FR3130153A1 - Use of at least one pyrimidine 3-oxide derivative to reinforce the barrier function of the skin - Google Patents

Abstract

Use of at least one pyrimidine 3-oxide derivative to reinforce the barrier function of the skin The present invention relates to the cosmetic use, in particular non-therapeutic use, of at least one pyrimidine 3-oxide derivative of formula (I) : (I)- and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof, as an agent for preventing the reduction of and/or reinforcing the barrier function of the skin, preferably the barrier function of the scalp.

Description

Use of at least one pyrimidine 3-oxide derivative to reinforce the barrier function of the skin

The present invention relates to the field of active agents used to reinforce the barrier function of the skin.

The epidermis is the first interface between an organism and the external environment. More particularly, the corneal envelope (EC: stratum corneum) is a specialized structure which represents the first rampart of the skin. Obtaining this first skin barrier corresponds to a process of terminal differentiation of epidermal keratinocytes. This process leads to the formation of a superficial layer resulting from the aggregation of dead and flattened keratinocyte cells whose cytosol, after the loss of the functional nucleus, has been replaced by a matrix of insoluble protein and lipid aggregates.

The skin thus constitutes a barrier against external attacks, in particular chemical or mechanical, and as such a certain number of defense reactions against environmental factors (climate, ultraviolet rays, etc.) occur at its level. This property is called barrier function.

An alteration of the cutaneous barrier can occur in the presence of external aggressions such as irritating agents (detergents, acids, bases, oxidants, reducers, concentrated solvents, toxic gases or fumes), mechanical stresses (friction, shocks, abrasion, tearing of the surface, projection of dust, particles, shaving or depilation), thermal or climatic imbalances (cold, dryness, radiation), xenobiotics (undesirable microorganisms, allergens) or internal attacks of the psychological stress type.

This alteration of the cutaneous barrier can in particular result in cutaneous discomfort, sensory phenomena and in particular unpleasant phenomena. The subject may then experience a sensation of cutaneous discomfort which may be manifested in particular by tingling, tightness, overheating or itching.

These feelings of skin discomfort are more frequent in the most exposed areas of the body, namely the hands, feet, face, scalp.

They can occur in particular on areas subject to certain daily or frequently renewed hygiene gestures such as shaving, hair removal, cleansing with toiletries or household products, application of adhesives (dressings, patches) or in the case of sports, professional gestures or simply linked to the way of life and the use of clothing, tools or equipment generating localized friction. They can also be amplified by psychological stress.

These feelings of discomfort also appear in the case of dry skin.

There is therefore a significant need for compositions making it possible to prevent a reduction in and/or to reinforce the skin barrier function, in particular to prevent and/or reduce the sensations of skin discomfort, tingling, tightness, heating and itching, or allowing to improve the state of hydration of the skin.

The barrier function of the skin can also be altered following aesthetic treatments, such as surface treatments of the epidermis implementing, for example, chemical peeling agents comprising glycolic or lactic acids, dermabrasion or laser resurfacing. Under these conditions, there is a significant need to accelerate the reconstitution of a protective surface barrier in order to ensure better and faster protection of the newly formed skin.

Galectins are skin barrier proteins that are part of the galactoside-binding lectin family. They are in particular known as being regulators of tissue homeostasis.

Galectin-7, encoded by the LGALS7 gene, is mainly expressed in stratified epithelia, particularly in the epidermis. Galectin-7 participates in particular in the proliferation and migration of keratinocytes during skin repair (Galectin-7 in the Control of Epidermal Homeostasis after Injury, Gaëlle Gendronneau et al, Molecular Biology of the Cell Vol. 19, 5541–5549, December 2008).

Strengthen the quality of the epidermis by favoring the proliferation and migration of keratinocytes, particularly during skin repair processes, thanks to the modulation of the level of expression of galectin-7 coded by the LGALS7 gene, helps maintain the functions of protection of the epidermis, as well as good hydration.

