Saccharomyces cerevisiae extract for exosome content modulation

Abstract

The invention is concerned with the cosmetic use of a composition comprising an extract of Saccharomyces cerevisiae for modulating exosome content, thereby preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging.

Description

Description SACCHAROMYCES CEREVISIAE EXTRACT FOR EXOSOME CONTENT MODULATION CLAIM OF PRIORITY

[0001] This patent application claims the benefit of priority to FR Application Serial No. 2408590, filed August 2, 2024, which is incorporated by reference herein in its entirety.

[0002] The invention is generally directed to active ingredients capable of preventing ageing and / or senescence and their manifestations, in particular intrinsic and / or extrinsic dermal aging and / or senescence, compositions containing them and their use as cosmetic dermal compositions.

[0003] Skin is the largest organ of the human body: it provides a barrier against harmful organisms and substances, protects against UV radiation and regulates water loss and body temperature. The skin is a complex organ, consisting of several compartments with different functions. The outermost epidermis is stratified into four sublayers (basal, spinous, granular and cornified layer) with keratinocytes being the predominant cell type. Pigment-producing melanocytes reside within the basal layer of the epidermis, determine skin color and possess photo-protecting properties. The dermal-epidermal junction (DEJ) connects the epidermis to the underlying dermis, which harbours dermal fibroblasts and appendages such as hair follicles, sebaceous glands, and sweat glands.

[0004] Skin aging is a multi-factorial process that affects nearly every aspect of its biology and function; it is driven by both intrinsic (e.g., time, genetic factors, hormones) and extrinsic (e.g., UV exposure, pollution) factors.

[0005] The apparent signs of intrinsic ageing include the loss and descent of underlying fat, leading to hollowed cheeks and eye sockets, as well as loss of firmness and sagging skin as the bones shrink away from the skin due to bone loss. Other visible signs include thin and dry skin, fine wrinkles, decreased elasticity, aberrant pigmentation, hair graying and hair loss.

[0006] Extrinsic aging is caused by external influences on the skin. The main culprit of premature aging of the skin is over-exposure to the sun’s UV radiation, but there are other contributing factors: air pollution, IR radiation, visible light and lifestyle choices such as smoking, excessive alcohol consumption and chronic stress to name a few.The most common external signs of extrinsic aging are thinning of the skin, laxity, fragility and the increased appearance of wrinkles, fine lines and dark spots.

[0007] Intrinsic and extrinsic aging are partly linked to the process of senescence, which represents an inevitable change attributable to the passage of time alone and is represented primarily by physiologic alterations with subtle but important consequences for both healthy and diseased skin. Senescence, and in particular skin senescence, is a continuous process that usually begins in the mid-20s but may not become evident for decades. In a person’s 20s collagen production begins to slow and elastin has a bit less spring. Dead skin cells do not shed as quickly and turnover of new skin cells decreases. The process of skin senescence resembles that seen in most internal organs and an explanation is thought to involve decreased proliferative capacity leading to altered biosynthetic activity of skin derived cells.

[0008] Senescent cells are characterized by stable cell cycle arrest as well as morphological and metabolic changes, chromatin reorganization, altered gene expression, and acquisition of the senescence-associated secretory phenotype (SASP). One important property of senescent cells is that they can also contaminate healthy cells, turning them into senescent cells too, and then accelerating their ageing. The new senescent cells adopt the same communication patterns with healthy cells, and the vicious cycle continues. Left unchecked, these cells can increase by up to three times after 65 years old.

[0009] Applied to the skin, this knowledge might reverse the concept of inside out beauty suggesting that the skin, our largest organ, could have an impact on how we age overall. It might be a whole new way to look at skin healthy longevity.

[0010] As mentioned above, the hallmark of senescent cells is the appearance of the senescence-associated secretory phenotype (SASP). The SASP includes several families of soluble and insoluble factors that can be globally divided into the following major categories: soluble signalling factors (interleukins, chemokines, and growth factors), secreted proteases and secreted insoluble proteins / extracellular matrix (ECM) components

[0011] The skin has three layers: The epidermis, dermis, and subcutaneous tissue. The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases. The reduction in the amount of collagen hinders themechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen.

