EP4262727A1

EP4262727A1 - Self-tanning compositions

Info

Publication number: EP4262727A1
Application number: EP21836544.3A
Authority: EP
Inventors: Leithe BUDEL; Dominik Imfeld; Joerg KREMP
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2020-12-16
Filing date: 2021-12-16
Publication date: 2023-10-25
Also published as: WO2022129265A1

Abstract

The present invention relates to self-tanning compositions that, through the combination of certain skin-tanning peptides and L-tyrosine or a derivative thereof, provide a synergistic effect on melanogenesis (tanning).

Description

Self-tanning compositions

Self-tanners are a safe, rapid and effective alternative for obtaining healthful skin coloration. These products have been more and more sought after, chiefly in countries where the presence of sunlight is scarce. By using self-tanners one can obtain the desired tan throughout the year, without skin damage preventing the risks of excessive exposure to sunlight and the use of tanning chambers. Recently, the scientific community alerts for the risks involving artificial tanning on tanning chambers. According to Dermatologists and researchers, irresponsible uses of tanning chambers may contribute to the increase of skin cancer and induce premature skin aging, since the equipment used in artificial tanning emit mainly Ultra Violet radiation Type A (UV-A), which is also responsible for skin cancer and skin photoaging. Premature skin photoaging is characterized by dark, clear or reddish spots, dry, thick and wrinkled skin, making a person look older than she/he really is.

Skin-tanning peptides are known from WO2018065345. However, there is still a need to further enhance the tanning effect thereof.

Surprisingly, it has now been found that the combination of L-tyrosine or a derivative thereof and a compounds of formula (I) as depicted below respectively a salt thereof synergistically enhances melanogenesis and can thus be used to provide highly efficient self-tanning compositions. Thus, in a first aspect, the invention relates to a cosmetic and/or dermatological self-tanning composition comprising L-tyrosine or a derivative thereof and at least one compound of formula wherein

R¹ is selected from the group consisting of a C₁-C₁₀ alkyl group, a C₃-C₆ cycloalkyl group, an aryl group or an aryl C₁-C₆ alkyl group;

R² is an amino acid side chain of a basic amino acid or an amino acid side chain of a 2-amino C_2-8 alkanoic acid;

R³ and R³’ are selected from the group consisting of H, an arylC₁-C₆ alkyl group or a heteroarylC₁-C₆ alkyl group, wherein the aryl respectively the heteroaryl can optionally be substituted,

R⁴ and R⁵ are, independently of each other, H or a C1-C10 alkyl group; and with the proviso that only one of R³ or R³’ is H and the respective other one of R³ and R³’ is not H or a salt thereof.

Another objective of the present invention is to use L-tyrosine or a derivative thereof in combination with a compound of formula (I) in preparing a self-tanning cosmetic and/or dermatological composition that has performance similar or superior to that of the presently available compositions.

A further objective of the present invention is to provide a skin self-tanning method through application of a cosmetic and/or dermatological composition containing L-tyrosine or a derivative thereof and at least one compound of formula (I) to the skin of a subject in need thereof.

It is well understood, that the combination of the compound of formula (I) and L-tyrosine respectively a derivative thereof excerpt a synergistic tanning effect, i.e. provide an improved tanning effect which is optionally appreciated by the person applying the skin self-tanning compositions according to the present invention.

The term ‘C_x-C_yalkyl group’ as used herein refers to unbranched C_x-C_yalkyl or branched C3-C_yalkyl groups such as methyl, ethyl, n-propyl, 1 -methylethyl, n-butyl, 1 -methylpropyl, 2-methylpropyl, 1 ,1 -dimethylethyl, n-pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1- ethylpropyl, n-hexyl, 1 ,1 -di methyl propyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1 -di methyl butyl, 1 ,2-dimethylbutyl, 1 ,3-di methyl butyl, 2,2- di methyl butyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl,

1 , 1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1-ethyl-1 -methylpropyl, 1-ethyl-2-methylpropyl and 3,5,5-trimethylhexyl groups.

The term ‘C₃-C₆cycloalkyl group’ as used herein refers to a saturated, 3 to 6 membered hydrocarbon ring such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Preferably in all embodiments of the present invention the C₃-C₆cycloalkyl group is cyclopropyl, cyclopentyl or cyclohexyl, most preferably cyclohexyl.

The term “aryl” as used herein refers to an aromatic substituent containing 5 to 15 carbon atoms and containing a single aromatic ring or multiple aromatic rings which are fused together, directly linked or indirectly linked (such that the different aromatic rings are bound to a common group such as a methylene or ethylene group). Particularly advantageous aryl groups according to the present invention contain 6 to 12 carbon atoms containing a single aromatic ring or multiple aromatic rings which are fused together or directly linked. Most preferred aryl residues in all embodiments of the present invention are phenyl, naphtyl and biphenyl.

The term "side chain" of an amino acid as used herein refers to that portion of the amino acid attached to the common NH₂-CH -COOH backbone of the respective amino acids. For instance, the side chain of serine is -CH₂-OH and the side chain of alanine is -CH₃.

