Skin brightening

Abstract

Provided is a composition of cosmetically active agents comprising a combination of at least two of Bisabol ol, Red salvia and Tranexamic acid. The composition effectively reduces the generation of melanin and its distribution throughout the skin, with the cosmetic effect of brightening the skin color, lightening spots, addressing hyperpigmentation like post inflammatory hyperpigmentation and improving dullness of the skin.

Description

SKIN BRIGHTENINGCLAIM OF PRIORITY

[0001] This patent application claims the benefit of priority to FR Application Serial No. 2413942, filed December 12, 2024, which is incorporated by reference herein in its entirety.FIELD OF THE INVENTION

[0002] The invention provides a composition of cosmetically active agents comprising a combination of at least two of Bisabol ol, Red salvia and Tranexamic acid. The composition effectively reduces the generation of melanin and its distribution throughout the skin, with the cosmetic effect of brightening the skin color, lightening spots like but not limited to chloasma, age spots, sunspots, freckles, addressing hyperpigmentation like post inflammatory hyperpigmentation and improving dullness of the skin.BACKGROUND OF THE INVENTION

[0003] The color of human skin is determined by the amount and the type of melanin produced by specialized cells, melanocytes, which are located in the basal layers of skin. Melanin, one of the most widely distributed natural pigments, is a homogeneous polyphenollike biopolymer with a complex structure and color varying from brown to black (eumelanin) and red to yellow (pheomelanin).

[0004] Overproduction of melanin can cause different types of abnormal skin color and other dermatological disorders, such as melasma, age spots and sites of actinic damage.

[0005] Melanin is produced through a series of oxidative reactions and polymerization steps starting with the amino acid tyrosine. It is therefore not a surprise that inhibitors of tyrosinase, which plays the key role in the process of melanin production, are often used as skinbrightening agents. Many tyrosinase inhibitors are resorcinol derivatives or polyphenol derivatives of flavonoids or of trans-stilbene, such as resveratrol or its derivatives. These types of compounds are known to form strong chelates with metal ions.

[0006] Agents commonly known for their skin brightening properties are arbutin, kojic acid, azelaic acid, aloesin, ascorbic acid, vitamin E, enoxolone, hydroquinone, licorice, resveratrol, cysteamine, flavonoids, linoleic acid, niacinamide and retinoids

[0007] Another approach commonly used, especially in Asian countries, for achieving skin brightening effects adopts the traditional powder film covering technology. However,although flaws are perfectly covered, because the powder film is too thick the refraction of light rays is blocked, so that the makeup looks dull. In addition, the traditional BB cream, CC cream and air cushion cream mostly adopt a water-in-oil system, and have the defects of poor spreadability, heavy skin feel, pore blockage, difficulty in cleaning and the like.

[0008] a-Bisabolol, also known as levomenol, is a monocyclic sesquiterpene alcohol commonly present in essential oils of many edible and ornamental plants. a-Bisabolol has been used as a skin conditioning agent where it is integrated in many cosmetic formulations due to its skin soothing effects, well documented dermal absorption and the absence of dermal irritations or photosensitivity following its application. a-Bisabolol can also be obtained synthetically.

[0009] Red sage (Salvia miltiorrhiza), dansam or danshen, is a traditional Chinese medicine made from the dried root of the red sage plant. It has a long history of use in China and other Asian countries. This herbal remedy has many potential health benefits, thanks to its polyphenol content. It can be obtained by extraction of the root and / or leaves and / or flowers of Salvia miltiorrhiza with an appropriate solvent according to processes known in the art, all of which are viable for the present invention.

[0010] Tranexamic acid (CAS Nr 1197-18-8) is an analog of the amino acid lysine. It is frequently used following major trauma and to prevent and treat blood loss in a variety of situations, such as dental procedures, heavy menstrual bleeding, and surgeries with high risk of blood loss.

[0011] Nelupure™ (INCI Propanediol (and) Glycerin (and) Nymphaea Caerulea Flower Extract (and) Nelumbo Nucifera Flower Extract) is a vegetal complex that contains a blended extract from two types of lotus flower, the Egyptian Lotus (Nymphaea caerulea) and the Sacred Lotus (Nelumbo nucifera), whose synergic action transmits purity and luminosity. It reduces excess sebum production in the skin and the processes that cause inflammation of the pores, leaving a smooth, radiant and pure complexion. As it is inter alia a commercially available product, at least one enabling method of extraction is known in the art.