Thus, it seems interesting to promote the expression of galectin-7 to strengthen the quality of the epidermis. Surprisingly, the inventors have indeed demonstrated the particular properties of 2,4-diaminopyrimidine-3-N-oxide which is a pyrimidine 3-oxide derivative, to modify the abundance of production of a precursor messenger RNA of the synthesis of LGALS7 on a model of reconstructed human epidermis.

All of these properties therefore advantageously make it possible to envisage the use of pyrimidine 3-oxide derivatives, in particular 2,4-diaminopyrimidine-3-N-oxide and/or one of its salts and/ or one of its solvates, and/or one of its isomers, or of a composition comprising it to prevent the reduction of and/or reinforce the barrier function of the skin.

2,4-diaminopyrimidine-3-N-oxide is known from patent EP540629B1 as an active ingredient intended for the cosmetic treatment by topical application of hair loss. 2,4-Diaminopyrimidine-3-N-oxide monohydrate has also previously been shown to modulate dermal biomarkers via modulation of lysyl hydroxylase activities suggesting a protective role on perifollicular hair fibrosis and in collagen cross-linking (WO96090048 and Mahe et al Skin Pharmacol 19969;177-183).

However, to the knowledge of the inventors, it has never been described as an active ingredient making it possible to reinforce the barrier function of the skin, in particular by reinforcing epidermal regeneration.

Thus, the first subject of the present invention is the cosmetic use, in particular non-therapeutic use, of at least one pyrimidine 3-oxide derivative of formula (I):

(I)
in which :
- R1 denotes a methyl group or NHR4 in which R4 denotes a C1-C4 alkyl group or a hydrogen atom;
- R2 denotes a methyl or NHR4 group in which R4 is as defined above, R2 can also denote methyl when R1 denotes methyl; when R1 denotes NH2, R2 cannot be hydrogen;
- R3 denotes a hydrogen atom, a halogen atom or a nitro or amino group, or a C1-C4 alkyl group which may optionally bear:
- an OR5 group in which R5 denotes a C1-C4 alkyl group, a benzene ring optionally substituted by one or more C1-C4 alkoxy groups;
- a benzene ring optionally substituted by one or more C1-C4 alkoxy groups;
- and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof,
as an agent for preventing the reduction of and/or reinforcing the barrier function of the skin, preferably the barrier function of the scalp.

Another object of the present invention is the cosmetic use, in particular non-therapeutic use, of at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts and/or at least of its solvates and/or at least one of its isomers, and mixtures thereof as agent for preparing the skin for external aggression and/or reinforcing the protection of the skin, preferably of the scalp, against external aggression.

Said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof, can in particular be used to prevent and/or reduce cutaneous discomfort of a skin, preferably of the scalp, in particular induced by an exogenous stress of chemical, environmental, mechanical origin and/or an endogenous stress.

The cutaneous discomfort can be characterized in particular by tightness, tingling, overheating and/or itching.

According to one embodiment, said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates , and their mixtures, according to the invention can be used in a subject having skin chosen from fragile skin, weakened skin and/or damaged skin, the skin preferably being the scalp.

Said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof, can also be used to improve the hydration state of the skin, preferably the scalp.

According to one embodiment, said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates , and mixtures thereof, can be used in a subject having dry skin, preferably a dry scalp.

On a physiological level, dry skin is often associated with a drop in the level of cutaneous hydration as well as a modification of the process of maturation of the stratum corneum. From a sensory point of view, dry skin can be characterized by a feeling of tightness and/or cutaneous tension.

Whatever the origin, skin affected by cutaneous dryness can generally present the following signs: rough to the touch and scaly appearance, as well as reduced suppleness and elasticity

According to one embodiment, a cosmetic, in particular non-therapeutic, use of the invention may advantageously be suitable for preventing and/or treating dry or fragile skin, and winter xerosis.

According to one embodiment, a cosmetic, in particular non-therapeutic, use of the invention may advantageously be suitable for preventing and/or treating the feelings of tightness associated with dry skin.

According to a particular embodiment, said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof, are suitable for preparing the skin for aesthetic treatment conditions during which its barrier function is impaired, such as surface treatments of the epidermis with chemical peeling agents using glycolic or lactic acids, or well still dermabrasion and laser resurfacing.