The term “basic amino acid” as used herein refers to any natural or unnatural amino acid that have basic side chains at neutral pH such as the natural occurring amino acids arginine (Arg), lysine (Lys), and histidine (His) as well as the unnatural amino acids 2,4-diaminobutyric acid, homolysine and ornithine without being limited thereto. Advantageous amino acid side in all embodiments of the present invention are the side chains of arginine, lysine, 2,4-diaminobutyric acid, homolysine and ornithine such as in particular the side chains of arginine and 2,4- diaminobutyaric acid.

The term “2-amino C_2-8alkanoic acid” as used herein refers to amino acids having a C_2-8 alkyl side chain, preferably a linear C4-7 alkyl side chain. Most preferred 2-amino C_2-8 alkanoic acids in all embodiments of the present invention are 2-amino butanoic acid, 2-amino pentanoic acid, 2- amino hexanoic acid or 2-amino heptanoic acid such as in particular 2-amino hexanoic acid.

The term “arylC₁-C₆ alkyl group” as used herein refers to a -C₁-C₆ alkyl-aryl group, wherein the term “aryl” is as defined above. Advantageous arylC₁-C₆ alkyl groups are arylC₁-C₂ alkyl groups such as in particular phenyl(m)ethyl or naphthyl(m)ethyl.

The term ‘heteroarylC₁-C₆ alkyl group’ as used herein refers to a -C₁-C₆ alkyl-heteroaryl wherein the term “heteroaryl” refers to a 5- or 6-membered aromatic ring containing one or more heteroatoms, viz., N, O or S; these heteroaromatic rings may be fused to other aromatic systems. Particularly preferred heteroaromatic rings encompass indole, pyridine and quinoline. In all embodiments of the present invention preferred heteroarylC₁-C₆ alkyl group are heteroarylC₁-C₂ alkyl groups such as (1 H-indol-3-yl)(m)ethyl, (pyridin-2-yl)(m)ethyl, (pyridin-3-yl)(m)ethyl, (quinolin-2-yl)(m)ethyl and (quinolin-3-yl)(m)ethyl groups.

The aromatic aryl respectively heteroaryl residues may, independently of each other, be unsubstituted or substituted with one or more substituents. In all embodiments of the present invention, such substituents are preferably selected from halogen, hydroxy, nitro, cyano, C₁-C₆ alkyl, C₁-C₆ alkoxy and C₁-C₆ alkanoyloxy. More preferably in all embodiments of the present invention the aryl respectively heteroaryl residues are, independently of each other, unsubstituted or substituted with one substituent selected from the group consisting of F, Cl, hydroxy, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy and C₁-C₃ alkanoyloxy such as in particular unsubstituted or substituted with one substituent selected from the group consisting of F or hydroxy. Most preferably, in all embodiments of the present invention, the aryl and the heteroaryl residues are unsubstituted.

In all embodiments of the present invention particular preferred heteroarylC₁-C₂ alkyl groups are (1 H-indol-3-yl)(m)ethyl, 5-fluoro(1 H-indol-3-yl)(m)ethyl, 6-fluoro(1 H-indol-3-yl)(m)ethyl, 5- hydroxy(1 H-indol-3-yl)(m)ethyl, (pyridin-2-yl)(m)ethyl, (pyridin-3-yl)(m)ethyl, (quinolin-2- yl)(m)ethyl and (quinolin-3-yl)(m)ethyl. Most preferred in all embodiments of the present invention are the heteroarylCi alkyl groups (1 H-indol-3-yl)methyl, 5-fluoro(1 H-indol-3-yl)methyl, 6- fluoro(1 H-indol-3-yl)8m)ethyl, 5-hydroxy(1 H-indol-3-yl)methyl, (pyridin-2-yl)methyl, (pyridin-3- yl)methyl, (quinolin-2-yl)methyl and (quinolin-3-yl)methyl and the heteroarylC₂ alkyl groups (1 H- indol-3-yl)ethyl such as in particular (1 H-indol-3-yl)methyl and (1 H-indol-3-yl)ethyl.

The term ‘or a salt thereof’ refers to all conventional non-toxic salts of compounds of formula (I), such as those formed from organic or mineral acids, such as for example the respective acetates, trifluoro acetates, mesylates, citrates, oleates, oxalates or gluconates as well as chlorides, sulfates, borates or carbonates. The nature of the salt is not critical, provided that it is cosmetically, dermatologically and/ or pharmaceutically acceptable. Such salts are well known to a person skilled in the art. The cosmetically, dermatologically or pharmaceutically acceptable salts of the compounds of formula (I) can be obtained by conventional methods that are well known in the state of the art.

Most preferred in all embodiments of the present invention are the compounds of formula (I) as such or in the form of their acetates, trifluoroacetates (i.e. as 2,2,2-trifluoroacetates) or mesylates. Such salts are easily prepared by a person skilled in the art.

It is well understood that the present invention encompasses the compounds of formula (I) as optically pure isomers such as e.g. as pure enantiomers or stereoisomers as well as mixtures of different isomers such as e.g. as racemates, or mixtures of diastereoisomers.