[0012] The use of dressings for the treatment of chloasma is known in the art. However, dressings have a number of disadvantages: they tend to stick to the skin and may be painful to remove, are either dry in which case they cannot control moisture level, or very wet in which case they must be quickly removed before they excessively soften the skin. Additionally, they are uncomfortable and un-aesthetic when applied on exposed skin surfaces like the face. As such, they do not meet the expectations of users.

[0013] In the light of the above-described state of the art, there is a compelling need for new compositions that can be applied to the skin without the aforementioned disadvantages and still are highly effective in brightening the skin and treat the un-aesthetic consequences of hyperpigmentation. Once applied, the compositions must remain at the site of application for the time necessary to exert their action even in the absence of a dressing.SUMMARY OF THE INVENTION

[0014] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify required or essential features of the claimed subject matter. Nor is this summary intended to be used to limit the scope of the claimed subject matter.

[0015] The present inventors have surprisingly found that a composition of cosmetically active agents comprising a combination of at least two of Bisabol ol, Red salvia and Tranexamic acid effectively reduces the generation of melanin and its distribution throughout the skin, with the cosmetic effect of brightening the skin color, lightening spots like but not limited to chloasma, age spots, sun spots, freckles, addressing hyperpigmentation like (but not limited to) post inflammatory hyperpigmentation and improving dullness of the skin.

[0016] An object of the present invention is therefore a cosmetic composition for skin brightening comprising cosmetically effective amounts of at least two of (i) bisabolol, (ii) red salvia and (iii) tranexamic acid.

[0017] In one embodiment the compositions according to the present invention may further comprise a blended extract from two types of lotus flower, the Egyptian Lotus (Nymphaea caerulea) and the Sacred Lotus (Nelumbo nucifera), a resorcinol derivative, kojic acid, niacinamide, palmaria palmata extract and / or combinations thereof. The extracts disclosed hereinabove are inter alia commercially available products, so that for each of them at least one enabling method of extraction is known in the art.

[0018] In one embodiment the two or all of Bisabolol, Red salvia and Tranexamic acid present in the compositions of the present invention act synergistically to reduce the generation of melanin and its distribution throughout the skin.

[0019] In one embodiment the cosmetic compositions according to the invention comprise one of the following (synergistic) combinations:(i) and (ii);(i) and (iii);(ii) and (iii);(i) and (ii) and (iii).

[0020] In one embodiment the cosmetic compositions according to the invention do not comprise the combination of only bisabolol and tranexamic acid. The combination of (i) and (ii) and (iii) is hereby not excluded.

[0021] In cosmetic compositions, xanthan gum functions as a thickener, stabilizer, and emulsifier, improving product texture and consistency. It prevents ingredients from separating, creates a smooth, uniform feel in products like lotions and serums, and can form gels. Xanthan gum also helps suspend insoluble ingredients and can moisturize the skin by forming a light barrier that locks in moisture. The Applicant has however found that formulating the compositions of the invention with xanthan gum may lead to noodling, i.e. pilling of the formulas when they are massaged on the skin.

[0022] This problem may be solved by formulating the compositions of the invention with a 2 / 1 to 1 / 2 ratio of Hydroxy ethyl Acrylate / sodium Acryloyldimethyl Taurate Copolymer & Polyacrylate Crosspolymer -6.

[0023] Further objects of the present invention are presented in the attached claims.DEFINITIONS

[0024] 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 clauses, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter.

[0025] 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,” unlessindicated 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.

[0026] 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.

[0027] 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.

[0028] 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%.

[0029] 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] When different embodiments are described that further specify different features of the present invention it is intended that these embodiments can be combined in a furtherembodiment specifying the two or more corresponding features of the present invention even when such combined embodiment is not explicitly described herein.

[0033] When the quantity of an ingredient of a composition is indicated as % it is intended over the total weight of the composition, unless otherwise indicated.