Said at least one pyrimidine 3-oxide derivative of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates and mixtures thereof, can also be used as a sun preparer, to prepare the skin for sun exposure or as a repairer after sun exposure.

Definitions

By "preventing a reduction in the barrier function of the skin", it is meant here preventing any alteration of said barrier function, in particular epidermal regeneration or re-epithelialization, below its natural level of effectiveness and which would have the consequence of initiate the manifestation of one or more skin discomforts.

By “strengthening the barrier function of the skin”, is meant here improving the barrier function of the skin, in particular epidermal regeneration or re-epithelialization.

By “environmental stress”, we mean in particular acute radical stresses such as those linked to excessive exposure to the sun (UVs), but also those with lower noise levels such as those linked to pollutants or xenobiotics.

By "the skin", we mean all of the skin of the human body, in particular the skin of the neckline, the neck, the arms and forearms, the feet, the skin of the face (in particular the forehead, nose, cheeks, lips, chin), as well as the skin of the scalp, preferably the skin of the scalp.

By “prevent” or “prevention” is meant according to the invention the fact of reducing the risk of occurrence or of slowing down the occurrence of a given phenomenon, namely, reducing the risk of appearance of cosmetic signs associated with dry skin.

By "treating" or "treatment" we mean any action aimed at improving the comfort and well-being of an individual, this term therefore covers both mitigation, relief and cure.

Claims (5)

Non-therapeutic cosmetic use of at least one pyrimidine 3-oxide derivative of formula (I):
(I)
in which :
- R1 denotes a methyl group or NHR4 in which R4 denotes a C1-C4 alkyl group or a hydrogen atom;
- R2 denotes a methyl or NHR4 group in which R4 is as defined above, R2 can also denote methyl when R1 denotes methyl; when R1 denotes NH2, R2 cannot be hydrogen;
- R3 denotes a hydrogen atom, a halogen atom or a nitro or amino group, or a C1-C4 alkyl group which may optionally carry:
- an OR5 group in which R5 denotes a C1-C4 alkyl group, a benzene ring optionally substituted by one or more C1-C4 alkoxy groups;
- a benzene ring optionally substituted by one or more C1-C4 alkoxy groups;
- and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof,
as an agent for preventing the reduction of and/or reinforcing the barrier function of the skin, preferably the barrier function of the scalp, by preventing and/or reducing cutaneous discomfort of the skin characterized by tightness, tingling , heating and/or itching, or by improving the state of hydration of the skin. Cosmetic use according to Claim 1, in which the said pyrimidine 3-oxide derivative is 2,4-diaminopyrimidine-3-N-oxide of formula (III), following:
(III)
its salts, isomers, solvates, and mixtures thereof. Cosmetic use according to any one of the preceding claims, in which the said pyrimidine 3-oxide derivative of formula (I), and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates, and mixtures thereof, is present in a composition, in an amount ranging from 0.001% to 20% by weight relative to the total weight of the composition, preferably in an amount ranging from 0.01% to 15 % by weight relative to the total weight of the composition, more preferably from 0.1% to 10% by weight relative to the total weight of the composition, even better in an amount ranging from 0.2% to 5% by weight per relative to the total weight of the composition. Cosmetic treatment method for preventing a reduction in and/or reinforcing the barrier function of the skin by preventing and/or reducing cutaneous discomfort of the skin characterized by tightness, tingling, heating and/or itching , or by improving the state of hydration of the skin comprising at least one step of applying topically to the skin, preferably the scalp, a composition comprising at least one pyrimidine derivative 3 -oxide of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates and mixtures thereof as defined according to any one of claims 1 at 3. Compound derived from pyrimidine 3-oxide of formula (I) and/or at least one of its salts, and/or at least one of its isomers, and/or at least one of its solvates and mixtures thereof as defined according to any one of claims 1 to 3, for its use for preventing a reduction in and/or for reinforcing the barrier function of damaged skin.