In all embodiments according to the present invention it is preferred that

• R³ and R³’ are selected from the group consisting of H, an unsubstituted aryl(m)ethyl group and an unsubstituted heteroaryl(m)ethyl group, most preferably R³ is selected from the group consisting of H, phenylmethyl, naphthylmethyl and (1 H-indol-3-yl)methyl and R³’ is H or (1 H-indol-3-yl)ethyl;

• R⁴ and R⁵ are, independently of each other, H or a C₃-C₈ alkyl group, most preferably H, propyl or octyl; and with the proviso that only one of R³ or R³’ is H and the respective other one of R³ and R³’ is not H (but the respective arylC₁-C₆ alkyl group or heteroarylC₁-C₆ alkyl group, with all the definitions and preferences as given herein for R³ and R³’). Particularly preferred compounds of formula (I) respectively a salt thereof such as in particular the acetate, trifluoroacetate or mesylate salt thereof in all embodiments of the present invention, are compounds of formula (I) wherein

R¹ is a C₁-C₂ alkyl group or a C₆-C₁₂ aryl group;

R² is an amino acid side chain of a basic amino acid;

R³ and R³’ are selected from the group consisting of H, an unsubstituted aryl(m)ethyl group or an unsubstituted heteroaryl(m)ethyl group; and

R⁴ and R⁵ are, independently of each other H or a C₁-C₁₀lkyl group; and with the proviso that only one of R³ or R³’ is H and the respective other one of R³ and R³’ is not H.

Even more preferred compounds of formula (I) or salts thereof such as in particular the (trifluoro)acetate or mesylate salt thereof in all embodiments of the present invention are the ones, wherein

R¹ is phenyl;

R² is the amino acid side chain of arginine or 2,4-diaminobutyric acid;

R³ is H, phenylmethyl, naphthylmethyl or (1 H-indol-3-yl)methyl and R³’ is H or (1 H-indol-3- yl)ethyl;

R⁴ and R⁵ are, independently of each other H, propyl or octyl; with the proviso that only one of R³ or R³’ is H and the respective other one of R³ and R³’ is not H.

Even more advantageous preferred compounds of formula (I) or salts thereof such as in particular the (trifluoro)acetate or mesylate salt thereof in all embodiments of the present invention are the ones, wherein

R¹ is are selected from the group consisting of a C1-C₁₀ alkyl group, a C₃-C₆ cycloalkyl group, an aryl group or an aryl C₁-C₆ alkyl group; preferably from C₁-C₂ alkyl group or a C₆-C₁₂ aryl group, most preferably phenyl;

R² is the amino acid side chain of arginine;

R³ is (1 H-indol-3-yl)methyl;

R⁴ and R⁵ are, independently of each other H or a C₁-C₁₀ alkyl group, preferably H, propyl or octyl. Even more preferably R⁴ = R⁵.

Most advantageous compounds are compounds of formula R¹-Gly-His-D-Phe-Arg-D-Trp- N(R⁴,R⁵) with all the definitions and preferences for R¹ and R⁴ and R⁵ as outlined herein. Most preferred in all embodiments according to the present invention are the compounds as listed in table 1 , respectively the respective (trifluoro)acetate or mesylate salts thereof:

Table 1

The compounds according to the present invention may be prepared by methods standard in peptide chemistry as e.g. illustrated in WO-2018065345.

Most preferred in all embodiments is Bz-Gly-His-D-Phe-Arg-D-Trp-N(Pr)2*2MSA [CAS No. 2210277-15-7], which preferably is used in the form of a solution in glycerin/ water, most preferably in a concentration of about 1000 ppm (w/w) which is commercially available under the tradename SYN®-GLOW at DSM Nutritional Products Ltd. L-Tyrosine (4-hydroxyphenylalanine) is one of the 20 standard amino acids that are used by cells to synthesize proteins. L-Tyrosine is e.g. commercially available at Sigma-Aldrich. Particularly suitable L-tyrosine derivatives in all embodiments of the present invention are selected from the group of N-Ci-18-acyl-L-tyrosine, preferably from N-acetyl-L-tyrosine, N-capryl-L-tyrosine and N-oleyl-L-tyrosine as well as mixtures thereof. Most preferably the derivative is N-acetyl-L- tyrosine, which is e.g. commercially available as Unipertan® VEG-2002 (A cety l-tyrosine) from Givaudan Active Beauty.

It is well understood by a person skilled in the art, that the self-tanning compositions according to the present invention are self-tanning composition further comprising a cosmetically or dermatologically acceptable carrier. Particularly suitable self-tanning compositions are cosmetic composition.

The term ‘cosmetic composition’ as used herein refers to compositions which are used to treat, care for or improve the appearance of the affected skin area. Particular advantageous self-tanning compositions according to the present invention are skin care compositions.

The term ‘cosmetically or dermatologically acceptable carrier’ as used herein refers to a physiologically acceptable medium which is compatible with keratinous substances such as the skin. Suitable carriers are well known in the art and are selected based on the end-use application.

