FR3039405A1 - COSMETIC AND / OR DERMATOLOGICAL AND / OR THERAPEUTIC COMPOSITION FOR STIMULATION OF THE HUMAN IMMUNE RECOGNITION SYSTEM - Google Patents

Abstract

The invention relates to a cosmetic and / or dermatological and / or therapeutic composition for the stimulation and / or regulation of the human immune recognition system of the skin and mucous membranes. The composition comprises as active principle a mineral thermal water comprising at least: - between 40 mg / l and 600 mg / l of calcium, and / or salts and / or derivatives thereof, - between 12.5 mg / l and 125 mg / l magnesium, and / or salts and / or derivatives thereof, - between 4 mg / l and 42 mg / l of silicon, and / or salts and / or derivatives of the latter, the other ingredients being constituted by compounds that are acceptable in the cosmetic and / or dermatological and / or therapeutic fields, and the said composition ensuring interaction of the glycosylated molecules with lectins.

Description

The technical field of the present invention is that of compositions intended to treat the skin of patients by modifying the interaction phenomena of a glycobiological nature.

Glycobiological interactions are known to work through adhesion proteins, lectins, which recognize saccharide ligands.

Lectins can be free (extra or intracellular) or transmembrane. Lectins specifically recognize mono- and oligosaccharide ligands.

The lectins specific for monosaccharides are classified into five groups, according to the ose for which they have the highest affinity: mannose (Man), fucose (Fuc), galactose (Gal) and N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), and sialic acid (NeuAc, N-acetylneuraminic acid).

The structural similarities between monosaccharides are crucial for the specificity of lectins. For example, most lectins that recognize Gai also bind to GalNAc.

Some mammalian lectins such as DC-SIGN, MBL and LANGERIN may recognize mannose, which is present on the surface of pathogenic microorganisms and absent in mammals.

Lectins are ubiquitous proteins found in all living organisms (eukaryotic or prokaryotic) and non-living (in the envelope of some viruses).

There is a wide variety of lectins with a high degree of structural diversity. The number of crystallographic structures of lectins is still growing, and today we know the three-dimensional structure of about 770 lectins.

Animal lectins are distributed in very different families. The three most studied families are galectins, type C lectins and siglecs: Galectins recognize lactosaminic structures. For example, they have a role in migration and re-epithelialization.

Type C lectins have a well-conserved CRD (Carbohydrate Recognition Domain) domain that involves a calcium atom in the protein-sugar interaction (Drickamer 1993). Type-C lectins are either circulating or attached to cell surfaces by the presence of a transmembrane segment. It includes MBL, DC SIGN, DECTIN-1 and LANGERINE. They have a role for example in innate immunity. Siglecs, or type I lectins, are a family of lectins that recognize sialic acid (Crocker 2002). They are members of the immunoglobulin superfamily and adopt an immunoglobulin-like folding.

Lectins intervene in individuals in the mechanisms of communication, mobility, differentiation, immune recognition, re-epithelialization.

For example, a low level of "Mannose Binding Lectin" (MBL: soluble lectin) has been associated with some skin infections. MBL can also be associated with serine protease (MASPs) for activation of the complement pathway and is essential for the innate immune response and early defenses against pathogens by opsonization.

Also membrane lectins such as DC-SIGN or DECTIN-1 participate in innate immune responses by recognition of glycosylated ligands from bacteria, viruses, circulating cells, toxins, hormones.

LANGERIN is a membrane lectin found for example in skin on Langerhans cells.

Any alteration in these recognition systems by glycobiological interaction can induce, for example, a modification of the innate immune response and immunodeficiency to nathooenes.

The plaintiff discovered in a totally fortuitous and surprising manner that mineral or mineralized water could modulate the interactions of a glycobiological nature.

