FR3039404A1 - COSMETIC AND / OR DERMATOLOGICAL AND / OR THERAPEUTIC COMPOSITION COMPRISING ARCHEES 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, 0.001 to 1% by weight of Archaea and 1 to 99.999% by weight of a mineral or mineralized 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 and 42 mg / 1 of silicon, and / or of 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 providing a interaction of 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 lectins can recognize mannose and fucose such as mammalian DC-SIGN.

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-preserved CRD (Carbohydrate Recognition 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 DC SIGN, DECTIN-1 and LANGERIN. 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 proteases (MASPs) and is essential for the innate immune response and early defenses against pathogens.

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.

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

The plaintiff discovered in a totally fortuitous and surprising manner that mineral or mineralized water incorporating either of the Archaea and / or their extracts, (both referred to in the following description by Archées) could modulate the glycobiological interactions of cells of the human body.

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 0.001 to 1% Archaea and 1 to 99.999% by weight of a mineral or mineralized water comprising at least: - between 40 mg / l and 600 mg / l of calcium, and / or salts and / or derivatives of this, - 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 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 interaction of the glycosylated molecules with lectins.

Archées means the Archées themselves or their extracts of membranes, cytoplasm, organelles or nuclei or also the molecules and metabolites that these Archaea can produce.

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 another characteristic of the invention, the archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a mass proportion of 1 to 15% for the stimulation of the human immune recognition system.

According to another characteristic of the invention, the archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a mass proportion greater than or equal to 30% for the inflammatory regulation of the human immune recognition system. .

According to another characteristic of the invention, the Archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a mass proportion of 10%.

According to yet another characteristic of the invention, the archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a mass proportion of 30%.

According to another characteristic of 1'invention, the mineral water is constituted by the Uriage Thermal Water, water, Avène Thermal Water, Thermal Water of La Roche-Posay, or the Thermal water of St. Gervais.

According to yet another characteristic of the invention, the composition according to the invention is in the form of a nasal aerosol 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) in the presence of the two active ingredients according to the invention.

Another advantage of the present invention lies in the increased interaction of type C lectins (DC-SIGN, DECTIN-1, LANGERIN).

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

Yet another advantage of the present invention is the strengthening of the body's defenses. This novel property can be used advantageously in cosmetic and / or dermatological and / or therapeutic compositions comprising, as active ingredients, mineral or mineralized water.

Another advantage of the invention lies in the possibility of varying the action of the Archaea and the mineral or mineralized water depending on the percentage of these in the composition. Thus, a small percentage of water, for example less than or equal to 15% by weight, combined with Archaea, stimulates immune defenses while a percentage of water greater than or equal to 30% and of Archaea 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 principle, archaea and 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 involved in the mechanisms of innate immunity, particularly at the level of keratinocytes and

Archaea can be derived from an underground continental hydrothermal source of mineral or mineral water. Archaea are small, coreless prokaryotic microorganisms that are morphologically distinct from bacteria. Their specificity was highlighted in 1977 by the work of Cari Woese and George E. Fox.

A new phylogenetic tree was published based on the sequences of the 16S ribosomal RNA molecules (16S rRNA) of the organisms studied, a tree in which the prokaryotes were split into two distinct branches, that of the Bacteria and that of the Archaea.

These analyzes showed that the sequences of the 16S rRNAs of the Archées were practically as far removed from the 16S rRNA sequences of the bacteria as from those of the 18S rRNAs of the Eukaryotes. The originality of the Archaea was quickly confirmed by the analysis of their membrane glycerolipids. While the glycerolipids of bacteria and eukaryotes are formed by the esterification of a glycerol molecule by two fatty acid molecules, the glycerolipids of the archeol (archaeol) are formed by the etherification of a glycerol molecule by two isoprenol molecules (branched long chain alcohols). In addition, the glycerolipids of Archées exhibit reversed optical isomerism compared with those of bacteria and eukaryotes (the central carbon of glycerol being asymmetrical, glycerolipid molecules exist in fact in two isomeric forms, as are the amino acids or sugars of nucleic acids).

Archaea have long been viewed as essentially extremophilic organisms, particularly in oceanic hydrothermal vents, volcanic hot springs and salt lakes, but a variety of biotopes that are not necessarily extreme, such as soil, seawater, swamps, intestinal flora and even the human belly button.

Archaea would be particularly abundant in the oceans, and plankton would be one of the most abundant groups of organisms on Earth.

The Archées also play a significant role in the carbon cycle and the nitrogen cycle.

There are not really any examples of pathogenic or parasitic archaea, but they are often mutualistic or commensal. The Methanogenic Archaea of the human intestine and ruminants thus contribute favorably to digestion.

However, no use of Archées has been proposed in the field of skin care.

The applicant has conducted new research to highlight the possible presence of Archées especially in thermal waters and conventional waters, and more particularly in the thermal waters of Uriage, and to identify them.

As a result, samples of thermal mineral water were collected in triplicate at the emergence of the source and at different points of the supply circuit to detect the presence of Archées in thermal mineral water.

The detection is done by the very sensitive method of qPCR. Initially, a "pan" general detection for prokaryotes was performed, covering respectively 98% and 94.6% of the gene sequences encoding the rRNA of Bacteria and Archaea. In a second step, a specific detection of the gene sequences coding for the ArRNA rRNAs was carried out.