[0012] MMPs are a family of ubiquitous endopeptidases that can degrade ECM proteins. MMPs can be categorized into five main subgroups, one of which (the collagenases) is composed of (MMP-1, MMP-8 and MMP-13). MMP-1 is the major protease that initiates fragmentation of collagen fibers, which are predominantly type I and III in human skin. After cleavage by MMP-1, collagen can be further degraded by MMP-3 and MMP-9. In the skin, the major source of MMPs are epidermal keratinocytes and dermal fibroblasts, although MMPs can also be produced by endothelial cells and immunocytes.

[0013] MMP-7 and MMP-12 are known to play a role in tissue remodelling and in the degradation of soluble and insoluble elastin.

[0014] WO2023 / 012115 discloses an active ingredient comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa. Preferably, said extract consists of the cytosolic fraction of a Saccharomyces cerevisiae yeast (INCI: Saccharomyces cerevisiae Extract). Said ingredient is proposed for use in ameliorating skin regeneration and in treating skin ageing, in particular wrinkles, dark circles and the radiance of the complexion. It is described as being able to improve the interplay of the cutaneous, vascular an immune systems by increasing the synthesis and secretion of the growth factors (KGF, EGF, IGF, FGF, PDGF, TGF-p and VEGF).

[0015] Extra-cellular vesicles represent the new frontier in the field of intercellular communication pathways. In particular, exosomes are nano- to micron-sized vesicles budding from cells that display specific organotropic behavior. Exosomes are cell- derived vesicles that convey key elements with the potential to modulate intercellular communication. They are known to be secreted from all types of cells and are crucial messengers that can regulate cellular processes by ‘trafficking’ molecules from cells of one tissue to another. The exosomal content has been shown to be broad, composed of different types of cytokines, growth factors, proteins, or nucleic acids. Besides messenger RNA (mRNA) they can also contain noncoding transcripts such as microRNAs (miRNAs), which are small endogenous cellular regulators of protein expression.

[0016] Confronted with what is known in the art, there is the need to develop new active agents to meet the desire to shift dermatological focus from ameliorating the cosmeticconsequences of skin aging and / or senescence to preventing the genuine morbidity associated with problems of the aging and / or senescent skin in the face of an aging population. SUMMARY OF THE INVENTION

[0017] The present invention is based in part on the observation that exosomes isolated from normal human keratinocytes treated with an extract of Saccharomyces cerevisiae for 48 hours, in particular when said extract corresponds to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, display reduced miRNA expression, in particular miR-29b, miR-27b and miR-181b, more particularly miR-155-5p and miR-181a-5p. The Applicant has further observed that fibroblasts incubated with exosomes previously treated with an extract of Saccharomyces cerevisiae, in particular when said extract corresponds to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, display increased gene expression of collagen I, collagen III and decorin, and decreased expression of matrix metalloproteinases, in particular MMP3.

[0018] Without being bound by theory, it is submitted that an extract of Saccharomyces cerevisiae is able to modify the gene expression of collagen I, collagen III, decorin and MMP3 by fibroblasts and so is able to maintain the normal homeostasis of the extra cellular matrix (ECM), decrease ECM stiffness by modulating cross-linking of the ECM fibres and modulate fibrosis, all of which is connected to skin aging and senescence.

[0019] Furthermore, modification of the gene expression of other matrix metalloproteinases like MMP-7, MMP-9 and MMP-12 inhibits degradation of soluble and insoluble elastin, which is also connected to skin aging and senescence.

[0020] Based on these observations, the present invention provides an active ingredient capable of preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging and / or senescence, by increasing gene expression of collagen I, collagen III and decorin, and decreasing expression of MMP3. Specifically, the active ingredient comprises an extract of Saccharomyces cerevisiae, in particular where said extract corresponds to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa.

[0021] By increasing gene expression of collagen I, collagen III and decorin, and decreasing expression of MMP3 and / or MMP12, the ingredient prevents the appearance of the apparent signs of intrinsic and extrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; decreased elasticity; and the progressive appearance of wrinkles and fine lines.

[0022] The present invention also provides the cosmetic use of an extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, for the in vitro modulation of exosomes isolated from normal (human) keratinocytes. In particular, the exosomes display reduced miRNA expression, in particular miR-29b, miR-27b and miR-181b and more particularly miR-155-5p and miR- 181a-5p.

[0023] The present invention also provides the cosmetic use of a composition comprising an extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, for preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging and / or senescence. FIGURES

[0024] [Fig 1] shows the miRNA expression of exosomes extracted from keratinocytes treated with Saccharomyces cervisiae.

