Novel Use

Abstract

The present invention relates to the use of neutral core human milk oligosaccharides, in particular lacto-N-(neo)tetraose, as anti-ageing active ingredients and their use in topical anti-ageing compositions.

Description

Detailed Description of the Invention

[0001] The present invention relates to the use of neutral core human milk oligosaccharides, in particular lacto-N-(neo)tetraose, as anti-ageing active ingredients and their use in topical anti-ageing compositions.

[0002] Human skin is the largest organ of the human body and a barrier that separates the body from the external environment. Human skin is composed of several layers classified as the epidermis, dermis and subcutaneous tissue. The epidermis is the outermost layer of the skin and is mainly formed from keratinocytes, which make up about 90% of the epidermis, and melanocytes, which are found in the basal layer of the epidermis and make melanin. The main function of the epidermis is to form a permeability barrier against environmental attacks such as ultraviolet light, heat, chemicals, pollutants and pathogens such as bacteria, fungi, parasites and viruses. The epidermis also protects the body from uncontrolled water evaporation from the inside and maintains the moisture balance and skin metabolism.

[0003] The dermis is the second layer of the skin. In the dermis, the most abundant cell type is the dermal fibroblast, which is responsible for creating connective tissue by producing the extracellular matrix (ECM). The ECM is a three-dimensional network of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins, and hydroxyapatite. The ECM provides strength and integrity to the skin.

[0004] As the major structural protein of the extracellular matrix (ECM), type I collagen is secreted by fibroblasts and forms more than 90% of the dry weight of the dermis. Type I collagen is produced as procollagen that is subsequently processed into mature collagen.

[0005] The aging process is a dynamic and constant phenomenon that affects all systems in the body. Intrinsic (due to aging) or extrinsic (habitual exposure to light, heat, pollutants, chemicals, toxins) aging is known to result in irreversible degeneration of tissues, especially the skin. In the skin, visible signs of aging are, among others, fine lines, wrinkles and sagging. Alterations in collagen, the most important protein of connective tissue, are the main cause of these anatomical changes. Even though collagen is constantly produced and recycled, with increasing age, the rate of collagen synthesis decreases significantly, thus resulting in the visible appearance of skin aging.

[0006] Thus, there continues to be a need for preferably natural ingredients that are capable of increasing collagen production and thus combating skin aging and the visible signs associated therewith.

[0007] Surprisingly, it has now been found that certain human milk oligosaccharides, namely neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides, such as lacto-N-tetraose (LNT) or lacto-N-neotetraose (LNnT), are capable of significantly increasing collagen synthesis in human dermal fibroblasts.

[0008] Thus, in a first embodiment, the present invention relates to the non-therapeutic use of neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides for preventing, reducing or treating skin aging in a subject in need thereof.

[0009] In another aspect, the present invention relates to neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides for preventing, reducing or treating skin aging in a subject.

[0010] In a further aspect, the present invention relates to a method for preventing, reducing or treating skin aging in a subject, comprising administering neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides to said subject, in particular to skin areas in need thereof, such as for example facial skin, hand skin and photoaged skin, and optionally assessing the effect.

[0011] Collagen plays a role in skin strength and structure; collagen homeostasis in the deeper layers of the skin is maintained by balancing the degradative and synthetic systems, and a distortion of the balance between collagen production and degradation can lead to skin aging.

[0012] It has been found according to the present invention that core human milk oligosaccharides, composed of galactose, N-acetylglucosamine and glucose monosaccharides, are able to increase type I collagen in human dermal fibroblasts and thus maintain skin homeostasis, especially in aging and / or aged skin.

[0013] Thus, the present invention also relates to the use of neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose to increase (type I) collagen production individually in fibroblasts in the skin (compared to untreated controls).

[0014] The present invention also relates to the use of neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides to increase the expression of (type I) collagen individually in fibroblasts in the skin (compared to untreated controls).

[0015] The present invention also relates to a non-therapeutic method for stimulating the synthesis of collagen I in skin cells, preferably fibroblasts, by topically applying to an area of ​​skin in need thereof neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides as defined herein or a composition comprising said neutral core human milk oligosaccharides.