For the first "pan" Prokaryotic detection, these were the following primers: 3 4 4 F: 5'-ACggggYgCAgCAggCgCgA-3 '8 0 6R: 5'-ggACTACVSgggTATCTAAT-3'

For the 16S rRNA specific for the Archées, these are the following primers: 340F: 5'-CCCTAYggggYgCASCAg-3 '10 0 0 R: 5'-ggCCATgCACYWCYTCTC-3'

The results obtained indicate the presence of Archées in the mineral water samples taken at the hydrothermal source of Uriage. The Archaea have been incorporated in the mineral or mineralized water to obtain the surprising effects indicated above.

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 that the salts and the derivatives of these to which the Archaea are added.

Tests carried out with mineralized water made from its individual components, to which is added the indicated percentage of Arches, confirm the properties indicated.

In the present invention, the tests were carried out with the Archaea and a mineral or mineralized water as the active ingredient, in particular the Uriage Thermal Water (ETU), having the following composition for a dry residue of 11,000 mg / 1: - Calcium: 600 mg / 1, - Magnesium: 125 mg / 1, - Potassium: 45.5 mg / 1, - Sodium: 2360 mg / 1, - Sulfates: 2860 mg / 1, - Chlorides: 3500 mg Bicarbonates: 390 mg / l; Silicon: 42 mg / l; Zn: 160 μg / l; Mn: 154 μg / liter; Cu: 75 μg / liter; Fe: 15 μg / liter; . ETU is recognized as one of the most balanced mineral thermal waters with trace elements and minerals. It has an effective moisturizing action when it is spray applied locally. This thermal water thus offers a source of mineral water combined with the Archées quite advantageous in the implementation of the invention. It goes without saying that one can use any other thermal water provided that it has a similar composition.

It is obvious to those skilled in the art that equivalent or non-natural mineralized mineral waters are possible if they are used in suitable proportions for the important elements underlined above or the salts and derivatives thereof. Thus, Avène Thermal Spring Water, which comprises 42.7 mg / l of calcium, 21.2 mg / l of magnesium, 14 mg / l of silica, or thermal water, can be used very well in suitable proportions. 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 of calcium and 28.1 mg / l of magnesium in combination with the Archées.

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

The following tests were carried out with Uriage mineral thermal water.

To carry out the tests, human cells which are normal keratinocytes from cells supplied with cryotubes were used. These cells are cultured and multiplied into 96-well plates so as to obtain a confluent cell mat having 8 to 10 generations to those of the starting cells. The cells are washed several times with standard buffer solution (PBS) at 4 ° C. Then each neoglycoprotein, diluted in PBS buffer containing 0.025% bovine serum albumin (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 adding 100 μl of PBS to each well.

In order to study the inhibition by the thermal water in which the Archées are incorporated, this water is mixed with the neoglycoproteins so as to obtain final concentrations of water of 10, 20 and 30% by mass.

To evaluate the potential action of the Archaea combined with the thermal water on the expression of the osidic receptors on the surface of the cells, this water is added directly to the culture medium so as to obtain a final concentration of thermal water and Archaea. 10, 20 and 30% by mass 48 hours before the examination.

The results obtained show that the thermal water incorporating the Archées leads to a reinforcement of the interaction intensities of the oses or glycans with the osidic receptors of the keratinocytes expressed on the surface of the cells as a function of the concentration of water.

The intensities of interaction of oses or glycans with the osidic receptors of the bacteria are also obtained.

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 incorporating the arches according to the invention 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, glycosaminoglycans (GAG) interact with GAG binding proteins within the matrix itself but also with the surrounding cells thus allowing tissue maintenance. The thermal water and the Arches allow this maintenance and reinforce it. It is the same of the other thermal waters mentioned before incorporating the Archées.

To determine the interaction activity provided by the mineral or mineralized water combined with the Archaeas, the following tests were performed. 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: in 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 was deposited at a concentration corresponding to 50% of the maximum binding on the respective lectin.

The results obtained show that the interaction of ligands with recombinant human lectins evolves differently according to lectins in the presence of thermal water combined with the Archaea. In the majority of cases, these interactions are sensitive to concentrations of 20 and 30% of thermal water. In contrast, the presence of 0.05% by mass areal and 10% thermal water significantly enhances the interaction of DC-SIGN, Langerine and Dectin-1 lectins. The thermal water combined with the Archaea thus has a general action of contribution and reinforcement of the glycobiological interactions with however certain specificities according to the lectin considered.

Claims (9)

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 ingredient 0.001 to 1% of And 1 to 99, 999% by weight of a mineral or mineralized 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 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. 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 Archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a proportion mass of 1 to 15% for the stimulation of the human immune recognition system. 5. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 3, characterized in that the Archées are present in a mass proportion of 0.05% and the mineral or mineralized water in a proportion mass greater than or equal to 30% for the inflammatory regulation of the human immune recognition system. 6. Cosmetic and / or dermatological and / or therapeutic composition according to claim 4, characterized in that the Archées are present in a mass proportion of 0.05% and the mineral or mineralized water in a mass proportion of 10%. 7. Cosmetic and / or dermatological and / or therapeutic composition according to claim 5, characterized in that the Archaea are present in a mass proportion of 0.05% and the mineral or mineralized water in a proportion by mass of 30%. 8. Cosmetic and / or dermatological and / or therapeutic composition according to any one of claims 1 to 7, characterized in that the mineral water is constituted by Uriage Thermal Water, water, thermal water. Avène, the Thermal Water of La Roche-Posay, or the Thermal Water of St. Gervais. 9. Cosmetic and / or dermatological and / or therapeutic composition according to any one of Claims 1 to 8, characterized in that the composition according to the invention is in the form of a nasal aerosol spray and nasal or nasal dose units. eyepieces.