The object of the present invention is to provide a person skilled in the art with a composition capable of ensuring and developing the immune defenses of patients. The subject of the invention is therefore a cosmetic and / or dermatological and / or therapeutic composition for the stimulation and / or regulation of the human immune recognition system of the skin and mucous membranes, characterized in that it comprises as active principle a water or mineralized product comprising at least: - between 40 mg / l and 600 mg / l of calcium, and / or of salts and / or derivatives thereof, - between 12.5 mg / l and 125 mg / l magnesium, and / or salts and / or derivatives thereof, - between 4 mg / l and 42 mg / l of silicon, and / or salts and / or derivatives thereof, the other ingredients being constituted by compounds that are acceptable in the cosmetic and / or dermatological and / or therapeutic fields, and said composition ensuring an interaction of the glycosylated molecules with lectins.

According to one characteristic of the invention, the calcium and magnesium and / or the salts and / or the derivatives thereof present in the mineral or mineralized water are in a mass ratio Ca / Mg of between 1 and 10.

According to another characteristic of the invention, the calcium and the silicon and / or the salts and / or the derivatives thereof present in the mineral or mineralized water are in a Ca / Si mass ratio between 1 and 20 .

According to yet another characteristic of the invention, the mineral or mineralized water is present in a mass proportion of 1 to 15% for the stimulation of the human immune recognition system.

According to yet another characteristic of the invention, the mineral or mineralized water is present in a ntonort i on τπΑ.ςςι πιιρ ςπηρ'τi nn pnal p to Sfl% r-inn-r 1 s inflammatory regulation of the human system of recognition immune.

According to another characteristic of the invention, the mineral or mineralized water is in a mass proportion of 10%.

According to yet another characteristic of the invention, the mineral or mineralized water is in a mass proportion of 30%.

According to another characteristic of the invention, calcium and magnesium and silicon and / or their salts and / or derivatives are present in the mineral or mineralized water in concentrations of 42.7 mg / 1, 21, 2 mg / l and 14 mg / l.

According to another characteristic of the invention, calcium and silicon and / or its salts and / or derivatives is present in mineral or mineralized water in concentrations of 140 mg / l and 30 mg / l.

According to yet another characteristic of the invention, the mineral water is constituted by Uriage Thermal Water.

According to yet another characteristic of the invention, the composition according to the invention is in the form of a nasal or facial spray, and nasal or ocular unit doses.

A very first advantage of the composition according to the invention lies in the surprising effect of the increase in the intensity of neoglycoprotein interactions on the osidic receptors on the surface of keratinocytes (NHEK) and on the surface of bacteria (S. aureus, S.epidermidis, P. acnes).

Another advantage of the present invention lies in the increase of the interaction of specific ligands for recombinant type C human lectins (DC-SIGN, DECTIN-1, LANGERIN).

Yet another advantage of the present invention is the gradual increase in the interaction intensity of specific ligands for the DECTIN-1 and LANGERINE lectins which decreases to 15% to vanish to 20%.

Yet another advantage of the present invention is that The novel property may be advantageously used in cosmetic and / or dermatological and / or therapeutic compositions comprising, as active ingredients, a thermal water. .

Another advantage of the invention lies in the possibility of varying the action of the mineral or mineralized water as a function of the percentage thereof in the composition. Thus, a low percentage, for example less than or equal to 15% by weight, stimulates immune defenses while a percentage greater than or equal to 30% regulates these immune defenses. Other characteristics, details and advantages of the invention will be better understood on reading the additional description which follows of embodiments given by way of illustration.

A composition comprising, as active ingredient, a mineral or mineralized water rich in trace elements and mineral salts makes it possible to act potentially on the interaction of glycosylated molecules (ligands) with lectins (osidic receptors) involved in the immunity mechanisms innate, particularly at the level of keratinocytes and bacteria.

By mineral or mineralized water rich in trace elements and mineral salts, is meant a water comprising at least, relative to common water (tap or even bottle), high proportions including the following elements: calcium, magnesium, silicon and salts and derivatives thereof and in trace elements.