[0016] Preferably, in all embodiments of the invention, the fibroblasts are human fibroblasts, most preferably dermal human fibroblasts.

[0017] The term "neutral core human milk oligosaccharides" (neutral core HMOs) as used herein refers to a family of structurally diverse unconjugated glycans that are highly abundant and unique in human milk and are preferably constructed from galactose, N-acetylglucosamine and glucose monosaccharide units linked to each other through β-(1-3) or β-(1-4) bonds. Preferably, in all embodiments herein, the galactose is D-galactose and the glucose is D-glucose.

[0018] In all embodiments of the invention, preferably the neutral core human milk oligosaccharide is a trisaccharide, tetrasaccharide, hexasaccharide, octasaccharide or decasaccharide, with trisaccharides, tetrasaccharides and hexasaccharides being particularly preferred, and tetrasaccharides being most preferred.

[0019] In all embodiments of the invention, it is further advantageous if the oligosaccharides are linear oligosaccharides, i.e. unbranched.

[0020] Exemplary oligosaccharides according to the invention are depicted below: [ka]

[0021] In all embodiments of the present invention, it is further advantageous that the oligosaccharides are characterized by a terminal D-galactose linked through a β-(1-3) or β-(1-4) bond to an N-acetyl-D-glucosamine (GlcNAc) unit.

[0022] In addition, in all embodiments of the present invention, it is also preferred that the oligosaccharides are characterized by a D-galactose linked to a reducing end D-glucose through a β-(1-4) bond.

[0023] Particularly suitable neutral core human oligosaccharides according to the invention are listed in Table 1.

[0024] [Table 1]

[0025] Advantageously, in all embodiments of the invention, lacto-N-triose II, LNT, LNnT, LNH, LNnH, pLNH and pLNnH and mixtures thereof are used.

[0026] In all embodiments of the invention, the use of lacto-N-(neo)tetraose, i.e. lacto-N-tetraose (CAS No: 14116-68-8) and / or lacto-N-neotetraose (CAS No: 13007-32-4), is most preferred. LNnT is most preferred, as it is the most active in inducing collagen synthesis.

[0027] HMOs can be isolated from breast milk or they can be produced chemically or biochemically according to methods well known in the art.

[0028] For purposes of the present invention, the source of the HMO is not essential, and it will be apparent that HMO from a variety of sources can be used.

[0029] The term "subject" as used herein means an animal having a membrane that separates and defines the interior of the animal from the exterior. Preferably, the subject is a human.

[0030] In one embodiment of the invention, the subject may be female. In another embodiment, the subject may be male. In a further embodiment, the subject may have a non-binary gender.

[0031] In a preferred embodiment, the subject is not a child.The term "child" as used herein means a human being 7 years old or less.Thus, in all embodiments of the present invention, the subject is a human being 8 years old or more, preferably, the subject is a human being 20 years old or more, preferably 30 years old or more, even more preferably 40 years old or more, for example, most preferably 50 years old or more.

[0032] In a further embodiment, the prevention, reduction or treatment of skin aging in a subject is achieved by increasing or maintaining production of or slowing the decline of type I collagen in the skin and / or maintaining or slowing the decline of collagen metabolism in the skin.

[0033] Preferably, in all embodiments of the invention, expression of collagen I (compared to untreated controls) is increased by at least 10%, more preferably at least 20%, most preferably at least 30%, for example at least 50%, most preferably in normal human dermal fibroblasts.

[0034] In a further embodiment, the present invention relates to the prevention, slowing down or treatment of skin aging caused by intrinsic and / or extrinsic factors such as, but not limited to, the sun, sunburn, collagen damage, aging, infrared radiation, heat, hormonal causes, malnutrition, temperature, smoking, stress, lack of sleep, pollutants or alcohol intake.

[0035] The term "preventing, reducing or treating skin aging" includes, but is not limited to, preventing, reducing or treating fine lines, wrinkles, crow's feet, sagging skin, thinning of the skin and / or rough skin texture, as well as improving skin elasticity or firmness.

[0036] The term "preventing, slowing or treating skin aging" includes smoothing wrinkles and fine lines as well as reducing their volume and depth in those in need thereof.

[0037] In all embodiments of the present invention, preferably the use is non-therapeutic, ie cosmetic use aimed at beautifying the skin.