Preferably, the carriers of the present invention are particularly suitable for application to skin (e.g., sunscreens, creams, milks, lotions, masks, serums (e.g. in ethanol or acetone), hydrodispersions, foundations, creams, creamgels, or gels etc.). Such carriers are well-known to one of ordinary skill in the art and can include one or more compatible liquid or solid filler diluent, excipient, additive or vehicle which are suitable for application to skin. The exact amount of carrier will depend upon the level of the compound of formula (I) and any other optional ingredients that one of ordinary skill in the art would classify as distinct from the carrier (e.g., other active components). The compositions of the present invention preferably comprise from about 75% to about 99.999%, more preferably from about 85% to about 99.99%, still more preferably from 90% to about 99%, and most preferably, from about 93% to about 98%, by weight of the composition, of a carrier. In a particular advantageous embodiment, the carrier consists furthermore of at least 30 wt. %, more preferably of at least 40 wt.-%, most preferably of at least 45 wt.-% of water, such as in particular of 50 to 90 wt.-% of water.

Preferably, the amount of the compound of formula (I) or a salt thereof in the self-tanning compositions according to the present invention is at least 1 ppm based on the total weight of the self-tanning composition. In all embodiments of the present invention the amount of the compound of formula (I) or a salt thereof is preferably selected in the range of about 0.00001 to 0.5 wt.-%, more preferably in the range of 0.0001 to 0.25 wt.-%, most preferably in the range of 0.0001 to 0.1 wt.-%, based on the total weight of the self-tanning composition. Further suitable ranges encompass from 0.0001 to 0.01 wt.-%, from 0.0025 to 0.1 , respectively from 1 ppm to 100 ppm. Other suitable ranges encompass from 0.001 to 0.1 wt.-%, from 0.001 to 0.075 wt.-%, from 0.001 to 0.05 wt.-%, from 0.002 to 0.1 wt.-%, from 0.002 to 0.075 wt.-% and from 0.002 to 0.05 wt.-%.

Preferably, the amount of L-tyrosine or a derivative thereof in the self-tanning compositions according to the present invention is at least 0.01 wt.-% and/ or at most 10 wt.-%, based on the total weight of the self-tanning composition. In all embodiments of the present invention the amount of L-tyrosine or a derivative thereof is preferably selected in the range of about 0.01 to 5.0 wt.-%, more preferably in the range of 0.1 to 2.0 wt.-%, most preferably in the range of 0.1 to 1.0 wt.-%, based on the total weight of the self-tanning composition. Other suitable ranges encompass from 0.5 to 5 wt.-%, from 1 to 5 wt.-%, from 2 to 5 wt.-%, from 2.5 to 5 wt.-% and from 3 to 5 wt.-%.

In all embodiments of the present invention, preferably L-tyrosine or a derivative thereof is used in an excess, such as in an amount of two times, preferably three times, more preferably 10 times, most preferably 100 times such as 1000 times of the amount (weight) of the compound of formula (I).

Even more preferably, in all embodiments of the present invention, the ratio (w/w) of L-tyrosine or a derivative thereof to the compound of formula (I) is selected in the range from 5000:1 to 1 :1 , preferably from 2500:1 to 1.5:1 , most preferably from 2000:1 to 2:1 , such as in the range from 2000:1 to 3:1 or from 2000:1 to 4:1. Further suitable ranges are from 2500:1 to 50:1 , or from 2000:1 to 100:1. The self-tanning compositions of the present invention can be formulated into a wide variety of product types, including creams, waxes, pastes, lotions, milks, mousses, gels, oils, tonics, and sprays. Preferably the compounds of formula (I) are formulated into lotions, creams, gels, and tonics. These product forms may be used for a number of applications, including, but not limited to, hand and body lotions, facial moisturizers, anti-ageing preparations, make-ups including foundations, and the like. Any additional components required to formulate such products vary with product type and can be routinely chosen by one skilled in the art. The composition may also be in the form of a shaving preparation or an aftershave product intended for application to the skin after shaving.

If the self-tanning compositions of the present invention are formulated as an aerosol and applied to the skin as a spray-on product, a propellant is added to the composition.

The self-tanning compositions according to the present invention may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of oil-in-water (O/W) or water-in-oil (W/O) type, silicone-in-water (Si/W) or water-in-silicone (W/Si) type, PIT-emulsion, multiple emulsion (e.g. oil-in-water-in oil (O/W/O) or water-in-oil-in-water (W/O/W) type), pickering emulsion, hydrogel, alcoholic gel, lipogel, one- or multiphase solution or vesicular dispersion or other usual forms, which can also be applied by pens, as masks or as sprays.

If the self-tanning composition according to the present invention is an emulsion, such as in particular an O/W, W/O, Si/W, W/Si, O/W/O, W/O/W multiple or a pickering emulsion, then the amount of the oily phase present in such cosmetic emulsions is preferably at least 10 wt.-%, such as in the range of 10 to 60 wt.-%, preferably in the range of 15 to 50 wt.-%, most preferably in the range of 15 to 40 wt.-%, based on the total weight of the self-tanning composition.

In one embodiment, the self-tanning compositions according to the present invention are advantageously in the form of an oil-in-water (O/W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier. The preparation of such O/W emulsions is well known to a person skilled in the art.

