Cosmetic composition to strengthen epidermal tight junctions for the prevention and / or treatment of atopic dermatitis
Patent Information
- Application Number
- DE602021023206
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2020-12-24
- Filing Date
- 2021-12-16
- Publication Date
- 2024-12-11
- Estimated Expiration
- 2041-12-16
AI Technical Summary
Current treatments for atopic dermatitis often involve undefined compositions of plant extracts and bacterial lysates, which can cause allergic or inflammatory reactions and vary significantly in composition, necessitating a need for a composition that restores tight junction functionality in the skin using pure, safe, and biomimetic active compounds.
A cosmetic composition comprising biomimetic compounds such as basic amino acids like arginine and glycosylceramides, which synergistically induce the expression of claudin-1, a key structural protein of tight junctions, to improve skin barrier function and treat atopic dermatitis.
The composition effectively enhances skin barrier function, reduces discomfort, and improves skin appearance by synergistically inducing claudin-1 expression, providing a safe and long-term solution for atopic dermatitis treatment.
Description
Technical field of the invention
[0001] The invention relates to the field of dermatological care, and more particularly to the treatment of inflammatory skin conditions. More specifically, the invention concerns a composition, advantageously cosmetic, for the prevention and / or treatment of atopic dermatitis. Technological background
[0002] Atopic dermatitis, or cutaneous atopy, is a chronic pruritic inflammatory dermatosis, that is, an inflammatory skin condition characterized by intense and chronic itching and recurrent eczematous lesions that occur in flare-ups (Mack and Kim, 2018; Weidinger). et al.,2018). This condition is linked to abnormalities in skin barrier function or the possible appearance of other symptoms such as allergic rhinitis, asthma, and hypersensitivity to environmental allergens that are normally tolerated in healthy individuals. JP2000264829 discloses a composition comprising at least one acrylic acid copolymer, a glucosylceramide, an oily ingredient, and at least one amino acid, specifically arginine, which is useful for treating atopic dermatitis.
[0003] Impairment of the epidermal barrier function plays a key role in the initiation of atopic dermatitis (Kuo et al., 2013). Indeed, this impaired barrier function of the epidermis induces a vicious cycle of itching and scratching (Mochizuki et al.,2019), which increases permeability to allergens, bacteria and viruses (Cipriani et al., 2014; Halling-Overgaard et al., 2017), which in turn act as mediators of the increased inflammation process.
[0004] Tight joints (or zonula occludens These are intercellular junctions crucial for epithelial adhesion (or intercellular adhesion) and barrier function. They are dynamic transmembrane complexes that open and close. These tight junctions are composed of structural proteins, cytoskeletal-associated proteins, and proteins involved in cell signaling and polarity mechanisms (Niessen, 2007).
[0005] In particular, tight junctions are composed of transmembrane proteins such as claudins, occludins, junctional adhesion molecules (JAMs), and tricellulins, which are structural proteins similar to occludins; and cytosolic proteins such as proteins zonula occludens (ZO), the cingulins, the protein multiple-PDZ domain protein 1 (MUPP1) or the protein Membrane-Associated Guanylate Kinase with Inverted orientation (MAGI).
[0006] Tight junctions are found particularly in the granular layer (or stratum granulosum ) of the epidermis (Brandner et al., 2002).
[0007] The main function of tight junctions in the skin is to establish a second skin barrier that intervenes instantly upon rupture of the stratum corneum of the skin (or stratum corneum ) .
[0008] Several scientific studies show that the expression of several proteins that make up tight junctions is altered in the skin of patients with atopic dermatitis; in particular, the expression of claudin-1 is significantly decreased in lesional areas of patients with atopic dermatitis (Batista). et al., 2015; Gruber et al., 2015; Yuki et al., 2011).
[0009] It follows from the above that restoring the expression and functionality of tight junctions offers a new avenue for strengthening or restoring the skin's barrier function, and thereby preventing and / or treating atopic dermatitis.
[0010] As an example, documents EP2 691 090 and EP 2 704 704 describe respectively the use of cosmetic active ingredients (plant polyphenol, flavonoids or cis-urocanic acid) and probiotic bacteria to strengthen tight junctions for the purpose of treating atopic dermatitis.
[0011] However, the solutions proposed by these documents correspond to undefined compositions of plant extracts and bacterial lysates which may give rise to allergic or inflammatory reactions following application to human skin and whose composition may vary significantly from batch to batch.
[0012] There therefore remains a clear need to develop a composition comprising pure dermatological active compounds that help restore the functionality of tight junctions in pre-atopic and atopic skin, which are also highly titrated in active molecules to prevent and / or treat atopic dermatitis, especially in the long term, and which are safe for human topical use, i.e., perfectly compatible with the skin and ideally biomimetic, i.e. identical to constituents of human skin. Description of the invention
[0013] The Applicant has found that, surprisingly, several dermatological active ingredients, which are perfectly safe and suitable for human cosmetic use, make it possible to overcome the disadvantages and meet the needs previously described.
[0014] The invention generally aims to meet a real need, particularly a cosmetic one, by moisturizing and soothing the skin, reducing feelings of discomfort, and In short, by improving the appearance of the skin.
[0015] In particular, the invention aims to treat atopic dermatitis in order to improve the appearance of the skin and reduce imperfections.
[0016] More specifically, the Applicant has observed that the compounds, or active ingredients, included in the composition according to the invention act synergistically to induce the expression of claudin-1, a key structural protein of tight junctions. These compounds, which are perfectly biomimetic, are suitable for use in the formulation of dermo-cosmetic products adapted for the prevention and / or treatment of atopic dermatitis.
[0017] For the purposes of this invention, "active ingredient" means a substance or compound which has biological and / or therapeutic properties which underlie a physiological effect.
[0018] The active ingredient is to be distinguished from at least one excipient, present in the composition according to the invention.
[0019] The term “excipient” refers to a substance other than the active ingredient that gives the composition properties, in particular, of consistency, galenic and / or vectorization of the active ingredient.
[0020] For the purposes of this invention, a "biomimetic compound" is defined as a compound that exists naturally on / in healthy skin and its appendages, or that, after hydrolysis or redox reaction, is transformed into compounds that also exist naturally on / in healthy skin and its appendages. According to this invention, this compound is considered in its isolated state, in a form identical to its natural form, or modified from its natural form, but remaining cytocompatible with the skin regardless of its method of extraction or production.
[0021] Thus, according to a first aspect, the invention relates to a composition comprising, at least one basic amino acid, advantageously selected from the group consisting of arginine, lysine, histidine, ornithine and hydroxyproline; and at least one glycosylceramide.
[0022] According to a particular embodiment, the composition according to the invention is a cosmetic or dermo-pharmaceutical composition, advantageously cosmetic.
[0023] Amino acids are totally biomimetic active ingredients because they are found in all living organisms, either as constituents of proteins, or in free form following a degradation process in a living organism.
[0024] For the purposes of the invention, "basic amino acid" means all forms of the amino acid, including any salt.