[0034] If any given chemical entity is generally known in the art to belong to two or more cosmetic functional classes (is for example known to be both a film former and an emollient) and those functional classes are part of the definition of the claimed subject matter, that chemical entity may be present only once in any embodiment of the claimed invention, i.e. it can belong to only one of those two or more functional classes.DETAILED DESCRIPTION OF THE INVENTION

[0035] An object of the present invention is therefore a cosmetic composition for skin brightening comprising cosmetically effective amounts of at least two of (i) bisabol ol, (ii) red salvia and (iii) tranexamic acid.

[0036] In one embodiment the cosmetic compositions according to the invention comprise one of the following combinations:(i) and (ii);(i) and (iii);(ii) and (iii);(i) and (ii) and (iii).

[0037] In one embodiment the cosmetic compositions according to the invention do not comprise the combination of only bisabolol and tranexamic acid. The combination of (i) and (ii) and (iii) is hereby not excluded.

[0038] The red salvia extract can be obtained from the roots and all aerial parts of the plant Salvia miltiorrhiza. In one embodiment of the present invention the extract is obtained from the roots, leaves and / or flowers of the plant. In a further embodiment of the present invention the extract is obtained from the roots of the plant. Examples of extracts that can be used to put into practice the present invention are registered as INCI: SALVIA MILTIORRHIZA FLOWER / LEAF / ROOT EXTRACT and INCI: S ALVIA MILTIORRHIZA ROOTEXTRACT.

[0039] In a further embodiment the red salvia extract is naturally enriched in salvianolic acid B and / or cryptotanshinone, in particular in salvianolic acid B (INCI: SALVIA MILTIORRHIZ A FLOWER / LEAF / ROOT EXTRACT).

[0040] In one embodiment the compositions according to the present invention may further comprise a blended extract from two types of lotus flower, the Egyptian Lotus (Nymphaea caerulea) and the Sacred Lotus (Nelumbo nucifera), a resorcinol derivative, kojic acid, niacinamide, palmaria palmata extract and / or combinations thereof.

[0041] In one embodiment of the present invention two or all of Bisabol ol, Red salvia and Tranexamic acid present in the compositions of the present invention act synergistically to reduces the generation of melanin and its distribution throughout the skin.

[0042] In the cosmetic compositions of the invention, bisabolol is present in an amount between about 0.00001 wt % and about 10 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0043] In the cosmetic compositions of the invention, red salvia is present in an amount between about 0.00001 wt % and about 2 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0044] In the cosmetic compositions of the invention, tranexamic acid is present in an amount between about 0.001 wt % and about 5 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0045] If present, each extract of the Egyptian Lotus (Nymphaea caerulea) and the Sacred Lotus (Nelumbo nucifera) is present in an amount between about 0.000075 wt % and about 2 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0046] If present the resorcinol derivative is present in an amount between about 0.0001 wt % and about 2 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0047] If present the kojic acid is present in an amount between about 0.00001 wt % and about 2 wt % relative to the total weight of the composition. All values between the limits of these ranges are hereby explicitly disclosed.

[0048] At least two of Bisabolol, Red salvia and Tranexamic acid are present in the compositions of the present invention. The two or all of Bisabolol, Red salvia and Tranexamicacid present in the compositions of the present invention may act synergistically to provide brightening of the skin.

[0049] A resorcinol derivative according to the present invention may be chosen from the list comprising phenylethyl resorcinol, hexyl resorcinol, butyl resorcinol, chlororesorcinol, resorcinol acetate, resorcinol, methyl resorcinol dimethoxytolyl propylresorcinol.

[0050] The cosmetic composition according to the present invention can be in the form of a topical formulation, in particular in the form of an oil-in-water emulsion, a water-in-oil emulsion, silicone / water emulsions, water / silicone emulsions, 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 cream or a mask. In a particular embodiment of the present invention the composition is not in the form of a dressing or patch.

[0051] The composition can also be suitable for enteral or parenteral administration, in particular intradermal or subcutaneous administration.