In a particular advantageous embodiment, the self-tanning compositions according to the present invention are in the form of O/W emulsions comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier, preferably in the presence of potassium cetyl phosphate. The amount of oily phase in such O/W emulsions is preferably at least 10 wt.-%, more preferably in the range of 10 to 60 wt.-%, most preferably in the range of 15 to 50 wt.-%, such as in the range of 15 to 40 wt.-%.

In another particular advantageous embodiment, the self-tanning compositions according to the present invention are after-shaves or toners in the form of aqueous solution or aqueous gels further containing at least one gelling and/ or thickening agent such as e.g. selected from the group of acrylate copolymers of sodium/lecithin, copolymer of hydroxyethyl acrylate/sodium acryloyldimethyl taurate, isohexadecane, polysorbate 60, xanthan gum, carrageenan and mixtures thereof.

The self-tanning compositions according to the invention in general have a pH in the range of 3 to 14. Generally self-tanning compositions for skin care preferably exhibit a pH in the range of 4 to 8 and most preferably a pH in the range of 4 to 7.5. The pH of depilatory creams, however, generally is selected in the range of > 12. The pH can easily be adjusted as desired with suitable acids, such as e.g. citric acid, or bases, such as sodium hydroxide (e.g. as aqueous solution), triethanolamine (TEA Care), Tromethamine (Trizma Base) and Aminomethyl Propanol (AMP- Ultra PC 2000), according to standard methods in the art.

The self-tanning compositions according to the present invention can be prepared by conventional methods in the art such as e.g. by admixing L-tyrosine or a derivative thereof and a compound of formula (I) or a salt thereof with all the definitions and preferences given herein with an appropriate carrier such as a cosmetically or pharmaceutically acceptable carrier. The self-tanning compositionsof the invention (including the carrier) may comprise further conventional cosmetic adjuvants and additives, such as preservatives/antioxidants, fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, antifoaming agents, aesthetic components such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorings/colorants, abrasives, absorbents, chelating agents and/ or sequestering agents, essential oils, skin sensates, astringents, pigments or any other ingredients usually formulated into such compositions.

The self-tanning compositions according to the present invention should be topically applied to a selected area of the body from which it is desired to reduce hair growth. For example, the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin.

The self-tanning composition according to the present invention can also be applied to the legs, groin region (bikini area), arms, torso or armpits. The self-tanning compositions according to the present invention are furthermore particularly suitable for application to normal to pallor skin but can also be applied to darker skin.

The amount of the self-tanning composition to be applied to the skin is not critical and can easily be adjusted by a person skilled in the art. Preferably the amount is selected in the range of 0.1 to 3 mg/cm² skin, such as preferably in the range of 0.1 to 2 mg/cm² skin and most preferably in the range of 0.5 to 2 mg/cm² skin.

Preferably, the compound of formula (I) or a salt thereof is applied to the skin in an amount of from 0.001 to 10 micrograms of the compound of formula (I) per square centimeter of skin.

In an advantageous embodiment, the present invention is directed to the use of a self-tanning compositions according to the present invention for enhancing the skin tan of a person in need thereof.

In a further embodiment, the present invention relates to the use of L-tyrosine or a derivative thereof in combination with a compound of formula (I) as defined herein in preparing a self-tanning cosmetic and/or dermatological composition. Said composition has a synergistic (over-additive) skin tanning effect compared to a composition comprising either a compound of formula (I) or L- tyrosine or a derivative thereof.

In a suitable embodiment the self-tanning composition according to the present invention may further contain organic or inorganic UV-filter substances (light screening agents) which are active in the IIV-A and/or IIV-B regions (absorbers) to protect the skin against the harmful effects of UV- radiation.