[0025] Glycosylceramides are glycolipids consisting of a ceramide linked by a beta-glycosidic bond to a single neutral sugar (monoglycosylceramide) or to several neutral sugars (polyglycosylceramide). A ceramide is the amide of a sphingosine and a fatty acid. Advantageously, the neutral sugar is a hexose or a deoxyhexose selected from the group consisting of allose, altrose, glucose, mannose, gulose, idose, galactose, fucose, and fructose. The fatty acid is advantageously long-chain and generally contains 16 to 18 carbon atoms, the chain possibly being hydroxylated. Preferably, the ceramides are chosen from the group comprising ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, ceramide 7.
[0026] Glycosylceramides are found in all organisms, particularly in humans where they are especially abundant in nerve and brain tissues as constituents of the myelin sheath. Therefore, glycosylceramides are considered biomimetic compounds.
[0027] According to a particular embodiment, the basic amino acid included in the composition according to the invention is arginine or one of its salts.
[0028] The different forms of arginine are, in general, D-arginine, D,L-arginine, and L-arginine. Examples of organic or mineral salts of arginine include hydrochlorides, glutamates, butyrates, and glycolates.
[0029] Advantageously, the composition according to the invention contains L-arginine.
[0030] According to a particular embodiment, the arginine used in the composition according to the invention is in purified form, preferably with a purity of at least 60%, preferably at least 70%, advantageously at least 80%, even more advantageously at least 90%, or even at least 95% or 98%. The arginine contained in the composition according to the invention may be of plant origin, chemical origin, or obtained by biotechnology. Thus, the cosmetic raw material L-Arginine marketed by Kyowa Hakko Kogyo Co., Ltd. and corresponding to the INCI name arginine may be used in the composition according to the invention.
[0031] According to a particular embodiment, the composition according to the invention comprises at least one glycosylceramide in the form of a monoglycosylceramide and / or a polyglycosylceramide, advantageously of a monoglycosylceramide and / or tetraglycosylceramide.
[0032] According to a preferred embodiment, the composition according to the invention comprises glycosylceramides in the form of monoglycosylceramide and tetraglycosylceramide.
[0033] According to a particular embodiment, the composition comprises a monoglycosylceramide corresponding to a glucuronic acid (or gluconic acid) covalently linked by a β-glycosidic bond to a ceramide.
[0034] According to a particular embodiment, the polyglycosylceramide according to the invention corresponds to an oligosaccharide covalently linked by a β-glycosidic bond to a ceramide.
[0035] Advantageously, the polyglycosylceramide according to the invention is a tetraglycosylceramide whose oligosaccharide corresponds to the following sequence of sugars: glucuronic acid-glucosamine-galactose-mannose (or GlcA-GlcN-Gal-Man).
[0036] According to a particular embodiment, the glycosylceramide(s) according to the invention are in purified form, of purity of at least 60%, preferably at least 70%, advantageously at least 80%, even more advantageously at least 90%, or even at least 95%.
[0037] The glycosylceramide(s) included in the composition according to the invention may be of plant origin, chemical origin, or obtained by biotechnology.
[0038] Advantageously, the composition according to the invention comprises at least one glycosylceramide of biotechnological origin.
[0039] Advantageously, all the glycosylceramides included in the composition according to the invention are of biotechnological origin.
[0040] According to a particular embodiment, the glycosylceramides of the invention are of biotechnological origin, in particular derived from the extraction of membranes from bacterial species that synthesize them, such as for example Pseudomonas spp. Advantageously, glucosylceramides are obtained from the bacterial species Pseudomonas paucimobilis. Thus, the cosmetic raw materials Glycosphingolipid and Biosphingo, marketed respectively by the companies THREE B CO., INC AND KIKKOMAN BIOCHEMIFA COMPANY, and corresponding to the INCI designation glycosphingolipids, can be used in the composition according to the invention.
[0041] According to a particular embodiment, at least one basic amino acid, advantageously arginine or one of its salts, represents between 0.001% and 2% by total weight of the composition, advantageously between 0.01% and 0.5%.
[0042] According to another particular embodiment, at least one glycosylceramide, advantageously glycosylceramides in the form of monoglycosylceramide and tetraglycosylceramide, represents between 0.0001% and 1% by total weight of the composition, advantageously between 0.001% and 0.1%.
[0043] In a particular embodiment, the composition according to the invention further comprises at least one triterpene saponoside or one of its derivatives selected from the group consisting of glycyrrhetinic acid, glycyrrhizin, stearyl glycyrrhetinate and dipotassium diglycyrrizinate.
[0044] These compounds, derived from licorice, have anti-inflammatory properties and are commonly used in the topical treatment of atopic dermatitis to combat the itching associated with this skin condition. For example, the cosmetic raw materials 18β-glycyrrhetic acid, dipotassium glycyrrhizinate, and glycyrrhizic acid, corresponding respectively to the INCI names glycyrrhetinic acid, dipotassium glycyrrhizate, and glycyrrhizic acid, and stearyl glycyrrhetinate (all designated by their INCI names and commercially available from producers listed, for example, in the INCI International Buyer's Guide), can be used in the compositions according to the invention.
[0045] Advantageously, the composition according to the invention comprises, in addition to the basic amino acid and at least one glycosylceramide, a combination of glycyrrhetinic acid and dipotassium diglycyrrizinate as anti-inflammatory agents.
[0046] According to a particular embodiment, at least one triterpene saponoside or one of its derivatives represents between 0.0001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.05% and 1%.
[0047] According to one embodiment, the composition according to the invention further comprises at least one non-ionic surfactant selected from sucrose esters and / or sorbitan esters.
[0048] According to a particular embodiment, at least one non-ionic surfactant according to the invention represents 0.1% and 5% by total weight of the composition, advantageously between 1% and 3%.
[0049] The sucrose esters and / or sorbitan esters adapted according to the invention are described in detail in document WO2014 / 023895, which is incorporated in full by reference. These agents, alone or in combination, reduce the adhesion and / or proliferation of Staphylococcus aureus on the skin and / or nasal mucosa, thereby improving the overall clinical course of atopic dermatitis.
[0050] According to a preferred embodiment, the non-ionic surfactant of the invention corresponding to a sorbitan ester is polysorbate 20 (INCI) or polysorbate 80 (INCI), advantageously polysorbate 20.
[0051] According to another preferred embodiment, the non-ionic surfactant of the invention corresponding to a sucrose ester is a sucrostearate having a Hydrophilic Lipophilic Balance (HLB) value of at least 16, which corresponds to a relative proportion of sucrose and stearic acid monoesters between 75% and 80% by weight of sucrose stearate (INCI).
[0052] According to a particular embodiment, the non-ionic surfactant of the invention represents between 0.1% and 5% by weight of the composition, advantageously between 1% and 3%.