[0052] 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

[0053] These compositions can be in particular in the form of oil-in-water emulsions, water-in-oil emulsions, silicone / water emulsions, water / silicone emulsions, a multiple emulsion (water / oil / water or oil / water / oil)which can optionally be microemulsions or nanoemulsions, or in the form of solutions, suspensions, hydrodispersions, oils, gels, ointments, pastes, aerosol foams or sprays, aqueous gels, powders, or foundations. 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.

[0054] A “gel” is a colloid in which the dispersed phase has combined with the continuous phase to produce a semi solid material, such as jelly.

[0055] 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.

[0056] 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 parti cles 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 being di spersed). 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 ph ase

[0057] “Diluents” may be included in the formulations to dissolve, di sperse 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 lowrmolecular weight glycols and polyols (e.g. propylene glycol, polypropylene glycol, glycerol, butylene glycol).

[0058] 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.

[0059] 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 thecontinuous phase, it s 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.

[0060] ‘‘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 w'ax, 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 ethylhexy I stearate and ethylhexyl palmitate.

[0061] “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.

[0062] “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: metal lic soaps, certain animal and vegetable oils, and various polar compounds. Suitable emulsifiers include acacia, anionic emulsifying w?ax, 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,monoethanol amine, nonionic emulsifying wax, oleic acid, poloxamer, pol oxamers, 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.

[0063] 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 the dispersed 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.

[0064] 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.

[0065] 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, yellow7ointment, and mineral oil); absorption bases (hydrophilic petrolatum, anhydrous lanolin, lanolin, and cold cream); waterremovable 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.

[0066] 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 orotherwise 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 hydroxy ethyl 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 fortheir 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.

[0067] ‘’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 (HF / \ 134a) and 1,1, 1,2, 3, 3, 3- heptafluoropropane (FIFA 227), but mixtures and admixtures of these and other HFAs that are currently approved or may become approved for medical use are suitable. In one embodiment the propellants are not hydrocarbon propellant gases which can produce flammable or explosive vapors during spraying. Furthermore, exemplary compositions according to the present invention contain no volatile alcohols, which can produce flammable or explosive vapors during use.

[0068] Buffers are used to control pH of a composition. In one embodiment, the buffers buffer the composition from a pH of about 4 to a pH of about 7.5, or from a pH of about 4 to a pH of about 7, or 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

[0069] 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.

[0070] Antioxidants can be used in the compositions of the present invention.Examples of antioxidants are tocopherol, hydroxyacetophenone, dimethylmethoxy chromanol and phenethyl alcohol.

[0071] 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.

[0072] Chelating agents may additionally be present, such as sodium glucuronate.

[0073] Fragrances may be added to the compositions of the invention.

[0074] 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, l-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 glyceryl monool eate, sorbitan esters, such as sorbitan monolaurate and sorbitan monool eate, other fatty acid esters such as isopropyl laurate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, propylene glycol monolaurate, propylene glycol monool eatea and non-ionic detergents such as BRU® 76 (stearyl poly(10 oxyethylene ether), BRU® 78 (stearyl poly(20)oxyethylene ether), BRU® 96 (oleyl poly(10)oxy ethylene ether), and BRU® 721 (stearyl poly (21) oxyethylene ether) (ICI Americas Inc. Corp.).

[0075] Emulsion stabilizers, surfactants and emulsifying agents may additionally be present, such as sorbitan isostearate, hydroxyethyl aery late / sodi urn acryloxydiethyl taurate copolymer and sorbitan isostearate.

[0076] Humectants are crucial in skincare by providing essential skin hydration and maintaining the skin's moisture balance. Exemplary humectants 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

[0077] 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.

[0078] 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.

[0079] Further natural extracts may be present in compositions of the present invention, for example Saccharomyces / Xylinum / Black Tea Ferment, Bellis Perennis (Daisy) Flower Extract, Thermits Thermophillus Ferment and Sphingomonas Ferment Extract.

[0080] 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.

[0081] The compositions according to the invention may additionally comprise one or more UVA filter(s), one or more UVB filter(s) and / or one or more UVA / UVB filter(s).