Exemplary UVA, UVB and/ or broadspectrum UV-filter substances encompass dibenzoylmethane derivatives such as e.g. butyl methoxydibenzoylmethane (PARSOL® 1789); acrylates such as e.g. octocrylene (PARSOL® 340); camphor derivatives such as e.g. 4-methyl benzylidene camphor (PARSOL® 5000) or terephthalylidene dicamphor sulfonic acid (Mexoryl® SX); cinnamate derivatives such as e.g. ethylhexyl methoxycinnamate (PARSOL® MCX) or isoamyl methoxycinnamate; p-aminobenzoic acid derivatives such as e.g. p-aminobenzoic acid or 2- ethylhexyl p-dimethylaminobenzoate; benzophenones such as e.g. benzophenone-3, benzophenone-4, 2,2',4,4'-tetrahydroxy-benzophenone or 2,2'-dihydroxy-4,4'- dimethoxybenzophenone; esters of benzalmalonic acid such as e.g. di-(2-ethylhexyl) 4- methoxybenzalmalonate; organosiloxane compounds carrying chromophore groups such as e.g. polysilicone-15 (PARSOL® SLX) or drometrizole trisiloxane (Mexoryl® XL); imidazole derivatives such as e.g. 2-phenyl benzimidazole sulfonic acid and salts thereof such as e.g. its sodium- or potassium salts (PARSOL® HS); salicylate derivatives such as e.g. ethylhexyl salicylate (PARSOL® EHS, Neo Heliopan® OS), isooctyl salicylate or homosalate (PARSOL® HMS, Neo Heliopan® HMS); triazine derivatives such as e.g. ethylhexyl triazone (Uvinul® T-150), diethylhexyl butamido triazone (Uvasorb® HEB), bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb® S) or Tris-Biphenyl Triazine (2,4,6-Tris(biphenyl-4-yl)-1 ,3,5-triazin, Tinosorb® A2B); Benzotriazole derivatives such as e.g. methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb® M); encapsulated UV-filters such as e.g. encapsulated ethylhexyl methoxycinnamate (Eusolex® UV- pearls); amino substituted hydroxybenzophenones such as e.g. diethylamino hydroxy benzoyl hexyl benzoate (Aminobenzophenon, Uvinul® A Plus); benzoxazol-derivatives such as e.g. 2,4- bis-[5-1(dimethylpropyl)benzoxazol-2-yl-(4-phenyl)-imino]-6-(2-ethylhexyl)-imino-1 ,3,5-triazin (Uvasorb® K2A); phenylene-1 ,4-bis-benzimidazolsulfonic acids or salts thereof such as e.g. disodium phenyl dibenzimidazole tetrasulfonate (2,2-(1 ,4-phenylene)bis-(1 H-benzimidazol-4,6- disulfonic acid, Neoheliopan® AP); 1 ,1’-(1 ,4-piperazinediyl)bis[1-[4-(diethylamino)-2- hydroxybenzoyl]phenyl]-methanone (CAS No. 919803-06-6); as well as Bis(butylbenzoate) diaminotriazine aminopropyltrisiloxane (CAS No. 207562-42-3).

Inorganic UV-filter substances encompass pigments such as e.g. microparticulated zinc oxide or titanium dioxide (e.g. commercially available as PARSOL®TX) The term "microparticulated" refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm. The particles may also be coated by other metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art. Preferred UVB-filter substances to be incorporated into the self-tanning compositions according to the invention encompass polysilicone-15, phenylbenzimidazol sulfonic acid, octocrylene, ethylhexyl methoxycinnamate, ethyl hexylsalicylate, tris-biphenyl triazine and/ or homosalate.

Preferred broadband UV-filter substances to be incorporated into the self-tanning compositions according to the invention encompass unsymmetrical s-triazine derivatives such as in particular bis-ethylhexyloxyphenol methoxyphenyl triazine, certain benzophenones such as e.g. 2-hydroxy- 4-methoxy-benzophenon, methylene bis-benzotriazolyl tetramethylbutylphenol and/ or titanium dioxide.

Preferred UVA-filter substances to be incorporated into the self-tanning compositions according to the invention encompass butyl methoxydibenzoylmethane, diethylamino hydroxybenzoyl hexyl benzoate, 2, 4-bis-[5-1(dimethylpropyl)benzoxazol-2-yl-(4-phenyl)-imino]-6-(2-ethylhexyl)-imino- 1 ,3,5-triazine and/ or disodium phenyl dibenzimidazole tetrasulfonate, in particular butyl methoxydibenzoylmethane and/ or diethylamino hydroxybenzoyl hexyl benzoate.

If the topical sunscreen emulsions comprise butyl methoxydibenzoylmethane, then they advantageously contain in addition at least one suitable photostabilizer for butyl methoxydibenzoylmethane. Besides specific UV-filters listed above which are known to a person skilled in the art to be able to photostabilize butyl methoxydibenzoylmethane, further exemplary photostabilizers encompass Polyester 8 (Polycrylene®); Methoxycrylene (Solastay); diethylhexyl syringylidene malonate (Oxynex ST liquid); diethylhexyl naphthalate (Corapan TQ) as well as Benzotriazolyl Dodecyl p-Cresol (Tinogard® TL) without being limited thereto. An overview on such photostabilizers is e.g. given in ‘SPF Boosters & Photostability of Ultraviolet Filters’, HAPPI, October 2007, p. 77-83 which is included herein by reference. These photostabilizers are generally used in an amount of 0.05 to 10 wt.-% with respect to the total weigh of the topical sunscreen emulsion.

If present, the amount of the UV-filter substances (i.e. the sum of all UV-filter substances present in the self-tanning composition) is preferably selected in the range of 0.1 to 40 wt. %, more preferably in the range of 0.2 to 20 wt. % and most preferably in the range of 0.5 to 15 wt.-% based on the total weight of the self-tanning composition. Further particular advantageous self-tanning compositions according to the present invention comprise one or more additional skin-coloring and/or skin-tanning agents. .

Such additional skin-coloring and/ or skin-tanning agent are well known to a person skilled in the art and encompass e.g. mono- or polycarbonyl compounds, such as, for example, isatin, alloxan, ninhydrin, glyceraldehyde, mesotartaric aldehyde, glutaraldehyde, erythrulose, the pyrazoline- 4, 5-dione derivatives as described in FR-2,466,492 and WO97/35842, di hydroxyacetone (DHA) or the 4,4-dihydroxy-pyrazolin-5-one derivatives as described in EP-903,342. Preferably, DHA and/or erythrulose (in D- or L-form or as the racemate) in particular erythrulose.