[0053] According to a particular embodiment, the composition according to the invention further comprises at least one lipid suitable for restoring the skin barrier, advantageously selected from the group consisting of: at least one exogenous lipid from the skin, advantageously a vegetable oil; a mixture of constituents naturally present in the skin including ceramides 1, 3, 6; cholesterol; free fatty acids and phytosphingosine; and squalane.
[0054] In one particular embodiment, the exogenous lipids of the skin correspond to sunflower oil (INCI: Helianthus annuus seed oil), rapeseed oil (INCI: canola oil) and / or jojoba oil (INCI: Simmondsia chinensis (jojoba) seed oil). These three vegetable oils have known emollient and anti-inflammatory properties.
[0055] In a particular embodiment, the mixture of constituents naturally present in the skin is presented in the form of a composition containing the lipids corresponding to the following INCI names: Sodium Lauroyl Lactylate, Ceramide NP, Ceramide AP, Phytosphingosine, Cholesterol, Ceramide EOP.
[0056] In one particular embodiment, the lipid capable of restoring the skin barrier is squalane, a lipid also found in the composition of the skin. The squalane used in this invention is advantageously of plant origin.
[0057] Preferably, lipids capable of restoring the skin barrier represent between 0.01% and 25% by weight of the composition, advantageously between 1% and 15%.
[0058] According to a particular embodiment, the composition of the invention further comprises at least one additional polyhydroxylated compound selected from the group comprising rhamnose, xylitol, and mannitol. These polyhydroxylated compounds contribute to reducing the adhesion of pathogenic bacteria, such as S . aureus, on the skin and mucous membranes in humans, including the nasal mucosa. Mannitol, for its part, possesses free radical scavenging activity.
[0059] In a particular embodiment of the invention, the composition comprises a mixture of the three additional polyhydroxylated compounds mentioned above. Advantageously, rhamnose represents between 0.01% and 1% by total weight of the composition, xylitol represents between 0.05% and 2% by total weight of the composition, and mannitol represents between 0.005% and 1% by total weight of the composition.
[0060] Advantageously, the composition of the invention further comprises vitamin PP, also known as vitamin B3, nicotinamide, or niacinamide, or one of its derivatives, compounds known to stimulate the synthesis of stratum corneum lipids, such as ceramides, free fatty acids, and cholesterol. Vitamin PP acts by stimulating the activity of serine palmitoyltransferase, a key enzyme in the synthesis of sphingosine, a precursor molecule of ceramides.
[0061] According to a particular embodiment, niacinamide and / or one of its derivatives constitutes between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 2%.
[0062] According to a particular embodiment, the composition of the invention comprises prebiotic substances, notably oligosaccharides such as fructooligosaccharides or FOS (INCI), short-chain dextrins (INCI), arabinogalactans (INCI), inulin (INCI), or lactulose (INCI). In a preferred embodiment, the composition according to the invention contains FOS, i.e., fructose and sucrose oligomers having a degree of polymerization between 2 and 10. FOS contribute to the induction of β-defensins and are also metabolized by saprophytic flora. FOS have antimicrobial properties and allow for a reduction in the use of artificial preservatives, as described in document FR 2 831 059.
[0063] Advantageously, FOS represent between 0.001% and 20% by total weight of the composition, advantageously between 0.01% and 10%, preferably between 0.1% and 5%.
[0064] According to a particular embodiment, the composition according to the invention further comprises at least one inducer of antimicrobial peptides, that is to say, an active ingredient capable of inducing the synthesis and / or secretion of antimicrobial peptides in humans (in particular, β-defensins) or by the microbiota. These properties have been demonstrated, in particular, in plant extracts, such as the extract of Peumus boldus (boldo) or extract from Filipendula ulmaria (meadowsweet).
[0065] Advantageously, the inducer of antimicrobial peptides is boldo extract, meadowsweet extract, or a mixture thereof.
[0066] According to a particular embodiment, the antimicrobial peptide inducer represents between 0.001% and 5% by total weight of the composition, preferably between 0.01% and 1%.
[0067] According to a particular embodiment, the composition according to the invention is presented in a form adapted to be cosmetically and / or dermatologically acceptable, i.e. compatible with the skin, mucous membranes, hair, nails and / or scalp.
[0068] According to a preferred embodiment, the composition according to the invention is presented in a form suitable for topical administration.
[0069] In another embodiment, the advantageously cosmetic composition according to the invention further comprises a bioactive system combining, on the one hand, a stable aqueous form of a nucleotide selected from ATP (adenosine triphosphate), Gp4G (diguanosine tetraphosphate), and Ap4A (diadenosine tetraphosphate); and on the other hand, at least one biomimetic peptide comprising at most six amino acids, advantageously different from that of the invention, mimicking a skin polypeptide or a skin protein, or a biomolecule that is an agonist or antagonist of said peptide or protein. In practice, the combination of these active ingredients catalyzes the metabolic activity of skin cells while achieving a dermocosmetic or therapeutic effect through the use of the biomimetic peptides.These can be selected to obtain the desired effect, for example, an inhibition effect on irritations of neurogenic origin, a depigmenting activity, an effect inhibiting any intolerance or sensitization, etc.
[0070] In practice, in the bioactive system according to the invention, the nucleotide represents at most 10% by total weight of the composition, preferably between 0.001% and 5%; and the biomimetic peptide represents between 0.001% and 1% by total weight of the composition.
[0071] According to another embodiment, the composition according to the invention may further comprise an extract of the bacteria Arthrobacter agilis, in particular an extract rich in carotenoids INCI: Micrococcus lysate). Advantageously, the composition according to the invention comprises such a dry extract which represents between 0.00001% and 0.1% by total weight of the composition, preferably between 0.0001% and 0.001%.
[0072] According to another embodiment, the composition according to the invention further comprises other components which may contribute to internal protection by an action which may consist of DNA protection, a reduction of immunosuppression induced by UV radiation, an antiradical action or a combined effect of these actions.
[0073] The protective action of a preparation according to the invention against oxidative stress or against the effect of free radicals can be further improved if it also includes one or more antioxidants, easily selected by a person skilled in the art from among the raw materials used in the cosmetic field.
[0074] In a particular embodiment of the invention, the composition according to the invention also contains active ingredients capable of stimulating the proliferation of skin cells, advantageously fibroblasts and / or keratinocytes, preferably human or animal fibroblasts. In particular, and according to this embodiment, the composition according to the invention further comprises: of α-lipoic acid or one of its salts; a vitamin C derivative selected from ethyl ascorbic acid and sodium ascorbate or a mixture thereof; and hyaluronic acid, the molecular weight (Mw) of which is advantageously between 0.5 and 15 kDa, preferably 0.5 and 10 kDa.
[0075] Advantageously, α-lipoic acid or one of its salts represents less than 0.1% by total weight of the composition, advantageously less than 0.01%, preferably between 0.001% and 0.0005%.
[0076] Advantageously, the vitamin C derivative chosen from ethyl ascorbic acid and sodium ascorbate or a mixture thereof, advantageously ethyl ascorbic acid, preferably 3-O ethyl ascorbic acid ether, represents between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 1%.
