New use of sugar mixtures comprising psicose, mannose, fructose and glucose

By using sugar mixtures of paclitaxel, mannose, fructose and glucose, the expression of skin cytokeratin-1 was stimulated, and the problem of impaired skin integrity and self-defense mechanisms was solved, significantly enhancing the skin's resistance to pathogenic bacteria Resistance.

CN119173246APending Publication Date: 2024-12-20DSM IP ASSETS BV
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Patent Information

Application Number
CN202380039391.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2022-05-11
Filing Date
2023-05-11
Publication Date
2024-12-20

AI Technical Summary

Technical Problem

The prior art is difficult to effectively stimulate the expression of skin cytokeratin-1, resulting in impairment of skin integrity and self-defense mechanisms, especially when pathogenic bacteria such as Staphylococcus aureus colonize.

Method used

Using a sugar mixture containing paclitaxel, mannose, fructose and glucose as a dermatological composition, topically applied to the skin to increase the expression of cytokeratin-1, thereby enhancing the skin's self-defense mechanism and keeping the skin intact sex.

Benefits of technology

It significantly increases the expression of cytokeratin-1 in skin tissues, enhances the skin's self-defense ability, and mitigates or counteracts negative diseases caused by colonization of pathogenic bacteria, especially in the presence of Staphylococcus aureus.

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Abstract

The present invention relates to the use of a sugar mixture comprising psicose, mannose, fructose and glucose to increase the expression of cytokeratin-1 in the skin to enhance the self-defense mechanism of the skin and maintain the integrity of the skin.
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Description

[0001] The present invention relates to the use of a sugar mixture comprising psicose, mannose, fructose and glucose to increase the expression of cytokeratin-1 in the skin, thereby strengthening the skin's self-defense mechanism and maintaining the integrity of the skin.

[0002] Keratin is a keratinized protein found in the cytoskeleton of epithelial tissues. Keratin is an important component of intermediate filaments and helps cells resist mechanical stress.

[0003] Cytokeratin-1 is a major component of the intermediate filament cytoskeleton in the suprabasal epidermis. Reduced levels of cytokeratin-1 lead to epidermolytic ichthyosis in humans. In the search for largely unknown pathological mechanisms and the role of keratins in barrier formation and inflammation control, cytokeratin-1 has been found to be essential for maintaining skin integrity and to participate in the inflammatory network of mouse keratinocytes.

[0004] Thus, there continues to be a need for ingredients that can stimulate cytokeratin-1 expression in skin tissue, particularly in the presence of microorganisms, such as particularly when the skin is colonized by one or more of Propionibacterium acnes (C. acnes), Staphylococcus epidermidis (S. Epidermidis), Corynebacterium striatum (C. striatum), and Staphylococcus aureus (S. aureus).

[0005] Without wishing to be bound by any particular theory or mechanism of action, the promotion of skin integrity may therefore be attributed to the presence of cytokeratin-1, which is known to be essential for the normal differentiation of simple and stratified epithelial tissues. Thus, the sugar mixture of the present invention may be used to strengthen the skin's own defense mechanisms and maintain skin integrity.

[0006] Thus, in a first embodiment, the present invention relates to a composition comprising an effective amount of a sugar mixture comprising psicose, mannose, fructose and glucose, the use of which is to be used as an agent for increasing the expression of cytokeratin-1 in skin tissue in the treatment of skin diseases, in particular, in cases where the skin is colonized by pathogenic bacteria such as, in particular, Staphylococcus aureus or is at risk of being colonized by pathogenic bacteria such as, in particular, Staphylococcus aureus. The use is particularly suitable for strengthening the skin's own defense mechanisms and maintaining skin integrity, in particular in the presence of pathogenic bacteria such as Staphylococcus aureus and the like. Thus, the use is able to reduce and / or counteract the negative diseases associated with the colonization of pathogenic bacteria (in particular, Staphylococcus aureus) on the skin.

[0007] In another embodiment, the present invention relates to a method for preventing or treating a skin disorder caused by reduced expression of cytokeratin-1 in skin tissue, in particular skin colonized with pathogenic bacteria, preferably Staphylococcus aureus, comprising the following steps:

[0008] a) providing a cosmetic or dermatological composition comprising a sugar mixture comprising psicose, mannose, fructose and glucose, and

[0009] b) applying to human skin an amount of the composition sufficient to increase the expression of cytokeratin-1, preferably to skin colonized with or at risk of being exposed to S. aureus.

[0010] The expression of cytokeratin-1 of the present invention is understood to strengthen the skin's self-defense mechanism and keep the skin in a healthy stage.