[0025] [Fig 2] shows the gene expression of fibroblasts incubated with exosomes extracted from keratinocytes treated with Saccharomyces cervisiae. DETAILED DESCRIPTION OF THE INVENTION

[0026] Reference will now be made in detail to certain aspects of the disclosed subject matter, examples of which are illustrated in part in the accompanying drawings. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter.

[0027] Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub- ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise.

[0028] In this document, the terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated. The statement “at least one of A and B” or “at least one of A or B” has the same meaning as “A, B, or A and B.” In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting; information that is relevant to a section heading may occur within or outside of that particular section. A comma can be used as a delimiter or digit group separator to the left or right of a decimal mark; for example, “0.000,1” is equivalent to “0.0001.” All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.

[0029] The term “about” as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range and includes the exact stated value or range. The term “substantially” as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term “substantially free of” as used herein can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that about 0 wt% to about 5 wt% of the composition is the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than or equal to about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%.

[0030] When percentages of ingredients in compositions are indicated, the standard error applies. For example, 3.0% is to be interpreted as 2.9% to 3.1%.

[0031] The term “comprises” and variations thereof is to be interpreted as meaning both “includes”, “substantially consists of” and “consists of”, and variations thereof.

[0032] The present invention provides an active ingredient capable of preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging and / or senescence, by increasing gene expression of collagen I, collagen III and decorin, and decreasing expression of MMP3 and / or MMP12. Specifically, the active ingredientcomprises an extract of Saccharomyces cerevisiae, in particular where said extract corresponds to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa.

[0033] By increasing gene expression of collagen I, collagen III and decorin, and decreasing expression of MMP3, the ingredient prevents the appearance of the apparent signs of intrinsic and extrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; decreased elasticity; and the progressive appearance of wrinkles and fine lines.

[0034] The present invention also provides the cosmetic use of an extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, for the in vitro modulation of exosomes isolated from normal (human) keratinocytes. In particular, the deactivated exosomes display reduced miRNA expression, in particular miR-29b, miR-27b and miR-181b.

[0035] The present invention also provides the cosmetic use of a composition comprising an extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, for preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging and / or senescence,.

[0036] According to the present invention, the composition can be for topical application, in particular in the form of an oil-in-water emulsion, a water-in-oil emulsion, a multiple emulsion (Water / Oil / Water or Oil / Water / Oil), a microemulsion, a nanoemulsion, a solution, a suspension, a hydrodispersion, a gel, an ointment, a paste, an aerosol foam, a spray, an aqueous gel, a powder, a foundation, a transdermal patch, a cream or a mask.

[0037] The composition can also be suitable for enteral or parenteral administration, in particular intradermal or subcutaneous administration.

[0038] According to the present invention, the extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo- β- glucans with a molar mass of between 2 and 5 kDa, can be present in a cosmetically or pharmaceutically useful amount in the compositions according to the present invention. For example, a cosmetic or therapeutic composition may comprise at least 0.00025% by weight, preferably between 0.001% and 2%, more preferably between 0.01% and 1%, even more preferably between 0.025% and 0.5% by weight of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolicfraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa based on the weight of the whole composition.

[0039] The compositions of the present invention may comprise other agents active in the prevention of senescence and aging in association with an extract of Saccharomyces cerevisiae, in particular wherein said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa.

[0040] The topical compositions according to the invention may comprise at least one further ingredient commonly found in topical cosmetic and / or medical (e.g. dermatological) compositions chosen from water, oils, which may be chosen in particular from volatile and / or non-volatile, linear or cyclic silicone oils, waxes (such as ozokerite, polyethylene wax, beeswax or carnauba wax), silicone elastomers, nonionic, anionic, cationic and / or amphoteric surfactants, co-surfactant (such as linear fatty alcohols), thickeners, gelling agents, humectants (such as polyols like glycerin), colorants, preservatives, fillers, tensors, sequestrants, perfumes, and mixtures hereof.

[0041] These compositions can be in particular in the form of oil-in-water emulsions, water-in-oil emulsions, multiple emulsions (Water / Oil / Water or Oil / Water / Oil) which can optionally be microemulsions or nanoemulsions, or in the form of solutions, suspensions, hydrodispersions, gels, ointments, pastes, aerosol foams or sprays, aqueous gels, powders, or foundations or transdermal patches. They can be more or less fluid and have the appearance of creams, emulsions, gels, masks or any other aspect of healthy skin care cosmetics. The person skilled in the art is aware of the procedures, ingredients and forms of common use in the preparation of dermal formulations.