[0077] Advantageously, hyaluronic acid, whose molecular weight (Mw) is advantageously between 0.5 and 15 kDa, preferably 0.5 and 10 kDa, represents between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 1%.
[0078] According to another embodiment of the invention, the composition further comprises at least one, or even all, of the following constituents exercising biological activity. vivo on skin, lip, hair and / or mucous membrane cells exposed to UV-A and / or UV-B radiation, respectively: an antiradical agent preserving cellular structures, such as, for example, vitamin E and / or its fat-soluble or water-soluble derivatives, in particular tocotrienol and / or tocopherol, advantageously representing between 0.001% and 10% by total weight of the composition, even more advantageously between 0.02% and 2%, preferably 0.04%; an immunosuppressive limiting agent, such as, for example, vitamin PP, advantageously representing between 0.001% and 1% by total weight of the composition, preferably between 0.01% and 0.3%; a p53 protein protecting agent, such as, for example, epigallocatechin gallate (EGCG), advantageously representing between 0.001% and 0.1% by total weight of the composition, preferably between 0.005% and 0.05%.
[0079] The composition according to the invention may also include, in addition, peptide extracts of soy and / or wheat.
[0080] In practice, peptide extracts from soybeans or wheat are obtained through enzymatic hydrolysis of the seeds by means of peptidases, which allows the recovery of peptides with an average size of 700 Da. Preferably, the soybean peptide extract is the extract identified under CAS number 68607-88-5 and / or the wheat peptide extract is the extract identified under CAS number 70084-87-6. Wheat and soybean extracts may correspond to the INCI designations Hydrolyzed wheat protein and Hydrolyzed soy protein, respectively.
[0081] In a particular embodiment, the peptide extracts of soy and wheat are used together, for example in a weight ratio of 80 / 20 and 20 / 80 respectively, advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40.
[0082] In an advantageous embodiment, the soy and / or wheat peptide extracts are free from the synthetic tripeptide GHK (glycylhistidyllysine; INCI: Tripeptide-1). In practice, the soy and / or wheat peptide extracts represent between 0.01% and 20% by weight of the total composition, advantageously between 0.1% and 10%, and preferably between 0.2% and 0.7%.
[0083] According to an alternative and advantageous embodiment, the composition according to the invention further comprises at least one UV filter. UV light filtration is known to improve the overall condition of the skin in individuals suffering from atopic dermatitis.
[0084] For the purposes of the invention, the term "UV filter" encompasses organic or mineral compounds capable of filtering UV-A, UV-B and / or UV-C.
[0085] According to the invention, these can be mineral filters as well as chemical or organic filters.
[0086] The compositions according to the invention may contain one or more broad-spectrum UV filters, i.e. compounds or mixtures that absorb UV-A, UV-B, UV-C and possibly visible light.
[0087] Among broad-spectrum organic filters, the filters corresponding to the following INCI designations can be used within the scope of the invention: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbutylphenol. Another example of a broad-spectrum filter suitable for the composition according to the invention corresponds to the INCI designation diethylhexyl butamido triazone.
[0088] Thus, and in a particular embodiment, the composition according to the invention comprises at least one filter selected from the following group of compounds identified by their INCI designation: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, and methylene bis-benzotriazolyl tetramethylbutylphenol, diethylhexyl butamido triazone, or mixtures thereof.
[0089] Advantageously, the composition includes the filter bis-ethylhexyloxyphenol methoxyphenyl triazine.
[0090] According to another embodiment, instead of or in addition to the broad spectrum filter(s), the composition contains at least one UV-A and / or UV-B filter, organic and / or mineral, which may be in aqueous (lipophilic) and / or oily (liposoluble) phase.
[0091] Thus, by way of example, the composition according to the invention may contain liposoluble UV-B filters, which may contribute to the stabilization or solubilization of broad-spectrum filters or stabilize each other and thereby increase the sun protection factor (SPF).
[0092] Advantageously, such filters correspond to the following INCI designations: homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl triazone.
[0093] In a preferred embodiment, the composition according to the invention comprises ethylhexyl triazone.
[0094] In another embodiment, the liposoluble UV-B filter is α-(trimethylsilyl)-ω-(trimethylsilyloxy)poly[oxy(dimethyl)silyne]-co-[oxy(methyl)(2-{4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy}-1-methyleneethyl)silyne]-co-[oxy(methyl)(2-(4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy)prop-1-enyl)silyne], a silicone polymer capable of filtering in the UV-B range (INCI: polysilicone-15).
[0095] In a preferred embodiment, the composition according to the invention comprises at least one UV-B filter selected from the following group of compounds identified by their INCI designation: homosalate, ethylhexyl salicylate, ethylhexyl triazone, polysilicone-15, or mixtures thereof.
[0096] In a particular embodiment, the composition is free from the following filters: 4-methylbenzylidene camphor, benzophenone-2, benzophenone-3, ethylhexyl methoxycinnamate, octocrylene.
[0097] In an advantageous embodiment, the composition according to the invention includes at least one UV-A filter, in order to ensure complete filtration of the harmful part of the solar spectrum.
[0098] Advantageous UV-A filters within the meaning of the present invention are butyl methoxydibenzoylmethane (INCI) and diethylamino hydroxybenzoyl hexyl benzoate (INCI).
[0099] In one particular embodiment, the UV-A filter is bis-(diethylaminohydroxybenzoyl benzoyl)piperazine (INCI) (CAS number 919803-06-8).
[0100] Thus, and in a preferred embodiment, the composition according to the invention comprises at least one filter selected from the following group of compounds identified by their INCI designation: butyl methoxydibenzoylmethane, diethylamino hydroxybenzoyl hexyl benzoate, bis-(diethylaminohydroxybenzoyl benzoyl)piperazine, or mixtures thereof.
[0101] Other advantageous UV filters within the meaning of the present invention are water-soluble filters, such as: The filter corresponding to the INCI designation disodium phenyl dibenzimidazole tetrasulfonate. The filter corresponding to the INCI designation phenylbenzimidazole sulfonic acid. In a preferred embodiment, the composition according to the invention comprises at least one water-soluble filter selected from the following group of compounds identified by their INCI designation: disodium phenyl dibenzimidazole tetrasulfonate, phenylbenzimidazole sulfonic acid, or mixtures thereof.
[0102] Advantageously, inorganic mineral filters, or mineral screens, are metallic oxides and / or other compounds that are difficult to dissolve or insoluble in water, in particular oxides of titanium (TiO2), zinc (ZnO), iron (Fe2O3), zirconium (ZrO2), silicon (SiO2), manganese (e.g., MnO), aluminum (Al2O3), or cerium (Ce2O3).
[0103] In a particular embodiment, inorganic mineral filters can be used in the form of commercially available oily or aqueous pre-dispersions. These pre-dispersions can advantageously be enhanced with dispersion aids and / or solubilization mediators.