[0011] In another aspect, the present invention relates to a sugar mixture comprising psicose, mannose, fructose and glucose (and / or to a cosmetic or dermatological composition comprising the sugar mixture): for use in preventing and / or treating skin disorders associated with reduced expression of cytokeratin-1; for use in treating skin disorders wherein reduced expression of cytokeratin-1 leads to the pathology and / or symptoms and / or progression of the skin disorders; for use in increasing the expression of cytokeratin-1 in skin tissue, particularly in skin colonized with, exposed to or at risk of being exposed to Staphylococcus aureus (including in subjects in need thereof); and / or as a cytokeratin-1 expression promoter.

[0012] In another aspect, a sugar mixture comprising psicose, mannose, fructose and glucose is provided for use in: treating a disease or disorder associated with reduced expression of cytokeratin-1; treating a disease or disorder in which reduced expression of cytokeratin-1 leads to the pathology and / or symptoms and / or progression of the disease / disorder; expressing cytokeratin-1 in skin tissue, particularly in skin colonized with, exposed to or at risk of being exposed to Staphylococcus aureus (including in a subject in need thereof); and / or as a cytokeratin-1 expression promoter.

[0013] In another aspect, there is provided a use of a sugar mixture comprising psicose, mannose, fructose and glucose (and / or a cosmetic or dermatological composition comprising the sugar mixture) in the preparation of a medicament for: treating a disease or disorder associated with reduced expression of cytokeratin-1; treating a disease or disorder wherein reduced expression of cytokeratin-1 leads to the pathology and / or symptoms and / or progression of the disease / disorder; and / or expression of cytokeratin-1 - particularly in skin colonized with, exposed to or at risk of being exposed to Staphylococcus aureus (including in a subject in need thereof).

[0014] In another aspect, a method is provided for treating a disease or disorder wherein reduced expression of cytokeratin-1 contributes to the pathology and / or symptoms and / or progression of the disease / disorder, the method comprising administering an effective amount of a sugar mixture comprising psicose, mannose, fructose and glucose, for example, to a subject (in need thereof), preferably a subject whose skin is colonized with, exposed to or at risk of being exposed to Staphylococcus aureus.

[0015] The present invention also relates to a sugar mixture comprising psicose, mannose, fructose and glucose, which serves as a cytokeratin-1 expression promoter, particularly in skin tissue.

[0016] The term "skin" as used herein is intended to encompass the outer surface of mammals, particularly humans, and includes the skin and scalp. In all embodiments of the present invention, preferred skin is facial skin and body skin, such as most preferred facial skin.

[0017] As used herein, the term "preventing" refers to reducing the risk of developing a skin disorder associated with reduced expression of cytokeratin-1.

[0018] As used herein, the term "treatment" refers to the improvement of symptoms, delayed onset and / or shortened duration of any disease associated with reduced expression of cytokeratin-1. Treatment may be preventive (cosmetic) or therapeutic. Preferably, the treatment is preventive.

[0019] The term "cytokeratin-1 expression promoter" as used herein refers to a compound that can stimulate the expression of cytokeratin-1 in skin tissue. The expression of cytokeratin-1 in skin tissue may be reduced due to the presence of pathogenic bacteria (such as Staphylococcus aureus) on the skin.

[0020] In a particularly advantageous embodiment of the invention, the use and method of the invention occur on human skin, wherein the microbiome of the skin comprises one or more, preferably all, of Propionibacterium acnes (C. acnes), Staphylococcus epidermidis, Corynebacterium striatum (C. striatum) and Staphylococcus aureus (S. aureus). The use and method may also occur on human skin, wherein the microbiome of the skin comprises one or more, preferably all, of Propionibacterium acnes, Staphylococcus epidermidis and Corynebacterium striatum, and wherein the human skin is exposed to or at risk of being exposed to Staphylococcus aureus.

[0021] As used herein, "effective amount" refers to the amount necessary to obtain a physiological effect. The physiological effect can be achieved by a single administration or by multiple administrations. Of course, the dosage administered can vary depending on known factors, such as: the physiological properties of the specific cosmetic or dermatological composition comprising a sugar mixture comprising psicose, mannose, fructose and glucose and its mode and route of administration; age, the nature and extent of the symptoms; and the mode of treatment; the frequency of treatment; and the desired effect and can be adjusted by those skilled in the art.

[0022] Preferably, in all embodiments of the present invention, the usage level of psicose is selected in the range of 0.0001 wt% to 0.5 wt%, more preferably in the range of 0.0005 wt% to 0.25 wt%, most preferably in the range of 0.00075 wt% to 0.2 wt%, for example in the range of 0.001 wt% to 0.15 wt%, based on the total weight of the composition. Other suitable ranges include 0.0001 wt% to 0.1 wt%, 0.0005 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.001 wt% to 0.1 wt%, 0.005 wt% to 0.1 wt%, 0.01 wt% to 0.1 wt%, and 0.01 wt% to 0.1 wt%, 0.001 wt% to 0.05 wt%, and 0.01 wt% to 0.05 wt%.