[0082] Sunscreen filters that may be present in a composition of the present invention may be:A. Screens, which use only inorganic compounds (mainly zinc oxide and / or titanium dioxide) as active ingredients. These ingredients primarily work by absorbing UV rays but also through reflection and refraction; andB. Chemical sunscreens, which use organic molecules as active ingredients; and / or C. Mixtures thereof.

[0083] 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 exemplarily 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 exemplarily 4-m ethylbenzylidenecamphor (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 methoxy cinnamate, diisopropyl methylcinnamate, dimethoxycinnamate glyceryl ethylhexanoate, isopropyl methoxycinnamate, isoamyl cinnamate, Kaempferia galanga root extract (TEGO GALANGA from EVONIK containing 98% ethyl-p-methoxy cinnamate) and exemplarily octylmethoxy cinnamate (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 methoxy dibenzoylmethane (Parsol 1789®); imidazolines, in particular ethylhexyl dimethoxybenzylidenedioxoimidazoline;PABA, in particular ethyl dihydroxypropyl PABA, ethyl hexyl di methyl 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 3 V Sigma), ethylhexyltriazone (Uvinul T150® available from B. A. S. F.), Tris-Biphenyl Triazine (Tinosorb A2B available from BASF), benzoates, in particular N-hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate (Uvinul A+ available from BASF) or as a mixture with octyl methoxy cinnamate (Uvinul A+B available from BASF),benzalmal onates, in particular Polysilicone-15 (Parsol SLX available from DSM), benzoxazoles, in particular 2, 4-bis[4-[5-(l.1 -dimethylpropyl)benzoxazol-2-yl]phenylimino]-6-[(2-ethylhexyl)imino]-l,3,5-triazine, (Uvasorb K2A available from Sigma 3 V);salicylates, in particular dipropylene glycol salicyclate, ethylhexyl salicylate, homosalate, butyloctyl salicylate (HALLBRITE BHB available from HALLSTAR or TEA salicylate;Phenylbenzimidazole sulfonic acid (eg Parsol HS), Octocrylene (eg Parsol 340), Ethylhexyl Methoxy cinnamate (eg Parsol MCX), Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (eg Tinosorb M), Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (eg Tinosorb S), Tris-Biphenyl Triazine (eg Tinosorb A2B), Ethylhexyl Triazone (eg UVINUL T150) and Diethylhexyl Butamido Triazone (eg UVASORB HEB), Diethylamino Hydroxybenzoyl Hexyl Benzoate (eg Uvinul APLUS), Butyl Methoxy dibenzoylmethane (eg Parsol 1789), Poly silicone- 15 (eg Parsol SLX), Benzophenone-4 (eg Uvinul MS 40), Benzophenone-3, Ethylhexyl Salicylate (eg Parsol EHS), Homosalate;and / or mixtures thereof.

[0084] In a preferred embodiment the sunlight protecting component of the cosmetic compositions according to the invention comprises a mixture of BIS-ETHYLHEXYLOXYPHENOL METHOXYPHENYL TRIAZINE (BEMT) and DIETHYLHEXYL BUTAMIDO TRIAZONE (DHBT).

[0085] In a further preferred embodiment, it may additionally comprise at least two of ETHYLHEXYL TRIAZONE (EHT), HOMOSALATE and / or BUTYL METHOXYDIBENZOYLMETHANE.

[0086] In a further preferred embodiment it may further additionally comprise PHENYLBENZIMIDAZOLE SULFONIC ACID (also together with OCTYL SALICYLATE) and / or DIETHYLAMINO HYDROXYBENZOYL HEXYL BENZOATE.

[0087] The inorganic UV screening agents used are metal oxide particles having an average elementary particle size between about 5 and about 600 nm. In particular embodiments the particle size is 15, 30, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550 nm. They may be chosen in particular from titanium oxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide, and mixtures thereof.

[0088] The titanium oxides may be in a crystallized form of the rutile and / or anatase type, and / or in an amorphous or substantially amorphous form. Such coated or uncoated metal oxide pigments are described in particular in patent application EP-A-0,518,773. As commercial pigments, mention may be made of the products sold by the companies Kemira, Tayca, Merck and Degussa.

[0089] The metal oxide pigments may be coated or uncoated.