[0042] A “gel” is a colloid in which the dispersed phase has combined with the continuous phase to produce a semisolid material, such as jelly.

[0043] An “oil” is a composition containing at least 95% wt of a lipophilic substance. Examples of lipophilic substances include but are not limited to naturally occurring and synthetic oils, fats, fatty acids, lecithins, triglycerides and combinations thereof.

[0044] A “continuous phase” refers to the liquid in which solids are suspended or droplets of another liquid are dispersed and is sometimes called the external phase. This also refers to the fluid phase of a colloid within which solid or fluid particles are distributed. If the continuous phase is water (or another hydrophilic solvent), water- soluble or hydrophilic drugs will dissolve in the continuous phase (as opposed to beingdispersed). In a multiphase formulation (e.g., an emulsion), the discreet phase is suspended or dispersed in the continuous phase. Excipients for topical administration may include anti-microbial compounds, e.g. parabens, antioxidants, e.g. sodium ascorbyl acetate and alpha-tocopherol, stabilizers, e.g. sorbitol, and / or emulsifying agents to produce a stable emulsion with both a hydrophilic and a hydrophobic phase.

[0045] “Diluents” may be included in the formulations to dissolve, disperse or otherwise incorporate the carrier. Examples of diluents include, but are not limited to, water, buffered aqueous solutions, organic hydrophilic diluents, such as monovalent alcohols, and low molecular weight glycols and polyols (e.g. propylene glycol, polypropylene glycol, glycerol, butylene glycol).

[0046] Appropriate excipients are selected based on the type of formulation. Standard excipients include gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glyceryl monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidol silicon dioxide, phosphates, sodium dodecyl sulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethycellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, polyvinylpyrrolidone, sugars, and starches.

[0047] An emulsion is a preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. The oil phase may consist at least in part of a propellant, such as an HFA propellant. Either or both of the oil phase and the aqueous phase may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. Preferred excipients include surfactants, especially non-ionic surfactants; emulsifying agents, especially emulsifying waxes; and liquid non-volatile non-aqueous materials, particularly glycols such as propylene glycol. The oil phase may contain other oily pharmaceutically approved excipients. For example, materials such as hydroxylated castor oil or sesame oil may be used in the oil phase as surfactants or emulsifiers.

[0048] “Emollients” are an externally applied agent that softens or soothes skin and are generally known in the art and listed in compendia, such as the “Handbook of Pharmaceutical Excipients”, 4thEd., Pharmaceutical Press, 2003. These include, without limitation, almond oil, castor oil, ceratonia extract, cetostearoyl alcohol, cetyl alcohol, cetyl esters wax, cholesterol, cottonseed oil, cyclomethicone, ethylene glycol palmitostearate, glycerin, glycerin monostearate, glyceryl monooleate, isopropyl myristate, isopropyl palmitate, lanolin, lecithin, light mineral oil, medium-chain triglycerides, mineral oil and lanolin alcohols, petrolatum, petrolatum and lanolin alcohols, soybean oil, starch, stearyl alcohol, sunflower oil, xylitol and combinations thereof. In one embodiment, the emollients are ethylhexylstearate and ethylhexyl palmitate.

[0049] “Surfactants” are surface-active agents that lower surface tension and thereby increase the emulsifying, foaming, dispersing, spreading and wetting properties of a product. Suitable non-ionic surfactants include emulsifying wax, glyceryl monooleate, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polysorbate, sorbitan esters, benzyl alcohol, benzyl benzoate, cyclodextrins, glycerin monostearate, poloxamer, povidone and combinations thereof. In one embodiment, the non-ionic surfactant is stearyl alcohol.