[0023] Preferably, in all embodiments of the present invention, the usage level of mannose is selected in the range of 0.0001 wt.% to 0.5 wt.%, more preferably in the range of 0.0005 wt.% to 0.25 wt.%, most preferably in the range of 0.00075 wt.% to 0.2 wt.%, for example in the range of 0.001 wt.% to 0.15 wt.%, based on the total weight of the composition. Other suitable ranges include 0.0001 wt% to 0.1 wt%, 0.0005 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.001 wt% to 0.1 wt%, 0.005 wt% to 0.1 wt%, 0.01 wt% to 0.1 wt%, and 0.01 wt% to 0.1 wt%, 0.001 wt% to 0.05 wt%, and 0.01 wt% to 0.05 wt%.

[0024] Preferably, in all embodiments of the present invention, the level of fructose used is selected in the range of 0.01 wt% to 2 wt%, more preferably in the range of 0.05 wt% to 1 wt%, most preferably in the range of 0.05 wt% to 0.75 wt%, for example in the range of 0.05 wt% to 0.5 wt%. Other suitable ranges include 0.01 wt% to 1 wt%, 0.05 wt% to 1 wt%, 0.01 wt% to 0.5 wt%, 0.05 wt% to 0.5 wt%, 0.1 wt% to 1 wt%, 0.1 wt% to 0.5 wt%.

[0025] Preferably, in all embodiments of the present invention, the use level of glucose is selected in the range of 0.01 wt % to 3 wt %, more preferably in the range of 0.05 wt % to 2.5 wt %, most preferably in the range of 0.075 wt % to 2 wt %, for example in the range of 0.1 wt % to 1 wt %. Other suitable ranges include 0.01 wt % to 1 wt %, 0.05 wt % to 1 wt %, 0.01 wt % to 0.5 wt %, 0.05 wt % to 0.5 wt %, 0.1 wt % to 1 wt %, 0.1 wt % to 0.5 wt %.

[0026] In all embodiments of the present invention, all isomers of sugars can be used, ie the respective D-isomers and L-isomers, as well as mixtures thereof. However, in all embodiments, natural sugars, ie the D-isomers, are particularly preferred.

[0027] Preferably, in all embodiments of the present invention, sugar is incorporated into the composition of the present invention in the form of a sugar premix, preferably an aqueous sugar premix A, said aqueous sugar premix A comprising:

[0028] a) 1 to 5 wt % of psicose based on the sugar premix;

[0029] b) 1 to 5% by weight of mannose, based on the sugar premix;

[0030] c) 10 to 30 wt. % fructose based on the sugar premix; and

[0031] d) 15 to 60% by weight of glucose, based on the sugar premix.

[0032] More preferably, in all embodiments of the present invention, the sugar premix is ​​an aqueous sugar premix B, said aqueous sugar premix B comprising:

[0033] a) 1 to 5 wt % of psicose based on the sugar premix;

[0034] b) 1 to 5% by weight of mannose, based on the sugar premix;

[0035] c) 10 to 30 wt. % fructose based on the sugar premix; and

[0036] d) 15 to 35% by weight of glucose, based on the sugar premix.

[0037] Most preferably, in all embodiments of the present invention, the aqueous sugar premix is ​​an aqueous sugar premix C, said aqueous sugar premix C comprising:

[0038] a) 2 to 3 wt % of psicose based on the sugar premix;

[0039] b) 1.5 to 3% by weight of mannose, based on the sugar premix;

[0040] c) 10 to 20 wt. % fructose based on the sugar premix; and

[0041] d) 20 to 30% by weight of glucose, based on the sugar premix.

[0042] The term "sugar premix" as used herein refers to a premixed mixture comprising psicose, mannose, fructose and glucose. The sugar premix may be prepared by mixing single sugars or by isomerization of glucose, preferably plant-derived glucose, before being incorporated into the composition of the present invention. The aqueous sugar premix preferably comprises 25 to 50 wt % of water, based on the total aqueous premix.

[0043] The isomerization of glucose is known to those skilled in the art. Preferably, the isomerization process comprises (a) dissolving glucose in water, then (b) isomerizing the glucose in the presence of a base, preferably in the presence of sodium hydroxide, more preferably at a temperature selected in the range of 25°C to 100°C, and (c) purifying the resulting reaction mixture by chromatography and optionally filtration.