[0104] Inorganic mineral filters can also be surface-treated or encapsulated to give them hydrophilic, amphiphilic, or hydrophobic properties. This surface treatment may involve coating the mineral filters with a thin hydrophilic and / or hydrophobic inorganic and / or organic film.
[0105] In a preferred embodiment, the composition according to the invention comprises at least one mineral screen selected from the following group of compounds identified by their INCI designation: Zinc oxide, Titanium dioxide, or mixtures thereof.
[0106] The lists of UV filters mentioned that can be implemented within the meaning of the present invention are of course given for information purposes only and are not exhaustive.
[0107] Advantageously, the UV filters as described above, present in the composition according to the invention, represent between 0.1% and 30% by total weight of the composition, advantageously between 0.5% and 20%, even more advantageously between 1% and 15%.
[0108] According to a particular embodiment, the composition according to the invention has a sun protection factor (“SPF” or FPS) greater than or equal to 10, preferably greater than or equal to 20, advantageously greater than or equal to 30, even more advantageously greater than or equal to 50.
[0109] According to a preferred embodiment, the composition according to the invention comprises a UV-A / UV-B protection ratio equal to or greater than 1 / 3.
[0110] The solar composition according to the invention comprises at least one solubilizer of solar filters.
[0111] The composition according to the invention may further comprise an SPF "booster," i.e., an agent that enhances the sun protection factor, and / or a photostabilizer, i.e., an ingredient that increases the SPF or photostabilizes the filters, such an ingredient not itself being considered a sunscreen. Examples include: Butyloctyl salicylate (INCI), a photostabilizer advantageously representing between 0.01% and 10% by total weight of the composition, even more advantageously between 0.1% and 2%; Benzotriazolyl dodecyl p-cresol (INCI), a photostabilizer advantageously representing between 0.01% and 10% by total weight of the composition, even more advantageously between 0.1% and 2%; Pongamol (INCI), a plant-based molecule absorbing UV-A rays, advantageously representing between 0.5% and 2% by total weight of the composition, even more advantageously around 1%; Ethylhexyl methoxycrylene (INCI), a photostabilizer, solubilizer, and SPF booster advantageously representing between 1% and 5% by total weight of the composition. a styrene acrylate copolymer (INCI: styrene / acrylate copolymer), preferably representing between 1% and 10% by total weight of the composition according to the invention.Diethylhexyl syringylidene malonate (INCI), advantageously representing between 1% and 10% by total weight of the composition. - A water-dispersible polyester, corresponding to the INCI designations polyester-5 (and) Sodium silicoaluminate, advantageously representing between 1% and 10% by total weight of the composition, an acrylate copolymer having a glass transition temperature of -5°C to -15°C as measured by differential scanning calorimetry, said copolymer advantageously representing between 1% and 10% by total weight of the composition.
[0112] According to a particular embodiment, the composition of the invention further comprises an advantageously colored blurring particle or a mixture of several blurring particles. These blurring particles are also referred to as "soft-focus particles" or "blurring particles."
[0113] For the purposes of this invention, a "blurring particle" is defined as a particle, advantageously colored, designed to give the complexion greater transparency and a blurring effect. In particular, the blurring particle allows the composition containing it to attenuate, through an optical effect, the skin's microrelief, and especially skin imperfections such as spots, wrinkles, and fine lines.
[0114] Several soft-focus or blurring particles are available on the market. For example, we can mention the raw materials of the Ronasphere range based on silica substrate, marketed by the company MERCK, as well as several raw materials marketed by the companies JGC-C&C (Coverleaf range based on sericite or sericite / talc substrate), NIHON KOKEN (Relief Color range, Silséem based on mica / silica substrate), or MIYOSHI KASEI (PC-Bail range based on silica substrate).
[0115] According to yet another embodiment, the raw material KSP-100 marketed by the company SHINETSU corresponding to the INCI designation Vinyl dimethicone / methicone silsesquioxane crosspolymer can be used as a blurring particle.
[0116] Preferably, the blurring particles included in the composition of the invention represent between 0.5% and 20% by total weight of the composition, advantageously between 1% and 10%, and even more advantageously between 1% and 5%.
[0117] According to a particular embodiment, the composition according to the invention may further comprise any fat commonly used in cosmetics. Examples include silicone-based fats such as silicone oils, gums, and waxes; as well as non-silicone-based fats such as oils and waxes of vegetable, mineral, animal, and / or synthetic origin. The oils may be volatile or non-volatile. Other examples include hydrocarbons, synthetic esters and ethers, fatty alcohols, and fatty acids.
[0118] According to a particular embodiment, the composition may further comprise an aqueous medium, a hydroalcoholic medium containing an alcohol such as ethanol, or an organic medium comprising common organic solvents such as C1-6 alcohols, in particular ethanol and isopropanol, glycols such as propylene glycol, ketones.
[0119] According to a particular embodiment, the composition according to the invention further comprises at least one conventional emulsifier, chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or in mixture.
[0120] According to a particular embodiment, the composition according to the invention further comprises the usual adjuvants in the field concerned, such as hydrophilic or lipophilic thickeners or gelling agents, hydrophilic or lipophilic additives, active ingredients in particular cosmetic, preservatives, antioxidants, perfumes, fillers, pigments, odor absorbers, colorants, moisturizers (glycerin), vitamins, essential fatty acids, liposoluble polymers in particular hydrocarbons, opacifiers, stabilizers, sequestrants, conditioners and propellants.
[0121] Of course, a person skilled in the art will take care to choose any additional adjuvants or excipients, and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or substantially not, altered by the envisaged addition.
[0122] The composition according to the invention is advantageously formulated to be cosmetically acceptable, that is, compatible with the skin, mucous membranes, hair, and scalp. Preferably, the composition of the invention is a composition for cutaneous application or topical use.
[0123] The term “composition for cutaneous application” or “for topical use” refers to a composition compatible with application to the skin, mucous membranes, hair and / or scalp, preferably human skin.
[0124] The composition of the invention can be presented in any suitable dosage form for topical application, including aqueous, hydroalcoholic, organic, or oily solutions; suspensions or dispersions in solvents or fatty substances, such as lotions or serums; vesicular dispersions; water-in-oil (W / O), oil-in-water (O / W), or multiple emulsions such as water-in-oil-in-water (W / O / W) emulsions. The emulsion can be more or less thick and may be in the form of a cream or lotion; the composition of the invention can also be in the form of an ointment, gel, solid stick, anhydrous paste or solid products, foam, including aerosols, a biphasic composition, or a sprayable composition.
[0125] The galenic form of the composition and its method of preparation, and consequently the excipients appropriate to the composition of the invention, can be chosen by a person skilled in the art on the basis of their general knowledge according to the type of composition sought.
[0126] It may be particularly advantageous to formulate the composition of the invention so that it is sprayable. This can be achieved, for example, by formulating specific emulsions comprising particular combinations of excipients. In another aspect, the invention relates to a cosmetic treatment method consisting of applying a composition as defined above to the skin. In yet another aspect, the invention relates to a composition, advantageously cosmetic, comprising at least one glycosylceramide, advantageously one monoglycosylceramide and / or one polyglycosylceramide, for the prevention and / or treatment of atopic dermatitis.