DHA can be used in the free form and/or in the encapsulated form, for example encapsulated in lipid vesicles, such as liposomes, which are described, in particular, in WO 97/25970.

The self-tanning compositions according to the present invention may also contain at least one synthetic or natural direct dye and/or at least one indole derivative, such as those described in EP-425,324 and EP-456,545 and/ or at least one synthetic or natural agent for coloring the skin.

The additional coloring agents can also be selected, for example, from among plant extracts, such as, for example, extracts of “insoluble” redwoods of the Pzerocarpus genus and of the Baphia genus, such as Pzerocarpus santalinus, Pterocarpus osun, Plerocarpus soyauxii, Plerocarpus erinaceus, Pterocarpus indicus or Baphia nitida, such as those described in EP-971 ,683.

The coloring agents can also be iron oxide nanopigments for which the mean size of the individual particles is less than 100 nm, such as those described in EP-966,953.

If present, the total amount of such additional skin-coloring and/ or skin-tanning agent(s) in the self-tanning compositions according to the invention is generally selected in proportions ranging from 0.1% to 20% by weight with respect to the total weight of the composition and preferably from 0.2% to 8% by weight with respect to the total weight of the self-tanning composition.

In a particular preferred embodiment, however, the self-tanning compositions according to the present invention only comprise L-tyrosine or a derivative thereof and the compound of formula (I) as skin-tanning agent. The invention is further illustrated with reference to the following, non-limiting examples, in which all percentages are by weight based on total weight unless otherwise specified.

Experimental part

1. Melanogenesis

Methodology

To investigate the effects of various bioactive compounds on cellular melanogenesis, we used 3D in vitro melanized human epidermis models (from StratiCELL). Our experimental part represented the following set of conditions: a negative control with just medium (as provided by StratiCELL), a solvent control (1 % DMSO and 20% Ethanol in 0,9% PBS), a 200 pM L-tyrosine condition, a 50 pM SYN-GLOW® condition, a 50 pM Rona Care Bronzyl condition, and a 50 pM SYN-GLOW® with 200 pM L-tyrosine condition. For each condition, there were 6 samples, which were used for a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay and for a melanin extraction analysis. A total of 25 pL compound was added three times during a period of eight days per condition. All sample conditions underwent treatment in a dark incubator supplying 5% CO2 and 37°C. At the eighth day, the samples were analyzed with the MTT viability assay and melanin extraction to determine pigment quantities.

Results

To investigate any potential toxic side effects from the compounds, an MTT assay was performed, see Table 1. Besides the untreated control, all conditions had a slight reduction in viability. As the solvent control also had a reduction in viable cells similar to the treatment ones with bioactives, no increased toxicity was found for the bioactive compounds at their used concentrations.

Table 1

Table 1. Cell viability of the MEL models did not reduce using the selected bioactive compounds. The MEL models were treated three times over a time span of eight days. At the final day, the MEL models were subjected to an MTT assay to determine cell viability. Data are normalized to the untreated control (100%) and expressed as the mean ± SD (n = 3).

Next, the melanin content in the cells of the MEL models was measured. This was done by dissolving the cell models and visualize from this mixture the melanin content using a standard with known melanin concentrations. The melanin analysis was performed on day 8 of treatment and showed that the SYN-GLOW® and L-tyrosine combination had the highest increase compared to the untreated control in melanin levels, see Table 2. Compared to the bioactives separately, a clear synergetic effect can be seen when SYN-GLOW® and L-tyrosine are combined.

Table 2

*Based on the peptide (i.e. Benzoyl Dipeptide-18 D-Phenylalanyl Arginyl D- Tryptophan Dipropylamide Mesylate)

Table 2. Melanin extraction shows a synergetic effect of SYN® -GLOW and L-tyrosine. The MEL models were treated three times over a time span of eight days. On day 8, the cell models were cut from their inserts and dissolved for melanin content analysis. Data are normalized to the untreated control, followed by normalization of the treatment samples to the solvent control and are expressed as the mean ± SD (n = 3). 2. Formulation

Table 3

Procedure

Mix A and heat up to 75-80°C

Disperse Keltrol in Zemea and add to A at 60°C

Mix B and heat up to 75-80°C

Add B to A at 75-80°C

Homogenize 1.5min with high shear

Cool down to room temperature

Add C

Add D to reach pH 6

3. In vivo assessment

To investigate the effect of the present invention on human skin, a cream formulation was prepared containing 3% SYN-GLOW® (0.003-0.03 wt.-% active i.e. peptide) and 5% N-acetyl-L- tyrosine (5 wt.-%) (Table 5); A total of 2 mg/cm² of placebo cream or cream with compounds was applied on a 3.5 x 3.5 cm area (= 12.25 cm2 = ~25 mg) on the volar forearm. The subjects applied the cream in the morning (except the morning application on measuring days) and in the evening by themselves at their home for a total of 14 days. The application site was covered from sunlight/UV (the application period was in November as well in Switzerland).