[0044] In particular, when the sugar premix is ​​prepared by isomerization of glucose, the sugar premix may further comprise up to 7.5 wt%, preferably up to 5 wt% of other sugars selected from the group consisting of pentoses, hexoses, disaccharides and oligosaccharides, such as in particular galactose, sorbose and disaccharides and oligosaccharides. Preferably, the amount of galactose and / or sorbose in the sugar premix of the present invention is selected in the range of 0 wt% to 4 wt%, such as in the range of 1 wt% to 3 wt%. The remaining amount of sugars contained in the premix is ​​disaccharides and oligosaccharides.

[0045] In a specific embodiment, the sugar premix of the present invention further comprises (e) sorbitol, and the amount of sorbitol is selected within the range of 1 wt % to 5 wt %, preferably within the range of 1 wt % to 3 wt %, based on the sugar premix.

[0046] Preferably, in all embodiments of the invention, sorbitol is used at a level selected in the range of 0.0001 wt% to 0.5 wt%, more preferably in the range of 0.0005 wt% to 0.25 wt%, most preferably in the range of 0.00075 wt% to 0.2 wt%, for example in the range of 0.001 wt% to 0.15 wt%, based on the total weight of the composition. Other suitable ranges encompass 0.0001 wt% to 0.1 wt%, 0.0005 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.00075 wt% to 0.1 wt%, 0.001 wt% to 0.1 wt%, 0.005 wt% to 0.1 wt%, 0.01 wt% to 0.1 wt% and 0.01 to 0.1 wt%, 0.001 to 0.05 wt%, and 0.01 to 0.05 wt%.

[0047] In a particularly advantageous embodiment, the sugar premix of the invention is an aqueous sugar premix, ie wherein the sugar is dissolved in water.

[0048] A particularly suitable aqueous sugar premix (sugar premix D) of the present invention is mainly composed of the following ingredients:

[0049] a) 1 to 5 wt %, preferably 2 to 3 wt % of psicose, based on the aqueous sugar premix;

[0050] b) 1 to 5 wt. %, preferably 1.5 wt. %, based on the aqueous sugar premix

[0051] to 3% mannose by weight;

[0052] c) 10 to 30 wt %, preferably 10 wt %, based on the aqueous sugar premix

[0053] to 20% by weight fructose;

[0054] d) 15 to 30 wt %, preferably 20 wt %, based on the aqueous sugar premix

[0055] to 30% by weight of glucose; and optionally

[0056] e) up to 7.5% by weight, preferably up to 5% by weight, based on the aqueous sugar premix, of other sugars;

[0057] f) 0.1 to 2 wt. % of an additive, based on the aqueous sugar premix, preferably citric acid and / or a salt thereof, such as preferably the sodium salt; and

[0058] g) up to 100% water based on the aqueous sugar premix.

[0059] The term "consisting mainly of ingredients" as used herein means that the total amount of ingredients a) to g) ideally reaches 100 wt%. However, it is not excluded that a small amount of unknown (sugar) impurities, such as impurities produced during the isomerization of glucose, may exist.

[0060] The aqueous sugar premix of the present invention may be prepared, for example, in the form of Commercially available from DSM Nutritional Products Ltd.

[0061] Based on the total weight of the aqueous composition, the total amount of sugar premix to be included in the composition of the present invention is preferably selected in the range of 0.01 wt % to 10 wt %, more preferably in the range of 0.1 wt % to 7.5 wt %, most preferably in the range of 0.2 wt % to 5 wt %. Other suitable ranges are 0.25 wt % to 2.5 wt % and 0.5 wt % to 2 wt %. According to the present invention, a particularly preferred range is 0.2 wt % to 1 wt %, a more preferred range is 0.25 wt % to 0.75 wt %, for example 0.3 wt % to 0.6 wt %.

[0062] As used herein, the term "dermatology" may refer to cosmetic (non-therapeutic) as well as medical (therapeutic) treatments. In all embodiments of the invention, cosmetic treatments, ie treatments for beautifying the skin, are preferred.

[0063] As used herein, the term "cosmetic or dermatological composition" refers to a composition used to treat, care for or improve the appearance of the skin and / or scalp. Particularly advantageous cosmetic or dermatological compositions are skin care preparations.

[0064] In all embodiments of the invention, preferred cells are skin cells, such as in particular epithelial cells, in particular keratinocytes, melanocytes, fibroblasts or dendritic cells.

[0065] In all embodiments of the invention, preferred treatments are non-therapeutic, ie cosmetic.

[0066] Preferably, the amount of the cosmetic or dermatological composition of the present invention to be applied to the skin is chosen in the range of 0.1 mg / cm2 of skin to 3 mg / cm2 of skin, for example preferably in the range of 0.1 mg / cm2 of skin to 2 mg / cm2 of skin, and most preferably in the range of 0.5 mg / cm2 of skin to 2 mg / cm2 of skin.