[0038] In all embodiments of the present invention, the neutral core HMO is applied to the external surface of the human body.

[0039] The term "external surface of the human body" as used herein includes the skin and scalp. Preferably, in all embodiments of the present invention, the external surface of the human body treated according to the present invention is the skin of the face, neck and / or body, most preferably the face (including the (lateral) cheeks, forehead, nose, chin).

[0040] In all embodiments of the present invention, the neutral core HMO is preferably provided in the form of a cosmetic or dermatological composition.

[0041] The term "cosmetic or dermatological composition" as used herein refers to a cosmetic or dermatological composition that is used to treat, care for or improve the appearance of the skin and / or scalp, preferably the skin, most preferably the skin of the face and / or the skin of the hands, i.e. intended to beautify the skin and / or scalp.

[0042] As used herein, the term "dermatological composition" refers to a composition used for application to the skin (topically).

[0043] The total amount of neutral core HMOs according to the invention in the composition according to the invention is preferably selected in the range of 0.01 to 10% by weight, more preferably in the range of 0.1 to 7.5% by weight, most preferably in the range of 0.2 to 5% by weight, based on the total weight of the composition. Further suitable ranges are 0.25 to 2.5% by weight, 0.5 to 2% by weight, 0.1 to 1% by weight, 0.25 to 0.75% by weight and 0.3 to 0.6% by weight. A particularly preferred range according to the invention is 0.1 to 5% by weight, more preferably 0.25 to 5% by weight, for example 0.3 to 5% by weight.

[0044] Unless otherwise stated herein, any parts and percentages given are by weight and are based on the total weight of the composition.

[0045] In certain embodiments, the composition according to the invention is a cosmetic or dermatological composition intended to be applied topically to mammalian keratinous tissue, such as in particular to the human skin or the human scalp. Such compositions are also called dermatological compositions. Thus, preferably, in all embodiments of the present invention, the cosmetic or dermatological composition is a topical cosmetic (i.e. dermatological) composition, the definitions and preferences of which are all as set out herein.

[0046] It is appreciated that the composition may contain only one or several HMOs as defined herein.

[0047] Topical cosmetic or dermatological compositions according to the present invention may be leave-on or wash-off compositions and include any product that is applied to the human body primarily to improve the appearance or general aesthetics. Preferably, the cosmetic or dermatological compositions of the present invention are leave-on compositions.

[0048] It is fully understood that the cosmetic or dermatological composition according to the invention intended for topical application comprises a physiologically acceptable material, i.e. a material compatible with keratinous materials such as the skin, mucous membranes and keratinous fibers. In particular, the physiologically acceptable material is a cosmetically acceptable carrier. In all embodiments of the invention, it is preferred that the carrier comprises water.

[0049] The term "cosmetically acceptable carrier" (also referred to herein as carrier) refers to all vehicles / carriers conventionally used in cosmetic or dermatological compositions, i.e., suitable for topical application to keratinous tissue, having good aesthetic properties, compatible with the active substances present in the composition and not raising undue safety or toxicity concerns. Such carriers are well known to those skilled in the art and may include one or more compatible liquid or solid filler diluents, excipients, additives or vehicles suitable for application to the skin.

[0050] The exact amount of carrier will depend on the actual level of the active ingredient and any other optional ingredients that one of ordinary skill in the art would classify as distinct from a carrier (eg, other active ingredients).

[0051] In an advantageous embodiment, the cosmetic or dermatological composition according to the invention comprises from about 50% to about 99%, preferably from about 60% to about 98%, more preferably from about 70% to about 98%, for example in particular from about 80% to about 95%, of a carrier, based on the total weight of the cosmetic or dermatological composition.

[0052] In a particularly advantageous embodiment, the carrier in the cosmetic or dermatological composition according to the invention consists of at least 30% by weight, more preferably at least 40% by weight, most preferably at least 45% by weight of water, such as in particular 50-90% by weight of water.

[0053] The cosmetic or dermatological composition according to the invention may take the form of a liquid, a lotion, a thickened lotion, a gel, a cream, a milk, an ointment, a paste, a powder, a cosmetic or a solid tube stick, and may optionally be packaged as an aerosol and may be provided in the form of a mousse, such as an aerosol mousse, a foam or spray-type foam, a spray, a stick.