[0050] “Emulsifiers” are surface active substances which promote the suspension of one liquid in another and promote the formation of a stable mixture, or emulsion, of oil and water. Common emulsifiers are: metallic soaps, certain animal and vegetable oils, and various polar compounds. Suitable emulsifiers include acacia, anionic emulsifying wax, calcium stearate, carbomers, cetostearyl alcohol, cetyl alcohol, cholesterol, diethanolamine, ethylene glycol palmitostearate, glycerin monostearate, glyceryl monooleate, hydroxpropyl cellulose, hypromellose, lanolin, hydrous, lanolin alcohols, lecithin, medium-chain triglycerides, methylcellulose, mineral oil and lanolin alcohols, monobasic sodium phosphate, monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer, poloxamers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, propylene glycol alginate, self-emulsifying glyceryl monostearate, sodium citrate dehydrate, sodium lauryl sulfate, sorbitan esters, stearic acid, sunflower oil, tragacanth, triethanolamine, xanthan gum and combinations thereof. In one embodiment, the emulsifier is glycerol stearate.

[0051] A “lotion” is a low- to medium-viscosity liquid formulation. A lotion can contain finely powdered substances that are in soluble in the dispersion medium through the use of suspending agents and dispersing agents. Alternatively, lotions can have as thedispersed phase liquid substances that are immiscible with the vehicle and are usually dispersed by means of emulsifying agents or other suitable stabilizers. In one embodiment, the lotion is in the form of an emulsion having a viscosity of between 100 and 1000 centistokes. The fluidity of lotions permits rapid and uniform application over a wide surface area. Lotions are typically intended to dry on the skin leaving a thin coat of their medicinal components on the skin's surface.

[0052] A “cream” is a viscous liquid or semi-solid emulsion of either the “oil-in-water” or “water-in-oil type”. Creams may contain emulsifying agents and / or other stabilizing agents. In one embodiment, the formulation is in the form of a cream having a viscosity of greater than 1000 centistokes, typically in the range of 20,000-50,000 centistokes. Creams are often time preferred over ointments as they are generally easier to spread and easier to remove.

[0053] An “ointment” is a semisolid preparation containing an ointment base and optionally one or more active agents. Examples of suitable ointment bases include hydrocarbon bases (e.g., petrolatum, white petrolatum, yellow ointment, and mineral oil); absorption bases (hydrophilic petrolatum, anhydrous lanolin, lanolin, and cold cream); water-removable bases (e.g., hydrophilic ointment), and water-soluble bases (e.g., polyethylene glycol ointments). Pastes typically differ from ointments in that they contain a larger percentage of solids. Pastes are typically more absorptive and less greasy that ointments prepared with the same components.

[0054] A “gel” is a semisolid system containing dispersions of small or large molecules in a liquid vehicle that is rendered semisolid by the action of a thickening agent or polymeric material dissolved or suspended in the liquid vehicle. The liquid may include a lipophilic component, an aqueous component or both. Some emulsions may be gels or otherwise include a gel component. Some gels, however, are not emulsions because they do not contain a homogenized blend of immiscible components. Suitable gelling agents include, but are not limited to, modified celluloses, such as hydroxypropyl cellulose and hydroxyethyl cellulose; Carbopol homopolymers and copolymers; and combinations thereof. Suitable solvents in the liquid vehicle include, but are not limited to, diglycol monoethyl ether; alklene glycols, such as propylene glycol; dimethyl isosorbide; alcohols, such as isopropyl alcohol and ethanol. The solvents are typically selected for their ability to dissolve the drug. Other additives, which improve the skin feel and / or emolliency of the formulation, may also be incorporated. Examples of such additives include, but are not limited, isopropyl myristate, ethyl acetate, C12-C15 alkyl benzoates, mineral oil, squalane, cyclomethicone, capric / caprylic triglycerides, and combinations thereof.

[0055] “Foams” consist of an emulsion in combination with a gaseous propellant. The gaseous propellant consists primarily of hydrofluoroalkanes (HFAs). Suitable propellants include HFAs such as 1,1,1,2-tetrafluoroethane (HFA 134a) and 1,1,1,2,3,3,3-heptafluoropropane (HFA 227), but mixtures and admixtures of these and other HFAs that are currently approved or may become approved for medical use are suitable. The propellants preferably are not hydrocarbon propellant gases which can produce flammable or explosive vapors during spraying. Furthermore, the compositions preferably contain no volatile alcohols, which can produce flammable or explosive vapors during use.

[0056] Buffers are used to control pH of a composition. Preferably, the buffers buffer the composition from a pH of about 4 to a pH of about 7.5, more preferably from a pH of about 4 to a pH of about 7, and most preferably from a pH of about 5 to a pH of about 7. In a preferred embodiment, the buffer is based on triethanolamine, citric acid, sodium hydroxyde, disodium phosphate and potassium phosphate.