In the present invention, the tests were carried out with a thermal water as the active ingredient, namely Uriage Thermal Water (ETU) having the following composition for a dry residue of 11,000 mg / l: - Calcium: 600 mg / 1, - Magnesium: 125 mg / 1, - Potassium: 45.5 mg / 1, - Sodium: 2360 mg / 1, - Sulfates: 2860 mg / 1, - Chlorides: 3500 mg / 1, - Ri carhonatpq ! 3PD mrr / 1. Silicon: 42 mg / l, Zn: 160 μg / l, Mn: 154 μg / l, Cu: 75 μg / l, Fe: 15 μg / l. The ETU is recognized as one of the mineralized thermal waters most balanced in trace elements and mineral salts. It has an effective moisturizing action when it is spray applied locally. It goes without saying that any other mineral or natural source water, such as thermal waters, or mineralized water of unnatural origin can be used, provided that the latter has a similar composition or that added minerals and trace elements in proportions close to those of a thermal water.

It is obvious to those skilled in the art that equivalent unnatural natural or mineral mineral waters are possible if they are used in appropriate proportions for the important elements underlined above or the salts and derivatives thereof as well as trace elements. Thus, one can very well use in appropriate proportions Avene Thermal Water which includes 42.7 mg / 1 of calcium, 21.2 mg / 1 of magnesium and 14 mg / 1 of silicates, or Thermal Water La Roche-Posay, which contains 140 mg / l of calcium and 30 mg / l of silicates, or Saint-Gervais Thermal Water which contains 236 mg / l calcium, 28.1 mg / l magnesium and 44 mg / 1 of silicon.

Typically, calcium and magnesium are naturally present in the thermal waters according to the invention in a respective mass ratio Ca / Mg of between 1 to 10.

Typically, calcium and silicon are naturally present in the thermal waters according to the invention in a respective Ca / Si mass ratio of between 1 and 20.

The following tests were conducted with Uriage Thermal Water (ETU).

To carry out the tests, human cells were used to express the cells supplied in cryotubes, which cells were cultured and multiplied into 96-well plates in order to obtain a carpet of cells. The cells are washed several times with a standard buffer solution (PBS) at 4 ° C. Then each neoglycoprotein, diluted in PBS buffer containing 0.025% bovine serum BSA) is deposited on the cell wells The plates are incubated for 4 hours at + 4 ° C. After incubation, the wells are gently washed with PBS (200 μl, 3 washes) and the fluorescence intensities are read after addition of 100 μΐ of PBS to each well.

To study the inhibition by the thermal water, this water is mixed with the neoglycoproteins so as to obtain final concentrations of water of 10, 20 and 30% by weight.

To evaluate the potential action of thermal water on the expression of cell surface receptors on osids, the thermal water is added directly to the culture medium in order to obtain a final thermal water concentration of 10, 20 and 30% by mass 48 hours before the examination.

The results obtained show that the thermal water causes a reinforcement of the interaction intensities of the neoglycoproteins (ligands) with the keratinocyte oside receptors expressed on the surface of the cells as a function of the concentration of water.

The interaction intensities of the neoglycoproteins with the osidic receptors of the bacteria are also increased.

Thus, the bacteria Staphylococcus aureus and Propiobacterium acnes show an increase in the interaction only of the mannosylated neoglycoprotein whereas Staphylococcus epidermidis shows an increase of interaction with all the neoglycoproteins. The thermal water thus makes it possible to maintain and reinforce the interactions of a glycobiological nature in the extracellular matrix, but also between the matrix and the cells. Indeed, the glycosaminoglycans (GAG) i nf praf7i sspnt avpr · Hp. = CAC bii nr-li nrn nrnl-ρι πς Pin qpiti Hp Ί pi matrix itself but also with the surrounding cells thus allowing the maintenance of tissues. The thermal water allows this maintenance and strengthens it. It is the same of the other thermal waters mentioned before.

Similar tests were carried out with mineralized water and obtained the results in accordance with the preceding ones.

To determine the interaction activity provided by the mineral or mineralized water, the following tests were carried out. The studies carried out are conducted with recombinant human lectins selected according to their action in immunity and / or cutaneous homeostasis. DC-SIGN: this lectin is involved in innate immunity; it is a marker of dendritic cells (which do not express langerin).