[0127] According to a particular embodiment, at least one glycosylceramide, advantageously a monoglycosylceramide and / or a polyglycosylceramide, is as described above.
[0128] The invention also relates to the composition as defined above for use in a method of treating atopic dermatitis by application to the skin.
[0129] According to another aspect, the invention relates to a composition, advantageously cosmetic, comprising: at least one basic amino acid selected from the group consisting of arginine, lysine, histidine, ornithine, hydroxyproline and one of their salts and at least one glycosylceramide, for use in the prevention and / or treatment of atopic dermatitis.
[0130] According to another particular aspect, the invention relates to a composition comprising at least one glycosylceramide, advantageously a monoglycosylceramide and / or a polyglycosylceramide, preferably in combination with at least one basic amino acid selected from the group consisting of arginine, lysine, histidine, ornithine, hydroxyproline and one of their salts, for use in: induce the expression, or increase the expression, of at least one gene encoding a transmembrane protein constituting tight junctions, advantageously claudin-1; and / or induce an increase in the content of at least one transmembrane protein constituting tight junctions, advantageously claudin-1; and / or improve the integrity of tight junctions; and / or strengthen, improve, the skin barrier function.
[0131] According to a particular embodiment, the basic amino acid included in the composition for its use according to the invention is arginine or one of its salts.
[0132] Advantageously, the composition for its use according to the invention contains L-arginine.
[0133] According to a particular embodiment, the composition for its use according to the invention comprises at least one glycosylceramide corresponding to a monoglycosylceramide and / or polyglycosylceramide, advantageously a monoglycosylceramide and / or tetraglycosylceramide.
[0134] According to a preferred embodiment, the composition for its use according to the invention comprises glycosylceramides in the form of monoglycosylceramide and tetraglycosylceramide.
[0135] According to a particular embodiment, the composition for its use according to the invention comprises a monoglycosylceramide corresponding to a glucuronic acid (or gluconic acid) covalently linked by a β-glycosidic bond to a ceramide.
[0136] According to a particular embodiment, the polyglycosylceramide included in the composition for its use according to the invention corresponds to an oligosaccharide covalently linked by a β-glycosidic bond to a ceramide.
[0137] Advantageously, the polyglycosylceramide included in the composition for its use according to the invention is a tetraglycosylceramide whose oligosaccharide corresponds to the following sequence of sugars: glucuronic acid-glucosamine-galactose-mannose (or GlcA-GlcN-Gal-Man).
[0138] The glycosylceramide(s) included in the composition for its use according to the invention may be of plant origin, chemical, or obtained by biotechnology.
[0139] Advantageously, the composition for its use according to the invention comprises at least one glycosylceramide of biotechnological origin.
[0140] Advantageously, all the glycosylceramides included in the composition for its use according to the invention are of biotechnological origin.
[0141] According to a particular embodiment, at least one basic amino acid, advantageously arginine or one of its salts, represents between 0.001% and 2% by total weight of the composition, advantageously between 0.01% and 0.5%.
[0142] According to another particular embodiment, at least one glycosylceramide, advantageously glycosylceramides in the form of monoglycosylceramide and tetraglycosylceramide, represents between 0.0001% and 1% by total weight of the composition, advantageously between 0.001% and 0.1%.
[0143] According to a particular embodiment, the composition for its use according to the invention is that described above (see the first aspect of the invention).
[0144] Advantageously and in relation to these different therapeutic applications, the composition of the invention is in a galenic form suitable for topical administration.
[0145] One way to demonstrate the effect of the composition according to the invention on the prevention and / or treatment of atopic dermatitis is, for example, by evaluating the expression of at least one gene encoding a transmembrane protein that is a component of tight junctions, such as claudin-1. Alternatively, it could involve a qualitative and / or quantitative analysis targeting at least one transmembrane protein that is a component of tight junctions, such as claudin-1. Examples include analysis by chromatography and / or mass spectrometry, by western blot, or by immunohistochemical staining.
[0146] The manner in which the invention can be implemented and the resulting advantages will be more clearly shown in the following examples of implementation, given by way of illustration and not limitation, in support of the attached figure. Description of the figures
[0147] There figure 1This study demonstrates the effect of arginine (A), glycosylceramides (GC), and their combinations (A + GC) on claudin-1 expression in a cellular model of atopic dermatitis. The "control" conditions correspond to the negative control (uninhibited or T ≤ ) and the positive control (inhibited or T ≥ ). The percentage of claudin-1 synthesis induction is reported relative to the inhibited positive control (100%). ** indicates a statistical significance threshold (p-value) between 0.001 and 0.01 (highly significant), and *** indicates a statistical significance threshold (p < 0.001) (extremely significant). Examples of completed projects EXAMPLE 1: COSMETIC COMPOSITION AS DEFINED IN THE INVENTION - SPRAY
[0148] A composition according to the invention is described in Table 1. Ingredient (INCI) Weight (in %) Aqua / water / eau qsp100 Glycerin 15,00 Dipropylene glycol 9,00 Isostearyl isostearate 2,00 Propylheptyl caprylate 1,999 Squalane 1,00 Sodium cocoyl glutamate 0,8825 Glycyrrhetinic acid 0,50 Pentylene glycol 0,50 Ornithine 0,30 Disodium EDTA 0,20 Citric acid 0,17 Propanediol 0,125 Xanthan gum 0,10 Tocopherol 0,036 Lecithin 0,0201 Helianthus annuus (sunflower) seed oil 0,015 Glycosphingolipids 0,007 EXAMPLE 2: COSMETIC COMPOSITION AS DEFINED IN THE INVENTION - FREEZE
[0149] A composition according to the invention is described in Table 2. Ingredient (INCI) Weight (in %) Aqua / Water / Water qsp 100 Glycerin 2,00 Hydroxyethyl Acrylate / Sodium Acryloyldimethyl Taurate Copolymer 1,125 Isohexadecane 0,765 Titanium Dioxide [Nano] 0,375 Phenoxyethanol 0,35 1,2-hexanediol 0,26 Lysine 0,20 Polysorbate 20 0,165 Alumina 0,045 Glycosphingolipids 0,005 EXEMPLE 3 : COMPOSITION COSMETIQUE AU SENS DE L'INVENTION - EMULSION H / E
[0150] A composition according to the invention is described in Table 3. Ingredient ( INCI) Poids (en %) Aqua / water / eau qsp 100 Glycerin 13,00 Brassica campestris (rapeseed) seed oil 11,00 Paraffinum liquidum / mineral oil / huile minerale 8,00 Behenyl alcohol 2,00 Dipropylene glycol 2,00 Sucrose stéarate 2,00 Simmondsia chinensis (jojoba) seed oil 1,00 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer 0,616 Pentylene glycol 0,50 Acrylates / c10-30 alkyl acrylate crosspolymer 0,30 Caprylyl glycol 0,2545 1,2-hexanediol 0,25 Arginine 0,20 Sodium citrate 0,20 Dipotassium glycyrrhizate 0,10 Glycyrrhetinic acid 0,10 Sodium lauroyl lactylate 0,10 Polysorbate 60 0,042 Sorbitan isostearate 0,042 Citric acid 0,040 Tocopherol 0,035 Methylpropanediol 0,0246 Phytosphingosine 0,02 Triethyl citrate 0,02 Helianthus annuus (sunflower) seed oil 0,015 Ceramide NP 0,01 Ceramide AP 0,006 Cholestérol 0,005 Carbomer 0,004 Xanthan gum 0,004 Glycosphingolipids 0,003 Phenylpropanol 0,0009 Ceramide EOP 0,00001 EXAMPLE 4: EFFECT OF THE COMPOSITION ACCORDING TO THE INVENTION ON THE EXPRESSION OF CLAUDIN-1 PROTEIN IN A CELL MODEL IN VITRO OF ATOPIC DERMATITIS 1. Matériel et méthodes 1. 1. Modèle biologique et lignées cellulaires Cell lineage:
[0151] Cell type: Normal human epidermal keratinocytes (NHEK; reference: Bioalternatives K34 1), used in the 3rd passage - culture conditions: 37°C, 5% CO2 - culture medium: Keratinocyte-SFM supplemented with epidermal growth factor (Epidermal Growth Factor or EGF) at a concentration of 0.25 ng / ml, a Pituitary Extract (PE) at a concentration of 25 µg / ml and gentamicin at a concentration of 25 µg / ml. Test medium used for this example: Keratinocyte - SFM supplemented with gentamicin at a concentration of 25 µg / ml.