[0057] Preservatives can be used to prevent the growth of fungi and microorganisms. Suitable antifungal and antimicrobial agents include, but are not limited to, benzoic acid, butylparaben, ethyl paraben, methyl paraben, propylparaben, sodium benzoate, sodium propionate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, potassium sorbate, caprylyl alcohol, 1,2-hexandiol, and thimerosal.

[0058] Antioxidants can be used in the compositions of the present invention. Examples of antioxidants are tocopherol, hydroxyacetophenone, dimethylmethoxy chromanol and phenethyl alcohol.

[0059] Viscosity modifiers can additionally be present, such as potassium chloride and natural gums such as xanthan gum, gum arabic, gum tragacanth, carrageenan, chitosan, guar gum, konjac gum, sclerotium gum, dextrins and starch.

[0060] Chelating agents may additionally be present, such as sodium glucuronate.

[0061] Fragrances may be added to the compositions of the invention.

[0062] Penetration enhancers are frequently used to promote transdermal delivery of drugs across the skin, in particular across the stratum corneum. The more commonly used enhancers include urea, (carbonyldiamide), imidurea, N, N-diethylformamide, N- methyl-2-pyrrolidine, 1-dodecal-azacyclopheptane-2-one, calcium thioglycate, 2- pyyrolidine, N,N-diethyl-m-toluamide, oleic acid and its ester derivatives, such as methyl, ethyl, propyl, isopropyl, butyl, vinyl and glycerylmonooleate, sorbitan esters,such as sorbitan monolaurate and sorbitan monooleate, other fatty acid esters such as isopropyl laurate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, propylene glycol monolaurate, propylene glycol monooleatea and non-ionic detergents such as BRIJ® 76 (stearyl poly(10 oxyethylene ether), BRIJ® 78 (stearyl poly(20)oxyethylene ether), BRIJ® 96 (oleyl poly(10)oxyethylene ether), and BRIJ® 721 (stearyl poly (21) oxyethylene ether) (ICI Americas Inc. Corp.).

[0063] Emulsion stabilizers, surfactants and emulsifying agents may additionally be present, such as sorbitan isostearate, hydroxyethyl acrylate / sodium acryloxydiethyl taurate copolymer and sorbitan isostearate.

[0064] Humectants are crucial in skincare by providing essential skin hydration and maintaining the skin's moisture balance. Exemplary humectant are Glycerin, Hyaluronic acid, Aloe vera, Honey, Hydrolyzed proteins, Panthenol, Allantoin, Seaweed & algae, Sodium PCA (sodium pyrrolidone carboxylic acid), Saccharide Isomerate, Sugar Alcohols (e.g. sorbitol), Hydroxy acids (e.g.. lactic acid and gluconolactone), Agave nectar, Betaine, Chitosan, Trehalose, Beta-glucan, Topical collagen, Galactoarabinan and propanediol.

[0065] Solvents used in the compositions of the present invention may include water, alcohols such as ethanol and isopropyl alcohol, alkanes such as C15-19 Alkane, silicone oils and mineral oils.

[0066] The compositions may additionally contain sunscreens.