[0090] The coated pigments are pigments which have undergone one or more surface treatments of chemical, electronic, mechanochemical and / or mechanical nature with compounds such as amino acids, beeswax, fatty acids, fatty alcohols, anionic surfactants,lecithin, sodium, potassium, zinc, iron or aluminum salts of fatty acids, metal (titanium or aluminum) alkoxides, polyethylene, silicones, proteins (collagen, elastin), alkanolamines, silicon oxides, metal oxides or hexametaphosphate of fatty acids.

[0091] Examples of coated titanium oxide pigments are:silica (SUNVEIL from IKEDA), silica and iron oxide (SUNVEIL F from IKEDA), silica and polyglyceryl- 10 stearate (COSMESERVE WP-40W from IWASE COSFA), silica and alumina (MICROTITANIUM DIOXIDE MT500 SA and MICROTITANIUM DIOXIDE MT 100 SA from TAYCA, TIOVEIL from TIOXIDE), alumina (TIPAQUE TTO-55 (B) and TIPAQUE TTO-55 (A) from ISHIHARA, and UVT 14 / 4 from KEMIRA), Rutile TiO2 treated with alumina and glycerol-coated silica (UV TITAN M212 from KEMIRA), Rutile TiO2 treated with alumina and dimethicone (UV TITAN Ml 95 from KEMIRA), Alumina and aluminum stearate (Microtitanium Dioxide MT 100 T, MT 100 TV, MT 100 TX, MT 100 Z, MT-01 from TAYCA, Solaveil CT- 10 W and Solaveil CT 100 from UNIQEMA and Eusolex T-AVO from MERCK), silica, alumina and alginic acid (MT-100 AQ from TAYCA), alumina and aluminum laurate (TAYCA MICROTITANIUM DIOXIDE MT 100 S), alumina, methicone and polyhydroxystearic acid (INP60T7 from KOBO), iron oxide and iron stearate (TAYCA MICROTITANIUM DIOXIDE MT 100 F), zinc oxide and zinc stearate (TAYCA BR 351), silica and alumina and treated with silicone (MICROTITANIUM DIOXIDE MT 600SAS, MICROTITANIUM DIOXIDE MT 500 SAS or MICROTITANIUM DIOXIDE MT 100 SAS from TAYCA), silica, alumina, aluminum stearate and treated with a silicone (STT-30-DS from TITAN KOGYO), alumina and treated with a silicone (TIPAQUE TTO-55 (S) from ISHIHARA, or UV TITAN M 262 from KEMIRA), triethanolamine (STT-65-S from TITAN KOGYO);stearic acid (TIPAQUE TTO-55 (C) from ISHIHARA, strearic acid (and) aluminium hydroxide (MPT- 186 SAKAI) or isostearic acid (MioShade T-Plus Natural Mioshy))sodium hexametaphosphate (MICROTITANIUM DIOXIDE MT 150 W TAYCA) TiO2 treated with octyl trimethyl silane (T 805 by the company DEGUSSA SILICES);TiO2 treated with a poly dimethylsiloxane (70250 UF TiO2S13 framework per framework);anatase / rutile TiO2 treated with a polydimethylhydrogenosiloxane (MICRO TITANIUM DIOXIDE USP GRADE HYDROPHOBIC by COLOR TECHNIQUES),Rutile TiO2 treated with alumina, stearic acid (UV TITAN Ml 60 by KEMIRA), TiO2 treated with alumina hydroxide, stearic acid and triethoxycaprylylsilane (ALT-T-400 by MAPRECOS)or alumina hydroxide, stearic acid (and) dimethicone (Mioshade T-clear Mioshi), or alumina and hydrogen dimethicone (TTO-MS4 KOBO): or manganese-doped TiO2 (Croda OPT 1 -PW);and / or their mixtures.

[0092] Examples of uncoated titanium oxide pigments are:MICROTITANIUM DIOXIDE MT 500 B or MICROTITANIUM DIOXIDE MT600 B by TAYCA;P 25 by DEGUSS A;Transparent titanium oxide PW by WACKER;UFTR by MIYOSHI KASEI;ITS by TOMEN;TIOVEIL AQ by the company TIOXIDEand / or their mixtures.