[0067] In all embodiments of the present invention, the composition is preferably applied to the skin before or after, preferably before, exposure to or contact with pathogenic bacteria, in particular Staphylococcus aureus.

[0068] The cosmetic or dermatological compositions according to the invention are intended for topical use, which is understood to be external application to keratinous substances, such as, in particular, the skin.

[0069] Since the cosmetic or dermatological composition according to the invention is intended for topical application, it comprises a physiologically acceptable medium, ie a medium that is compatible with keratinous substances, such as in particular the skin. In particular, the physiologically acceptable medium is a cosmetically or dermatologically acceptable carrier.

[0070] The term "cosmetically acceptable carrier" or "dermatologically acceptable carrier" as used herein refers to a physiologically acceptable medium that is compatible with keratinous substances, respectively. Suitable carriers are well known in the art and are selected according to the end-use application. Preferably, the carrier of the present invention is suitable for application to the skin (e.g., sunscreen, cream, emulsion, lotion, mask, essence, hydrodispersion, foundation, cream, milk gel or gel, etc.). These carriers are well known to those of ordinary skill in the art and may include one or more compatible liquid or solid filler diluents, excipients, additives or carriers suitable for application to the skin. The exact amount of the carrier depends on the level of the active ingredient, or active mixture and any other optional ingredients (e.g., other active ingredients) that are classified by those of ordinary skill in the art as being different from the carrier. The cosmetic composition of the present invention preferably comprises about 70% to about 99.999%, more preferably about 85% to about 99.99%, more preferably 90% to about 99%, and most preferably about 93% to about 98% of the carrier based on the weight of the cosmetic composition.

[0071] The cosmetic composition of the present invention can be formulated into a variety of product types, including creams, waxes, pastes, emulsions, creams, mousses, gels, oils, skin revitalizers and sprays. Preferably, one or more active substances or active mixtures are formulated into emulsions, creams, gels and skin revitalizers, respectively. These product forms can be used for a variety of applications, including but not limited to hand and body lotions, facial moisturizers, anti-aging preparations, and cosmetics including foundations. Any additional components required for the preparation of such products vary with the product type and can be routinely selected by those skilled in the art.

[0072] Suitable compositions of the present invention are leave-on or rinse-off products and include any product suitable for application to the human body. Preferred in all embodiments of the present invention are leave-on products.

[0073] As used herein, rinse-off and leave-on are defined in accordance with Regulation (EC) No. 1223 / 2009 of the European Parliament and of the Council of November 2009 on cosmetic products (recast), i.e., a cosmetic product or composition is a rinse-off cosmetic product or composition when it is intended to be removed after application to the skin, hair or mucous membranes of a human subject; and a leave-on cosmetic product or composition when it is intended to be left on after application to the skin, hair or mucous membranes of a human subject.

[0074] If the cosmetic or dermatological composition of the present invention is formulated as an aerosol and applied to the skin as a spray product, a propellant is added to the cosmetic composition.

[0075] The cosmetic or dermatological compositions of the invention can be prepared by conventional methods in the art, for example by mixing the active or active mixture of the invention with a cosmetically acceptable carrier.

[0076] The cosmetic or dermatological compositions according to the invention (including the carrier) may comprise further conventional adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, emollients, emulsifiers, defoamers, aesthetic components such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidulants or alkalizers, dyes, colorants, abrasives, absorbents, chelating and / or isolating agents, essential oils, skin sensitizers, astringents, pigments or any other ingredient usually formulated into such cosmetic or dermatological compositions.

[0077] According to the invention, the cosmetic or dermatological composition of the invention may also contain other cosmetic active ingredients commonly used in cosmetic and / or dermatological compositions. Exemplary active ingredients include skin lighteners; UV-filters, agents for treating pigmentation; agents for preventing or treating inflammation; firming agents; moisturizers; soothing agents and / or activators and agents for improving elasticity and the skin barrier.

[0078] Examples of cosmetic or dermatological excipients, diluents, adjuvants, additives and active ingredients commonly used in the skin care industry that are suitable for use in the cosmetic or dermatological composition of the present invention are described, for example, in the International Cosmetic Ingredient Dictionary & Handbook by Personal Care Product Council (http: / / www.personalcarecouncil.org / ), accessible by the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp), but are not limited thereto.

[0079] The necessary amounts of other active ingredients as well as excipients, diluents, adjuvants, additives, etc. can be readily determined by a skilled person depending on the desired product form and application. Additional ingredients can be added to the oil phase, the aqueous phase or separately.

