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Topical use of thiazolidine derivatives against consequences of oxidative stress of skin

Topical use of thiazolidine derivatives against consequences of oxidative stress of skin description/claims

The invention concerns the cosmetic use of thiazolidine derivatives, particularly in the domain of skin protection and more especially in the struggle against oxidative stress and its cutaneous consequences.

By its role as an external envelope of the body against the atmosphere, skin is an organ particularly sensitive to the environment to which it is submitted. This can be of a pro-oxidant nature, due to prolonged exposure to the sun's ultraviolet rays, smoky atmospheres or those containing atmospheric chemical pollutants. These aggressions of an exogenous nature generate an excess of very reactive species, radical or not, with a strong oxidant potential. These are notably species derived from molecular oxygen, which are often named reactive oxygen species or ROS, like the superoxide anion O2o−, the hydrogen peroxide H2O2, the oxygen singulet 1O2, the hydroxyl radical OHo.

This overproduction of ROS is then responsible for biological constituent alterations of skin, in particular of those met in the cutaneous cells (DNA, proteins, lipids, glucides). The formation of by-products issued from degradation of these biological molecules, and in particular of those issued from the peroxidised membrane phospholipids by the ROS, is also harmful to skin. Finally, exposure of a skin to an overproduction of ROS also initiates complex biochemical reactions, which are at the origin of pro-inflammatory cytokine production, mutagen metabolites, and the death of cutaneous cells (Briganti S, and al., J. Eur. Acad. Dermatol. Venereol. (2003), vol. 17, pp. 663-669).

In general, all these phenomena are harmful to skin, more particularly when they reach the deep layers, notably in the dermis. It is also well established today that a loss of control by the skin caused by the excessive presence of ROS, leading to a state commonly designated as “oxidative stress”, is clearly involved in the start of numerous cutaneous disorders or anomalies: induced ageing, immunosuppression, inflammation/erythema, carcinogenesis, irritation, etc (Bickers D. R. and al., J. Invest. Dermatol. (2006), vol. 126, pp. 2565-2575 and quoted references).

Physiologically, and despite the existence of natural antioxidant systems of regulation and protection, enzymatic (superoxide dismutase, catalase, peroxidase, etc) or non-enzymatic (vitamins A, C, D or E, carotenoids, glutathione, trace elements, etc), the skin displays a quick depletion of defence, when confronted with an important flux of free radicals or ROS.

For many years, the conception of systems capable of limiting the deleterious effects of this reactive species overproduction, or even to capture or to trap them, has become a major research topic. Thus in order to palliate the skin's physiological insufficiencies, numerous natural or synthetic molecules (plant or animal extracts) have been developed and proposed as antioxidant or antiradical supplements administered orally or by topical application (Darvin M. and al., Skin Pharmacol. Physiol. (2006), vol. 19, pp. 238-247).

However, according to the invention, an efficient protection against these so-called first generation ROS is shown for a number of antioxidant or antiradical molecules belonging to the state of the technique. By “first generation ROS”, it is to necessary to understand the species derived from molecular oxygen reduction (O2o−, H2O2, 1O2, OHo, ONOO−, etc). On the other hand, an action regarding the oxidation by-products or so-called second generation products (toxic aldehydes, final products issued from the lipid peroxidation, etc) which are also toxic and result in chain reactions of primary species with the biochemical components of the cell is more rarely justified.

In general, it remains that the selection of an antioxidant substance said to be “efficient”, notably for human administration, is difficult. It is also to note that it is often considered an in vitro benefit, which is seldom confirmed clearly in vivo (Bickers D. R. and al., J. Invest. Dermatol. (2006), vol. 126, pp. 2565-2575).

Indeed, in addition to the multi-layered structural complexity of human skin and in consequence to an oxidative stress expressing itself differently, the previously mentioned antioxidant substance must combine: an efficiency towards the largest possible panel of reactive oxygen species, and in consequence possess a broad spectra of “anti-stress” properties, an efficiency towards toxic by-products of oxidative stress, a reactivity in contact with ROS such as it does not lead to toxic rearrangement product formation, a favourable cutaneous penetration (and thus a bioavailability) in order to reach different cutaneous tissue sites, finally, a resistance to hydrolytic skin systems (and thus a resistance to its metabolization), which is a guarantee of its in situ activity.

The present invention has been developed in this context to satisfy this request for products or preparations able to oppose the destructive effects of oxidative stress and its toxic by-products as efficiently as possible, notably in the deep skin layers.

Thus, the applicant's choice falls on thiazolidine heterocyclic derivatives, in particular on 2-oxo-1,3-thiazolidine. Reasons for this selection are multiple:

• Provisional Patent
• Utility Patent

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