[0093] Examples of uncoated zinc oxide pigments are:Z-cote by Sunsmart;Nanox by Element! s;Nanogard WCD 2025 by Nanophase Technologiesand / or their mixtures.

[0094] Coated zinc oxide pigments are, for example:zinc oxide CS-5 by Toshibi (ZnO coated with polymethylhydrogenesil oxane); Nanogard Zinc Oxide FN by Nanophase Technologies (40% dispersion in Finsolv TN, C12-C15 alcohol benzoate);DAITOPERSION ZN-30 and DAITOPERSION Zn-50 by the company Daito (dispersions in cyclopolymethylsiloxane / oxyethylenated polydimethylsiloxane, containing 30% or 50% of zinc nano-oxides coated with silica and polymethylhydrogenenesiloxane);NFD Ultrafine ZnO by Daikin (ZnO coated with perfluoroalkyl phosphate and perfluoroalkyl ethyl copolymer in dispersion in cyclopentasiloxane);SPD-Z1 by Shin-Etsu (ZnO coated with silicone grafted acrylic polymer, dispersed in cyclodimethylsiloxane);Escalol Z 100 by the company ISP (ZnO treated with alumina and dispersed in the mixture of ethylhexyl methoxycinnamate / PVP-hexadecene / methicone copolymer);Fuji ZnO-SMS-10 by Fuji Pigment (ZnO coated silica and polymethylsilsesquioxane);Nanox Gel TN by the company Elementis (ZnO dispersed at 55% in C12-C15 alcohol benzoate with hydroxystearic acid polycondensate);OTS-5 MZ-500 by DAITO (ZnO dispersed in triethoxycaprylylsilane); natural coatings for example jojoba esters (ZnO-750-NJE7 KOBO) Hydrogenated Olive Oil Stearyl Esters (MZO-35-NOE7 KOBO)and / or their mixtures.

[0095] The uncoated cerium oxide pigments may be, for example, those sold under the name Colloidal Cerium Oxide by the company Rhone Poulenc.

[0096] In one embodiment, the zinc and titanium filters are coated, for example they are Zinc Oxide (and) Triethoxycaprylylsilane (INCI) and / or Titanium dioxide (And) Aluminum hydroxide (And) Aluminum stearate (INCI). In another embodiment they are Zinc Oxide (and) Triethoxycaprylylsilane (and) Ethyl Ferulate (INCI), Zinc Oxide (And) Stearoyl Glutamic Acid (INCI) or Titanium Dioxide (and) Isostearic Acid (INCI)

[0097] If they are both present the ratio depends on the target SPF: for example, for SPF 50 they are present at a ratio ZnO: TiO2 between 3: 1 and 4:1.EXAMPLES

[0098] Melanin synthesis on NHEM without UVB irradi tionNormal human epidermal melanocytes (NHEM) were incubated for 72h with the components at 37°C in a humidified 5% CO2 atmosphere, then the intracellular melanin content wasquantified. Melanin was extracted with NaOH-DMSO solution, heated at 80°C, then optical density (DO) was recorded at 405nm. A standard curve with synthetic melanin was done in the same conditions, allowing the expression of DO into melanin concentration. Melanin level was normalized with total cells number.Melanin synthesis on NHEM with UVB irradiation

[0099] Normal human epidermal melanocytes (NHEM) were incubated for 8 days with the components at 37°C in a humidified 5% CO2 atmosphere. During this period, cells were daily exposed to UVB radiation. Then the intracellular melanin content was quantified. Melanin was extracted with NaOH-DMSO solution, heated at 80°C, then optical density (DO) was recorded at 405nm. A standard curve with synthetic melanin was done in the same conditions, allowing the expression of DO into melanin concentration. Melanin level was normalized with total cells number.