[0054] Preferably, one or more neutral core HMOs according to the present invention are formulated into lotions, creams, gels and tonics. These product forms may be used for many applications, including, but not limited to, hand and body lotions, (facial) anti-aging preparations, cosmetics including foundations, sunscreens, sunless tanners and the like. Any additional components required to formulate such products vary depending on the type of product and can be routinely selected by those skilled in the art.

[0055] If the cosmetic or dermatological composition of the present invention is formulated as an aerosol and applied to the skin as a spray-on product, a propellant is added to the composition.

[0056] The cosmetic or dermatological compositions according to the present invention can be prepared by conventional methods in the art, such as, for example, by mixing the respective neutral core HMOs, all of whose definitions and preferences are as set forth herein, with a cosmetically acceptable carrier.

[0057] The cosmetic or dermatological composition may contain further ingredients, which may form part of the carrier. Such ingredients are in particular surfactants, emulsifiers, thickeners and oils. Such suitable surfactants, emulsifiers, thickeners and oils are well known to those skilled in the art.

[0058] The cosmetic or dermatological compositions of the present invention (including the carrier) may contain further conventional (cosmetic) adjuvants and additives such as preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, emollients, emulsifiers, antifoaming agents, aesthetic constituents such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, pigments, colorants / dyes, abrasives, absorbents, chelating and / or sequestrants, essential oils, skin sensates, astringents, pigments or any other ingredient normally formulated in such compositions.

[0059] According to the present invention, the composition according to the present invention may also contain further cosmetic active ingredients conventionally used in cosmetic or dermatological compositions.Exemplary active ingredients include skin lightening agents; UV filters; agents for treating hyperpigmentation; agents for preventing or reducing inflammation; stabilizers, moisturizers, soothing agents and / or activators, and agents for improving elasticity and skin barrier.

[0060] If not otherwise stated, the excipients, additives, diluents, etc. mentioned below are suitable for the compositions according to the invention. The required amounts of cosmetic and dermatological adjuvants and additives can be easily determined by the skilled artisan based on the desired product.

[0061] Additional ingredients can be added to the oil phase, the water phase or separately if deemed appropriate. The manner of addition can be easily varied by one skilled in the art.

[0062] Examples of cosmetic excipients, diluents, adjuvants, additives and active ingredients commonly used in the skin care industry that are suitable for use in the cosmetic or dermatological compositions of the present invention are described, but are not limited to, in the International Cosmetic Ingredient Dictionary & Handbook by Personal Care Product Council (http: / / www.personalcarecouncil.org / ), which can be accessed, for example, via the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp).

[0063] The cosmetic actives useful herein can in some cases provide more than one benefit or operate via more than one mode of action.

[0064] Naturally, the skilled artisan will take care to select the optional additional components, adjuvants, diluents and additives mentioned above and / or their amounts such that the advantageous properties inherently associated with the combination according to the invention are not adversely affected or are not substantially adversely affected by the envisaged addition.

[0065] The cosmetic or dermatological composition according to the invention is in particular a skin care preparation or a functional (anti-ageing) preparation.

[0066] Examples of skin care preparations are in particular photoprotection preparations (sun care preparations), anti-ageing preparations, preparations for treating photoageing, moisturizing preparations such as body oils, body lotions, body gels, treatment creams, skin protective ointments, moisturizing gels or moisturizing sprays, face and / or body moisturizers and skin whitening preparations.

[0067] Examples of functional preparations are, but are not limited to, cosmetic or dermatological compositions containing active ingredients such as hormone preparations, vitamin preparations, vegetable extract preparations, anti-aging preparations and / or antimicrobial (antibacterial or antifungal) preparations.

[0068] The cosmetic or dermatological compositions according to the invention can take a wide variety of forms, non-limiting examples include simple solutions (e.g. aqueous, organic solvent or oil-based), emulsions or microemulsions (especially of the oil-in-water (O / W) or water-in-oil (W / O) type, silicone-in-water (Si / W) or water-in-silicone (W / Si) type, PIT emulsions, multiple emulsions (e.g. oil-in-water-in-oil (O / W / O) or water-in-oil-in-water (W / O / W) type) or Pickering emulsions) as well as solid forms (e.g. hydrogels, alcoholic gels, lipogels, sticks, flowable solids or amorphous materials).