[0067] By way of illustration of organic UV filters and in a non-limiting manner, mention may be made of: - anthranilates, in particular menthyl anthranilate; - benzophenones, in particular 1-benzophenone, 3-benzophenone or oxybenzone, 5- benzophenone, 6-benzophenone, 8-benzophenone, 9-benzophenone, 12- benzophenone, and preferably 2-benzophenone (Oxybenzone), or 4-benzophenone (Uvinul MS40® available from B.A.S.F.); - benzylidenecamphor, in particular 3-benzylidenecamphor, benzylidenecamphorsulphonic acid, benzalkoniumcamphor methosulfate, polyacrylamidomethylbenzylidenecamphor, terephthalylidenecamphorsulphonic acid, and preferably 4-methylbenzylidenecamphor (Eusolex 6300® available from Merck); - benzimidazoles, in particular benzimidazilate (Neo Heliopan AP® available from Haarmann and Reimer), or phenylbenzimidazole sulfonic acid (PARSOL HS® available from DSM);- benzotriazoles, in particular drometrizole trisiloxane, or methylene bis- benzotriazolyltetramethylbutylphenol (Tinosorb M® available from Ciba); - cinnamates, in particular cinoxate, DEA methoxycinnamate, diisopropyl methylcinnamate, dimethoxycinnamate glyceryl ethylhexanoate, isopropyl methoxycinnamate, isoamyl cinnamate, Kaempferia galanga root extract (TEGO GALANGA from EVONIK containing 98% ethyl-p-methoxycinnamate) and preferably octylmethoxycinnamate (Parsol MCX® available from Hoffmann La Roche); - diphenylacrylates, in particular ethocrylene (Uvinul N35® available from B.A.S.F.), or octocrylene (Uvinul 539® available from B.A.S.F.) or Ethylhexyl methoxycrylene (SOLASTAY available from HALLSTAR); - dibenzoylmethanes, in particular butyl methoxydibenzoylmethane (Parsol 1789®); imidazolines, in particular ethylhexyl dimethoxybenzylidenedioxoimidazoline; - PABA, in particular ethyl dihydroxypropyl PABA, ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-25 PABA, or ethyl PABA (benzocaine); - triazines, in particular anisotriazine (Tinosorb S® available from Ciba) or diethylhexylbutamido-triazone (Uvasorb HEB® available from 3V Sigma), ethylhexyltriazone (llvinul T150® available from B. A. S. F.), Tris-Biphenyl Triazine (Tinosorb 2AB available from BASF), benzoates, in particular N-hexyl 2-(4- diethylamino-2-hydroxybenzoyl)benzoate (llvinul A+ available from BASF) or as a mixture with octyl methoxycinnamate (Uvinul A+B available from BASF); - benzalmalonates, in particular Polysilicone-15 (Parsol SLX available from DSM), - benzoxazoles, in particular 2,4-bis[4-[5-(1 .1 -dimethylpropyl)benzoxazol-2- yl]phenylimino]-6-[(2-ethylhexyl)imino]-1 .3,5-triazine, (Uvasorb K2A available from Sigma 3 V); - salicylates, in particular dipropylene glycol salicylate, ethylhexyl salicylate, homosalate, butyloctyl salicylate (HALLBRITE BHB available from HALLSTAR) or TEA salicylate; - Phenylbenzimidazole sulfonic acid (eg Parsol HS), Octocrylene (eg Parsol 340), Ethylhexyl Methoxycinnamate (eg Parsol MCX), Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (eg Tinosorb M), Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (eg Tinosorb S), Tris-Biphenyl Triazine (eg Tinosorb 2AB), Ethylhexyl Triazone (eg UVINUL T150) and Diethylhexyl Butamido Triazone (eg UVASORB HEB), Diethylamino Hydroxybenzoyl Hexyl Benzoate (eg Uvinul A PLUS), Butyl Methoxydibenzoylmethane (eg Parsol 1789), Polysilicone-15 (eg Parsol SLX), Benzophenone-4 (eg Uvinul MS 40), Benzophenone-3, Ethylhexyl Salicylate (eg Parsol EHS), Homosalate; - and mixtures thereof.

[0068] Inorganic UV screening agents can be used, for example metal oxide particles having an average elementary particle size of less than or equal to 100 nm. They may be chosen in particular from titanium oxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide, and mixtures thereof.

[0069] Sun Protection Factor (SPF) indicates a sunscreen’s, cosmetic or pharmaceutical preparation’s or homecare product’s ability to protect against UVB rays but does not adequately designate to what extent (if any) a sunscreen composition protects against UVA radiation. SPF is a measure of how much solar energy (UV radiation) is required to produce sunburn on protected skin, i.e., in the presence of sunscreen, relative to the amount of solar energy required to produce sunburn on unprotected skin. As the SPF value increases, sunburn protection increases.

[0070] Skin conditioning agents may be added to the compositions of the present invention, for example caprylic / capric triglyceride, alpha-glucan triglycerides, palmitoyl tripeptide-5, glycerine, diglucosyl gallic acid, panthenol, pantolactone, sodium stearoyl glutamate, lactic acid, hydrolysed hyaluronic acid, sodium hyaluronate and maltodextrin.

[0071] Further natural extracts may be present in compositions of the present invention, for example Saccharomyces / Xylinum / Black Tea Ferment, Bellis Perennis (Daisy) Flower Extract, Thermus Thermophillus Ferment and Sphingomonas Ferment Extract.