[0100] In the examples, red salvia is a commercially available product (INCI:SALVIA MILTIORRHIZA ROOT EXTRACT).Table I: Melanin Synthesis on Normal Human Melanocytes without UVB Irradiation Melanin content p value p value compared (pg / Cell mean ± sd) compared to to BisabololNon Treated + Red SalviaNon Treated 71.19 ± 0.89 - p<0.0001 Bisabolol 0.0002% 61.57 ± 1.89 p<0.0001 p<0.0001Red Salvia 0.0024% 61.43 ± 1.39 p<0.0001 p<0.0001 Bisabolol 0.0002% + 49.36 ± 1.66 p<0.0001Red Salvia 0.0024%Table II: Melanin Synthesis on Normal Human Melanocytes with UVB Irradiation Melanin p value vs. non p value vs. content treated UVB Bisabolol+ (pg / Cell) Exposed Red Salvia Non-Treated 38.14 ± 0.60 pO. OOOl pO. OOOl Non UVB ExposedNon Treated 58.16 ± 1.55 - pO. OOOl UVB ExposedBisabolol 0.0002% 53.04 ± 3.21 p=0.0012 p=0.0002 UVB ExposedRed Salvia 0.0024% 52.64 ± 1.22 p=0.0006 p=0.0003 UVB ExposedBisabolol 0.0002% ± 46.61 ± 1.37 pO. OOOl - Red Salvia 0.0024%UVB Exposed

Claims

CLAIMSWhat is claimed is:

1. Cosmetic composition for skin brightening comprising cosmetically effective amounts of at least two of (i) bisabolol, (ii) red salvia and (iii) tranexamic acid.

2. Cosmetic composition according to claim 1 comprising cosmetically effective amounts of (i) bisabolol, (ii) red salvia and (iii) tranexamic acid.

3. Cosmetic composition according to claim 1 or 2 further comprising a blended extract of Egyptian Lotus (Nymphaea caerulea) and of Sacred Lotus (Nelumbo nucifera), a resorcinol derivative, kojic acid, niacinamide, palmaria palmata extract and / or combinations thereof.

4. Cosmetic composition according to any of the preceding claims wherein bisabolol is present in an amount between about 0.00001 wt % and about 10 wt % relative to the total weight of the composition.

5. Cosmetic composition according to any of the preceding claims wherein red salvia is present in an amount between about 0.00001 wt % and about 2 wt % relative to the total weight of the composition.

6. Cosmetic composition according to any of the preceding claims wherein tranexamic acid is present in an amount between about 0.001 wt % and about 5 wt % relative to the total weight of the composition.

7. Cosmetic composition according to any of the preceding claims wherein the formulation is for topical administration.

8. Cosmetic composition according to claim 7 wherein the formulation is a solution, a cream, a lotion, an ointment, a gel, a paste, a spray or a powder.

9. Cosmetic composition according to any of claims 7 or 8 wherein the composition is in the form a W / O emulsion, an O / W emulsion, a W / O / W emulsion.

10. Cosmetic composition according to any of the preceding claims further comprising one or more UVA filter, one or more UVB filter and / or one or more UVA / UVB.

11. Cosmetic composition according to claim 8 wherein the one or more filter is organic or inorganic.

12. Cosmetic composition according to any of the preceding claims, wherein red salvia and bisabol ol are present in a 8: 1 to 15: 1 weight ratio.

13. Cosmetic composition according to claim 12 wherein the vehicle comprises one or more ingredient selected from the group consisting of water and / or one or more oil, alcohol or glycol, preservative, emulsifier, absorption promoter and fragrance and mixtures thereof.

14. Cosmetic composition according to claim 13, wherein the vehicle comprises Hydroxyethyl Acrylate / sodium Acryloyldimethyl Taurate Copolymer & Polyacrylate Crosspolymer -6 as thickener.

15. Cosmetic composition according to any of the preceding claims wherein the composition is not in the form of a dressing or a patch.

16. Cosmetic composition according to any of the preceding claims wherein the red salvia extract is obtained from the flowers, leaves and roots of the plant Salvia miltiorrhiza.

17. Cosmetic composition according to any of the preceding claims, wherein the red salvia extract is obtained from the roots of the plant Salvia miltiorrhiza.

18. Use of a cosmetic composition according to any of the preceding claims for brightening the skin.

19. Use of a cosmetic composition according to any of claims 1 to 17 to modulate melanin production.

20. Use of a cosmetic composition according to claim 19 for the cosmetic or medical treatment and / or prevention of skin cellular senescence.

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