[0069] These product forms may be used for many applications including, but not limited to, gels, creams, ointments, lotions, serums, powders, aerosol sprays or two-component dispensing devices.

[0070] In a preferred embodiment, the cosmetic or dermatological composition according to the invention is an emulsion and / or a gel. Even more preferably, the cosmetic or dermatological composition is an emulsion containing an oil phase and an aqueous phase, in particular an O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple or Pickering emulsion.

[0071] The amount of oil phase (i.e. the phase containing all fats and oils including polar oils) present in such emulsions, in particular O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple or Pickering emulsions, is preferably at least 10% by weight, for example in the range of 10 to 60% by weight, preferably in the range of 15 to 50% by weight, most preferably in the range of 15 to 40% by weight, based on the total weight of the composition.

[0072] The oil phase according to the invention preferably comprises an oil selected from butylene glycol dicaprylate / dicaprate, propylene glycol dicaprylate / dicaprate, dicaprylyl ether, C12-15-alkyl benzoate, C18-38-fatty acid triglyceride, dibutyl adipate, cyclomethicone, dimethicone, 2-phenylethyl benzoate, isopropyl lauroyl sarcosinate, caprylic / capric triglyceride and mixtures thereof.

[0073] The amount of aqueous phase present in such emulsions is preferably at least 20% by weight, for example in the range of 20 to 90% by weight, preferably in the range of 30 to 80% by weight, most preferably in the range of 30 to 70% by weight, based on the total weight of the composition.

[0074] Advantageously, in all emulsions of the invention, the ratio of oil phase to water phase is chosen in the range from 40:60 to 30:70.

[0075] In one particularly advantageous embodiment, the cosmetic or dermatological composition according to the invention is in the form of an oil-in-water (O / W) emulsion comprising an oily 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.

[0076] When the cosmetic or dermatological composition according to the invention is an O / W emulsion, it advantageously contains at least one O / W- or Si / W-emulsifier selected from the list: glyceryl stearate citrate, glyceryl stearate SE (self-emulsifying), stearic acid, salts of stearic acid, polyglyceryl-3-methylglycol distearate. Further suitable emulsifiers are phosphate esters and their salts, such as cetyl phosphate (e.g. as Amphisol® A from DSM Nutritional Products Ltd.), diethanolamine cetyl phosphate (e.g. as Amphisol® DEA from DSM Nutritional Products Ltd.), potassium cetyl phosphate (e.g. as Amphisol® K from DSM Nutritional Products Ltd.), sodium cetearyl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glycerides phosphate and mixtures thereof. Further suitable emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, cetearyl glucoside, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutene. Furthermore, one or more synthetic polymers may be used as emulsifiers, such as PVP eicosene copolymer, acrylates / C10-30 alkyl acrylate crosspolymer and mixtures thereof.

[0077] The at least one O / W, Si / W emulsifier, respectively, is preferably used in an amount ranging from 0.5 to 10% by weight, in particular from 0.5 to 6% by weight, for example more particularly in the range from 0.5 to 5% by weight, for example most particularly in the range from 1 to 4% by weight, based on the total weight of the cosmetic or dermatological composition.

[0078] Particular suitable O / W emulsifiers for use in the cosmetic or dermatological compositions according to the invention include phosphate ester emulsifiers, such as advantageously 8-10 alkyl ethyl phosphate, C9-15 alkyl phosphate, ceteareth-2 phosphate, ceteareth-5 phosphate, ceteth-8 phosphate, ceteth-10 phosphate, cetyl phosphate, C6-10 pareth-4 phosphate, C12-15 pareth-2 phosphate, C12-15 pareth-3 phosphate, ceteareth-2 phosphate DEA, cetyl phosphate DEA oleth-3 phosphate, potassium cetyl phosphate, deceth-4 phosphate, deceth-6 phosphate and trilaureth-4 phosphate.

[0079] A particularly suitable O / W emulsifier for use in the cosmetic or dermatological composition according to the invention is, for example, potassium cetyl phosphate, commercially available as Amphisol® K from DSM Nutritional Products Ltd Kaiseraugst.