[0080] In some cases, the further cosmetic active ingredients useful herein may provide more than one benefit or operate via more than one mode of action.

[0081] Of course, the skilled person will carefully select the abovementioned optional additional ingredients, adjuvants, diluents and additives and / or their amounts such that the advantageous properties essentially associated with the combination according to the invention are not adversely affected by the envisaged additive or additives.

[0082] The cosmetic or dermatological composition of the invention may be in the form of a suspension or dispersion in a solvent or a fatty substance, or may be in the form of an emulsion or microemulsion (in particular of the oil-in-water (O / W) or water-in-oil (W / O) type, the silicon-in-water (Si / W) or water-in-silicon (W / Si) type, a PIT-emulsion, a multiple emulsion (for example of the oil-in-water-in-oil (O / W / O) or water-in-oil-in-water (W / O / W) type), a Pickering emulsion, a hydrogel, an alcohol gel, a lipogel, a monophasic or multiphasic solution or a vesicular dispersion or other general forms, which can be applied in the form of a pen, as a mask or as a spray.

[0083] If the cosmetic and dermatological composition is an emulsion, such as in particular an O / W emulsion, a W / O emulsion, a Si / W emulsion, a W / Si emulsion, an O / W / O emulsion, a W / O / W multiple emulsion or a Pickering emulsion, the amount of the oil phase present in this cosmetic and dermatological emulsion is preferably at least 10 wt.-%, such as in the range of 10 wt.-% to 60 wt.-%, preferably in the range of 15 wt.-% to 50 wt.-%, most preferably in the range of 15 wt.-% to 40 wt.-%, based on the total weight of the cosmetic and dermatological composition.

[0084] In one embodiment, the cosmetic or dermatological composition of the invention is advantageously in the form of an oil-in-water (O / W) emulsion comprising an oil phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to those skilled in the art.

[0085] If the cosmetic or dermatological composition according to the invention is an O / W emulsion, it advantageously contains at least one O / W-emulsifier or Si / W-emulsifier selected from the group consisting of glyceryl stearate citrate, glyceryl stearate SE (self-emulsifying), stearic acid, salts of stearic acid, polyglyceryl-3-methylsaccharide stearate. Other suitable emulsifiers are phosphoric acid esters and their salts, such as cetyl phosphoric acid (e.g. available from DSM Nutritional Products Ltd. as A), diethanolamine hexadecyl phosphate (e.g. available from DSM Nutritional Products Ltd. DEA), potassium cetyl phosphate (e.g. available from DSM Nutritional Products Ltd. K), sodium cetyl sulfate, sodium oleyl glyceride phosphate, hydrogenated vegetable glyceride phosphate and mixtures thereof. Other suitable emulsifiers include sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, waxy glucoside, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutylene. In addition, one or more synthetic polymers can be used as emulsifiers. For example, PVP diene copolymer, acrylate / C10-30 alkyl acrylate crosspolymer and mixtures thereof.

[0086] At least one O / W emulsifier or Si / W emulsifier is used in an amount in the range of 0.5 to 10 wt.-%, particularly in the range of 0.5 to 6 wt.-%, such as more particularly in the range of 0.5 to 5 wt.-%, such as most particularly in the range of 1 to 4 wt.-%, respectively, based on the total weight of the cosmetic or dermatological composition.

[0087] Particularly suitable O / W emulsifiers for use in the cosmetic or dermatological composition according to the invention include: phosphate emulsifiers, such as advantageously 8-10 alkyl ethyl phosphate, C9-15 alkyl phosphate, ceteareth-2phosphate, ceteareth-2phosphate, ceteareth-5phosphate, ceteth-8phosphate, ceteth-10phosphate, cetyl phosphate, C6-10 pareth-4phosphate, C12-15 pareth-2phosphate, C12-15 pareth-3phosphate, C12-15 DEA-ceteareth-2phosphate, DEA-cetyl phosphate, DEA-oleth-3phosphate, potassium cetyl phosphate, decene-4 phosphate, decene-6 phosphate and tri(laureth-4) phosphate.

[0088] A particularly suitable O / W emulsifier to be used in the cosmetic or dermatological compositions according to the invention is potassium cetyl phosphate, for example in the form of K is commercially available from DSM Nutritional Products Ltd Kaiseraugst.

[0089] Another particularly suitable class of O / W emulsifiers are the nonionic self-emulsifying systems derived from olive oil, known, for example, as (INCI name) cetearyl olivate and sorbitanolivate (chemical composition: sorbitan esters and cetyl esters of olive oil fatty acids), sold under the trade name OLIVEM 1000.