Dectin-1: it is a beta-glucan receptor, major component of the cell wall of yeasts and mycobacteria. Dectin-1 is expressed at the level of monocytic cells and T and B lymphocytes. This lectin is known for interaction functions with respect to pathogens.

Langerine, CD207: it is a marker of Langerhans cells that recognizes the motives mannose, N-acetyl-glucosamine and fucose.

Galectin 3: at the level of the skin, Gai 3 is expressed by dendritic cells, keratinocytes, melanocytes, fibroblasts and epithelial cells.

Ficoline 2: this lectin is expressed on the cell surface in soluble form. This family of lectins has an affinity for the acetylated units and has properties in terms of recognition of microorganisms and activation of the complement cascade to lead to their destruction.

The direct interaction behavior between each respective ligand-lectin pair was compared, with or without different concentrations of thermal water. For this purpose, each ligand has been deposited at a concentration corresponding to RflS: ## EQU1 ## ## STR1 ##

The results obtained show that the interaction of ligands with human recombinant lectins varies in a different way depending on the lectins in the presence of thermal water. In the majority of cases, these interactions are sensitive to concentrations of 20 and 30% of thermal water. In contrast, the presence of 10% thermal water significantly enhances the interaction of DC-SIGN, Langerine and Dectin-1 lectins. The thermal or mineralized water thus has a general action of contribution and reinforcement of the glycobiological interactions with however certain specificities according to the lectin considered.

Claims (11)

1. Cosmetic and / or dermatological and / or therapeutic composition for the stimulation and / or regulation of the human immune recognition system of the skin and mucous membranes, characterized in that it comprises as active principle a mineral or mineralized water comprising at least: - between 40 mg / l and 600 mg / l calcium, and / or salts and / or derivatives thereof, - between 12.5 mg / l and 125 mg / l magnesium, and / or salts and / or derivatives thereof, - between 4 mg / l and 42 mg / l silicon, and / or salts and / or derivatives thereof, the other ingredients being compounds in the cosmetic and / or dermatological and / or therapeutic fields, and said composition ensuring an interaction of the glycosylated molecules with lectins. 2. Cosmetic and / or dermatological and / or therapeutic composition according to claim 1, characterized in that the calcium and magnesium and / or the salts and / or the derivatives thereof present in the mineral or mineralized water are in a mass ratio Ca / Mg of between 1 and 10. 3. Cosmetic and / or dermatological and / or therapeutic composition according to claim 1, characterized in that the calcium and silicon and / or the salts and / or the derivatives thereof present in the mineral or mineralized water are in a mass ratio Ca / Si of between 1 and 20. 4. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 3, characterized in that the mineral or mineralized water is present in a mass proportion of 1 to 15% for the stimulation of the human system immune recognition. 5. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 3, characterized in that the mineral or mineralized water is nrp Prit · Hsns nnp nrnnnr) ·! In the case of inflammatory regulation of the human immune recognition system, it is necessary to use 30% or more. 6. Cosmetic and / or dermatological and / or therapeutic composition according to claim 4, characterized in that the mineral or mineralized water is in a mass proportion of 10%. 7. Cosmetic and / or dermatological and / or therapeutic composition according to claim 5, characterized in that the mineral or mineralized water is in a proportion by mass of 30%. 8. Cosmetic and / or dermatological and / or therapeutic composition according to any one of the preceding claims, characterized in that calcium, magnesium and silicon and / or their salts and / or derivatives are present in the mineral thermal water. or mineralized at respective concentrations of 42.7 mg / l, 21.2 mg / l and 14 mg / l. 9. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 7, characterized in that calcium and silicon and / or its salts and / or derivatives is present in the mineral thermal water at concentrations of 140 mg / l and 30 mg / l, respectively. 10. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 9, characterized in that the mineral water is constituted by Uriage Thermal Water. 11. Cosmetic and / or dermatological and / or therapeutic composition according to any one of Claims 1 to 10, characterized in that the composition according to the invention is in the form of a nasal or facial spray and nasal or ocular unit doses.