[0080] Another particularly suitable class of O / W emulsifiers are the non-ionic self-emulsifying systems derived from olive oil, known for example as cetearyl olivate and sorbitan olivate (chemical composition: sorbitan and cetearyl esters of olive oil fatty acids) sold under the trade name OLIVEM 1000 (INCI name).

[0081] In one particular embodiment, the present invention relates to a cosmetic or dermatological composition, all as defined and preferred herein, in the form of an O / W emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier, the O / W emulsifier being potassium cetyl phosphate. The amount of oily phase in such an O / W emulsion is preferably at least 10% by weight, more preferably in the range of 10-60% by weight, most preferably in the range of 15-50% by weight, for example in the range of 15-40% by weight, based on the total weight of the composition.

[0082] Preferably, the cosmetic or dermatological composition according to the invention further comprises at least one fatty alcohol (co-emulsifier), in particular cetyl alcohol, cetearyl alcohol and / or behenyl alcohol. The total amount of the one or several fatty alcohols for the topical composition according to the invention is preferably chosen in the range of about 0.1 to 10.0% by weight, in particular in the range of about 0.5 to 6.0% by weight, relative to the total weight of the topical composition.

[0083] Preferably, the topical composition according to the present invention comprises a thickener to assist in making the product consistency suitable, especially when the topical composition is in the form of an emulsion.Preferred thickeners are aluminum silicate, xanthan gum, hydroxypropyl methylcellulose, hydroxyethylcellulose, polyacrylates such as carbopole® (e.g. Carbopole 980, 981, 1382, 2984, 5984) or mixtures thereof.Further preferred thickeners include acrylic acid / C10-30 alkyl acrylate copolymers (e.g. Pemulen TR 1, Pemulen TR 2, Carbopol 1328 by NOVEON, etc.) and Aristoflex AVC (INCI: Ammonium acryloyldimethyltaurate / VP copolymer).

[0084] The cosmetic or dermatological composition according to the invention advantageously comprises a preservative, if present, which is preferably used in an amount ranging from 0.1 to 2% by weight, more preferably from 0.5 to 1.5% by weight, based on the total weight of the composition.

[0085] Cosmetic or dermatological compositions according to the invention will generally have a pH in the range of 3 to 10, preferably a pH in the range of 4 to 8, most preferably a pH in the range of 4 to 7.5, for example a pH in the range of 5 to 6.5. The pH can be readily adjusted as desired according to standard methods in the art, for example with a suitable acid such as citric acid or a base such as sodium hydroxide (for example as an aqueous solution), triethanolamine (TEA Care), tromethamine (Trizma Base) and aminomethylpropanol (AMP-Ultra PC2000).

[0086] The amount of cosmetic or dermatological composition to be applied to the skin is not critical and can be easily adjusted by one skilled in the art. Preferably, the amount is between 0.1 and 3 mg / cm. 2 In the area of ​​the skin, for example, preferably 0.1 to 2 mg / cm 2 In the skin area, most preferably 0.5 to 2 mg / cm 2 Selected areas of the skin.

[0087] Instead, for topical application, the daily dose of the composition, all preferences and definitions being as set out herein, is preferably selected in the range of 1 ml, preferably 2 ml, most preferably 5 ml / day.

[0088] In all embodiments of the present invention, the cosmetic or dermatological composition according to the present invention is applied topically to the skin of a subject in need thereof for at least 7 days, preferably at least 28 days.

[0089] In another preferred embodiment, the cosmetic or dermatological composition according to the invention is applied once or preferably twice per day.

[0090] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the present invention in any way.

[0091] [Example] [Brief Description] The neutral core human milk oligosaccharides LNT and LNnT were investigated for their effect on collagen type 1. This was done using an in vitro skin fibroblast collagen assay. Both LNT and LNnT were found to increase collagen expression. For comparative reasons, another human milk oligosaccharide, namely 6'-sialyllactose (6'SL), was also tested.

