrogen atom, a radical chosen from a linear, cyclic or branched, saturated or unsaturated, C
1
to C
30
aliphatic hydrocarbon radical, which is optionally hydroxylated, and a substituted or unsubstituted aryl radical, an amino acid residue, a peptide residue or a sugar residue.
The subject of the present invention is thus the use of oxamate derivatives of formula (I) in and/or for the manufacture of a cosmetic and/or dermatological composition for depigmenting and/or bleaching human skin and/or for removing skin pigmentation marks and/or depigmenting head hair and/or other hairs.
The subject of the present invention is also the use of these oxamate derivatives in and/or for the manufacture of a cosmetic and/or dermatological composition, as tyrosinase inhibitors and/or as melanin synthesis inhi

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