[0090] In a specific embodiment, the present invention relates to a cosmetic or dermatological composition in the form of an O / W emulsion with all the definitions and preferences given herein, comprising an oil phase dispersed in an aqueous phase in the presence of an O / W emulsifier, wherein the O / W emulsifier is potassium cetyl phosphate. The amount of oil phase in such an O / W emulsion is preferably at least 10% by weight, more preferably in the range of 10% to 60% by weight, most preferably in the range of 15% to 50% by weight, for example in the range of 15% to 40% by weight.

[0091] The pH value of the cosmetic or dermatological composition of the present invention is generally in the range of 3 to 10, preferably in the range of pH 4 to 8, and most preferably in the range of pH 4 to 7.5. The pH value can be easily adjusted as required according to standard methods in the art using a suitable acid, such as citric acid, or a suitable base, such as sodium hydroxide (e.g., aqueous solution), triethanolamine (TEA Care), tromethamine (Tromethamine (Trizma Base)) and aminomethylpropanol (AMP-Ultra PC 2000).

[0092] The following examples are provided to further illustrate the effects of the present invention. These examples are merely illustrative and are not intended to limit the scope of the present invention in any way. Example

[0093] This experiment was designed to investigate the protective effects of a sugar mixture containing psicose, mannose, fructose, and glucose on the skin and microbiome by assessing skin integrity by immunostaining for cytokeratin-1 after colonization with the pathogen Staphylococcus aureus.

[0094] Test substance

[0095] The following substances were topically applied to the 3D skin tissue:

[0096] Vehicle control (ultrapure water)

[0097] Sugar premix (1% in ultrapure water) prepared by isomerization of plant-derived glucose; (approximately 25% glucose, 15% fructose, 2% mannose, 2.5% psicose and 50% water)

[0098] method

[0099] 1. Preparation of 3D skin

[0100] Primary adult human dermal fibroblasts were embedded in a fibrin matrix to produce a dermal equivalent (DE). DE was cultured to allow fibroblasts to remodel the matrix. Primary human neonatal keratinocytes were applied to the DE surface and cultured in a liquid environment for 48 hours. 3D skin was cultured at an air-liquid interface until a stratified epidermis was formed. The inoculation conditions for all cultures were 37°C, 5% (v / v) CO2, >95% RH.

[0101] 2. Testing Process

[0102] 3D skins were maintained in deep-well plates throughout the study. Maintenance medium was replaced with symbiotic consortia on the day of colonization.

[0103] 2.1. Propionibacterium acnes NCTC 737 was cultured anaerobically at 37°C for 5 days using Reinforced Clostridial Agar Medium.

[0104] 2.2. Staphylococcus epidermidis NCTC 11047 and Corynebacterium striatum NCTC 764 were cultured aerobically on Mueller-Hinton agar and aerobic Corynebacterium agar for 18-24 hours, respectively.

[0105] 2.3. Bacteria from the above culture were used to prepare an initial inoculation mixture containing approximately 1.1×10 6 cfu mL -1 of each bacterium (3xMix Consortium) using inoculation buffer GS25.

[0106] 2.4. An initial inoculum of 10 μL was used to colonize each 3D skin unit with approximately 104 cfu cm-2 of bacteria.

[0107] 2.5.3D skin at 37°C, 5% (v / v) CO 2 , >95% RH conditions for about 2 hours (until the 3D skin surface is dry).

[0108] 2.6. Colonized 3D skin units were treated with 10 μL of each test sample or with vehicle control.

[0109] 2.7.3D skin at 37°C, 5% (v / v) CO 2 , >95% RH conditions for about 24 hours.

[0110] 2.8. On the same day as the 3D skin was colonized with 3xMix, Staphylococcus aureus strain NCTC 13435 was cultured in Mueller-Hinton agar at 37°C for 18-24 hours.

[0111] 2.9. Bacteria from an overnight culture of the above-mentioned Staphylococcus aureus type strain NCTC 13435 were used to prepare a bacterial suspension in buffer GS25.

[0112] 2.10. Previously colonized with 1x104 cfu / cm 2 The 3D skin of 3xMix was infected with 102 cfu / cm-2 of Staphylococcus aureus.

[0113] 2.11. Colonized 3D skin was inoculated at 37°C, 5% (v / v) CO2, >95% RH for approximately 48 hours.

[0114] Approximately 72 hours after treatment with the test samples, tissues were fixed in 10% neutral buffered formalin, processed, paraffin embedded and sectioned. Immunohistochemistry and staining quantification of cytokeratin-1 expression in tissues was performed (3 test samples: untreated, vehicle control and sugar premix).

[0115] Results (histology): Cytokeratin expression compared with the untreated group

[0116]

[0117] The results showed that a 1% sugar mixture increased tissue expression of cytokeratin-1 by 68% in dermal fibroblasts colonized with Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium striatum, and Staphylococcus aureus, compared to samples treated with vehicle control alone.