The determination of skin pigmentation was done using a chromameter with three repeated measurements per area. The L*, A*, and B* values were obtained. The assessment times included a baseline (day 0, before first application), day 7, day 14, and day 21 (1 week after last application). From this assessment, the ITA° of the skin was determined using the L* and B* values with the following formula: ITA° = [Arc Tangent ((L* - 50)/b] * 180 /3.1416; a lower ITA corresponds to darker skin.

To evaluate the skin pigment differences, the AAITA° was calculated. The AITA° was obtained by comparing day 0 and day x (day with highest difference, e.g., day 14) of placebo cream and cream with compounds. Next, the AAITA° was determined directly between placebo and cream with compounds. Based on this, the following formula was applicable: (SG+TY day 0 vs. day x) vs. (Placebo day 0 vs. day x), where x represents the day with the largest difference. A negative AAITA° value represents a darkened skin pigmentation. As can be retrieved from the results depicted in the table 4 below, the combination leads to an improved pigmentation.

Table 4

Table5

Claims

1 . A cosmetic and/or dermatological self-tanning composition comprising L-tyrosine or a derivative thereof and at least one compound of formula (I) wherein

R¹ is are selected from the group consisting of a C₁-C₁₀ alkyl group, a C₃-C₆ cycloalkyl group, an aryl group or an aryl C₁-C₆ alkyl group;

R² is an amino acid side chain of a basic amino acid or an amino acid side chain of a 2-amino C_2-8alkanoic acid;

R⁴ and R⁵ are, independently of each other, H or a C₁-C₁₀ alkyl group; and with the proviso that only one of R³ or R³’ is H and the respective other one of R³ and R³’ is not H or respective salts thereof.

2. The cosmetic and/or dermatological self-tanning composition according to claim 1 , wherein

R¹ is phenyl;

R² is the amino acid side chain of arginine or 2,4-diaminobutyric acid;

R³ is selected from the group consisting of H, phenylmethyl, naphthylmethyl or (1 H-indol-3-yl)methyl and R³’ is H or (1 H-indol-3-yl)ethyl; and

R⁴ and R⁵ are, independently of each other H, propyl or octyl.

3. The cosmetic and/or dermatological self-tanning composition according to claim 1 , wherein the compound of formula (I) is Bz-Gly-His-D-Phe-Arg-Trp-N(Propyl)2, preferably in the form of its mesylate salt. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the amount of the compound of formula (I) or the salt thereof in the composition is selected in the range of about 0.00001 to 0.5 wt.-%, preferably in the range of 0.0001 to 0.25 wt.-%, more preferably in the range of 0.0001 to 0.1 wt.-%, based on the total weight of the composition. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the compound of formula (I) or the salt thereof is applied to the skin in an amount of from 0.001 to 10 micrograms of the compound of formula (I) or the salt thereof per square centimeter of skin. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the L-tyrosine derivative is selected from the group of N-C_1-18- acyl-L-tyrosine, preferably from N-acetyl-L-tyrosine, N-capryl-L-tyrosine and N-oleyl-L- tyrosine, most preferably the L-tyrosine derivative is N-acetyl-L-tyrosine. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the amount of L-tyrosine or a derivative thereof in the composition is selected in the range of about 0.01 to 5.0 wt.-%, based on the total weight of the self-tanning composition. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein L-tyrosine or a derivative thereof and the at least one compound of formula (I) are used as sole skin-tanning agents. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the composition further comprises at least one UV-filter substance. The cosmetic and/or dermatological self-tanning composition according to claim 9, wherein the at least one UV-filter substance is selected from the group consisting of polysilicone-15, phenylbenzimidazol sulfonic acid, octocrylene, ethylhexyl methoxycinnamate, ethyl hexylsalicylate, tris-biphenyl triazine, homosalate, bisethylhexyloxyphenol methoxyphenyl triazine, 2-hydroxy-4-methoxy-benzophenon, methylene bis-benzotriazolyl tetramethylbutylphenol, optionally surface-coated titanium dioxide, butyl methoxydibenzoylmethane, diethylamino hydroxybenzoyl hexyl benzoate, 2, 4-bis-[5-1(dimethylpropyl)benzoxazol-2-yl-(4-phenyl)-imino]-6-(2-ethylhexyl)-imino- 1 ,3,5-triazine and disodium phenyl dibenzimidazole tetrasulfonate as well as mixtures thereof. The cosmetic and/or dermatological self-tanning composition according to claim 9 or 10, wherein the amount of the UV-filter substances is selected in the range of 0.1 to 40 wt. %, preferably in the range of 0.2 to 20 wt. %, most preferably in the range of 0.5 to 15 wt.-%, based on the total weight of the self-tanning composition. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, wherein the composition is in the form of an oil-in-water (O/W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier. The cosmetic and/or dermatological self-tanning composition according to anyone of the preceding claims, characterized by being intended for application to normal-to-pallor skin. A skin self-tanning method, characterized by applying, onto the skin, the cosmetic and/or dermatological composition as defined in any of claims 1-13 and optionally appreciating the (synergistic) effect. Use of L-tyrosine or a derivative thereof in combination with a compound of formula (I) as defined in claims 1 to 3 in preparing a self-tanning cosmetic and/or dermatological composition.