[0152] A culture of normal human keratinocytes is performed to test the substances; briefly, the protocol is as follows: induction of keratinocyte differentiation by calcium at 0.75 mM for 24h; treatment with the compound, 1 hour before induction by the alarmins; treatment with the following alarmins: histamine, IL-33 and IL-1β, in the following respective concentrations: 50 µM, 100 ng / ml and 100 ng / ml, in order to induce the atopic dermatitis phenotype, characterized by a decrease in the expression of claudin-1.
[0153] Immunostaining of claudin-1 is then performed. 1.2. Active compounds of the composition according to the invention
[0154] The compounds used, alone or in combination, in this example are shown in Table 4 below. Active compounds according to the invention Stock solution Concentrations tested Arginine 10% ultrapure water 0.02%, 0.04%, 0.1% and 0.2% Glycosylceramides 5% ultrapure water 0.0003%, 0.0006%, 0.0015% and 0.003% 1.3. Cytotoxicity Test
[0155] Preliminary cytotoxicity tests are performed on normal human keratinocytes in a test medium also containing CaCl2 at a concentration of 0.75 mM. These preliminary tests combine the MTT tetrazolium salt reduction method (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and morphological observations under the microscope.
[0156] At the end of the treatment (72 h incubation), the cells were incubated in the presence of MTT, the transformation of which into blue formazan crystals is proportional to the activity of succinate dehydrogenase (a mitochondrial enzyme). After cell dissociation and solubilization of the formazan by the addition of DMSO, the optical density (OD), representative of the number of viable cells and their metabolic activity, was measured with a spectrophotometer (VERSAmax, Molecular Devices) at 540 nm.
[0157] The results of the MTT viability test and the observation of the cell mats led to the selection of the concentrations of the active compounds according to the composition of the invention to be tested in the continuation of the study for the compound of interest (see table 2). 1.4. Culture and processing
[0158] Keratinocytes were seeded into 96-well plates and cultured in culture medium for 72 hours, then in test medium containing the differentiation inducer CaCl₂ (0.75 mM) for an additional 24 hours. The medium was then replaced with test medium containing the inducer CaCl₂ (0.75 mM) and either containing (control) the active compounds of the invention, alone or in combination, or with solvent control (DMSO tested at 0.02%). The cells were then pre-incubated for 1 hour. The mixture of alarmins: histamine, IL-33, and IL-1β (in the following respective concentrations: 50 µM, 100 ng / ml, and 100 ng / ml) was then added, and the cells were incubated for 72 hours. In parallel, an unstimulated / undifferentiated and uninhibited control condition (test medium without CaCl2 and without alarmins) and an uninhibited control condition (test medium with CaCl2 and without alarmins) were carried out.
[0159] For each condition, the analysis was performed using 30 image quantifications (n=30), except for the control conditions, which were performed using 60 image quantifications (n=60). An initial analysis of the results was carried out considering all quantifications, followed by a second analysis using only the results from culture replicates, either in triplicates (n=3), except for the control conditions, which were performed in hexolicates (n=6). 1.5. In situ immunomarginalization
[0160] After incubation, the medium was removed, and the cells were rinsed, fixed, and permeabilized. The cells were then labeled with the primary antibody against claudin-1. This antibody was subsequently detected by a secondary antibody coupled to a fluorochrome (GAM-Alexa 488). In parallel, the cell nuclei were stained with Hoechst 33258 (bisbenzimide). 1.6. Microscopic observations and image analysis
[0161] Image acquisition was performed using a high-resolution imaging system, INCell Analyzer™ 2200 (GE Healthcare; 20x objective). Ten digitized image captures were performed for each well.
[0162] The markings were quantified by measuring the fluorescence intensity of the proteins relative to the total number of cells identified by staining with bis-benzimide (integration of numerical data by the Developer Toolbox 1.5 software, GE Health care). 1.7. Data Processing
[0163] The raw data was transferred and processed using Microsoft Excel ® software.
[0164] Intergroup comparisons were performed using the unpaired two-tailed Student's t-test. Statistical analyses can be interpreted if n ≥ 5. However, for n < 5, the calculated data are provided for illustrative purposes only.
[0165] Formulas used in this report: The standard error of the mean (SEM) represents the deviation of the sample mean from the true population mean. The SEM is calculated by dividing the standard deviation (SD) by the square root of the sample size using the following formula: SEM = standard deviation (SD) / √n. The percentage of viability is calculated using the following formula: viability (%) = (combination OD / control OD) x 100. The threshold for statistical significance is as follows: ns: > 0.05 (not significant); * = 0.01 to 0.05 (significant); ** = 0.001 to 0.01 (highly significant); *** = < 0.001 (extremely significant). Significance was calculated by statistically comparing the difference between the results of the active ingredient alone and the combination at each dose.
[0166] The results are represented in the figure 1 . 2. Results
[0167] In control conditions not stimulated / not differentiated by calcium (CaCl2), claudin-1 immunostaining is present in some cells punctiformly in the cytoplasm and sometimes in the membranes.
[0168] As expected, differentiation with CaCl₂ at a concentration of 0.75 mM induced an increase in the expression of the analyzed tight junction protein (claudin-1). This induction is strong and clearly significant, resulting in a substantial increase in claudin-1 expression at both the membrane and cytoplasmic levels.