Claims

1. A cosmetic use of a composition as an agent for increasing the expression of cytokeratin-1 in skin tissue in the treatment of skin diseases, the composition comprising an effective amount of a sugar mixture comprising psicose, mannose, fructose and glucose, wherein the microbiome of the skin comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium striatum and Staphylococcus aureus; or wherein the microbiome of the skin comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis and Corynebacterium striatum and is exposed to Staphylococcus aureus or is at risk of being exposed to Staphylococcus aureus.

2. The cosmetic use according to claim 1, wherein the sugar mixture is used to strengthen the skin's self-defense mechanism and maintain the skin integrity of the skin.

3. The cosmetic use according to claim 1 and / or 2, wherein the composition is applied to the skin before exposure to Staphylococcus aureus and the skin is then contacted with Staphylococcus aureus.

4. The cosmetic use according to any one or more of claims 1 to 3, wherein the effective amount of psicose is selected in the range of 0.0001 wt% to 0.5 wt%, preferably in the range of 0.005 wt% to 0.25 wt%, and most preferably in the range of 0.0075 wt% to 0.2 wt%, based on the total weight of the composition.

5. The cosmetic use according to any one or more of claims 1 to 4, wherein the effective amount of mannose is selected in the range of 0.001 wt.% to 0.5 wt.%, preferably in the range of 0.005 wt.% to 0.25 wt.%, most preferably in the range of 0.0075 wt.% to 0.2 wt.%, based on the total weight of the composition.

6. The cosmetic use according to any one or more of claims 1 to 5, wherein the effective amount of fructose is selected in the range of 0.01 wt.% to 2 wt.%, preferably in the range of 0.05 wt.% to 1 wt.%, most preferably in the range of 0.05 to 0.75 wt.%, based on the total weight of the composition.

7. The cosmetic use according to any one or more of claims 1 to 6, wherein the effective amount of glucose is selected in the range of 0.01 wt.% to 3 wt.%, preferably in the range of 0.05 wt.% to 2.5 wt.%, and most preferably in the range of 0.075 wt.% to 2 wt.%, based on the total weight of the composition.

8. The cosmetic use according to any one or more of claims 1 to 7, wherein the sugar is incorporated into the composition in the form of an aqueous premix comprising, based on the total weight of the premix: a) 1 to 5 wt %, preferably 2 to 3 wt % of psicose; b) 1 to 5% by weight, preferably 1.5 to 3% by weight, of mannose; c) 10 to 30 wt. %, preferably 10 to 20 wt. % fructose; and d) 15 to 30% by weight, preferably 20 to 30% by weight, of glucose.

9. The cosmetic use according to claim 8, wherein the premix is ​​obtained by isomerization of glucose derived from plants.

10. A method for preventing or treating a skin disorder caused by reduced expression of cytokine-1 in the skin, wherein the microbiome of the skin comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, and Corynebacterium striatum, and wherein the skin is to be exposed to Staphylococcus aureus, the method comprising the steps of: a) providing a topical composition comprising a sugar mixture comprising psicose, mannose, fructose and glucose, and b) applying to the human skin or scalp an amount of the topical composition sufficient to increase the expression of cytokeratin-1, and then, c) exposing said skin to Staphylococcus aureus.

11. A method for treating a skin condition in which reduced expression of cytokeratin-1 contributes to the pathology and / or symptoms and / or progression of the skin condition, and wherein the skin's microbiome comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium striatum, and Staphylococcus aureus, or wherein the skin's microbiome comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, and Corynebacterium striatum and is exposed to or at risk of being exposed to Staphylococcus aureus, the method comprising administering to a subject in need thereof an effective amount of a sugar mixture comprising psicose, mannose, fructose, and glucose.

12. A method for strengthening the skin's self-defense mechanism and maintaining skin integrity, wherein the skin's microbiome comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium striatum and Staphylococcus aureus, or wherein, The skin's microbiome comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, and Corynebacterium striatum and is exposed to or at risk of being exposed to Staphylococcus aureus, and the method comprises the step of applying an effective amount of a sugar mixture comprising psicose, mannose, fructose, and glucose to the skin area in need of the boost.

13. Cosmetic use of a sugar mixture comprising allulose, mannose, fructose and glucose as a cytokeratin-1 promoter in the skin, wherein the microbiome of the skin comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium striatum and Staphylococcus aureus, or wherein the microbiome of the skin comprises one or more of Propionibacterium acnes, Staphylococcus epidermidis and Corynebacterium striatum and is exposed to Staphylococcus aureus or is at risk of being exposed to Staphylococcus aureus.