[0092] [Method] Normal human dermal fibroblasts were seeded in cell culture medium (Dulbecco's modified Eagle's medium supplemented with 10% serum and 1% antibiotics) and allowed to attach in a humidified cell incubator maintained at 37°C and 5% CO2. The cells were then starved with serum-free culture medium for 16-24 hours to synchronize the cells to their cell cycle. The starvation medium was removed and various concentrations of cell culture medium + LNT or LNnT, respectively, "6'SL, were added to the cells. The cells were treated for 72 hours. The cells were then fixed and immunolabeled with an antibody specific for collagen 1. These labeled cells were analyzed using flow cytometry and compared to untreated ones (medium without LNT, LNnT or 6'SL, respectively).

[0093] [Table 2]

[0094] Table 1. Normal human dermal fibroblasts were treated with several concentrations of LNT for 72 hours, which resulted in an increase in collagen type 1 protein. Data were normalized to the untreated control (100%) and are expressed as mean ± SD (n=4).

[0095] [Table 3]

[0096] Table 2. Normal human dermal fibroblasts were treated with several concentrations of LNnT for 72 hours, which resulted in an increase in collagen type 1 protein. Data were normalized to the untreated control (100%) and are expressed as mean ± SD (n=4).

[0097] [Table 4]

[0098] Table 3. Normal human dermal fibroblasts were treated with several concentrations of 6'SL for 72 hours, which resulted in a slight increase in collagen type 1 protein at low concentrations, but lost significance at concentrations per μM and above 1 μM. Data are normalized to the untreated control (100%) and expressed as mean ± SD (n=4). Compared to human milk oligosaccharides according to the invention, 6'SL has a much lesser effect. At high concentrations, in contrast to human milk oligosaccharides according to the invention, this effect also lost its statistical significance (p-value < 0.05) compared to LNT and LNnT.

Claims

1. Non-therapeutic use of neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides to prevent, reduce or treat skin aging in a subject.

2. 2. The non-therapeutic use of claim 1, wherein the neutral core human milk oligosaccharides are selected from the group consisting of trisaccharides, tetrasaccharides, hexasaccharides, octasaccharides and decasaccharides, preferably from the group of trisaccharides, tetrasaccharides and hexasaccharides, most preferably from the group of tetrasaccharides.

3. 2. The non-therapeutic use of claim 1, wherein the galactose, N-acetylglucosamine and glucose monosaccharides are linked to each other through a β-(1-3) or β-(1-4) bond.

4. 2. The non-therapeutic use according to claim 1, wherein the neutral core human milk oligosaccharides are selected from the group consisting of lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-hexaose, lacto-N-neohexaose, para-lacto-N-hexaose and para-lacto-N-neohexaose and mixtures thereof, preferably lacto-N-triose II, lacto-N-tetraose and / or lacto-N-neotetraose, most preferably lacto-N-tetraose and / or lacto-N-neotetraose.

5. 5. The non-therapeutic use of any one of claims 1 to 4, wherein the neutral core human milk oligosaccharides increase or maintain the production of type I collagen or slow the decline of type I collagen in the skin.

6. A cosmetic or dermatological composition for use in preventing, reducing or treating skin aging in a subject, comprising:

1. A composition comprising neutral core human milk oligosaccharides selected from the group consisting of lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-hexaose, lacto-N-neohexaose, para-lacto-N-hexaose and para-lacto-N-neohexaose and mixtures thereof, preferably lacto-N-triose II, lacto-N-tetraose and / or lacto-N-neotetraose, most preferably lacto-N-tetraose and / or lacto-N-neotetraose.

7. 7. The composition of claim 6, wherein the amount of neutral core human milk oligosaccharides in the composition is selected in the range of 0.01 to 10 wt. %, preferably in the range of 0.1 to 7.5 wt. %, most preferably in the range of 0.2 to 5 wt. %, based on the total weight of the composition.

8. 7. The composition of claim 6, wherein the composition comprises a carrier consisting of at least 30% by weight, more preferably at least 40% by weight, most preferably at least 45% by weight of water, such as especially 50 to 90% by weight of water.

9. The composition according to any one of claims 6 to 8, wherein the composition is an O / W emulsion comprising an oil phase dispersed in an aqueous phase.

10. Non-therapeutic use of neutral core human milk oligosaccharides composed of galactose, N-acetylglucosamine and glucose monosaccharides to increase type I collagen expression in human fibroblasts.