[0169] Treatment with the alarmin mixture (histamine + IL-1 + IL-33 tested at 50 µM + 100 ng / ml + 100 ng / ml) on keratinocytes stimulated / differentiated by calcium (CaCl 2) at 0.75 mM, induced a significant inhibitory effect on the expression of claudin-1 (mean of approximately 61.5% of the control).
[0170] The effect of treatment with the active compounds of the invention, alone or in combination, on the expression of claudin-1 is represented by the figure 1 .
[0171] It appears from these results that arginine (A) and glycosylceramides (GC) tested alone (% relative to T +< ) significantly reverse the inhibitory effect of the alarmin mixture on claudin-1 expression.
[0172] The combination of arginine and glycosylceramides (A + GC) exerts a greater effect on inducing claudin-1 expression than when these compounds are tested alone. At all concentration combinations tested, the increase was either highly significant (***) or extremely significant (**) and, in each case, more than complementary, signifying an unexpected potentiating synergy of the arginine and glycosylceramide combination in inducing claudin-1 expression and, consequently, in strengthening the skin barrier function and preventing and / or treating atopic dermatitis. BIBLIOGRAPHY
[0173] Batista, D.I.S., Perez, L., Orfali, R.L., Zaniboni, M.C., Samorano, L.P., Pereira, N.V., Sotto, M.N., Ishizaki, A.S., Oliveira, L.M.S., Sato, M.N., et al. (2015). Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1 / Th2 / Th17 cytokines in adults with atopic dermatitis. J. Eur. Acad. Dermatol. Venereol. 29: 1091-1095.
[0174] Brandner, J.M., Kief, S., Grund, C., Rendl, M., Houdek, P., Kuhn, C., Tschachler, E., Franke, W.W., and Moll, I. (2002). Organization and formation of the tight junction system in human epidermis and cultured keratinocytes. Eur. J. Cell Biol. 81: 253-263.
[0175] Cipriani, F., Dondi, A., and Ricci, G. (2014). Recent advances in epidemiology and prévention of atopic eczema. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 25: 630-638.
[0176] Gruber, R., Börnchen, C., Rose, K., Daubmann, A., Volksdorf, T., Wladykowski, E., Vidal-Y-Sy, S., Peters, E.M., Danso, M., Bouwstra, J.A., et al. (2015). Diverse régulation of claudin-1 and claudin-4 in atopic dermatitis. Am. J. Pathol. 185: 2777-2789.
[0177] Halling-Overgaard, A.-S., Kezic, S., Jakasa, I., Engebretsen, K.A., Maibach, H., and Thyssen, J.P. (2017). Skin absorption through atopic dermatitis skin: a systematic review. Br. J. Dermatol. 177: 84-106.
[0178] Mack, M.R., and Kim, B.S. (2018). The Itch-Scratch Cycle: A Neuroimmune Perspective. Trends Immunol. 39: 980-991.
[0179] Mochizuki, H., Lavery, M.J., Nattkemper, L.A., Albornoz, C., Valdes Rodriguez, R., Stull, C., Weaver, L., Hamsher, J., Sanders, K.M., Chan, Y.H., et al. (2019). Impact of acute stress on itch sensation and scratching behaviour in patients with atopic dermatitis and healthy controls. Br. J. Dermatol. 180: 821-827.
[0180] Weidinger, S., Beck, L.A., Bieber, T., Kabashima, K., and Irvine, A.D. (2018). Atopic dermatitis. Nat. Rev. Dis. Primer 4: 1.
Claims
1. Composition comprising: - at least one basic amino acid selected from the group constituted by arginine, lysine, histidine, ornithine, hydroxyproline and one of their salts; and - at least one glycosylceramide in the form of a monoglycosylceramide corresponding to a glucuronic acid covalently bonded to a ceramide and / or a polyglycosylceramide corresponding to an oligosaccharide covalently bonded to a ceramide.
2. Composition as claimed in claim 1, characterized in that the basic amino acid is arginine or one of its salts.
3. Composition as claimed in any one of the preceding claims, characterized in that the polyglycosylceramide is in the form of a tetraglycosylceramide.
4. Composition as claimed in claim 1 or claim 2, characterized in that the glycosylceramide is in the form of a monoglycosylceramide and a tetraglycosylceramide.
5. Composition as claimed in claim 4, characterized in that: - the oligosaccharide which is covalently bonded to the ceramide is glucuronic acid-glucosamine-galactose-mannose.
6. Composition as claimed in any one of the preceding claims, characterized in that the at least one glycosylceramide is obtained by extraction from membranes of at least one bacterial species.
7. Composition as claimed in any one of the preceding claims, characterized in that the at least one basic amino acid, advantageously arginine, represents between 0.001% and 2% of the total weight of the composition, advantageously between 0.01% and 0.5%.
8. Composition as claimed in any one of the preceding claims, characterized in that the at least one glycosylceramide represents between 0.0001% and 1% of the total weight of the composition, advantageously between 0.001% and 0.1%.
9. Composition as claimed in any one of the preceding claims, characterized in that it comprises, in addition: - at least one triterpene saponoside or one of its derivatives selected from the group constituted by glycyrrhetinic acid, glycyrrhizin, stearyl glycyrrhetinate and dipotassium diglycyrrizinate; and / or - at least one non-ionic surfactant selected from sorbitan esters and / or saccharose esters.
10. Composition as claimed in claim 9, characterized in that: - the at least one triterpene saponoside or one of its derivatives represents between 0.0001% and 10% of the total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.05% and 1%; and / or - the at least one non-ionic surfactant represents between 0.1% and 5% of the total weight of the composition, advantageously between 1% and 3%.
11. Composition as claimed in claim 9 or claim 10, characterized in that the non-ionic surfactant is polysorbate 20 or a sucrostearate with a Hydrophilic Lipophilic Balance (HLB) of at least 16.
12. Composition as claimed in any one of the preceding claims, characterized in that it additionally comprises at least one lipid which is capable of restoring the skin barrier, advantageously selected from the group constituted by: - at least one lipid which is exogenous to the skin, advantageously a vegetable oil; - a mixture of constituents which are naturally present in the skin, comprising ceramide-1, ceramide-3, ceramide-6; cholesterol; free fatty acids and phytosphingosine; and - squalane.
13. Composition as claimed in any one of the preceding claims, characterized in that it is a cosmetic composition.
14. Composition as claimed in any one of the preceding claims, characterized in that it is in a form which is suitable for topical administration.
15. Composition comprising - at least one basic amino acid selected from the group constituted by arginine, lysine, histidine, ornithine, hydroxyproline and one of their salts; and - at least one glycosylceramide in the form of a monoglycosylceramide corresponding to a glucuronic acid covalently bonded to a ceramide and / or a polyglycosylceramide corresponding to an oligosaccharide covalently bonded to a ceramide for the prevention and / or treatment of atopic dermatitis.
16. Composition as claimed in any one of claims 1 to 14, for use in the prevention and / or treatment of atopic dermatitis.