[0072] After formulation, the product is filled into an appropriate dispenser and shipped to the end user. Examples of final container may include a pump bottle, squeeze bottle, jar, tube or vial.

[0073] The invention will now be illustrated by non-limiting examples of compositions according to the invention and by test results. EXAMPLES Example 1

[0074] Normal human keratinocytes were treated with Saccharomyces cerevisiae for 48 hours. Then, the supernatants were collected and cell debris were removed by centrifugation. The supernatants were concentrated on column filter (amicon ultra-15 50K centrifugal) and the exosomes were isolated using EXOPrep kit (Hansabiomed).

[0075] Analysis of exosomes miRNA content: miRNA were extracted and purified using PureLink miRNA Isolation Kit (Invitrogen). The total RNA was reverse transcribed withmiRCURY LNA RT Kit (Qiagen, 339340). PCR reaction was performed with a miRCURY LNA SYBR Green PCR Kit (Qiagen) using the CFX-connect (Biorad). The results were normalized against U6 expression. Example 2

[0076] The exosomes of Example 1 were resuspended in PBS. Normal human fibroblasts were treated during 48 hours with exosomes diluted in culture medium.

[0077] Analysis of genes expression on fibroblasts: Total RNAs were extracted and purified using PureLink™ miRNA Isolation Kit (Invitrogen). Total RNA was reverse transcribed with the Superscript VILO cDNA Synthesis Kit (ThermoFisher). Quantitative PCR was performed with a Platinum Quantitative PCR SuperMix-UDG Kit (Invitrogen) using the CFX-connect (Biorad). The results were normalized to endogenous control GAPDH expression.

[0078] The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the embodiments of the present invention. Thus, it should be understood that although the present invention has been specifically disclosed by specific embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those of ordinary skill in the art, and that such modifications and variations are considered to be within the scope of embodiments of the present invention.

Claims

CLAIMS What is claimed is:

1. Cosmetic use of a composition comprising an extract of Saccharomyces cerevisiae for modulating exosome content.

2. Cosmetic use according to claim 1 for preventing aging and / or senescence, in particular intrinsic and / or extrinsic dermal aging and / or senescence.

3. Cosmetic according to any of the preceding claims, wherein the extract of Saccharomyces cerevisiaecorresponds to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa.

4. Use according to any of the preceding claims, wherein the composition is for topical application.

5. Use according to claim 4, wherein the composition is in the form of an oil-in- water emulsion, a water-in-oil emulsion, a multiple emulsion (Water / Oil / Water or Oil / Water / Oil), a microemulsion, a nanoemulsion, a solution, a suspension, a hydrodispersion, a gel, an ointment, a paste, an aerosol foam, a spray, an aqueous gel, a powder, a foundation, a transdermal patch, a cream or a mask.

6. Use according to any of claims 1-3, wherein the composition is for enteral or parenteral administration.

7. Use according to claim 6, wherein the composition is for intradermal or subcutaneous administration.

8. Use according to any of the preceding claims, wherein the extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, is present in a cosmetically or pharmaceutically effective amount.

9. Use according to claim 8, wherein the extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, is present in at least 0.00025% by weight, preferably between 0.001% and 2%, more preferably between 0.01% and 1%, even more preferably between 0.025% and 0.5% by weight based on the weight of the whole composition.

10. Use according to any of the preceding claims, wherein the composition comprises at least one further ingredient chosen from water, oils, which may be chosen in particular from volatile and / or non-volatile, linear or cyclic silicone oils, waxes (such asozokerite, polyethylene wax, beeswax or carnauba wax), silicone elastomers, nonionic, anionic, cationic and / or amphoteric surfactants, co-surfactant (such as linear fatty alcohols), thickeners, gelling agents, humectants (such as polyols like glycerin), colorants, preservatives, fillers, tensors, sequestrants, perfumes, and mixtures hereof.

11. A method for preventing the aesthetic aging of skin comprising topically applying thereto a therapeutically effective amount of an extract of Saccharomyces cerevisiae, in particular said extract corresponding to the cytosolic fraction comprising oligo-β- glucans with a molar mass of between 2 and 5 kDa, wherein the extract increases gene expression of collagen I, collagen III and decorin, and decreases expression of MMP3 and / or MMP12 when applied to fibroblasts at a concentration of at least 0.00025% by weight in a cosmetically acceptable vehicle for a time sufficient to achieve an improvement in the appearance of said skin of said human.

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